Early vasopressor dosing associated with mortality risk in septic shock

In the first six hours of septic shock, mortality risk was associated with relative dosing of vasopressors and fluid, but in the first 24 hours, there was a direct association between higher vasopressor doses and higher mortality, a prospective study found.

Receiving more vasopressors in the first 24 hours after septic shock diagnosis was associated with a higher risk of death, a study found.

The prospective cohort study used data on patients requiring admission to the ICU with septic shock between September 2017 and February 2018 at 32 U.S. hospitals and one hospital in Jordan. All of the included patients were treated with at least one vasopressor (most commonly norepinephrine), and researchers defined dosing intensity as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. Results were published by Critical Care Medicine on July 16.

Out of 1,639 consecutive patients screened, 616 were included in the results. In the 24 hours after shock diagnosis, patients received a median of 3,400 mL of vasopressors (interquartile range [IQR], 1,851 to 5,338 mL), with a median dosing intensity of 8.5 μg/min norepinephrine equivalents (IQR, 3.4 to 18.1 μg/min). In the first six hours, higher vasopressor dosing intensity was associated with increased risk of 30-day in-hospital mortality, but the strength of association depended on concomitant fluid administration, so there was no association between higher doses and mortality in patients receiving at least 2 L of fluid.

In the first 24 hours, every 10 μg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16 to 1.53), and this association did not vary with the amount of fluid administered. Patients treated with an early high/late low dose pattern had lower mortality rates than those treated with early low/late high dosing or sustained high dosing.

“Taken together, we hypothesize that early aggressive vasopressor titration may be preferred compared to slower titration to high doses, but that this strategy must be accompanied by adequate fluid resuscitation in the early hours after shock onset to avoid potential deleterious effects of high-dose vasopressors. If true, this hypothesis has important implications, given the recent interest in early vasopressors to prevent excessive fluid resuscitation,” the authors wrote.

They noted that the results “are in agreement with previous data that has linked the early administration of vasopressors in lieu of fluid therapy with increased mortality” and that although they couldn't identify a threshold for adequate early fluid resuscitation, the quantity of fluid at which early high vasopressors doses stopped being associated with mortality (2 L) was much lower than that included in early goal-directed therapy protocols (6 L).

However, the authors noted that the observational study was subject to confounding and didn't allow examination of potential interaction mechanisms and therefore should be considered hypothesis-generating only.

An article in the April ACP Hospitalist offered expert perspectives on fluid resuscitation from the Critical Care Congress, held in February in Orlando.