CONSIDERATIONS WHEN PRESCRIBING OPIOIDS FOR PATIENTS WITH HEART FAILURE*

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This module provides additional details and risk-reduction guidance specific for this risk factor for serious prescription opioid overdose. It supplements but does not replace the general best practices for opioid prescribing presented in the “Considerations for Safe and Responsible Opioid Prescribing“ module.

 

Background

  1. Approximately 5.7 million U.S. adults have heart failure, and 1 million are hospitalized each year. Approximately 50% of patients will die within 5 years of diagnosis.1
  2. The prevalence of heart failure rises exponentially with advancing age, ranging from 6% in persons aged 60 to 79 years to 14% among those aged >80 years. Eighty percent of heart failure occurs in those >65 years of age.2
  3. Opioid use is common in patients with heart failure, occurring in up to 25% of those hospitalized with heart failure and is associated with increased morbidity and mortality.3-5

 

Heart failure and opioid overdose

  1. Reduced cardiac output and/or compensatory neuro-humoral reactions decrease blood flow (and drug delivery) to the liver and kidneys, and cause pulmonary and systemic vascular congestion.
    1. The pharmacokinetics of many drugs may be altered due to impaired intestinal absorption and changes in drug distribution, metabolism, and elimination by the liver and kidneys.6,7
      1. Decreased clearance of certain opioids and their metabolites may lead to their accumulation, resulting in an enhanced and prolonged duration action, thereby increasing the risk of over-sedation, hypotension, bradycardia, respiratory depression, and death. (see “Renal Impairment” module)
    1. Cognitive impairment is common in patients with heart failure, correlates with the degree of left ventricular dysfunction, and may be exacerbated by opioid use.
      1. Cognitive impairment can increase the risk for medication administration errors and overdose.8-9 (see “Cerebrovascular disease” module)
  2. Age-related changes in the respiratory system that reduce the ability to tolerate opioid-induced respiratory depression include decreased sensitivity of central and peripheral chemoreceptors to hypercapnia and hypoxia, and diminished compensatory respiratory drive.10-12
  3. Older patients with heart failure commonly have comorbidities that increase the risk for opioid-induced respiratory depression such as coronary heart disease, stroke, chronic obstructive pulmonary disease (see “Chronic Pulmonary Disease” module), and sleep-disordered breathing.13,14

 

Risk-mitigating interventions to consider when prescribing opioids for patients with heart failure

[Refer to the full prescribing information (FDA label) for important product-specific details]

  1. Optimize medical management of heart failure to restore normal oxygenation and improve the patient’s volume status and symptoms.15,16
  2. Optimize non-opioid and non-pharmacologic measures to control pain in patients with heart failure. Avoid nonsteroidal anti-inflammatory drugs, as they may impair renal function, lead to fluid retention, and heart failure exacerbation.16,17
  3. If opioid analgesic therapy is indicated in heart failure:
    1. Start with a short-acting opioid at the lowest effective dose (25% to 50% below the usual adult dose.8,18 (see “Considerations for Safe and Responsible Opioid Prescribing”)
    2. Slowly and cautiously titrate dosage by 25% increments based on clinical effectiveness and tolerability.8,18
    3. Monitor hemodynamic status and renal and hepatic function closely and select/adjust the choice of opioid and dosage accordingly.8,18
    4. Use caution if initiating opioid therapy during acute decompensated heart failure or in patients who are dehydrated.
      1. A retrospective study of 150,000 patients in the Acute Decompensated Heart Failure Na­tional Registry found that use of intravenous morphine during acute decompensated heart failure was associated with an increase in mechanical ventilation, intensive care unit admissions, length of hospitalization, and a nearly fivefold higher mortality.5
    5. Long-term opioids may be continued cautiously to manage chronic non-cancer pain during decompensated heart failure at reduced dosage and with close monitoring for adverse effects.3
  4. Closely monitor opioid-treated patients with heart failure for respiratory depression, over-sedation, hypotension, and bradycardia, particularly during opioid initiation and after dosage escalation. The risk for overdose is greatest during the first 3 to 7 days after starting an opioid or increasing the dosage. This occurs because tolerance to an opioid’s respiratory depressant effects is slower to develop and less complete than tolerance to its analgesic or euphoric effects.8,18-20
  5. Avoid concurrent use of other medications or substances that are central nervous system depressants, such as benzodiazepines, sedatives/hypnotics, and alcohol in opioid-treated patients. The combination can result in profound sedation, respiratory depression, coma, and death and should be restricted to the minimum required dosage and duration in patients for whom alternative treatment options are inadequate.8,18,21 (see also: FDA label)
  6. Consider consultation or co-management with a specialist in pain medicine and/or cardiovascular medicine when prescribing opioids to manage pain in patients with heart failure.8
  7. Consider prescribing take-home naloxone for opioid-treated patients with heart failure to reverse life-threatening respiratory depression if an overdose occurs. Educate the patient, family/household members, and caregivers about signs and symptoms of opioid overdose and train them to properly use naloxone if an opioid-related overdose is suspected.8,22 (see ‘Follow Up’ section, #5 in the “Considerations for Safe and Responsible Opioid Prescribing” module)

 

Additional Resources

*The information presented in this module highlights some fundamental concepts of opioid prescribing for adult outpatients. It excludes certain populations (pediatrics, pregnancy, patients with active cancer or receiving palliative or end-of-life care) and settings (perioperative, emergency, in-patient). The information provided is intended to support safe and effective opioid therapy and minimize serious adverse outcomes, particularly overdose. It is not intended to be exhaustive nor substitute for consulting a medication’s full prescribing information for complete details and warnings. Links and references to selected, more comprehensive clinical and prescribing resources are provided to facilitate safe and effective opioid prescribing.

