The next shift.
The next responsibility.
The next paper.
The next presentation.
The next thing that needed to be done.

And somewhere in between all of that, I had stopped appreciating how far I had already come. A colleague recently reminded me of that.

They congratulated me - not for an award, a publication, or anything particularly tangible but for inspiring them to work harder.

That conversation made me pause. Because some of the things that I now consider ordinary were things I had quietly hoped for six or twelve months ago.

And perhaps that is something we all do. We achieve something, get used to it, and immediately move the goalpost.

What was once a dream becomes today’s normal. And then we start feeling as though we haven’t done enough.

But perhaps we are measuring ourselves against the wrong people. Medicine makes comparison almost inevitable.

Someone has more publications.
Someone is giving more talks.
Someone is more senior.
Someone has achieved something earlier.
Someone seems to be progressing faster.

And if we constantly look sideways, there will always be someone ahead. There will always be another milestone.

Another CV.
Another achievement.
Another person who seems to have figured it all out.

So perhaps the more meaningful question isn’t:

“Am I doing better than them?”

It is:

“Am I doing better than the person I was six months ago?”

That is the comparison that matters.

Did I learn something I didn’t know before?
Did I handle a difficult situation better?
Did I become a little calmer?
Did I become more patient?
Did I listen better?
Did I become a better teammate?
Did I recover from setbacks a little faster?
Did I become a doctor I would have trusted a year ago?

Sometimes growth is not something you can put on a CV. Sometimes it is simply becoming a little better version of yourself. And that deserves recognition too.

As we become more senior in Emergency Medicine or in any branch of medicine—the job slowly changes.

Clinical knowledge and technical excellence remain essential. But they are no longer enough. You begin to understand that medicine is a team sport.

In Emergency Medicine, the patient doesn’t belong to one doctor. The resuscitation belongs to the entire team.

Doctors.
Nursing officers.
Technicians.
Radiographers.
Laboratory teams.
Housekeeping.
Security.

Every person who keeps the system moving.

And as you become more senior, leadership becomes less about being the person with all the answers and more about helping the entire team move forward.

Sometimes you compromise.
Sometimes you make a decision that isn’t your personal preference because it is better for the group. Sometimes you absorb the pressure so someone else doesn’t have to. And sometimes you do something important without anyone ever knowing that you did it.

There isn’t always recognition for leadership. And perhaps there shouldn’t be. Some of the most important things a leader does happen quietly, behind the stage.

You learn to remain calm when everyone around you is anxious. You learn to observe before reacting. You learn that not every problem needs an immediate answer. You learn that uncertainty isn’t always something to eliminate.

Sometimes, it is something you learn to navigate. And perhaps that is what fascinates me most about Emergency Medicine.

The art of uncertainty.
The art of acute care.
The ability to find some calm in chaos.
To make decisions with incomplete information.
To keep moving even when the outcome isn’t guaranteed.

Medicine also teaches us resilience. We see people arrive at some of the worst moments of their lives. Sometimes we help them through. Sometimes we don’t.

We experience failure, rejection, exhaustion, disappointment and uncertainty , professionally and personally.

And slowly, we learn that life will always bring obstacles. We cannot control all of them.But we can learn how to respond to them.

One of the hardest things to train is the mind itself. Especially when it naturally focuses on what went wrong, what is missing, or what could go wrong next.

But perhaps gratitude can be trained too. To notice the good. The colleague who supported you. The patient who got better. The mentor who believed in you. The team that stood beside you. The opportunity you once hoped for. The ordinary day when nothing went wrong. The quiet walk home after a difficult shift.

And sometimes, simply the realisation that you are already living a part of the life you once wished for.

Medicine also teaches us resilience. We see people arrive at some of the worst moments of their lives. Sometimes we help them through. Sometimes we don’t.

We experience failure, rejection, exhaustion, disappointment and uncertainty—professionally and personally.

And slowly, we learn that life will always bring obstacles. We cannot control all of them. But we can learn how to respond to them.

One of the hardest things to train is the mind itself. Especially when it naturally focuses on what went wrong, what is missing, or what could go wrong next.

Over time, I have realised that one part of resilience is actively choosing where to place your attention. Not pretending that the negative things didn’t happen. Not ignoring the difficult shifts, the mistakes, the losses or the disappointments.

But refusing to let them become the only story you tell yourself.

If a shift had ten difficult moments and one meaningful positive outcome, the mind can spend hours replaying the ten difficult ones. Sometimes, you have to consciously redirect it.

Remember the patient who improved.

Remember the decision that helped.

Remember the person you supported.

Remember the small thing that went right.

The negative deserves reflection. The positive deserves remembrance.

Perhaps that is another skill medicine teaches us—the ability to acknowledge what went wrong, learn from it, and then deliberately turn our attention back toward what went right.

Because what we repeatedly focus on eventually shapes how we experience our lives.

So this is my pulse check today.

Not a celebration of achievements.

Not a comparison with anyone else.

Just a reminder to myself to stop occasionally and look back.

To compare myself with the person I was—not with the person standing next to me.

To recognise the small changes.

The lessons.

The failures I survived.

The things I learned.

The person I am slowly becoming.

Because perhaps growth isn’t about constantly proving that you are ahead.

Perhaps it is simply being able to look back and say:

“I am not where I was.”

And maybe, for today, that is enough.

Keep growing.

Keep learning.

Keep moving forward.

But don’t forget to pause.

Look back.

Take a breath.

And be grateful.

Because somewhere behind you is a version of yourself who would probably be incredibly proud to see where you are today.

Pulse check: When was the last time you stopped; not to ask how far you still have to go, but to appreciate how far you’ve already come?

‘Medicine teaches us how to save lives.
Perhaps the journey also teaches us how to live one.’

- Dr Arihant Jain, MD

The recent r…

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Hyponatremia is one of the most common electrolyte abnormalities encountered in acute care. Yet when the sodium comes back at 118 mmol/L, the first instinct is often:

“How do I increase the sodium?”

That is not the first question we should ask.

Questions are:

Is the patient symptomatic?
Is this truly hypotonic hyponatremia?
How quickly did it develop?
And what is driving it?

Once those questions are answered, treatment becomes much easier. The following is a practical approach to hyponatremia for the ED and acute-care setting.

Step 1: Is the patient symptomatic?

This is the first and most important question.

Hyponatremia can range from completely asymptomatic to severe neurological deterioration.

Severe symptoms → treat as a neurological emergency

Think “cerebral edema / impending brain injury.”

• Seizures

• Marked reduction in consciousness

• Coma / GCS ≤8

• Deep or abnormal somnolence

• Persistent vomiting

• Cardiorespiratory distress/arrest

• Features suggesting raised ICP, such as bradycardia + hypertension + abnormal respiration, may occur in extreme cases

Severe neurological symptoms suggest clinically significant cerebral edema. Acute or severe symptomatic hyponatremia is a medical emergency. Do not wait for the complete diagnostic work-up before treating the cerebral edema.

US vs European Guidelines: How Should We Treat Symptomatic Hyponatremia?

Both the US and European recommendations consider acute or severe symptomatic hyponatremia a medical emergency and recommend 3% hypertonic saline as the treatment of choice. The important principle is that treatment is aimed at rapidly reversing cerebral edema and improving neurological symptoms but not normalizing the serum sodium concentration. The two approaches are broadly similar but differ in the dose and delivery of hypertonic saline.
The US recommendations suggest 100 mL of 3% saline over 10 minutes, which may be repeated up to three times, with an initial goal of increasing serum sodium by approximately 4–6 mmol/L. The European guideline instead recommends 150 mL of 3% saline over 20 minutes, with sodium reassessed after 20 minutes and the bolus repeated if necessary, up to three times, aiming for approximately a 5 mmol/L increase during the first hour or until symptoms improve.

The difference becomes more interesting when symptoms are moderate rather than severe. The European guideline recommends a single 150-mL bolus of 3% saline over 20 minutes, while the US recommendations describe a more controlled continuous infusion of 3% saline at 0.5–2 mL/kg/hour. The European approach emphasizes that moderately symptomatic patients should undergo prompt diagnostic assessment and cause-specific treatment, with a relatively modest sodium rise targeted over 24 hours.

The two guidelines also differ somewhat in how they approach the rate of correction. The European guideline recommends limiting the sodium increase to 10 mmol/L during the first 24 hours and an additional 8 mmol/L during each subsequent 24-hour period. The US recommendations are somewhat more conservative in their suggested correction target, generally aiming for 4–8 mmol/L/day, while allowing a maximum of approximately 10–12 mmol/L/day in patients without major risk factors for osmotic demyelination. In patients at particularly high risk of ODS such as those with alcohol excess, malnutrition, hypokalemia, or advanced liver disease the US recommendations advocate an even more conservative approach, with a maximum correction of approximately 4–8 mmol/L/day. Importantly, these numbers should be understood as upper limits, not therapeutic targets.

A practical way to reconcile the two approaches at the bedside is therefore: if the patient has severe neurological symptoms, do not delay treatment while completing the diagnostic work-up—give 3% saline as a monitored bolus and reassess both symptoms and sodium frequently. Once neurological symptoms improve after a modest rise in sodium, stop hypertonic saline and move toward cause-specific treatment. If symptoms fail to improve, reconsider whether hyponatremia is actually responsible for the neurological presentation and continue treatment only with close biochemical monitoring. The European guideline specifically recommends stopping hypertonic saline once symptoms improve after an approximately 5 mmol/L rise, while continuing therapy and reassessing alternative causes if symptoms persist.

Finally, both approaches place major emphasis on avoiding overcorrection. If the sodium begins rising faster than intended, treatment should be interrupted and free-water losses replaced; desmopressin can be used to stop ongoing water diuresis, with hypotonic fluid such as 5% dextrose used when relowering is required. The attached review emphasizes that the combination of desmopressin and free-water replacement can both prevent further sodium rise and, when necessary, actively relower the sodium toward the intended target.

The bedside takeaway

US: 100 mL 3% saline → 10 min → repeat as needed → aim for ~4–6 mmol/L rise.

Europe: 150 mL 3% saline → 20 min → repeat as needed → aim for ~5 mmol/L rise in the first hour.

Both: Treat the neurological emergency, reassess frequently, and never mistake the correction limit for the correction target.

Step 2: How quickly did the sodium fall?

The brain adapts to chronic hyponatremia.

That means the speed of onset matters at least as much as the absolute sodium value.

Acute

<48 hours

Chronic

>48 hours

Unknown duration?

For practical purposes, treat it as chronic when you cannot establish that it is acute.

Why?

Because a chronically hyponatremic brain has adapted to the low osmolality. Rapidly increasing plasma osmolality can injure the adapted brain and cause osmotic demyelination syndrome (ODS).

So remember:

A sodium of 118 is not automatically an indication to rapidly normalize the sodium.

The clinical context matters.

Step 3: Is this actually hypotonic hyponatremia?

A low serum sodium does not always mean that the plasma is hypotonic.

This is where serum osmolality becomes useful.

Low sodium + LOW serum osmolality

→ Hypotonic hyponatremia (True Hyponatremia)

This is the major group we need to investigate further.

Low sodium + NORMAL osmolality

→ Think pseudo-hyponatremia

• Hyperproteinemia

  • Multiple myeloma

  • Waldenström macroglobulinemia

  • Marked hypergammaglobulinemia

• Hyperlipidemia

  • Severe hypertriglyceridemia

  • Occasionally severe hypercholesterolemia

Low sodium + HIGH osmolality

→ Think hypertonic hyponatremia

A classic example is severe hyperglycemia, where glucose contributes to plasma osmolality and lowers the measured sodium concentration.

So:

Do not start by asking “Why is the sodium low?”
First ask: “Is this true hypotonic hyponatremia?”

Step 4: If it is hypotonic — what is the kidney doing?

This is where the diagnostic approach becomes much simpler.

Send:

Urine osmolality + urine sodium

Ideally, obtain the urine sample before major therapeutic interventions whenever possible.

Urine osmolality <100 mOsm/kg

Think:

AVP (ADH) is off

The kidney is appropriately trying to get rid of free water.

Consider:

• Excess water intake

• Primary polydipsia

• Low-solute intake

The urine is maximally dilute because the kidney is capable of excreting free water.

Urine osmolality >100 mOsm/kg

Think:

AVP is ON

The kidney is retaining water when, in a hypotonic state, it should be trying to excrete it.

Now ask:

Why is AVP switched on?

And this is where we move to the clinical phenotype.

STEP 5 — WHERE IS THE SODIUM GOING?

Urine Na <20–30 mmol/L → Sodium conserving

Urine Na >30 mmol/L → Renal sodium loss OR SIAD

Step 6: What is the patient’s volume status?

There are three broad phenotypes:

1. Hypovolemic

2. Euvolemic

3. Hypervolemic

But there is an important caveat:

Clinical assessment of volume status is imperfect.

It is actually one of the least accurate parts of the diagnostic process, with reported sensitivity and specificity below 50%.

So don’t let the words “euvolemic” or “hypovolemic” end your diagnostic reasoning.

This is why urine studies are so helpful.

1. Hypovolemic hyponatremia

Think:

“The patient has lost sodium and water — but has lost relatively more sodium.”

Common causes include:

• Vomiting

• Diarrhea

• Gastrointestinal losses

• Diuretics, particularly thiazides

• Renal salt losses

• Adrenal insufficiency

Volume depletion activates baroreceptor-mediated AVP secretion.

So even though the plasma is hypotonic, the kidney continues to retain water.

That combination produces hyponatremia.

Urine sodium helps

Broadly:

Low urine Na⁺ → suggests sodium conservation, often from extrarenal losses.

Higher urine Na⁺ → consider renal sodium loss, diuretics or other causes.

But remember:

Diuretics can make urine sodium difficult to interpret.

2. Euvolemic hyponatremia

This is where SIAD enters the picture.

The patient appears clinically euvolemic, but there is excess total body water relative to sodium.

Common triggers of inappropriate antidiuresis include:

• CNS disease

• Pulmonary disease

• Malignancy

• Drugs

• Pain

• Nausea

• Surgery

But don’t call every euvolemic patient with hyponatremia “SIAD.”

A diagnosis of SIAD requires a compatible biochemical picture and exclusion of important alternatives.

Think:

Hypotonic hyponatremia

• UOsm >100 mOsm/kg

• Urine Na⁺ >30 mmol/L

• No significant renal failure

• No recent diuretic use

• Exclude adrenal insufficiency and hypothyroidism

This last point is important:

Adrenal insufficiency can look remarkably similar to SIAD.

So before labeling a patient as SIAD, make sure you have considered cortisol deficiency.

3. Hypervolemic hyponatremia

Here the patient has an excess of total body sodium and water — but proportionally more water.

Think:

• Heart failure

• Cirrhosis

• Renal failure

• Nephrotic states

The treatment is primarily directed at the underlying disease and the abnormal sodium/water balance.

Now comes the most important part: Treatment

There is no single treatment for “hyponatremia.”

Treatment depends on why the sodium is low and whether the patient is symptomatic.

1. Hypertonic saline: treat symptomatic cerebral edema

For acute or severe symptomatic hyponatremia, 3% saline is the treatment of choice.

The review describes bolus-based approaches from both US and European recommendations.

US approach

100 mL of 3% saline over 10 minutes

May be repeated, with a maximum of three boluses.

European approach

150 mL of 3% saline over 20 minutes

Again, repeat dosing may be required according to clinical and biochemical response.

The important concept is:

Give enough hypertonic saline to improve the neurological emergency — not enough to normalize the sodium.

2. Isotonic saline: treat hypovolemic hyponatremia

If the problem is volume depletion:

Restore circulating volume.

Giving isotonic saline reduces the non-osmotic stimulus for AVP release.

As AVP falls, the kidney can suddenly begin excreting large amounts of free water.

And this creates an important ED trap:

The sodium can suddenly rise much faster than expected.

An increase in urine output—particularly >100 mL/hour—can be an early warning sign of impending overcorrection.

So after starting fluids:

Don’t just watch the sodium.

Watch the urine output.

3. Fluid restriction: mainly for SIAD

For patients with SIAD without severe neurological symptoms, fluid restriction is commonly used.

But its effectiveness depends on how strongly AVP is driving water retention.

A very concentrated urine—for example, UOsm >500 mOsm/kg—predicts a poorer response to fluid restriction.

So:

Fluid restriction is not automatically effective just because the patient has SIAD.

4. Other options

Depending on the underlying cause and clinical setting, other approaches may include:

SIAD

• Fluid restriction

• Oral urea

• Loop diuretic + oral sodium in selected patients

• Vasopressin receptor antagonists in selected circumstances

Hypervolemic hyponatremia

• Treat the underlying disease

• Fluid/sodium restriction where appropriate

• Diuretics

• Selected use of vasopressin antagonists

The evidence and guideline recommendations differ for some of these therapies, particularly vaptans and loop-diuretic strategies.

And finally: Don’t forget overcorrection

This may be the most important safety principle in managing chronic or unknown-duration hyponatremia.

The correction limit is a ceiling — not a target.

For chronic or unknown-duration hyponatremia, the review summarizes:

• European guidance: maximum 10 mmol/L in the first 24 h, then 8 mmol/L/day

• US recommendations: generally a more conservative target of 4–8 mmol/L/day, with a maximum limit of 8–12 mmol/L/day

• In patients at high risk of ODS—such as those with alcoholism, malnutrition, hypokalemia or advanced liver disease—more conservative correction is advised.

The exact threshold should therefore be interpreted in the context of chronicity and ODS risk.

What if the sodium is rising too quickly?

Stop the process.

Then:

Replace free-water losses

Desmopressin

±

5% dextrose / free water

The combination of desmopressin and free-water replacement can be used to stop further sodium rise or, when necessary, actively relower the sodium toward the intended target.

This is particularly important when the patient suddenly begins producing large volumes of dilute urine after the underlying stimulus for AVP secretion disappears.

One final principle

Hyponatremia is not simply a problem of “too little sodium.”

It is usually a problem of too much water relative to sodium.

Once you start thinking in terms of:

Symptoms → Osmolality → AVP → Urine Osm → Urine Na → Cause → Treatment

the seemingly complicated hyponatremic patient becomes much easier to approach.

Treat the brain.
Define the physiology.
Find the cause.
Correct carefully.

That is the bedside approach to hyponatremia.

DISCLAIMER: For Educational Purposes only!

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You look at the ABG:

pH 7.20
PaCO₂ 40 mmHg
HCO₃⁻ 15 mmol/L

The diagnosis seems straightforward:

Metabolic acidosis.

But then comes the more important question:

Why is the bicarbonate low?

Is it lactate?
Too much chloride?
Hypoalbuminemia masking the acidosis?
Renal dysfunction?
Ketones?
Unmeasured anions?
Or a combination of several processes occurring simultaneously?

This is where the Stewart approach becomes useful. Not because the traditional Henderson–Hasselbalch approach is wrong.

But because sometimes:

Henderson–Hasselbalch tells you what is happening. Stewart helps you understand what is driving it.

Don’t throw away the traditional ABG approach

For most patients in the ED, start conventionally as we discussed in the previous post ABG Series #4

pH → PaCO₂ → HCO₃⁻ → anion gap → compensation → clinical context

This is fast, familiar and clinically useful.

The problem arises when the patient has multiple simultaneous processes.

A critically ill patient may have:

• lactic acidosis from shock

• hyperchloremia from saline

• hypoalbuminemia

• renal dysfunction

• unmeasured anions

• and a respiratory disorder

…and these processes can partially cancel each other out. The ABG may therefore look deceptively simple. This is exactly where a quantitative approach can add another layer of understanding.

The Stewart idea: What actually determines pH?

Stewart’s approach starts with a different question. Instead of treating bicarbonate and hydrogen ions as independent causes of acid–base disturbance, it considers three major independent variables:

1️⃣ PaCO₂

The respiratory component.

2️⃣ Strong Ion Difference — SID

The difference between fully dissociated cations and anions.

3️⃣ Total concentration of weak acids — Aₜₒₜ

Primarily albumin and phosphate in plasma.

In the full Stewart model, these variables interact through the principles of mass conservation, electrical neutrality and chemical equilibrium. As Story explains, H⁺ and HCO₃⁻ are dependent variables in this framework; their concentrations are determined by PaCO₂, SID and Aₜₒₜ. (Story, 2016). modified abg (1)(4)

That sounds intimidating. Fortunately, you don’t need six simultaneous equations to use the concept at the bedside.

The Physician-friendly version

David Story proposed a simplified bedside approach that translates the Stewart concept into something much more practical. (Story, 2016).

The idea is to deconstruct the base excess (BE) into clinically recognizable components. Think of BE as the net metabolic effect.

Then ask:

What is making the patient acidotic, and what is simultaneously pushing the pH in the opposite direction?

Story’s simplified approach breaks this into:

1. Na⁺–Cl⁻ effect

2. Lactate effect

3. Albumin effect

4. Other ions* - most important component

And together:

BE = Na–Cl effect + Lactate effect + Albumin effect + Other ions

Let me explain simply

Total metabolic component = NAGMA + HAGMA + Met. Alkalosis

Total Metabolic component = Base Excess

NAGMA plus Met. Alkalosis = Na- Cl Component - SID

HAGMA = lactate plus ketones plus urea and other unmeasured causes

and Albumin effect

1. The Na⁺–Cl⁻ component

This is one of the most clinically useful Stewart concepts in the ED. For the simplified bedside calculation:

NAGMA and Metabolic alkalosis component = (Na − Cl) − 35

Na - Cl > 35 - Met alkalosis

Na- Cl < 35 - NAGMA

The reference Na−Cl difference is approximately 35 mEq/L.

If the difference becomes smaller, the effect is acidifying.

Example

Na = 140
Cl = 115

Na − Cl = 25

Therefore:

25 − 35 = −10 mEq/L

That’s a substantial acidifying effect. And this is where the familiar ED scenario becomes relevant:

Large-volume normal saline.

Normal saline contains a relatively high chloride concentration. As chloride accumulates, the Na−Cl difference narrows → SID decreases → metabolic acidosis develops.

This is the physiological basis behind hyperchloremic metabolic acidosis.

The clinical example also highlights how fluid choice can influence this component: a lower-chloride fluid would be expected to widen the Na−Cl difference and reduce this acidifying effect.

So instead of simply saying:

“The patient has NAGMA.”

Stewart lets you ask:

“Is chloride actually driving part of this acidosis?”

That’s a much more actionable question.

2. Lactate

The next component is easier.

Lactate effect = 1 − measured lactate

with 1 mmol/L as the reference value.

So if lactate = 5:

1 − 5 = −4 mEq/L

That’s an acidifying effect. This immediately links the physiology to the clinical picture:

Shock → tissue hypoperfusion → increased lactate → increased strong anion burden → metabolic acidosis.

But here’s an important point:

Lactate may not explain the entire acidosis.

A patient with lactate 5 may have:

• lactate-driven acidosis

• hyperchloremic acidosis

• hypoalbuminemic alkalinization

• and another unidentified acidifying process

all at the same time. And that’s where the next component becomes important.

3. Albumin: the hidden alkalinizer

This is probably one of the most clinically useful lessons from the Stewart framework. Albumin is a weak acid. Therefore:

Lower albumin → less weak acid → alkalinizing effect.

Story’s simplified calculation is:

Albumin effect = 0.25 × (42 − albumin in g/L)

with 42 g/L as the reference albumin concentration.

For example:

Albumin = 22 g/L

0.25 × (42 − 22)
= +5 mEq/L approximately

That’s an alkalinizing effect. And this matters enormously in critically ill patients. Because a patient can simultaneously have:

Lactic acidosis + hyperchloremia while hypoalbuminemia is partially masking the severity of the metabolic acidosis.

So a “not too bad” pH does not necessarily mean a mild metabolic disturbance. The patient may have several opposing processes.

4. And then comes the most interesting component:

“Other ions”

This is where Stewart becomes particularly interesting clinically.

After accounting for:

• Na–Cl

• lactate

• albumin

there may still be an unexplained component of the base excess. Story refers to this as other ions, encompassing measured and unmeasured cations and anions. Ketoacids, Phosphate, sulfate and other unmeasured ions may become particularly relevant in organ dysfunction.

You can calculate it as a residual:

Other ions = BE − (Na–Cl effect + lactate effect + albumin effect)

And this is where the calculation can become a clinical clue.

What if “Other ions” is −6?

Imagine:

Other ions = −6 mEq/L

after accounting for lactate and albumin.

That means:

Your currently identified causes don’t completely explain the metabolic acidosis.

And this is the key clinical interpretation:

The “other ions” component doesn’t tell you what the diagnosis is. It tells you that your current explanation is incomplete.

Now broaden the differential.

