In this episode, I’ll discuss whether vasopressin should be started sooner rather than later in septic shock.
Sepsis guidelines recommend starting vasopressin once the norepinephrine dose reaches 0.25 to 0.5 mcg/kg/min if the patient’s MAP is not adequate.
However the best timing for the addition of vasopressin is still a subject of debate. Researchers recently published in Critical Care Medicine a retrospective cohort study that looked at the association of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.
Over 1600 patients at multiple hospitals within the Cleveland Clinic Health System were included in the analysis.
At the time of vasopressin initiation the median lactate level was 4 mmol/L and the median norepinephrine dose was 25 mcg/min.
The authors found that the odds of in-hospital mortality increased 20.7% for every 10 µg/min increase in norepinephrine-equivalent dose at the time of vasopressin initiation. There was a cap on this association however with no association detected when the norepinephrine-equivalent dose exceeded 60 µg/min.
The authors also found a significant interaction between timing of vasopressin initiation and lactate concentration for the association with in-hospital mortality however no association was found when time elapsed from shock onset to vasopressin start was analyzed.
Unfortunately, the authors used mcg/min for describing the norepinephrine dose and not mcg/kg/min as the sepsis guidelines describe. The mean weight was reported as 89 kg but the norepinephrine dose was reported as the median, making an attempt to convert to mcg/kg/min imprecise. With these limitations, the calculation is that vasopressin was started when the weight-based norepineprhine dose was about 0.28 mcg/kg/min. This is at the lower end of what the sepsis guideline authors describe.
It is nice to see a study that matches the practice described in the sepsis guidelines, however the observational and retrospective nature of the trial leave many possible confounders that could explain the benefits of starting vasopressin before lactate levels or norepinephrine dose gets too high. Until prospective data become available, it is reasonable to consider adding vasopressin if the MAP goal is inadequate before exceeding about 25 mcg/min or 0.28 mcg/kg/min of norepinephrine.
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