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#Thiamine in the ICU: 10 high-yield pearls
1. Unexplained lactate? Think thiamine.
Thiamine is required for pyruvate dehydrogenase. Deficiency blocks conversion of pyruvate to acetyl-CoA, shunting pyruvate toward lactate and impairing mitochondrial aerobic metabolism. Thus, thiamine deficiency belongs in the differential diagnosis for otherwise unexplained lactic acidosis.
2. Thiamine deficiency in the ICU is not rare.
~30-70% of critically ill patients are thiamine-deficient. Many arrive deficient; others develop deficiency during critical illness because of increased metabolic demand, inadequate intake, or losses.
3. The bedside phenotype is more important than waiting for a thiamine level.
High-risk situations include malnutrition, alcohol-related liver disease, bariatric surgery, renal replacement therapy, polyuria/DKA, chronic diuretic therapy, unexplained encephalopathy, unexplained lactate elevation, and sepsis.
4. Starting nutrition can unmask the deficiency.
Glucose administration increases carbohydrate metabolism and thiamine utilization. A malnourished patient may therefore develop rising lactate after initiation of enteral/parenteral nutrition. Refeeding syndrome is not simply a phosphorus/potassium problem; thiamine deficiency can be central to its pathophysiology.
5. Dialysis and polyuria are major clues.
Thiamine can be lost during continuous RRT, hemodialysis, and peritoneal dialysis. Renal losses also rise with polyuria, including the diuretic phase of AKI, post-transplant polyuria, DKA, and chronic diuretic therapy in heart failure.
6. Do not wait for the classic Wernicke's triad.
Altered mental status, ocular abnormalities, and gait ataxia are rarely all present together. I think I have seen it only a few times. In an at-risk ICU patient with otherwise unexplained encephalopathy, absence of the complete triad should not reassure you.
7. A plasma thiamine concentration is not a great “rule-out” test.
Testing is often unavailable and expensive, and blood concentration does not necessarily reflect tissue thiamine status. I don't even remember when I last ordered the test (if ever...). Erythrocyte transketolase activity is physiologically more informative, but its cutoffs are poorly defined. Just recognize the risk population and consider a therapeutic trial rather than wait for laboratory confirmation.
8. The sepsis data are more nuanced than “thiamine works” or “thiamine doesn't work.”
Thiamine is not expected to improve hard outcomes in the overall septic-shock population. Some subgroup analyses and meta-analyses suggest signals for improved lactate clearance and organ function, particularly renal outcomes. I don't consider it a magic drug...
9. Thiamine alone ≠ HAT (hydrocortisone + ascorbic acid +thiamine) therapy.
Do not interpret negative trials of HAT as proof that correcting thiamine deficiency is useless. Large HAT RCTs failed to demonstrate the dramatic clinical benefit initially claimed, and a VICTAS secondary analysis raised concerns about longer-term outcomes. That is a different question from replacing thiamine in a patient likely to be deficient.
10. The kidney may be an important target organ.
Renal tubular cells are highly energy dependent. Across secondary analyses, observational data, and meta-analytic evidence, thiamine supplementation -particularly in deficient patients- shows a signal toward less AKI progression, better renal recovery, and less need for RRT, although individual RCTs have not consistently demonstrated significant benefit in unselected populations.
Rule of thumb:
“⬆️ lactate + risk factor + no good explanation" → think B1 deficiency”
Especially think about it when you see malnutrition/refeeding, alcoholism/cirrhosis, dialysis, polyuria/DKA, chronic diuretics, unexplained encephalopathy, sepsis, or otherwise unexplained persistent hyperlactatemia.
I usually include it in the admission orders for most of my ICU patients along with DVT and GI prophylaxis...!
Thiamine deficiency behaves less like an obscure vitamin deficiency and more like a potentially reversible form of mitochondrial energy failure. Or that's how I like to think about it.
#foamed #foamcc #meded
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🆕 ICUOnePager on Central Venous Pressure (CVP) monitoring. CVP is not useful for fluid responsiveness but the trend and the waveform can provide many physiological insights! The central oxygen sat (ScvO2) can also provide clues.
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Four claims about vasopressin and the RV. Which one do you think has the weakest human evidence?
#ICU Physiology Secrets: Is vasopressin really “pulmonary-friendly”?
I’ve heard several times that vasopressin is “lung-friendly.” That it may even dilate the pulmonary vasculature. Or that the pulmonary circulation has no vasopressin receptors. Have you heard the same?
It made me wonder how much human evidence actually supports these claims. Does vasopressin constrict the pulmonary circulation less than norepinephrine? Does it lower PVR? Does it improve RV function? Or does it simply raise systemic pressure without raising PA pressure as much? These are related questions, but they are not the same question.
