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Long-term effects of opioids on the cardiovascular system

Examine the evidence

Corbett, Keegan, BSN, RN; Dugan, Amelia, BSN, RN; Vitale, Christina, BSN, RN; Gravel, Tammy, MS, EdD, RN

doi: 10.1097/01.NURSE.0000554247.12754.28
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Abstract: This article provides an integrative review of the literature on long-term opioid use, its effects on the cardiovascular system, and its implications for nurses.

As this literature review shows, long-term opioid use can adversely affect the heart. Learn about cardiovascular risks so you can educate patients who may be at risk.

Keegan Corbett and Christina Vitale are RNs at Stony Brook University Hospital in Stony Brook, N.Y. Amelia Dugan is an RN at Fairlawn Rehabilitation Hospital in Worcester, Mass. Tammy Gravel is senior associate dean of curriculum and assessment at MCPHS University in Worcester, Mass.

The authors have disclosed no financial relationships related to this article.

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CURRENTLY, THE NUMBER ONE cause of death in the US is heart disease, with 610,000 deaths reported annually.1,2 Given the magnitude of the opioid epidemic, nurses will care for more patients who have or will develop cardiovascular disease while taking prescribed or illicit opioids. Nurses need to understand how these drugs affect the cardiovascular system to deliver the best possible care and appropriate patient education. This article reviews research literature focused on the effects of opioids (both prescription and illicit) and their impact on the human heart. It also discusses recommended interventions for nurses who assess, educate, and care for patients taking opioids long-term. For the purpose of this discussion, long-term is defined as at least 3 months for opioid medications and at least 4 weeks for opioid agonist medications.

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Reviewing the literature

The authors conducted a systematic review of the literature using Medline, Ovid, and CINAHL. An exhaustive search was performed including the keywords opioid, opiate, cardiovascular, heart, and cardiac. The search was limited to peer-reviewed articles published from 2013 through 2017 with humans as the subject.

The authors identified seven studies relevant to this review. Each of the studies noted an effect of opioids on the cardiovascular system when used long-term. Although research questions and methodology differed, each group of researchers found effects directly harmful to the heart.

According to Seltenhammer and colleagues, long-term opioid exposure may lead to structural cardiac changes.3 These researchers studied myocardial tissue samples from 76 heroin- and morphine-related deaths and 23 nondrug-related deaths. They found a significant correlation between long-term abuse of opioids and myocardial fibrosis.

The heart's electrical system can suffer detrimental effects from long-term opioid use, specifically a prolonged QT interval. Mason and colleagues found a 7.2 millisecond increase in QT interval correction Fridericia (QTcF) in patients being treated for pain with chronic opioids, specifically hydrocodone, oxycodone, and morphine.4 The QTcF is used to compare QT intervals across a range of heart rates. A prolonged QT interval is associated with a slower heart rate and places patients at a greater risk for torsades de pointes.5

Isbister and colleagues studied 19 patients consuming methadone and 20 patients prescribed buprenorphine for opioid agonist treatment who were monitored for 24 hours on an ambulatory electrocardiography device.6 Seven patients on methadone maintenance developed a prolonged QT interval that was considered significant (P value, .008). The other patients on methadone were found to have longer QT intervals compared with patients in the control group, although their values were still considered to be in the normal range. Patients prescribed methadone in this study had no known risk factors that would contribute to a prolonged QT interval, such as medication use and personal or family history of cardiac disease. No association between methadone dose and QT interval prolongation was found.

In a study of 58 patients, Keller and colleagues found that meperidine can also prolong the QT interval, independent of heart rate, in correlation with the plasma drug level.7 Similarly, three other studies showed that various opioids can prolong the QT interval.4,6,7

The long-term use of opioids may lead to an increased risk for cardiovascular disease and death. Khodneva and colleagues studied prescription opioid use for noncancer chronic pain in a population of 29,025 participants.8 They found a significant risk of cardiovascular death and coronary heart disease in those who use prescription opioids.

