Ultra-Rapid Opioid Detoxification

Anisa Moore, Medical Student, University of Colorado Health Sciences Center

What is ultra-rapid opioid detoxification? 

Ultra-rapid opioid detoxification (UROD) is swiftly gaining popularity in the United States and Europe because of the relapse problems associated with more traditional methods.  As anyone with a severe opiate addiction can attest, going ìcold turkeyî can be both agonizing and dangerous, because the intensity of withdrawal symptoms is much worse when the opiate is abruptly removed from the body.  On the other hand, gradual withdrawal programsóusually involving pharmacological agents like methadone and LAAMóreduce the severity of symptoms, but they also increase both the length of time that a person is dependent on drugs and the temptation to relapse.  UROD tries to combine the best of both worlds: the quickness of the ìcold turkeyî approach with the relative painlessness of the gradual approach.  The concept involved is fairly simple.  A patient is placed under general anesthesia and given an opiate antagonist to accelerate the withdrawal.  An opiate antagonist is a drug like naloxone hydrochloride or naltrexone hydrochloride that prevents heroin or another opioid from binding to the bodyís receptors, effectively neutralizing the heroinís impact on the central nervous system (Stephenson, 1997a).  The worst of the withdrawal occurs while the patient is unconscious, and so, when he or she awakens, the physical craving for opiates is gone. 

What are the long-term consequences of opiate addiction that may justify UROD? 

The long-term consequences of untreated opiate addiction are severe and frequently fatal.  So, even if UROD is somewhat risky, many patients (especially those who are not on a maintenance treatment like methadone or LAAM) feel they have little to lose by trying it.  Once persistent opioid use has been established, at least 25 percent of abusers are likely to die within 10 to 20 years of active abuse, with death from suicide, homicide, accidents, and infectious diseases such as tuberculosis or serum hepatitis particularly common (Wilson, 1991).  More recently, the mortality rate has increased drastically due to the AIDS epidemic among IV drug users (Wilson, 1991).  Furthermore, heroin users run the risk of being poisoned by impurities like strychnine and quinine.  Street heroin, for example, contains only ì5 to 10 percentî of the opioid, with the remainder typically composed of lactose and fruit sugars, quinine, powdered milk, phenacetin, caffeine, antipyrine, and strychnine (Wilson, 1991).  In addition to the risks associated with using impure drugs, there is always the risk of overdose, which may lead to dangerous complications like shallow respirations, pupillary miosis [pinpoint pupils], bradycardia [a slow heart rate], a decrease in body temperature, and a general absence of responsiveness to external stimulation (Wilson, 1991).  If this medical emergency is not treated rapidly, death can occur in a matter of minutes from respiratory depression and cardiac arrest (Wilson, 1991).  Moreover, street addicts tend to develop compromised health because of poor nutrition and living conditions.  Middle-class users, while insulated from homelessness, crime, and hypothermia, still risk the loss of their jobs, loved ones, and financial standing, if they are not appropriately treated.  If UROD gives them a high chance of recovery, many are willing to accept whatever risks and costs are associated with it in the hope of a drug-free life.                            

What are some of the pros and cons regarding UROD? 

UROD sounds idealóit appears to be the medical ìcureî that many addicts and their families have been seeking.  Its proponents tout success rates that greatly exceed those claimed by practitioners of other treatments.  Some individuals who are being effectively treated for their heroin addition with more traditional maintenance treatments, such as methadone or LAAM, may be ìluredî away from a treatment that works well for them by the temptation to be ìcuredî or free of drugs forever. Nevertheless, there are many factors that undermine URODís promise as a ìmiracle cureî that any ethical and objective consideration of UROD must take into account.  To begin with, the numbers cited by UROD practitioners may be skewed by a variety of factors, including the patientís overall physical health, financial resources, and social support.  Medically, there are the inherent risks associated with general anesthesia, such as pulmonary edema and cardiac arrest, both of which, while rare, can be life-threatening.  Moreover, if patients relapse after UROD, the dose of heroin is more likely to be fatal because their tolerance has decreased.  UROD is also not appropriate for a patient with any complicating factors, such as liver failure or alcohol abuse.  In addition to the medical issues, there are a number of concerns regarding the practitioners and the accessibility of UROD.  There is no standard of care or national licensing of providers, so the quality of care and follow-up can vary considerably, depending on the individual providerís training and ethics.  Furthermore, the procedure is not widely available, it typically costs several thousand dollars, and insurance may not cover the expense.  To compound matters, there are very few studies that examine the long-term recovery rates of UROD compared with other treatment approaches.  The studies available typically involve small samples, so very little data is available to support the safety and efficacy of UROD.  To some, however, the benefits of UROD may outweigh these concerns.  Given the high morbidity and mortality associated with untreated opiate addiction and the frequent concomitant use of needles, the prospect of a quick, relatively painless detoxification may justify the risks associated with UROD. 

