Clinical impact of analgesic-sedative agents and peri-operative clinical status on white matter brain injury in preterm infants following surgical NEC

Article type: Research Article

Authors: Garg, P. M.^{a; b; *} | Rebentisch, A.^c | Zhang, M.^d | Ware, J.^b | Pippins, M.^b | Taylor, C.^e | Reddy, K.^e | Lewis, T.^f | Inder, T. E.^g | Hillegass, W. B.^{d; h}

Affiliations: [a] Department of Pediatrics/Neonatology, Atrium Health Wake Forest Baptist, Wake Forest School of Medicine, Winston Salem, NC, USA | [b] Department of Pediatrics/Neonatology, University of Mississippi Medical Center, Jackson, MS, USA | [c] Department of Neonatal Pharmacy, University of Mississippi Medical Center, Jackson, MS, USA | [d] Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA | [e] Department of Radiology, University of Mississippi Medical Center, Jackson, MS, USA | [f] The Hospital for Sick Children, Divisions of Clinical Pharmacology & Neonatology, Toronto, ON, Canada | [g] Children Hospital of Orange County, University of California, Irvine, Orange, CA, USA | [h] Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA

Correspondence: [*] Address for correspondence: Parvesh M. Garg, Department of Pediatrics/Neonatology, Atrium Health Wake Forest Baptist, Wake Forest School of Medicine, Winston Salem, NC, USA. Tel.: +1 252 364 5800; E-mail: [email protected].

Abstract: BACKGROUND:The potential influence of exposure to analgesic-sedative agents (ASA) before, during, and after surgical NEC and peri-operative clinical status on white matter injury (WMI) in preterm infants has not been fully defined, and a comprehensive evaluation may inform future research and clinical interventions. METHODS:A retrospective study comparing ASA exposure before/during /after surgical NEC and peri-operative clinical status in neonates with and without WMI. RESULTS:Infants with any WMI (grade 2–4, n = 36/67, 53.7%) had a higher number of surgical procedures receiving ASA (5 [IQR: 3, 8] vs. 3 [2, 4]; p = 0.002) and had a longer duration of hypotension during their first (48.0 hours [26.0, 48.0] vs. 15.5 [6, 48]; p = 0.009) and second surgery (20 hours [0, 48h] vs. 0 [0, 22]; p = 0.017), received more hydrocortisone (35% vs.13.3%,p = 0.04) than those without any WMI. There were no differences in fentanyl/morphine/midazolam exposure before/during/after the NEC onset in the two groups.Infants with severe WMI (19/67, 28.3%, grade 3/4) had a higher incidence of AKI (P = 0.004), surgical morbidity (p = 0.047), more surgical procedures (6.5 [3, 10] vs. 4 [2, 5]; p = 0.012), and received higher mean fentanyl doses(p = 0.03) from birth until NEC onset than those without severe WMI. The univariate associations between these factors and severe WMI remained insignificant after multivariable logistic regression. CONCLUSION:Infants with WMI had more surgical procedures receiving ASA and had a longer duration of hypotension during surgeries. A large multicenter prospective study is needed to understand the full impact of ASA.

Keywords: Analgesics-sedatives, brain injury, neonate, outcomes, preterm infant

DOI: 10.3233/NPM-230084

Journal: Journal of Neonatal-Perinatal Medicine, vol. 16, no. 3, pp. 527-537, 2023