  1. FDA Online Label Repository or Daily Med (NIH/National Library of Medicine)
  2. Heart Failure Society of America
  3. Clinical Tools for Heart Failure-American Heart Association

 

References

  1. Hall MJ, Levant S, DeFrances CJ. Hospitalization for congestive heart failure: United States, 2000–2010. NCHS Data Brief 2012;(108):1–8.
  2. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke, statistics: 2018 update. A report from the American Heart Association. Circulation 2018 Mar 20;137:e67-e492. PMID: 29386200
  3. Dawson NL, Roth V, Hodge DO, Vargas ER, Burton MC. Opioid use in patients with congestive heart failure. Pain Medicine 2018;19:485-490. PMID: 28460060
  4. Mosher MJ, Jiang L, Sarrazin V, et al. Prevalence and characteristics of hospitalized adults on chronic opioid therapy. J Hosp Med 2014;9:82-7. PMID: 24311455
  5. Peacock WF, Hollander JE, Diercks DB, et al. Morphine and outcomes in acute decompensated heart failure: an ADHERE analysis. Emerg Med 2008;25:205–9. PMID: 18356349
  6. Ogawa R, Stachnik JM, Echizen H. Clinical pharmacokinetics of drugs in patients with heart failure: An update (part 2, drugs administered orally). Clin Pharmacokinet. 2014;53(12):1083-1114. PMID: 25248847
  7. Correale M, Tarantino N, Petrucci R, Tricarico L, Laonigro I, Di Biase M, Brunetti ND. Liver disease and heart failure: Back and Forth. European Journal of Internal Medicine 2018;48:25-34. PMID: 29100896
  8. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain – United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. PMID: 26987082
  9. Huijts M, van Oostenbrugge RJ, Duits A, et al. Cognitive impairment in heart failure: Results from the trial of intensified versus standard medical therapy in elderly patients with congestive heart failure (TIME-CHF) randomized trial. Eur J Heart Fail. 2013;15(6):699-707. PMID: 23384944
  10. Cepeda MS, Farrar JT, Baumgarten M, et al. Side effects of opioids during short term administration: Effect of age, gender, and race. Clin Pharmacol Ther 2003;74:102-12. PMID: 2891220
  11. Davies GA, Bolton CE. Chapter 15. Age related changes in the respiratory system. In: Fillit HM, Rockwood K, Woodhouse K, eds. Brockelhurst’s Textbook of Geriatric Medicine and Gerontology, 7th ed, 2010.
  12. GOLD 2018: Global Strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. http://goldcopd.org/gold-reports/
  13. Zedler B, Xie L, Wang L, et al. Risk factors for serious prescription opioid-related toxicity or overdose among veterans health administration patients. Pain Med. 2014;15:1911-1929. PMID: 24931395
  14. Nadpara PA, Joyce AR, Murelle EL, et al. Risk factors for serious prescription opioid induced respiratory depression or overdose: Comparison of commercially insured and veterans health affairs populations. Pain Medicine 2018;19:79-86. PMID: 28419384
  15. Kuo DC, Peacock WF. Diagnosing and managing acute heart failure in the emergency department. Clin Exp Emerg Med 2015;2(3):141-149. PMID: 27752588
  16. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: A report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America. Circulation. 2017;136(6):e137-e161. PMID: 28455343
  17. Page RL, O’Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure.  A scientific statement from the American Heart Association. Circulation. 2016 Aug 9;134(6):e32-69. doi: 10.1161/CIR.0000000000000426. Epub 2016 Jul 11. Review. Erratum in: Circulation. 2016 Sep 20;134(12):e261. PMID: 27647303
  18. Washington State Agency Medical Directors’ Group (WSAMDG). Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain: An Educational Aid to Improve Care and Safety With Opioid Treatment. Corvallis, WA: Washington Department of Health, 2015. Washington State Agency Medical Director’s Group
  19. Dumas EO, Pollack GM. Opioid tolerance development: a pharmacokinetic/pharmacodynamic perspective. AAPS J. 2008;10:537-51. PMID: 18989788
  20. White JM, Irvine RJ. Mechanisms of fatal opioid overdose. Addiction 1999;94:961-72. PMID: 10707430
  21. Busse J, Craigie S, Juurlink D, et al. Guideline for opioid therapy and chronic noncancer pain: Appendix. CMAJ 2017. PMID: 26461074
  22. Federation of State Medical Boards (FSMB). Guidelines for the Chronic Use of Opioid Analgesics. April 2017. Federation of State Medical Boards