Efficacy and Safety of Vasopressin and Terlipressin in Preterm Neonates: A Systematic Review

Abstract

Introduction: The use of arginine vasopressin (AVP) and terlipressin to treat hypotension in preterm neonates is increasing. Our aim was to review the available evidence on the efficacy and safety of AVP and terlipressin for use in preterm neonates. Methods: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and Google Scholar from inception to September 2021 were searched for studies of AVP and terlipressin in the treatment of hypotension of any cause in preterm neonates. Primary outcomes were improvement in end-organ perfusion and mortality. The risk of bias assessment and certainty of the evidence were performed using appropriate tools. Results: Fifteen studies describing the use of AVP (n = 12) or terlipressin (n = 3) among 148 preterm neonates were included. Certainly, the available evidence for the primary outcome of end-organ perfusion rated as very low. AVP or terlipressin were used to treat 144 and 4 neonates, respectively. Improvement in markers of end-organ perfusion was reported in 143 (99%) neonates treated with AVP and 3 (75%) treated with terlipressin. The mortality rate was 41% (n = 59) and 50% (n = 2) for neonates who received AVP and terlipressin, respectively. Hyponatremia was the most frequently reported adverse event (n = 37, 25%). Conclusion: AVP and terlipressin may improve measured blood pressure values and possibly end-organ perfusion among neonates with refractory hypotension. However, the efficacy–safety balance of these drugs should be assessed on an individual basis and as per the underlying cause. Studies on the optimal dosing, efficacy, and safety of AVP and terlipressin in preterm neonates with variable underlying conditions are critically needed.

An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication

“…Several systematic reviews and meta-analyses have evaluated the effectiveness of AVP and/or terlipressin as rescue or adjuvant therapy of fluid-and catecholamine-refractory shock in mixed pediatric/neonatal populations. It was reported that AVP or terlipressin administration resulted in a significant increase in AP, with a reduction in the inotropic score, HR, and serum lactate levels, along with improved end-organ perfusion and urine output [83,158,171]. On the other hand, no significant beneficial effect of either medication, in terms of mortality, length of stay in the intensive care unit, or tissue ischemia was found [83,158,171].…”

“…Terlipressin (triglycyl-lysine vasopressin) is a non-selective synthetic analogue of AVP acting via stimulation of V1 (vascular), V2 (renal), and V3 (pituitary) receptors [83,154,155]. In the circulation, it is converted to lysine AVP that is slowly released.…”

“…Terlipressin has hemodynamic actions comparable to those of AVP, albeit with a different pharmacokinetic profile. It has a higher affinity to V1 receptors, and a longer half-life (6 h versus 6 min), which leads to an AP increase lasting for about 5 h. Early pharmacokinetic studies of terlipressin in adult volunteers suggested an intermittent intravenous bolus dose of 5, 10, or 20 mcg/kg every 4 to 6 h [83,86,159,168]. The reported doses given to neonates with refractory hypotension were 5-20 mcg/kg bolus, followed by maintenance doses of 5-20 mcg/kg every 4 h [169].…”

“…Our search in PubMed revealed that only 13 cases of neonates with volume and catecholamine-refractory hypotension treated with terlipressin have been reported thus far. Terlipressin effectively restored AP in 12/13 neonates, improved tissue perfusion, and decreased the use of catecholamines [80,[83][84][85][86][87][88][89][90][91]. The all-cause mortality rate was 46% (6/13).…”

“…The all-cause mortality rate was 46% (6/13). No adverse effects were reported, while ND outcome in two survivors, who were followed up, was normal [83,84,[86][87][88][89][90][91]170].…”