In another study regarding the use of opioid prescriptions for chronic noncancer pain, LoCasale and colleagues studied 36,839 patients and found an increased risk of unstable angina, myocardial infarction, heart failure, transient ischemic attack, and stroke in patients with preestablished cardiovascular disease who took opioids for more than 6 months.9

Ray and colleagues found that patients taking a long-acting opioid for chronic noncancer pain had a greater risk for death compared with those taking other analgesics, antiepileptic drugs, or cyclic antidepressants.10 Of 53 patients who died from a nonoverdose-related cause, 36 died from cardiac-related conditions. This study demonstrated a significant relationship between cardiac-related deaths and long-acting opioids (P value, .02). All three studies regarding the use of opioids for chronic noncancer pain found a detrimental effect on the cardiovascular system.8-10

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Gaps in the literature

The literature has demonstrated a possible relationship between the use of prescribed opioids for chronic pain and adverse cardiovascular reactions. Additional research should be conducted on those who use illicit opioids as well as those recovering from opioid addiction to investigate the effects of opioids on the cardiovascular system in these patients. In addition, no evidence-based screening tool or educational guideline is available to help nurses assess and counsel patients who are at risk for cardiovascular complications due to long-term opioid use.

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Implications for nursing practice

The evidence reviewed by the authors demonstrated the effects of long-term opioid use on the cardiovascular system. The implication for nursing practice is the need for nurses to screen, assess, and educate patients who take opioids. In collaboration with healthcare providers, nurses can assess heart structure and function with studies such as electrocardiography and continuous ambulatory ECG monitoring to screen for dysrhythmias and disorders of myocardial repolarization, such as prolonged QT intervals.

In addition, nurses should continue to assess use, misuse, and abuse of opioids among all patients. Appropriate counseling and referrals for addiction treatment should be offered to patients for continuity of care. Equally important, nurses must educate patients about cardiovascular risks associated with long-term opioid use. Nurses should continue to reinforce education on diet, exercise, smoking cessation, stress management, and annual physical exams to promote cardiovascular health.

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Responding to the epidemic

The reviewed literature demonstrated that many opioids have adverse effects on the cardiovascular system that may lead to structural, electrical, and functional complications. In view of the opioid epidemic and the high rate of cardiovascular disease and death in the US, nurses must understand how opioids affect the cardiovascular system during long-term use. By remaining current with the evidence, nurses can more effectively care for patients using opioids chronically and lower their risk of cardiovascular disease and death.

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REFERENCES

1. Centers for Disease Control and Prevention. Leading causes of death. 2017. http://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm.
2. Centers for Disease Control and Prevention. Opioid overdose: understanding the epidemic. 2018. http://www.cdc.gov/drugoverdose/epidemic/index.html.
3. Seltenhammer MH, Marchart K, Paula P, et al Micromorphological changes in cardiac tissue of drug-related deaths with emphasis on chronic illicit opioid abuse. Addiction. 2013;108(7):1287–1295.
4. Mason JW, Schwertschlag US, Klutzaritz V, Canafax DM. Electrocardiographic and cardiovascular diagnostic characteristics of patients receiving long-term opioid therapy for pain. J Opioid Manag. 2014;10(2):103–109.
5. Ignatavicius DD, Workman ML. Medical-Surgical Nursing: Patient-Centered Collaborative Care. 8th ed. St. Louis, MO: Elsevier, Inc.; 2016.
6. Isbister GK, Brown AL, Gill A, Scott AJ, Calver L, Dunlop AJ. QT interval prolongation in opioid agonist treatment: analysis of continuous 12-lead electrocardiogram recordings. Br J Clin Pharmacol. 2017;83(10):2274–2282.
7. Keller GA, Villa Etchegoyen MC, Fernández N, et al Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations. Int J Clin Pharmacol Ther. 2017;55(3):275–285.
8. Khodneva Y, Muntner P, Kertesz S, Kissela B, Safford MM. Prescription opioid use and risk of coronary heart disease, stroke, and cardiovascular death among adults from a prospective cohort (REGARDS Study). Pain Med. 2016;17(3):444–455.
9. LoCasale R, Kern DM, Chevalier P, Zhou S, Chavoshi S, Sostek M. Description of cardiovascular event rates in patients initiating chronic opioid therapy for noncancer pain in observational cohort studies in the US, UK, and Germany. Adv Ther. 2014;31(7):708–723.
10. Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315(22):2415–2423.
Keywords:

cardiac; cardiovascular disease; opioids; QT interval; torsades de pointes

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