So I went looking for the human evidence. With the caveat that I did not have full-text access to a few potentially relevant studies, this is what I found:
1. Start with the receptor, but don’t stop there
Liu et al. examined human arterial samples and found V1a receptor (AVPR1A) protein was abundant in pulmonary arteries: about 2.2× mesenteric, 2.2× coronary and 1.9× peripheral arteries, and similar to renal arteries. Six samples of each artery type were studied. So the pulmonary circulation clearly does not lack V1a receptors. But expression is not function, and this study didn’t show what a human pulmonary artery does when exposed to vasopressin.
2. Put human pulmonary arteries in an organ bath, and things get interesting
Currigan et al. compared isolated human pulmonary and radial arteries. Vasopressin was a potent radial-artery vasoconstrictor but produced no significant change in pulmonary arterial tone. Norepinephrine constricted both.
Hussain et al. found an even more striking contrast. Maximal contraction of human pulmonary-artery rings was 61% of the KCl response with norepinephrine (12 rings from 4 patients) versus 0.18% with vasopressin (8 rings from 2 patients). That 0.18% gets my attention, but so does the denominator: eight rings from two patients...
These experiments provide a compelling physiologic basis for vasopressin behaving differently in systemic and pulmonary arteries. Still, these are isolated vessels in a bath, not PVR measured in a hypoxemic, ventilated patient with pulmonary hypertension and a failing RV.
3. What happens in actual patients?
Mizota et al. reported a lung-transplant patient with pulmonary hypertension in whom, during pulmonary-artery clamping, a 0.5-U vasopressin bolus raised systemic systolic pressure 35.2% with minimal change in PA pressure. Norepinephrine boluses in the same patient raised systemic systolic pressure 14.8% and PA systolic pressure 6.7%. A beautiful physiologic observation but n = 1, during major surgery, with other vasoactive infusions running.
Tayama et al. studied 9 post-cardiotomy patients with vasodilatory hypotension and pulmonary hypertension. Vasopressin raised mean systemic pressure from 47.3 ± 9.5 to 76.5 ± 12.2 mmHg, while PVR did not change significantly. Cardiac index fell, although it remained in the normal range. The pulmonary/systemic pressure ratio fell from 0.66 to 0.47. Be careful with that: a ratio can fall simply because the systemic denominator rises. A falling ratio is not pulmonary vasodilation.
Adamson et al. studied 28 Fontan patients undergoing catheterization. Vasopressin raised systemic pressure and SVR while PVR fell by 0.4 ± 0.4 Wood units, with no significant change in PA pressure or cardiac index. That is human PVR data, but a small effect from a single study. And Fontan physiology has no subpulmonary ventricle, so it is not a model of the adult ICU patient whose RV is failing against a high pulmonary vascular load.
4. What does the larger comparative evidence show?
Gordon et al. analyzed 779 septic-shock patients from VASST, 241 of them managed with a PA catheter. At similar systemic pressures, vasopressin reduced norepinephrine requirements and heart rate. In the PA-catheter subset, there was no detected difference in cardiac index or stroke-volume index over the first 96 hours. Inotropes were used more often in the vasopressin group.
That is much stronger comparative evidence than an organ bath or a case report. But PVR wasn’t reported, RV function wasn’t measured directly, PA-catheter use wasn’t randomized, and these were septic-shock patients, not patients selected for RV failure.
Geube et al. studied 153 elective cardiac-surgery patients who developed intraoperative hypotension in a single-center, cluster-randomized, multiple-crossover study. They found no statistically significant difference between vasopressin and norepinephrine in the primary time-weighted mPAP/MAP ratio or in RV free-wall strain, a secondary endpoint. That doesn’t support a simple claim of pulmonary selectivity or better RV function in this setting. But a pressure ratio is not PVR and can move with the systemic denominator, and these patients weren’t selected for established RV failure.
5. PA pressure may be the wrong scorecard
Dalla et al. studied 11 septic-shock patients (a small study) in whom norepinephrine was titrated in random sequence to MAP targets of 60, 75 and 90 mmHg. At the highest versus lowest MAP, mean PA pressure rose 19%, which at first glance sounds bad for the RV. But PVRI and effective pulmonary arterial elastance did not increase, while RV function improved: free-wall strain became more negative (−19% to −25%), TAPSE rose 22% and RV stroke-work index rose 15%.
This doesn’t prove norepinephrine is better than vasopressin. It shows why PA pressure alone is a poor scorecard for what the RV is doing.
So where do I land?
Vasopressin’s “pulmonary-friendly” reputation has a legitimate physiologic basis. In small organ-bath studies, human pulmonary arteries show very little direct constriction to vasopressin. In small clinical series, systemic pressure rose without a clear rise in PA pressure. Fontan patients' data show a small fall in PVR, about 0.4 Wood units, in a circulation with no subpulmonary ventricle.
