Dissatisfaction with current approaches to detoxification has led to interest in using relatively high doses of opioid antagonists, such as naltrexone, naloxene or nalmefene, under deep sedation with benzodiazepine or general anesthesia. This strategy has been referred to as "ultra-rapid," "anesthesia-assisted" or "one-day" detoxification. The use of opioid antagonists accelerates the acute phase of detoxification, which can be completed within 24-48 hours. Since the individual is under anesthesia, he/she has no discomfort or memory of the symptoms of acute withdrawal. Various other drugs are also administered to control acute withdrawal symptoms, such as clonidine (to attenuate sympathetic and hemodynamic effects of withdrawal), ondansetron (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.

Investigational/Not Medically Necessary:

Opioid antagonists under heavy sedation or general anesthesia, as a technique of opioid detoxification, are considered investigational/not medically necessary.
 

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 number 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 an important outcome (Bovill, 2000; Gooberman, 1998).  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 individuals may drop out of traditional inpatient detoxification programs (Scherbaum, 1998). 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, individuals 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-fast detoxification may be offered to individuals on methadone maintenance, in a final effort to render these individuals 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 (Hensel, 2000).

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 (Brewer, 1998).

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.

Reported Data
A search of the peer-reviewed literature did not identify any 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 and 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 (Gowing, 2002; O’Connor, 1998).  Two randomized studies 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 (Kienbaum, 2000; Seoane, 1997).

Regarding severity and duration of withdrawal symptoms, Gowing's review (2002) suggests that most patients experienced moderate withdrawal symptoms lasting a few days post-anesthesia or sedation, including nausea, vomiting, diarrhea, and sleep disturbances.   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 have reported conflicting results.  For example, Seoane and colleagues (1997) reported that 279 of the 300 patients treated were abstinent after one month, 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 (Cucchia, 1998).  Albanese assessed relapse at six months in 120 patients. Relapse data was available for 111 patients; 55% were relapse free (Albanese, 2000). 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 rhythmic disturbances, pulmonary dysfunction, and renal insufficiency (Gowing, 2002). 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 (Bearn, 2000; Dyer, 1998; Gold, 1999; Solomont, 1997). In addition, deaths subsequent to ultra-rapid detoxification have been reported (Brewer, 1998).  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 (O’Connor, 1998).

In a trial by Collins and colleagues (2005), 106 heroin addicts were randomized to undergo detoxification with an anesthesia-assisted rapid opioid detoxification, buprenorhine-assisted rapid opioid detoxification, or clonidine-assisted opioid detoxification. All patients received an additional 12 weeks of outpatient naltrexone maintenance. Mean withdrawal severities were similar among the three groups, and treatment retention in the 12-week follow-up period was similar. However, the anesthesia procedure was associated with three potentially significant life-threatening adverse events. The authors concluded that the data did not support the use of general anesthesia for heroin detoxification. Recently, a randomized trial from a European center reported that the initial improvement in the rate of opiate detoxification and abstinence (three months) with anesthesia was not maintained with long-term follow-up; both groups (36 patients treated with anesthesia and 34 with classical clonidine detoxification) showed less than 5% abstinence after 12 months (Favrat, 2006). In addition, 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 anesthesia is not supported” (Gowing, 2006).

In summary, the lack of controlled trials and the lack of a standardized approach to ultra-rapid detoxification do 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.

The traditional treatment of opioid addiction involves substituting the opiate (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 is a substitution of 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 patients 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 buprenophrine (an opioid agonist-antagonist), treatment with a combination of buprenophrine and naloxene (an opioid antagonist), 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, and many patients may be unwilling to attempt detoxification.  In addition, detoxification is only the first stage of treatment. Without ongoing medication and psychosocial support after detoxification, the probability is low that any detoxification procedure alone will result in lasting abstinence.  Opioid antagonists, such as naltrexone, may also be used as maintenance therapy to reduce drug craving and thus reduce the risk of relapse.

Ultra-rapid detoxification may be offered by specialized facilities such as Neuraad™ Treatment Centers, Nutmeg Intensive Rehabilitation, and Center for Research and Treatment of Addiction (CITA).  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 reducing the incidence of relapse.