How successful is UROD? 

The recovery rates that UROD advocates claim are extremely highóperhaps unrealistically so.  The Center for the Investigation and Treatment of Addiction (CITA), a Spanish-Israeli organization with several centers in the United States, guarantees prospective patients a 100% effective rapid acute detoxification.  More important, however, are the long-term outcome data.  An Israeli group of researchers claimed an 80% abstinence rate six months after the procedure, a claim that was not substantiated by urine samples but was considered to be credible by consultants for the National Institute on Drug Abuse (Herman, 1996).  Another group of researchers who detoxified patients with naltrexone, but without anesthesia, claimed an 80% success rate after six months, as evidenced by urine testing (Simon, 1997).  Most recently, CITA reported a 55% long-term abstinence rate (CITA, 1998).  Conventional detoxification treatments, in contrast, average a success rate of approximately 20% to 30% (Stephenson, 1997a).  Thus, the much higher reported recovery rates of UROD patients, combined with the painless nature of the procedure, is naturally appealing.   

Do recovery rates tell the whole story? 

Unfortunately, these statistics may not be an accurate reflection of URODís efficacy.  Patients with multiple addictions or physical complications are not typically candidates for general anesthesia.  In addition, because the procedure is expensive and frequently not covered by insurance, patients who can pay for the procedure are more likely to have better finances, motivation, and social support.  As a consequence, it would be reasonable to expect better outcomes from those patients than from a more representative cross section of opiate addicts (Stephenson, 1997a).  Comparing the abstinence rates of UROD versus other treatments, therefore, may be unfair.  As a result, critics argue that the statistics reflect more on the patient selection than on the procedureís efficacy (Brewer, 1997).  Such concerns may be legitimate, since URODís success rate would certainly be lower if the procedure were available to higher-risk or less motivated addicts, and large, randomized clinical trials comparing UROD with other procedures have not yet been performed to support or refute URODís comparative effectiveness. 

What medical risks are associated with UROD? 

The fact that UROD is limited to patients without complicating factors emphasizes the inherent risks of undergoing general anesthesia.  Certainly young people are not likely to have surgical complications while under general anesthesia (Gevirtz, 1998).  Nevertheless, the risks of the accelerated withdrawal cannot be discounted.  As Anthony Tommasello, MS and director of substance abuse studies at the University of Maryland School of Pharmacy, observes, ìAnesthetizing someone and then putting them through a precipitated narcotic withdrawal with an antagonist such as naloxone is inherently somewhat risky from a pharmacological point of viewî (Stephenson, 1997a).  More specifically, studies have found a small, but significant, incidence of cardiac arrest and pulmonary edema in anesthetized patients given naloxone (Stephenson, 1997a).  Although these cardiovascular complications may be rare, their potentially fatal outcomes justify concern. 

What happens if a patient relapses after UROD? 

The possibility of overdose in the event of a relapse after UROD presents an even higher risk of death than general anesthesia.  If addicts who undergo UROD relapse, they will probably take the dose of heroin their drug-tolerant bodies required before the procedure; after the procedure, their bodies are no longer tolerant to the drug, so it is easier for them to overdose.  The biochemical process appears to involve the regulation of mu receptors in the locus coeruleus (LC), a part of the brain which secretes norepinephrine into the body (Simon, 1997).  When the body has a high dose of an opioid drug, these receptors become less sensitive (downregulation) to the drugís effects, leading to an increase in tolerance (Simon, 1997).  UROD, however, completely blocks the mu receptors, removing the opioid from them, and they become more sensitive (upregulation) to the drug.  As a result, some practitioners recommend warning patients to take smaller amounts of opioid if they should relapse after the procedure to prevent overdose (Simon, 1997).  

Who is a good candidate for UROD?  

