Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2019

Open Access 01-12-2019 | Visceral Ischemia | Research

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

Authors: Libing Jiang, Yi Sheng, Xia Feng, Jing Wu

Published in: Critical Care | Issue 1/2019

Login to get access

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; I2 = 0%). Nevertheless, they had no significant effects on ICU length of stay (mean deviation (MD) − 0.08, 95% CI, − 0.68 to 0.52, I2 = 0%) and duration of mechanical ventilation (MD − 0.58, 95% CI − 1.47 to 0.31, I2 = 57%). Additionally, there was no significant difference in total adverse events between two groups (RR 1.28, 95% CI 0.87 to 1.90, I2 = 57%), but vasopressin receptor agonists administration could significantly increase the risk of digital ischemia (RR 4.85, 95% CI 2.81 to 8.39, I2 = 26%). Finally, there was no statistical difference of cardiovascular events (RR 0.91, 95% CI 0.53 to 1.57, I2 = 1%), arrhythmia (0.77, 95% CI 0.48 to 1.23, I2 = 23%), mesenteric ischemia (0.83, 95% CI 0.44 to 1.55, I2 = 0%), diarrhea (2.47, 95% CI 0.77 to 7.96, I2 = 49%), cerebrovascular events (1.36, 95% CI 0.18 to 10.54, I2 = 0%), and hyponatremia (1.47, 95% CI 0.84 to 2.55, I2 = 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.
Appendix
Available only for authorised users
Literature
1.
Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect Dis. 2017;17(11):1180–9.PubMed
2.
SepNet Critical Care Trials Group. Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study. Intensive Care Med. 2016;42(12):1980-9.
3.
Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111–24.PubMed
4.
Scheeren TWL, Bakker J, De Backer D, Annane D, Asfar P, Boerma EC, Cecconi M, Dubin A, Dunser MW, Duranteau J, et al. Current use of vasopressors in septic shock. Ann Intensive Care. 2019;9(1):20.
5.
Maas JJ, Pinsky MR, de Wilde RB, de Jonge E, Jansen JR. Cardiac output response to norepinephrine in postoperative cardiac surgery patients: interpretation with venous return and cardiac function curves. Crit Care Med. 2013;41(1):143–50.PubMed
6.
Russell JA. Vasopressin in vasodilatory and septic shock. Curr Opin Crit Care. 2007;13(4):383-91.
7.
Sharshar T, Blanchard A, Paillard M, Raphael JC, Gajdos P, Annane D. Circulating vasopressin levels in septic shock. Crit Care Med. 2003;31(6):1752–8.PubMed
8.
Landry DW, Levin HR, Gallant EM, Ashton RC, Seo S, DAlessandro D, Oz MC, Oliver JA. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation. 1997;95(5):1122–5.PubMed
9.
De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779–89.PubMed
10.
Hammond DA, Ficek OA, Painter JT, McCain K, Cullen J, Brotherton AL, Kakkera K, Chopra D, Meena N. Prospective open-label trial of early concomitant vasopressin and norepinephrine therapy versus initial norepinephrine monotherapy in septic shock. Pharmacotherapy. 2018;38(5):531–8.PubMed
11.
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–77.PubMed
12.
Capoletto C, Almeida J, Ferrari G, Fukushima J, Nakamura R, Risk S, Osawa E, Park C, Oliveira G, Galas F, et al. 37th International Symposium on Intensive Care and Emergency Medicine (part 2 of 3) abstracts. Critical Care. 2017;21(Suppl 1):P168
13.
Acevedo JG, Fernandez J, Escorsell A, Mas A, Gines P, Arroyo V. Clinical efficacy and safety of terlipressin administration in cirrhotic patients with septic shock. J Hepatol. 2009;50:S73.
14.
Han XD, Sun H, Huang XY, Zhang SY, Wang YD, Ren K, Li F. A clinical study of pituitrin versus norepinephrine in the treatment of patients with septic shock. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2012;24(1):33–7.PubMed
15.