Could there be significant renal dysfunction with retention of acidifying ions such as urate, sulfate, phosphate and other organic anions?

Could there be ketones?

Could there be another unmeasured anion?

And if those explanations don’t fit, particularly in the right clinical context, could this represent a toxic ingestion?

For example:

• methanol

• ethylene glycol

• other toxic causes of high-anion-gap metabolic acidosis

The ED may not immediately have access to every specific toxin assay. But the physiology can tell you:

“There is something here that I haven’t accounted for.”

That should trigger targeted investigation rather than premature closure. And importantly, a negative “other ions” residual does not diagnose a toxin. It is a signal to reconsider the differential using the history, renal function, ketones, lactate, anion/osmolal gaps and clinical context.

Let’s put everything together

A worked example makes this much easier to understand.

Patient:

• Na⁺ = 133 mmol/L

• Cl⁻ = 110 mmol/L

• Albumin = 22 g/L

• Lactate = 5 mmol/L

• pH = 7.20

• PaCO₂ = 40 mmHg

• HCO₃⁻ = 15 mmol/L

• BE = −11.5 mmol/L

At first glance:

Metabolic acidosis.

But Stewart asks:

What all is contributing to that BE = − 11.5?

a. Na–Cl ( sum of NAGMA plus Met. Alkalosis component)

(133 − 110) − 35 = −12 mEq/L

Strong acidifying effect.

b. Lactate

1 − 5 = −4 mEq/L

Another acidifying effect.

c. Albumin

0.25 × (42 − 22) = +5.5 mEq/L

An alkalinizing effect.

d. Other ions

We already know:

BE = −11.5

So:

Other ions = −11.5 − [−12 + (−4) + 5.5] = approximately −1 mEq/L

Put everything together:

BE = −12 − 4 + 5.5 − 1

BE ≈ −11.5 mEq/L

Exactly matching the measured BE.

Now the ABG is no longer simply:

“Metabolic acidosis.”

We can tell a much richer story:

Hyperchloremic/low Na–Cl contribution

• lactic acidosis

• hypoalbuminemic alkalinization

• small residual other-ion effect

And there is another important observation.

With HCO₃⁻ around 15 mmol/L, expected PaCO₂ by Winter’s formula would be approximately 30–32 mmHg.

But PaCO₂ is 40 mmHg.

So this patient also has a respiratory acidosis.

Now the physiology starts making sense:

Multiple disorders are occurring simultaneously—and some are masking others.

Why does this matter in the ED and acute care?

Because ED patients rarely arrive with a single textbook disorder. Consider the septic patient who has:

Lactate ↑
Normal saline resuscitation
Albumin ↓
AKI developing
Possible ketosis
Respiratory fatigue

The traditional approach may tell you:

“Mixed metabolic acidosis.”

Useful - but incomplete. The Stewart lens asks:

Which processes are actually pushing the pH in each direction?

That distinction matters because the answer may influence what you do next.

If chloride is the problem:

Think about ongoing chloride-rich fluid exposure.

If lactate dominates:

Treat the underlying perfusion problem.

If hypoalbuminemia is substantial:

Recognize that it may be masking part of the metabolic acidosis.

If renal dysfunction is present:

Think beyond urea alone—the acidifying effect is related to retention of sulfate, phosphate and other acids/anions.

If a significant unexplained residual remains:

Look for ketones, unmeasured anions and—when clinically appropriate—toxic causes.

The point isn’t to calculate numbers for the sake of calculation.

The point is to connect the ABG to the patient’s physiology.

Why is it particularly relevant in acute care?

Because acute-care medicine is full of rapidly changing iatrogenic physiology. The patient’s acid–base status is not static. Fluids change chloride. Blood products and medications alter the ionic environment. Resuscitation changes lactate. Renal function evolves. Albumin changes. Ventilation changes PaCO₂.

And the patient may move from one dominant process to another within hours.

Story specifically emphasizes that the simplified Stewart approach can help understand the patient’s current acid–base status and anticipate the acid–base consequences of future fluids and therapies. modified abg (1)(4)

That makes it particularly relevant to:

Resuscitation → ICU transfer → ventilation → renal replacement → ongoing fluid therapy

rather than being merely an academic alternative to Henderson–Hasselbalch.

But is Stewart better than the traditional approach?

This is where we need to be honest.

Not necessarily.

The Stewart approach provides a mechanistic framework and can make complex mixed disorders easier to understand.

But it is more cumbersome. Studies comparing Stewart-based approaches with traditional methods have often found that much of the additional information can also be obtained using albumin-corrected anion gap and conventional acid–base analysis.

Rastegar (2009), for example, concluded that Stewart’s method offers a mechanistic explanation but did not demonstrate clear superiority in diagnostic, management or prognostic performance over traditional approaches.

More recent work continues to support a pragmatic position: conventional approaches work well for many patients, while a simplified Stewart approach becomes particularly useful when multiple metabolic processes coexist or appear to be offsetting each other.

So the message isn’t:

❌ “Forget Henderson–Hasselbalch.”

It is:

✅ “Know when the traditional framework isn’t telling you enough.”

The take-home message

Stewart can initially feel unnecessarily complicated.

But at the bedside, its most useful lesson is actually quite simple:

Acid–base disorders are often not one problem. They are several processes happening simultaneously.

A patient can be:

acidotic from chloride
acidotic from lactate
acidotic from unmeasured ions
while being
alkalotic from hypoalbuminemia

—all at the same time.

And the final pH is simply the result of those competing forces.

So remember:

—> Henderson–Hasselbach tells you WHAT is happening.

—> Base excess tells you the NET metabolic effect.

—> Stewart helps you understand WHAT is DRIVING that effect.

And perhaps the most useful lesson of all:

When the “other ions” component is abnormal, don’t immediately ask, “What toxin is this?”

Ask, “What have I not explained yet?”

Because in acute care, an unexplained residual is often more valuable than a falsely reassuring explanation.

Preferred Reads -

1. Story DA. Stewart acid-base: a simplified bedside approach. Anesth Analg. 2016;123(3):511-515. doi:10.1213/ANE.0000000000001261

2. Rastegar A. Clinical utility of Stewart’s method in diagnosis and management of acid-base disorders. Clin J Am Soc Nephrol. 2009;4(7):1267-1274. doi:10.2215/CJN.01870309

3. Duška F, Krbec M, Heldeweg M, Elbers PWG, Giosa L. A pragmatic approach to complex acid base disturbances of critical illness: the “Stewart light.” Intensive Care Med. 2026;52(6):1322-1325. doi:10.1007/s00134-026-08416-3.

A patient arrives tachypneic.

ABG:

pH 7.21
PaCO₂ 24 mmHg
HCO₃⁻ 10 mmol/L

You say:

“Metabolic acidosis.”

But is that the whole diagnosis?

What does acidemia actually mean?
Is acidosis the same thing?
What does the base excess tell you?
Is this HAGMA or NAGMA?
Is the respiratory response appropriate?
Could there be a second metabolic disorder hiding underneath?

And importantly:

Can a patient have a normal pH and still have a major acid–base disorder?

This is where we move beyond simply reading the bicarbonate.

1. Acidemia ≠ Acidosis

This should be the first major teaching point.

Acidemia

A state of the blood in which:

pH < 7.35

Acidosis

A physiological process that tends to lower pH.

Similarly:

Alkalemia

pH > 7.45

Alkalosis

A physiological process that tends to raise pH.

Why does this distinction matter?

Because a patient can have multiple simultaneous processes. For example:

Metabolic acidosis + metabolic alkalosis

may produce a near-normal pH.

So:

A normal pH does not exclude an acid–base disorder.

And:

Acidemia tells you the net result. Acidosis tells you about one of the processes producing that result.

2. Where does the metabolic component fit?

Once you identify the pH, look at:

PaCO₂ + HCO₃⁻

Metabolic acidosis

HCO₃⁻ ↓

Metabolic alkalosis

HCO₃⁻ ↑

But don’t immediately label the disorder.

First ask:

Is the change appropriate compensation, or is another disorder present?

3. Base Excess: the often-underused number on the ABG

Base excess summarises the complete metabolic component of an acid–base disorder, independent of the respiratory component.

Base excess is the amount of strong acid or base required to return blood to pH 7.40 under standardized conditions, with a normal range around −3 to +3 mmol/L. modified abg (1)(3)

Think of it simply:

Negative BE → metabolic acidosis
Positive BE → metabolic alkalosis

For example:

BE −12 → significant metabolic acid load / base deficit.

BE +8 → metabolic alkalosis.

Base deficit vs base excess

Be careful with terminology:
Base excess −10
and
Base deficit +10

describe the same direction of metabolic disturbance but use opposite signs.

Practical message

HCO₃⁻ tells you the bicarbonate concentration. Base excess helps quantify the metabolic component.

4. Metabolic Acidosis

Now build the actual framework.

Typical ABG:

pH ↓
HCO₃⁻ ↓

The PaCO₂ should fall as respiratory compensation develops.

But we need to determine:

1. Is compensation appropriate?

2. Is there an anion gap?

3. If there is an anion gap, is there another metabolic disorder?

5. Step 1 — Check respiratory compensation

Winter’s formula

Expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2

Example

HCO₃⁻ = 12

Expected:

1.5 × 12 + 8 = 26

Expected PaCO₂:

24–28 mmHg

If actual PaCO₂ is:

26

→ appropriate compensation

40

→ metabolic acidosis + respiratory acidosis

18

→ metabolic acidosis + respiratory alkalosis

So:

Compensation should be calculated, not assumed.

6. Step 2 — Find the Anion Gap

AG = Na⁺ − (Cl⁻ + HCO₃⁻)

12 ± 4 mEq/L as the conventional normal range. (Confirm with your own lab)

The conceptual question is:

Why has bicarbonate fallen?

7. HAGMA (High-Anion-Gap Metabolic Acidosis)

Here, acids accumulate and their accompanying anions are not routinely measured.

Think:

“New unmeasured anions have appeared.”

GOLD MARK

G — Glycols
O — Oxoproline
L — L-lactate
D — D-lactate
M — Methanol
A — Aspirin
R — Renal failure
K — Ketoacidosis

Then add the clinical context:

• DKA

• Alcoholic ketoacidosis

• Starvation ketoacidosis

• Lactic acidosis

• Renal failure

• Toxic alcohols

• Salicylates

8. Don’t forget albumin

Albumin is an important unmeasured anion.

Therefore:

Hypoalbuminemia can make the anion gap look deceptively normal.

Corrected AG

Corrected AG = measured AG + 2.5 × (4 − albumin g/dL)

Your source gives this correction explicitly. modified abg (1)(3)

Example

AG = 14
Albumin = 2 g/dL

Corrected AG:

14 + 2.5 × (4−2) = 19

So what initially looked like a modest AG may actually represent a significant HAGMA.

9. NAGMA (Normal-Anion-Gap Metabolic Acidosis)

Also called:

Hyperchloremic metabolic acidosis

Here:

HCO₃⁻ ↓ but:

Cl⁻ ↑

maintains electrical neutrality.

Major causes

GI bicarbonate loss

• Diarrhea

• High-output intestinal losses

Renal

• Renal tubular acidosis

Drugs

• Acetazolamide

Iatrogenic

• Large-volume 0.9% saline

The key mental model:

HAGMA = addition of unmeasured acid/anions
NAGMA = bicarbonate loss/reduction with relative chloride increase

10. But what if the patient has TWO metabolic disorders?

This is where the article becomes more interesting.

Delta gap / Delta ratio

Once you identify HAGMA:

ΔAG

AG − 12

ΔHCO₃

24 − measured HCO₃

Then:

Delta ratio = ΔAG / ΔHCO₃

<1 - HAGMA + NAGMA
1–2 - Predominantly HAGMA
>2 - HAGMA + metabolic alkalosis

11. Why is this useful?

Imagine: AG = 30

Therefore: ΔAG = 18

And: HCO₃⁻ = 18

Therefore: ΔHCO₃ = 6

Delta ratio:

18 / 6 = 3

That’s too high for a pure HAGMA.

It suggests:

HAGMA + metabolic alkalosis

This is exactly the type of patient we miss if we stop at:

“The patient has DKA.”

12. Metabolic Alkalosis

the other side of the metabolic spectrum.

Typical pattern:

pH ↑

HCO₃⁻ ↑

The respiratory response should be:

PaCO₂ ↑

because hypoventilation provides respiratory compensation.

A useful approximation:

Expected PaCO₂ ≈ 0.7 × (HCO₃⁻ − 24) + 40 ± 2

Again:

If the PaCO₂ is substantially outside the expected range, think:

Metabolic alkalosis + a second respiratory disorder.

13. Causes of metabolic alkalosis

I’d keep this clinically oriented rather than getting too deep into renal physiology.

Vomiting / gastric losses

Loss of:

H⁺ + Cl⁻

→ metabolic alkalosis

Nasogastric suction

Same principle.

Diuretics

Especially:

• Loop diuretics

• Thiazides

Volume/chloride depletion

The alkalosis can be maintained by continued volume and chloride depletion.

Mineralocorticoid excess

Think:

• Primary hyperaldosteronism

• Cushing physiology

• Other mineralocorticoid states

Hypokalemia

Can contribute to maintenance of alkalosis.

14. Chloride-responsive vs chloride-resistant

Chloride-responsive

Think:

Vomiting | NG suction | prior diuretic use | volume depletion

Chloride-resistant

Think:

Mineralocorticoid excess | ongoing renal causes | severe hypokalemia

This gives the reader a practical next step after simply identifying metabolic alkalosis.

15. Mixed metabolic disorders

Example 1

DKA + diarrhea

→ HAGMA + NAGMA

Example 2

DKA + vomiting

→ HAGMA + metabolic alkalosis

Example 3

Diarrhea + vomiting

→ NAGMA + metabolic alkalosis

Example 4

Sepsis + lactic acidosis + vomiting

→ HAGMA + metabolic alkalosis

And these can coexist with a respiratory disorder as well.

16. The “normal pH” trap

pH 7.40 does not mean normal.

look at the anion gap, normal pH with increased anion gap, might mean it is mixed disorder

look at base excess/deficit if abnormal , it is mixed disorder (respiratory plus metabolic)

A patient may have:

Metabolic acidosis + metabolic alkalosis

with the two processes partially cancelling each other.

(to look at elevated anion gap for this)

Or:

Metabolic acidosis + respiratory alkalosis

producing a relatively normal pH.

(To look at anion gap and base excess for this)

Final message of the article

Don’t let the pH fool you.

Acidemia is a state. Acidosis is a process.

Base excess tells you about the metabolic component.

The anion gap tells you where to look.

The delta ratio tells you whether one metabolic process is enough.

And compensation tells you whether the lungs are responding appropriately — or whether another respiratory disorder is hiding underneath.

The goal isn’t to name the abnormal number.

The goal is to explain the entire acid–base picture.

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We often learn a simple rule:

PaCO₂ 35–45 mmHg = normal ventilation.

But physiology doesn’t always follow the reference range.

PaCO₂ has to be interpreted in context.

Here are 3 patients who can make a “normal” PaCO₂ look very different.

CASE 1 — The acidotic patient with a PaCO₂ of 30

A 24-year-old man with severe DKA arrives tachypnoeic and dehydrated.

ABG:

pH 7.10
HCO₃⁻ 8 mmol/L
PaCO₂ 25 mmHg

At first glance:

“PaCO₂ is low. He’s ventilating well.”

But here’s the important question:

Is PaCO₂ of 25 actually appropriate for this degree of metabolic acidosis?

Use Winter’s formula:
Expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2

= 1.5 × 8 + 8
= 20 ± 2 mmHg

His PaCO₂ is 25 mmHg.

So despite the fact that his PaCO₂ is low, it is higher than expected. He is not compensating adequately.

There may already be an additional respiratory acidosis. This is one of the most important concepts when assessing ventilation:

The “normal” PaCO₂ is not necessarily 40.
The appropriate PaCO₂ depends on the metabolic disturbance.

In severe metabolic acidosis, the patient’s low PaCO₂ is part of the compensatory response. The ventilatory response can become so important that losing it during intubation may cause a rapid rise in PaCO₂ and worsening acidemia.

I wrote about this in detail here:

Ventilating the Acidotic Patient: VCV Strategies to Preserve Compensation

The key lesson:
Don’t ask:

“Is the PaCO₂ normal?”

Ask:

“Is the PaCO₂ appropriate for this patient’s metabolic state?”

CASE 2 — The pregnant patient with a PaCO₂ of 40

A 30-year-old woman in her third trimester presents with dyspnea.

ABG:
pH 7.40
PaCO₂ 40 mmHg
HCO₃⁻ 24 mmol/L

Looks completely normal. Right?

Not necessarily.

Pregnancy changes the baseline. Progesterone increases respiratory drive, producing increased minute ventilation and a physiological respiratory alkalosis.

Typical pregnancy values are approximately:

PaCO₂: 28–32 mmHg
HCO₃⁻: 18–21 mmol/L
pH: ~7.40–7.47

So in a pregnant patient:
PaCO₂ of 40 mmHg is not reassuring.

It may represent relative hypoventilation compared with the expected pregnancy baseline. In fact, literature describing obstetric critical illness notes that a PaCO₂ of 35–40 mmHg during pregnancy can indicate respiratory compromise.

Why does this matter? Because maternal CO₂ needs to remain lower than fetal CO₂ to maintain the maternal–fetal CO₂ gradient and facilitate fetal CO₂ elimination.

So remember:

A “normal” PaCO₂ in pregnancy may actually be abnormal.

Reference ranges are not universal truths.

They are population-dependent.

CASE 3 — The patient with hypercapnia

Now let’s say the PaCO₂ really is high. PaCO₂ 65 mmHg

What do you do? Don’t immediately write:

“Hypercapnic respiratory failure.”

Instead ask:

WHY is the CO₂ high?

Because hypercapnia is a physiological signal, not a diagnosis.

My previous Life on the Frontline post frames it beautifully:

Hypercapnia means alveolar ventilation is inadequate relative to CO₂ production.

And that can happen through several mechanisms.

Quick link : Acute Hypercapnia: A Mechanistic Approach to Ventilator Troubleshooting

1. The patient WON’T breathe

Central / drive problem

The respiratory drive is inadequate.

Think:

• Opioids

• Sedatives

• CNS disease

• Brainstem injury

• Central hypoventilation

• Inadequate ventilatory response to metabolic demand

The lungs may actually be structurally normal.

The problem is control.

2. The patient CAN’T breathe

Mechanical / pump problem

The patient has respiratory drive — but effective ventilation is limited.

Think:

• COPD

• Asthma

• Airway obstruction

• Dynamic hyperinflation

• Intrinsic PEEP

• Increased dead space

Here, simply increasing the respiratory rate may actually make things worse if it further reduces expiratory time and increases air trapping.

3. The patient is being asked to do more than they can

This is an under-appreciated mechanism.

For example:

Severe metabolic acidosis

The metabolic demand for CO₂ elimination is enormous.

The patient may be breathing at 30–40/min and generating huge minute ventilation just to maintain the compensatory PaCO₂.

If that compensation becomes inadequate:

PaCO₂ rises → pH falls further → physiology deteriorates.

This is why a rising PaCO₂ in severe metabolic acidosis can be particularly dangerous.

So how should we read ventilation on an ABG?

Don’t use:

PaCO₂ = 35–45 → “normal ventilation”

as your only rule.

Instead:

STEP 1

Look at PaCO₂.

Is it high, low or apparently normal?

STEP 2

Ask whether it is appropriate for the metabolic state.

In metabolic acidosis:

Use Winter’s formula.

STEP 3

Know the patient’s physiological baseline.

Pregnancy is a classic example.

STEP 4

If PaCO₂ is elevated:

Find the mechanism.

Won’t breathe?
Can’t breathe?
Or simply can’t meet the metabolic demand?

Read next

For a deeper dive into the mechanisms behind rising PaCO₂ and how to troubleshoot hypercapnia:

Acute Hypercapnia: A Mechanistic Approach to Ventilator Troubleshooting

And for the special problem of preserving respiratory compensation in severe metabolic acidosis:

Ventilating the Acidotic Patient: VCV Strategies to Preserve Compensation

Next in ABG Series → Deep dive into metabolic problems

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We often look at an ABG, see a low PaO₂, and immediately say:

“The patient is hypoxic.”

But technically, that may not be correct.

Hypoxemia and hypoxia are related—but they are not the same thing.

And when reading an ABG, PaO₂ is only the beginning of the oxygenation story.

This is ABG Series #2 — a practical approach to understanding oxygenation before we dive into acid–base disorders.

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1. Hypoxemia vs Hypoxia

1.1. Hypoxemia

Low oxygen in arterial blood.

On an ABG, we primarily assess this using:

• PaO₂

• SaO₂

A typical PaO₂ of 70–100 mmHg and SaO₂ of 93–98% as reference values at room air.

1.2. Hypoxia

Inadequate oxygen delivery or utilization at the tissue level.

This is a broader physiological problem.

A patient can therefore have:

Hypoxemia → impaired oxygen delivery → tissue hypoxia

…but tissue hypoxia can also occur without significant hypoxemia.

The infographic above shows four broad mechanisms of hypoxia: hypoxemic, ischemic, anemic and cytopathic hypoxia.

Think of it this way:

Hypoxemia = problem with oxygen in arterial blood

Hypoxia = problem with oxygen availability/use at the tissue level

2. So what exactly does the PaO₂ tell me?

PaO₂ = partial pressure of oxygen dissolved in arterial plasma.

It tells us about the oxygen tension in arterial blood.

It does not directly tell us:

• how much oxygen is carried by haemoglobin

• whether tissues are receiving enough oxygen

• whether cardiac output is adequate

• whether cells can utilize oxygen

That’s why PaO₂ should not be interpreted in isolation.

The ABG itself is designed to assess oxygenation, ventilation and acid–base status, while also providing information relevant to oxygen-carrying capacity.

3. The oxygenation question I ask first

When I see an ABG, don’t simply ask:

“Is PaO₂ low?”

Ask:

“Is this PaO₂ appropriate for the amount of oxygen the patient is receiving?”

That’s a much more useful question.

Because:

PaO₂ 80 mmHg on room air

is very different from

PaO₂ 80 mmHg on FiO₂ 0.80.

The number is identical.

The physiology isn’t.

4. Steps to decipher oxygenation status

4.1. Step 1 — Know the FiO₂

Before interpreting PaO₂, determine:

What is the patient breathing?

Room air:

FiO₂ ≈ 0.21

Supplemental oxygen:

FiO₂ depends on the device, flow, patient breathing pattern and interface.

This is particularly important because calculations such as the A–a gradient require an accurate FiO₂; estimation becomes less reliable with devices such as nasal cannulae , simple face masks and NRBM.

4.2. Step 2 — Look at PaO₂ and SaO₂

A “normal” PaO₂ doesn’t automatically mean normal oxygenation.

Always interpret it in relation to FiO₂.

4.3. Step 3 — Calculate the P/F ratio

One of the simplest ways to account for the inspired oxygen is:

P/F ratio = PaO₂ ÷ FiO₂

Example:

PaO₂ = 60 mmHg

FiO₂ = 0.50

Therefore:

P/F = 60 ÷ 0.5 = 120 mmHg

The source material describes a normal P/F ratio as approximately 300–500 mmHg, with lower values indicating impaired gas exchange.

Why is this useful?

Because:

PaO₂ tells you the oxygen tension.

P/F tells you how effectively the lungs are achieving that PaO₂ given the oxygen being supplied.

A simple bedside comparison

Patient A

PaO₂ = 80
FiO₂ = 0.21

P/F ≈ 381

Reasonable oxygenation.

Patient B

PaO₂ = 80
FiO₂ = 0.80

P/F = 100

Very different story.

Same PaO₂.

Completely different oxygenation efficiency.

That’s why:

Never interpret PaO₂ without looking at FiO₂.

4.4. Step 4 — When you need to know why the PaO₂ is low: A–a gradient

The alveolar–arterial oxygen gradient compares:

Oxygen in the alveoli with Oxygen actually reaching arterial blood.

A–a gradient = PAO₂ − PaO₂

The A–a gradient as a way of assessing the efficiency of pulmonary oxygen transfer and differentiating pulmonary from extrapulmonary causes of hypoxemia.

How do we calculate PAO₂?

Using the alveolar gas equation:

PAO₂ = FiO₂ × (Patm − PH₂O) − PaCO₂/R

At sea level:

• Patm ≈ 760 mmHg

• PH₂O ≈ 47 mmHg

• R ≈ 0.8

So on room air:

PAO₂ ≈ 0.21 × (760 − 47) − PaCO₂/0.8

The ABG material provides this equation and notes that the respiratory quotient is approximately 0.8 under steady-state conditions.

