Abstract

Effective analgesia in neonates is relevant not only because of ethical aspects or empathy, but it is a crucial and integral part of medical and nursing care. However, there is also emerging evidence - although mainly in animal models - on the relation between the exposure to narcotics and impaired neurodevelopmental outcome, resulting in a CATCH-22 scenario. Consequently, a balanced approach is needed with the overarching intention to attain adequate pain management with minimal side effects. Despite the available evidence-based guidance on narcotics in ventilated neonates, observations on drug utilization still suggest an overall increase in exposure with extensive variability between units. This increased exposure over time and the extensive variability is concerning given the limited evidence of benefits and potential harm.Implementation strategies are effective to reduce exposure to narcotics but result in increased paracetamol exposure. We therefore summarized the evidence on paracetamol use in procedural pain management, in minor to moderate as well as major pain syndromes in neonates. While there are sufficient data on short-term safety, there are still concerns on long-term side effects. These concerns relate to neurobehavioral outcome, atopy or fertility, and are at present mainly driven by epidemiological perinatal observations, together with postulated mechanisms.We conclude that future clinical research objectives should still focus on the need to develop better assessment tools to quantify pain and on the need for high-quality data on long-term outcome of therapeutic interventions - also for paracetamol - and exploration of the mechanisms involved.

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