Chen Z, Zhou P, Lu Y, Yang C. Comparison of effect of norepinephrine and terlipressin on patients with ARDS combined with septic shock: a prospective single-blind randomized controlled trial. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017;29(2):111–6.PubMed
16.
Morelli A, Ertmer C, Rehberg S, Lange M, Orecchioni A, Cecchini V, Bachetoni A, D'Alessandro M, Van Aken H, Pietropaoli P, et al. Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study. Crit Care. 2009;13(4):R130.PubMedPubMedCentral
17.
Oliveira S, Dessa F, Rocha C, Oliveira F. Early vasopressin application in shock study. Crit Care. 2014;18(1):P158.PubMedCentral
18.
Prakash V, Choudhury AK, Sarin SK. Early introduction of a combination of low dose terlipressin and noradrenaline as vasopressors is superior to hig dose noradrenaline alone in patients of cirrhosis with septic shock (NCT02468063). The 68th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2017. Hepatology. 2017;66(S1):1–1185.
19.
Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock the VANISH randomized clinical trial. J Am Med Assoc. 2016;316(5):509–18.
20.
Malay MB, Ashton RC Jr, Landry DW, Townsend RN. Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma. 1999;47(4):699–703 discussion 703-695.PubMed
21.
Clem O, Painter J, Cullen J, McCain K, Kakkera K, Meena N, Hammond D. Norepinephrine and vasopressin vs norepinephrine alone for septic shock randomized controlled trial. Crit Care Med. 2016;44(12):413.
22.
Choudhury A, Kedarisetty CK, Vashishtha C, Saini D, Kumar S, Maiwall R, Sharma MK, Bhadoria AS, Kumar G, Joshi YK, et al. A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock. Liver Int. 2017;37(4):552–61.PubMed
23.
Russell JA, Vincent JL, Kjolbye AL, Olsson H, Blemings A, Spapen H, Carl P, Laterre PF, Grundemar L. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients. Critical care (London, England). 2017;21(1):213.
24.
Hua F, Wang X, Zhu L. Terlipressin decreases vascular endothelial growth factor expression and improves oxygenation in patients with acute respiratory distress syndrome and shock. The Journal of emergency medicine. 2013;44(2):434–9.PubMed
25.
Svoboda P, Scheer P, Kantorova I, Doubek J, Dudra J, Radvan M, Radvanova J. Terlipressin in the treatment of late phase catecholamine-resistant septic shock. Hepato-gastroenterology. 2012;59(116):1043–7.PubMed
26.
Albanese J, Leone M, Delmas A, Martin C. Terlipressin or norepinephrine in hyperdynamic septic shock: a prospective, randomized study. Crit Care Med. 2005;33(9):1897–902.PubMed
27.
Liu ZM, Chen J, Kou Q, Lin Q, Huang X, Tang Z, Kang Y, Li K, Zhou L, Song Q, et al. Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial. Intensive Care Med. 2018;44(11):1816-25.
28.
Barzegar E, Ahmadi A, Mousavi S, Nouri M, Mojtahedzadeh M. The therapeutic role of vasopressin on improving lactate clearance during and after vasogenic shock: microcirculation, is it the black box? Acta medica Iranica. 2016;54(1):15–23.PubMed
29.
Fonseca-Ruiz N, Lemos Cano A, Ortiz Carmona PD, Correa Aguirre M, Gómez Hernández PM, Osorio García C, Cuesta D, Molina Saldarriaga JF. Uso de vasopresina en pacientes con choque séptico refractario a catecolaminas. Acta Colombiana de Cuidado Intensivo. 2013;13(2):114-23.
30.
Lauzier F, Levy B, Lamarre P, Lesur O. Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med. 2006;32(11):1782–9.PubMed
31.
Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877–87.PubMed
32.
McIntyre WF, Um KJ, Alhazzani W, Lengyel AP, Hajjar L, Gordon AC, Lamontagne F, Healey JS, Whitlock RP, Belley-Cote EP. Association of vasopressin plus catecholamine vasopressors vs catecholamines alone with atrial fibrillation in patients with distributive shock: a systematic review and meta-analysis. JAMA. 2018;319(18):1889–900.PubMedPubMedCentral
33.
