Mental Health Section - Opioid Antagonists Under Heavy Sedation or General Anesthesia as a Technique of Opioid Detoxificatione

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

The traditional treatment of opioid addiction involves substituting the opioid (i.e., heroin) with an equivalent dose of a longer acting opioid antagonist, i.e., methadone, followed by tapering to a maintenance dose. Methadone maintenance therapy does not resolve opioid addiction, but has been shown to result in improved general health, retention of patients in treatment, and a decrease in the risk of transmitting HIV or hepatitis. However, critics of methadone maintenance point out that this strategy substitutes one drug of dependence for the indefinite use of another.

Detoxification followed by abstinence is another treatment option, which can be used as the initial treatment of opioid addiction, or offered as a final treatment strategy for people on methadone maintenance. Detoxification is associated with acute symptoms followed by a longer period of protracted symptoms (i.e., six months) of withdrawal. Although typically not life threatening, acute detoxification symptoms include irritability, anxiety, apprehension, muscular and abdominal pains, chills, nausea, diarrhea, yawning, lacrimation, sweating, sneezing, rhinorrhea, general weakness, and insomnia. Protracted withdrawal symptoms include a general feeling of reduced well being and drug craving. Relapse is common during this period.

Detoxification may be initiated with tapering doses of methadone or buprenorphine (an opioid agonist-antagonist), treatment with a combination of buprenorphine and an opioid antagonist (i.e., naloxone) or discontinuation of opioids and administration of oral clonidine and other medications to relieve acute symptoms. However, no matter what type of patient support and oral medications are offered, detoxification is associated with patient discomfort, such that many may be unwilling to attempt detoxification. Additionally, detoxification is only the first stage of treatment. Without ongoing medication and psychosocial support after detoxification, there is a low probability that any detoxification procedure alone will result in lasting abstinence. Opioid antagonists, such as naltrexone, may also be used as maintenance therapy to reduce craving and thus reduce the risk of relapse.

Dissatisfaction with current approaches to detoxification has led to interest in using relatively high doses of opioid antagonists, such as naltrexone, naloxone or nalmefene under deep sedation with benzodiazepine or general anesthesia. This strategy has been referred to as "rapid", "ultra-rapid", "anesthesia-assisted" or "one-day" detoxification. The use of opioid antagonists accelerates the acute phase of detoxification, which can be completed within 24 to 48 hours. Since the patient is under anesthesia, there is no patient discomfort or memory of the symptoms of acute withdrawal, although protracted symptoms of withdrawal may still be present post anesthesia. Various other drugs are also administered to control acute withdrawal symptoms, such as clonidine (to attenuate sympathetic and hemodynamic effects of withdrawal), odensetron (to control nausea and vomiting) and somatostatin (to control diarrhea). Hospital admission is required if general anesthesia is used. If heavy sedation is used, the program can potentially be offered on an outpatient basis. Initial detoxification is then followed by ongoing support for the protracted symptoms of withdrawal. In addition, naltrexone may be continued to discourage relapse.

Ultra rapid detoxification may be offered by specialized facilities. Neuraad Treatment Centers, Nutmeg Intensive Rehabilitation Centers, and Center for Research and Treatment of Addiction (CITA) are examples. These programs typically consist of three phases: a comprehensive evaluation, inpatient detoxification under anesthesia, and finally, mandatory post-detoxification care and follow-up. The program may be offered to patients addicted to opioid or narcotic drugs such as opium, heroin, methadone, morphine, demerol, dilaudid, fentanyl, oxycodone, hydrocodone, or butorphanol. Once acute detoxification is complete, the opioid antagonist naltrexone is often continued to decrease drug craving, thus hopefully reducing the incidence of relapse.

Policy/Criteria

Opioid antagonists under heavy sedation or general anesthesia (i.e., ultra-rapid detoxification) are considered investigational as a technique for opioid detoxification.