But there’s an evidentiary ladder:
Little pulmonary-artery constriction → lower PVR → better RV performance → clinical superiority over another vasopressor.
Those are four different claims, and the human evidence gets thinner with each step.
What I’d really like to see is a prospective vasopressin-vs-norepinephrine comparison in patients who actually have RV dysfunction with elevated pulmonary vascular load. It should measure systemic and PA pressures, PAOP, cardiac output, PVR, RV function, tissue perfusion and, ultimately, clinical outcomes.
Until then, I’ll still consider vasopressin an attractive pressor when the RV is in trouble. That’s a physiologically informed choice, not a proven RV-outcome advantage. “Pulmonary-friendly” is a compelling hypothesis with human support, not a guarantee that the RV benefited.
When your RV is failing, what pressor do you reach for first and what do you measure to decide whether it helped?
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#ICU Physiology Secrets: Is vasopressin really “pulmonary-friendly”?
I’ve heard several times that vasopressin is “lung-friendly.” That it may even dilate the pulmonary vasculature. Or that the pulmonary circulation has no vasopressin receptors. Have you heard the same?
It made me wonder how much human evidence actually supports these claims. Does vasopressin constrict the pulmonary circulation less than norepinephrine? Does it lower PVR? Does it improve RV function? Or does it simply raise systemic pressure without raising PA pressure as much? These are related questions, but they are not the same question.
So I went looking for the human evidence. With the caveat that I did not have full-text access to a few potentially relevant studies, this is what I found:
1. Start with the receptor, but don’t stop there
Liu et al. examined human arterial samples and found V1a receptor (AVPR1A) protein was abundant in pulmonary arteries: about 2.2× mesenteric, 2.2× coronary and 1.9× peripheral arteries, and similar to renal arteries. Six samples of each artery type were studied. So the pulmonary circulation clearly does not lack V1a receptors. But expression is not function, and this study didn’t show what a human pulmonary artery does when exposed to vasopressin.
2. Put human pulmonary arteries in an organ bath, and things get interesting
Currigan et al. compared isolated human pulmonary and radial arteries. Vasopressin was a potent radial-artery vasoconstrictor but produced no significant change in pulmonary arterial tone. Norepinephrine constricted both.
Hussain et al. found an even more striking contrast. Maximal contraction of human pulmonary-artery rings was 61% of the KCl response with norepinephrine (12 rings from 4 patients) versus 0.18% with vasopressin (8 rings from 2 patients). That 0.18% gets my attention, but so does the denominator: eight rings from two patients...
These experiments provide a compelling physiologic basis for vasopressin behaving differently in systemic and pulmonary arteries. Still, these are isolated vessels in a bath, not PVR measured in a hypoxemic, ventilated patient with pulmonary hypertension and a failing RV.
3. What happens in actual patients?
Mizota et al. reported a lung-transplant patient with pulmonary hypertension in whom, during pulmonary-artery clamping, a 0.5-U vasopressin bolus raised systemic systolic pressure 35.2% with minimal change in PA pressure. Norepinephrine boluses in the same patient raised systemic systolic pressure 14.8% and PA systolic pressure 6.7%. A beautiful physiologic observation but n = 1, during major surgery, with other vasoactive infusions running.
Tayama et al. studied 9 post-cardiotomy patients with vasodilatory hypotension and pulmonary hypertension. Vasopressin raised mean systemic pressure from 47.3 ± 9.5 to 76.5 ± 12.2 mmHg, while PVR did not change significantly. Cardiac index fell, although it remained in the normal range. The pulmonary/systemic pressure ratio fell from 0.66 to 0.47. Be careful with that: a ratio can fall simply because the systemic denominator rises. A falling ratio is not pulmonary vasodilation.
Adamson et al. studied 28 Fontan patients undergoing catheterization. Vasopressin raised systemic pressure and SVR while PVR fell by 0.4 ± 0.4 Wood units, with no significant change in PA pressure or cardiac index. That is human PVR data, but a small effect from a single study. And Fontan physiology has no subpulmonary ventricle, so it is not a model of the adult ICU patient whose RV is failing against a high pulmonary vascular load.
4. What does the larger comparative evidence show?
Gordon et al. analyzed 779 septic-shock patients from VASST, 241 of them managed with a PA catheter. At similar systemic pressures, vasopressin reduced norepinephrine requirements and heart rate. In the PA-catheter subset, there was no detected difference in cardiac index or stroke-volume index over the first 96 hours. Inotropes were used more often in the vasopressin group.