Martin C, Viviand X, Leone M, Thirion X. Effect of norepinephrine on the outcome of septic shock. Crit Care Med. 2000;28(8):2758–65.PubMed
34.
Levy B, Collin S, Sennoun N, Ducrocq N, Kimmoun A, Asfar P, Perez P, Meziani F. Vascular hyporesponsiveness to vasopressors in septic shock: from bench to bedside. Intensive Care Med. 2010;36(12):2019–29.PubMed
35.
Schmittinger CA, Torgersen C, Luckner G, Schroder DCH, Lorenz I, Dunser MW. Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study. Intensive Care Med. 2012;38(6):950–8.PubMed
36.
Ba ZF, Chaudry IH. Role of estrogen receptor subtypes in estrogen-induced organ-specific vasorelaxation after trauma-hemorrhage. Am J Phys Heart Circ Phys. 2008;295(5):H2061–7.
37.
Russell JA. Bench-to-bedside review: vasopressin in the management of septic shock. Critical Care (London, England). 2011;15(4):226.
38.
Yang G, Li T, Xu J, Liu L. PKC plays an important mediated effect in arginine vasopressin induced restoration of vascular responsiveness and calcium sensitization following hemorrhagic shock in rats. Eur J Pharmacol. 2010;628(1–3):148–54.PubMed
39.
O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet (London, England). 2002;359(9313):1209–10.
40.
Kopel T, Losser MR, Faivre V, Payen D. Systemic and hepatosplanchnic macro- and microcirculatory dose response to arginine vasopressin in endotoxic rabbits. Intensive Care Med. 2008;34(7):1313–20.PubMed
41.
Yang G, Liu L, Xu J, Li T. Effect of arginine vasopressin on vascular reactivity and calcium sensitivity after hemorrhagic shock in rats and its relationship to Rho-kinase. J Trauma. 2006;61(6):1336–42.PubMed
42.
Holmes CL, Walley KR. Vasopressin in the ICU. Curr Opin Crit Care. 2004;10(6):442–8.PubMed
43.
Morelli A, Ertmer C, Pietropaoli P, Westphal M. Terlipressin: a promising vasoactive agent in hemodynamic support of septic shock. Expert Opin Pharmacother. 2009;10(15):2569–75.PubMed
44.
Lange M, Ertmer C, Westphal M. Vasopressin vs. terlipressin in the treatment of cardiovascular failure in sepsis. Intensive Care Med. 2008;34(5):821–32.PubMed
45.
Asfar P, Hauser B, Ivanyi Z, Ehrmann U, Kick J, Albicini M, Vogt J, Wachter U, Bruckner UB, Radermacher P, et al. Low-dose terlipressin during long-term hyperdynamic porcine endotoxemia: effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism. Crit Care Med. 2005;33(2):373–80.PubMed
46.
Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34(2):344–53.PubMed
47.
Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011;39(2):259–65.PubMed
48.
Boucheix O, Blakytny R, Haroutunian G, Henriksson M, Laporte R, Milano S, Reinheimer TM. Selepressin and arginine vasopressin do not display cardiovascular risk in atherosclerotic rabbit. PLoS One. 2016;11(10):e0165422.PubMedPubMedCentral
49.
Saad AF, Maybauer MO. The role of vasopressin and the vasopressin type V1a receptor agonist selepressin in septic shock. J Crit Care. 2017;40:41–5.PubMed
50.
Belletti A, Musu M, Silvetti S, Saleh O, Pasin L, Monaco F, Hajjar LA, Fominskiy E, Finco G, Zangrillo A, et al. Non-adrenergic vasopressors in patients with or at risk for vasodilatory shock. A systematic review and meta-analysis of randomized trials. PloS one. 2015;10(11):e0142605.PubMedPubMedCentral
51.
Polito A, Parisini E, Ricci Z, Picardo S, Annane D. Vasopressin for treatment of vasodilatory shock: an ESICM systematic review and meta-analysis. Intensive Care Med. 2012;38(1):9–19.PubMed
52.
Serpa Neto A, Nassar AP, Cardoso SO, Manetta JA, Pereira VG, Esposito DC, Damasceno MC, Russell JA. Vasopressin and terlipressin in adult vasodilatory shock: a systematic review and meta-analysis of nine randomized controlled trials. Crit Care. 2012;16(4):R154.PubMedPubMedCentral
53.