The A–a gradient gives you a physiological clue

Normal/near-normal A–a gradient

Think:

The lungs are transferring oxygen reasonably well.

Possible causes of hypoxemia include:

• low inspired oxygen

• hypoventilation

Increased A–a gradient

Think:

There is a problem with pulmonary oxygen transfer.

Common mechanisms include:

• V/Q mismatch

• shunt

• diffusion limitation

The infographic illustrates these mechanisms and shows that V/Q mismatch, shunt and diffusion limitation produce an increased A–a gradient, whereas low inspired oxygen and hypoventilation can have a relatively preserved gradient.

5. But here’s where hypoxemia ≠ hypoxia becomes important

Imagine a patient with:

Severe anaemia

PaO₂ → normal
SaO₂ → normal

Yet the patient may have impaired oxygen delivery because there isn’t enough haemoglobin available to carry oxygen.

Similarly, a patient with:

Low cardiac output

may have adequate arterial oxygenation but inadequate oxygen delivery to tissues.

And in certain toxic states, cells may be unable to utilize oxygen despite adequate arterial oxygen.

So:

Normal PaO₂ does not guarantee normal tissue oxygenation.

6. The bigger equation: Oxygen delivery

Ultimately, tissue oxygen delivery depends on:

DO₂ = Cardiac Output × CaO₂

And arterial oxygen content:

CaO₂ ≈ (1.34 × Hb × SaO₂) + (0.003 × PaO₂)

The important takeaway is that most oxygen content is carried by haemoglobin, while only a very small amount is dissolved in plasma. The ABG infographic in the source explicitly illustrates this relationship.

So a useful mental model is:

PaO₂

→ oxygen tension

SaO₂

→ percentage of Hb binding sites occupied

Hb

→ how much oxygen-carrying protein is available

Cardiac output

→ how much oxygenated blood reaches tissues

Cellular utilization

→ whether tissues can actually use the delivered oxygen

7. My bedside oxygenation checklist

When I open an ABG, I would go:

1. Is it actually arterial?

2. What is the FiO₂?

3. What is the PaO₂?

4. What is the SaO₂?

5. Is the PaO₂ appropriate for the FiO₂?

6. Calculate P/F ratio when clinically useful

PaO₂ ÷ FiO₂

7. If hypoxemia is present, ask:

Is the A–a gradient increased?

8. Finally ask the bigger question:

Is this only hypoxemia—or is the patient actually suffering from impaired oxygen delivery?

The one-minute takeaway

1. HYPOXEMIA

⬇️
Low arterial oxygen

Think: PaO₂ / SaO₂

↓

2. HYPOXIA

⬇️
Inadequate oxygen availability or utilization at the tissue level

Think: DO₂ = CO × CaO₂

↓

3. ABG oxygenation

Don’t stop at PaO₂.

PaO₂ → FiO₂ → P/F ratio → A–a gradient → oxygen content → tissue oxygen delivery

ABG Series #1 — The take-home message

A low PaO₂ tells you that the blood is hypoxemic.
It doesn’t, by itself, tell you whether the tissues are hypoxic.

And conversely:

Normal PaO₂ doesn’t guarantee adequate tissue oxygen delivery.

Read the ABG.
Then read the physiology.

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Before asking “What is the acid–base disorder?”, first ask:

Was this ABG collected, handled and processed correctly?

And then:

Is the ABG internally consistent?

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1. Why do we perform an ABG?

An arterial blood gas can help assess:

Oxygenation
→ PaO₂, SaO₂

Ventilation
→ PaCO₂

Acid–base status
→ pH, PaCO₂

Oxygen-carrying capacity
→ PaO₂, Hb, total Hb and dyshemoglobins

Electrolytes, Hb, Hct, Osmolality, etc.

It can also be used to assess response to interventions such as oxygen therapy and to monitor the severity or progression of disease.

2. Getting the sample right

Before puncture

• Allen’s test as a prerequisite

• Slight wrist extension for radial artery sampling

• Clean the site with 70% alcohol

• Use an appropriate heparinised syringe

• Enter the skin at approximately 45° for radial artery sampling

• Obtain approximately 1 mL of blood

• Do not pull back the syringe plunger

If an air bubble enters the syringe:

Remove it immediately.

Then apply firm pressure to the puncture site for at least 5 minutes.

3. The sample can be wrong even when the puncture was right

Several pre-analytical errors can alter the ABG:

Too much or too little anticoagulant

The source highlights the potential effects of excess/inadequate anticoagulant, including electrolyte binding.

Venous contamination

Mixing venous and arterial blood during puncture can produce misleading values.

Air bubbles

Air exposure can:

↑ PaO₂
↓ PaCO₂

Inadequate mixing

Can cause RBC stacking and compromise the sample.

4. Time matters

Analyse within 5 minutes
Maximum: 15 minutes

If a delay of >30 minutes is expected, it is recommended to keep in a glass syringe with an ice slurry, with iced-sample analysis possible for up to approximately 1 hour.

Practical takeaway:

Don’t let a good arterial puncture become a bad ABG because of poor handling.

5. When should you avoid a particular puncture site?

These cautions:

• Negative Allen’s test

• Surgical shunt/fistula or bypass graft

• Infection at the site

• Limb ischemia/Raynaud’s disease

• Bleeding diathesis — described as a relative contraindication in the post-thrombolysis setting

6. Complications of ABG sampling

Even a routine ABG is an arterial puncture. Potential complications include:

Arterial spasm
Hematoma
Arterial occlusion
Air/thrombus embolism
Local infection
Nerve or vessel injury
Vasovagal response
Needle-stick injury

7. Now comes the part most people skip…

CHECK THE ABG BEFORE INTERPRETING IT

Before jumping to:

❌ “It’s metabolic acidosis.”
❌ “It’s respiratory alkalosis.”
❌ “The patient is hypoxic.”

First ask:

Does the ABG make physiological sense?

The modified Henderson–Hasselbalch relationship

[H⁺] = 24 × PaCO₂ / HCO₃⁻

Use the reported PaCO₂ and HCO₃⁻ to estimate the corresponding hydrogen ion concentration.

Then compare it with the reported pH.

If the pH and calculated H⁺ are inconsistent:

Question the validity of the ABG.

A corresponding pH–H⁺ table as a bedside reference.

The Frontline Takeaway

Don’t interpret the numbers before validating the sample.

Good ABG interpretation begins before the ABG reaches the analyser.

Collect correctly → Handle correctly → Process promptly → Check consistency → Then interpret.

Coming next…

ABG series #2 — Oxygenation

Hypoxemia ≠ Hypoxia

We’ll start with:

PaO₂ → SaO₂ → FiO₂ → P/F ratio → A–a gradient

And then ask the more important question:

Why is this patient hypoxemic?

Follow @humans.of.em for the next part of the ABG series.

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A patient arrives in the ED with severe dyspnoea. Bibasal crackles. B-lines on lung ultrasound. A raised NT-proBNP. Perhaps some peripheral oedema.

The reflex is familiar:

“This is acute heart failure. Give IV Lasix.”

But the 2026 ESC Guidelines for the management of heart failure encourage a more nuanced approach. The question is not simply:

“Does this patient have heart failure?”

Nor even:

“How much furosemide should I give?”

The better questions are:

What is the clinical phenotype?
Where is the congestion?
Is the patient perfused?
Is this true volume overload or predominantly fluid redistribution?
And, after treatment, how will I know that decongestion is actually occurring?

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For every physicians, this may be one of the most useful ways to translate the 2026 ESC update into bedside practice.

1. First, the terminology has changed

The 2026 ESC Guidelines have eliminated the previous HFmrEF category.

The new classification is:

• HFrEF: LVEF <50% with symptoms and/or signs of HF

• HFpEF: LVEF ≥50% with symptoms/signs of HF plus objective evidence of structural and/or functional abnormalities consistent with LV diastolic dysfunction or raised LV filling pressures, supported by elevated natriuretic peptides.

The guideline has also replaced the term “acute heart failure” with “decompensated heart failure (DHF)”.

For the acute care physician, however, the more important change is conceptual:

DHF is not one phenotype, and therefore it should not have one reflex treatment.

2. Start with phenotype, not the prescription pad

The 2026 ESC framework separates patients into clinically important phenotypes:

• Cardiogenic shock

• Acute pulmonary oedema

• Decompensated left-sided HF

• Decompensated right-sided HF

And these phenotypes can overlap.

Figure 1. Diagnosing decompensated heart failure. Source: 2026 ESC Guidelines for the management of heart failure.

The guideline also provides non-age-adjusted natriuretic peptide rule-out thresholds for DHF:

• NT-proBNP <300 pg/mL

• BNP <100 pg/mL

• MR-proANP <120 pg/mL

Age-related NT-proBNP thresholds can then support a likely diagnosis in older patients.But once DHF is suspected, the next question is:

What phenotype am I treating?

3. Congestion and perfusion: the two questions that matter

The guideline provides a useful separation between left-sided congestion, right-sided congestion and hypoperfusion.

Left-sided congestion

Think:

• Dyspnoea

• Orthopnoea

• Cough

• Tachypnoea

• Rales

• S3

• Pleural effusion

• Elevated natriuretic peptides

Right-sided congestion

Think:

• Peripheral oedema

• Abdominal distension

• Hepatomegaly

• Raised JVP

• Hepatojugular reflux

• Pleural effusion

Hypoperfusion

Think:

• Cold/sweaty extremities

• Pale skin

• Dizziness

• Confusion

• Oliguria

• Narrow pulse pressure

• Elevated lactate

• AKI

• Hepatic injury.

So at the bedside, I would simplify it to:

WET or DRY?
WARM or COLD?
LEFT, RIGHT or BOTH?

That is more useful than simply labelling the patient “acute HF.”

4. Not every “wet” patient needs aggressive Lasix

This is perhaps the most important message for acute care physicians.

Figure 2. Initial management of decompensated heart failure. Source: 2026 ESC Guidelines for the management of heart failure.

The hypertensive pulmonary oedema patient is the classic example

Consider:

BP 200/110 mmHg
Severe respiratory distress
Diffuse B-lines
Orthopnoea

It is tempting to interpret this as:

“Massive fluid overload → massive dose of furosemide.”

But the guideline specifically highlights that acute pulmonary oedema can occur predominantly because of fluid redistribution into the pulmonary circulation, rather than massive total-body volume overload.

These patients usually do not need high doses of diuretics and may instead require vasodilator therapy. The guideline allows IV vasodilators to be considered as initial therapy in DHF when SBP >110 mmHg, particularly to improve symptoms and reduce congestion.

So:

Pulmonary congestion ≠ automatically massive volume overload.

And:

B-lines ≠ a prescription for high-dose Lasix.

The clinical context matters.

5. Right-sided failure is another phenotype where “Lasix first” deserves caution

Decompensated isolated right-sided HF is characterized by elevated right-sided pressures, systemic congestion and, in advanced disease, hypoperfusion.

The guideline specifically highlights the importance of RV function, ventricular interdependence and the effects on kidney and liver function. Pulmonary embolism and RV infarction may also need to be excluded as acute causes. So a patient with:

Raised JVP + oedema + hepatomegaly + hypotension

is not simply a “fluid overloaded patient.”

The question becomes:

Is this a congested patient who needs decongestion, or a preload-dependent/hypoperfused patient whose haemodynamics need stabilization first?

That distinction is critical.

6. If the patient IS congested, then decongestion becomes the goal

For the genuinely congested patient, IV loop diuretics remain the cornerstone of treatment.

—> For a diuretic-naïve patient:

40 mg IV furosemide or equivalent

—> For a patient already receiving oral loop diuretics:

approximately twice the usual daily oral loop-diuretic dose IV can be considered.

But here’s where the approach becomes much more interesting.

The dose is not the endpoint. The response is.

7. Don’t just give Lasix. Test the response.

Historically, the question after giving furosemide was often:

“Did the patient pee?”

The 2026 ESC approach is more objective.

At approximately 2 hours:

Spot urinary sodium ≥70 mEq/L

OR

During the first 6 hours:

Urine output ≥100 mL/hour

These are the guideline’s markers of a satisfactory early diuretic response.

This gives us a very useful bedside concept:

Don’t ask only how much diuretic you gave.
Ask how much sodium and water the patient actually removed.

The PUSH-AHF and ENACT-HF studies showed that uNa-guided strategies can increase natriuresis/diuresis, although importantly, no trial has yet demonstrated a mortality or recurrent-HF-hospitalization benefit from uNa-guided therapy itself.

So uNa should be viewed as a response-monitoring tool, not a magic prognostic marker.

8. What if the patient doesn’t respond?

This is where the guideline becomes particularly practical.

Figure 15. Management of decongestion. Source: 2026 ESC Guidelines for the management of heart failure.

If congestion persists, progressively escalate pharmacological decongestion and consider sequential nephron blockade. In refractory cases despite maximal pharmacological therapy, ultrafiltration may be considered.

9. Sequential nephron blockade: don’t just keep pushing the loop

The guideline incorporates acetazolamide and thiazide-type therapy into the strategy for inadequate diuretic response. In ADVOR, adding IV acetazolamide 500 mg daily to loop diuretics increased successful decongestion, defined as absence of signs of volume overload within three days.

Hydrochlorothiazide increased weight loss and 24-hour diuresis in CLOROTIC, but was associated with more worsening kidney function and hypokalaemia and did not improve patient-reported dyspnoea. Neither trial demonstrated benefit on hard clinical endpoints.

This is an important distinction:

More diuresis is not automatically better medicine.

The objective remains:

Effective, safe decongestion. Not maximum urine output at any cost.

10. The creatinine trap

One of the commonest reasons we stop effective decongestion is:

“Creatinine has gone up.”

But the ESC guideline specifically cautions against interpreting kidney function in isolation. Small, transient rises in serum creatinine during diuresis are not associated with poor outcomes when adequate decongestion is achieved.

Therefore:

Creatinine ↑ + congestion improving + perfusion adequate

does not automatically mean: STOP DIURESIS.

Compare that with:

Creatinine ↑ + persistent congestion + hypotension/hypoperfusion + poor diuretic response

Now we have a completely different problem. The kidney number needs to be interpreted alongside:

Congestion + perfusion + BP + urine output + natriuresis + trajectory.

11. How congested is the patient?

This is where the concept of a congestion score becomes useful.

The ESC clinical congestion score considers:

• Dyspnoea

• Orthopnoea

• Fatigue

• Rales

• Oedema

• JVP distension

A score of 0 represents absence of clinical congestion, while 1–2 represents mild congestion.

The key is not necessarily the number itself.

It is the trend.

On arrival, After treatment, Before discharge:

Is congestion actually gone?

That is much more meaningful than:

“He made 2.5 litres of urine.”

12. Decongestion is multimodal

Figure 4. Tools used for assessment of decongestion during the pre-discharge phase. Source: 2026 ESC Guidelines for the management of heart failure.

This is an excellent figure for acute care physicians because it brings together several domains.

Clinical

• Congestion score

• Weight loss

• NYHA class

Laboratory

• BNP

• NT-proBNP

Imaging

• Chest X-ray / congestion score index

• LV filling pressure parameters

• IVC

• Lung ultrasound

The guideline recommends assessment of residual congestion before discharge using clinical, laboratory and imaging techniques.

But there is an important caveat:

These tools are optional, because randomized trial evidence demonstrating improved outcomes from their use is lacking.

So POCUS is not a replacement for examination . It is another piece of the puzzle.

13. The POCUS question should change

Instead of simply asking:

“Does this patient have B-lines?”

ask:

“Where is the congestion, and is it resolving?”

Lung ultrasound

Are there B-lines?
Are they diffuse?
Are they changing with treatment?

Heart

What does LV/RV function look like?

Venous system

Is there evidence supporting systemic venous congestion?

Pleura

Is there an effusion?

And then integrate this with:

JVP + oedema + respiratory examination + urine output + uNa + renal function + BP + perfusion.

The guideline itself includes LUS and other imaging modalities as components of decongestion assessment rather than prescribing one imaging measurement as definitive.

14. “Dry” is not the same as “better”

One of the most important messages in the 2026 guideline is residual congestion.

A patient can:

• breathe better,

• have less oedema,

• produce several litres of urine,

and still be congested. Residual congestion is associated with poor outcomes and increased risk of rehospitalization. Therefore, the guideline recommends careful evaluation before discharge to exclude persistent congestion.

This changes our discharge question.

Not:

“Does the patient feel better?”

But:

“Have we achieved adequate decongestion?”

15. Decongestion is only one phase of the hospitalization

Figure 5. Phases and goals for in-hospital management of decompensated heart failure. Source: 2026 ESC Guidelines for the management of heart failure.

The ESC framework divides inpatient management into three broad phases:

Phase 1 — Initial management

• Treat life-threatening conditions

• Identify and treat precipitating factors

• Stabilize haemodynamics

• Initiate treatment of decompensation

Phase 2 — Stabilization

• Consolidate haemodynamic stability

• Attempt full decongestion

• Initiate/optimize foundational medical therapy

• Identify and manage comorbidities

Phase 3 — Pre-discharge and early post-discharge

• Exclude persistent congestion

• Optimize FMT

• Determine need for additional/interventional therapies

• Plan long-term management.

This is an important departure from the old mental model:

“Treat the acute episode and then deal with chronic HF later.”

16. Start disease-modifying therapy during the hospitalization

The guideline emphasizes that decongestion and foundational medical therapy should proceed in parallel once the patient is stabilized. MRAs, SGLT2 inhibitors and ARNIs can be initiated during the stabilization phase, and the traditional sequential approach to FMT is considered time-consuming; simultaneous implementation is preferred when feasible, with more conservative approaches for selected high-risk patients.

In-hospital initiation of an SGLT2 inhibitor after initial stabilization is recommended to improve quality of life/congestion symptoms and reduce HF hospitalization. And importantly, if a patient was already receiving foundational therapy, discontinuation is not recommended unless there are clear signs of hypoperfusion or another specific clinical indication.

17. The patient with shock is a different conversation

A congested patient who is also hypoperfused cannot simply be treated using the same algorithm as an uncomplicated “warm and wet” patient. The guideline emphasizes that cardiogenic shock is defined by critical end-organ hypoperfusion, and there is no single blood-pressure threshold that defines it. Hypoperfusion can occur even with normal blood pressure.

Look for:

Cold extremities
Confusion
Oliguria
Narrow pulse pressure
Lactate elevation
AKI/hepatic injury

The guideline uses the SCAI shock stages from:

A — At risk
B — Beginning/pre-shock
C — Classic shock
D — Deteriorating
E — Extremis.

And when cardiogenic shock with potential need for temporary mechanical circulatory support is suspected, consultation with a Shock Team is recommended.

18. The bedside algorithm I want to remember

If I had to reduce the 2026 ESC approach to one ED mental model:

The bigger mindset shift

Lasix is a tool. Decongestion is the goal. Phenotyping determines the strategy. And on the frontline, that distinction matters.

Must Read : ESC 2026 Heart Failure Guidelines

This is Part 3.

If you haven’t read Part 1 and Part 2, stop here and read them first.

Part 1 built the foundation:
Troponin → Myocardial Injury ≠ Myocardial Infarction

Part 2 took it further:
Troponin Matrix → Trop-Zones → Delta → Five questions

This post assumes you already have that framework.

Because the Fifth Universal Definition of Myocardial Infarction (2026) doesn’t make us throw that framework away.

It makes us update it.

Start here:
→ Part 1: Troponin Is Not an MI Test
→ Part 2: Troponin Is Not an MI Test

Then come back here.

Let’s see what changed in 2026.
If you have read Part 1 and Part 2 of this series, you already know the central message:

Troponin detects myocardial injury. It does not diagnose myocardial infarction.

We built the Troponin Triangle.

We moved from:

“Is the troponin positive?”

to:

“Is there myocardial injury → Is it acute → Is there evidence of ischemia → If yes, what is the mechanism?”

We discussed the Troponin Matrix, Type 1 versus Type 2 MI, the Trop-Zones, and why the delta is often more informative than the first troponin.

All of that came from the framework of the Fourth Universal Definition of Myocardial Infarction (2018). Now, the Fifth Universal Definition of Myocardial Infarction (2026) has arrived.

And importantly, it does not throw away the mental model. It makes it more sophisticated.

The fundamental question remains:

Is this myocardial injury or myocardial infarction?

But the Fifth UDMI gives us better tools for answering the questions that come after the troponin comes back.

What actually changed?

There are several important updates. But for the acute-care physician, I think three deserve particular attention:

1. The delta is no longer just “rise or fall”

2. Imaging becomes much more important in determining what the injury actually represents

3. The classification of MI has been reorganized around clinical setting and pathophysiology

Let’s unpack these.

1. The Delta Is Not a Number

In Part 2, we called the delta:

“The most important number you never memorized.”

The Fifth UDMI adds an important qualification:

There is no single absolute or relative troponin change that works for every patient, every assay, and every clinical situation.

Why?

Because the meaning of a delta depends on three things.

Factor 1: Time from symptom onset

Troponin does not behave like a light switch. It follows a biological curve. Early after an ischemic event, the absolute change may be small. Several hours later, the rise can become much more pronounced. Around the peak, the change may become relatively small again. And during the later phase, the troponin begins to fall.

The Fifth UDMI therefore emphasizes that the same delta can mean very different things depending on when the patient presents.

Think about two patients:

Patient A

Chest pain started 45 minutes ago.

Troponin:
10 → 14 ng/L

Patient B

Chest pain started 10 hours ago.

Troponin:
10 → 14 ng/L

Same delta.

Very different biological stories.

This is why:

Delta without a timeline is incomplete information.

Factor 2: Time between samples

The second troponin is not simply “another troponin.” It is a measurement taken at a particular point in time.

A 1-hour delta and a 6-hour delta are not interchangeable.

The longer the interval, the greater the opportunity for a biological rise or fall to occur. This is one reason accelerated diagnostic pathways use fixed sampling intervals, such as 0/1-hour or 0/2-hour strategies. But even here, the Fifth UDMI emphasizes that the thresholds and deltas are assay-specific.

So:

A delta without knowing the interval between samples is also incomplete information.

Factor 3: The baseline troponin

This one is particularly important.

Suppose the troponin is:

8 → 18 ng/L

A 10 ng/L rise. That absolute change may be quite meaningful when the baseline is low.

Now consider:

800 → 810 ng/L

Same absolute change. But the biological interpretation is very different.

The Fifth UDMI highlights that the relationship between absolute and relative change depends on the baseline concentration.

When troponin is around or below the 99th percentile, absolute changes can be particularly useful. When baseline troponin is already substantially elevated, relative change may be easier to interpret.

And importantly:

Absolute delta thresholds cannot simply be transferred from one assay to another.

They are assay-specific. So the new mental model becomes:

Don’t ask:

“What is the delta?”

Ask:

“What is the delta, over what interval, from what baseline, and at what point in the patient’s illness?”

The New Delta Triangle

I would therefore modify our Part 2 framework.

Previously:

TROPONIN → DELTA → ACUTE INJURY

Now:

DELTA =

Time from symptom onset

+

Time between samples

+

Baseline troponin

Only then does the number start to make biological sense.

2. Imaging Moves Further Into the Story

This may be the most important conceptual change for me. And there is an important caveat:

Imaging is not new to the Universal Definition.

The Fourth UDMI already included imaging as evidence of ischemia and myocardial infarction. So the Fifth UDMI does not suddenly “introduce imaging.”

Instead, it expands and organizes the role of multimodality coronary and cardiac imaging in determining the mechanism and consequences of myocardial injury.

And this is where things become particularly interesting for emergency and acute-care medicine. Because sometimes:

The troponin tells you that myocardium is injured.

But it cannot tell you:

What happened to the myocardium?

And it certainly cannot always tell you:

What happened to the coronary artery?

That is where imaging comes in.

Think of the modalities as answering different questions

Troponin

Is the myocardium injured?

ECG

Is there evidence of electrical ischemia?

Echocardiography

Is there a new functional consequence?

But then we have:

CMR

What happened to the myocardium?

CCTA

What does the coronary anatomy and plaque look like?

IVUS/OCT

What actually happened inside the coronary artery?

This is a very different way of thinking about imaging.

CMR: What happened to the myocardium?

Cardiac MRI is particularly powerful because it can characterize myocardial tissue.

It can demonstrate:

• myocardial infarction

• edema

• inflammation

• microvascular obstruction

• intramyocardial haemorrhage

• patterns of myocardial injury

using multimodality tissue-characterization sequences. This becomes particularly important when the diagnosis is not obvious from the initial presentation.

A patient has:

Chest pain + troponin elevation + non-obstructive coronaries.

What now? The answer is not:

“Angiogram is normal, so nothing happened.”

The myocardium may have infarcted. Or the patient may have myocarditis. Or Takotsubo syndrome. Or another cardiomyopathy.