That is much stronger comparative evidence than an organ bath or a case report. But PVR wasn’t reported, RV function wasn’t measured directly, PA-catheter use wasn’t randomized, and these were septic-shock patients, not patients selected for RV failure.
Geube et al. studied 153 elective cardiac-surgery patients who developed intraoperative hypotension in a single-center, cluster-randomized, multiple-crossover study. They found no statistically significant difference between vasopressin and norepinephrine in the primary time-weighted mPAP/MAP ratio or in RV free-wall strain, a secondary endpoint. That doesn’t support a simple claim of pulmonary selectivity or better RV function in this setting. But a pressure ratio is not PVR and can move with the systemic denominator, and these patients weren’t selected for established RV failure.
5. PA pressure may be the wrong scorecard
Dalla et al. studied 11 septic-shock patients (a small study) in whom norepinephrine was titrated in random sequence to MAP targets of 60, 75 and 90 mmHg. At the highest versus lowest MAP, mean PA pressure rose 19%, which at first glance sounds bad for the RV. But PVRI and effective pulmonary arterial elastance did not increase, while RV function improved: free-wall strain became more negative (−19% to −25%), TAPSE rose 22% and RV stroke-work index rose 15%.
This doesn’t prove norepinephrine is better than vasopressin. It shows why PA pressure alone is a poor scorecard for what the RV is doing.
So where do I land?
Vasopressin’s “pulmonary-friendly” reputation has a legitimate physiologic basis. In small organ-bath studies, human pulmonary arteries show very little direct constriction to vasopressin. In small clinical series, systemic pressure rose without a clear rise in PA pressure. Fontan patients' data show a small fall in PVR, about 0.4 Wood units, in a circulation with no subpulmonary ventricle.
But there’s an evidentiary ladder:
Little pulmonary-artery constriction → lower PVR → better RV performance → clinical superiority over another vasopressor.
Those are four different claims, and the human evidence gets thinner with each step.
What I’d really like to see is a prospective vasopressin-vs-norepinephrine comparison in patients who actually have RV dysfunction with elevated pulmonary vascular load. It should measure systemic and PA pressures, PAOP, cardiac output, PVR, RV function, tissue perfusion and, ultimately, clinical outcomes.
Until then, I’ll still consider vasopressin an attractive pressor when the RV is in trouble. That’s a physiologically informed choice, not a proven RV-outcome advantage. “Pulmonary-friendly” is a compelling hypothesis with human support, not a guarantee that the RV benefited.
When your RV is failing, what pressor do you reach for first and what do you measure to decide whether it helped?
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IMCrit retweeted
Excellent summary! I’ve recently presented at a conference on this exact topic. I would add one additional study to your list of human data: Jeon 2006 (16675238). This was an RCT in 50 off-pump CABG pts with milrinone-induced hypotension where pts were randomized to vaso vs norepi. There was a small decrease in the PVR/SVR ratio with vaso but no change with norepi. If I remember correctly, the PVR did increase with vaso though.
Overall I reached the same conclusions that you did in my review: the evidence supporting the claim that vaso is “better for the RV” is very weak. It essentially comes from basic research which often doesn’t translate into real clinical benefit, as we all know.
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Thanks for voting!
311 votes: 41.5% inotrope first, 36% norepinephrine, 12.5% vasopressin, 10% both.
There’s no single right answer here, and that’s the point of the vasopressin post. Nobody has proven which drug is best in this exact setting. We’re reasoning from physiology. Here’s how I think about this patient.
Let’s look at the numbers. CI 1.9 and SvO₂ 54% say the RV isn’t delivering enough flow. A MAP of 55 with CVP 16 and PA 55/28 says it’s working against a high load with its own perfusion at risk. So this RV may need pressure, contractility and less afterload at the same time. That’s why inotrope-first made sense to so many of you.
Norepinephrine: raises MAP and provides some β₁ support. For me, a very defensible first go-to drug.
Inotrope alone: addresses the low flow directly, but dobutamine or milrinone can lower systemic pressure, which is a problem when MAP is already 55. Epinephrine is different because it can support both pressure and contractility.
Vasopressin: raises MAP without direct inotropy and, in the limited human data, may have relatively little pulmonary pressor effect. In the small post-cardiotomy series I cited, cardiac index fell. That’s a reason to watch output, not proof it would hurt this patient. I see it as a strong add-on or alternative pressor.
Norepinephrine + vasopressin: common and reasonable if pressure remains inadequate, but they still don’t directly solve low contractility.
My sequence: norepinephrine -or epinephrine in the right patient- then early inotropic support if CI and SvO₂ don’t improve. If elevated pulmonary vascular load remains an important part of the problem, I’d consider an inhaled pulmonary vasodilator. Vasopressin can come alongside as an adjunct pressor.
