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Opioid Antagonists under Heavy Sedation or General Anesthesia as a Technique of Opioid Detoxification

Policy Number: MP-091

Latest Review Date: September 2023

Category: Pharmacology                                                       


The techniques of rapid opioid detoxification (ROD) and ultra-rapid opioid detoxification (UROD) and related services, using opioid antagonists under heavy sedation or anesthesia, are considered investigational.


The use of relatively high doses of opioid antagonists under deep sedation or general anesthesia is a technique for opioid detoxification and is known as ultra-rapid detoxification. It is a potential alternative to standard detoxification that allows individuals to avoid the acute symptoms associated with initial detoxification. Ultra rapid detoxification is used in conjunction with maintenance treatments, e.g., oral opioid antagonists and psychosocial support.

The traditional treatment of opioid addiction involves substituting the opioid, i.e., heroin, with an equivalent close of a long-acting opioid antagonist, i.e., methadone, and tapering to a maintenance dose. Methadone maintenance therapy does not resolve opiate addiction, but along with education and counseling, it has been shown to result in improved general health, retention of individuals in treatment, and a decrease in the risk of transmitting HIV or hepatitis. However, critics of methadone maintenance point out that this strategy substitute’s one drug for 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 individuals on methadone maintenance. Detoxification is associated with acute symptoms, followed by a longer period of protracted symptoms which can last up to six months. Although typically not life threatening, acute detoxification symptoms include anxiety, apprehension, irritability, chills, nausea, diarrhea, coughing, sneezing, lacrimation, rhinorrhea, sweating, yawning, muscular and abdominal pains, general weakness and insomnia. Protracted withdrawal symptoms include changes in pupillary size, autonomic dysfunction, changes in sleep pattern, a general feeling of reduced well-being and drug cravings. 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 naloxone (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 individual support and oral medications are offered, detoxification is associated with discomfort, and many 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.

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 "ultra-rapid," "anesthesia-assisted," or "one-day" detoxification.

A rapid opioid detoxification (ROD) technique is designed to shorten detoxification by precipitating withdrawal through the administration of opioid antagonists such as naloxone hydrochloride or naltrexone in awake individuals. This approach gets individuals through detoxification rapidly to minimize the risk of relapse, and quickly initiate treatment with naltrexone maintenance and psychosocial intervention.

The use of opioid antagonists accelerates the acute phase of detoxification, which can be completed in 24 to 48 hours. Individuals have no discomfort or memory of the symptoms of acute withdrawal. A variety of other medications may be used 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). The procedure is done as an inpatient if general anesthesia is used or possibly as an outpatient if heavy sedation is used. Initial detoxification is followed by ongoing support for the protracted symptoms of withdrawal. In addition, naltrexone may be continued to discourage relapse.

UROD 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 mandatory post detoxification care and follow up. The program may be offered to individuals addicted to opioid or narcotic drugs such as opium, heroin, methadone, morphine, meperidine, hydromorphone, fentanyl, oxycodone, hydrocodone, or butorphanol. Once acute detoxification is complete, the opioid antagonist naltrexone is often continued to decrease drug craving, with the hope of reducing the incidence of relapse.


This policy’s most recent literature review was performed through September 20, 2023. The following information is a summary of the key literature.

Summary of Evidence

The evidence for ultra-rapid detoxification under general anesthesia in individuals with opioid addiction includes both randomized and nonrandomized clinical trials, as well as prospective follow-up studies, which compare other approaches not involving deep or general anesthesia. Relevant outcomes are change in disease status, treatment-related morbidity and mortality, in addition to continued abstinence from opioids or relapse to daily opioid use. There is a paucity of data in the controlled trials and a lack of standardized approach to ultra-rapid detoxification. Additionally, significant adverse effects, including life-threatening complications, are a concern using this treatment. Most patients subsequently return to daily use shortly after this technique. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

National Collaborating Centre for Mental Health

In 2019, National Collaborating Centre for Mental Health, commissioned by the National Institute for Health and Clinical Excellence issued a minor update to clinical practice guidelines on “drug misuse, opioid detoxification.” The guidelines included the following statement regarding ultra-rapid detoxification. “Ultra-rapid detoxification has courted controversy; the main issues with such an approach involve the high degree of risk, including fatalities. This is particularly striking given that opioid withdrawal alone rarely results in death. Furthermore, the associated costs required to give the appropriate medical support are much greater than for other methods of detoxification. There has been much debate over its effectiveness, with limited long-term outcome data available.”

