Chronic Opioid Use Following Surgery for Oral Cavity Cancer | Head and Neck Cancer | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Chua  KS, Reddy  SK, Lee  MC, Patt  RB.  Pain and loss of function in head and neck cancer survivors.  J Pain Symptom Manage. 1999;18(3):193-202.PubMedGoogle ScholarCrossref
Bianchini  C, Malagò  M, Crema  L,  et al.  Post-operative pain management in head and neck cancer patients: predictive factors and efficacy of therapy.  Acta Otorhinolaryngol Ital. 2016;36(2):91-96.PubMedGoogle Scholar
Deandrea  S, Montanari  M, Moja  L, Apolone  G.  Prevalence of undertreatment in cancer pain. A review of published literature.  Ann Oncol. 2008;19(12):1985-1991.PubMedGoogle ScholarCrossref
Denlinger  CS, Carlson  RW, Are  M,  et al.  Survivorship: introduction and definition. Clinical practice guidelines in oncology.  J Natl Compr Canc Netw. 2014;12(1):34-45.PubMedGoogle ScholarCrossref
Compton  WM, Jones  CM, Baldwin  GT.  Relationship between nonmedical prescription-opioid use and heroin use.  N Engl J Med. 2016;374(2):154-163.PubMedGoogle ScholarCrossref
Florence  CS, Zhou  C, Luo  F, Xu  L.  The economic burden of prescription opioid overdose, abuse, and dependence in the United States, 2013.  Med Care. 2016;54(10):901-906.PubMedGoogle ScholarCrossref
Goudas  LC, Bloch  R, Gialeli-Goudas  M, Lau  J, Carr  DB.  The epidemiology of cancer pain.  Cancer Invest. 2005;23(2):182-190.PubMedGoogle ScholarCrossref
Schug  SA, Chandrasena  C.  Pain management of the cancer patient.  Expert Opin Pharmacother. 2015;16(1):5-15.PubMedGoogle ScholarCrossref
DeVeaugh-Geiss  A, Kadakia  A, Chilcoat  H, Alexander  L, Coplan  P.  A retrospective cohort study of long-term immediate-release hydrocodone/acetaminophen use and acetaminophen dosing above the Food and Drug Administration recommended maximum daily limit among commercially insured individuals in the United States (2008-2013).  J Pain. 2015;16(6):569-79.e1.PubMedGoogle ScholarCrossref
Clarke  H, Soneji  N, Ko  DT, Yun  L, Wijeysundera  DN.  Rates and risk factors for prolonged opioid use after major surgery: population based cohort study.  BMJ. 2014;348:g1251.PubMedGoogle ScholarCrossref
Jiang  X, Orton  M, Feng  R,  et al.  Chronic opioid usage in surgical patients in a large academic center.  Ann Surg. 2017;265(4):722-727.PubMedGoogle ScholarCrossref
Chang  CM, Yin  WY, Wei  CK,  et al.  Adjusted age-adjusted Charlson Comorbidity Index score as a risk measure of perioperative mortality before cancer surgery.  PLoS One. 2016;11(2):e0148076.PubMedGoogle ScholarCrossref
Charlson  M, Szatrowski  TP, Peterson  J, Gold  J.  Validation of a combined comorbidity index.  J Clin Epidemiol. 1994;47(11):1245-1251.PubMedGoogle ScholarCrossref
The National Institutes of Health. National Institute on Alcohol Abuse and Alcoholism. Drinking Levels Defined. 2016; Accessed November 12, 2016.
Gardner  M, Altman  DG.  Statistics with confidence. BMJ Books. 1989.
Childers  JW, King  LA, Arnold  RM.  Chronic Pain and Risk Factors for Opioid Misuse in a Palliative Care Clinic.  Am J Hosp Palliat Care. 2015;32(6):654-659.PubMedGoogle ScholarCrossref
Ciesielski  T, Iyengar  R, Bothra  A, Tomala  D, Cislo  G, Gage  BF.  A tool to assess risk of de novo opioid abuse or dependence.  Am J Med. 2016;129(7):699-705.e4.PubMedGoogle ScholarCrossref
Anghelescu  DL, Ehrentraut  JH, Faughnan  LG.  Opioid misuse and abuse: risk assessment and management in patients with cancer pain.  J Natl Compr Canc Netw. 2013;11(8):1023-1031.PubMedGoogle ScholarCrossref
Wunsch  H, Wijeysundera  DN, Passarella  MA, Neuman  MD.  Opioids prescribed after low-risk surgical procedures in the United States, 2004-2012.  JAMA. 2016;315(15):1654-1657.PubMedGoogle ScholarCrossref
Davis  MP, Mehta  Z.  Opioids and chronic pain: where is the balance?  Curr Oncol Rep. 2016;18(12):71.PubMedGoogle ScholarCrossref
Zenda  S, Matsuura  K, Tachibana  H,  et al.  Multicenter phase II study of an opioid-based pain control program for head and neck cancer patients receiving chemoradiotherapy.  Radiother Oncol. 2011;101(3):410-414.PubMedGoogle ScholarCrossref
Chen  L, Vo  T, Seefeld  L,  et al.  Lack of correlation between opioid dose adjustment and pain score change in a group of chronic pain patients.  J Pain. 2013;14(4):384-392.PubMedGoogle ScholarCrossref
Carmona-Bayonas  A, Jiménez-Fonseca  P, Castañón  E,  et al.  Chronic opioid therapy in long-term cancer survivors.  Clin Transl Oncol. 2017;19(2):236-250.PubMedGoogle ScholarCrossref
Chou  R, Turner  JA, Devine  EB,  et al.  The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop.  Ann Intern Med. 2015;162(4):276-286.PubMedGoogle ScholarCrossref
Fletcher  D, Martinez  V.  Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis.  Br J Anaesth. 2014;112(6):991-1004.PubMedGoogle ScholarCrossref
