Norepinephrine vs Vasopressin: Which Vasopressor Should Be Discontinued First in Septic Shock? A Meta-Analysis

Background: Patients with septic shock in whom norepinephrine (NE) infusion alone is insufficient to raise blood pressure require the concomitant administration of vasopressin (VP). However, current guidelines do not advise clinicians as to which vasoactive agent to discontinue first once the patient's septic shock begins to resolve. Moreover, there is controversial data guiding clinicians on how to discontinue vasopressors for septic shock patients who are receiving a combination therapy of NE and VP. Methods: The PubMed, EMBASE, and Cochrane Central Register databases were searched from the database inception until October 18, 2018. Studies were limited to adult patients with septic shock who received concomitant NE and VP treatment, that included different orders of vasopressor discontinuation. The primary outcome was the incidence of hypotension. Overall mortality, ICU mortality, and length of stay (LOS) in the ICU were secondary outcomes. Sensitivity and subgroup analyses as well as trial sequential analysis were performed. Results: One prospective randomized controlled trial and seven retrospective cohort studies were included in present meta-analysis. Compared with discontinuing VP first, the incidence of hypotension was significantly lower when NE was discontinued first (odds ratio, OR 0.3, 95% confidence interval, CI 0.10 to 0.86,P = 0.02;I-2 = 91%). No significant difference was detected in either overall mortality (OR 1.28, 95% CI 0.77 to 2.10,P = 0.34) or ICU mortality (OR 0.99, 95% CI 0.74 to 1.34,P = 0.96) between these two groups. Furthermore, ICU LOS was also evaluated in five studies, and no statistical significance was observed between the two groups with different orders in weaning vasopressors (mean difference 1.35, 95% CI -2.05 to 4.74,P = 0.44). The subgroup analyses suggested a significant association between hypotension and the practice of discontinuing VP first specifically in patients with a low usage rate of corticosteroids (odds ratio, OR 0.18, 95% confidence interval, CI 0.04 to 0.78,P = 0.02). The trial sequential analysis indicated a lack of sufficient evidence to draw conclusions from the current results (required information size = 11 821). Conclusions: In adults with septic shock treated with concomitant VP and NE therapy, discontinuing VP first may lead to a higher incidence of hypotension but is not associated with mortality or ICU LOS. Further prospective studies with larger sample sizes are warranted.