Vasopressin Versus Norepinephrine for the Management of Septic Shock in Cancer Patients: The VANCS II Randomized Clinical Trial*

Abstract

Objectives: Previous trials suggest that vasopressin may improve outcomes in patients with vasodilatory shock. The aim of this study was to evaluate whether vasopressin could be superior to norepinephrine to improve outcomes in cancer patients with septic shock. Design: Single-center, randomized, double-blind clinical trial, and meta-analysis of randomized trials. Setting: ICU of a tertiary care hospital. Patients: Two-hundred fifty patients 18 years old or older with cancer and septic shock. Interventions: Patients were assigned to either vasopressin or norepinephrine as first-line vasopressor therapy. An updated meta-analysis was also conducted including randomized trials published until October 2018. Measurements and Main Results: The primary outcome was all-cause mortality at 28 days after randomization. Prespecified secondary outcomes included 90-days all-cause mortality rate; number of days alive and free of advanced organ support at day 28; and Sequential Organ Failure Assessment score 24 hours and 96 hours after randomization. We also measure the prevalence of adverse effects in 28 days. A total of 250 patients were randomized. The primary outcome was observed in 71 patients (56.8%) in the vasopressin group and 66 patients (52.8%) in the norepinephrine group (p = 0.52). There were no significant differences in 90-day mortality (90 patients [72.0%] and 94 patients [75.2%], respectively; p = 0.56), number of days alive and free of advanced organ support, adverse events, or Sequential Organ Failure Assessment score. Conclusions: In cancer patients with septic shock, vasopressin as first-line vasopressor therapy was not superior to norepinephrine in reducing 28-day mortality rate.

Effect of Vasopressin and its Analogs versus Catecholamines on the Renal Outcomes in Septic Shock:A Systematic Review and Meta-Analysis of Randomized Trials

“…Although several studies reported an overall higher creatinine clearance or urine output in patients treated with Vasopressin (20,23,25,30,33), we failed to show a signi cant effect when we pooled the data. We think this could be due to the small sample size affected by the predetermined time point.…”

“…Two studies evaluated kidney function as a primary outcome with vasopressin infusion (20,25). Six RCTs (20,23,25,36,37,39) reported the use of RRT, with a total of 1,555 patients. The number of events in the Vasopressin or analogs group was 223 out of 772 versus 251 out of 741 in the control group.Vasopressin or analogs use was associated with less need for RRT (RR, -0.05 [-0.10, -0.01] I² = 0%, p value = 0.02).…”

“…Previous studies have demonstrated the bene cial effects of Vasopressin and analogs on renal function. Increased creatinine clearance, higher urinary output, lower acute kidney injury (AKI) incidence, and a reduced need for renal replacement therapy (RRT) in patients with septic shock treated with Vasopressin compared to other vasopressors were reported (19)(20)(21)(22)(23)(24)(25)(26). However, de nitive evidence analyzing the data only on patients with septic shock is lacking.…”

The order of vasopressor discontinuation and incidence of hypotension: a retrospective cohort analysis

“…Likewise, previous investigations showed that sustained VP therapy could be kidney-protective 34 – 36 , based on VP maintenance of glomerular filtration rate and improved creatinine clearance compared with NE 37 , 38 . However, we found no such protective effect in our study as there was no significant difference in AKI incidence between VP and NE discontinued first groups.…”

Efficacy and Safety of Vasopressin Alone or in Combination With Catecholamines in the Treatment of Septic Shock: A Systematic Review

“…The V1a-in vessels and liver, V1b-in anterior pituitary where it releases Corticotropin Releasing Hormone (CRH) which ultimately releases adreno-cortico-tropic hormone (ACTH) and V2-found in the kidney [ 17 - 19 ]. Furthermore, VP has a significant effect on reducing inflammatory cytokines compared with NE [ 20 ].…”