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Apnea and Oxygen Desaturations in Children Treated with Opioids after Adenotonsillectomy for Obstructive Sleep Apnea Syndrome

A Prospective Pilot Study

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Abstract

Background: Recent case reports have alerted the medical community of fatality in children receiving codeine after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome.

Objective: The objective of this study was to compare the rates of oxygen desaturation before and after adenotonsillectomy in children with obstructive sleep apnea syndrome (OSAS), and to examine the relationship between cytochrome P450 2D6 (CYP2D6) genotype and respiratory events.

Study Design: This was a prospective observational study.

Methods: Twenty-six children with OSAS (mean age 78 months, range 1.8–17 years) who underwent adenotonsillectomy were studied. CYP2D6 genotype was characterized in 21 of these children. The primary endpoints of the study were the change in the rate of desaturation and in the nadir oxygen saturation values before and in the first 24 hours after surgery as measured by pulse oximetry.

Results: Twenty-two children received codeine and four were managed with hydrocodone. There was no post-operative improvement in the mean rate of desaturation (1.84±1.45/hour pre-operative vs 2.97±3.3/hour post-operative; p = 0.119; 95% CI −2.56, 0.313), or the post-operative nadir of oxygen saturation (85.2±5.8% pre-operative vs 84.0±6.8% post-operative; p = 0.632; 95% CI −3.00, 4.84) on the night after surgery. Prior to surgery, six children had an oxygen saturation nadir <80%, while post-surgery, the number increased to eight children. Ten children improved their parameters after surgery. CYP2D6 genotype by itself did not predict the changes in desaturation or nadir.

Conclusion: Post-operative use of opioids following OSAS may not be safe for all children. It is conceivable that if the child is among the significant proportion that experiences increased oxygen desaturations, the CNS depressing effects of codeine or hydrocodone and their respectively potent morphine or hydromorphone metabolites can further compromise respiratory drive. Larger studies are needed to investigate the potential contribution of CYP2D6 genotype.

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Acknowledgments

GK, DDS, JDK, and DR designed the study and came up with the concept; JDK, DDS, and DR collected data; PM, JS, CJDR, BCC, MRH, GK planned and/or conducted genetic analysis; all authors were involved in data interpretation and/or analysis; JDK, GK and PM drafted the manuscript; DDS, PM, and GK conducted the literature search; and all authors contributed to the final draft of this report.

This study was supported, in part, by grants from the Canadian Institutes for Health Research-Drug Safety and Effectiveness Network (CIHR-DSEN), and the Canadian Pharmacogenomics Network for Drug Safety. Oxygen saturation monitors were provided by Covidien-Nellcor, Boulder, CO, USA. The funding sources of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Surgery, Otolaryngology/Head & Neck Surgery Division, McMaster University, Hamilton, Ontario, Canada

    Justin D. Khetani & Doron D. Sommer

  2. Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, ON M5G 1X8, Canada

    Parvaz Madadi &  Gideon Koren MD, FRCPC, FACMT

  3. Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada

    Desigen Reddy

  4. Child and Family Research Institute, Children’s and Women’s Health Centre of British Columbia, Vancouver, British Columbia, Canada

    Johanna Sistonen, Colin J. D. Ross, Bruce C. Carleton & Michael R. Hayden

  5. Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada

    Johanna Sistonen, Colin J. D. Ross & Michael R. Hayden

  6. Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada

    Bruce C. Carleton

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  1. Justin D. Khetani
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  2. Parvaz Madadi
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  9. Gideon Koren MD, FRCPC, FACMT
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Correspondence to Gideon Koren MD, FRCPC, FACMT.

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Khetani, J.D., Madadi, P., Sommer, D.D. et al. Apnea and Oxygen Desaturations in Children Treated with Opioids after Adenotonsillectomy for Obstructive Sleep Apnea Syndrome. Pediatr Drugs 14, 411–415 (2012). https://doi.org/10.1007/BF03262421

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