This is where CMR can help establish the final diagnosis. The Fifth UDMI specifically emphasizes its role in situations such as MINOCA and unrecognized myocardial infarction.

CCTA: What do the coronaries look like?

CT coronary angiography provides another piece of the puzzle.

It can evaluate:

• coronary anatomy

• obstructive CAD

• plaque characteristics

• graft patency

and newer CT techniques are expanding its ability to characterize myocardial viability and alternative diagnoses. But this does not mean:

“Every patient with a raised troponin needs a CCTA.”

Absolutely not. The Fifth UDMI still recognizes that its role depends on clinical context and pre-test probability.

The important change is conceptual:

Coronary anatomy can become part of the diagnostic explanation for myocardial injury.

IVUS/OCT: What actually happened to the plaque?

This is perhaps the most fascinating part.

Sometimes angiography tells us:

“There is no major obstruction.”

But that does not necessarily mean:

“There is no coronary pathology.”

Intravascular imaging with IVUS or OCT can reveal pathology that angiography may miss, including:

• plaque rupture

• plaque erosion

• mural thrombus

• spontaneous coronary artery dissection

• stent-related pathology

• other subtle coronary abnormalities.

And this is especially relevant to MINOCA.

Because:

MINOCA is not necessarily the final diagnosis.

It can be a working diagnosis that tells us:

“The patient appears to have had an MI, but we have not yet established why.”

Further investigation may involve intravascular imaging, functional coronary testing and CMR to identify the underlying mechanism.

The New Imaging Mental Model

This is how I would now think about it:

TROPONIN

↓

MYOCARDIAL INJURY

↓

IS IT ISCHEMIC?

↓

If yes:

WHAT HAPPENED TO THE CORONARY?
→ Angiography
→ IVUS/OCT
→ Functional testing

WHAT HAPPENED TO THE MYOCARDIUM?
→ CMR
→ Echo
→ Other appropriate imaging

WHAT IS THE UNDERLYING MECHANISM?

That is a much richer diagnostic pathway than:

Troponin positive → NSTEMI

3. MINOCA: “Nothing Significant on Angiography” Is Not the End

This is where the imaging emphasis becomes clinically relevant.

Imagine:

Chest pain

Dynamic troponin rise

Ischemic ECG changes

Angiography: no obstructive coronary lesion

The old instinct might be:

“The angiogram is normal.”

The better question is:

“Why did this patient have an infarction?”

Possibilities include plaque disruption, coronary spasm, microvascular dysfunction, SCAD and other mechanisms.

The Fifth UDMI therefore reinforces MINOCA as a working diagnosis requiring further investigation, rather than simply a final label.

And that is exactly where multimodality imaging becomes clinically useful.

4. The Type 1–5 World Has Been Reorganized

There is another major change.

For years, we have taught:

Type 1 MI
Type 2 MI
Type 3 MI
Type 4 MI
Type 5 MI

The Fifth UDMI replaces this numerical classification with three broader clinical settings:

Primary MI

Secondary MI

Procedure-related MI

This is not simply a change in vocabulary. It is an attempt to align the classification more closely with the clinical setting and underlying pathophysiology. The underlying concepts have not disappeared. The point is to make the classification more clinically intuitive.

5. What About the 99th Percentile?

Here is another important nuance.

The Fifth UDMI continues to define acute myocardial injury using a rise and/or fall in cardiac troponin with at least one value above the assay’s sex-specific 99th percentile URL.

But don’t read this as:

“Sex-specific 99th percentile is a completely new 2026 concept.”

It isn’t. The Fourth UDMI had already recommended sex-specific 99th-percentile values for hs-cTn assays.

What the Fifth UDMI does is further emphasize and operationalize this issue, recognizing the potential for under-recognition of myocardial injury when a single threshold is applied across sexes. And another important distinction:

The 99th percentile defines myocardial injury.

It is not automatically the same thing as a rule-in threshold for MI. Accelerated diagnostic pathways may use assay-specific thresholds and deltas that are different from the 99th percentile.

So What Should We Change at the Bedside?

Let’s go back to the five questions from Part 2.

They still work. But the Fifth UDMI makes them better.

Question 1

Is there myocardial injury?

Look at the assay-specific 99th percentile.

Question 2

Is it acute or chronic?

Look at the pattern over time.

Question 3

Is there evidence of ischemia?

Symptoms.
ECG.
Imaging.
Coronary findings.

Question 4

If ischemic, what is the mechanism?

Primary?
Secondary?
Procedure-related?

Question 5

If the mechanism is unclear, what additional information do I need?

And this is where the Fifth UDMI pushes us further.

Maybe the answer is:

Repeat troponin.

Maybe:

Repeat ECG.

Maybe:

Echo.

But sometimes:

CMR.

CCTA.

IVUS/OCT.

Functional coronary assessment.

The Updated Troponin Mental Model

So perhaps our original framework needs one more layer.

The old shortcut:

TROPONIN → MI

was wrong.

Our Part 1 model:

TROPONIN

↓

INJURY

↓

ACUTE OR CHRONIC

↓

ISCHEMIC OR NON-ISCHEMIC

↓

MI

was much better.

The 2026 model:

TROPONIN

↓

MYOCARDIAL INJURY

↓

ACUTE OR CHRONIC

↓

INTERPRET THE DELTA

Time from onset
Sampling interval
Baseline concentration

↓

IS THERE ISCHAEMIA?

↓

USE CLINICAL + ECG + IMAGING EVIDENCE

↓

IS IT INFARCTION?

↓

WHAT IS THE MECHANISM?

↓

PRIMARY / SECONDARY / PROCEDURE-RELATED

And when the answer remains unclear:

↓

IMAGE THE CORONARY. IMAGE THE MYOCARDIUM.

The Take-Home Message

The Fifth Universal Definition does not overturn the central lesson of our previous two posts. It reinforces it. Troponin still detects myocardial injury. It does not tell you whether that injury is an infarction. But the 2026 update makes us more precise about two things.

First:

The delta is not a magic number.

Its interpretation depends on:

when the injury occurred + when you sampled + where the troponin started.

Second:

The diagnosis does not necessarily end with the troponin—or even the angiogram.

Modern MI diagnosis increasingly asks:

What happened to the myocardium?

and

What happened to the coronary artery?

Sometimes the answer comes from the ECG.

Sometimes from echocardiography.

Sometimes from angiography.

But increasingly, the answer may require:

CMR.

CCTA.

IVUS/OCT.

Functional coronary testing.

And perhaps that is the most important evolution from our original mental model.

One Last Time

The next time someone tells you:

“The troponin is positive.”

Don’t ask:

“Is this an NSTEMI?”

Ask:

Is there myocardial injury?

Is it acute?

Does the delta make biological sense given the timing, sampling interval and baseline?

Is there evidence of ischemia?

If there is ischemia, what is the mechanism?

And if the answer is still unclear—what does the coronary artery and the myocardium actually look like?

Because:

Troponin tells you that the myocardium is speaking.

The Fifth UDMI reminds us that we still have to listen to the whole story.

References

1. Fifth Universal Definition of Myocardial Infarction. ESC/ACC/AHA/WHF, 2026.

2. Jain A. Troponin Is Not an MI Test: Part 1 — A New Mental Model for Acute Care Physicians. Life on the Frontline. July 1, 2026. Read Part 1

3. Jain A. Troponin Is Not an MI Test: Part 2 — A New Mental Model for Acute Care Physicians. Life on the Frontline. July 4, 2026. Read Part 2

Who are our teachers ?

The answer is rarely just our seniors. In fact, if we pay enough attention, the Emergency Department may be one of the largest classrooms we will ever enter.

And almost everyone in it is teaching us something.

The Patient

The patient is often our first teacher. Not every patient presents like a textbook.

Sometimes the history is incomplete. Sometimes the examination finding is subtle. Sometimes the diagnosis we initially considered doesn’t quite fit. And sometimes, the patient teaches us simply by reminding us that the person in front of us is more complicated than the label we are trying to assign. Every patient adds another piece to our clinical experience. The more patients we see, the more patterns we recognise.

But importantly, the more we should also realise that not every patient follows the pattern. That is where learning happens.

The Attendant

Then there is the patient’s attendant. They may arrive frightened, angry, confused, impatient or overwhelmed. They may ask the same question repeatedly.

“Is he going to be okay?”

“Why is this taking so long?”

“Can you please tell me what is happening?”

These interactions teach something that no clinical guideline can fully teach:

Communication under pressure.

Emergency medicine is not only about identifying illness and treating it. It is also about explaining uncertainty. About setting expectations. About listening when you are busy. About remembering that for the family sitting across from you, this may be one of the most frightening days of their lives.

Sometimes, the attendant teaches us to be better doctors by forcing us to become better humans.

The Nursing Team

There are lessons that are difficult to learn from books. How to recognise that something is changing before the numbers become alarming. How to prioritise when three things happen simultaneously. How to prepare for the next deterioration while managing the current one. How a small practical adjustment can make a major difference during a resuscitation.

Our nursing colleagues accumulate an enormous amount of practical wisdom through experience. If we are willing to listen, they teach us every day.

Clinical expertise in the ED is a team sport. And good teams learn from each other.

The Seniors

Our seniors teach us in obvious and less obvious ways. They teach us how to approach uncertainty. How to make decisions with incomplete information. How to remain calm when everyone around us is becoming anxious. Sometimes they teach us through a carefully chosen question. Sometimes through a difficult case discussion.

Sometimes simply through watching how they behave when things don’t go according to plan. And occasionally, the most valuable teaching moment comes from hearing:

“Why did you choose this?”

Not because the answer is necessarily wrong. But because being asked to explain our reasoning forces us to examine it.

And Then Come the Juniors

Perhaps the most unexpected teachers in the Emergency Department are the people we are supposed to be teaching.

Our juniors.

Their questions can be remarkably powerful.

“Why are we doing it this way?”

“Could this be something else?”

“What happens if we don’t do this?”

“Is that really the best evidence?”

And occasionally:

“But why?”

That last question can be dangerous. Because sometimes we realise we don’t actually remember. Not because we are incompetent. Not because we have forgotten medicine. But because medicine is vast, and clinical practice is busy. Knowledge that was once clear can become rusty.

A junior’s question can expose that gap. And suddenly, the teacher becomes the student again. You go back to the textbook. You search the literature. You revisit the guideline.

You reconsider something you have been doing almost automatically.

And you learn. Perhaps this is one of the greatest gifts juniors give their seniors. They make us uncomfortable enough to keep learning.

A Classroom

Maybe we have misunderstood what teaching looks like. Teaching isn’t always a lecture. It isn’t always a PowerPoint. It isn’t always a journal club or a grand-round presentation.

Sometimes teaching is:

A patient’s unusual presentation.
An attendant’s difficult question.
A nurse’s practical suggestion.
A senior’s challenging question.
A junior’s seemingly simple doubt.
And sometimes, teaching is the mistake we almost made—but caught because someone asked the right question at the right time.

For me, The Emergency Department is constantly generating these moments. We just have to notice them.

A Pulse Check for Teachers’ Day

So, on this Teachers’ Day, perhaps the question isn’t:

“Who was your favourite teacher?”

Perhaps the more useful question for those of us working in Emergency Medicine is:

“Who taught you something today?”

And an even harder one:

“When was the last time a junior taught you something?”

If you can’t remember, perhaps that’s worth reflecting on. Because being senior does not mean we have finished learning. And being a teacher does not mean we stop being students. In Emergency Medicine, the roles constantly change.

Today I teach.
Tomorrow I learn.
Sometimes, I do both in the same resuscitation bay.

That may be one of the most beautiful things about our specialty.

This Teachers’ Day

To the patients who challenged our clinical thinking.

To the attendants who taught us empathy.

To the nursing teams who taught us the practical art of emergency care.

To the seniors who shaped our judgement.

And to the juniors whose questions make us open the books again—

Thank you.

You may not always realise that you are teaching us. But you are. And perhaps the best teachers are not the ones who give us all the answers. They are the ones who make us ask better questions.

Pulse Check

Who has been your unexpected teacher in the Emergency Department?

A patient?
A nurse?
A senior?
A junior?

Tell me about one lesson you learned from someone you weren’t expecting to learn from.

Life on the Frontline is a space for reflections on Emergency Medicine, medical education, clinical practice and the people behind the work.

Happy Teachers’ Day.

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We teach intubation relentlessly.

Indications.
Preoxygenation.
Drug choices.
Laryngoscopy.
Bougie.
Video laryngoscopy.
Failed-airway algorithms.

But once the tube is successfully placed, the attention often shifts.

The patient is stable.
The ventilator is doing the work.
The crisis seems over.

And then, sometime later, someone says:

“They passed the SBT. Let’s extubate.”

Perhaps that sentence deserves a little more hesitation.

Not because extubation should be delayed unnecessarily but because extubation is itself an airway procedure.

The 2026 Project for Universal Management of Airways (PUMA) guidelines make this point clearly: tracheal extubation warrants an equivalent level of evaluation, strategy, preparation and vigilance to tracheal intubation (Ellard et al., 2026).

And that changes how we should think about the tube coming out.

Extubation is not simply “successful weaning”

A spontaneous breathing trial answers an important question:

Can this patient sustain spontaneous breathing?

But it does not answer everything.

A patient may breathe adequately and still fail because they cannot:

• protect their airway

• clear secretions

• maintain upper-airway patency

• tolerate airway stimulation

• maintain adequate oxygenation

• recover rapidly if re-intubation becomes necessary.

Passing an SBT therefore does not automatically mean that the patient is ready for extubation. Airway protection and the risk of post-extubation airway problems must also be considered (Farkas, 2023).

So perhaps the better question isn’t:

“Did they pass the SBT?”

It is:

“If I remove this tube, what happens next and am I prepared for it?”

Think of extubation as a three-question problem

The PUMA guideline offers a useful way of translating risk assessment into strategy (Ellard et al., 2026).

1. Should I extubate now?

Look beyond the ventilator.

Has the reason for intubation improved?

Is the patient physiologically stable?

Are sedation and neuromuscular blockade adequately reversed?

Is there uncontrolled metabolic or respiratory pathology?

And importantly:

Will waiting actually make extubation safer?

Planned extubation is elective. That means we have something we rarely have during emergency intubation:

control over the circumstances.

We can choose the timing, location, personnel and resources. The PUMA guideline therefore recommends considering deferral when waiting is expected to significantly reduce extubation risk (Ellard et al., 2026).

2. What happens if it fails?

This is where extubation becomes an airway strategy rather than merely a ventilator decision.

Ask:

If the patient deteriorates, can I rapidly restore oxygenation?

And not just:

“Can I intubate them?”

But:

“Can I successfully manage their airway using the available airway lifelines?”

The PUMA framework emphasizes that if achieving airway success with a facemask, supraglottic airway or tracheal tube is not expected to be rapid and reliable, the extubation should be considered at risk (Ellard et al., 2026).

That is a powerful shift. The patient’s airway risk is not determined only by how difficult the original intubation was.

Something may have changed.

Edema.
Bleeding.
Trauma.
Surgery.
Secretions.
Reduced physiological reserve.
A deteriorated cardiopulmonary state.

The airway you had earlier may not be the airway you have after extubation.

3. What support will they need after extubation?

The procedure doesn’t end when the ETT leaves the mouth.

Some patients may benefit from high-flow nasal cannula (HFNC), while selected patients—particularly those with conditions such as COPD, heart failure or significant obesity—may benefit from non-invasive positive-pressure support (Farkas, 2023).

The post-extubation strategy should therefore be considered before extubation, not after the patient begins deteriorating.

The SBT is necessary but it isn’t the finish line

A practical SBT approach described in the IBCC is approximately:

Pressure support 5 + PEEP 5 cmH₂O for 30 minutes

or

CPAP ~5 cmH₂O with automatic tube compensation (Farkas, 2023).

During the trial, look at the whole patient rather than one number.

Oxygenation

Can they maintain acceptable oxygen saturation without excessive FiO₂?

Ventilation

Is tidal volume maintained?

Is minute ventilation falling?

Is EtCO₂ rising?

Respiratory mechanics

Are they developing:

• marked tachypnoea?

• diaphoresis?

• accessory muscle use?

• agitation?

• fatigue?

And then there is the famous RSBI.

RR / tidal volume in litres

Traditionally:

RSBI <105 = reassuring.

But a number should never replace clinical reasoning.

An elevated RSBI should be interpreted in context rather than used as an absolute contraindication to extubation. Patients with chronic tachypnoea or respiratory dysfunction may have persistently elevated values despite being appropriate candidates for extubation (Farkas, 2023).

The patient is not a ratio.

Then ask the four questions the SBT cannot answer

After the breathing trial:

1. Are they awake enough?

Not necessarily perfectly normal—but sufficiently arousable to maintain their airway (Farkas, 2023).

2. Can they handle their secretions?

A patient requiring frequent suctioning is telling you something.

3. Do they have a cough?

A strong cough can be more clinically useful than another decimal point from the ventilator (Farkas, 2023).

4. Can they maintain ventilation?

This becomes particularly important in patients with chronic hypercapnia or impaired respiratory drive (Farkas, 2023).

And then comes the question we often forget:

What kind of extubation is this?

Not every tube removal is the same.

A patient with:

• uncomplicated intubation

• normal airway anatomy

• reliable mask ventilation

• reliable supraglottic airway rescue

• adequate physiological reserve

is very different from a patient with:

• difficult intubation

• airway edema

• facial trauma

• bleeding

• questionable mask ventilation

• questionable SGA rescue

• poor safe-apnoea time.

The PUMA framework therefore links risk to strategy (Ellard et al., 2026).

Low-risk airway

Standard extubation may be appropriate.

At-risk airway

Consider an awake extubation with an airway exchange catheter and a clear rescue strategy when this is required to provide an adequate margin of safety (Ellard et al., 2026).

Unreconstructible airway

The question may become whether extubation should occur at all—or whether conversion to a more secure airway is required (Ellard et al., 2026).

The key concept is beautifully simple:

Risk assessment is useful only when it changes what you do.

The PUMA guideline specifically emphasizes linking identified risks to the actual extubation strategy (Ellard et al., 2026).

The extubation moment itself matters

Extubation is not simply:

Deflate cuff → pull tube → oxygen.

The PUMA approach emphasizes preparation of the team, equipment, oxygenation, positioning and rescue plan before the tube comes out (Ellard et al., 2026).

And why all this preparation?

Because extubation can provoke airway stimulation, coughing, laryngospasm, obstruction, aspiration and other complications (Ellard et al., 2026).

Airway stimulation may be particularly important as sedatives and neuromuscular blocking drugs wear off, and laryngospasm can result in significant morbidity, including airway obstruction, negative-pressure pulmonary oedema and aspiration (Ellard et al., 2026).

What happens after the tube comes out?

The tube is out. But the procedure isn’t over.

Now comes the next phase:

Can the patient maintain the airway and ventilation without invasive support?

This is where planned post-extubation support matters. HFNC has been shown to reduce re-intubation and ICU length of stay in appropriate populations, while non-invasive positive-pressure ventilation may be particularly useful in selected high-risk groups (Farkas, 2023).

So before extubation, know what comes next.

Room air?

Conventional oxygen?

HFNC?

NIV?

The answer should not be decided only after the patient starts struggling.

Perhaps we need to change the language

One idea from the Critical Care Time discussion deserves to stay with us. (Critical Care Time, 2025)

We often say:

“The patient failed extubation.”

But perhaps a better phrase is:

“We failed to successfully extubate the patient.”

Because extubation is our clinical decision.

We choose the timing.
We assess readiness.
We assess the airway.
We choose the rescue strategy.
We choose the post-extubation support.

And sometimes, despite doing all of this correctly, re-intubation will still be necessary. That does not automatically mean the original decision was wrong.

Extubation cannot be predicted with perfect certainty. The IBCC describes it as a trial of extubation, recognising that both premature and unnecessarily delayed extubation can cause harm (Farkas, 2023).

The real goal isn’t zero re-intubations

Zero re-intubations sounds like excellent performance. But if achieving zero means keeping patients intubated longer than necessary, we may simply be exchanging one problem for another.

Prolonged mechanical ventilation carries its own burden, including delirium, infection, weakness, deconditioning and impaired mobility (Critical Care Time, 2025).

The Critical Care Time discussion highlights the substantial burden associated with each additional day of mechanical ventilation (Critical Care Time, 2025).

So the goal isn’t:

“Never re-intubate.”

And it isn’t:

“Extubate as early as possible.”

It is:

Extubate when the patient is ready,

with an airway strategy matched to their risk,

and with a rescue plan that is ready before the tube comes out.

A final thought from the ED

In the emergency department, extubation can be particularly easy to overlook.

The patient was intubated for a seizure.
Or an overdose.
Or a procedure.
Or transient respiratory failure.

The underlying problem improves. And suddenly the question becomes:

“Can we get the tube out?”

Maybe we should replace that question with:

“If I take this tube out right now, have I deliberately designed what happens next?”

That is the mindset shift. Intubation secures the airway. Extubation asks whether the patient can safely own it again. And that deserves just as much thought.

The Frontline Takeaway

Before every extubation, ask:

READY?
Has the patient recovered enough physiologically?

AIRWAY?
Can they protect and maintain it?

RISK?
Is this a low-risk or at-risk extubation?

RESCUE?
If they deteriorate, can I rapidly restore oxygenation?

SUPPORT?
What will they breathe through after the tube comes out?

If you cannot answer the last four questions, passing an SBT may not be enough.

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References

1. Ellard L, Higgs A, Cooper RM, et al. Project for Universal Management of Airways: guidelines for tracheal extubation. Anaesthesia. 2026;81:1–31.

2. Farkas J. Liberation from the ventilator. Internet Book of Critical Care (IBCC). EMCrit Project. 2023.

3. Critical Care Time. Episode 47: Extubation: Tube Be or Not Tube Be. 2025.

We have become very good at giving antibiotics early. Perhaps less good at knowing exactly why we are giving them. That is not necessarily a failure of clinical practice. It is, in many ways, an unavoidable consequence of emergency medicine.

The patient arrives hypotensive, tachypneic, febrile, confused, or simply “looks septic.” Microbiology is unavailable. Definitive imaging may still be pending. The emergency department is designed around action under uncertainty.

So we do what we are taught to do:

Recognize sepsis.
Resuscitate.
Give antibiotics early.

But there is a paradox embedded within this approach.

The moment when we need to make the antibiotic decision fastest is often the moment when we know the least about the diagnosis.

Diagnostic uncertainty can drive broad-spectrum empiricism, while antibiotics started during the initial resuscitation phase may continue even when subsequent information reduces the likelihood of bacterial infection (Tamma et al., 2011; Schoffelen et al., 2024).

This raises a different question about antimicrobial stewardship in the emergency department:

What if the problem isn’t simply how quickly we give antibiotics—but how quickly we can improve the certainty behind that decision?

And what if one of the tools for doing that is already in our hands?

POCUS.

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The POCUS we use today is not necessarily the POCUS we need tomorrow

Point-of-care ultrasound has become deeply embedded in emergency medicine.

We use it to assess shock.
To evaluate dyspnea.
To identify pneumothorax.
To assess cardiac function.
To guide procedures.
But most of these applications are framed around diagnosis, resuscitation, or procedural safety.

Antimicrobial stewardship is rarely the stated endpoint.

Yet multiorgan POCUS can potentially do something highly relevant to stewardship:

It can change the information available at the moment the antibiotic decision is being made.

The literature increasingly suggests that bedside ultrasound can identify infectious sources, recognize non-infectious mimics of sepsis, and facilitate source-control procedures (Perera et al., 2010; Cortellaro et al., 2017; Verras et al., 2023).

That led me to a simple question:

Could POCUS itself become part of an antimicrobial stewardship pathway in the first hour of emergency care?

Not as an antibiotic “rule-out” test. Not as a replacement for microbiology. Not as another acronym to memorize. But as a structured diagnostic intervention that changes the pathway from uncertainty toward specificity.

From “Does this patient have sepsis?” to “Where is the problem?”

One of the biggest problems with the early sepsis phenotype is that it is nonspecific.

Hypotension.

Tachycardia.

Tachypnea.

Altered mentation.

Elevated lactate.

These findings tell us that something is wrong.

They do not necessarily tell us what is wrong.

This is where POCUS can contribute to what we might call diagnostic stewardship.

Instead of stopping at:

“Possible sepsis.”

we can begin asking:

“Is there a probable anatomical source?”

That is a fundamentally different question.

And it can be surprisingly actionable.

FIND

Find the infection.

Consider three common scenarios.

The lung

Consolidation with dynamic air bronchograms can support a diagnosis of pneumonia.

