Analgesia and sedation in premature infants receiving invasive ventilation: a systematic scoping review

Premature neonates often require mechanical ventilation during intensive care. However, there is a lack of clinical consensus on the provision, type, and dosage of analgosedatives. The purpose of this scoping review is to assess the risks and benefits of providing analgesic and sedative drugs to ventilated premature infants.

We sourced primary empirical research reporting outcomes related to the use of pharmacological analgesics and sedatives in ventilated premature infants. We included articles published in any language in peer-reviewed journals before February 2024 from MEDLINE, Embase, Web of Science, Cochrane Library, and Google Scholar databases. We present the overall study characteristics, and the reported risks and benefits of analgosedatives within drug sub-groups.

80 studies were included in the scoping review. Morphine was the most studied drug (39 studies), followed by fentanyl (19 studies). Midazolam (8 studies) and dexmedetomidine (3 studies) were the most frequently studied sedatives. Analgesic efficacy was more consistently reported for fentanyl than morphine. The sedative effect of opioids was rarely assessed. Respiratory, cardiovascular, gastrointestinal, neurological and neurodevelopmental risks were unclear for all opioids. Alternative synthetic opioids and midazolam appear to be associated with significant risks in the absence of clear benefits. Dexmedetomidine shows encouraging but limited results and merits further investigation as an opioid-sparing adjunct.

At present, fentanyl appears to have the best efficacy and safety profile for analgosedation in this patient population. This scoping review will support clinicians in their analgosedative management of ventilated premature infants and identifies research gaps and priorities.

This systematic scoping review provides a comprehensive summary of the evidence of the risks and benefits of analgesics and sedatives in ventilated premature infants. Although morphine is the most extensively studied and used drug, its analgesic effect has been less consistently reported than that of fentanyl. Sedation has rarely been assessed and dexmedetomidine seems a promising sedative adjunct as midazolam use is not supported by evidence.