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Efficacy and safety of dexmedetomidine for analgesia and sedation in neonates: a systematic review

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Abstract

Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.

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References

  1. Perry M, Tan Z, Chen J, Weidig T, Xu W, Cong XS. Neonatal Pain: Perceptions and Current Practice. Crit Care Nurs Clin North Am. 2018;30:549–61.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Vinall J, Grunau RE. Impact of repeated procedural pain-related stress in infants born very preterm. Pediatr Res. 2014;75:584–7. https://doi.org/10.1038/pr.2014.16.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fitzgerald M, Shaw A, MacIntosh N. Postnatal development of the cutaneous flexor reflex: comparative study of preterm infants and newborn rat pups. Dev Med Child Neurol. 1988;30:520–6.

    Article  CAS  PubMed  Google Scholar 

  4. Anand KJ. Neonatal stress responses to anesthesia and surgery. Clin Perinatol. 1990;17:207–14.

    Article  CAS  PubMed  Google Scholar 

  5. Fitzgerald M, Millard C, McIntosh N. Cutaneous hypersensitivity following peripheral tissue damage in newborn infants and its reversal with topical anaesthesia. Pain 1989;39:31–6.

    Article  PubMed  Google Scholar 

  6. McPherson C, Miller SP, El-Dib M, Massaro AN, Inder TE. The influence of pain, agitation, and their management on the immature brain. Pediatr Res. 2020;88:168–75.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Stevens B, Yamada J, Ohlsson A, Haliburton S, Shorkey A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2016;7:CD001069.

    PubMed  Google Scholar 

  8. Anand KJ, Barton BA, McIntosh N, Lagercrantz H, Pelausa E, Young TE, et al. Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates. Arch Pediatr Adolesc Med. 1999;153:331–8.

    Article  CAS  PubMed  Google Scholar 

  9. Durrmeyer X, Vutskits L, Anand KJ, Rimensberger PC. Use of analgesic and sedative drugs in the NICU: integrating clinical trials and laboratory data. Pediatr Res. 2010;67:117–27.

    Article  PubMed  Google Scholar 

  10. Bhandari V, Bergqvist LL, Kronsberg SS, Barton BA, Anand KJ. NEOPAIN Trial Investigators Group. Morphine administration and short-term pulmonary outcomes among ventilated preterm infants. Pediatrics 2005;116:352–9.

    Article  PubMed  Google Scholar 

  11. Menon G, Boyle EM, Bergqvist LL, McIntosh N, Barton BA, Anand KJ. Morphine analgesia and gastrointestinal morbidity in preterm infants: secondary results from the NEOPAIN trial. Arch Dis Child Fetal Neonatal Ed. 2008;93:F362–7.

    Article  CAS  PubMed  Google Scholar 

  12. Rao R, Sampers JS, Kronsberg SS, Brown JV, Desai NS, Anand KJ. Neurobehavior of preterm infants at 36 weeks postconception as a function of morphine analgesia. Am J Perinatol. 2007;24:511–7.

    Article  PubMed  Google Scholar 

  13. de Graaf J, van Lingen RA, Simons SHP, Anand KJS, Duivenvoordan HJ, Weisglas-Kuperus N, et al. Long-term effects of routine morphine infusion in mechanically ventilated neonates on children’s functioning: five-year follow-up of a randomized controlled trial. Pain 2011;152:1391–7.

    Article  PubMed  Google Scholar 

  14. O’Mara K, Gal P, Wimmer J, Laurence-Ransom J, Carlos RQ, Dimaguila MAVT, et al. Dexmedetomidine versus standard therapy with fentanyl for sedation in mechanically ventilated premature neonates. J Pediatr Pharm Ther. 2012;17:252–62.

    Google Scholar 

  15. Sellas MN, Kyllonen KC, Lepak MR, Rodriguez RJ. Dexmedetomidine for the management of postoperative pain and sedation in newborns. J Pediatr Pharm Ther. 2019;24:227–33.

    Google Scholar 

  16. Bong CL, Tan J, Lim S, Low Y, Sim S-W, Rajadurai VS, et al. Randomised controlled trial of dexmedetomidine sedation vs general anaesthesia for inguinal hernia surgery on perioperative outcomes in infants. Br J Anaesth. 2019;122:662–70.

    Article  CAS  PubMed  Google Scholar 

  17. Kinoshita M, Stempel K, do Nascimento IJB, Vejayaram DN, Norman E, Bruschettini M. Opioids and alpha-2-agonists for analgesia and sedation in newborn infants: protocol of a systematic review. Syst Rev. 2020;9:183.

    Article  PubMed  PubMed Central  Google Scholar 

  18. McPherson C, Grunau RE. Neonatal pain control and neurologic effects of anesthetics and sedatives in preterm infants. Clin Perinatol. 2014;41:209–27.

    Article  PubMed  Google Scholar 

  19. Zedan M, Mostafa M, Thabet E, Nour I. Short-term respiratory outcome of mechanically ventilated preterm infants treated by dexmedetomidine: randomized controlled trial. J Pediatr. 2020;33:136–43.

    Google Scholar 

  20. Cosnahan AS, Angert RM, Jano E, Wachtel EV. Dexmedetomidine versus intermittent morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia. J Perinatol. 2021;41:2284–91.

    Article  CAS  PubMed  Google Scholar 

  21. Xue H, Wu Z, Xu Y, Gao Q, Zhang Y, Li C, et al. Dexmedetomidine post-conditioning ameliorates long-term neurological outcomes after neonatal hypoxic ischemia: The role of autophagy. Life Sci. 2021;270:118980.

    Article  CAS  PubMed  Google Scholar 

  22. Bao N, Tang B. Organ-protective effects and the underlying mechanism of dexmedetomidine. Mediators Inflamm. 2020;2020:6136105.