Scientific Background

Evaluation of the safety and effectiveness of ultra-rapid treatment of opioid withdrawal using sedation or general anesthesia involves consideration of a variety of outcomes. For example, one might consider the numbers of patients enrolling in detoxification programs. Many opioid addicts may be fearful of prolonged detoxification programs and thus may only seek treatment in an accelerated detoxification program. Advocates of ultra-rapid detoxification point out that an increasing enrollment in detoxification programs is and of itself an important outcome. (2,3) In addition, proponents suggest that the procedure is a rapid and painless method of detoxification. Therefore, an important outcome is the comparison of the duration and severity of withdrawal symptoms associated with ultra-rapid detoxification and other detoxification strategies.

The completion rate of a detoxification program is another possible outcome. As noted by Scherbaum, up to 30% of patients may drop out of traditional inpatient detoxification programs. (4) Using sedation or anesthesia, one is assured of 100% completion of detoxification. However, as is commonly pointed out, detoxification is only the first step in treating opiate addiction, and ultra-rapid detoxification programs may offer different types of long-term follow-up care, based on ongoing psychosocial support with or without additional medication, such as naltrexone. Therefore, the rate of abstinence during both the short-term six-month period of protracted withdrawal symptoms and longer-term abstinence are also important outcomes. For example, traditional methods of withdrawal (i.e., tapering doses of methadone or buprenophrine) require the patient to be in a therapeutic environment for a prolonged period of time, potentially reducing the risk of long-term relapse.

In addition, the success of any detoxification program must be evaluated according to the patient populations treated. For example, patients addicted to heroin may respond differently than those addicted to oxycodone, and response may vary according to duration of addiction, or prior attempts at traditional detoxification. Also, ultra-rapid detoxification may be offered to patients on methadone maintenance, in a final effort to render these patients drug-free. These patients may have been in a therapeutic environment for a prolonged period of time, and may have more stable personal lives than those attempting initial detoxification from heroin use. However, symptoms associated with methadone withdrawal are thought to be more severe than those associated with heroin or codeine withdrawal. (5)

The major safety considerations regarding ultra-rapid detoxification are the risks associated with general anesthesia in combination with opioid antagonists. While patients are generally intubated and ventilated, eliminating the risk of choking, intravenous naloxone has been associated with cardiovascular complications such as cardiac arrest and pulmonary edema. These potential safety issues are particularly important, since opioid withdrawal itself is not associated with life-threatening complications. In contrast, advocates of ultra-rapid detoxification point out that detoxification is a painful procedure, and that the risk of anesthesia has generally been considered acceptable when used to relieve pain. (6)

Given the above considerations, assessment of ultra-rapid opioid detoxification will focus on data reporting the severity and duration of withdrawal symptoms and the short- and long-term outcomes of maintenance of abstinence in distinct populations of patients, based on type and duration of addiction. Efficacy outcomes will be balanced against the safety considerations of deep sedation or general anesthesia in conjunction with naloxone.

The initial MEDLINE search of the published medical literature did not identify any controlled studies that directly compared the outcomes of ultra rapid detoxification with other methods of detoxification. As also noted by two published reviews, the majority of the published literature consists of single institution case series including a variety of patient populations, a variety of protocols, varying in the opioid antagonist used, the dose and mode of administration, the anesthetic agent, duration of anesthesia and adjunct medications used. (7,8) Two randomized trials were identified; however, these studies focused on treatment regimens that varied only in the level of sedation used, and did not include a conventionally treated control group. (9,10)

Regarding severity and duration of withdrawal symptoms, a review conducted by Gowing and colleagues for the Cochrane Library suggests that most patients did experience moderate withdrawal symptoms lasting a few days post anesthesia or sedation, including nausea, vomiting, diarrhea and sleep disturbances. (7) In addition, withdrawal severity may also be related to the anesthetic used. However, without a controlled trial, no conclusion can be made regarding the duration or severity of withdrawal symptoms compared to other techniques of detoxification.

Most of the studies did not report short or long term follow-up of abstinence, and those studies that did include follow up reported conflicting results. For example, Seoane and colleagues reported that 279 of the 300 patients treated were abstinent after one month, (10) while in Cucchia's study of 20 patients, 16 reported some resumption of heroin in the six months following detoxification, with 60% considered to have relapsed. (11) Albanese assessed relapse at six months in 120 patients. Relapse data were available for 111 patients; 55% were relapse free. (12) Again, without controlled studies in similar populations of patients, no conclusions can be drawn about the relative long-term efficacy of ultra-rapid detoxification compared with other treatment strategies.