Lung ultrasound has demonstrated high diagnostic accuracy for pneumonia, with a systematic review cited in our review reporting pooled sensitivity of approximately 92% and specificity of 94% (Desai et al., 2024).

The gallbladder

Gallstones, gallbladder wall thickening and pericholecystic fluid can shift the diagnostic pathway toward a biliary source.

Emergency physician-performed ultrasound has demonstrated approximately 87% sensitivity and 82% specificity for acute cholecystitis in the cited literature (Summers et al., 2010).

The soft tissues

A patient labelled as having “cellulitis” may actually have a drainable abscess.

POCUS can identify the collection and peripheral vascularity that distinguish an abscess from simple cellulitis—and that distinction immediately changes management (Tayal et al., 2006; Guillén-Astete & Naredo, 2025).

The broader principle is more important than any individual ultrasound sign:

POCUS can move us from a syndrome-based diagnosis toward a source-specific diagnosis.

And source-specific diagnosis is inherently more compatible with targeted antimicrobial therapy than indefinite broad-spectrum empiricism.

But stewardship isn’t only about finding infection

This is where the concept becomes more interesting. If antimicrobial stewardship is only about finding infection, we are missing half of the problem. Sometimes the most important finding is:

There is no infection.

Consider a patient with:

Hypoxia + tachypnea + bilateral B-lines.

The reflex interpretation may be pneumonia. Perhaps ARDS. But bilateral B-lines are not synonymous with infection.

Add focused cardiac ultrasound.

Now suppose we find significant cardiac dysfunction alongside the diffuse interstitial pattern. The diagnostic probability changes.

The patient may have cardiogenic pulmonary edema.

And that can change the antibiotic decision.

Lung and cardiac POCUS can therefore be used together to interrogate an important diagnostic overlap. A systematic review and meta-analysis reported lung ultrasound sensitivity of approximately 88% and specificity of 90% for acute decompensated heart failure (Maw et al., 2019).

But there is an important caveat.

A patient can have both infection and cardiac dysfunction.

POCUS should therefore never become:

“B-lines = no antibiotics.”

That would simply replace one form of diagnostic error with another. Instead, POCUS should be understood as a tool for updating diagnostic probability.

That distinction matters.

DE-SELECT

Find the mimic.

A structured multiorgan examination can reveal diagnoses that look remarkably similar to sepsis.

Cardiogenic shock.

Pulmonary embolism.

Hemorrhagic shock.

Obstructive pathology.

Severe dengue.

Renal obstruction.

These conditions can generate physiological patterns that trigger reflexive antibacterial treatment (Volpicelli et al., 2013; Polyzogopoulou et al., 2023; Dewan et al., 2021).

This is where POCUS potentially becomes therapeutic stewardship. The objective is not to prove that the patient does not have infection. It is to acquire enough additional information to ask:

“Does the current probability of bacterial infection justify continuing this antimicrobial strategy?”

That is a much more sophisticated stewardship question.

And then comes the part we often forget:

CONTROL

Suppose POCUS identifies an abscess. Finding it is only the beginning. The clinically meaningful next step is:

Drain it.

A complex pleural effusion?

Drain it.

An infected obstructed collecting system?

Decompress it.

This leads to what I think is one of the most important ideas in this framework:

Source control is antimicrobial stewardship.

An undrained abscess is not merely a diagnostic problem. It is a persistent bacterial reservoir.

When source control is delayed, persistent infection can be interpreted as antimicrobial failure, potentially prompting broader or prolonged antibiotic therapy even when the original regimen may have been appropriate (Santos et al., 2026).

POCUS can accelerate recognition of drainable collections and facilitate bedside interventions, including drainage of abscesses and pleural infection and decompression of obstructed systems (Tayal et al., 2006; Santos et al., 2026).

And there is an interesting quantitative signal here. In the liver-abscess literature cited in the review, percutaneous catheter drainage was associated with approximately four fewer days of intravenous antibiotics compared with needle aspiration (Lin et al., 2023).

That is an important conceptual shift. We usually think of antimicrobial stewardship as:

Which antibiotic?
What dose?
For how long?

But sometimes the most effective antimicrobial intervention is not another change in the prescription.

It is:

Drain the collection.

So what would a POCUS stewardship protocol actually look like?

This is where the idea becomes practical. I am not proposing that every patient receiving antibiotics undergo a comprehensive ultrasound examination. Nor am I suggesting that POCUS replace microbiology, biomarkers, CT, formal radiology or clinical judgment.

Instead, imagine a protocolized multiorgan POCUS assessment for patients with sepsis or undifferentiated critical illness in whom the infectious source remains uncertain.

POCUS should not become an “antibiotic oracle”

This distinction is important.

POCUS does not tell us:

Antibiotics: YES.

or

Antibiotics: NO.

It gives us additional information.The proposed model is therefore:

POCUS + microbiology + biomarkers + clinical judgment

POCUS provides rapid anatomical and physiological information. Microbiology provides pathogen-specific information. Biomarkers provide additional probability information. Clinical judgment integrates everything with the patient’s presentation.

This is consistent with current antimicrobial stewardship guidance emphasizing diagnostic accuracy and appropriate empiric antimicrobial therapy within ED practice (Schoffelen et al., 2024). The manuscript therefore proposes POCUS as a bedside diagnostic adjunct within an integrated stewardship pathway, rather than as a standalone intervention.

And I think this is an important distinction. Because the goal of antimicrobial stewardship is not to give fewer antibiotics at any cost.

The goal is to give the right antibiotics to the right patient, for the right reason, for the right duration.

Sometimes POCUS may help us narrow. Sometimes it may help us stop. Sometimes it may tell us that we need to broaden.

And sometimes it may tell us that the most important intervention is not another antibiotic at all. It is source control.

But here is where we need to be honest

This is the most important limitation of the entire concept.

The evidence is not yet where the hypothesis is.

Current studies demonstrate that POCUS can improve diagnostic clarification and frequently change early management.

In undifferentiated shock, studies cited in the review report management changes in approximately 24–53% of cases (Cortellaro et al., 2017; Zieleskiewicz et al., 2015).

But management change is not the same thing as antimicrobial stewardship.

We still need to know:

Does POCUS reduce days of therapy?

Does it reduce spectrum days?

Does it increase appropriate de-escalation?

Does it reduce unnecessary antibiotics?

Does it improve the appropriateness of empiric therapy?

These are the outcomes that matter.

And remarkably few studies have directly measured them.

Most available evidence evaluates diagnostic accuracy, management modification or time to intervention rather than antibiotic-specific outcomes (Schoffelen et al., 2024; Lhopitallier et al., 2021).

So this review does not claim that POCUS has already been proven to reduce antibiotic consumption.

It proposes something different:

A clinically plausible framework that now needs to be tested.

The next POCUS study shouldn’t just ask, “Can ultrasound diagnose this?”

We have already spent years answering questions about diagnostic accuracy.

The next generation of studies should ask a different question:

“What happens to antimicrobial use when POCUS becomes part of the decision pathway?”

Imagine a prospective multicentre study.

Standard sepsis care

versus

Standard sepsis care + structured POCUS stewardship pathway

And measure outcomes that antimicrobial stewardship programs actually care about:

• Days of therapy

• Spectrum days

• Appropriateness of empiric therapy

• Time to antimicrobial de-escalation

• Time to source identification

• Time to source control

• Unnecessary antibiotic exposure

These are precisely the types of outcomes identified as priorities for future research in the review. The question is no longer whether POCUS can see pathology. The question is whether seeing pathology earlier changes what we do with antibiotics.

A different way to think about the probe

Perhaps we have been thinking about POCUS too narrowly.

We call it a diagnostic tool.

A resuscitation tool.

A procedural tool.

But perhaps, in the emergency department, its greatest stewardship value lies in something more fundamental:

It reduces uncertainty.

And uncertainty is one of the drivers of broad empiricism.

So perhaps the sequence should not always be:

Sepsis → Antibiotics → Investigations → Reassessment

Perhaps, whenever clinically appropriate, we should increasingly think:

Suspected sepsis → POCUS-informed phenotype → Source / mimic / source control → More targeted antimicrobial decision

Not instead of early antibiotics when they are clearly indicated.

But alongside them.

Because early treatment and diagnostic precision do not have to be opposing philosophies.

We can give antibiotics early and improve the information behind that decision early.

FIND. DE-SELECT. CONTROL.

That is the framework I would like to leave you with.

Find the infection.

Move from possible sepsis toward a probable anatomical source.

De-select the mimic.

Recognize when a non-infectious diagnosis better explains the physiology.

Control the source.

Because definitive source control may be more important than escalating antimicrobial therapy.

And perhaps this is the larger opportunity for POCUS in antimicrobial stewardship:

The probe may not tell us which antibiotic to give.

It may help us understand why we are giving one in the first place.

And perhaps antimicrobial stewardship in the emergency department shouldn’t begin with the antibiotic.

Perhaps it begins with the POCUS probe.

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References

• Cortellaro F, Ferrari L, Molteni F, et al. Accuracy of POCUS to identify sepsis source. Academic Emergency Medicine. 2017;24:737–744.

• Desai D, Shah AB, Dela JRC, et al. Lung ultrasonography accuracy for diagnosis of adult pneumonia: systematic review and meta-analysis. Advances in Respiratory Medicine. 2024;92:241–253.

• Dewan N, Zuluaga D, Osorio L, et al. Ultrasound in dengue: a scoping review. American Journal of Tropical Medicine and Hygiene. 2021;104:826–835.

• Lhopitallier L, Kronenberg A, Meuwly JY, et al. Procalcitonin and lung ultrasonography point-of-care testing to determine antibiotic prescription. BMJ. 2021;374:n2132.

• Lin JW, Chen CT, Hsieh MS, et al. Percutaneous catheter drainage versus percutaneous needle aspiration for liver abscess. BMJ Open. 2023;13:e072736.

• Maw AM, Hassanin A, Ho PM, et al. Diagnostic accuracy of point-of-care lung ultrasonography and chest radiography in adults with symptoms suggestive of acute decompensated heart failure. JAMA Network Open. 2019;2:e190703.

• Perera P, Mailhot T, Riley D, et al. The role of ultrasound in sepsis. Critical Care Medicine. 2010;38:2030–2037.

• Schoffelen T, Papan C, Carrara E, et al. European Society of Clinical Microbiology and Infectious Diseases guidelines for antimicrobial stewardship in emergency departments. Clinical Microbiology and Infection. 2024;30:1384–1407.

• Summers SM, Scruggs W, Menchine MD, et al. A prospective evaluation of emergency department bedside ultrasonography for the detection of acute cholecystitis. Annals of Emergency Medicine. 2010;56:114–122.

• Tamma PD, Cosgrove SE, et al. Antimicrobial stewardship. Infectious Disease Clinics of North America. 2011;25:245–260.

• Tayal VS, Hasan N, Norton HJ, et al. Ultrasound in soft tissue infection. Academic Emergency Medicine. 2006;13:384–388.

• Verras C, Ventoulis I, Bezati S, et al. Point-of-care ultrasonography for the septic patient in the emergency department: a literature review. Journal of Clinical Medicine. 2023;12:1105.

• Volpicelli G, Lamorte A, Tullio M. Point-of-care multiorgan ultrasonography for evaluation of undifferentiated hypotension in the emergency department. Intensive Care Medicine. 2013;39:1290–1298.

• Zieleskiewicz L, Muller L, Lakhal K, et al. Point-of-care ultrasound in intensive care units: assessment of 1073 procedures in a multicentric prospective observational study. Intensive Care Medicine. 2015;41:1638–1647.

A patient stops drinking → becomes tremulous and agitated → the CIWA score rises → benzodiazepines are given.

But severe alcohol withdrawal is not a scoring problem. It is a dynamic neuro-physiologic syndrome, and the most important decisions happen before the number on the chart tells you what to do.

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I went through two useful approaches to alcohol withdrawal (Josh Farkas’ EMCrit/IBCC approach and the 2024 Annals of Emergency Medicine review by Gottlieb, Chien and Long) and tried to translate them into something that is practical at the ED bedside. The goal is not to create another “CIWA protocol.”

The goal is to answer:

Who is actually withdrawing, how sick are they, what should I give, and when should I stop giving it?

1. First question: Is this actually alcohol withdrawal?

Alcohol withdrawal syndrome occurs after cessation or reduction of heavy, prolonged alcohol use, with symptoms developing over hours to days. The underlying physiology is a shift toward CNS hyper-excitability: chronic alcohol exposure downregulates GABAergic activity and increases glutamatergic activity. When alcohol is removed, the inhibitory “brake” disappears while the excitatory system remains activated.

The bedside history matters more than the score

Ask:

• How much alcohol does the patient usually drink?

• Daily drinking or binge pattern?

• When was the last drink?

• What happens when they stop drinking?

• Previous withdrawal seizures?

• Previous delirium tremens?

• Previous ICU admission/intubation for withdrawal?

• Previous detoxification/rehabilitation?

• Concomitant benzodiazepine or other sedative use?

EMCrit particularly emphasizes obtaining collateral history when the patient cannot provide a reliable history.

Don’t let a positive alcohol level reassure you

A patient can be actively withdrawing despite still having alcohol in the bloodstream.

In fact, the EMCrit review notes that an admission alcohol level >200 mg/dL may identify a patient at particularly high risk of withdrawal, especially when combined with a history suggesting dependence.

2. Know the clock

The timeline helps you anticipate what comes next.

The 2024 Annals review describes initial symptoms beginning around 6–8 hours, with withdrawal generally peaking around 72 hours.

A practical implication

Time is not just documentation - it is a diagnostic tool.

A patient becoming delirious on day 5 should make you reconsider the assumption that “this is just alcohol withdrawal.”

Think:

• Sepsis

• Hypoglycemia

• Head injury

• Hepatic encephalopathy

• Medication toxicity

• Other withdrawal states

• Metabolic abnormalities

• Non-alcohol-related delirium

Both sources emphasize that alcohol withdrawal and particularly delirium tremens

is a clinical diagnosis of exclusion.

3. Before treating the agitation, ask: “What else could this be?”

This is probably the most important bedside step. A tachycardic, hypertensive, confused patient with a history of alcohol use does not automatically have delirium tremens.

Check:

Glucose → temperature → electrolytes → trauma → infection → liver disease → medications/toxins → neurologic pathology.

EMCrit review specifically recommends glucose and electrolyte assessment including Mg and phosphate, along with CBC, coagulation studies and liver tests; chest imaging and CT head should be considered when clinically indicated, particularly with trauma risk.

4. The cirrhotic patient is a diagnostic trap

One of the most dangerous mistakes is:

“Cirrhosis + agitation = alcohol withdrawal.”

Hepatic encephalopathy and alcohol withdrawal can look very different physiologically.

EMCrit emphasizes that patients with hepatic encephalopathy may be unusually sensitive to GABAergic drugs. Benzodiazepines and barbiturates can therefore produce prolonged sedation, and hepatic encephalopathy is considered a strong contraindication to phenobarbital in that framework.

So in a patient with advanced liver disease, ask:

Does the patient actually have the sympathetic/autonomic and motor findings of withdrawal?

Look for:

• Tremor

• Diaphoresis

• Tachycardia

• Hypertension

• Hyperreflexia

• Agitation

• Hallucinations

• Recent cessation/reduction

If those aren’t present, repeatedly escalating GABAergic sedation may be treating the wrong disease.

5. PAWSS answers a different question from CIWA

This distinction is extremely useful.

PAWSS = “Who is at risk of complicated withdrawal?”

CIWA/RASS = “How symptomatic/agitated is the patient right now?”

PAWSS is a validated screening tool intended to identify patients at risk for complicated withdrawal and is suggested early in the assessment of patients with chronic alcohol use. The Annals review notes that it may have value in the ED, although further ED validation is still needed.

So:

PAWSS → risk prediction
CIWA/RASS → treatment monitoring

Don’t use a high CIWA score to retrospectively establish the diagnosis.

6. CIWA is useful, but it has limitations

CIWA-Ar is probably the most familiar alcohol-withdrawal tool.

But it has a major limitation:

The patient has to participate in it.

It requires communication and can be confounded by other illnesses, anxiety, psychiatric disease and other physiologic abnormalities. It is also labor intensive.

That makes CIWA problematic in:

• Delirious patients

• Intubated patients

• Patients unable to communicate

• Severe agitation

• Head injury

• Critically ill patients

• Patients with competing causes of tachycardia/agitation

Where does RASS fit?

RASS is objective, faster and does not require patient participation. The 2024 review describes a target of light sedation, approximately RASS +1 to −1.

EMCrit particularly favors RASS as the bedside target for phenobarbital titration.

My practical interpretation

Don’t treat the number. Treat the patient’s physiology, and use the score to help you track response.

7. Phenobarbital vs Benzodiazepines: Which One Should I Choose in the ED?

For decades, benzodiazepines have been the default treatment for alcohol withdrawal syndrome (AWS).

And for good reason.

They are effective, familiar, rapidly titratable, and have the strongest historical evidence for preventing withdrawal seizures and delirium. The ASAM guideline continues to describe benzodiazepines as first-line therapy for moderate and severe AWS.

But phenobarbital has made a significant comeback.

The question at the bedside is therefore not:

“Is phenobarbital better than benzodiazepines?”

A more useful question is:

“Which patient is better suited to phenobarbital, and which patient is better suited to benzodiazepines?”

The pharmacologic difference matters

Both drugs ultimately enhance inhibitory GABAergic neurotransmission, but they do it differently.

Benzodiazepines

Benzodiazepines increase the frequency of GABA-A chloride channel opening when GABA is present. This is important because chronic alcohol exposure produces neuroadaptation with reduced GABAergic responsiveness.

Phenobarbital

Phenobarbital increases the duration of GABA-A channel opening and also has effects on excitatory glutamatergic signaling. This broader pharmacologic activity is one reason it has theoretical and clinical appeal in severe or benzodiazepine-resistant withdrawal.

So the conceptual difference is:

Benzodiazepine → predominantly GABAergic amplification

Phenobarbital → GABAergic amplification + suppression of excitatory signaling

This may be particularly relevant in patients who become resistant to escalating benzodiazepine doses.

What does the comparative evidence actually show?

The evidence is encouraging—but not definitive.

The 2023 ED systematic review/meta-analysis included 8 studies, 1,507 patients and 2,012 treatment encounters. It found no significant difference between phenobarbital and benzodiazepines in ICU admission, hospital admission, ED readmission or adverse events. Importantly, the authors rated the overall evidence as low-to-moderate quality with moderate-to-high risk of bias and heterogeneity.

So:

Phenobarbital has not yet earned the label “universally superior.”

But newer observational data are increasingly interesting.

A 2026 propensity-matched cohort suggests lower rates of withdrawal seizures and delirium tremens with phenobarbital monotherapy without an apparent increase in mortality, mechanical ventilation or aspiration.

That fits with the broader direction of the literature: phenobarbital appears to be a reasonable alternative, and in some populations may have clinically important advantages.

But the important word is alternative, not replacement.

Where phenobarbital may have an advantage

a. Severe withdrawal

Phenobarbital becomes particularly attractive as withdrawal severity increases.

The 2024 Annals of Emergency Medicine review describes phenobarbital loading with 5–10 mg/kg IV, with additional dosing according to clinical response, as one option for severe AWS.

ASAM similarly recognizes phenobarbital as an appropriate alternative to benzodiazepines for severe withdrawal, particularly when used by clinicians experienced with the drug and with close monitoring.

b. Benzodiazepine-resistant withdrawal

This may be the most compelling indication. Some patients simply require progressively larger benzodiazepine doses without achieving adequate control.

At that point, continuing:

diazepam → diazepam → diazepam → lorazepam → more lorazepam

may not be the best strategy.

EMCrit specifically suggests transitioning toward phenobarbital in benzodiazepine-resistant delirium tremens. The pharmacology provides a plausible explanation: phenobarbital acts through mechanisms that are not identical to benzodiazepines.

c. A history of severe withdrawal

Consider phenobarbital early when the patient has a history of:

• Previous withdrawal seizures

• Previous delirium tremens

• Previous ICU admission for withdrawal

• Previous intubation

• Recurrent severe withdrawal

• High-risk withdrawal despite a currently modest CIWA score

These historical features are more useful than a single snapshot of the patient’s current score.

Some institutional phenobarbital protocols specifically identify previous withdrawal hospitalization, seizures/DTs, high admission alcohol levels and persistent symptoms despite benzodiazepines as triggers for a phenobarbital pathway.

d. When you want a long pharmacologic “tail”

This is one of phenobarbital’s practical advantages.

Phenobarbital has a very long half-life, allowing a loading strategy to provide sustained withdrawal suppression.

Instead of repeatedly chasing breakthrough symptoms with short-acting doses, an adequately loaded patient can effectively have a pharmacologic “self-taper.”

EMCrit uses this property as one of the major arguments for phenobarbital-based management. But this advantage becomes a disadvantage when you have chosen the wrong patient.

Because:

A long half-life is wonderful when you chose the right drug—and unforgiving when you chose the wrong diagnosis.

Where benzodiazepines may be the better choice

Phenobarbital should not become a reflex.There are several situations in which I would favor a benzodiazepine strategy.

a. Diagnostic uncertainty

This is an underappreciated reason. Phenobarbital is long acting.

If the patient’s agitation is actually due to:

• Sepsis

• Hepatic encephalopathy

• Intracranial pathology

• Toxicologic delirium

• Hypoglycemia

• Pain

• Other withdrawal

• Primary delirium

you have given a drug that may remain pharmacologically active for days.

EMCrit specifically warns against using phenobarbital when the diagnosis of AWS is uncertain because adverse effects are also prolonged. In such situations, titratable benzodiazepine therapy may be preferable.

b. Advanced liver disease / hepatic encephalopathy

This deserves special attention. Phenobarbital is hepatically metabolized, and the drug label lists marked hepatic impairment as a contraindication.

More importantly at the bedside:

Don’t confuse hepatic encephalopathy with alcohol withdrawal.

EMCrit considers hepatic encephalopathy a strong contraindication to phenobarbital because GABAergic drugs may produce prolonged sedation/coma in these patients.

ASAM recommends that when significant liver disease is present, a benzodiazepine with less hepatic metabolism should be used rather than relying on hepatically metabolized long-acting agents.

Practical distinction

Cirrhosis alone ≠ automatic contraindication to phenobarbital.

But:

Advanced hepatic dysfunction + suspected/known hepatic encephalopathy = strong reason to avoid phenobarbital.

And importantly, a patient can have both AWS and hepatic encephalopathy.

That is where the clinical examination matters most.

c. Respiratory compromise

Both drugs can cause respiratory depression. Phenobarbital’s narrow therapeutic window makes this particularly important. The ASAM guideline emphasizes that phenobarbital can cause respiratory depression and oversedation and is best used in settings with close monitoring by clinicians experienced with the drug.

The drug labeling lists severe respiratory distress with dyspnea or obstruction as a contraindication.

So a patient who is already:

• Hypoventilating

• Hypercapnic

• Difficult to protect their airway

• Receiving substantial opioids/sedatives

• Experiencing significant respiratory compromise

requires extreme caution before additional long-acting CNS depressants are administered.

d. The patient has already received a large benzodiazepine load

This is one of the most important ED situations.

Phenobarbital + benzodiazepines are not pharmacologically independent drugs.

Their sedative effects can be synergistic. EMCrit explicitly warns that a phenobarbital dose that is safe by itself can become dangerous when combined with large benzodiazepine exposure.

So don’t look only at:

“Phenobarbital dose = 10 mg/kg.”

Also ask:

“How much benzodiazepine has this patient already received?”

This is why cumulative sedative exposure is more important than the individual medication order.

e. Important drug interactions

Phenobarbital is a potent hepatic enzyme inducer and can alter the metabolism of multiple medications.

This matters in patients taking:

• Anticoagulants

• Antiretrovirals

• Immunosuppressants

• Antiseizure medications

• Other CYP-metabolized drugs

The interaction profile is substantially more complicated than many clinicians appreciate. Some institutional protocols specifically exclude patients receiving medications with important phenobarbital interactions.

So what are the “absolute” indications?

I would actually avoid the term “absolute indication.”

There is no universally accepted guideline that says:

“This patient must receive phenobarbital.”

Instead, think in terms of strong indications.

Strong reasons to consider phenobarbital

• Severe AWS

• Benzodiazepine-resistant AWS

• Previous severe/complicated withdrawal

• Withdrawal seizures where phenobarbital is an appropriate seizure/withdrawal agent

• Need for a long-acting agent with sustained withdrawal suppression

• A clinical environment where the treating team is experienced with phenobarbital and continuous monitoring is available

ASAM explicitly recognizes phenobarbital as an alternative to benzodiazepines in severe/complicated withdrawal and in patients with contraindications to benzodiazepines, provided the clinician is experienced and appropriate monitoring is available.

