Opioids for newborn infants receiving mechanical ventilation

• Published in: Cochrane database of systematic reviews 2021-03, Vol.3 (3), p.CD013732
• Main Authors: Bellù, Roberto, Romantsik, Olga, Nava, Chiara, de Waal, Koert A, Zanini, Rinaldo, Bruschettini, Matteo
• Format: Article
• Language: English
• Subjects: Analgesics, Opioid - adverse effects; Analgesics, Opioid - therapeutic use; Bias; Child Development - drug effects; Child health; Fentanyl - adverse effects; Fentanyl - therapeutic use; Heroin - adverse effects; Heroin - therapeutic use; Humans; Hypnotics and Sedatives - adverse effects; Hypnotics and Sedatives - therapeutic use; Infant; Infant Mortality; Infant, Newborn; Infant, Premature; Midazolam - adverse effects; Midazolam - therapeutic use; Morphine - adverse effects; Morphine - therapeutic use; Pain Management; Pain, Procedural - prevention & control; Placebos - therapeutic use; Randomized Controlled Trials as Topic; Remifentanil - adverse effects; Remifentanil - therapeutic use; Respiration, Artificial - adverse effects; Respiration, Artificial - statistics & numerical data; Sufentanil - adverse effects; Sufentanil - therapeutic use
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD013732.pub2

Mechanical ventilation is a potentially painful and discomforting intervention that is widely used in neonatal intensive care. Newborn infants demonstrate increased sensitivity to pain, which may affect clinical and neurodevelopmental outcomes. The use of drugs that reduce pain might be important in improving survival and neurodevelopmental outcomes. To determine the benefits and harms of opioid analgesics for neonates (term or preterm) receiving mechanical ventilation compared to placebo or no drug, other opioids, or other analgesics or sedatives. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 9), in the Cochrane Library; MEDLINE via PubMed (1966 to 29 September 2020); Embase (1980 to 29 September 2020); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 29 September 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We included randomised and quasi-randomised controlled trials comparing opioids to placebo or no drug, to other opioids, or to other analgesics or sedatives in newborn infants on mechanical ventilation. We excluded cross-over trials. We included term (≥ 37 weeks' gestational age) and preterm (< 37 weeks' gestational age) newborn infants on mechanical ventilation. We included any duration of drug treatment and any dosage given continuously or as bolus; we excluded studies that gave opioids to ventilated infants for procedures. For each of the included trials, we independently extracted data (e.g. number of participants, birth weight, gestational age, types of opioids) using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria and assessed the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence. We included 23 studies (enrolling 2023 infants) published between 1992 and 2019. Fifteen studies (1632 infants) compared the use of morphine or fentanyl versus placebo or no intervention. Four studies included both term and preterm infants, and one study only term infants; all other studies included only preterm infants, with five studies includin