In parallel, I’d look for fixable causes: tamponade, bleeding, graft or valve problems, ischemia, rhythm, ventilator settings, hypoxia and CO₂. That search can’t delay supporting a MAP of 55.
What would I measure to decide it worked? Everything: MAP and CVP, PA pressure, CO and SvO₂, lactate, RV size and function on echo, and tissue perfusion by every bedside sign we have: urine output, mentation, skin.
One number moving while the others don’t is not a win.
That’s physiology, not proof. I’m not aware of a randomized trial that answers this exact question.
What would make you change course first: MAP, PAP, cardiac output, SvO₂, or the echo?
After my vasopressin “pulmonary-friendly” post:
Hypothetical case: POD 0 after MVR + CABG. MAP 55, HR 95, CVP 16, PA 55/28 (mean 37), PAOP 14, CO 3.6 / CI 1.9, SvO2 54%. Echo: dilated, hypokinetic RV. No vasoactives yet.
What do you start first?
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After my vasopressin “pulmonary-friendly” post:
Hypothetical case: POD 0 after MVR + CABG. MAP 55, HR 95, CVP 16, PA 55/28 (mean 37), PAOP 14, CO 3.6 / CI 1.9, SvO2 54%. Echo: dilated, hypokinetic RV. No vasoactives yet.
What do you start first?
36%
Norepinephrine
13%
Vasopressin
10%
Both
41%
Inotrope
311 votes • Final results
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After you start your first drug, what tells you it worked? And which single number do you trust?
Context: my review on vasopressin and the pulmonary circulation
#ICU Physiology Secrets: Is vasopressin really “pulmonary-friendly”?
I’ve heard several times that vasopressin is “lung-friendly.” That it may even dilate the pulmonary vasculature. Or that the pulmonary circulation has no vasopressin receptors. Have you heard the same?
It made me wonder how much human evidence actually supports these claims. Does vasopressin constrict the pulmonary circulation less than norepinephrine? Does it lower PVR? Does it improve RV function? Or does it simply raise systemic pressure without raising PA pressure as much? These are related questions, but they are not the same question.
So I went looking for the human evidence. With the caveat that I did not have full-text access to a few potentially relevant studies, this is what I found:
1. Start with the receptor, but don’t stop there
Liu et al. examined human arterial samples and found V1a receptor (AVPR1A) protein was abundant in pulmonary arteries: about 2.2× mesenteric, 2.2× coronary and 1.9× peripheral arteries, and similar to renal arteries. Six samples of each artery type were studied. So the pulmonary circulation clearly does not lack V1a receptors. But expression is not function, and this study didn’t show what a human pulmonary artery does when exposed to vasopressin.
2. Put human pulmonary arteries in an organ bath, and things get interesting
Currigan et al. compared isolated human pulmonary and radial arteries. Vasopressin was a potent radial-artery vasoconstrictor but produced no significant change in pulmonary arterial tone. Norepinephrine constricted both.
Hussain et al. found an even more striking contrast. Maximal contraction of human pulmonary-artery rings was 61% of the KCl response with norepinephrine (12 rings from 4 patients) versus 0.18% with vasopressin (8 rings from 2 patients). That 0.18% gets my attention, but so does the denominator: eight rings from two patients...
These experiments provide a compelling physiologic basis for vasopressin behaving differently in systemic and pulmonary arteries. Still, these are isolated vessels in a bath, not PVR measured in a hypoxemic, ventilated patient with pulmonary hypertension and a failing RV.
3. What happens in actual patients?
Mizota et al. reported a lung-transplant patient with pulmonary hypertension in whom, during pulmonary-artery clamping, a 0.5-U vasopressin bolus raised systemic systolic pressure 35.2% with minimal change in PA pressure. Norepinephrine boluses in the same patient raised systemic systolic pressure 14.8% and PA systolic pressure 6.7%. A beautiful physiologic observation but n = 1, during major surgery, with other vasoactive infusions running.
Tayama et al. studied 9 post-cardiotomy patients with vasodilatory hypotension and pulmonary hypertension. Vasopressin raised mean systemic pressure from 47.3 ± 9.5 to 76.5 ± 12.2 mmHg, while PVR did not change significantly. Cardiac index fell, although it remained in the normal range. The pulmonary/systemic pressure ratio fell from 0.66 to 0.47. Be careful with that: a ratio can fall simply because the systemic denominator rises. A falling ratio is not pulmonary vasodilation.
Adamson et al. studied 28 Fontan patients undergoing catheterization. Vasopressin raised systemic pressure and SVR while PVR fell by 0.4 ± 0.4 Wood units, with no significant change in PA pressure or cardiac index. That is human PVR data, but a small effect from a single study. And Fontan physiology has no subpulmonary ventricle, so it is not a model of the adult ICU patient whose RV is failing against a high pulmonary vascular load.