    Article  PubMed  PubMed Central  Google Scholar 

  23. McAdams RM, Pak D, Lalovic B, Phillips B, Shen DD. Dexmedetomidine Pharmacokinetics in neonates with hypoxic-ischemic encephalopathy receiving hypothermia. Anesthesiol Res Pr. 2020;2020:2582965.

    Google Scholar 

  24. Naveed M, Bondi DS, Shah PA. Dexmedetomidine versus fentanyl for neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia. J Pediatr Pharm Ther. 2022;27:352–7.

    Google Scholar 

  25. Ojha S, Abramson J, Dorling J. Sedation and analgesia from prolonged pain and stress during mechanical ventilation in preterm infants: is dexmedetomidine an alternative to current practice? BMJ Paediatr Open. 2022;6:e001460.

    Article  PubMed  PubMed Central  Google Scholar 

  26. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. J Clin Epidemiol. 2016;75:40–6.

    Article  PubMed  Google Scholar 

  27. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al. (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.1 (updated September 2020). Cochrane, 2020. Available from www.training.cochrane.org/handbook.

  28. Higgins JPT, Savovic J, Page MJ, Sterne JAC. Revised Cochrane risk-of-bias tool for randomized trials (RoB 2) Template for completion, version 22 (updated August 2019). Cochrane, 2910. Available from https://drive.google.com/file/d/18Zks7k4kxhbUUlbZ51Ya5xYa3p3ECQV0/view.

  29. Joanna Briggs Institute (JBI). Checklist for Case Series. Critical Appraisal tools for use in JBI Systematic Reviews. https://jbi.global/sites/default/files/2020-07/Checklist_for_Case_Series_0.pdf. July 2020, accessed August 2020.

  30. Chrysostomou C, Schulman SR, Herrera Castellanos M, Cofer BE, Mitra S, Garcia da Rocha M, et al. A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates. J Pediatr. 2014;164:276–82.

    Article  CAS  PubMed  Google Scholar 

  31. Chen K, Lu Z, Xin YC, Cai Y, Chen Y, Pan SM. Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients. Cochrane Database Syst Rev. 2015;1:CD010269.

    PubMed  Google Scholar 

  32. Plambech MZ, Afshari A. Dexmedetomidine in the pediatric population: a review. Minerva Anestesiol. 2015;81:320–32.

    CAS  PubMed  Google Scholar 

  33. Kawasaki T, Kawasaki C, Ueki M, Hamada K, Habe K, Sata T. Dexmedetomidine suppresses proinflammatory mediator production in human whole blood in vitro. J Trauma Acute Care Surg. 2013;74:1370–5.

    Article  CAS  PubMed  Google Scholar 

  34. Jiang Y, Xia M, Xu J, Huang Q, Dai Z, Zhang X. Dexmedetomidine alleviates pulmonary edema through the epithelial sodium channel (ENaC) via the PI3K/Akt/Nedd4-2 pathway in LPS-induced acute lung injury. Immunol Res. 2021;69:162–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth. 2008;22:221–8.

    Article  PubMed  Google Scholar 

  36. Cho JS, Kim HI, Lee KY, An JY, Bai SJ, Cho JY, et al. Effect of Intraoperative Dexmedetomidine Infusion on Postoperative Bowel Movements in Patients Undergoing Laparoscopic Gastrectomy: A Prospective, Randomized, Placebo-Controlled Study. Med (Baltim). 2015;94:e959.

    Article  CAS  Google Scholar 

  37. De Ponti F, Giaroni C, Cosentino M, Lecchini S, Frigo G. Adrenergic mechanisms in the control of gastrointestinal motility: from basic science to clinical applications. Pharm Ther. 1996;69:59–78.

    Article  Google Scholar 

  38. Lu Y, Fang PP, Yu YQ, Cheng XQ, Feng XM, Wong GTC, et al. Effect of Intraoperative Dexmedetomidine on Recovery of Gastrointestinal Function After Abdominal Surgery in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2021;4:e2128886.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Baserga M, DuPont TL, Ostrander B, Minton S, Sheffield M, Balch AH, et al. Dexmedetomidine use in infants undergoing cooling due to neonatal encephalopathy (dice trial): a randomized controlled trial: background, aims and study protocol. Frontiers in Pain. Research 2021;2:770511.

    Google Scholar 

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Acknowledgements

The authors would like to thank information specialists Michelle Ryu and Christopher Walsh for their database services in running our search strategy and compiling the results for analysis.

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Authors and Affiliations

  1. Department of Pediatrics, Mount Sinai Hospital, Toronto, ON, Canada

    Katelyn Portelli, Hemasree Kandraju & Prakesh S. Shah

  2. Department of Pediatrics, McMaster Children’s Hospital, Hamilton, ON, Canada

    Katelyn Portelli

  3. Department of Pediatrics, University of Toronto, Toronto, ON, Canada

    Hemasree Kandraju & Prakesh S. Shah

  4. Library and knowledge services, Trillium Health Partners, Ontario, Canada

    Michelle Ryu

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  1. Katelyn Portelli
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Contributions

KP and PS contributed to the study’s conception and design. KP and HK reviewed the literature search results and PS provided third-party decisions on articles that they could not come to a consensus on. KP, HK, and MR contributed to the initial draft of the manuscript. PS edited, revised and approved the final version of the manuscript.

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Correspondence to Prakesh S. Shah.

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Portelli, K., Kandraju, H., Ryu, M. et al. Efficacy and safety of dexmedetomidine for analgesia and sedation in neonates: a systematic review. J Perinatol 44, 164–172 (2024). https://doi.org/10.1038/s41372-023-01802-5

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