The risks of general anesthesia and overdose are some of the medical complications, but there are some candidacy problems with UROD as well.  UROD is recommended only for patients with uncomplicated opioid addiction.  The Norfolk Mental Health Center, for example, recommends the exclusion of patients who may be withdrawing hazardously from other drugs, especially benzodiazepines and alcohol; patients regularly using large amounts of opiates or illicit drugs which cannot be quantified; and patients with serious physical disorders or a lack of venous access (Rumball and Williams, 1997).  So there are several factors which would exclude candidates for UROD.  Given the poor health and multiple chemical dependencies that frequently plague addicts, those criteria would exclude most addicts except those few who are addicted only to opiates and otherwise in good health.     

Is there a standard of care established for UROD? 

Unfortunately, the quality of care varies widely because there is no standard of care or certification necessary for UROD.  Depending on the facility, a patient undergoing UROD might be placed under anesthesia by either an anesthesiologist or a psychiatrist, the former being obviously better equipped to address cardiopulmonary complications.  As a result, life-threatening complications have been reported because providers who are not trained in anesthesiology place their patients in a state of deep sedation without the proper precautionsónamely, endotracheal intubationóto protect the patientís airway.  As recently as 1995, for example, a patientís heart rate and oxygen saturation (the amount of oxygen circulating in his blood) dropped drastically in the middle of surgery; the patient was not intubated and went on to experience diarrhea and vomit fecaloid material (Simon, 1997).  Vomiting while unconscious is highly dangerous because the patient might aspirate the vomit, leading to a blocked airway and/or lung damage.  Simon cites several other cases of ìunacceptable patient management by practitioners unskilled and inexperienced in managing a scenario which would be better managed by qualified anesthesia providersî (1997).  Employing an anesthesiologist undoubtedly raises the cost of the procedure, but many providers refuse to perform UROD without one.  As UROD providers in Great Britain observe, using anesthesiologists for the procedure ìis safer than prolonged detoxification with benzodiazepine sedation under supervision by psychiatristsî because deep sedation can lead to ìagitated and obtunded patients with compromised airwaysî (Laban, 1997).  Interestingly enough, CITA claims to have treated over 3,500 patients with no surgical complications (Simon, 1997).  Those figures are unsubstantiated by external observers, but CITA employs both anesthesiologists and intensive care specialists to supervise the treatment (Simon, 1997).  The quality of care, therefore, depends largely on the providersí training and ethics.  

How available is UROD in the United States?  

UROD is not widely available in the United States, and traveling to the provider may be difficult for patients both in terms of cost and follow-up care.  CITA has four centers in the United States: New York, Miami, Los Angeles, and Chicago (CITA, 1998).  Non-CITA clinics are also available in Connecticut, New Jersey, and Oregon (Stephenson, 1997a); another clinic has recently opened in Denver.  Therefore, the procedure is limited mostly to major cities in the East and West Coasts, a distribution that makes sense given the density of addicts in urban populations, but which may make the procedure inaccessible for others.  An addict in Georgia, for example, would have to travel a significant distance for UROD, and even assuming that he or his family could afford the additional expense, he would be unlikely to remain in the area for the months of recommended follow-up counseling and treatment.  As Charles OíBrien, professor of psychiatry at the University of Pennsylvania School of Medicine, remarks, ìAddiction is a chronic disease . . . and it needs to be managed like one.  We withdraw thousands of patients, but the big problem is preventing them from relapsingî (Stephenson, 1997a).  Traveling to New York for a week of detoxification may address the immediate physical aspects of addiction, but not the psychosocial problems that led to the addiction or that may contribute to relapse.  If facilities cannot provide a continuity of care that addresses the patientís underlying problems, then the patient is more likely to relapse or develop a new addiction.  Detoxification is, after all, only the first step; without follow up treatment, relapse rates following detoxification are extremely high (OíConnor and Kosten, 1998b).  When a patient travels a large distance for UROD, however, programs may be tempted to discharge a patient with a prescription for naltrexone and the number for a local chapter of Narcotics Anonymous (Stephenson, 1997a).  The limited availability of UROD, then, with its implications for poor follow-up care, may impair the procedureís long-term effectiveness. 

How much does UROD cost? 

Even if patients are physically qualified to undergo UROD, they may not be able to afford it, and insurance companies vary in their coverage.  The cost of the procedure ranges from $2,500 to $7,500óa reasonable fee given the need for general anesthesia, medical facilities, equipment, and qualified anesthesiologists, psychiatrists, and nurses, but a fee still out of reach for many (OíConnor and Kosten, 1998b).  CITA asserts that the cost is covered by various union health care plans, insurance companies, HMOs, and employee assistance plans (CITA, 1998).  However, many addicts are unlikely to have a well-paying job with benefits, much less valid insurance coverage; the fee for them must either be paid out-of-pocket or by their family members, assuming that a UROD provider is in the local area.  If travel and follow-up costs are added, the procedure could easily cost several thousand dollars more.  As a result, expense may be a prohibitive factor for many. 

