Anesthesia-Assisted Rapid Opioid Detoxification

By Lori Karan, MD, FASAM and Judith Martin, MD

[Note: Early this year, Blue Shield Health Plan asked the California Society of Addiction Medicine to participate in a expert advisory panel to assess the safety and efficacy of Anesthesia-Assisted Rapid Opioid Detoxification (AAROD).  CSAM’s Executive Council appointed two of its members Lori Karan, MD and Judith Martin, MD to represent CSAM as experts on the panel.  CSAM’s participation  is seen as part of a larger effort to influence managed care on the appropriate treatment of addiction.  This is the text of a paper prepared by Drs. Karan and Martin for their presentation to the panel.]

Thank you for the opportunity to comment upon the role of Anesthesia-Assisted Rapid Opioid Detoxification (AAROD) in addiction medicine. The mission of the California Society of Addiction Medicine is to improve the treatment of alcoholism and other addictions, educate physicians and medical students, promote research and prevention, and enlighten and inform the medical community and the public about these issues.  The following opinion was developed based on comments from the Committee on the Treatment of Opioid Dependence, and the Executive Council of CSAM.

CSAM aligns itself with the NIH consensus statement of 1997, which defines heroin addiction as a chronic disease.1For any patient who has been addicted for at least a year, and who wishes such treatment, methadone maintenance represents the standard of care. Methadone maintenance has been shown to lower mortality, lower criminality, enhance functionality, and to reduce the incidence of seroconversion to HIV.2-4

Patients who decide not to engage in maintenance pharmacotherapy face decisions on how to withdraw from the opioid to which they are addicted. Since naturally occurring withdrawal from opioids is not in itself life-threatening, some patients withdraw with no treatment at all.  Other patients choose to be treated symptomatically with agents such as clonidine.  When more severe symptoms are anticipated, patients may choose to undergo a gradual withdrawal in an inpatient or outpatient licensed opioid treatment program.  The most common approach during medically supervised withdrawal is to utilize a progressive taper of a long acting opiate, such as methadone. Although safe, these standard forms of detoxification, even when enriched with psychosocial services, do not usually result in long-term abstinence, and relapse rates are high.5, 6

Kleber et al. developed rapid opioid detoxification (ROD) in the 1980’s to reduce patients’ length of hospitalization and to facilitate their placement upon naltrexone, an opioid antagonist.7-9During rapid opioid detoxification without anesthesia, patients receive graduated doses of antagonist (naltrexone) to precipitate withdrawal while they are simultaneously given clonidine and other symptomatic treatments.  Rapid opioid detoxification without anesthesia is more gradual and less risky than anesthesia assisted rapid opioid detoxification.  Patients are awake and able to tell the treating physician what they are feeling as they undergo withdrawal.  However, even though this procedure has been developed and researched, it has not received wide acceptance by addiction medicine practitioners or their patients.  Although the reasons for this lack of acceptance have not been well studied, it is likely that patients do not opt for experiencing an increased intensity of symptoms during withdrawal.  Rapid opioid detoxification without anesthesia has limited use with persons who are extremely motivated for abstinence, those who need to attain abstinence rapidly due to external factors, those who are not anticipating a severe withdrawal, and those who want to facilitate being placed upon a chronic antagonist, such as naltrexone.

Abruptly precipitating withdrawal produces more severe symptoms, including hypertension, tachycardia, vomiting and diarrhea.10Anesthesia-assisted opiate detoxification (sometimes called Ultra Rapid Opioid Detoxification) uses antagonists to precipitate withdrawal, with the patient heavily sedated.11Some protocols also call for ECG monitoring and pretreatment with clonidine to control the cardiac effects of precipitated withdrawal, or post-procedure treatment with antiemetics for days to weeks.12, 13In addition, most protocols include ongoing antagonist after the acute procedure.

Anesthesia assisted rapid opiate detoxification appeals to patients who want a ‘magic bullet’ to treat their addiction.  Patients do not wish to feel the pain of withdrawal.  Rather they want to go to sleep and ‘wake up clean.’  Too often, treatment providers marketing AAROD play into their patient’s unrealistic expectations.  Although anesthesia may prevent a person undergoing precipitated withdrawal from being conscious of the most intense withdrawal symptoms, the duration of the withdrawal process has not been completely studied.  Patients often have severe symptoms for several days after the procedure.  The duration of the withdrawal is not known because patients are often given multiple medications for several weeks that mask their symptoms.  Neuroscience does not support instantaneous neuroadaptation when an antagonist suddenly occupies a receptor.14Rather, intracellular pathways and their gene regulation are affected, as well as multiple brain circuits and body systems.  Thus, there is no reason to believe that a patient’s withdrawal is complete when they wake up from anesthesia.15, 16

Anesthesia assisted rapid opiate detoxification is not a standardized procedure.  Multiple variables include the timing of the last dose of opiate, the anesthetic agents utilized, the level sedation and of respiratory support, the antagonist or combinations thereof (i.e., narcan, naltrexone, and/or nalmefene), the doses and route of delivery of the antagonist(s) (NG tube versus IV), the duration of the procedure, and the intensity of monitoring thereafter.  These variables may each affect the safety and efficacy of the AAROD.

