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Renal Outcomes of Vasopressin and Its Analogs in Distributive Shock: A Systematic Review and Meta-Analysis of Randomized Trials

Nedel, Wagner L. MD, MSc1–3; Rech, Tatiana H. MD, PhD1,4; Ribeiro, Rodrigo A. MD, PhD5,6; Pellegrini, José Augusto S. MD, PhD1; Moraes, Rafael B. MD, PhD1,3

doi: 10.1097/CCM.0000000000003471
Online Review Articles

Objectives: To systematically review the literature and synthesize evidence concerning the effects of vasopressin and its analogs compared with other vasopressors in distributive shock, focusing on renal outcomes.

Data Sources: We performed a systematic review in MEDLINE, Embase, Cochrane Central, and databases.

Study Selection: Randomized clinical trials that compared vasopressin and its analogs with other vasopressors and reported renal outcomes in adult patients with distributive shock.

Data Extraction: Paired reviewers independently screened citations, conducted data extraction and assessed risk of bias. Three prespecified subgroup analyses were conducted. Three main outcomes related to acute renal failure were analyzed: the need for renal replacement therapy, acute kidney injury incidence, and acute kidney injury-free days. I2 test was used to evaluate heterogeneity between studies. Substantial heterogeneity was defined as I2 greater than 50%. A random-effects model with Mantel-Haenszel weighting was used for all analyses. Heterogeneity was explored using subgroup analysis. The quality of evidence for intervention effects was summarized using Grading of Recommendations Assessment, Development, and Evaluation methodology. This study was registered in the PROSPERO database (CRD42017054324).

Data Synthesis: Three-thousand twenty-six potentially relevant studies were identified, and 30 articles were reviewed in full. Seventeen studies met the inclusion criteria, including a total of 2,833 individuals. Of these, 11 studies (2,691 individuals) were suitable for quantitative meta-analysis. Overall, the evidence was of low to moderate quality. Patients who received vasopressin and its analogs had a reduced need for renal replacement therapy (odds ratio, 0.59 [0.37–0.92]; p = 0.02; I2 = 49%) and a lower acute kidney injury incidence (odds ratio, 0.58 [0.37–0.92]; p = 0.02; I2 = 63%). These results should be interpreted with caution, due to excessive heterogeneity. Acute kidney injury-free data was not pooled, since the small number of studies and extreme heterogeneity.

Conclusions: In patients with distributive shock, vasopressin and its analogs use is associated with a reduced need for renal replacement therapy and lower acute kidney injury incidence. These results are supported by high risk of bias evidence.

1Intensive Care Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil.

2Post-Graduate Program in Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

3Intensive Care Unit, Grupo Hospitalar Conceição (GHC), Porto Alegre, Brazil.

4Post-Graduate Program in Medical Sciences: Endocrinology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

5Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

6Faculdade Meridional (IMED-RS), Porto Alegre, Brazil.

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Supported, in part, by Fundo de Incentivo à Pesquisa e Ensino do Hospital de Clínicas de Porto Alegre (project number 17–0264).

Dr. Nedel disclosed that this study was supported by Fundo de Incentivo à Pesquisa e Ensino do Hospital de Clínicas de Porto Alegre (project number 17–0264). Dr. Ribeiro received funding from Celgene (health economics project in hematology), Jonhson Medical (real-world evidence analysis in electrophysiology and abdominal surgery), UCB (health technology assessment in Parkinson disease and rheumatology), Novo Nordisk (advisory board in diabetes), and Boehringer Ingelheim (consultancy in health technology assessment). The remaining authors have disclosed that they do not have any potential conflicts of interest.

Address requests for reprints to: Wagner L. Nedel, MD, MSc, Rua Ramiro Barcelos, 2350, 13° Andar, 90035-003 - Porto Alegre, Brazil. E-mail:

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