Sleeping Through Detox Poses Hazards

Anesthesia-assisted opioid withdrawal, offered asquicker and easier than other rapid detoxification methods, was recently foundto be comparable on several measures, but with greater risk forlife-threatening adverse events. A randomized trial comparing anesthesia-, buprenorphine- (Subutex) and clonidine- (Catapres) assistedheroin detoxification found similarity in withdrawal symptom severity, lowrates of inpatient program completion and high proportion of follow-up opioid-positive urine tests (Collins et al., 2005). Whileno detoxification procedure appeared "painless" or to facilitate programcompliance or long-term abstinence, the anesthesia- and buprenorphine-assistedprotocols were superior to the clonidine program infacilitating the naltrexone (ReVia)induction to rapidly counter opioid effect. Theanesthesia-assisted protocol was distinct, however, in that three of 35patients experienced serious adverse events.

One patient developed severe pulmonary edema and aspiration pneumoniaapproximately 14 hours after extubation. That patientsubsequently admitted to a history of complicated pneumonia and possibleobstructive sleep apnea; both of which were added to the exclusionary criteriafor potential participants. A second patient who had concealed a history ofbipolar illness developed a mixed bipolar state with suicidal ideation thatnecessitated rehospitalization five days afteranesthesia.

The third patient had not disclosed a previous episode of diabetic ketoacidosis during screening and after anesthesia haduncontrolled glucose serum levels and developed ketoacidosistwo days later. The investigators attributed the falsifying of medical orpsychiatric histories in the screening interviews to patients hoping to beselected for anesthesia due to their expectation that it would obviate thesevere discomfort of opioid withdrawal.

Costing as much as $15,000 and not covered by health insurance, according tothe investigators, the anesthesia-assisted procedure is promoted to thewell-heeled addict as a means to painlessly sleep through an opioid antagonist induction. The procedure is offered,however, without good evidence to support efficacy and despitenumerous reports of serious adverse events, according Collins and colleagues(2005):

The eagerness with which both patients and the public have acceptedclaims of success highlights the desperation many patients and families feelabout treating opioid dependence.

To evaluate the safety, tolerability and efficacy of anesthesia-assistedrapid opioid detoxification, the investigatorscompared the procedure to two other withdrawal programs that incorporate naltrexone induction. The study cohort consisted of 106heroin users meeting DSM-IV criteriafor opioid dependence for at least six months.Following each procedure, patients received clonidineto mitigate withdrawal symptoms as well as clonazepam(Klonopin) and ancillary medications as required.After hospital discharge, all patients were followed for 12 weeks, receiving naltrexone 50 mg daily and twice-weekly, manual-guidedrelapse-prevention psychotherapy. The researchers noted that an anticipateddepot naltrexone formulation is likely to increaseparticipation in, and success of, such programs, in contrast to the currentpoor rate of compliance with oral naltrexone.

Anesthesia was maintained for four to six hours, during which the opioid antagonist nalmefene (Revex) was infused intravenously 4 mg over 30 minutes,followed by naltrexone 50 mg via nasogastrictube. In the buprenorphine-assisted protocol, asingle 8 mg sublingual "bridging" dose of this partial opioidagonist was administered to facilitate a more comfortable naltrexoneinduction two days later. Collins and colleagues explained that buprenorphine shortens the time until naltrexonecan be administered and that it has a longer duration of action and less severewithdrawal than heroin. The initial naltrexone dosewas 12.5 mg, increased to 25 mg on day 3 and then to 50 mg daily.

In the clonidine-assisted procedure, it wasposited that clonidine, an a2-adrenergic agonist,mitigates the withdrawal symptoms in the first week by acting on the locus coeruleus to decrease norepinephrinerelease. Naltrexone was administered on day 7, aftera naloxone (Narcan)short-acting opioid antagonist challenge confirmedthe absence of opioid. Naltrexonewas initiated at 12.5 mg and increased to 50 mg on day 9.

Collins and colleagues reported that mean withdrawal severity scores werecomparable across the three treatments and noted that the anesthesia-assistedgroup reported the highest severity on day 1 immediately before the procedure.The researchers attributed this to anticipatory anxiety and possibly toreceiving less clonazepam before anesthesia.

The groups also had similarly low rates of completing their 12-weekprograms, with less than 50% remaining in each group by week 3 and an overalldropout rate of 82% by end of study at 12 weeks. The anesthesia- and buprenorphine-assisted detoxification had significantlygreater rates of naltrexone induction (94% and 97%,respectively) than the 21% with clonidine; and theresearchers noted a lower dropout rate among those who received the naltrexone.

The findings suggested to Collins and colleagues, "that general anesthesiafor rapid antagonist induction does not currently have a meaningful role toplay in the treatment of opioid dependence."

Further, the unimpressive outcomes from each procedure led them toemphasize, "physicians must recognize that the methodused to achieve opioid abstinence does not appear toaffect the course of this chronic relapsing disease."

In an accompanying editorial, Patrick O'Connor, M.D., M.P.H., (2005) fromthe Yale University School of Medicine concurred with this acknowledgment ofthe limitations of detoxification procedures, characterizing them as only thevery first steps of treatment.

Beyond the comparisons made in this study, detoxification-basedapproaches that are not followed by effective means of post-detoxificationtreatment are overwhelmingly likely to fail.

O'Connor argued that buprenorphine is betterutilized in the newly authorized office-based maintenance programs than indetoxification procedures and that maintenance therapy should be consideredfirst-line treatment of opioid addiction. Furtherresearch on detoxification-based treatments, O'Connor recommended, "shouldfocus on how to provide effective relapse prevention treatment."

References:

References

1.

Collins ED, Kleber HD, Whittington RA, Heitler NE (2005), Anesthesia-assisted vsbuprenorphine- or clonidine-assistedheroin detoxification and naltrexone induction: arandomized trial. JAMA 294(8):903-913 [see comment].

2.

O'Connor PG (2005), Methods of detoxification and their role in treatingpatients with opioid dependence. JAMA 294(8):961-963[editorial].