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Review
. 2017 Jun;30(3):349-356.
doi: 10.1097/ACO.0000000000000455.

Codeine and opioid metabolism: implications and alternatives for pediatric pain management

Vidya Chidambaran  1 , Senthilkumar Sadhasivam, Mohamed Mahmoud
Affiliations
Review

Codeine and opioid metabolism: implications and alternatives for pediatric pain management

Vidya Chidambaran et al. Curr Opin Anaesthesiol. 2017 Jun.

Abstract

Purpose of review: Use of perioperative opioids for surgical pain management of children presents clinical challenges because of concerns of serious adverse effects including life-threatening respiratory depression. This is especially true for children with history of obstructive sleep apnea. This review will explore current knowledge of clinically relevant factors and genetic polymorphisms that affect opioid metabolism and postoperative outcomes in children.

Recent findings: Within the past several years, an increasing number of case reports have illustrated clinically important respiratory depression, anoxic brain injuries and even death among children receiving appropriate weight-based dosages of codeine and other opioids for analgesia at home setting particularly following tonsillectomy. Several national and international organizations have issued advisories on use of codeine in pediatrics, based on cytochrome P450 family 2 subfamily D type 6 (CYP2D6) pharmacogenetics. We have discussed the pros and cons of alternatives to codeine for pain management.

Summary: Although routine preoperative genotyping to identify children at risk and personalized opioid use for pediatric perioperative pain management is still a distant reality, current known implications of CYP2D6 pharmacogenetics on codeine use shows that pharmacogenetics has the potential to guide anesthesia providers on perioperative opioid selection and dosing to maximize efficacy and safety.

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Conflict of interest statement

Conflicts of interest: Authors have no conflicts of interest.

Figures

Figure
Figure
CYP2D6 metabolic pathway of common oral opioids resulting in biologically active metabolites. Depending on CYP2D6 metabolic activity (poor, intermediate, extensive or ultrarapid metabolizing status) varying levels of respective active metabolites from codeine, tramadol, hydrocodone and oxycodone are formed resulting in clinically unpredictable inter-individual variations in responses. Oral morphine, hydromorphone and tapentadol are not affected by the CYP2D6 metabolic pathway.
See this image and copyright information in PMC

References

    1. Lotsch J, Dudziak R, Freynhagen R, Marschner J, Geisslinger G. Fatal respiratory depression after multiple intravenous morphine injections. Clinical pharmacokinetics. 2006;45(11):1051–60. - PubMed
    1. Overdyk FJ. Postoperative opioids remain a serious patient safety threat. Anesthesiology. 2010;113(1):259–60. - PubMed
    1. Fecho K, Jackson F, Smith F, Overdyk FJ. In-hospital resuscitation: opioids and other factors influencing survival. Therapeutics and clinical risk management. 2009;5:961–8. - PMC - PubMed
    1. Voepel-Lewis T, Marinkovic A, Kostrzewa A, Tait AR, Malviya S. The prevalence of and risk factors for adverse events in children receiving patient-controlled analgesia by proxy or patient-controlled analgesia after surgery. Anesth Analg. 2008;107(1):70–5. - PubMed
    1. Overdyk FJ, Carter R, Maddox RR, Callura J, Herrin AE, Henriquez C. Continuous oximetry/capnometry monitoring reveals frequent desaturation and bradypnea during patient-controlled analgesia. Anesth Analg. 2007;105(2):412–8. - PubMed

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