Rapid Opioid Detoxification: Deaths and Adverse Events

Editorial Note

Opioid abuse and dependence is a serious public health problem in the United States. During 1999–2008, emergency department visits, overdose deaths, and substance abuse treatment admissions related to prescription opioids increased substantially.^[1] Opioid dependence is a chronic and relapsing illness. Evidence-based treatment options include medication-assisted treatment (MAT) with long-acting opioid agonists (e.g., methadone or buprenorphine), maintenance treatment with opioid antagonists (e.g., naltrexone), or counseling and behavioral interventions.^[2,3–5] Treatment goals include long-term abstinence or reduction in illicit and nonmedical drug use. MAT is considered first-line treatment among the evidence-based options listed previously and, compared with other treatments, is associated with lower mortality, improved treatment retention, and decreased incidence of comorbid illnesses, including human immunodeficiency virus infection.^[2] However, MAT treatment capacity is insufficient to meet demand in the United States, and patients frequently are placed on waiting lists.^[6]

Opioid detoxification refers to the discontinuation of opioid use under medical supervision and includes prescribing or administering medications to decrease withdrawal symptoms. Standard detoxification methods include administering gradually reduced doses of long-acting opioid agonists during a 3–21 day period or discontinuing opioids and administering nonopioid medications to block withdrawal symptoms. These methods ameliorate withdrawal symptoms and carry <1% risk for serious adverse events.^[3,4] The effect of detoxification on long-term abstinence is negligible without the addition of longer term evidence-based substance abuse treatment.^[5] Medically supervised opioid detoxification, however, when closely associated with substance abuse treatment programs, can provide an entry point to care.

AAROD was developed during the 1980s with the goal of reducing the discomfort of withdrawal and thereby encouraging patients to enter substance abuse treatment. However, AAROD and standard opioid detoxification do not differ in subjective withdrawal symptom scores or in achievement of short-term abstinence.^[7] Few long-term studies of AAROD exist, but published data indicate that AAROD does not improve 12-month abstinence rates, compared with standard detoxification.^[7] Furthermore, AAROD is associated with a substantial rate of serious adverse events in the research setting, 8.6% in one study.^[8]

Government agencies and professional societies,* including the American Society of Addiction Medicine, have recommended against using AAROD in clinical settings.^[9] There is insufficient knowledge regarding how widely AAROD is used in the United States and the frequency of AAROD-associated adverse events in community practice settings. At least seven deaths occurred following AAROD among 2,350 procedures performed in one practice during 1995–1999.†

The New York City clinic investigation revealed that AAROD was performed on 75 patients during January–September 2012 and was associated with two deaths and five additional adverse events requiring hospitalization, a serious adverse event rate of 9.3%. No standard protocol exists for AAROD; however, the clinic's practice was consistent with AAROD use described elsewhere.^[7] All events occurred after and in close temporal proximity to AAROD. Although a common mechanism linking these events to AAROD is not evident, the events are consistent with previously proposed mechanisms of AAROD-associated adverse events, including electrolyte disturbance, catecholamine release, altered cardiopulmonary functioning, acute lung injury, and other physiologic effects associated with administration of high doses of opioid antagonists under general anesthesia.^[10] Given the ongoing epidemic of prescription opioid dependence, further increases in the demand for substance use disorder services are to be expected. AAROD has substantial risks, including a risk for death, and little to no evidence to support its use. Safe, evidence-based treatments of opioid dependence (e.g., MAT) exist and are preferred.^[2]

* Additional information available at https://www.nice.org.uk/cg052.
† Additional information available at https://njlaw.rutgers.edu/collections/oal/final/bds10905-99_2.pdf