Carullo  V, Fitz-James  I, Delphin  E.  Opioid-induced hyperalgesia: a diagnostic dilemma.  J Pain Palliat Care Pharmacother. 2015;29(4):378-384.PubMedGoogle ScholarCrossref
Scherrer  JF, Salas  J, Sullivan  MD,  et al.  The influence of prescription opioid use duration and dose on development of treatment resistant depression.  Prev Med. 2016;91:110-116.PubMedGoogle ScholarCrossref
Barry  DT, Cutter  CJ, Beitel  M, Kerns  RD, Liong  C, Schottenfeld  RS.  Psychiatric disorders among patients seeking treatment for co-occurring chronic pain and opioid use disorder.  J Clin Psychiatry. 2016;77(10):1413-1419.PubMedGoogle ScholarCrossref
Webster  LR, Choi  Y, Desai  H, Webster  L, Grant  BJ.  Sleep-disordered breathing and chronic opioid therapy.  Pain Med. 2008;9(4):425-432.PubMedGoogle ScholarCrossref
Sharkey  KM, Kurth  ME, Anderson  BJ, Corso  RP, Millman  RP, Stein  MD.  Obstructive sleep apnea is more common than central sleep apnea in methadone maintenance patients with subjective sleep complaints.  Drug Alcohol Depend. 2010;108(1-2):77-83.PubMedGoogle ScholarCrossref
Baldacchino  A, Balfour  DJ, Passetti  F, Humphris  G, Matthews  K.  Neuropsychological consequences of chronic opioid use: a quantitative review and meta-analysis.  Neurosci Biobehav Rev. 2012;36(9):2056-2068.PubMedGoogle ScholarCrossref
Brown  RT, Zuelsdorff  M, Fleming  M.  Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain.  J Opioid Manag. 2006;2(3):137-146.PubMedGoogle Scholar
Dublin  S, Walker  RL, Jackson  ML,  et al.  Use of opioids or benzodiazepines and risk of pneumonia in older adults: a population-based case-control study.  J Am Geriatr Soc. 2011;59(10):1899-1907.PubMedGoogle ScholarCrossref
Waljee  JF, Cron  DC, Steiger  RM, Zhong  L, Englesbe  MJ, Brummett  CM.  Effect of preoperative opioid exposure on healthcare utilization and expenditures following elective abdominal surgery.  Ann Surg. 2017;265(4):715-721.PubMedGoogle ScholarCrossref
Kim  DH, Park  JY, Karm  MH,  et al.  Smoking may increase postoperative opioid consumption in patients who underwent distal gastrectomy with gastroduodenostomy for early stomach cancer: a retrospective analysis  [published online January 23, 2017].  Clin J Pain. 2017. doi:10.1097/ajp.0000000000000472PubMedGoogle Scholar
Bastian  LA, Driscoll  MA, Heapy  AA,  et al.  Cigarette smoking status and receipt of an opioid prescription among veterans of recent wars  [published online September 21, 2016].  Pain Med. 2016;pnw223. doi:10.1093/pm/pnw223PubMedGoogle Scholar
Scott  DJ, Domino  EF, Heitzeg  MM,  et al.  Smoking modulation of mu-opioid and dopamine D2 receptor-mediated neurotransmission in humans.  Neuropsychopharmacology. 2007;32(2):450-457.PubMedGoogle ScholarCrossref
Kalso  E, Tasmuth  T, Neuvonen  PJ.  Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer.  Pain. 1996;64(2):293-302.PubMedGoogle ScholarCrossref
Mitra  R, Jones  S.  Adjuvant analgesics in cancer pain: a review.  Am J Hosp Palliat Care. 2012;29(1):70-79.PubMedGoogle ScholarCrossref
Pergolizzi  JV  Jr, Gharibo  C, Passik  S,  et al.  Dynamic risk factors in the misuse of opioid analgesics.  J Psychosom Res. 2012;72(6):443-451.PubMedGoogle ScholarCrossref
Casellas  AM, Guardiola  H, Renaud  FL.  Inhibition by opioids of phagocytosis in peritoneal macrophages.  Neuropeptides. 1991;18(1):35-40.PubMedGoogle ScholarCrossref
Roy  S, Wang  J, Kelschenbach  J, Koodie  L, Martin  J.  Modulation of immune function by morphine: implications for susceptibility to infection.  J Neuroimmune Pharmacol. 2006;1(1):77-89.PubMedGoogle ScholarCrossref
Szabo  I, Rojavin  M, Bussiere  JL, Eisenstein  TK, Adler  MW, Rogers  TJ.  Suppression of peritoneal macrophage phagocytosis of Candida albicans by opioids.  J Pharmacol Exp Ther. 1993;267(2):703-706.PubMedGoogle Scholar
Pacifici  R, di Carlo  S, Bacosi  A, Pichini  S, Zuccaro  P.  Pharmacokinetics and cytokine production in heroin and morphine-treated mice.  Int J Immunopharmacol. 2000;22(8):603-614.PubMedGoogle ScholarCrossref
Meissner  W, Dohrn  B, Reinhart  K.  Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia.  Crit Care Med. 2003;31(3):776-780.PubMedGoogle ScholarCrossref
Singleton  PA, Mirzapoiazova  T, Hasina  R, Salgia  R, Moss  J.  Increased μ-opioid receptor expression in metastatic lung cancer.  Br J Anaesth. 2014;113(suppl 1):i103-i108.PubMedGoogle ScholarCrossref
Janku  F, Johnson  LK, Karp  DD, Atkins  JT, Singleton  PA, Moss  J.  Treatment with methylnaltrexone is associated with increased survival in patients with advanced cancer.  Ann Oncol. 2016;27(11):2032-2038.PubMedGoogle ScholarCrossref
Abraham  NS, Noseworthy  PA, Yao  X, Sangaralingham  LR, Shah  ND.  Gastrointestinal safety of direct oral anticoagulants: a large population-based study.  Gastroenterology. 2017;152(5):1014-1022.e1.PubMedGoogle ScholarCrossref
Original Investigation
From the American Head and Neck Society
December 2017

