Systematic Review and Meta-Analysis of Cardiovascular Medications in Neonatal Hypotension

Abstract

<b><i>Background:</i></b> Comparative studies among the various cardiovascular medications used for the treatment of neonatal hypotension are lacking. <b><i>Methods:</i></b> This systematic review and pairwise meta-analysis of the anti-hypotensive treatments in preterm and term infants was conducted to evaluate efficacy and impact on outcome. Electronic databases were searched up to February 2021 for relevant articles. As an extension of the current approach for study selection, a machine learning technique was used. Only randomized controlled trials (RCTs) of inotropes, pressors, volume therapy, and corticosteroids were included. Response to treatment was the primary outcome while secondary outcomes included mortality and common morbidities. <b><i>Results:</i></b> Nineteen RCTs involving 758 preterm and term neonates were found, and 8 treatments were evaluated. Most studies involved subjects with early hypotension associated with prematurity. Pairwise meta-analysis among treatments showed that dopamine was more effective than dobutamine regarding the response to treatment (restoration of normotension or normalization of blood pressure) (7 trials, 286 neonates, odds ratio, 3.06 [95% CI = 1.06–8.87]; <i>I</i><sup>2</sup> = 49%, very low quality of the evidence per GRADE). Comparisons of other treatments were not significant. No differences were found among regimens regarding survival and other secondary outcomes. <b><i>Conclusion:</i></b> In this systematic review and pairwise meta-analysis, only the comparison of dopamine versus dobutamine provided evidence for efficacy of treatment and favored dopamine. No safe conclusions could be reached in regard to other treatments. Data regarding the management of arterial hypotension in conditions other than transition after birth in preterm newborns are sparse both in preterm and term infants.

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

“…Moreover, DOP, but not DOB, was associated with suppression of TSH, T4, and prolactin that was reversed soon after treatment stopped [116]. These findings were confirmed by systematic reviews and meta-analyses that regarded existing data insufficient to support a definite suggestion, mainly due to sparse data on the long-term ND effects [16,61].…”

“…Two early studies comparing DOP with placebo (dextrose in water) or volume expansion (using plasma protein fraction) in 14 severely asphyxiated term neonates and 39 hypotensive VLBWI, respectively, showed that DOP was more effective in increasing AP and improving echocardiographic indices without any significant change in HR or systolic time intervals [209,227]. These findings were confirmed by systematic reviews [61,232]. Dopamine vs. dobutamine.…”

Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis

“…[19][20][21] There are three systematic reviews published until now on the efficacy of different inotropes in preterm neonates with shock. [22][23][24] Outcomes (O): The primary outcomes were mortality and major brain injury (MBI) (intraventricular haemorrhage >grade 2 or cystic periventricular leukomalacia). Secondary outcomes included response to treatment and NEC ≥stage 2.…”

“… 22 23 Sarafidis et al compared different inotropes in preterm neonates with shock in pairwise meta-analyses. 24 Most of the aforementioned systematic reviews included neonates with shock of varying aetiopathogenesis. Henceforth, we undertook this systematic review and network meta-analysis (NMA) with an aim to study the efficacy and safety of various interventions in preterm neonates with probable TCI.…”

Strong Association between Inotrope Administration and Intraventricular Hemorrhage, Gestational Age, and the Use of Fentanyl in Very Low Gestational Age Infants: A Retrospective Study

“…This could justify the slight decrease in the use of inotropes observed overtime (from 2009-2013 to 2014-2015) [10]. Nevertheless, irrespective of the existing controversy surrounding the definition of AH in neonates, and the lack of randomized clinical trials (RCTs) [11], inotropes are still given in a considerable proportion of preterm infants. Published data from the US and Norway show that the rate of inotrope administration to NICU patients ranges between 2.7% and 25%, depending on gestational age (GA) [12,13].…”