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

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

Nephrotoxic effects of aminoglycosides on the developing kidney

Aminoglycosides are the most commonly used antibiotics in infants hospitalized in neonatal intensive care units. Despite their outstanding efficacy profile, aminoglycosides remain relatively toxic with a narrow therapeutic index and a potential to cause nephrotoxicity and/or ototoxicity. Although aminoglycoside-induced nephrotoxicity has been the subject of multiple studies, the short- and long-term effect of aminoglycosides administration on the developing kidney of the fetus or premature newborn has not yet been determined. In this review the currently available evidence about the effects of aminoglycosides on the developing kidney and the mechanisms involved in aminoglycoside-induced nephrotoxicity are presented.   Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy) · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge researc

Topical nitroglycerin in neonates with tissue injury: A case report and review of the literature

Peripheral tissue injury is one of the well-described morbidities associated with stays in the neonatal intensive care unit. Despite the potential long-term disability associated with this event, the current available therapeutic options remain very limited. Topical nitroglycerin has emerged as a promising agent for the treatment of tissue injury in infants. The present article includes a review of the currently available evidence on the use of topical nitroglycerin in the neonatal population, and describes a unique case involving successful use of 2% nitroglycerin in the late treatment of prolonged tissue ischemia in a newborn infant

Safety of sildenafil in infants

OBJECTIVE: In view of the recent U.S. Food and Drug Administration’s warning against the use of sildenafil in pediatric patients, we aimed to provide an updated overview of the dosing and safety of sildenafil in infants and to explore the relevance of the present safety concerns to the infant population. DATA SOURCE: The National Library of Medicine PubMed and Cochrane Database of Systematic Reviews were searched using the following terms: Sildenafil AND (infant OR infants OR newborn OR newborns OR child OR children OR childhood OR pediatric OR pediatrics OR paediatric OR paediatrics). STUDY SELECTION: Studies presenting original clinical data regarding the dosing, use, or safety of sildenafil in infants with pulmonary hypertension would be included. DATA EXTRACTION: Of the 49 included studies, case reports and case series were the most common type of publications (n = 25). The identified trials included 625 children, with more than 140 infants. Persistent pulmonary hypertension of the newborn and pulmonary hypertension associated with other conditions were the most common underlying diagnoses. CONCLUSION: There is currently no evidence of serious adverse event in infants exposed to sildenafil. Present safety concerns regarding the use of sildenafil in pediatric patients should be further explored before being applied to infant population. Sildenafil remains a valuable option for the treatment of pulmonary hypertension in young infants. Prospective studies should be designed in such a way that they include a safety assessment to evaluate potential adverse outcomes of sildenafil therapy in this population

Pharmacometric evaluation of umbilical cord blood concentration-based early initiation of treatment in methadone-exposed preterm neonates

In methadone-exposed preterm neonates, early identification of those at risk of severe neonatal abstinence syndrome (NAS) and use of a methadone dosing regimen that can provide effective and safe drug exposure are two important aspects of optimal care. To this end, we reviewed 17 methadone dosing recommendations in the international guidelines and literature and explored their variability in key dosing strategies. We selected three of the reviewed dosing regimens for their pharmacokinetics (PK) characteristics and their exposure–response relationship in three gestational age groups of preterm neonates (28, 32 and 36 gestational age weeks) at risk for development of severe NAS (defined as an umbilical cord methadone concentration of ≤60 ng/mL, following fetal exposure). We applied early (12 h after birth) vs. typical (36 h after birth) initiation of treatment. We observed that use of universally recommended dosing regimens in preterm neonates can result in under-or over-exposure. Use of a PK-guided dosing regimen resulted in effective target exposures within 24 h after birth with early initiation of treatment (12 h after birth). Future prospective studies should explore the incorporation of umbilical cord methadone concentrations for early identification of preterm neonates at risk of developing severe NAS and investigate the use of a PK-guided methadone dosing regimen, so that treatment failure, prolonged length of stay and opioid over-exposure can be avoided