Title | Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Natarajan G, Shankaran S, Laptook AR, McDonald SA, Pappas A, Hintz SR, Das A |
Corporate Authors | NICHD Neonatal Research Network(NRN) Whole Body Hypothermia Subcommittee |
Journal | J Perinatol |
Volume | 38 |
Issue | 8 |
Pagination | 1060-1067 |
Date Published | 2018 08 |
ISSN | 1476-5543 |
Keywords | Analgesics, Anticonvulsants, Developmental Disabilities, Female, Humans, Hypnotics and Sedatives, Hypothermia, Induced, Hypoxia-Ischemia, Brain, Infant, Infant, Newborn, Logistic Models, Male, Pain Management, Severity of Illness Index, United States |
Abstract | OBJECTIVE: 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). DESIGN: 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. RESULTS: 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. CONCLUSIONS: The risk benefits of SA in HIE need further investigation. |
DOI | 10.1038/s41372-018-0126-7 |
Alternate Journal | J Perinatol |
PubMed ID | 29795315 |
PubMed Central ID | PMC6092226 |
Grant List | U10 HD027856 / HD / NICHD NIH HHS / United States U10 HD021373 / HD / NICHD NIH HHS / United States UL1 RR024139 / RR / NCRR NIH HHS / United States U10 HD021385 / HD / NICHD NIH HHS / United States U10 HD021364 / HD / NICHD NIH HHS / United States U10 HD027880 / HD / NICHD NIH HHS / United States UG1 HD027853 / HD / NICHD NIH HHS / United States U10 HD040521 / HD / NICHD NIH HHS / United States UG1 HD087229 / HD / NICHD NIH HHS / United States M01 RR008084 / RR / NCRR NIH HHS / United States U10 HD040461 / HD / NICHD NIH HHS / United States M01 RR016587 / RR / NCRR NIH HHS / United States U10 HD040689 / HD / NICHD NIH HHS / United States U10 HD040492 / HD / NICHD NIH HHS / United States U10 HD027853 / HD / NICHD NIH HHS / United States U10 HD027904 / HD / NICHD NIH HHS / United States U10 HD021397 / HD / NICHD NIH HHS / United States U10 HD027871 / HD / NICHD NIH HHS / United States UG1 HD027904 / HD / NICHD NIH HHS / United States U10 HD027851 / HD / NICHD NIH HHS / United States UG1 HD021385 / HD / NICHD NIH HHS / United States UG1 HD027880 / HD / NICHD NIH HHS / United States U10 HD034216 / HD / NICHD NIH HHS / United States U10 HD036790 / HD / NICHD NIH HHS / United States |