Vasopressin vs Norepinephrine Infusion in Patients With Septic Shock
Russell JA, Walley KR Singer J, et al
N Engl J Med. 2008;358:877-887

Septic shock remains one of the most difficult conditions to treat in the intensive care unit. Prior studies have shown that patients with septic shock demonstrate a state of "relative vasopressin deficiency," with circulating levels significantly lower than expected for the degree of hypotension. In addition, what little evidence exists suggests that vasopressin administration in septic shock may improve blood pressure even in patients with high catecholamine vasopressor requirements (ie, high-dose norepinephrine). The authors of the current study sought to determine whether vasopressin administration to patients with septic shock might better support blood pressure and improve survival. The Vasopressin and Septic Shock Trial (VASST) randomized 778 patients with septic shock to receive blinded vasopressin (0.01 to 0.03 U/min) or norepinephrine (5 to 15 micrograms [mcg]/min) in addition to other vasopressor agents. Overall, there were no differences in adverse events or survival rates between the vasopressin and norepinephrine groups. In patients with less severe septic shock (norepinephrine dose <15 mcg/minute at randomization), the mortality rate at 28 days was lower with vasopressin (26.5% vs 35.7%, P = .05). The authors concluded that low-dose vasopressin does not reduce mortality in patients with septic shock.

Over the past decade, vasopressin administration in septic shock has become more frequent, based on the limited clinical evidence cited above showing that its use often reduces the infusion requirements for other vasopressors. Its use was supported by the international Surviving Sepsis Campaign guidelines, and thus, warranted this complete clinical investigation. Although this study found improved survival in patients with less severe septic shock, as defined by lower norepinephrine requirements, that does not justify protocolized vasopressin use in these patients. As with any clinical trial, subset analyses must be viewed with caution because there are many factors that may have accounted for the difference aside from vasopressin. This study does provide evidence that vasopressin, given in a fixed dose (not titrated to blood pressure) can be administered safely to patients with septic shock, with the caveat that patients with heart disease and peripheral or central nervous system vascular insufficiency were not included or reported and thus, may not tolerate vasopressin administration as well as healthier patients. The other major question not answered by the VASST is whether vasopressin may improve survival in patients with septic shock and persistent hypotension or hypoperfusion (ie, refractory septic shock). It seems intuitive that any intervention to improve perfusion may prevent organ dysfunction and improve survival. Because vasopressin works via a different mechanism than catecholamine vasopressors (eg, norepinephrine), it may be capable of improving perfusion in refractory septic shock, but this has yet to be proven. Based on the results of the VASST, vasopressin cannot be recommended for routine use in septic shock, but in selected patients it can be used safely and may improve blood pressure and reduce the infusion requirements of other traditional vasopressor agents. As with many areas of critical care, individual patient management must be considered when choosing vasopressor agents and their combinations.

Abstract