Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal

Abstract

Background: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term opioid replacement treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system.

Objectives: To assess the effectiveness of interventions involving the administration of opioid antagonists to induce opioid withdrawal with concomitant heavy sedation or anaesthesia, in terms of withdrawal signs and symptoms, completion of treatment and adverse effects.

Search strategy: We searched the Drugs and Alcohol Group register (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2004), Medline (January 1966 to January 2005), Embase (January 1985 to January 2005), PsycINFO (1967 to January 2005), and Cinahl (1982 to December 2004) and reference lists of studies.

Selection criteria: Controlled trials comparing antagonist-induced withdrawal under heavy sedation or anaesthesia with another form of treatment, or a different regime of anaesthesia-based antagonist-induced withdrawal.

Data collection and analysis: One reviewer assessed studies for inclusion and undertook data extraction and assessed quality. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers.

Main results: Six studies (five randomised controlled trials) involving 834 participants met the inclusion criteria for the review.Antagonist-induced withdrawal is more intense but less prolonged than withdrawal managed with reducing doses of methadone, and doses of naltrexone sufficient for blockade of opioid effects can be established significantly more quickly with antagonist-induced withdrawal than withdrawal managed with clonidine and symptomatic medications. The level of sedation does not affect the intensity and duration of withdrawal, although the duration of anaesthesia may influence withdrawal severity. There is a significantly greater risk of adverse events with heavy, compared to light, sedation (RR 3.21, 95% CI 1.13 to 9.12, P = 0.03) and probably also other forms of detoxification.

Authors' conclusions: Heavy sedation compared to light sedation does not confer additional benefits in terms of less severe withdrawal or increased rates of commencement on naltrexone maintenance treatment. Given that the adverse events are potentially life-threatening, the value of antagonist-induced withdrawal under heavy sedation or anaesthesia is not supported. The high cost of anaesthesia-based approaches, both in monetary terms and use of scarce intensive care resources, suggest that this form of treatment should not be pursued.