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Pre-emptive opioid sedation during therapeutic hypothermia for neonatal encephalopathy: a national survey

Presented at the Neonatal Society 2018 Autumn Meeting (programme).

Markati D1, Vakharia A1, Montaldo P1, Mendoza J1, Serra S1, Shankaran S2, Thayyil S1

1 Imperial College London, UK
2 Wayne State University, USA

Background: Although none of the major cooling trials mandated routine pre-emptive sedation, anecdotal evidence suggests that opioids are widely used during neonatal cooling therapy in the UK. Cooling reduces opioids clearance; hence inadvertent toxic levels may occur with standard doses (1). Recent secondary analysis the first whole body cooling trial data reported that routine sedation during cooling therapy increased the duration of ventilation and hospital stay, without any additional neuroprotective benefit (2). We conducted a survey of all UK cooling centres to ascertain the current practice of sedation during cooling therapy.

Methods: We requested the lead consultant of all cooling centres (n=52) in the UK to complete an electronic survey (Qualtrics® (Qualtrics LLC, Provo, Utah, U.S.A.) relating to sedation practices in their unit for babies with neonatal encephalopathy undergoing therapeutic hypothermia. Responses were then screened for duplications and data completeness assessed before analysis, using SPSS (Version 25, IBM, New York).

Results: All the 52 UK cooling centres completed the survey, of which 51 (98%) used intravenous morphine infusion for sedation/analgesia during therapeutic hypothermia (Table). Twenty-six (50%) units continued morphine infusion for the full 72 hours of therapeutic hypothermia irrespective of the ventilation status, while 3 (6%) stopped at 48 hours. The practice of the remaining centres was variable and was based on the clinical condition. The reasons for using morphine infusion were – alleviating discomfort of cooling and to reduce shivering (81%); invasive ventilation (29%); optimise neuroprotection (44%); analgesia (21%); and compliance with TOBY protocol (35%). Fourteen (27%) units used oral/rectal sedation-analgesia with chloral hydrate or paracetamol during cooling therapy.

Conclusion: Despite the lack of evidence of safety and efficacy, pre-morphine is widely used in the UK during cooling therapy, and the doses exceeded the recommended safe levels. Carefully designed clinical trials are required to examine the optimal sedation-analgesia during hypothermic neuroprotection.

Corresponding author:

1. Frymoyer A et al. Decreased morphine clearance in neonates with hypoxic ischemic encephalopathy receiving hypothermia. J Clin Pharmacol 2017;57:64-76
2. Natarajan et al. Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy. J Perinatol. 2018;38:1060-1067

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