A variety of adverse events have been reported in small numbers of patients, including vomiting while under anesthesia or sedation, various cardiac rhythm disturbances, pulmonary dysfunction and renal insufficiency. (7) Vomiting under sedation is particularly worrisome due to the threat of aspiration. Techniques reported to minimize this risk include intubation, use of prophylactic antibiotics, and the use of medication to diminish the volume of gastric secretions. Several deaths occurring either during anesthesia or immediately afterward have been reported. (13-16) Also, deaths subsequent to ultra-rapid detoxification have been reported. (17) Of particular concern is the fact that the use of opioid antagonists results in loss of tolerance to opioids, rendering the patients susceptible to overdose if the patient returns to his/her pre-detoxification dosage of illicit drugs. (18)

In 2000 the American Society of Addiction Medicine published a public policy statement regarding opiate detoxification under sedation or anesthesia. (18) This policy statement enumerated a number of positions, with the following two most relevant to this discussion:

"Opioid antagonist agent detoxification under sedation or anesthesia (OADUSA) can be an appropriate withdrawal management intervention for selected patients, provided that such services are performed by adequately trained staff with access to appropriate emergency medical equipment.

Although there is medical literature describing various techniques of OADUSA, more research is needed to better define its role in opioid detoxification. Further studies of outcomes are needed, including both the safety and efficacy of OADUSA as compared to other opioid detoxification modalities, as well as any differential effects on the long term rehabilitation of opioid addicts."

An updated search of the literature through March 25, 2008 returned three new randomized clinical trials. (19, 20, 22) All studies found that rapid detoxification with general anesthesia did not improve treatment retention, overall recidivism, or significantly improve severity of withdrawal symptoms compared to standard detoxification procedures without general anesthesia.

De Jong and colleagues randomized 272 opioid-dependent patients attending methadone clinics to rapid detoxification without anesthesia (RD) or rapid detoxification with general anesthesia (RD-GA). (19) All patients were treated for seven days at an addiction treatment center. The patients randomized to RD-GA received four hours of general anesthesia and the opioid antagonist. They were monitored another four hours and discharged back to the treatment center. Opioid abstinence was monitored in both groups with urinalysis and the intensity of the signs and symptoms of withdrawal during and after treatment was assessed in both groups using subjective and objective measures. One month following rapid detoxification 62.8% of the RD-GA patients and 60.0% of the RD group were abstinent from opioids (p=0.71). No adverse events or complications occurred during RD; however, in the RD-GA group five serious adverse events occurred necessitating hospital admission. According to subjective reports the RD-GA group experienced more craving and withdrawal distress. However, the differences were not significant at one week. The authors also conducted a cost analysis and found that the cost of treatment with general anesthesia was much higher than RD without anesthesia. Because both treatments showed an equivalent efficacy in this study, the authors concluded that rapid detoxification without general anesthesia is the most cost-effective treatment.

Collins and colleagues randomized heroin-addicted patients to three study arms: rapid detoxification with general anesthesia, buprenorphine followed by naltrexone induction beginning on day two, or clonidine plus a variety of supportive medications for one week followed by naltrexone induction beginning day seven. (20) Following discharge all patients were treated with naltrexone for 12-weeks and relapse-prevention psychotherapy. Treatment retention at 12-weeks did not differ significantly across the three groups (20% RD-GA group, 24% buprenorphine group and 9% in the clonidine group). By week three more than 50% of patients had dropped out of each treatment arm. Three patients in the RD-GA group experienced life-threatening events immediately following general anesthesia which included pulmonary edema and aspiration pneumonia in one patient, diabetic ketoacidosis in another, and mixed bipolar episode with suicidal ideation that required hospitalization at five days in one patient. During the outpatient phase, no group differences occurred in number of urine samples positive for opiates. The authors conclude that general anesthesia for rapid detoxification for rapid antagonist induction does not currently have a meaningful role to play in the treatment of opioid dependence.