American Psychiatric Association

In 2007, the American Psychiatric Association Work Group on Substance Use disorders released a practice guideline for the treatment of patients with substance use disorders. The practice guideline includes the following recommendation “anesthesia-assisted rapid opioid detoxification (AROD) is not recommended because of lack of proven efficacy and adverse risk-benefit ratios.”

The American Society of Addiction Medicine

In 2015, the American Society of Addiction Medicine published a public policy statement regarding opiate detoxification under sedation or anesthesia (OADUSA) (update of their 2005 statement). It included the following position statements:

  • Opioid withdrawal management using anesthesia ultra-rapid opioid detoxification (UROD) is not recommended because of high risk for adverse events or death.
  • Ultra-Rapid Opioid Detoxification (UROD) is a procedure with uncertain risks and benefits, and its use in clinical settings is not supportable until a clearly positive risk-benefit relationship can be demonstrated. Further research on UROD should be conducted.
  • Although there is medical literature describing various techniques of Rapid Opioid Detoxification (ROD), further research into the physiology and consequences of ROD should be supported so that patients may be directed to the most effective treatment methods and practices.

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force recommendations for opioid detoxification under heavy sedation or general anesthesia have been identified.


Detoxification, opioids, opioid agonist and antagonist, naloxone, naltrexone, buprenorphine, clonidine, methadone, rapid opioid detoxification (ROD), ultra-rapid opioid detoxification (UROD), general anesthesia, opioid antagonist agent detoxification under sedation or anesthesia (OADUSA), one day detox


Not applicable.


Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP: Special benefit consideration may apply. Refer to member’s benefit plan. 


CPT codes:


Unlisted anesthesia procedure


  1. American Society of Addiction Medicine (ASAM). Public policy statement on opioid antagonist agent detoxification under sedation or anesthesia (OADUSA), J Addictive Disease 2000; 19(4): 109-112.
  2. Bearn J, Gossop M, Strang J. Rapid opiate detoxification treatments. Drug Alcohol Rev 1999; 18(1):75-81.
  3. Brewer C, Laban M, Schmulian C 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.
  4. Camarasa X, Khazaal Y, Besson J and Zullino DF. Naltrexone-assisted rapid methadone discontinuation: A pilot study. Eur Addict Res 2007; 13(1): 20-24.
  5. Collins ED, Kleber HD, Whittington RA et al. Anesthesia-assisted vs buprenorphine- or clonidine-assisted heroin detoxification and naltrexone induction: a randomized trial. JAMA 2005; 294(8):903-13.
  6. Dyer C. Addict died after rapid opiate detoxification. BMJ 1998; 316(7126):170.
  7. 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 randomised clinical trial. Drug Alcohol Depend, February 2006; 81(2): 109-116.
  8. Forozeshfard M, Hosseinzadeh Zoroufchi B, Saberi Zafarghandi MB, et al. Six-month follow-up study of ultra-rapid opiate detoxification with naltrexone. Int J High Risk Behav Addict. Dec 2014;3(4):e20944.
  9. 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.
  10. Gowing L, Ali R, White J. Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal. Cochrane Database Syst Rev 2010; (1):CD002022.
  11. Hensel, M., Kox, W.J. Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anesthesia: A prospective study in methadone, heroin, codeine, and morphine addicts, Octa Anesthesiology Scandinavia, March 2000; 44 (3), pp. 326-33.
  12. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  13. Kampman K, Jarvis M. American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med. 2015 Sep-Oct;9(5):358-67.
  14. 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.
  15. Kleber HD, Weiss RD, Anton RF, et al. Treatment of patients with substance use disorders, second edition. American Psychiatric [sic] Association. Am J Psychiatry, August 2006; 163 (8 Suppl): 5-82.
  16. Krambeer, Ll., von McKnelly Jr., W., et al. Methadone therapy for opioid dependence, American Family Physician, June 15, 2001; 63(12): 2404-10.
  17. Nasr DA, Omran HA, Hakim SM et al. Ultra-rapid opiate detoxification using dexmedetomidine under general anesthesia. J Opioid Manag 2011; 7(5):337-44.
  18. National Institute for Health and Clinical Evidence. Drug misuse, opioid detoxification. NICE Clinical Guideline 52. Available at 
  19. O’Connor, Patrick G., Kosten, Thomas R. Review: Rapid and ultra-rapid opioid detoxification techniques, JAMA, January 21, 1998, Vol. 279, No. 3, pp. 229-234.
  20. Qiu YW, Jiang GH, Su HH, et al. Short-term UROD treatment on cerebral function in codeine-containing cough syrups dependent male individuals. Eur Radiol. 2016; 26(9):2964-2973.
  21. Salimi A, Safari F, Mohajerani SA, et al. Long-term relapse of ultra-rapid opioid detoxification. J Addict Dis. 2014;33(1):33-40.
  22. Saxon AJ, McCance-Katz EF. Some Additional Considerations Regarding the American Society of Addiction Medicine National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. J Addict Med. 2016 May-Jun;10(3):140-2.
  23. Scherbaum, N., Klein, S., and Kaube, H. Alternative strategies of opiate detoxification: Evaluation of the so-called ultra-rapid detoxification, Pharmacopsychiatry, November 1998; 31(6), pp. 205-9.
  24. 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(October):340-5.
  25. Sevarino K, Saxon A, Friedman M. Medically supervised opioid withdrawal during treatment for addiction. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed April 12, 2022. 
  26. Solomont JH. Opiate detoxification under anesthesia. JAMA 1997; 278(16):1318-9.


Medical Policy Group, January 2003 (3)

Medical Policy Administration Committee, January 2003

Available for comment February 19-April 7, 2003

Medical Policy Group, March 2006 (3)

Medical Policy Administration Committee, March 2006

Available for comment March 14-April 27, 2006

Key Points updated, references updated March 2008 (1)

Medical Policy Group, March 2010 (1): Key points updated, references added

Medical Policy Group, January 2011 Key points updated, references added

Medical Policy Group, March 2012 (3): 2012 Literature review, References updated

Medical Policy Panel, December 2012.

Medical Policy Group, December 2012 (3): 2012 Literature review. References updated.  Policy statement remains unchanged.

Medical Policy Group, October 2013 (3): Removed ICD-9 Diagnosis codes; no change to policy statement.

Medical Policy Panel, December 2013

Medical Policy Group, January 2014 (3): 2013 Updates to Key Points and References; no change in policy statement

Medical Policy Panel, December 2014

Medical Policy Group, January 2015 (3): 2014 Updates to Key Points and References; no change in policy statement

Medical Policy Panel, January 2016

Medical Policy Group, January 2016 (3): Updates to Description, Key Points and References. No change to policy statement. As of January 28, 2016: Active policy but no longer scheduled for regular updates.

Medical Policy Group, July 2019 (3): 2019 Updates to Key Points. A peer reviewed literature analysis was completed and no new information was identified that would alter the coverage statement of this policy.

Medical Policy Group, August 2021 (3): 2021 Updates to Key Points, Practice Guidelines and Position Statements, and References. A peer reviewed literature analysis was completed and no new information was identified that would alter the coverage statement of this policy.

Medical Policy Group, September 2022 (3): 2022 Updates to Key Points, Practice Guidelines and Position Statements, and Key Words: added UROD, ROD. Reviewed by consensus. References added. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, September 2023 (11): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy.  Updates to Key Points, Benefit Application and References. Policy Statement updated to remove the word “patient” and replace it with the word “individual”. No change to policy intent.

 This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.


This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.


Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.