There are reasons for concern about patient safety.  For instance, Keinbaum et al. noted profound epinephrine release and cardiovascular stimulation during AAROD.17There are reports of QT prolongation,18tachypnea,19increased metabolism and muscle activity,20and death.13Patients who undergo AAROD may need to be carefully selected to include only healthy persons without major comorbidity.  As with other procedures under anesthesia, careful preoperative clearance is needed.

Anesthesia assisted rapid opiate detoxification has not been shown to be any better at preventing relapse than the already existing outpatient detoxifications that do not call for precipitated withdrawal or anesthesia.21, 22Clinicians in the field comment that patients who are doing well on methadone are sometimes targeted for this procedure, and subsequently relapse, losing hard-earned clinic take-home privileges or jobs, in addition to the money for the procedure.23

Therefore, when discussing the modalities which facilitate opiate withdrawal CSAM endorses a limited role for rapid opioid detoxification (without anesthesia).  CSAM, however, does not support the routine use of Anesthesia Assisted Opioid Detoxification. AAROD may have a role in helping persons enter and engage into opioid anagonist maintenance, or non-opioid based treatment.  However, until its safety and efficacy have been proven, and the procedure has been standardized, AAROD should only be used under research conditions with careful informed consent, monitoring, and treatment evaluation. Two components of this procedure, precipitated withdrawal and anesthesia, are known to have risks that are not present in the more commonly used detoxification and withdrawal treatments. Any benefits of the procedure have not yet been shown to be worth these added risks.

However, focusing our discussion upon facilitating alternative methods of opiate detoxification is in many ways misleading. No matter the method of detoxification, and no matter the criteria for patient selection for detoxification, poor long-term outcomes ( 40-60% relapse by six months, approaching 90% by 12 months) suggest a chronic disease  - perhaps a long lasting abstinence syndrome -  that is not being addressed by detoxification of any kind.5, 6, 21, 24, 25The excellent outcomes of methadone maintenance and the poor outcomes of opiate abstinence raise questions about the role of detoxification for the treatment for opiate addicted patients.  If an analogy were to be drawn with other chronic illnesses5, one might question supporting the withdrawal of blood pressure medications from patients who are hypertensive and the taking away insulin from patients who are diabetic.

All too often CSAM physicians see their patients work towards a false goal of medication-free abstinence that is reinforced by societal prejudice and a system of reimbursement that pays for detoxification but not maintenance.  When patients risk relapse back to illicit opiates, they jeopardize relationships with the ones they love.  Patients who relapse back to opiate addiction endanger their jobs, threaten their quality of life, and most importantly, imperil their health.  The risks of relapse are especially dangerous amidst the current HIV and hepatitis C epidemics

Methadone maintenance is a treatment for opiate addiction that is safe, efficacious, and well-studied.  Patients stabilized on methadone maintenance reach a new homeostatic set point that enables them to function maximally.  It is the hope of members of the California Society of Addiction Medicine that Blue Shield of California and United Behavioral Health Systems will utilize their technology assessment system to review methadone maintenance and consider this important treatment for future reimbursement.  Although it might seem an obvious benefit, most private insurers do not provide for methadone maintenance treatment.  If Blue Shield of California takes on this examination, it will lead the country in this most important endeavor.

REFERENCES

1.         NIH Consensus Statement. Effective Medical Treatment of Opiate Addiction. Rockville, Maryland: National Institutes of Health; 1997. p. 1-38.

2.         Novick DM, Salsitz EA, Kalin MF, Keefe JB, Miller EL, Richman BL. Outcomes of treatment of socially rehabilitated methadone maintenance patients in physician's offices (medical maintenance): Follow-up at three and a half to nine and a fourth years. Journal of General Internal Medicine 1994;9:127-30.

3.         Ball J, Ross A. The Effectiveness of Methadone Maintenance Treatment. New York: Springer-Verlag; 1991.

4.         Appel PW, Joseph H, Kott A, Nottingham W, Tasiny E, Habel E. Selected In-Treatment Outcomes of Long-Term Methadone Maintenance Treatment Patients in New York State. The Mount Sinai Journal of Medicine 2001;68(1):55-61.

