Faculty Opinions recommendation of Vasopressin versus norepinephrine infusion in patients with septic shock.

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Abstract
In the pediatric field, no randomized, double-blind, prospective studies have evaluated the beneficial effects of vasopressin; only pediatric case series and case reports have been published {1}. Thus, the results of this adult study can be applied to children. This multicenter randomized, stratified, double-blind study included 778 patients older than 16 years of age who had septic shock and were receiving a minimum of 5mcg/min (around 0.06-0.07mcg/kg/min) of norepinephrine. Patients were assigned to receive either low-dose vasopressin (0.01-0.03U/min, i.e. 0.6-1.8U/h) or norepinephrine (5-15mcg/min, i.e. around 0.06-0.2mcg/kg/min) titrated to maintain a target mean arterial pressure of 65-75mmHg. The primary outcome measure was death from any cause 28 days after the start of infusion. Several secondary outcomes were evaluated (90-day mortality, days alive and free of organ dysfunction during the first 28 days, length of stay in the ICU and hospital), as well as rates of serious adverse events. There was no difference between the two groups in the 28-day mortality rate (vasopressin 35.4%, norepinephrine 39.3%; p=0.26) and secondary outcomes, and the overall rates of serious events (10.3% and 10.5 respectively; p=1.00). In the subgroup of 107 patients in whom plasma vasopressin levels were measured, the levels were extremely low at baseline, did not change in the norepinephrine group, and increased in the vasopressin group reaching a level markedly higher than that of patients with cardiogenic shock {2}. As underlined by the authors themselves, this study has several limitations: mean arterial pressure at baseline was 72-73mmHg, and, thus, this study essentially evaluated the effects of vasopressin as a ‘cathecholamine-sparing drug’. The mean time from meeting the entry criteria to infusion was 12 hours, and this may be too late for any vasopressor agent to show a significant effect on mortality. Vasopressin levels as a guide to the dose or duration of vasopressin infusion were not measured. My temporary conclusions are that infusion of vasopressin (initiated earlier, within six hours or preferably within one or two hours, because timing is decisive), bolus or infusion of terlipressin (as excellently discused by Lange et al. {2}) should probably be limited to controlled clinical trials. Until more data are available, the use of vasopressin or telipressin as a rescue therapy should be considered on an individual basis. In future randomized controlled studies, the important point of doses of drugs should be taken into account. In fact, if the dose of vasopressin used in the study by Russell et al. was in accordance with the literature data {2}, the mean ± SD norepinephrine dosage at randomization was low (0.28 ± 0.26mcg/kg/min in the norepinephrine group; 0.26 ± 0.27mcg/kg/min in the vasopressin group). Also, norepinephrine was titrated to a maximum of 15mcg/min in the norepinephrine group after randomization, probably because the target mean arterial pressure was reached. Nonetheless, norepinephrine doses or requirements reported in the literature are often higher; in most studies, the mean dose was 0.2-1.3mcg/kg/min {3}, and a surviving patient received up to 20 mcg/kg/min {4}.

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