And what are the “absolute” contraindications?

Again, I would distinguish formal drug contraindications from clinical situations in which I would avoid it.

Formal phenobarbital contraindications include:

• Known hypersensitivity to barbiturates

• Manifest or latent porphyria

• Marked hepatic impairment

• Severe respiratory distress with dyspnea/obstruction

Strong clinical reasons to avoid or reconsider phenobarbital:

• Known/suspected hepatic encephalopathy

• Significant pre-existing respiratory depression

• Major diagnostic uncertainty

• Large recent benzodiazepine exposure

• Significant concomitant CNS depressant exposure

• Important drug interactions

• Lack of appropriate monitoring or clinician experience

My practical ED decision tree

8. If using benzodiazepines: front-load, don’t drip-feed endlessly

The Annals review emphasizes early, adequate treatment.For mild–moderate withdrawal, its practical algorithm describes:

Diazepam 10–20 mg IV/PO every hour until stabilized
or
Lorazepam 2–4 mg IV/PO every hour

followed by symptom-triggered maintenance therapy.

For severe withdrawal, it describes more aggressive IV titration, including diazepam 20 mg IV every 10 minutes or lorazepam 4 mg IV every 10 minutes, with higher doses potentially required when symptoms do not rapidly improve.

EMCrit favors IV diazepam because of its rapid onset and longer duration, reducing the risk of repeated doses being given before the previous dose has taken effect.

The bedside lesson

If the patient is truly withdrawing: Under-treatment is a problem.

Repeated tiny doses that never adequately control the syndrome can result in escalating requirements and delayed control.

9. A practical phenobarbital approach

The 2024 Annals review describes:

Initial loading

Phenobarbital 5–10 mg/kg IV over ~30 min

Additional doses can be given, with a maximum of 15 mg/kg in its algorithm. If weight-based loading is delayed or the patient has already received benzodiazepines:

130–260 mg IV every 15–30 min is described as an incremental strategy.

EMCrit describes another titration strategy using 130 mg IV approximately every 30 minutes, targeting a RASS of 0 to +1.

Why the difference?

The exact dosing strategy is protocol-dependent.

The shared principle is:

Give enough drug to control the withdrawal, reassess frequently, and keep track of the cumulative dose.

10. Don’t blindly stack phenobarbital + benzodiazepines

This is one of the most important safety points.

Phenobarbital and benzodiazepines have synergistic sedative effects. EMCrit specifically cautions against simultaneously titrating both upward and recommends keeping track of the cumulative phenobarbital exposure.

So if you’ve decided:

“This patient is going down the phenobarbital pathway.”

then avoid reflexively continuing to pile on benzodiazepines.

And if a patient has already received substantial benzodiazepine doses, recognize that the phenobarbital loading strategy may need modification.

11. What if the patient remains agitated?

This is where clinicians can get into trouble.
Agitation ≠ automatically more withdrawal.

If the patient has received an adequate amount of GABAergic therapy but remains agitated, reassess the diagnosis.

Look again for:

• Sepsis

• Hypoglycemia

• Head injury

• Hepatic encephalopathy

• Drug toxicity

• Pain

• Urinary retention

• Hypoxia

• Metabolic abnormalities

• ICU/non-alcohol-related delirium

EMCrit specifically describes a transition to non-alcohol-related delirium, where continued escalation of benzodiazepines or phenobarbital can worsen the situation.

This is a powerful bedside rule:

If the treatment isn’t working, don’t just increase the treatment. Reconsider the diagnosis.

14. Withdrawal seizures are different from “seizure in an alcoholic”

Alcohol withdrawal seizures are usually generalized tonic-clonic, brief and self-limited, and typically occur within 12–48 hours of cessation. But don’t assume every seizure in a patient with alcohol use is a withdrawal seizure.

Think about:

• Trauma/intracranial hemorrhage

• Metabolic abnormalities

• Epilepsy

• Infection

• Other toxicologic causes

• SESA syndrome

EMCrit notes that withdrawal seizures tend to recur if untreated and recommends treatment directed at the withdrawal physiology rather than relying on traditional antiseizure medications such as phenytoin.

Phenobarbital is particularly attractive here because the same drug can address both withdrawal physiology and seizure activity.

13. Adjuncts are adjuncts

This is where many protocols go wrong.

Dexmedetomidine

Useful for controlling persistent sympathetic activation and providing titratable sedation, particularly when large doses of benzodiazepines/barbiturates are already being used. But it does not replace definitive withdrawal therapy.

The Annals review notes reduced benzodiazepine requirements with dexmedetomidine but also an increased risk of bradycardia and hypotension.

EMCrit similarly emphasizes that alpha-2 agonists and antipsychotics should not be used as the primary treatment for withdrawal because they do not address the underlying GABA/glutamate imbalance or provide adequate antiseizure therapy.

Ketamine

Ketamine is an NMDA antagonist and therefore has a mechanistically attractive role in benzodiazepine-refractory withdrawal. The 2024 review describes limited evidence suggesting reduced benzodiazepine requirements and potentially lower intubation rates/ICU length of stay.

For the patient who is already intubated with severe refractory withdrawal, either ketamine or propofol may be reasonable.

14. Don’t forget the “boring” part of the resuscitation

Alcohol withdrawal is rarely just a neurotransmitter problem. These patients are frequently malnourished and electrolyte depleted.

Think:

Glucose

Patients with alcoholism and cirrhosis may have impaired glycogen reserves and are vulnerable to hypoglycemia.

Magnesium

Total-body magnesium deficiency can be substantial and may require repeated replacement.

Phosphate

Consider phosphate depletion and refeeding syndrome, particularly in severely malnourished patients.

Thiamine

If Wernicke encephalopathy is possible, EMCrit recommends high-dose IV thiamine 500 mg every 8 hours; in patients without altered mental status, it describes 100 mg IV daily for prevention.

The practical message:

Treat the patient, not just the withdrawal score.

15. What should the ED disposition look like?

The decision isn’t simply:

CIWA high → admit

or

CIWA low → discharge.

Think about:

• Severity and trajectory

• History of seizures/DT

• PAWSS/high-risk history

• Comorbid illness

• Electrolyte abnormalities

• Ability to maintain oral intake

• Social support

• Reliability of follow-up

• Risk of recurrent withdrawal

• Need for repeated IV medication

• Need for monitoring/airway support

Patients with severe or complicated withdrawal generally require monitored settings, while selected patients with mild disease and reliable follow-up may be candidates for outpatient management.

The 2024 review describes a short course of diazepam as possible bridging therapy in carefully selected patients only when an appropriately trained caregiver can monitor and administer it, reinforcing that discharge is a structured clinical decision rather than simply a low score.

16. And don’t discharge without addressing the underlying AUD

One of the missed opportunities in the ED is treating the withdrawal and forgetting the disease that caused it. Alcohol withdrawal is an acute complication of alcohol use disorder.

EMCrit describes naltrexone and acamprosate as the principal pharmacologic options, with medication ideally combined with psychosocial interventions. This doesn’t mean every ED patient needs medication started immediately. But every ED encounter should create an opportunity for:

Withdrawal treatment → brief intervention → treatment linkage → AUD pharmacotherapy when appropriate.

The bedside algorithm I would actually use

The take-home message

Alcohol withdrawal is often taught as:

“Calculate CIWA → give benzodiazepine → repeat.”

But the bedside reality is more nuanced.

Diagnose clinically.

Predict risk early.

Understand the timeline.

Choose your primary sedative strategy deliberately.

Treat the underlying neurophysiology rather than chasing agitation.

Use CIWA/RASS as tools—not as substitutes for clinical judgment.

And when treatment stops making sense, reconsider the diagnosis.

That last step may be the most important one.

‘For educational purposes only; local protocols, monitoring capability, comorbidities, and specialist input should guide actual patient care.’

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References

1. Farkas J. Alcohol withdrawal & alcohol use disorder. EMCrit/Internet Book of Critical Care. 2023.

2. Gottlieb M, Chien N, Long B. Managing Alcohol Withdrawal Syndrome. Ann Emerg Med. 2024;84:29–39. doi:10.1016/j.annemergmed.2024.02.016.

“The monitor alarms. The heart rate is 165 beats per minute. The nurse asks, ‘Doctor, should we shock?’

If you’ve worked in an emergency department, ICU, operating room, or acute medical unit, you’ve probably faced this exact moment.

Atrial fibrillation (AF) and atrial flutter are among the most common arrhythmias encountered in acute care, yet they remain one of the most misunderstood. The temptation is almost instinctive including reach for amiodarone, prepare for cardioversion, or aggressively lower the heart rate. However, the monitor often tells only a part of the story.

In acute illness, AF is frequently a manifestation of physiological stress rather than the primary disease itself. Systemic inflammation, catecholamine excess, hypoxaemia, metabolic disturbances, myocardial dysfunction, and atrial stretch create an environment where atrial fibrillation becomes almost inevitable. Consequently, suppressing the arrhythmia without addressing the underlying trigger often results in treatment failure or early recurrence (Sibley et al., 2025; Farkas, 2024).

This distinction is important because AF during critical illness is not a benign event. New-onset atrial fibrillation (NOAF) develops in approximately 5–15% of critically ill patients and may occur in nearly half of patients with septic shock. Although some patients revert to sinus rhythm as their illness resolves, it is associated with prolonged hospitalization, thromboembolic complications, heart failure, recurrent AF, and increased long-term mortality (Sibley et al., 2025).

The challenge for the acute care physician, therefore, is not simply how to treat atrial fibrillation, but rather how to understand why it appeared in the first place.

Think Physiology Before Pharmacology

One of the most important messages from both the 2025 Intensive Care Medicine review and the EMCrit approach is that AF in acute care should be viewed differently from chronic outpatient AF.

In the outpatient clinic, management revolves around long-term stroke prevention, symptom control, and maintenance of sinus rhythm. In the ICU or emergency department, priorities are entirely different.

The clinician must determine:

• Is AF causing the patient’s instability?

• Or is AF merely reflecting worsening physiological stress?

Those two questions determine almost every subsequent management decision.

Many critically ill patients develop AF because the atria are exposed to inflammation, adrenergic stimulation, electrolyte abnormalities, fluid shifts, hypoxia, or myocardial dysfunction. In such situations, AF behaves less like an isolated arrhythmia and more like a marker of systemic illness. Treating only the rhythm while ignoring the underlying physiology rarely succeeds (Sibley et al., 2025).

The Four Questions Every Acute Care Physician Should Ask

1. Is this really atrial fibrillation?

Although telemetry frequently suggests AF, diagnosis should always be confirmed with a 12-lead ECG. An irregularly irregular rhythm without discernible P waves strongly supports the diagnosis. Clinicians should also differentiate AF from multifocal atrial tachycardia, or atrial tachycardia, as management strategies differ (Farkas, 2024).

2. Why did AF occur today?

This may be the single most important question in the entire approach. Rather than immediately reaching for anti-arrhythmics, clinicians should actively search for reversible precipitants.

Common triggers include:

• Sepsis

• Septic shock

• Pulmonary embolism

• Acute myocardial ischaemia

• Respiratory failure

• Hypoxaemia

• Hypercapnia

• Hypokalaemia

• Hypomagnesaemia

• Thyrotoxicosis

• Pain

• Agitation

• Alcohol withdrawal

• Catecholamine infusions

• Fluid overload

• Hypovolaemia

• Major surgery

(Farkas, 2024).

These triggers are not merely associated with AF—they often sustain it. Consequently, correcting the underlying pathology frequently results in spontaneous cardioversion without the need for anti-arrhythmic therapy (Sibley et al., 2025).

Frontline Pearl

Every episode of AF deserves a search for the trigger before a search for the right drug.

3. Is AF causing instability or is instability causing AF?

This question separates experienced clinicians from reflexive treatment. Not every patient with hypotension and AF requires immediate cardioversion.

Instead, ask:

• Did hypotension begin after AF?

• Is the ventricular rate extremely rapid?

• Does the patient have severe mitral stenosis, pulmonary hypertension, or marked diastolic dysfunction where loss of atrial contraction is poorly tolerated?

Heart rates below approximately 150 beats/min are less likely to be the sole cause of haemodynamic collapse. Conversely, severe sepsis, haemorrhage, pulmonary embolism, or cardiogenic shock frequently precipitate AF, making the arrhythmia a consequence rather than the cause of instability (Farkas, 2024).

“Not every hypotensive patient with atrial fibrillation needs cardioversion. The challenge is determining whether the arrhythmia is the culprit—or merely a witness to a much larger physiological crisis.”

One of the most common cognitive errors in acute care is assuming that the abnormal rhythm displayed on the monitor is responsible for the patient’s instability. In reality, atrial fibrillation is frequently a secondary manifestation of systemic physiological stress, particularly in critically ill patients. Sepsis, hypoxaemia, catecholamine excess, pulmonary embolism, myocardial ischaemia, electrolyte abnormalities, and acute volume shifts all increase atrial electrical instability and may precipitate AF. In these situations, the arrhythmia is often an epiphenomenon rather than the primary haemodynamic insult (Sibley et al., 2025).

Recognising this distinction is crucial because the management pathways diverge dramatically. Electrical cardioversion or aggressive rate reduction may rapidly improve a patient whose instability is directly attributable to AF. Conversely, if AF has developed as a consequence of severe sepsis or circulatory shock, suppressing the rhythm without correcting the underlying pathology is unlikely to improve haemodynamics and may even reduce compensatory cardiac output (Farkas, 2024).

4. What physiology needs to be restored?

Reviewed sources consistently emphasise that general physiological optimisation is often the most effective anti-arrhythmic intervention.

This includes:

• Optimising oxygenation and ventilation

• Correcting hypokalaemia and hypomagnesaemia

• Treating sepsis

• Managing pain and agitation

• Reviewing vasoactive medications

• Optimising intravascular volume

• Addressing fluid overload when present

General supportive care frequently contributes more to successful rhythm restoration than antiarrhythmic drugs themselves (Farkas, 2024; Sibley et al., 2025).

Rate Control or Rhythm Control?

Perhaps no debate in acute care generates more discussion. Interestingly, there are no large randomized trials directly comparing rate and rhythm control in general ICU populations.
Consequently, management must be individualized rather than algorithmic (Farkas, 2024).

Patients who often favour rate control

A rate-control strategy may be appropriate in patients with:

• Chronic AF

• AF lasting more than 48 hours without anticoagulation

• Severe left atrial enlargement

• Persistent physiological stress

• Low likelihood of successful cardioversion.

In these patients, forcing sinus rhythm may be difficult, transient, or increase thromboembolic risk if atrial thrombus has developed.

Patients who may benefit from rhythm control

Rhythm control deserves stronger consideration in:

• New-onset AF during critical illness

• Pulmonary hypertension

• Significant diastolic dysfunction

• Mitral stenosis

• Heart failure with reduced ejection fraction

• Persistent atrial flutter

• Failure of adequate rate control

These patients often depend on atrial contraction to maintain cardiac output, making restoration of sinus rhythm physiologically advantageous (Farkas, 2024).

Choosing the Right Drug

Drug selection should be guided by physiology rather than habit.

Magnesium

Magnesium deserves consideration early in many critically ill patients. Beyond correcting deficiency, intravenous magnesium has favourable safety data, may facilitate cardioversion, improve response to other antiarrhythmics, and assist with ventricular rate control (Farkas, 2024).

Amiodarone

Amiodarone remains one of the most frequently used antiarrhythmics in acute care because it provides both rhythm and rate control. Although cardioversion success varies, combining amiodarone with magnesium may improve rhythm maintenance (Sibley et al., 2025).
Look at QTc and hemodynamic trend before starting it.

Beta-blockers

Short-acting beta-blockers are increasingly supported in selected patients, particularly when adrenergic excess is driving tachycardia. Emerging data suggest effective heart-rate control without major haemodynamic compromise in carefully selected critically ill patients (Sibley et al., 2025).

Digoxin

Digoxin has a more limited role but may be useful in patients with reduced systolic function or decompensated heart failure where negative inotropic drugs are undesirable (Sibley et al., 2025).

What About Electrical Cardioversion?

Electrical cardioversion occupies an important place in advanced life support, but its role in critical illness is often overestimated.

Immediate cardioversion is appropriate when AF is clearly the primary cause of severe haemodynamic instability. However, this situation is less common than many clinicians assume.

When AF develops secondary to ongoing physiological stress, cardioversion alone frequently fails because the underlying substrate remains unchanged. Initial success rates are modest, and recurrence is common unless the precipitating illness is corrected (Sibley et al., 2025; Farkas, 2024).

Frontline Pearl

Shocking the rhythm without treating the physiology often produces only temporary success.

Why Atrial Flutter Deserves Separate Attention

Although often discussed alongside AF, atrial flutter behaves differently.

The ventricular response is frequently fixed around 150 beats/min because of 2:1 atrioventricular conduction, making pharmacological rate control frustratingly difficult. Consequently, rhythm-control strategies are often more successful and clinically attractive in atrial flutter than in AF (Farkas, 2024).

Recognising this distinction prevents repeated escalation of rate-control medications that may never adequately control ventricular rate.

Putting It All Together: A Bedside Framework

This physiology-first approach aligns with the central themes of both the 2025 narrative review and the EMCrit framework, emphasising individualized management rather than reflexive adherence to a single algorithm.

Take-Home

AF in acute care is rarely “just an arrhythmia.” More often, it is a window into the patient’s underlying physiology. Successful management begins not with amiodarone or cardioversion, but with understanding why the rhythm developed in the first place. Treat the sepsis, optimise oxygenation, correct electrolytes, restore haemodynamics, and reassess the rhythm. Drugs and shocks certainly have their place, but they are most effective when the underlying pathophysiological drivers have already begun to resolve.

Ultimately, the monitor should guide your attention but the patient’s physiology should guide your treatment.

References
1. Sibley S, Bedford J, Wetterslev M, et al. Atrial fibrillation in critical illness: state of the art. Intensive Care Med. 2025;51(5):904-916. doi:10.1007/s00134-025-07895-0

2. Farkas J. Atrial fibrillation (AF) & flutter complicating critical illness. Internet Book of Critical Care (IBCC), EMCrit Project. Updated April 6, 2024. Accessed August 6, 2026. https://emcrit.org/ibcc/af/

Summarised By -
Dr Arihant Jain, MD | lifeonthefrontline.com
Instagram: @humans.of.em
X | Linkedin | ORCID
—————————————————————
It Started Like Every Other Night Shift

It was 2:17 a.m.

The emergency call from triage was brief.

“Sixty-eight-year-old male. Severe breathlessness. Oxygen saturation 84%.”

Within minutes, he was wheeled into the resuscitation bay. He looked frightened.

His respiratory rate was nearly 40 breaths per minute. Every breath was laboured. The accessory muscles in his neck were contracting with each inspiration, and despite receiving oxygen through a non-rebreather mask at 15 litres per minute, his oxygen saturation refused to climb beyond 86%.

The chest radiograph showed bilateral infiltrates. The arterial blood gas confirmed severe hypoxaemia. There was no significant hypercapnia.

The respiratory therapist looked at me.

“Should we start High-Flow Nasal Cannula?”

Across the room another physician asked,

“What about non-invasive ventilation?”

Meanwhile, someone quietly prepared the intubation drugs.

Three experienced clinicians.
Three different answers.
One patient.

Ten years ago, all three decisions could probably have been justified.

Today, the conversation is different—not because we have better machines, but because we have better evidence.

The recently published 2026 American Thoracic Society (ATS) Clinical Practice Guideline on Non-Invasive Respiratory Support for Adult Patients with Acute Respiratory Failure brings together nearly two decades of research to answer one simple question:

Which respiratory support should we choose, and more importantly, why?

Interestingly, the guideline is not organised around devices like HFNC, NIV or CPAP. Instead, it focuses on clinical syndromes—acute hypoxaemic respiratory failure, acute hypercapnic respiratory failure, pre-intubation support and post-extubation care. That shift may seem subtle, but it fundamentally changes how we think about respiratory support.

Stop Choosing Devices.
Start Understanding Physiology.

One of the biggest lessons from this guideline is that respiratory failure is not a single disease. Our patient with pneumonia is hypoxaemic because oxygen cannot effectively cross injured alveoli into the bloodstream.

A patient with COPD, on the other hand, often fails because they cannot ventilate adequately. Carbon dioxide accumulates, respiratory muscles fatigue and the work of breathing becomes unsustainable.

Both patients may look equally distressed. Both may have similar oxygen saturations. Yet they need completely different treatments. The question therefore is no longer,

“Which machine should I use?”

Instead, it becomes,

“What physiological problem am I trying to solve?”

That single question explains almost every recommendation in the ATS guideline.

How Are Guidelines Actually Made?

Most of us skip straight to the recommendations.

Strong recommendation.
Conditional recommendation.
Use.
Don’t use.
Move on.

But recommendations don’t appear overnight.

The ATS panel reviewed the available evidence using systematic reviews, network meta-analyses and the GRADE Evidence-to-Decision framework. Rather than asking whether a single trial was “positive” or “negative,” they looked at the totality of evidence, considering benefits, harms, certainty of evidence, patient values, feasibility and resource implications before making each recommendation.

This explains something many clinicians find confusing.

A strong recommendation does not necessarily mean there is overwhelming evidence for mortality benefit.

Instead, it means the panel is confident that, for most patients, the overall benefits outweigh the harms.

That distinction becomes very important as we return to our patient.

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The Story of High-Flow Nasal Cannula

Twenty years ago, patients like ours had very few options. They usually received conventional oxygen therapy until one of two things happened. Either they improved or they deteriorated enough to require intubation.

Conventional oxygen therapy has obvious limitations. Patients with severe respiratory distress often generate inspiratory flow rates much higher than the oxygen delivered through a face mask. As a result, room air becomes entrained, reducing the effective oxygen concentration reaching the lungs.

Clinicians therefore began looking for better alternatives.

High-flow nasal cannula (HFNC) appeared promising because it could deliver heated, humidified oxygen at much higher flow rates while maintaining a more consistent inspired oxygen concentration. Physiological studies also suggested that HFNC reduced anatomical dead space, generated a small amount of positive airway pressure and decreased the work of breathing.

The physiology made sense.

But physiology alone is never enough.

Clinical trials had to prove that these benefits translated into better patient outcomes.

The Trial That Changed the Conversation

A major turning point came with the FLORALI trial by Frat and colleagues (2015).

The investigators compared HFNC with conventional oxygen therapy and non-invasive ventilation in patients with acute hypoxaemic respiratory failure.

Although the primary outcome did not show a statistically significant reduction in intubation across the entire study population, HFNC demonstrated encouraging results, particularly among patients with more severe hypoxaemia. Mortality also appeared lower in some groups.

Perhaps more importantly, patients tolerated HFNC remarkably well. Suddenly, clinicians began asking a new question. Could HFNC become the first-line treatment for hypoxaemic respiratory failure?

FLORALI did not answer that question completely. But it changed the direction of research for the next decade.

Then Came COVID-19

The COVID-19 pandemic accelerated respiratory research more than anyone could have imagined. Hospitals across the world faced thousands of patients with severe viral pneumonia. Researchers rapidly compared HFNC, CPAP and non-invasive ventilation in randomised clinical trials.

Studies such as HENIVOT (Grieco et al., 2021) and RECOVERY-RS (Perkins et al., 2022) added valuable evidence, although they did not always reach identical conclusions. Some trials suggested benefits with CPAP. Others supported HFNC.

Some remained inconclusive.

Instead of providing one clear answer, the growing evidence highlighted an important reality:

No single trial should determine clinical practice.

This is exactly why the ATS panel performed a comprehensive evidence synthesis rather than relying on individual studies.

So Why Does ATS Recommend HFNC?

This is perhaps the most important question.

After reviewing 39 randomised controlled trials, the ATS panel concluded that HFNC should be preferred over conventional oxygen therapy for adults with de novo acute hypoxaemic respiratory failure, issuing a strong recommendation.

At first glance, that may seem surprising. The evidence for reducing mortality is not definitive. So why such a strong recommendation?

Because mortality is not the only outcome that matters.

Across multiple studies, HFNC consistently reduced the need for invasive mechanical ventilation, improved patient comfort and was generally well tolerated. Patients could communicate, eat, drink and clear secretions more easily than those receiving tightly fitting masks.

Importantly, HFNC also carried relatively few serious adverse effects.

When the ATS panel weighed all these outcomes together, the balance clearly favoured HFNC. This is an important reminder that evidence-based medicine is about more than a single p-value.

Why Not Simply Use NIV?

Many clinicians naturally ask another question. If non-invasive ventilation provides positive pressure, shouldn’t it work even better?