A randomized trial from a European center reported that the initial improvement in rate of opiate detoxification and abstinence with anesthesia was not maintained with longer-term follow-up. (22) Both cohorts (36 patients treated with anesthesia and 34 with classical clonidine detoxification) showed less than 5% abstinence after 12 months.

In April 2006 a Cochrane Review on heavy sedation or anesthesia for opioid withdrawal concluded that "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." (21)

Summary

The small number of controlled trials and the lack of a standardized approach to ultra-rapid detoxification does not permit scientific conclusions regarding the safety or efficacy of ultra-rapid detoxification compared to other approaches that do not involve deep sedation or general anesthesia.

References

1. BlueCross and BlueShield Association Medical Policy Reference Manual, Policy No. 3.01.02
2. Gooberman LL. Rapid opioid detoxification. JAMA 1998;279(23):1871-2
3. Bovill JG. Opioid detoxification under anesthesia. Eur J Anaesthesiol 2000;17(11):657-61
4. Scherbaum N, Klein S, Kaube H et al. Alternative strategies of opiate detoxification: evaluation of the so-called ultra-rapid detoxification. Pharmacopsychiatry 1998;31(6):205-9
5. Hensel M, Kox WJ. Safety, efficacy and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: a prospective study in methadone, heroin, codeine and morphine addicts. Acta Anaesthesiol Scand 2000;44(3):326-33
6. Brewer C. Opiate detoxification under general anesthesia. BMJ 1998;316(7149):1983-4
7. Gowing L, Ali R, White J. Opioid antagonists under heavy sedation or anesthesia for opioid withdrawal. The Cochrane Library, Issue 2, 2002. Oxford: Update Software
8. O'Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA 1998;279:229-234
9. Kienbaum P, Scherbaum N, Thurauf N et al. Acute detoxification of opioid-addicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic and cardiovascular patterns. Crit Care Med 2000;28(4):969-76
10. Seoane A, Carrasco G, Cabre L et al. Efficacy and safety of two new methods of rapid intravenous detoxification in heroin addicts. Br J Psychiatry. 1997;171;340-345
11. Cucchia AT, Monnat M, Spagnoli J et al. Ultra-rapid opiate detoxification using deep sedation with oral midazolam: short and long-term results. Drug Alcohol Depend 1998;52(3):243-50
12. Albanese AP, Gevirtz C, Oppenheim B et al. Outcome and six-months follow up of patients after Ultra Rapid Opiate Detoxification (UROD). J Addict Dis 2000;19(2):11-28
13. Dyer C. Addict died after rapid opiate detoxification. BMJ 1998;316(7126):170
14. Bearn J, Gossop M, Strang J. Rapid opiate detoxification treatments. Drug Alcohol Rev 1999;18:75-81
15. Solomount JH. Opiate detoxification under anesthesia. JAMA 1997;278(16):1318-9
16. Gold CG, Cullen DJ, Gonzales S et al. Rapid opioid detoxification during general anesthesia: a review of 20 patients. Anesthesiology 1999;91(6):1639-47
17. Brewer C, Laban M, Schmulian et al. Rapid opiate detoxification and naltrexone induction under general anaesthesia and assisted ventilation: experience with 510 patients in four different centres. Acta Psychiatr Belg 1998;98:181-9
18. American Society of Addiction Medicine. Public Policy Statement on Opioid Antagonist Agent Detoxification Under Sedation or Anesthesia (OADUSA). J Addictive Dis 2000;19:109-112
19. De Jong CA, Laheij JF, Krabbe PF. General anesthesia does not improve outcome in opioid antagonist detoxification treatment: a randomized controlled trial. Addiction 2005;100:206-15
20. Collins E, Kleber HD, Whittington RA et al. Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction. JAMA 2005;294:903-13
21. Gowing L, Ali R, White J. Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD002022 Update of: Cochrane Database Syst Rev. 2002;(2):CD002022
22. Favrat B, Zimmermann G, Zullino D et al.  Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychological support: a randomized clinical trial.  Drug Alcohol Depend  2006;81(2):109-16

Cross References

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