Abstract
BackgroundVasopressin (AVP) and terlipressin (TP) have been used as last-line therapy in refractory shock in children. However, the efficacy and safety profiles of AVP and TP have not been determined in pediatric refractory shock of different origins. We aimed to assess the efficacy and safety of the addition of AVP/TP therapy in pediatric refractory shock of all causes compared to conventional therapy with fluid resuscitation and vasopressor and inotropic therapy.MethodsWe conducted a systematic review, meta-analysis, and trial sequential analysis (TSA) comparing AVP and TP to conventional therapy. MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched up to February 2016. The systematic review included all reports of AVP/TP use in the pediatric population. Reports of clinical trials were pooled using random-effects models and TSA. Main outcomes were mortality and tissue ischemia.ResultsThree randomized controlled trials and five “before-and-after clinical” trials (without comparator) met the inclusion criteria. Among 224 neonates and children (aged 0 to 18 years) with refractory shock, 152 received therapy with AVP or TP. Pooled analyses showed no association between AVP/TP treatment and mortality (relative risk (RR),1.19; 95% confidence interval (CI), 0.71–2.00), length of stay in the pediatric intensive care unit (PICU) (mean difference (MD), –3.58 days; 95% CI, –9.05 to 1.83), and tissue ischemia (RR, 1.48; 95% CI, 0.47–4.62). In TSA, no significant effect on mortality and risk for developing tissue ischemia was observed with AVP/TP therapy.ConclusionOur results emphasize the lack of observed benefit for AVP/TP in terms of mortality and length of stay in the PICU, and suggest an increased risk for ischemic events. Our TSA suggests that further large studies are necessary to demonstrate and establish benefits of AVP/TP in children.PROSPERO registry: CRD42016035872
Highlights
Vasopressin (AVP) and terlipressin (TP) have been used as last-line therapy in refractory shock in children
Our meta-analysis indicates that AVP/TP therapy is ineffective in reducing mortality in refractory shock in the pediatric population
The forest plot demonstrates point estimates of mean difference surrounded by 95% confidence interval (CI). (DOCX 138 kb) Additional file 6: Figure S5
Summary
Vasopressin (AVP) and terlipressin (TP) have been used as last-line therapy in refractory shock in children. The efficacy and safety profiles of AVP and TP have not been determined in pediatric refractory shock of different origins. We aimed to assess the efficacy and safety of the addition of AVP/TP therapy in pediatric refractory shock of all causes compared to conventional therapy with fluid resuscitation and vasopressor and inotropic therapy. Hemodynamic shock is a leading cause of morbidity and mortality in the pediatric population worldwide [1]. Aggressive fluid resuscitation is the first line of therapy for shock [7]. Reduced vasoconstrictor sensitivity to vasopressors in shock can lead to vasodilation, severe hypotension, and vasoparalysis [8]. There is, a pressing need for agents which target other pathways involved in the development of shock
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