The answer is more nuanced.

NIV certainly has physiological advantages. It can reduce the work of breathing and improve gas exchange. However, it also comes with important drawbacks.

Tight-fitting masks are often uncomfortable.

Air leaks are common.

Pressure injuries may develop.

Patients frequently struggle to tolerate prolonged treatment.

Perhaps the greatest concern is delayed recognition of treatment failure. Continuing NIV in a patient who is steadily worsening may postpone intubation, potentially worsening outcomes. The ATS panel also discussed concerns that excessive spontaneous tidal volumes during NIV could contribute to further lung injury in some patients.

For these reasons, the guideline makes only a conditional recommendation for NIV in de novo hypoxaemic respiratory failure, while strongly recommending HFNC as the preferred initial strategy.

Back to Our Patient

The high-flow nasal cannula is connected.

Warm, humidified oxygen begins flowing.

Within minutes, his breathing slows.

His oxygen saturation climbs into the low 90s.

He is still critically ill.

But he is more comfortable.

More importantly, we have bought ourselves time to reassess, investigate and decide whether he truly needs intubation.

That is perhaps the biggest lesson from this part of the ATS guideline.

HFNC is not simply a better oxygen mask. It is a form of respiratory support that allows us to treat hypoxaemic respiratory failure while reducing the need for invasive ventilation in many patients. But as we leave this patient and walk toward the next bed, we encounter a completely different problem.

A woman with severe COPD.

She is not hypoxaemic because her lungs cannot absorb oxygen. She is hypercapnic because her lungs cannot eliminate carbon dioxide.

The same device that helped our first patient may not be the best choice for her.

Because in acute care, the right treatment is determined not by the machine, but by the physiology.

A Different Patient. A Different Problem.

As we finished stabilising our patient with severe pneumonia, another call came from the acute care unit. A 72-year-old woman with severe chronic obstructive pulmonary disease (COPD) had become progressively drowsy over the past few hours.

Unlike the previous patient, she was not gasping for breath.

She looked tired.

Every breath was shallow.

Her respiratory rate was only 24 breaths per minute, but her accessory muscles had clearly been working for hours.

The arterial blood gas told the real story.

pH: 7.22

PaCO₂: 78 mmHg

PaO₂: 64 mmHg

This wasn’t simply hypoxaemia.

This was ventilatory failure.

The resident, fresh from treating the previous patient, asked confidently,

“Should we start High-Flow Nasal Cannula?”

The consultant smiled.

“Different physiology, Different treatment.”

That single sentence probably summarises the entire ATS guideline better than any recommendation table.

When Carbon Dioxide Is the Problem

The patient with pneumonia struggled because oxygen couldn’t cross injured alveoli. The patient with COPD struggles because she cannot remove carbon dioxide. Years of airway obstruction have increased airway resistance, caused dynamic hyperinflation and placed enormous demands on already fatigued respiratory muscles.

Each breath requires tremendous effort. Eventually those muscles tire. Ventilation falls. Carbon dioxide rises. Acidosis develops. Unlike hypoxaemic respiratory failure, simply increasing oxygen does not solve the problem.

The patient needs assistance with ventilation, not just oxygenation.

That distinction explains why the ATS guideline makes very different recommendations for acute hypercapnic respiratory failure.

The Trial That Changed Everything

If there is one landmark trial that transformed acute respiratory care, it is the study by Brochard et al. (1995). Before this study, many patients with severe COPD exacerbations progressed directly to invasive mechanical ventilation.

Brochard and colleagues demonstrated that non-invasive ventilation (NIV) significantly reduced the need for intubation and improved clinical outcomes in carefully selected patients. For the first time, clinicians realised they could support ventilation without placing an endotracheal tube.

Several years later, Plant et al. (2000) showed that NIV could also be successfully delivered outside the intensive care unit, making this therapy available to far more patients. Together, these studies changed clinical practice worldwide.

Unlike many newer respiratory interventions, the evidence supporting NIV in COPD has remained remarkably consistent over time.

Does High-Flow Change the Story?

Over the past decade, enthusiasm for HFNC naturally extended to patients with COPD. After all, HFNC improves comfort, reduces anatomical dead space and decreases the work of breathing.

Could it replace NIV?

Several recent randomised trials explored this possibility. Some suggested that HFNC produced similar improvements in carefully selected patients with mild hypercapnia. Others showed better patient comfort and tolerance. These findings generated considerable excitement.

But the ATS panel looked beyond individual studies.

They examined the entire body of evidence. Most of these trials enrolled patients with relatively mild respiratory acidosis. Many allowed patients to cross over from HFNC to NIV when deterioration occurred. Very few included patients with severe hypercapnic respiratory failure. As a result, the evidence remained less certain than it initially appeared.

Why NIV Still Comes First

After reviewing 43 randomised controlled trials, the ATS panel concluded that NIV remains the preferred initial treatment for adults with acute hypercapnic respiratory failure, issuing a strong recommendation.

The reasoning is straightforward. NIV does something HFNC cannot reliably achieve. It actively assists ventilation. Inspiratory pressure support unloads fatigued respiratory muscles. Minute ventilation improves. Carbon dioxide falls. Acidosis begins to correct.

HFNC certainly has physiological benefits, but the available evidence does not yet demonstrate that it consistently replaces NIV in patients with clinically significant ventilatory failure.

That is why the ATS guideline takes a cautious approach.

HFNC may be considered in selected patients with mild respiratory acidosis, particularly when NIV is poorly tolerated, provided clinicians monitor the patient closely and are prepared to escalate treatment rapidly if deterioration occurs.

Once again, the recommendation reflects physiology.

Patients who cannot ventilate generally require ventilatory assistance.

Another Critical Moment: PreIntubation

Our first patient with pneumonia initially improved on HFNC. Six hours later, everything changed. His oxygen requirement continued to increase. He became increasingly confused. His respiratory muscles finally began to fail.

Now there was no debate.

He needed intubation. A new question emerged.

How should we oxygenate him before laryngoscopy?

For years, clinicians relied on conventional bag-mask ventilation. More recently, HFNC and NIV have both been proposed as superior preoxygenation strategies.

Randomised studies have shown benefits with both approaches in different clinical settings.

After reviewing the available evidence, the ATS guideline concludes that either HFNC or NIV is preferable to conventional oxygen therapy before intubation in acute hypoxemic respiratory failure, while recognising that current evidence is insufficient to recommend one clearly over the other.

Perhaps the most important message is that preoxygenation should not be an afterthought.

A patient with severe respiratory failure has very little physiological reserve.

Optimising oxygenation before induction may reduce life-threatening desaturation during airway management.

The Journey Doesn’t End After Extubation

Several days later, our patient improved. The infection resolved. Vasopressors were discontinued. He successfully completed a spontaneous breathing trial. Now another important decision awaited.

Should he receive conventional oxygen after extubation?

HFNC?

Or NIV?

Extubation is often viewed as the finish line. In reality, it is another high-risk transition. Some patients develop respiratory failure shortly after extubation and require re-intubation, an event associated with increased morbidity and mortality.

The ATS guideline therefore addresses respiratory support after extubation separately.

Rather than recommending the same strategy for every patient, the panel emphasises individual risk assessment.

Patients at higher risk of extubation failure may benefit from NIV, whereas HFNC represents an effective alternative in many others. Both strategies are favoured over conventional oxygen in appropriate clinical settings.

Once again, the message is remarkably consistent. Choose the therapy that matches the patient’s physiology and clinical risk.

What Makes This Guideline Different?

Every guideline tells us what to do. Good guidelines explain why. This ATS guideline succeeds because it avoids oversimplifying respiratory support. It does not claim that HFNC is universally superior. It does not suggest NIV is obsolete. Instead, it reminds us that every device has strengths, limitations and an appropriate clinical context.

Perhaps more importantly, it demonstrates how recommendations should be developed. The panel did not rely on a single influential study.

Instead, they systematically reviewed the available evidence, evaluated its certainty, balanced benefits against harms and considered patient values, feasibility and resource implications before issuing recommendations. For clinicians, this approach is just as valuable as the recommendations themselves.

Five Lessons I’ll Take Back to the Bedside

After reading the guideline, five practical lessons stand out.

1. Treat physiology before devices.

The question is never “HFNC or NIV?”

It is “What type of respiratory failure does this patient have?”

2. High-flow nasal cannula is no longer just an oxygen device.

It is a form of respiratory support that has become the preferred first-line therapy for many patients with de novo acute hypoxaemic respiratory failure.

3. NIV remains the cornerstone of acute hypercapnic respiratory failure.

Despite exciting research on HFNC, patients with significant ventilatory failure still benefit most from ventilatory assistance.

4. Strong recommendations are not based on mortality alone.

Comfort, avoidance of intubation, adverse events and patient preferences all matter.

5. Reassessment is more important than the initial device.

No form of respiratory support is successful if clinicians fail to recognise deterioration and escalate treatment when necessary.

Pulse Check

When I first started training, respiratory support often felt like choosing between machines. Today, I realise it is really about understanding physiology. The patient with pneumonia and the patient with COPD may arrive breathless, frightened and hypoxic. They may even occupy neighbouring beds. But their lungs are failing for completely different reasons.

The 2026 ATS guideline reminds us that evidence-based medicine is not about finding one device that works for everyone.

It is about recognising the physiological problem in front of us and choosing the therapy most likely to solve it. Technology will continue to evolve. New interfaces will emerge. Future trials may modify today’s recommendations.

But one principle is unlikely to change:

The best respiratory support is not the newest machine. It is the one that best matches the patient’s physiology, is supported by the strongest available evidence and is accompanied by continuous bedside reassessment.

That is the real lesson from twenty years of research—and perhaps the most important lesson for every acute care clinician.

Suggested Reading -
Goel A, Rochwerg B, Nava S, et al. Noninvasive respiratory support for adult patients with acute respiratory failure: An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2026;214(4):e30-e58. doi:10.1164/rccm.202607-1135ST

The Patient in Front of You

It’s 2 AM.

A 72-year-old woman arrives in your Emergency Department with new-onset atrial fibrillation. Her CHA₂DS₂-VASc score is 4.

A few bays away, a 55-year-old man is diagnosed with a segmental pulmonary embolism.

Meanwhile, the oncology service calls regarding a patient with metastatic colon cancer and recurrent DVT despite anticoagulation.

Three patients. Three thrombotic problems. One recurring question:

Which anticoagulant should we choose ?

Not long ago, the answer was usually warfarin.

Today, Direct Oral Anticoagulants (DOACs) have fundamentally changed how we prevent and treat thromboembolic disease. The recently released 2026 ACC Scientific Statement represents perhaps the most comprehensive modern review of DOAC use across atrial fibrillation, venous thromboembolism, cancer-associated thrombosis, stroke prevention, and special populations (Kumbhani et al., 2026).

But while DOACs have become standard therapy, their optimal use remains surprisingly misunderstood. This article explores what has changed, what hasn’t, and how acute care physicians should approach anticoagulation in 2026.

Why DOACs Changed Everything

For decades, warfarin dominated anticoagulation. It worked, but it came with significant challenges:

• Narrow therapeutic window

• Frequent INR monitoring

• Numerous food interactions

• Multiple drug interactions

• High variability between patients

DOACs were developed to overcome these limitations and now account for nearly 80% of oral anticoagulant prescriptions in many regions (Kumbhani et al., 2026).

The currently available DOACs include:

Factor Xa inhibitors

• Apixaban

• Rivaroxaban

• Edoxaban

Direct thrombin inhibitor

• Dabigatran

(Kumbhani et al., 2026)

Unlike warfarin, these agents provide predictable pharmacokinetics, fixed dosing, and generally do not require routine laboratory monitoring (Kumbhani et al., 2026).

The result?

A simpler, safer, and often more effective approach to anticoagulation.

The Most Important Update: Think Risk, Not Scores

One of the subtle but important shifts highlighted in the ACC statement is that anticoagulation decisions should increasingly be based on absolute thromboembolic risk rather than rigid dependence on CHA₂DS₂-VASc alone (Kumbhani et al., 2026).

Historically, clinicians memorized:

• CHA₂DS₂-VASc ≥2 → anti-coagulate

• CHA₂DS₂-VASc <2 → don’t

Reality is more nuanced. Patients with similar scores may have markedly different actual stroke risks depending on AF burden, cardiac substrate, renal function, and co-morbidities.

The modern approach emphasizes:

• Shared decision-making

• Individualized risk assessment

• Consideration of additional modifiers beyond traditional scoring systems

(Kumbhani et al., 2026).

Atrial Fibrillation: DOACs Are the New Default

For most patients with atrial fibrillation requiring anticoagulation, DOACs are now unequivocally preferred over warfarin (Kumbhani et al., 2026).

The reasons are straightforward:

• Similar or better stroke prevention

• Less intracranial hemorrhage

• Easier use

• No INR monitoring

The ACC Scientific Statement strongly supports DOACs as first-line therapy for non-valvular AF.

But There Are Two Major Exceptions

1. Mechanical Heart Valves

Despite years of hope, DOACs remain unsuitable. The RE-ALIGN trial demonstrated excess thromboembolic events and bleeding with dabigatran compared with warfarin in mechanical valve patients (Eikelboom et al., 2013).

More recently, the PROACT Xa trial showed higher rates of valve thrombosis and thromboembolic events with apixaban compared with warfarin (Kumbhani et al., 2026).

For mechanical valves:

Warfarin remains king.

2. Rheumatic Mitral Stenosis

The INVICTUS trial demonstrated superior outcomes with vitamin K antagonists compared with rivaroxaban among patients with rheumatic heart disease and AF (Connolly et al., 2022; Kumbhani et al., 2026).

This remains another domain where warfarin continues to outperform DOACs.

Acute VTE: The Era of DOAC Dominance

The management of DVT and PE has changed dramatically. Multiple pivotal trials and meta-analyses have demonstrated that DOACs achieve similar efficacy with less major bleeding than warfarin (Kumbhani et al., 2026).

Today:

DOACs are first-line treatment for most patients with acute VTE.

(Kumbhani et al., 2026)

Is Apixaban Becoming the Preferred DOAC?

If one theme repeatedly emerges throughout contemporary literature, it is the growing prominence of apixaban.

The 2026 ACC statement notes that recent evidence suggests an apixaban-based strategy may be associated with lower bleeding compared with rivaroxaban during VTE treatment (Kumbhani et al., 2026).

The COBRRA trial further strengthened this observation, showing lower bleeding rates with apixaban in acute VTE management (Kumbhani et al., 2026).

Additionally, the ACC consensus highlights apixaban as the preferred option in:

• Frailty

• Advanced age

• Prior bleeding

• Chronic kidney disease

(Kumbhani et al., 2026).

This does not mean rivaroxaban is obsolete. It means that when uncertainty exists, apixaban increasingly appears to offer the best balance between efficacy and safety.

The Most Common Mistake: Stopping Too Early

Many clinicians continue to think of anticoagulation as a 3–6 month treatment. For many patients, this is no longer true.

The ACC statement emphasizes extended anticoagulation for:

• Unprovoked VTE

• Recurrent VTE

• Persistent risk factors

• High recurrence risk profiles

(Kumbhani et al., 2026).

In these patients:

The question is not whether treatment lasts beyond six months.

The question is whether treatment should ever stop.

Cancer-Associated Thrombosis: One of the Biggest Changes in Modern Medicine

Perhaps no area has evolved faster than cancer-associated thrombosis (CAT). For years, LMWH was the unquestioned standard.

That paradigm has shifted. A 2022 meta-analysis by Frère et al. demonstrated significantly lower recurrent VTE rates with DOACs compared with LMWH, without differences in mortality.

Similarly, Schrag et al. (2023) reported recurrent VTE rates of 6.1% versus 8.8% in favor of DOACs during a randomized trial involving cancer patients.

The strongest contemporary evidence supports:

• Apixaban

• Edoxaban

• Rivaroxaban

for selected cancer patients (Masini et al., 2023; Fujisaki et al., 2024).

But Not Every Cancer Patient Is the Same

Bleeding risk remains highly tumor-specific. The literature consistently identifies:

• Gastrointestinal cancers

• Gastroesophageal tumors

• Some genitourinary malignancies

as populations where bleeding risk may outweigh benefits (O’Connell et al., 2020; Sabatino et al., 2020; Masini et al., 2023).

This is where individualized medicine still matters.

Chronic Kidney Disease: A Persistent Challenge

Anticoagulation in advanced CKD remains difficult. Evidence remains limited, particularly in dialysis populations.

The ACC statement concludes:

• Apixaban may be considered in dialysis patients

• Dabigatran should generally be avoided

(Kumbhani et al., 2026).

For acute care physicians, this often translates into one practical rule:

If severe renal dysfunction is present, pause before reflexively prescribing a DOAC.

Obesity: Time to Retire an Old Myth

Many clinicians remain hesitant to prescribe DOACs in severe obesity. Current evidence no longer strongly supports this concern.

The ACC statement specifically endorses:

• Apixaban

• Rivaroxaban

for patients with BMI ≥40 kg/m² (Kumbhani et al., 2026). The assumption that obesity automatically requires warfarin is increasingly outdated.

What If Your Hospital Doesn’t Have Reversal Agents?

This question frequently arises in low- and middle-income settings. Can DOACs still be used if idarucizumab or andexanet alfa are unavailable?

The literature suggests yes.

Reviews by Weitz (2017), Chaudhary et al. (2019), and Grottke et al. (2024) conclude that most DOAC-associated bleeding can be managed through supportive care, temporary drug interruption, and standard resuscitative measures.

Specific antidotes are primarily reserved for:

• Life-threatening bleeding

• Catastrophic hemorrhage

• Emergency surgery

(Gómez-Outes et al., 2023; Grottke et al., 2024).

When antidotes are unavailable, PCCs remain a reasonable rescue strategy despite lower-quality evidence (Pozzi et al., 2024; Tran et al., 2025).

The practical message:

DOACs do not require onsite antidotes to be prescribed safely.

However, hospitals should maintain protocols for catastrophic bleeding management.

The Future: Beyond AF and DVT

The 2026 ACC Scientific Statement hints at the future direction of anticoagulation.

Emerging areas include:

• Device-detected subclinical AF

• Atrial myopathy

• Post-ablation anticoagulation

• Left atrial appendage closure strategies

• Expanded cancer-associated thrombosis pathways

(Kumbhani et al., 2026).

Many of tomorrow’s anticoagulation decisions may depend less on rhythm and more on underlying atrial disease biology.

Pulse Check

A decade ago, anticoagulation was largely a warfarin-versus-not-warfarin discussion.

In 2026, the conversation has evolved.

DOACs have become the default anticoagulants for most patients with atrial fibrillation and venous thromboembolism. Yet success lies not in prescribing them blindly, but in selecting the right drug, at the right dose, for the right patient.

The emergency physician’s challenge is no longer:

“Should I anticoagulate?”

It is:

“Which anticoagulant offers this patient the greatest net clinical benefit?”

Increasingly, the answer is a DOAC.

And more often than not, it may be apixaban.

References

• Kumbhani DJ, et al. 2026 ACC Scientific Statement on Direct Oral Anticoagulants.

• Frère C, et al. 2022.

• Schrag D, et al. JAMA. 2023.

• Fujisaki T, et al. JACC CardioOncology. 2024.

• Grottke O, et al. Eur J Anaesthesiol. 2024.

• Tran HA, et al. Internal Medicine Journal. 2025.

• Weitz JI. Semin Respir Crit Care Med. 2017.

• Chaudhary R, et al. J Thromb Thrombolysis. 2019.

• Masini M, et al. Curr Oncol Rep. 2023.

• O’Connell C, et al. The Oncologist. 2020.

• Sabatino J, et al. JACC CardioOncology. 2020.

A Case We Have All Seen

A 58-year-old man collapses in a shopping mall. Bystander CPR is initiated. EMS arrives within 6 minutes.

• Initial rhythm: Ventricular fibrillation (VF)

• Shock #1 → VF persists

• Shock #2 → VF persists

• Epinephrine administered

• Shock #3 → VF persists

The monitor continues to display coarse VF. The question now is no longer:

“Should we shock again?”

The question is:

“Should we shock differently?”

For decades, resuscitation algorithms largely focused on repeating the same intervention: deliver another shock through the same pad position using the same vector. Recent evidence suggests that in refractory VF, changing how we defibrillate may be more important than simply shocking again.

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The Problem: Refractory Ventricular Fibrillation

Traditionally, refractory VF has been defined as VF persisting after three consecutive defibrillation attempts. Although only a minority of cardiac arrest patients develop refractory VF, they account for a disproportionate share of cardiac arrest mortality.

The challenge is straightforward:

• Every additional minute spent in VF worsens myocardial ischemia.

• Prolonged VF reduces the likelihood of ROSC.

• Neurologic outcomes deteriorate as low-flow time increases.

The goal therefore becomes:

Terminate VF as early as possible.

Why Standard Defibrillation May Fail

Several mechanisms may contribute to shock failure:

1. Inadequate Current Delivery

Not all delivered energy reaches the myocardium.

Current must pass through:

• Chest wall

• Lung tissue

• Thoracic structures

before reaching the heart.

Higher trans-thoracic impedance means lower effective myocardial current.

2. Suboptimal Shock Vector

Standard anterior-lateral pad placement delivers current along a single pathway.

Some regions of myocardium may receive inadequate current density.

If enough critical myocardium is not depolarized simultaneously, VF may continue.

3. Progressive Electrical Remodeling

The longer VF persists:

• ATP stores deplete

• Cellular acidosis develops

• Myocardial excitability changes

The heart becomes progressively harder to defibrillate.

This is why time in VF matters.

The Evolution of Alternative Defibrillation Strategies

Several strategies have emerged:

Escalating Shock Energy

Increasing delivered joules.

Vector Change (VC)

Changing pad position from:

Anterior-Lateral → Anterior-Posterior

Double Sequential External Defibrillation (DSED)

Using two sets of pads and two defibrillators. Among these, DSED has generated the greatest interest.

What Exactly Is DSED?

Double Sequential External Defibrillation (DSED) uses:

First Defibrillator

Anterior-Lateral pads

Second Defibrillator

Anterior-Posterior pads

Two shocks are delivered in rapid succession after three failed standard shocks. The goal is to expose the myocardium to multiple shock vectors and potentially greater current delivery.

Why Might DSED Work?

Several physiologic explanations have been proposed.

1. Multiple Shock Vectors

Different vectors may recruit myocardial regions not adequately exposed by standard defibrillation.

More myocardium depolarized simultaneously increases the probability of VF termination.

2. Higher Current Delivery

Investigators observed:

• Lower transthoracic impedance with anterior-posterior pads

• Greater estimated myocardial current delivery

Current—not energy—is the primary determinant of successful defibrillation.

3. Reduced Total Time in VF

Alternative defibrillation strategies appear to terminate VF earlier.

The shorter the duration of VF:

• The lower the low-flow state

• The greater the chance of neurologically intact survival

This may be the most important mechanism of all.

The Landmark Trial: DOSE-VF

Everything changed in 2022. The DOSE-VF Trial compared:

Standard Defibrillation

versus

Vector Change Defibrillation

versus

Double Sequential External Defibrillation

in patients who remained in VF after three standard shocks.

What Did DOSE-VF Show?

Compared with standard defibrillation:

DSED Improved

✅ VF termination

✅ ROSC

✅ Survival to hospital discharge

✅ Neurologically intact survival

DSED demonstrated superiority across every clinically meaningful outcome.

Vector Change Also Helped

Compared with standard defibrillation:

• Better VF termination

• Better survival to discharge

However, DSED remained the only strategy associated with improved neurologically intact survival.

The Most Important Clinical Message

The DOSE-VF investigators found that:

The greatest benefit occurred immediately after introducing DSED or vector-change shocks.

This suggests that refractory VF may not need more of the same therapy. It may need a different therapy.

DSED vs Vector Change: Which Should We Use?

This remains controversial.

The trial was not powered to directly compare DSED and vector change.

However:

• Point estimates favored DSED.

• Neurologically intact survival favored DSED.

• Rearrest rates were lower with DSED.

Current expert opinion:

Two Defibrillators Available?

Use DSED.

Only One Defibrillator Available?

Use Vector Change Defibrillation.

What About Defibrillator Damage?

Perhaps the most common concern.

Fortunately, available evidence is reassuring.

A survey involving over 1,100 DSED cases found:

Defibrillator Damage Rate

~0.4%

Importantly:
No damage was reported when using the sequential technique employed in DOSE-VF. Most reported cases occurred with simultaneous shock delivery or non-standard pad positioning.

Simultaneous vs Sequential Shocks

Interestingly, newer analyses suggest:

Very short intervals between shocks may terminate VF more effectively than longer delays. Some data suggest that nearly simultaneous shocks may produce the highest VF termination rates.

