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

Abstract

Background: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21^st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.

Interventions: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo.

Main outcome measures: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author).

Results: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment.

Conclusions: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.

Keywords: Cardiology; Infant; Low and Middle Income Countries; Neonatology.

Figure 1

Network geometry, SUCRA ranking and network meta-analysis forest plot with ‘placebo’ as the common comparator for the primary outcomes: mortality and major brain injury (intraventricular haemorrhage ≥grade 2 and/or cystic periventricular leukomalacia). NMA, network meta-analysis; SUCRA, surface under the cumulative ranking curve.

Figure 2

Network geometry, SUCRA ranking and network meta-analysis forest plot with ‘placebo’ as the common comparator for the secondary outcomes: necrotising enterocolitis (NEC) ≥stage 2 and response to treatment. NMA, network meta-analysis; SUCRA, surface under the cumulative ranking curve.