4. What does the larger comparative evidence show?
Gordon et al. analyzed 779 septic-shock patients from VASST, 241 of them managed with a PA catheter. At similar systemic pressures, vasopressin reduced norepinephrine requirements and heart rate. In the PA-catheter subset, there was no detected difference in cardiac index or stroke-volume index over the first 96 hours. Inotropes were used more often in the vasopressin group.
That is much stronger comparative evidence than an organ bath or a case report. But PVR wasn’t reported, RV function wasn’t measured directly, PA-catheter use wasn’t randomized, and these were septic-shock patients, not patients selected for RV failure.
Geube et al. studied 153 elective cardiac-surgery patients who developed intraoperative hypotension in a single-center, cluster-randomized, multiple-crossover study. They found no statistically significant difference between vasopressin and norepinephrine in the primary time-weighted mPAP/MAP ratio or in RV free-wall strain, a secondary endpoint. That doesn’t support a simple claim of pulmonary selectivity or better RV function in this setting. But a pressure ratio is not PVR and can move with the systemic denominator, and these patients weren’t selected for established RV failure.
5. PA pressure may be the wrong scorecard
Dalla et al. studied 11 septic-shock patients (a small study) in whom norepinephrine was titrated in random sequence to MAP targets of 60, 75 and 90 mmHg. At the highest versus lowest MAP, mean PA pressure rose 19%, which at first glance sounds bad for the RV. But PVRI and effective pulmonary arterial elastance did not increase, while RV function improved: free-wall strain became more negative (−19% to −25%), TAPSE rose 22% and RV stroke-work index rose 15%.
This doesn’t prove norepinephrine is better than vasopressin. It shows why PA pressure alone is a poor scorecard for what the RV is doing.
So where do I land?
Vasopressin’s “pulmonary-friendly” reputation has a legitimate physiologic basis. In small organ-bath studies, human pulmonary arteries show very little direct constriction to vasopressin. In small clinical series, systemic pressure rose without a clear rise in PA pressure. Fontan patients' data show a small fall in PVR, about 0.4 Wood units, in a circulation with no subpulmonary ventricle.
But there’s an evidentiary ladder:
Little pulmonary-artery constriction → lower PVR → better RV performance → clinical superiority over another vasopressor.
Those are four different claims, and the human evidence gets thinner with each step.
What I’d really like to see is a prospective vasopressin-vs-norepinephrine comparison in patients who actually have RV dysfunction with elevated pulmonary vascular load. It should measure systemic and PA pressures, PAOP, cardiac output, PVR, RV function, tissue perfusion and, ultimately, clinical outcomes.
Until then, I’ll still consider vasopressin an attractive pressor when the RV is in trouble. That’s a physiologically informed choice, not a proven RV-outcome advantage. “Pulmonary-friendly” is a compelling hypothesis with human support, not a guarantee that the RV benefited.
When your RV is failing, what pressor do you reach for first and what do you measure to decide whether it helped?
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#ICU Physiology Secrets: Is vasopressin really “pulmonary-friendly”?
I’ve heard several times that vasopressin is “lung-friendly.” That it may even dilate the pulmonary vasculature. Or that the pulmonary circulation has no vasopressin receptors. Have you heard the same?
It made me wonder how much human evidence actually supports these claims. Does vasopressin constrict the pulmonary circulation less than norepinephrine? Does it lower PVR? Does it improve RV function? Or does it simply raise systemic pressure without raising PA pressure as much? These are related questions, but they are not the same question.
So I went looking for the human evidence. With the caveat that I did not have full-text access to a few potentially relevant studies, this is what I found:
1. Start with the receptor, but don’t stop there
Liu et al. examined human arterial samples and found V1a receptor (AVPR1A) protein was abundant in pulmonary arteries: about 2.2× mesenteric, 2.2× coronary and 1.9× peripheral arteries, and similar to renal arteries. Six samples of each artery type were studied. So the pulmonary circulation clearly does not lack V1a receptors. But expression is not function, and this study didn’t show what a human pulmonary artery does when exposed to vasopressin.
2. Put human pulmonary arteries in an organ bath, and things get interesting
Currigan et al. compared isolated human pulmonary and radial arteries. Vasopressin was a potent radial-artery vasoconstrictor but produced no significant change in pulmonary arterial tone. Norepinephrine constricted both.
Hussain et al. found an even more striking contrast. Maximal contraction of human pulmonary-artery rings was 61% of the KCl response with norepinephrine (12 rings from 4 patients) versus 0.18% with vasopressin (8 rings from 2 patients). That 0.18% gets my attention, but so does the denominator: eight rings from two patients...