However:
Current guideline-supported practice remains the sequential technique used in DOSE-VF until additional evidence emerges.

The 2023 ILCOR Recommendation

Following DOSE-VF, ILCOR updated its guidance:

DSED or vector-change defibrillation may be considered in adults with VF/pVT persisting after three consecutive shocks.

If DSED is used:

• Follow a protocol similar to DOSE-VF

• A single operator should activate both defibrillators sequentially

Where Does ECMO Fit?

For many refractory VF patients, the discussion eventually becomes:

DSED or ECPR?

The answer is likely:

DSED first.

ECMO second.

DSED is:

• Fast

• Widely available

• Low cost

• Immediately deployable

ECMO requires:

• Specialized teams

• Transport logistics

• Significant resources

A reasonable strategy is:

Attempt advanced defibrillation first, then escalate to ECPR if ROSC is not achieved.

What Does the Future Look Like?

Several ongoing trials are now investigating:

Earlier DSED

Instead of waiting for three failed shocks.

Researchers are asking:

• Should DSED be used after the first failed shock?

• Should DSED be the initial strategy?

• Can AI identify patients likely to develop shock-refractory VF?

These studies may fundamentally reshape future cardiac arrest algorithms.

Practical Takeaways for Acute Care Physicians

1. Refractory VF is a Defibrillation Problem

Think beyond drugs.

The intervention most likely to change outcomes remains successful defibrillation.

2. After Three Failed Shocks, Change Your Strategy

Consider:

• Vector Change Defibrillation

• DSED

rather than simply repeating standard shocks.

3. If Two Defibrillators Are Available, Learn DSED

The strongest evidence currently favors DSED for refractory VF.

4. Time in VF Matters

Every minute spent in VF reduces survival.

Earlier VF termination may be the key mechanism behind improved outcomes.

5. The Defibrillation Landscape Is Changing

The future of cardiac arrest may not depend on more medications.

It may depend on delivering the right shock, through the right vector, at the right time.

Closing Thoughts

For decades, defibrillation was viewed as a binary intervention:

Shock or don’t shock.

The emerging evidence from DOSE-VF challenges that mindset. The next evolution in resuscitation may not come from a new drug or a new device. It may come from recognizing that when VF refuses to die, how we shock matters just as much as when we shock.

Read more here - Original Review Article

It’s 2:17 a.m.

A 58-year-old man arrives clutching his chest. The ECG leaves little room for doubt, an anterior STEMI. While the cath lab is being activated, the nurse turns to you.

“Doctor, which anti-platelet should I load?”

Before you’ve answered, another patient rolls in. A 72-year-old woman with a minor ischemic stroke, well within 4.5 hours of symptom onset.

Should she receive aspirin alone? Or dual anti-platelet therapy? or nothing at all?

As you’re reviewing her CT, the surgical registrar calls.

“We’ve got a patient with a perforated bowel. He’s on aspirin and ticagrelor after a stent placed three months ago. Can we stop them?”

Three patients. Three anti-platelet decisions. Three completely different answers.

Yet every one of them starts with the same question.

Why is this patient need an anti-platelet?

Not which drug. Not how long they’ve been taking it. But why?

‘If this article helped simplify a difficult bedside decision, consider sharing it with your ED or acute care team, leave your thoughts in the comments, and subscribe to Life on the Frontline for more practical, evidence-based guides from the world of emergency and acute care.’

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Because modern anti-platelet therapy is no longer about memorizing drugs. It’s about understanding the balance between thrombosis and bleeding, and recognizing that this balance changes with time (Kumbhani et al., 2026).

In the ED, we are often the first physicians to influence that balance. We decide what gets loaded, what gets withheld, what should continue before surgery, and what should never be stopped. This article isn’t a cardiology review.

It’s a practical guide to the anti-platelet decisions emergency and acute care physicians make every shift.

A Mental Model Before We Begin

Whenever you encounter a patient on anti-platelets, pause and ask three questions.

1. Why was it started?

• Acute coronary syndrome?

• PCI?

• Stroke?

• Peripheral arterial disease?

• Primary prevention?

2. How recent was the event?

Hours? Days? Weeks? Years?

A patient one week after PCI is very different from one who had a stent placed five years ago.

3. What is the biggest threat today?

Bleeding? Or thrombosis?

Everything else follows from these three questions.

Decision 1

Which Anti-platelet Should I Load in the Emergency Department?

This is probably the most common and one of the most important antiplatelet decisions we make.

The answer depends entirely on where the patient is going next.

• Primary PCI?

• Fibrinolysis?

• Early invasive NSTEMI?

• Conservative management?

Each pathway has a different strategy.

Scenario 1: STEMI Going for Primary PCI

Imagine you’re in the resuscitation bay. The ECG shows a large anterior STEMI. The cath lab has accepted the patient. Your priority is simple:

Achieve rapid and potent platelet inhibition before coronary instrumentation.

The current standard is:

• Chewed aspirin 162–325 mg

• Plus a P2Y12 inhibitor

For most patients undergoing primary PCI, ticagrelor or prasugrel are preferred over clopidogrel because they produce faster, more potent, and more predictable platelet inhibition, reducing ischemic events and stent thrombosis (Wallentin et al., 2009; Wiviott et al., 2007; Kumbhani et al., 2026).

Which P2Y12 Inhibitor Should I Choose?

Ticagrelor

Ticagrelor has become the default choice in many emergency departments. Why?

• Rapid onset

• No metabolic activation required

• Potent platelet inhibition

• Reversible receptor binding

The PLATO trial demonstrated lower cardiovascular mortality compared with clopidogrel without increasing overall major bleeding, making it an attractive first-line agent in ACS (Wallentin et al., 2009).

Prasugrel

Prasugrel is equally potent and in PCI-treated patients may even outperform ticagrelor in selected populations (Schüpke et al., 2019).

However, remember its major limitations. Avoid prasugrel in patients with:

• Previous stroke or TIA

• Age ≥75 years (unless benefits clearly outweigh risks)

• Weight <60 kg

Unlike ticagrelor, many operators prefer administering prasugrel after coronary anatomy has been defined, particularly if there is a realistic possibility the patient will require CABG.

Clopidogrel

Clopidogrel still has an important place. It remains reasonable when:

• Ticagrelor or prasugrel are unavailable

• Bleeding risk is high

• Cost is a major issue

• Potent P2Y12 inhibitors are contraindicated

Think of clopidogrel not as an “inferior” drug—but as the right drug for selected patients.

Frontline Pearl

PCI favors potent platelet inhibition. If the patient is heading to the cath lab, think ticagrelor or prasugrel first.

Scenario 2: STEMI Receiving Thrombolysis

Now imagine a different hospital. No PCI capability. Transfer will take four hours. The patient is receiving tenecteplase. Should you still load Ticagrelor or Prasugrel?

No.

This is one of the most common misconceptions among junior doctors. The evidence supporting fibrinolysis was built around clopidogrel, not the newer P2Y12 inhibitors.

Recommended Strategy

Why Not Ticagrelor?

Could ticagrelor work? Possibly.

Should it replace clopidogrel routinely with thrombolysis? Not yet.

The strongest evidence for pharmaco-invasive STEMI still supports aspirin plus clopidogrel after fibrinolysis, and contemporary guidelines continue to recommend this approach (Kumbhani et al., 2026).

Scenario 3: NSTE-ACS

Very High Risk or High Risk NSTE- ACS , continue same approach as of STEMI requiring PCI.
but for others,
This is where things become less straightforward. For years, many of us loaded clopidogrel as soon as we diagnosed NSTEMI. That practice has changed.

Modern evidence suggests routine pretreatment before coronary anatomy is known offers little benefit and may complicate patients who ultimately require CABG (Kumbhani et al., 2026).

My Practical Approach

If early angiography (<24 hours) is planned:

• Give aspirin.

• Discuss P2Y12 timing with cardiology.

• In many patients, defer loading until coronary anatomy is defined.

If angiography will be delayed or the patient is managed conservatively:
Loading with ticagrelor or clopidogrel when appropriate is reasonable.

Common ED Pitfalls

❌ Giving prasugrel to a patient with previous stroke.

❌ Loading ticagrelor in a patient receiving thrombolysis because “it’s newer.”

❌ Automatically loading every NSTEMI before discussing the invasive strategy.

❌ Forgetting that patients over 75 years receiving fibrinolysis do not receive a clopidogrel loading dose.

Decision 2

Does Every ACS Patient Still Need 12 Months of Dual Anti-platelet Therapy?

For years, the answer was simple. Every patient with ACS received 12 months of dual antiplatelet therapy (DAPT)—usually aspirin plus a P2Y12 inhibitor.

It was easy to remember. It was also easy to teach. But like many “rules” in medicine, it turned out to be only partly true. Over the past decade, improvements in stent technology, PCI techniques, and the availability of more potent anti-platelet agents have fundamentally changed the conversation. Today’s question is no longer:

“Should every patient receive 12 months of DAPT?”

Instead, we ask:

“How long does this particular patient need protection from thrombosis before the risk of bleeding becomes the greater threat?”

That shift—from fixed-duration therapy to individualized therapy—is perhaps the biggest conceptual change in modern anti-platelet management (Kumbhani et al., 2026).

The first month after an ACS is a dangerous time. Platelets are highly activated. The stent is still endothelializing. The culprit plaque remains biologically unstable.

This is precisely when dual antiplatelet therapy (DAPT) provides its greatest benefit. But as weeks turn into months, something interesting happens—the risk of stent thrombosis falls rapidly, while the cumulative risk of bleeding continues to rise.

That’s why modern antiplatelet therapy is no longer about one duration for everyone. It is about matching the duration of DAPT to the patient’s evolving balance between ischemic and bleeding risk (Kumbhani et al., 2026).

The New Way to Think About DAPT

Instead of asking:

“Should I stop DAPT at 12 months?”

Ask:

“Has the patient’s bleeding risk now become greater than their ischemic risk?”

If the answer is yes, shortening DAPT may be safer. If the answer is no, prolonged therapy may still provide benefit.

When Can We Shorten DAPT?

Several contemporary trials have shown that selected patients can safely transition to P2Y12 inhibitor monotherapy after 1–3 months of DAPT, reducing bleeding without a significant increase in ischemic events (Mehran et al., 2019; Valgimigli et al., 2021).

Who should you think about?

• Older adults

• Previous GI bleeding

• Chronic kidney disease

• Frailty

• Need for future surgery

• Concurrent anticoagulation

De-escalation: Less Can Be More

Imagine your patient returns three months after PCI. No recurrent ischemia. Now they develop upper GI bleeding.

Do they still need potent DAPT? Maybe not.

In carefully selected patients, switching from ticagrelor or prasugrel to clopidogrel, or stopping aspirin and continuing a P2Y12 inhibitor alone, can substantially reduce bleeding while maintaining acceptable ischemic protection (Kumbhani et al., 2026).

Decision 3

The Patient Has an Acute Ischemic Stroke. Should I Give Aspirin, Dual Antiplatelet Therapy, or Neither?

A 69-year-old man presents 90 minutes after sudden right arm weakness and aphasia. His CT brain shows no hemorrhage.

Before you think about aspirin or clopidogrel, ask yourself one question:

Is this patient a candidate for reperfusion therapy?

This is arguably the most important antiplatelet decision in acute stroke care. Giving anti-platelets too early in a patient proceeding for intravenous thrombolysis or mechanical thrombectomy can increase bleeding risk without improving outcomes.

Step 1: Is the Patient Eligible for Reperfusion?

Intravenous thrombolysis

Eligible?
Do NOT administer aspirin or any P2Y12 inhibitor before thrombolysis.

Following alteplase or tenecteplase, all antiplatelet and anticoagulant therapy should be withheld for the first 24 hours.

A repeat CT (or MRI) demonstrating no intracranial hemorrhage is required before initiating antiplatelet therapy (Powers et al., 2019; European Stroke Organisation, 2023).

Mechanical thrombectomy

Patients proceeding directly for thrombectomy without thrombolysis similarly should not receive routine antiplatelet loading before reperfusion, unless there is another specific indication (such as emergent intracranial stenting).

Once post-procedure imaging excludes hemorrhage, antiplatelet therapy can be started according to the underlying stroke mechanism and procedural findings.

(Kumbhani et al., 2026)

Minor Stroke: Aspirin Alone or Dual Antiplatelet Therapy?

A 69-year-old man presents with sudden right arm weakness that resolved within 20 minutes. His CT brain is normal. He has a National Institutes of Health Stroke Scale (NIHSS) score of 1.

Should he receive aspirin? Or dual antiplatelet therapy? The answer depends on stroke severity.

Minor Stroke and High-Risk TIA

Three landmark trials—CHANCE, POINT, and THALES—changed our practice. For patients with:

• Minor ischemic stroke (NIHSS ≤3)

• High-risk TIA (ABCD² ≥4)

Early initiation of DAPT reduces recurrent stroke, particularly during the first three weeks (Wang et al., 2013; Johnston et al., 2018).

Why Only 21 Days?

Because recurrent stroke risk is highest immediately after the event. After three weeks, the incremental benefit of DAPT diminishes, while bleeding risk continues to increase. Unlike ACS, where DAPT is measured in months, stroke DAPT is measured in weeks. (Kumbhani et al., 2026)

Decision 4

The Surgeon Wants to Stop the Anti-platelets

Few phone calls create more anxiety than this one.

“Doctor, can we stop the aspirin before surgery?”

The answer isn’t simply yes or no. It depends on why the patient is taking it. A patient taking aspirin for primary prevention is very different from one who underwent PCI six weeks ago.

Elective Surgery After PCI

Whenever possible:

• Delay surgery at least 6 months after PCI for chronic coronary disease.

• Delay surgery 12 months after PCI for ACS.

(Kumbhani et al., 2026)

Emergency Surgery

Sometimes surgery simply cannot wait.

Options include:

• Proceeding despite antiplatelet therapy when delay would be more dangerous.

• Platelet transfusion in selected life-threatening bleeding scenarios.

• Bridging with intravenous cangrelor in carefully selected recent PCI patients.

(Kumbhani et al., 2026)

Decision 5

The Patient Is Already Taking a DOAC

An 80-year-old patient with atrial fibrillation undergoes PCI.

Should you prescribe:

Aspirin + Clopidogrel + Apixaban?

That used to be standard practice. Today, prolonged triple therapy has largely disappeared.

Modern Strategy

For most patients:

• Short course of triple therapy (1–4 weeks)

• Then discontinue aspirin

• Continue DOAC + clopidogrel

This strategy substantially reduces bleeding while preserving ischemic protection (Kumbhani et al., 2026).

Final Thoughts

Antiplatelet therapy has become far more nuanced than it was a decade ago. Yet the bedside approach remains surprisingly simple. Understand why the therapy was started. Recognize how the patient’s risk changes with time. And remember that the best antiplatelet strategy is rarely the most aggressive one—it is the one that strikes the right balance between preventing thrombosis and avoiding harm.

As emergency and acute care physicians, we are often the first to make that decision. It may be as simple as choosing the correct loading dose in a STEMI, or as difficult as deciding whether to stop DAPT before emergency surgery. Either way, our decisions shape what happens long after the patient leaves the Emergency Department.

References

1. Kumbhani DJ, Gibson CM, Kinlay S, et al. Antiplatelet Therapy in the Management of Atherosclerotic Cardiovascular Disease: 2026 ACC Scientific Statement. J Am Coll Cardiol. 2026.

2. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009.

3. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in ACS undergoing PCI. N Engl J Med. 2007.

4. Schüpke S, Neumann FJ, Menichelli M, et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med. 2019.

5. Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or without aspirin after PCI (TWILIGHT). N Engl J Med. 2019.

6. Valgimigli M, Frigoli E, Heg D, et al. Dual antiplatelet therapy after PCI in high bleeding risk patients (MASTER DAPT). N Engl J Med. 2021.

7. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or TIA (CHANCE). N Engl J Med. 2013.

8. Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA (POINT). N Engl J Med. 2018.

Let’s start from where we left in Part -1.

Step Three:

Is There Evidence of Ischemia?

An elevated troponin is a laboratory finding. Ischemia is a clinical diagnosis. And this distinction changes everything.

The Fourth Universal Definition of Myocardial Infarction requires

Acute myocardial injury plus evidence of acute myocardial ischemia to establish the diagnosis of myocardial infarction (Thygesen et al., 2018).

That evidence for myocardial ischemia may include:

• Symptoms suggestive of myocardial ischemia.

• New ischemic ECG changes.

• Development of pathological Q waves.

• Imaging evidence of new regional wall motion abnormalities.

• Identification of a coronary thrombus by angiography or autopsy (Thygesen et al., 2018).

Without ischemia, there is no myocardial infarction. There is only myocardial injury.

The Forgotten Truth

For years, clinicians learned a dangerous shortcut:

Elevated troponin = NSTEMI.

High-sensitivity assays have exposed the flaws in that thinking.

As Rokos, Mattu, and Jaffe emphasize, a substantial proportion of elevated troponin values encountered in contemporary practice arise from conditions entirely unrelated to acute coronary syndromes (Rokos, Mattu, & Jaffe, 2025).

The biomarker is extraordinarily sensitive. It is not extraordinarily specific. The physician must provide the specificity.

The Troponin Matrix

A more useful framework is to think in four quadrants:

This simple matrix explains why two patients with identical troponin values may require entirely different management strategies. The number alone never tells the whole story.

Type 1 Myocardial Infarction:

The Classical Paradigm

Type 1 MI remains the condition most clinicians immediately think of when they encounter elevated troponin levels.

It results from:

• Plaque rupture.

• Plaque erosion.

• Coronary thrombosis.

• Acute atherothrombotic occlusion (Thygesen et al., 2018).

The pathophysiology is straightforward: A disrupted plaque causes coronary obstruction, leading to myocardial ischemia, necrosis, and biomarker release.

This is the disease for which our traditional ACS therapies were designed:

• Dual antiplatelet therapy.

• Anticoagulation.

• Early angiography.

• Revascularization.

The challenge is that not every elevated troponin belongs in this category.

Type 2 MI:

The Most Misunderstood Diagnosis in Acute Care

Perhaps no concept creates more confusion than Type 2 myocardial infarction.

The Fourth UDMI defines Type 2 MI as:

Acute myocardial injury with evidence of ischemia resulting from an imbalance between myocardial oxygen supply and demand, unrelated to acute coronary thrombosis (Thygesen et al., 2018).

Examples include:

• Severe anemia.

• Sustained tachy-arrhythmias.

• Hypertensive emergencies.

• Profound hypotension.

• Coronary vasospasm.

• Severe hypoxemia.

Importantly:

Type 2 MI still requires ischemia. That sentence deserves repetition.

Type 2 MI still requires ischemia.

A septic patient with elevated troponin but no ischemic symptoms, ECG changes, or imaging evidence does not automatically have Type 2 MI.

They may simply have acute non-ischemic myocardial injury. This distinction matters because inappropriate labeling influences:

• Cardiology referrals.

• Antiplatelet prescriptions.

• Long-term diagnoses.

• Insurance coding.

• Patient expectations.

Sometimes, the most accurate diagnosis is also the simplest:

Acute myocardial injury secondary to sepsis.

No infarction. No thrombosis. No unnecessary complexity.

The Trop-Zone Concept:

Thinking Beyond Positive and Negative

One of the most elegant recent approaches to high-sensitivity troponin interpretation comes from Rokos, Mattu, and Jaffe (2025). Rather than forcing clinicians through increasingly complex algorithms, they propose thinking in terms of Troponin Zones.

This framework aligns naturally with bedside decision-making.

Zone 1:

The Whisper Zone

Very low values. Typically near the limit of quantification. The myocardium is quiet. For many assays, extremely low troponin levels carry an exceptionally high negative predictive value for acute MI (Rokos, Mattu, & Jaffe, 2025).

But caution remains essential:

Early presenters may still evolve. Clinical context always supersedes a single number.

Zone 2:

The Thinking Zone

Values around the 99th percentile. This is where emergency medicine earns its salary.

The diagnosis depends upon:

• Serial measurements.

• Delta changes.

• Symptoms.

• ECG findings.

• Risk factors.

• Alternative explanations.

Here, the question shifts from:

“Is the troponin elevated?”

to:

“Why is it elevated?”

Zone 3:

The Alarm Zone

Substantially elevated values. The probability of infarction rises. But certainty remains elusive. Massive troponin elevations may occur in:

• Fulminant myocarditis.

• Takotsubo syndrome.

• Massive pulmonary embolism.

• Septic shock.

• Electrical storms.

• Type 1 MI.

Magnitude informs probability. It does not establish diagnosis. The heart only has a limited vocabulary. Troponin is one of its distress signals. It does not tell us why it is suffering.

The Delta:

The Most Important Number You Never Memorized

High-sensitivity assays changed our relationship with time. The absolute troponin value matters. The trend often matters more.

As Januzzi and colleagues noted, one of the greatest advantages of high-sensitivity assays is their ability to detect very small changes over short intervals (Januzzi et al., 2019).

The second troponin frequently provides information that the first cannot. Think of it this way:

The first troponin is a photograph.

The delta is a movie.

Movies tell better stories. A stable troponin suggests chronic injury. A dynamic change suggests an acute process. What remains is determining whether that process is ischemic.

The Five Questions Every Troponin Demands

This is perhaps the most useful bedside framework.

Question 1:

Is the troponin above the 99th percentile?

If no:

No myocardial injury currently.
Do follow up troponin still if high clinical suspicion.

If yes:

Proceed.

Question 2:

Is there a rise or fall?

If yes:
Acute myocardial injury.

If no:
Chronic myocardial injury.

Question 3:

Is there evidence of ischemia?

Look for:

• Symptoms.

• ECG changes.

• Imaging findings.

• Angiographic evidence.

No ischemia?
Stop calling it MI.

If clinical evidence of Ischemia is present.
Repeat Trop, if initially below 99th centile,
monitor patients, repeat ECGs, keep cardiologist in loop.

Question 4:

If ischemia exists, why?

Type 1 to 5 MI.

Question 5:

What disease process explains the injury, if no evidence of myocardial ischemia?

Sepsis?
Pulmonary embolism?
Heart failure?
Myocarditis?
Arrhythmia?
Renal disease?

The troponin tells us that myocardium has suffered. It is our responsibility to determine why.

Three Patients, Three Diagnoses

Case One:

The Septic Patient

A 72-year-old woman with septic shock. Troponin rises from 24 ng/L to 68 ng/L. No chest pain. No ischemic ECG changes. Bedside echo shows global hyperdynamic function.

Diagnosis?

Acute non-ischemic myocardial injury secondary to sepsis.

Not NSTEMI. Not Type 2 MI. The injury is real. The ischemia is absent.

Case Two:

The Tachyarrhythmia Patient

A 58-year-old man presents with atrial fibrillation at 180 beats per minute. Chest discomfort occurs during the episode. Troponin rises from 18 ng/L to 95 ng/L. Diffuse ST depressions resolve after rate control.

Diagnosis?

Type 2 myocardial infarction due to oxygen supply-demand mismatch.

Acute injury. Evidence of ischemia. No plaque rupture.

Case Three:

The Dialysis Patient

A chronic hemodialysis patient presents with pneumonia.

Troponin is 140 ng/L.

Repeat value six hours later remains 142 ng/L. NO symptoms suggestive of ACS. No ischemic ECG changes.

Diagnosis? Chronic myocardial injury.

The elevated number is background information. The stability is the key.

The New Philosophy of Troponin

The era of:

Positive versus negative

is over.

The era of:

Injury versus infarction

has begun.

High-sensitivity assays did not simply improve diagnostics. They forced us to rethink the biology of myocardial damage itself.

They taught us that:

• Injury can be acute or chronic.

• Acute injury can be ischemic or non-ischemic.

• Infarction is only one subset of myocardial injury.

The biomarker became more precise. Our thinking must become equally precise.

Final Reflections

The next time someone tells you:

“The troponin is positive i.e. above 99th percentile URL.”

Pause.

Ask five questions.

Is there injury? Is it acute? Is it ischemic? If ischemic, is it Type 1 or Type 2?

And what underlying disease process explains it? Because the elevated troponin is rarely the diagnosis. It is the heart asking for context. And modern acute care begins by listening carefully to that question.

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References

Januzzi JL Jr, Mahler SA, Christenson RH, et al. Recommendations for institutions transitioning to high-sensitivity troponin testing. Journal of the American College of Cardiology. 2019;73(9):1059-1077.

Rokos IC, Mattu A, Jaffe AS. High-sensitivity troponin zones: An alternative approach to clinical decisions. The Journal of Emergency Medicine. 2025.

Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). Circulation. 2018;138:e618-e651.