How much do we know about UROD?   

Physicians and other providers have been understandably reluctant to endorse UROD because of the paucity of data.  Very few studies on UROD have been published, and those that are published are generally small in scope.  Stephenson (1997a), for example, observes that ìpublished studies in peer-reviewed journals examining clinical outcomes are surprisingly sparse, and the numbers of patients included in these studies are small.î  Furthermore, those studies fail to examine long-term outcomes with any thoroughness.  OíConnor and Kostenís (1998b) review found that only 4 out of 21 studies provided follow-up beyond detoxification, and the amount of detail provided was minimal.  These authors stated that more detailed assessments of postdetoxification outcomes (such as rates of drug use assessed by urine toxicology, rates of medication compliance, clinic attendance, and level of social functioning) are needed to accurately assess the long-term success of UROD.  Given the fact that UROD has been practiced for the last thirty years, however, it is disturbing that it has not been more systematically studied.  As a consequence, the National Institute on Drug Abuse report concluded that UROD should be used ìonly in very carefully considered and rigorously designed studiesî (Herman, 1996).  In short, UROD may be prove to be either a long-term solution or a quick fix; there is simply not enough data available to make an informed assessment at this point.     

How painful is UROD compared to other detoxification methods? 

The relative painlessness of UROD has strong appeal for many.  Conscious addicts in withdrawal may suffer from nausea and diarrhea, coughing, lacrimation [crying], rhinorrhea [a runny nose], profuse sweating, twitching muscles, and piloerection [goose bumps] (Wilson, 1991). In addition, they may experience diffuse body pain and insomnia, and their body temperature, respiratory rate, and blood pressure may become elevated (Wilson, 1991).   As previously noted, the intensity of these symptoms increases with the speed of the withdrawal, so an addict going ìcold turkeyî may endure almost unbearable pain.  It is true that some symptoms may persist after the UROD procedure; there is one reported case of an addict who underwent UROD experiencing low blood pressure, dehydration, abdominal cramps, tremors, and disorientation afterwards (Stephenson, 1997a).  Nevertheless, the addict experiences the worst of withdrawal symptoms while unconscious, and the post-treatment symptoms, although uncomfortable, are bearable.  

Why are addicts willing to try UROD? 

Many individuals who might be deterred from quitting because they fear withdrawal symptoms may be more likely to give up their addiction if they can do so without pain.  After all, many people refuse dental careówhether it is a root canal or a routine cleaningóbecause they are afraid of dentists.  If psychologically healthy individuals are prone to rationalization, excuses, and avoidance because they are afraid of a needle, it is not surprising that people who are chemically addicted to an opioid and afraid of withdrawal pain would be able to rationalize the continued use of drugs.  The effectiveness of any treatment is directly proportional to the patientís compliance with it.  Even if providers could offer a magic pill that was 100% effective, it would do no good if patients were too frightened to take it.  If detoxification is the first step to recovery, then any procedure that encourages addicts to take that step may be beneficial. 

What benefits are associated with UROD? 

With all the risks and costs associated with UROD, why should anyone consider it?  Why would anyone pay thousands of dollars to undergo a relatively new and medically risky procedure?  As mentioned earlier, opiate addiction is a physically, financially, and psychologically debilitating affliction.  Risks that would be inappropriate for patients with less debilitating diseases may be appropriate for patients who are slowly destroying their health with heroin.  Given the morbidity and mortality rates associated with addiction, therefore, even risky procedures may be medically justified.  UROD does have several significant benefits to its credit: it is relatively painless, and it presents a chance for individuals to escape the severe consequences of addiction. 

Conclusion 

Opiate addiction generally has profound physical, psychological, and social consequences.  Although pharmacological treatments for opiate addiction (especially methadone and LAAM) are now frequently utilized in the treatment of this disorder, many individuals addicted to opioids are attracted to the apparent high success rates, the relative painlessness, and the speed of ultra-rapid opioid detoxification.  Patients considering this approach need to be aware of potential risks and complications of this procedure, the lack of controlled research to support the long-term efficacy of this treatment, and the variability in the quality of care provided by different centers offering this treatment.  In addition, not all individuals with opiate dependence are suitable for this procedure, and patients who undergo this procedure are more likely to overdose if they relapse due to their lowered tolerance to the drug as a result of the procedure.  Patients considering this procedure should carefully weight the risks and benefits of this approach, along with that of the more traditional maintenance treatments, such as methadone or LAAM. Finally, ultra-rapid detoxification can be an expensive procedure, and it is not yet readily available in all parts of the country, limiting its widespread use.   
  
