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


RESULTS
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.


CONCLUSIONS
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.
Department of Anesthesiology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
Vidya
V
Chidambaran
Senthilkumar
S
Sadhasivam
Mohamed
M
Mahmoud
D000698:Analgesia / Q000009:adverse effects* / Q000379:methods / Q000592:standards / Q000639:trends; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000758:Anesthesia / Q000009:adverse effects / Q000379:methods / Q000592:standards / Q000639:trends; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002648:Child; D002985:Clinical Protocols; D003061:Codeine / Q000494:pharmacology / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005838:Genotype; D006801:Humans; D002534:Hypoxia, Brain / Q000139:chemically induced; D009293:Opioid-Related Disorders / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D059408:Pain Management / Q000009:adverse effects / Q000379:methods* / Q000592:standards / Q000639:trends; D010149:Postoperative Pain / Q000188:drug therapy*; D019990:Perioperative Care / Q000009:adverse effects / Q000379:methods; D011110:Polymorphism, Genetic; D017410:Practice Guidelines as Topic; D012131:Respiratory Insufficiency / Q000139:chemically induced; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications; D014068:Tonsillectomy / Q000009:adverse effects*
D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine