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Dexmedetomidine versus intermittent morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia

Abstract

Objective

In March 2019, the sedative in the therapeutic hypothermia protocol at Bellevue Hospital Center and NYU Langone Health changed from morphine to dexmedetomidine. This study evaluated the impact of this change on efficacy and safety parameters.

Study design

This was a retrospective, observational cohort study including neonates with HIE undergoing therapeutic hypothermia (N = 70) at two regional perinatal medical centers.

Results

Baseline demographics, pain scores, hemodynamics, and time to enteral feeds were similar between dexmedetomidine (N = 34) and morphine (N = 36) patients. Dexmedetomidine patients received more breakthrough morphine (0.13 ± 0.13 vs 0.04 ± 0.09 mg/kg, p = 0.001), but less cumulative morphine (0.13 ± 0.13 vs 1.79 ± 0.23 mg/kg, p < 0.0001). Morphine patients on invasive ventilation required increased support (0 vs 31.58%, p = 0.02).

Conclusion

Dexmedetomidine is effective and safe for sedation and analgesia during therapeutic hypothermia. It reduced total opioid usage, with no increased incidence of adverse events.

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Fig. 1: Median N-PASS scores during therapeutic hypothermia.
Fig. 2: Mean heart rate during therapeutic hypothermia.
Fig. 3: Mean arterial pressure during therapeutic hypothermia.
Fig. 4: Mean oxygen saturation during therapeutic hypothermia.

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References

  1. Wassink G, Lear CA, Gunn KC, Dean JM, Bennet L, Gunn AJ. Analgesics, sedatives, anticonvulsant drugs, and the cooled brain. Semin Fetal Neonat. 2015;20:109–14.

    Article  Google Scholar 

  2. Yildiz EP, Ekici B, Tatli B. Neonatal hypoxic ischemic encephalopathy: an update on disease pathogenesis and treatment. Expert Rev Neurotherapeutics. 2017;17:449–59.

    Article  CAS  Google Scholar 

  3. Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Oddama A, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N. Engl J Med. 2014;371:140–9.

    Article  CAS  Google Scholar 

  4. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicenter randomized trial. Lancet. 2005;365:663–70.

    Article  Google Scholar 

  5. Guillet R, Edwards AD, Thorasen M, Ferriero DM, Gluckman PD, Whitelaw A, et al. Seven to eight year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy. Pediatr Res. 2012;71:205–9.

    Article  Google Scholar 

  6. McAdams RM, Juul SE. Neonatal encephalopathy: update on therapeutic hypothermia and other novel therapeutics. Clin Perinatol. 2016;43:485–500.

    Article  Google Scholar 

  7. Gunn AJ, Thorasen M. Hypothermic neuroprotection. NeuroRx. 2006;3:154–69.

    Article  CAS  Google Scholar 

  8. Angeles DM, Wycliffe N, Michelson D, Hoslhouser BA, Deming DD, Pearce WJ, et al. Use of opioids in asphyxiated term neonates: effects on neuroimaging and clinical outcomes. Pediatr Res. 2005;57:873–8.

    Article  CAS  Google Scholar 

  9. Thorasen M, Satas S, Lobert EM, Whitelaw A, Acolet D, Lindgren C, et al. Twenty four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic ischemic insult is not neuroprotective. Pediatr Res. 2003;50:405–11.

    Article  Google Scholar 

  10. Pokela ML. Effect of opioid-induced analgesia on beta-endorphin, cortisol and glucose responses in neonates with cardiorespiratory problems. Biol Neonate. 1993;64:360–7.

    Article  CAS  Google Scholar 

  11. Festekjian A, Ashwal S, Obenaus A, Angeles DM, Denmark TK. The role of morphine in a rat model of hypoxic-ischemic injury. Pediatr Neurol. 2011;45:77–82.

    Article  Google Scholar 

  12. Dahmani S, Paris A, Jannier V, Hein L, Rouelle D, Scholz J, et al. Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an alpha-2 adrenoreceptor-independent mechanism. Anesthesiology. 2008;108:457–66.

    Article  CAS  Google Scholar 

  13. Paris A, Mantz J, Tonner PH, Hein L, Brede M, Gressens P. The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha-2a-adrenoreceptor subtype. Anesth Analg. 2006;102:456–61.

    Article  CAS  Google Scholar 

  14. Ren X, Ma H, Zuo Z. Dexmedetomidine postconditioning reduces brain injury after brain hypoxia-ischemia in neonatal rats. J Neuroimmune Pharm. 2016;11:238–47.

    Article  Google Scholar 

  15. Ma D, Hossain M, Rajakumaraswamy N, Arshad M, Sanders RD, Franks NP, et al. Dexmedetomidine produces its neuroprotective effect via the alpha-2a-adrenoreceptor subtype. Eur J Pharm. 2004;502:87–97.

    Article  CAS  Google Scholar 

  16. Ezzati M, Broad K, Kawano G, Faulkner S, Hassell J, Fleiss B, et al. Pharmacokinetics of dexmedetomidine combined with therapeutic hypothermia in a piglet asphyxia model. Acta Anaesthesiol Scand. 2014;58:733–42.

    Article  CAS  Google Scholar 

  17. McPherson C. Sedation and analgesia in mechanically ventilated preterm neonates: continue standard of care or experiment. J Pediatr Pharm Ther. 2012;17:351–64.

    Google Scholar 

  18. McAdams RM, Pak D, Lalovic B, Phillips B, Shen DD. Dexmedetomidine pharmacokinetics in neonates with hypoxic-ischemic encephalopathy receiving hypothermia. Anesthesiol Res Pract. 2020;2020:1–15.

    Article  Google Scholar 

  19. O’Mara K, Weiss MD. Dexmedetomine for sedation of neonates with HIE undergoing therapeutic hypothermia: a single-center experience. Am J Perinat Rep. 2018;8:e168–73.

    Article  Google Scholar 

  20. Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med. 2004;32:1322–6.

    Article  CAS  Google Scholar 

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Correspondence to Anna S. Cosnahan.

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Cosnahan, A.S., Angert, R.M., Jano, E. et al. Dexmedetomidine versus intermittent morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia. J Perinatol 41, 2284–2291 (2021). https://doi.org/10.1038/s41372-021-00998-8

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