Nagendran M, Maruthappu M, Gordon AC, Gurusamy KS. Comparative safety and efficacy of vasopressors for mortality in septic shock: a network meta-analysis. J Intensive Care Soc. 2016;17(2):136–45.PubMed
54.
Tan JX, Chen H, Chen XY, Zhang D, He FM. Vasopressin and its analog terlipressin versus norepinephrine in the treatment of septic shock: a meta-analysis. Int J Clin Exp Med. 2016;9(7):14183–90.
55.
Klinzing S, Simon M, Reinhart K, Bredle DL, Meier-Hellmann A. High-dose vasopressin is not superior to norepinephrine in septic shock. Crit Care Med. 2003;31(11):2646–50.PubMed
56.
Gordon AC, Wang N, Walley KR, Ashby D, Russell JA. The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock. Chest. 2012;142(3):593–605.PubMed
57.
Gordon AC, Russell JA, Walley KR, Singer J, Ayers D, Storms MM, Holmes CL, Hebert PC, Cooper DJ, Mehta S, et al. The effects of vasopressin on acute kidney injury in septic shock. Intensive Care Med. 2010;36(1):83–91.PubMed
58.
Sacha GL, Lam SW, Duggal A, Torbic H, Bass SN, Welch SC, Butler RS, Bauer SR. Predictors of response to fixed-dose vasopressin in adult patients with septic shock. Ann Intensive Care. 2018;8(1):35.PubMedPubMedCentral
59.
Nascente AP, Freitas FG, Bakker J, Bafi AT, Ladeira RT, Azevedo LC, Lima A, Machado FR. Microcirculation improvement after short-term infusion of vasopressin in septic shock is dependent on noradrenaline. Clinics. 2017;72(12):750–7.PubMedPubMedCentral
60.
Russell JA, Walley KR, Gordon AC, Cooper DJ, Hebert PC, Singer J, Holmes CL, Mehta S, Granton JT, Storms MM, et al. Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock. Crit Care Med. 2009;37(3):811–8.PubMed
61.
Hammond DA, Cullen J, Painter JT, McCain K, Clem OA, Brotherton AL, Chopra D, Meena N: Efficacy and safety of the early addition of vasopressin to norepinephrine in septic shock. J Intensive Care Med 2017:885066617725255.
62.
Reardon DP, DeGrado JR, Anger KE, Szumita PM. Early vasopressin reduces incidence of new onset arrhythmias. J Crit Care. 2014;29(4):482–5.PubMed
63.
Bihari D, Prakash S, Bersten A. Low-dose vasopressin in addition to noradrenaline may lead to faster resolution of organ failure in patients with severe sepsis/septic shock. Anaesth Intensive Care. 2014;42(5):671–4.PubMed
64.
Wu JY, Stollings JL, Wheeler AP, Semler MW, Rice TW. Efficacy and outcomes after vasopressin guideline implementation in septic shock. Ann Pharmacother. 2017;51(1):13–20.PubMed
65.
Musallam N, Altshuler D, Merchan C, Zakhary B, Aberle C, Papadopoulos J. Evaluating vasopressor discontinuation strategies in patients with septic shock on concomitant norepinephrine and vasopressin infusions. Ann Pharmacother. 2018;52(8):733–9.PubMed
Metadata
Title
The effects and safety of vasopressin receptor agonists in patients with septic shock: a meta-analysis and trial sequential analysis
Authors
Libing Jiang
Yi Sheng
Xia Feng
Jing Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2362-4

Other articles of this Issue 1/2019

Critical Care 1/2019 Go to the issue

Research

Driving pressure is not associated with mortality in mechanically ventilated patients without ARDS

Letter

Sevoflurane and nephrogenic diabetes insipidus on the rise: copeptin to the rescue?

Research

Safety and efficacy of volume-based feeding in critically ill, mechanically ventilated adults using the ‘Protein & Energy Requirements Fed for Every Critically ill patient every Time’ (PERFECT) protocol: a before-and-after study

Editorial

Humanizing the intensive care unit

Research

Vascular endothelial cadherin shedding is more severe in sepsis patients with severe acute kidney injury

Letter

Comment upon “Time to epinephrine treatment is associated with the risk of mortality in children who achieve sustained ROSC after traumatic out-of-hospital cardiac arrest”