Buprenorphine: a partial opioid agonist and potent antagonist, buprenorphine is a potent analgesic that can be administered once a day to block withdrawal symptoms

Detoxification: a short-term approach designed to help selected individuals achieve a drug-free state

Naltrexone: a derivative of naloxone, approved by the FDA in 1984, an opioid antagonist used for maintenance treatment of opioid dependence

Opioids: meaning opiate like, derivatives of opium; all opioids can produce euphoria, can be used as analgesics, and are the most powerful known pain relievers

Opioids can be classified as the following: 

• Naturally occurring opium derivatives - morphine, codeine 
• Partially synthetic derivatives of morphine - heroin, oxycodone, oxymorphone 
• Synthetic compounds - fentanyl, alffentanil, levorphanol, meperidine, methadone, propoxyphene

Opioid antagonists: agents which block opioid effects, thereby eliminating opioid-induced euphoria, diminishing the reinforcing effects of heroin, and potentially extinguishing the association between conditioned stimuli and opioid use; opioid antagonists offer the advantage of treatment with medications that have no addictive potential or tolerance

Opioid maintenance agonists: long-acting noneuphorigenic opioids with relative steady-state pharmacokinetics are used to replace heroin, a short-acting, euphorigenic opioid is characterized by rapidly changing serum levels

The following codes for treatments and procedures applicable to this policy are included below for informational purposes Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Services are Investigational/Not Medically Necessary:
When the code describes a procedure indicated in the Policy section as investigational/not medically necessary.

CPT

ICD-9 Diagnosis

Peer Reviewed Publications:

1. 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. 
2. Bearn J, Gossop M, Strang J. Rapid opiate detoxification treatments. Drug Alcohol Rev. 1999; 18(1):75-81.
3. Bovill JG. Opioid detoxification under anesthesia. Eur J Anaesthesiol. 2000; 17(11):657-661.
4. 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; 98:181-189.
5. Brewer C. Opiate detoxification under anesthesia. BMJ. 1998; 316(7149):1983-1984.
6. Collins ED, Kleber HD, Whittington RA, Heitler NE. Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: a randomized trial. JAMA. 2005; 294(8):903-913.
7. 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):243-250.
8. Day E, Ison J, Strang J. Inpatient versus other settings for detoxification for opioid dependence. Cochrane Database Syst Rev. 2005; (2):CD004580. 
9. Dyer C. Addict died after rapid opiate detoxification. BMJ. 1998; 316(7126):170.
10. Favrat B, Zimmerman G, Zullino D, et al. Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomized clinical trial. Drug Alcohol Depend. 2006. 81(2):109-116.
11. Fiellin DA, O'Conner PG. Office-based treatment of opioid-dependent patients. NEJM. 2002; 347(11):817-823.
12. Gold CG, Cullen DJ, Gonzales S, et al. Rapid opioid detoxification during general anesthesia: a review of 20 patients. Anesthesiology. 1999; 91(6):1639-1647.
13. Gooberman LL. Rapid opioid detoxification. JAMA. 1998; 279(23):1871-1872.
14. 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. 
15. 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):326-333.
16. 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):969-976.
17. O’Connor PG, Kosten TR. Rapid and ultrarapid opioid detoxification techniques. JAMA. 1998; 279(3):229-234.
18. 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):205-209.
19. Seoane A, Carrasco G, Cabre L, et al. Efficacy and safety of two new methods of rapid intravenous detoxification in heroin addicts previously treated without success. Br J Psychiatry. 1997; 171:340-345.
20. Solomont JH. Opiate detoxification under anesthesia. JAMA. 1997; 278(16):1318-1319.
21. Teplin D, Raz B, Daiter J, et al. Measurement of symptom withdrawal severity in a 24-hour period after the anesthesia-assisted rapid opiate detoxification procedure. Am J Drug Alcohol Abuse. 2005; 31(2):327-335.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Society of Addiction Medicine. Public policy statement on opioid antagonist agent under sedation or anesthesia (OADUSA). J Addict Dis. 2000; 19(4):109-112.
2. Centers for Medicare and Medicaid Services (CMS). National Coverage Determination for Treatment of Drug Abuse (Chemical Dependency). NCD #130.6. Effective date not posted.  Available at:  http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd.  Accessed on March 23, 2007.

1. American Society of Addiction Medicine. Available at:  http://www.asam.org/.  Accessed on March 23, 2007.
2. American Society of Addiction Medicine. Public policy statement on rapid and ultra rapid opioid detoxification. April 2000. Revised April 2005. Available at:  http://www.asam.org/. Assessed on March 23, 2007.   
3. Substance Abuse and Mental Health Services Administration (SAMHSA).  Available at:  http://alt.samhsa.gov/about/background.htm. Accessed on March 23, 2007.
4. Substance Abuse and Mental Health Services Administration (SAMHSA). Office of Applied Studies. Results from the 2005 National Survey on Drug Use and Health: National Findings.  Available at:  http://www.drugabusestatistics.samhsa.gov/nsduh/2k5nsduh/2k5Results.pdf.  Accessed on March 23, 2007.

Anesthesia Assisted Detoxification
Opioid Detoxification, Opioid Antagonists
Rapid Detox
Ultra-Rapid Detoxification

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