These experiments provide a compelling physiologic basis for vasopressin behaving differently in systemic and pulmonary arteries. Still, these are isolated vessels in a bath, not PVR measured in a hypoxemic, ventilated patient with pulmonary hypertension and a failing RV.
3. What happens in actual patients?
Mizota et al. reported a lung-transplant patient with pulmonary hypertension in whom, during pulmonary-artery clamping, a 0.5-U vasopressin bolus raised systemic systolic pressure 35.2% with minimal change in PA pressure. Norepinephrine boluses in the same patient raised systemic systolic pressure 14.8% and PA systolic pressure 6.7%. A beautiful physiologic observation but n = 1, during major surgery, with other vasoactive infusions running.
Tayama et al. studied 9 post-cardiotomy patients with vasodilatory hypotension and pulmonary hypertension. Vasopressin raised mean systemic pressure from 47.3 ± 9.5 to 76.5 ± 12.2 mmHg, while PVR did not change significantly. Cardiac index fell, although it remained in the normal range. The pulmonary/systemic pressure ratio fell from 0.66 to 0.47. Be careful with that: a ratio can fall simply because the systemic denominator rises. A falling ratio is not pulmonary vasodilation.
Adamson et al. studied 28 Fontan patients undergoing catheterization. Vasopressin raised systemic pressure and SVR while PVR fell by 0.4 ± 0.4 Wood units, with no significant change in PA pressure or cardiac index. That is human PVR data, but a small effect from a single study. And Fontan physiology has no subpulmonary ventricle, so it is not a model of the adult ICU patient whose RV is failing against a high pulmonary vascular load.
4. What does the larger comparative evidence show?
Gordon et al. analyzed 779 septic-shock patients from VASST, 241 of them managed with a PA catheter. At similar systemic pressures, vasopressin reduced norepinephrine requirements and heart rate. In the PA-catheter subset, there was no detected difference in cardiac index or stroke-volume index over the first 96 hours. Inotropes were used more often in the vasopressin group.
That is much stronger comparative evidence than an organ bath or a case report. But PVR wasn’t reported, RV function wasn’t measured directly, PA-catheter use wasn’t randomized, and these were septic-shock patients, not patients selected for RV failure.
Geube et al. studied 153 elective cardiac-surgery patients who developed intraoperative hypotension in a single-center, cluster-randomized, multiple-crossover study. They found no statistically significant difference between vasopressin and norepinephrine in the primary time-weighted mPAP/MAP ratio or in RV free-wall strain, a secondary endpoint. That doesn’t support a simple claim of pulmonary selectivity or better RV function in this setting. But a pressure ratio is not PVR and can move with the systemic denominator, and these patients weren’t selected for established RV failure.
5. PA pressure may be the wrong scorecard
Dalla et al. studied 11 septic-shock patients (a small study) in whom norepinephrine was titrated in random sequence to MAP targets of 60, 75 and 90 mmHg. At the highest versus lowest MAP, mean PA pressure rose 19%, which at first glance sounds bad for the RV. But PVRI and effective pulmonary arterial elastance did not increase, while RV function improved: free-wall strain became more negative (−19% to −25%), TAPSE rose 22% and RV stroke-work index rose 15%.
This doesn’t prove norepinephrine is better than vasopressin. It shows why PA pressure alone is a poor scorecard for what the RV is doing.
So where do I land?
Vasopressin’s “pulmonary-friendly” reputation has a legitimate physiologic basis. In small organ-bath studies, human pulmonary arteries show very little direct constriction to vasopressin. In small clinical series, systemic pressure rose without a clear rise in PA pressure. Fontan patients' data show a small fall in PVR, about 0.4 Wood units, in a circulation with no subpulmonary ventricle.
But there’s an evidentiary ladder:
Little pulmonary-artery constriction → lower PVR → better RV performance → clinical superiority over another vasopressor.
Those are four different claims, and the human evidence gets thinner with each step.
What I’d really like to see is a prospective vasopressin-vs-norepinephrine comparison in patients who actually have RV dysfunction with elevated pulmonary vascular load. It should measure systemic and PA pressures, PAOP, cardiac output, PVR, RV function, tissue perfusion and, ultimately, clinical outcomes.
Until then, I’ll still consider vasopressin an attractive pressor when the RV is in trouble. That’s a physiologically informed choice, not a proven RV-outcome advantage. “Pulmonary-friendly” is a compelling hypothesis with human support, not a guarantee that the RV benefited.
When your RV is failing, what pressor do you reach for first and what do you measure to decide whether it helped?