Chronic Opioid Use Following Surgery for Oral Cavity Cancer

Author Affiliations
  • 1Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego School of Medicine, San Diego
  • 2Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 3Department of Anesthesiology, University of California, San Diego School of Medicine, San Diego
  • 4Department of Pharmacy, University of California, San Diego School of Medicine, San Diego
  • 5Division of Medical Oncology, Department of Medicine, University of California, San Diego School of Medicine, San Diego
JAMA Otolaryngol Head Neck Surg. 2017;143(12):1187-1194. doi:10.1001/jamaoto.2017.0582
Key Points

Question  How prevalent is chronic opioid use after surgery for oral cavity cancer, and are there identifiable clinical risk factors for chronic opioid use?

Findings  A cohort study of 99 patients with oral cavity cancer undergoing surgery determined the prevalence of chronic opioid use to be 41%. Preoperative opioid use, prior tobacco use, and development of persistence, recurrence, or a second primary tumor were associated with chronic opioid use, and opioid use was associated with decreased survival.

Meaning  Strategies to reduce the likelihood of opioid dependence after oral cavity cancer surgery should consider targeting those patients who are current opioid users, prior tobacco users, and those who develop persistence, recurrence, or a second primary tumor.


Importance  Opioid misuse and overuse has become an epidemic. Chronic opioid use among oral cavity cancer patients after surgery has not been described.

Objectives  To assess the prevalence of chronic opioid use in patients undergoing surgery for oral cavity cancer, and evaluate possible associated clinical factors; and the association between opioid use and survival.

Design, Setting, and Participants  For this retrospective cohort study of patients undergoing surgery for oral cavity cancer a consecutive sample of 99 patients between January 1, 2011, and September 30, 2016, were identified through the institutional cancer registry from a single academic center.

Exposures  Surgery for oral cavity cancer.

Main Outcomes and Measures  Chronic opioid use, defined as more than 90 days from surgery. Factors associated with chronic opioid use were investigated by univariable and multivariable logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess overall survival and disease-free survival.

Results  The mean (SD) patient age was 62.6 (14.3) years; 60 patients (60%) were male. Chronic opioid use was observed in 41 patients (41%). On multivariable logistic regression, preoperative opioid use (odds ratio [OR], 5.6; 95% CI, 2.2-14.3), tobacco use (OR, 2.8; 95% CI, 1.0-8.0), and development of persistence, recurrence, or a second primary tumor (OR, 2.8; 95% CI, 1.0-7.4) were associated with chronic opioid use. Among preoperative opioid users, estimated overall survival (hazard ratio [HR], 3.2; 95% CI, 1.4-7.1) was decreased, and chronic opioid use was associated with decreased disease-free survival (HR, 2.7; 95% CI, 1.1-6.6).

Conclusions and Relevance  In patients undergoing surgery for oral cavity tumors, the prevalence of chronic opioid use was considerable. Preoperative opioid use, tobacco use, and development of persistence, recurrence, or a second primary tumor were associated with chronic opioid use after surgery, and both preoperative and chronic opioid use were associated with decreased survival.