title: Role of vasopressin and terlipressin in refractory shock compared to conventional therapy in the neonatal and pediatric population: a systematic review, meta-analysis, and trial sequential analysis.
abstract: Vasopressin (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.
  
  
  
  We 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.
  
  
  
  Three 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.
  
  
  
  Our 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.
authors.affiliation: Division of Clinical Pharmacy, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.|Department of Pediatrics, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel.
authors.forename: Reem
authors.initials: R
authors.lastname: Masarwa
authors.affiliation: Department of Pediatric Intensive Care Medicine, Safra Children's Hospital, Chaim Sheba Medical Center, Ramat-Gan, Israel.|Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
authors.forename: Gideon
authors.initials: G
authors.lastname: Paret
authors.affiliation: Division of Clinical Pharmacy, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Amichai
authors.initials: A
authors.lastname: Perlman
authors.affiliation: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Ein-Kerem, Jerusalem, Israel.
authors.forename: Shimon
authors.initials: S
authors.lastname: Reif
authors.affiliation: Division of Clinical Pharmacy, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Bruria Hirsh
authors.initials: BH
authors.lastname: Raccah
authors.affiliation: Division of Clinical Pharmacy, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. ilan.matok@ekmd.huji.ac.il.
authors.forename: Ilan
authors.initials: I
authors.lastname: Matok
mesh_terms: D000293:Adolescent; D022561:Advanced Cardiac Life Support / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007902:Length of Stay; D008236:Lypressin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010372:Pediatrics / Q000379:methods* / Q000639:trends; D012769:Shock / Q000188:drug therapy* / Q000401:mortality; D000077585:Terlipressin; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014667:Vasopressins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014662:Vasoconstrictor Agents; D014667:Vasopressins; D008236:Lypressin; D000077585:Terlipressin
keywords: Pediatrics; Refractory; Refractory hypotension; Septic; Shock; Terlipressin (TP); Vasodilatory; Vasopressin (AVP)