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References:
Liu X et al. Distribution and relative expression of vasoactive receptors on arteries. Sci Rep. 2020. PMID: 32958803
Currigan DA et al. Vasoconstrictor responses to vasopressor agents in human pulmonary and radial arteries: an in vitro study. Anesthesiology. 2014. PMID: 25198173
Hussain A et al. The differential effects of systemic vasoconstrictors on human pulmonary artery tension. Eur J Cardiothorac Surg. 2017. PMID: 28164217
Mizota T et al. Effect of arginine vasopressin on systemic and pulmonary arterial pressure in a patient with pulmonary hypertension secondary to pulmonary emphysema: a case report. JA Clin Rep. 2017. PMID: 29492440
Tayama E et al. Arginine vasopressin is an ideal drug after cardiac surgery for the management of low systemic vascular resistant hypotension concomitant with pulmonary hypertension. Interact Cardiovasc Thorac Surg. 2007. PMID: 17704123
Adamson GT et al. Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin. Pediatr Crit Care Med. 2023. PMID: 37462430
Gordon AC et al. The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock. Chest. 2012. PMID: 22518026
Geube M et al. Cardiopulmonary effects of vasopressin versus norepinephrine in patients undergoing cardiac surgery: A single-center, cluster-randomized crossover trial. J Thorac Cardiovasc Surg. 2026. PMID: 41270859
Dalla K et al. Impact of norepinephrine on right ventricular afterload and function in septic shock-a strain echocardiography study. Acta Anaesthesiol Scand. 2019. PMID: 31361336
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We have entered the era of MedEd hyperabundance.
I spent the last two weeks exploring and reviewing new medical education sites and resources. There is now more great content than any of us could possibly read, watch, listen to, think about, and digest.
Finding good content is no longer the problem. Finding the time to actually consume it is.
I think the Frank-Starling curve of medical education is approaching its flat part. The content keeps coming. Our time and cognitive bandwidth don’t.
At some point, more content raises the filling pressure, not the stroke volume.
(Yes, I’m part of the problem.)
MedEd hyperabundance → study paralysis?
#MedEd #FOAMed
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And the answer is… complicated.
The course says amiodarone.
But there are two problems with this question:
1. Where are we in the algorithm?
Persistent VF/pVT alone doesn’t tell us what drug comes next.
After the 2nd shock → epinephrine
After the 3rd shock → amiodarone OR lidocaine
2. And that “OR” matters.
If we’re at the antiarrhythmic step, the AHA algorithm doesn’t say “amiodarone, and lidocaine if amiodarone isn’t available.” It says amiodarone OR lidocaine.
Maybe the real ACLS pearl here is:
Before asking “which drug?”, tell me where we are in the algorithm.
Thoughts?
#ACLS recertification adventures continue…
Cardiac arrest. CPR in progress. Rhythm check shows persistent VF/pVT.
According to the ACLS guidelines, what is the next drug of choice?
Vote below 👇
And before you answer: read the question carefully. 👀
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My #ACLS recertification adventures continue…
The “correct” course answer here is SpO₂ ≥94%.
But should post-ROSC oxygen really have a floor and no ceiling? 🤔
2025 AHA:
→ 100% FiO₂ until SpO₂/PaO₂ can be measured reliably
→ Then target SpO₂ 90–98% (PaO₂ 60–105 mmHg)
After ROSC, oxygen is a drug.
Avoid hypoxemia. Avoid hyperoxemia. Titrate.
#ACLS recertification journey continues…
We’ve achieved ROSC. Now comes the oxygen question.
Which target would I choose from these four options?
And would the answer change once I had a reliable pulse-ox reading?
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A small #ACLS pearl from something I have actually seen done mistakenly during codes:
An advanced airway is in place and someone shouts: “Stop compressions; we need to give 2 breaths.”
Please don’t. 😅
Once an advanced airway is in place during cardiac arrest:
→ Continuous chest compressions
→ 100–120/min
→ 1 breath every 6 sec (10/min)
→ No more 30:2
An advanced airway should make interruptions in #CPR fewer, not create new ones.
Keep the blood moving!
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And here is the course's answer: amiodarone 300 mg
But wait… when did our patient go into cardiac arrest? 🤔
The question never tells us whether the patient has a pulse or whether #CPR is even in progress.
Yet the explanation suddenly says: “during CPR.”
That distinction matters:
Pulseless VT → CPR + defibrillation → -> amiodarone 300 mg for refractory VF/pVT
VT with a pulse → assess stability → synchronized cardioversion if unstable; if stable and amiodarone is used, 150 mg iv over 10 min
Treat the patient, not just the rhythm strip.
My #ACLS recertification adventures continue…
You hear the monitor alarm in the recovery room and find this rhythm.
The question asks for the antiarrhythmic of choice and dose.
What should I answer? 🤔
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