The VANISH study recently showed that vasopressin could be used as a first-line vasopressor in septic shock. Patients treated with vasopressin had a lower incidence of renal failure requiring hemodialysis, compared to patients receiving norepinephrine. However, this was a secondary endpoint which seemed to contradict the primary endpoint (defined as a milder degree of kidney injury). Given prior evidence, it seemed likely that vasopressin was improving renal function. However, this remains controversial.
Hajjar 2017: Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery
This is a single-center double-blind RCT comparing vasopressin (0.01-0.06 U/min) vs. norepinephrine (10-60 ug/min) among patients with vasoplegic shock following elective cardiac surgery. Vasoplegic shock was defined as hypotension refractory to volume resuscitation, with a cardiac index >2.2.
The primary endpoint was the modified Society of Thoracic Surgeons score, a composite of post-surgical complications including the following items:
- stroke
- requirement for ventilation >48 hours
- deep sternal wound infection
- renal failure, defined as any of the following:
- renal failure requiring dialysis
- creatinine increase by >2 mg/dL
- creatinine increase above twice the pre-operative level
300 patients received study medication. Only 11% of patients in the vasopressin group required open-label norepinephrine. About one third of patients received dobutamine intraoperatively, which was weaned off over about 1-3 days. The primary outcome was less common in the vasopressin group, with differences driven by a reduction in renal failure:
As discussed previously, defining renal failure is tricky. The most meaningful patient-centered outcome is arguably the requirement for dialysis (rather than an asymptomatic rise in creatinine). Vasopressin decreased the requirement for dialysis from 14% to 3% (p=0.002). This is consistent with a similar reduction in dialysis rates found in the VANISH trial. It's possible that these authors could demonstrate this more clearly, because cardiac surgery patients are less heterogeneous than septic patients.
Reduced atrial fibrillation
The other notable finding was that vasopressin caused a reduction in the rate of atrial fibrillation compared to norepinephrine (64% vs. 82%, p=0.0004, NNT=5). This makes sense given that norepinephrine causes beta-adrenergic stimulation, promoting atrial fibrillation. Alternatively, vasopressin may decrease heart rate via the baroreceptor reflex. It was previously proven in the VASST trial that norepinephrine generates faster heart rates compared with vasopressin.
Unfortunately, the presence of dobutamine may confound matters. Patients treated with vasopressin required dobutamine for a shorter duration than patients treated with norepinephrine (average 40 vs. 54 hours, p=0.007). Thus, it is possible that the lower rate of atrial fibrillation in the vasopressin group could partially reflect faster weaning off dobutamine.
If vasopressin causes a lower rate of atrial fibrillation than norepinephrine, this could be very useful in septic shock. The SEPSISPAM study randomized septic patients to target a MAP of 80-85mm versus 65-70mm using catecholamine drugs (mostly norepinephrine). A higher blood pressure target reduced the rate of renal failure among patients with chronic hypertension, but increased the rate of atrial fibrillation. One wonders whether using vasopressin to target a higher MAP could reduce renal failure while simultaneously avoiding atrial fibrillation.
Global outcomes
There were no mortality differences at either 30-days or 90-days. This isn't surprising, given that the study wasn't powered to detect a mortality difference.
Vasopressin did reduce the length of ICU stay and hospital stay (with a three-day difference in median hospital stay, p=0.002). This is probably a consequence of reduced rates of atrial fibrillation and dialysis-dependent renal failure, both issues which often delay disposition.
Safety outcomes
The use of vasopressin as a front-line vasopressor remains a newer concept, making safety a primary consideration. As shown below, there were no significant differences in adverse events. The trend towards reduced myocardial infarction with vasopressin is reassuring, because one concern regarding vasopressin is that it could cause coronary vasoconstriction.
Study limitations (from standpoint of septic shock management)
The main limitation from my standpoint is whether this study is generalizable to patients with septic shock. The ability of vasopressin to improve renal function has been shown in numerous RCTs of septic shock, so this seems to be a generalizable. Whether vasopressin can reduce new-onset atrial fibrillation in sepsis remains unknown. The safety of vasopressin in this cohort of post-operative cardiac patients may not translate directly to septic patients, yet remains reassuring.
Another limitation is that dobutamine was started intraoperatively in about a third of patients and continued postoperatively. Thus, this may not have been purely a study of vasopressin vs. norepinephrine, but rather occasionally a study of {vasopressin + dobutamine} vs. {norepinephrine + dobutamine}.
- Hajjar et al. 2017 is a prospective single-center RCT comparing vasopressin vs. norepinephrine as first-line vasopressors among patients with vasodilatory shock following cardiothoracic surgery.
- Vasopressin reduced rates of acute kidney injury, hemodialysis, and atrial fibrillation. Patients treated with vasopressin had reduced ICU and hospital lengths of stay.
- Vasopressin appeared safe in these patients, when used at doses up to 0.06 U/min.
- It is unclear how well this study may generalize to septic patients. However, it does support the concept that vasopressin reduces the need for dialysis (as previously found in the VANISH trial).
Related:
- Hajjar LA et al. Vasopressin versus norepinephrine in patients with vasoplegic shock after cardiac surgery: The VANCS Randomized Controlled Trial. Anesthesiology 2017; 126(1) 1-9.
- Renoresuscitation 12/2014
- Vasopressin & renal function 12/2014
- VANISH trial & vepinephrine 8/2016
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You say, “The ability of vasopressin to improve renal function has been shown in numerous RCTs of septic shock, so this seems to be a generalizable”, which RCTs are you referring to, any references? The VANISH trial would be one, the cardiac surgery study you reference would be two, as far as I can tell the VASST study did not show any difference in renal outcomes, can’t think of any others…
discussed here: https://emcrit.org/pulmcrit/renal-microvascular-hemodynamics-in-sepsis-a-new-paradigm/
Opinions about the implementation of vasopressin seem to vary so widely they have the eau du voodoo. Some clinicians seem to feel that it is only physiologically active in vasopressin-depleted patients, and thus in others it will have little to no pharmacological effect. Obviously, this would imply that for non-vasopressin-depleted (but still hypotensive) patients, there would be no vasoactive benefit, and it would essentially be a saline drip. Thoughts?
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