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      The effects and safety of vasopressin receptor agonists in patients with septic shock: a meta-analysis and trial sequential analysis

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      Author(s): 2 , , 1 , 3 , 2
      Publication date (Electronic):
      Journal: Critical Care
      Publisher: BioMed Central
      Keywords: Vasopressin, Catecholamine, Septic shock, Meta-analysis

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          Abstract

          Background

          The aim of this study was to evaluate the effects and safety of vasopressin receptor agonists in patients with septic shock.

          Methods

          PubMed, EMBASE, and Cochrane library were searched for randomized controlled trials evaluating the effects of vasopressin receptor agonists in septic shock patients. Two reviewers performed literature selection, data extraction, and quality evaluation independently. The primary outcome was mortality. And secondary outcomes included intensive care unit (ICU) length of stay, duration of mechanical ventilation, and incidence of adverse events. In addition, a trial sequential analysis (TSA) was performed.

          Results

          Twenty studies were eligible for meta-analysis. The results showed vasopressin receptor agonists use was associated with reduced mortality (relative risk (RR) 0.92; 95% confidence interval (CI) 0.84 to 0.99; I 2 = 0%). Nevertheless, they had no significant effects on ICU length of stay (mean deviation (MD) − 0.08, 95% CI, − 0.68 to 0.52, I 2 = 0%) and duration of mechanical ventilation (MD − 0.58, 95% CI − 1.47 to 0.31, I 2 = 57%). Additionally, there was no significant difference in total adverse events between two groups (RR 1.28, 95% CI 0.87 to 1.90, I 2 = 57%), but vasopressin receptor agonists administration could significantly increase the risk of digital ischemia (RR 4.85, 95% CI 2.81 to 8.39, I 2 = 26%). Finally, there was no statistical difference of cardiovascular events (RR 0.91, 95% CI 0.53 to 1.57, I 2 = 1%), arrhythmia (0.77, 95% CI 0.48 to 1.23, I 2 = 23%), mesenteric ischemia (0.83, 95% CI 0.44 to 1.55, I 2 = 0%), diarrhea (2.47, 95% CI 0.77 to 7.96, I 2 = 49%), cerebrovascular events (1.36, 95% CI 0.18 to 10.54, I 2 = 0%), and hyponatremia (1.47, 95% CI 0.84 to 2.55, I 2 = 0%) between two groups. Egger’s test showed there was no significant publication bias among studies ( P = 0.36).

          Conclusions

          The use of vasopressin might result in reduced mortality in patients with septic shock. An increased risk of digital ischemia must be taken into account.

          Electronic supplementary material

          The online version of this article (10.1186/s13054-019-2362-4) contains supplementary material, which is available to authorized users.

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          Most cited references47

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          The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study

          M. RODRIGUES, R Lopez, M Dias … (2017)
          Article 0 comments Cited 138 times – based on 0 reviews     Review now
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            Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study.

            Martin W Dünser, Ingo Lorenz, Günter Luckner … (2012)
            To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure. The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h. Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8-57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08-2.77; p = 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1-1.01; p = 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (p < 0.001) and mechanical ventilation (p < 0.001) for longer and had longer intensive care unit stays (p < 0.001) and greater mortality (25.9 vs. 1.7 %; p < 0.001) than patients who did not. Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.
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              Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study

              Andrea Morelli, Christian Ertmer, Sebastian Rehberg … (2009)
              Introduction Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements. Methods We enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 μg·kg-1·h-1), vasopressin (.03 U·min-1) or norepinephrine (15 μg·min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA. Results There were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 μg·min-1 of norepinephrine, 1.3 μg·kg-1·h-1 of terlipressin allowed a marked reduction in catecholamine requirements (0.8 ± 1.3 and 1.2 ± 1.4 vs. 0.2 ± 0.4 μg·kg-1·min-1 at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 ± 2.8 and 2.8 ± 2.5 vs. 0.9 ± 0.3 mg·dL-1; each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL). Conclusions The present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements. Trial registration ClinicalTrial.gov NCT00481572.
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                Author and article information

                Contributors
                Libing Jiang:
                ORCID: http://orcid.org/0000-0002-7425-2345
                +086057187783921 , 2515168@zju.edu.cn
                Yi Sheng: sshengyi@126.com
                Xia Feng: f405776789@163.com
                Jing Wu: 21618157@zju.edu.cn
                Journal
                Journal ID (nlm-ta): Crit Care
                Title: Critical Care
                Publisher: BioMed Central (London )
                ISSN (Print): 1364-8535
                ISSN (Electronic): 1466-609X
                Publication date (Electronic): 14 March 2019
                Publication date PMC-release: 14 March 2019
                Publication date Collection: 2019
                Volume: 23
                Electronic Location Identifier: 91
                Affiliations
                [1 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Yuhang Branch of The Second Affiliated Hospital of Zhenjiang University, ; No.369 Yingbin Road, Yuhang District, Hangzhou, 311100 Zhenjiang Province China
                [2 ]ISNI 0000 0004 1759 700X, GRID grid.13402.34, Department of Emergency Medicine, Second Affiliated Hospital, School of Medicine & Institute of Emergency Medicine, , Zhejiang University, ; No 88, Jiefang Rd, Hangzhou, China
                [3 ]GRID grid.440280.a, Department of Respiratory, , The Third People’s Hospital of Hangzhou, ; West Lake Avenue 38, Hangzhou, China
                Author information
                http://orcid.org/0000-0002-7425-2345
                Article
                Publisher ID: 2362
                DOI: 10.1186/s13054-019-2362-4
                PMC ID: 6419432
                PubMed ID: 30871607
                SO-VID: 5df0f796-d21c-440a-afdb-227924a75a1b
                Copyright © © The Author(s). 2019
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 18 September 2018
                Date accepted : 17 February 2019
                Funding
                Funded by: Zhejiang medical and health science and technology project (2017ky372)
                Award ID: 2017ky372
                Award Recipient :
                Funded by: Hangzhou yuhang district medical and health research key subject construction
                Award ID: 2016009
                Award Recipient :
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: vasopressin,catecholamine,septic shock,meta-analysis
                Data availability:
                ScienceOpen disciplines: Emergency medicine & Trauma
                Keywords: vasopressin, catecholamine, septic shock, meta-analysis

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