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J Perinatol. 2018 Aug;38(8):1060-1067. doi: 10.1038/s41372-018-0126-7. Epub 2018 May 24.

Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy.

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Division of Neonatology, Department of Pediatrics, Wayne State University, Detroit, MI, USA.
Division of Neonatology, Department of Pediatrics, Wayne State University, Detroit, MI, USA.
Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI, USA.
Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, Durham, NC, USA.
Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.



To evaluate the association between sedation-analgesia (SA) during initial 72 h and death/disability at 18 months of age in neonatal hypoxic-ischemic encephalopathy (HIE).


This was a secondary analysis of the NICHD therapeutic hypothermia (TH) randomized controlled trial in moderate or severe HIE. Receipt of SA and anticonvulsant medications at five time points were considered: prior to and at baseline, 24, 48, and 72 h of TH or normothermia. Disability was defined as mental developmental index <85, cerebral palsy, blindness, hearing impairment, or Gross Motor Function Classification System 2-5.


Of the 208 RCT participants, 38 (18%) infants had no exposure to SA or anticonvulsants at any of the five time points, 20 (10%) received SA agents only, 81 (39%) received anticonvulsants only, and 69 (33%) received both SA and anticonvulsants. SA category drugs were not administered in 57% of infants while 18% received SA at ≥3 time points; 72% infants received anticonvulsants during 72 h of intervention. At 18 months of age, disability among survivors and death/disability was more frequent in the groups receiving anticonvulsants, with (48 and 65%) or without (37 and 58%) SA, compared to groups with no exposure (14 and 34%) or SA (13 and 32%) alone. Severe HIE (aOR 3.60; 1.59-8.13), anticonvulsant receipt (aOR 2.48; 1.05-5.88), and mechanical ventilation (aOR 7.36; 3.15-17.20) were independently associated with 18-month death/disability, whereas TH (aOR 0.28; 0.13-0.60) was protective. SA exposure showed no association with outcome.


The risk benefits of SA in HIE need further investigation.

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