  
Bibliography 

American Psychiatric Association. Practice Guideline for the Treatment of Patients With Substance Use Disorders: Alcohol, Cocaine, Opioids. American Journal of Psychiatry 1995; 152 (11 and Supplement): 5-47. 

Bickel W, Amass L, Higgins S, Badger G, and Esch R. Effects of Adding Behavioral Treatment to Opioid Detoxification With Buprenorphine. Journal of Consulting and Clinical Psychology 1997; 65(5): 803-810. 

Brewer C and Maksoud N. Opiate Detoxification Under Anesthesia. Journal of American Medical Association 1997; 278(16): 1318. 

Brewer, C. To the Editor. Journal of American Medical Association 1998; 279(23): 1872. 

Caplehorn, J. Ultrarapid Opiate Detoxification: Whatís All the Fuss About? Medical Journal of Australia 1997; 167: 393. 

CITA web site. http://www.cita1.com 

Gevirtz C, Subhedar D, and Choi C. Rapid Opioid Detoxification. Journal of American Medical Association 1998; 279(23): 1871. 

Gooberman, L. To the Editor. Journal of American Medical Association 1998; 279(23): 1871. 

Hall W and Mattick R. Ultrarapid Opiate Detoxification. Medical Journal of Australia 1997; 167: 393-394. 

Herman B and Czechowicz D. NIDA Scientific Report of Ultra Rapid Detoxification with Anesthesia (UROD): Opinion of the Consultants and Criteria Relating to Evaluating the Safety and Efficacy of UROD; February 23, 1996.  

Kaltenbach K, Berghella V, and Finnegan L. Opioid Dependence During Pregnancy. Obstetrics and Gynecology Clinics of North America 1998; 25(1): 139-149. 

Laban M, Laishley R, and Schmulian C.  Acute Withdrawal of Opiates Is Indication for Anaesthesia. British Medical Journal 1997; 315(7109): 682-683. 

McConnell E. Myths and Facts . . . about Naloxone. Nursing 1996; 26(8): 17. 

OíConnor P and Kosten T. In Reply. Journal of American Medical Association 1998a; 279(23): 1872. 

OíConnor P and Kosten T. Rapid and Ultrarapid Opioid Detoxification Techniques. Journal of American Medical Association 1998b; 279(3): 229-234. 

Rabinowitz J, Cohen H, Tarrasch R, and Kotler M. Compliance to Naltrexone Treatment after Ultra-Rapid Opiate Detoxification: An Open Label Naturalistic Study. Drug and Alcohol Dependence 1997; 47: 77-86. 

Rumball D and Williams J. Rapid Opiate Detoxification: Assessment Is Needed to Exclude Certain Patients Before Detoxification. British Medical Journal 1997; 315(7109): 682. 
  
Simon D. Rapid Opioid Detoxification Using Opioid Antagonists: History, Theory and State of the Art. Journal of Addictive Diseases 1997; 16(1): 103-122. 

Solomont, J. To the Editor. Journal of American Medical Association 1997; 278(16): 1318. 

Stephenson, J. Experts Debate Merits of 1-Day Opiate Detoxification Under Anesthesia. Journal of American Medical Association 1997a; 277(5): 363-364. 

Stephenson, J. In Reply. Journal of American Medical Association 1997b; 278(16): 1319. 

Strang J, Bearn J, and Gossop M. Opiate Detoxification Under Anaesthesia. British Medical Journal 1997; 315(7118): 1249-1250. 

Tretter F, Burkhardt D, Bussello-Spieth B, Reiss J, Walcher S, and Buchele W. Clinical Experience with Antagonist-Induced Opiate Withdrawal Under Anaesthesia. Addiction 1998; 93(2): 269-275. 

Vining E, Kosten T, and Kleber H. Clinical Utility of Rapid Clonidine-Naltrexone Detoxification for Opioid Abusers. British Journal of Addiction 1988; 83: 567-575.           
    
Wilson J, Braunwald E, Isselbacher K, Petersdorf R, Martin J, Fauci A, and Root R. Harrisonís Principles of Internal Medicine. 12th ed. New York: McGraw, 1991.