Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS)

BACKGROUND: Vasopressin (AVP) is commonly added to norepinephrine (NE) to reverse shock in patients with sepsis. However, there are no data to support the appropriate strategy of vasopressor tapering in patients on concomitant NE and AVP who are recovering from septic shock. Therefore, the objective of this study was to evaluate the incidence of hypotension while tapering vasopressors in patients on concomitant NE and AVP recovering from septic shock. METHODS: Patients with septic shock receiving concomitant NE and AVP were randomly assigned to taper NE first (NE group) or AVP first (AVP group). The primary end point was the incidence of hypotension within one hour of tapering of the first vasopressor. We also evaluated the association between serum copeptin levels and the occurrence of hypotension. RESULTS: The study was stopped early due to a significant difference in the incidence of hypotension after 38 and 40 patients were enrolled in the NE group and the AVP group, respectively. There were 26 patients (68.4%) in the NE group versus 9 patients (22.5%) in the AVP group who developed hypotension after tapering the first vasopressor (p < 0.001). There was a similar finding during the subsequent tapering of the second vasopressor (64.5% in the NE vs 25.0% in the AVP group, p = 0.020). Finally, NE tapering was significantly associated with hypotension during the study period (hazard ratio, 2.221; 95% confidence interval, 1.106–4.460; p = 0.025). The serum copeptin level was lower in patients in whom hypotension developed during tapering of AVP than it was in those without hypotension. CONCLUSIONS: Tapering NE rather than AVP may be associated with a higher incidence of hypotension in patients recovering from septic shock who are on concomitant NE and AVP. However, further studies with larger sample sizes are required to better determine the appropriate strategy for vasopressor tapering. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01493102. Registered on 15 December 2011.