Concomitant arginine-vasopressin and hydrocortisone therapy in severe septic shock: association with mortality

Abstract

Purpose: To evaluate the association between concomitant arginine-vasopressin (AVP)/hydrocortisone therapy and mortality in severe septic shock patients. Methods: This retrospective study included severe septic shock patients treated with supplementary AVP. To test the association between concomitant AVP/hydrocortisone use and mortality, a multivariate regression and Cox model (adjusted for admission year, initial AVP dosage and the Sepsis-related Organ Failure Assessment score before AVP) as well as a propensity score-based analysis were used. In both models, intensive care unit (ICU) and 28-day mortality served as outcome variables. Results: One hundred fifty-nine patients were included. Hydrocortisone was administered to 76 (47.8%) at a median daily dosage of 300 (200-300) mg. In the multivariate logistic regression model, concomitant use of AVP and hydrocortisone was associated with a trend towards lower ICU (OR, 0.51; CI 95%, 0.24-1.08; p = 0.08) and 28-day (HR, 0.69; CI 95%, 0.43-1.08; p = 0.11) mortality. The probability of survival at day 28, as predicted by the regression model, was significantly higher in patients treated with concomitant AVP and hydrocortisone compared to those receiving AVP without hydrocortisone (p = 0.001). In a propensity score-based analysis, ICU (45 vs. 65%; OR, 0.69; CI 95% 0.38-1.26; p = 0.23) and 28-day mortality (35.5 vs. 55%; OR, 0.59; CI 95%, 0.27-1.29; p = 0.18) was not different between patients treated with (n = 40) or without concomitant hydrocortisone (n = 40). Conclusion: Concomitant AVP and hydrocortisone therapy may be associated with a survival benefit in septic shock. An adequately powered, randomised controlled trial appears warranted to confirm these preliminary, hypothesis-generating results.

Therapeutic Strategies for High-Dose Vasopressor-Dependent Shock

“…Steroids use also increased plasma vasopressin levels by 33% [52]. Similar findings were described in retrospective studies in different populations [12, 13]. While such interaction could be a good alternative to treat refractory shock, randomized trials are necessary to validate this hypothesis.…”

“…The threshold of approximately 0.5 mcg/kg/min of NE is often used in clinical trials as a definition of refractory shock [8, 9, 13]. In 2011, Benbenishty et al used a ROC analysis to determine the correlation between maximum dose of vasopressors and death.…”

“…Relative arginine vasopressin (AVP) deficiency is common in vasodilatory shock [50], and exogenous infusion is often used as rescue therapy in refractory shock [13–15]. In 2003, Dünser et al specifically addressed the question whether there was benefit from adding AVP 0.067 U/min in hypotensive patients requiring NE > 0.5 mg/kg/minute in a randomized trial including 48 patients with vasodilatory shock.…”

Did the beneficial renal outcomes with vasopressin VANISH?

“…Prior studies have shown a positive effect of AVP use on kidney function (3,7,17) and a positive interaction between AVP and corticosteroid use (4,18), both findings which were not corroborated in VANISH. There are many differences in the prior trials and VANISH, including how AVP was utilized and the timing of corticosteroid initiation.…”

Year in review in Intensive Care Medicine 2011. II. Cardiovascular, infections, pneumonia and sepsis, critical care organization and outcome, education, ultrasonography, metabolism and coagulation

“…In a retrospective cohort of 155 patients with septic shock receiving vasopressin, Torgersen et al [15] evaluated the impact of combined treatment with hydrocortisone. Hydrocortisone was administered to almost half of the patients (47.8%).…”