5.         Ball JC, Lange WR, Myers CP, Friedman SR. Reducing the risk of AIDS through methadone maintenance treatment. Journal of Health and Social Behavior 1988;29(September):214-26.

6.         Sees KL, Delucchi KL, Masson C, Rosen A, Clark HW, Robillard H, et al. Methadone Maintenance vs 180-Day Psychosocially Enriched Detoxification for Treatment of Opioid Dependence. JAMA 2000;283(10):1303-10.

7.         Vining E, Kosten TR, Kleber HD. Clinical Utility of rapid clonidine-naltrexone detoxification for opioid abusers. Br. J. Addict. 1988;83(5):567-75.

8.         Riordan CE, Kleber HD. Rapid Opiate Detoxification with Clonidine and Naloxone. The Lancet 1980;8177(1):1079-80.

9.         Kosten TR, Krystal JH, Charney DS, Price LH, Morgan CH, Kleber HD. Rapid Detoxification from Opioid Dependence. Am. J. Psychiatry 1989;146(10):1349.

10.       Kienbaum P, Thurauf N, Michel MC, Scherbaum N, Gastpar M, Peters J. Profound Increase in Epinephrine Concentration in Plasma and Cardiovascular Stimulation after mu-Opioid Receptor Blockade in Opioid-addicted Patients during Barbiturate-induced Anesthesia for Acute Detoxification. Anesthesiology 1998;88(5):1154-61.

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12.       Tretter F, Burkhardt D, Bussello-Spieth B, Reiss J, Walcher S, Buchele W. Clinical Experience with Antagonist-induced opiate withdrawal under anesthesia. Addiction 1998;93(2):269-75.

13.       Gold CG, cullen DJ, Gaonzales S, Houtmeyers D, Dwyer MJ. Rapid Opioid Detoxification during General Anesthesia: a Review of 20 Patients. Anesthesia 1999;91(6):1639-47.

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15.       Spanagel R, Kirschke C, Tretter F, Holsboer F. Forced opiate withdrawal under anaesthesia augments and prolongs the occurrence of withdrawal signs in rats. Drug and Alcohol Dependence 1998;52:251-56.

16.       McDonald T, Berkowitz R, Hoffman WE. Plasma Naltrexone During Opioid Detoxification. Journal of Addictive Diseases 2000;19(4):59-64.

17.       Keinbaum P, Thurauf N, Michel MC, Scherbaum N, Gastpar M, Peters J. Profound Increase in Epinephrine Concentration in Plasma and Cardiovascular Stilmulation after mu-Opioid Receptor Blockade in Opioid-addicted Patients during Barbiturate-induced Anesthesia for Acute Detoxification. Anesthesiology 1998;88(5):1154-61.

18.       Allhof T, Renzig-Kohler K, Keinbaum P, Sack S, Scherbaum N. Electrocardiographic abnormalities during recovery from ultra-short opiate detoxification. Addiction Biology 1999;4:337-44.

19.       Elman I, D'Ambra MN, Krause S, Breiter H, Kane M, Morris R, et al. Ultrarapid opioid detoxification: effects on cardiopulmonary physiology, stress hromones and clinical outcomes. Drug and Alcohol Dependence 2001;61(2):163-72.

20.       Hoffman WE, Berkowitz R, McDonald T, Hass F. Ultra-rapid opioid detoxification increases spontaneous ventilation. Journal of Clinical Anesthesia 1998;10(5):372-76.

21.       Albanese AP, Gevirtz C, Oppenheim B, Field JM, Abels I, Eustace JC. Outcome and Six Month Follow Up of Patients After ultra Rapid Opiate Detoxification (UROD sm). J. Addictive Diseases 2000;19(2):11-28.

22.       Bell JR, Young MR, Masterman SC, Morris A, Mattick RP, Bammer G. A pilot study of naltrexone-accelerated detoxification in opioid dependence. MJA 1999;171:26-30.

23.       Advertisement RAOD. "First it was heroin, then I got stuck on methadone. Yesterday, I woke up drug free and ready for a new start.". SF Chronicle; 2002.

24.       Hser Y-I, Hoffman V, Grella C, Anglin MD. A 33-year follow-up of narcotics addicts. Archives of General Psychiatry 2001;58:503-08.

25.       Magura S, Rosenblum A. Leaving Methadone Treatment: Lessons Learned, Lessons Forgotten, Lessons Ignored. The Mount Sinai Journal of Medicine 2001;68(1):62-74.