Vasopressors in septic shock: a systematic review and network meta-analysis

Abstract

Feihu Zhou,1,* Zhi Mao,1,* Xiantao Zeng,2,* Hongjun Kang,1 Hui Liu,1 Liang Pan,1 Peter C Hou31Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, 2Center for Evidence-Based and Translational Medicine, Zhongnan Hospital, Wuhan University, Wuhan, People’s Republic of China; 3Department of Emergency Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA*These authors contributed equally to the paper Objective: Vasopressor agents are often prescribed in septic shock. However, their effects remain controversial. We conducted a systematic review and Bayesian network meta-analysis to compare the effects among different types of vasopressor agents.Data sources: We searched for relevant studies in PubMed, Embase, and the Cochrane Library databases from database inception until December 2014.Study selection: Randomized controlled trials in adults with septic shock that evaluated different vasopressor agents were selected.Data extraction: Two authors independently selected studies and extracted data on study characteristics, methods, and outcomes.Data synthesis: Twenty-one trials (n=3,819) met inclusion criteria, which compared eleven vasopressor agents or vasopressor combinations (norepinephrine [NE], dopamine [DA], vasopressin [VP], epinephrine [EN], terlipressin [TP], phenylephrine [PE], TP+NE, TP + dobutamine [DB], NE+DB, NE+EN, and NE + dopexamine [DX]). Except for the superiority of NE over DA, the mortality of patients treated with any vasopressor agent or vasopressor combination was not significantly different. Compared to DA, NE was found to be associated with decreased cardiac adverse events, heart rate (standardized mean difference [SMD]: -2.10; 95% confidence interval [CI]: -3.95, -0.25; P=0.03), and cardiac index (SMD: -0.73; 95% CI: -1.14, -0.03; P=0.004) and increased systemic vascular resistance index (SVRI) (SMD: 1.03; 95% CI: 0.61, 1.45; P<0.0001). This Bayesian meta-analysis revealed a possible rank of probability of mortality among the eleven vasopressor agents or vasopressor combinations; from lowest to highest, they are NE+DB, EN, TP, NE+EN, TP+NE, VP, TP+DB, NE, PE, NE+DX, and DA.Conclusion: In terms of survival, NE may be superior to DA. Otherwise, there is insufficient evidence to suggest that any other vasopressor agent or vasopressor combination is superior to another. When compared to DA, NE is associated with decreased heart rate, cardiac index, and cardiovascular adverse events, as well as increased SVRI. The effects of vasopressor agents or vasopressor combinations on mortality in patients with septic shock require further investigation.Keywords: norepinephrine, dopamine, vasopressors, sepsis, shock, network meta-analysis