American Journal of Drug and Alcohol Abuse
Volume 22, No. 4, pp. 489-495(1996)
Lance Gooberman, M.D., Thaddeus Bartter, M.D.
Opiate addiction is a growing health-care problem in the United States. The U.S. Department of Health and Human Services’ Substance Abuse branch issued a report in December 1994 stating that the number of emergency department visits directly related to heroin use rose from 48,000 in 1992 to 63,000 in 1993, a 31% increase. The rate of heroin-related episodes per 100,000 people rose 81%, from 15 to 28 per 100,000 during the interval 1990 to 1993. Breakdown of the heroin-using population into ethnic groups and age groups demonstrated that all subsets have increased rates for the interval studied. Heroin use is also moving to the suburbs. The lay press states that both heroin usage and heroin-related deaths in middle-class and wealthy suburbs have increased dramatically from 1990 to 1994.
Opiate addiction engenders intense physical dependence. Apart from psychosocial issues, the chemical dependence makes the transition to abstinence extremely difficult. Not only do individuals lose the euphoric effects of opiates, they also have to run the gauntlet of an extremely uncomfortable withdrawal. Traditional methods of detoxification, still commonly used have been slow, uncomfortable, expensive, and have had high dropout rates.
The availability of new drugs and several findings have led to a potential solution to many of the problems cited above. First, it was found that administration of opiate antagonists accelerates opiate withdrawal, allowing one to telescope a 1-3-week process into a few hours. Second, it was shown that clonidine and sedative-hypnotic drugs[6-8] are capable of attenuating the abstinence syndrome. Third, studies have demonstrated that naloxone reverses the respiratory depression associated with sedative-hypnotics, and thus might allow one to administer doses of sedative-hypnotics that might produce respiratory depression without the naloxone[9, 10]. The respiratory effects of naltrexone may be the same but have not been documented. In recent years, a few physicians have given opiate antagonists to accelerate withdrawal under the cover of drugs that attenuate the abstinence syndrome[6-8, 11-13]. Some studies have involved intubation[6-8, 11], while some have used sedation without intubation[4, 5, 12, 13].
The increases in opiate addiction will lead to an increased need for effective detoxification. Humane opiate detoxification is now possible. Although the principles and efficacy of rapid opiate detoxification (ROD) have been established, details about exactly how and where ROD should be performed still need to be worked out. We describe the experience with a series of patients who underwent opiate detoxification at our institution.
Over a 4-month period, 25 patients underwent 29 separate detoxifications. There were 14 women and 12 men. Mean age was 32.6 years, with a range of 24 to 48 years. Changes in approach with experience allow subdivision of the detoxifications into four distinct subgroups as discussed below.
The first 9 detoxifications (group 1) were accomplished with PO (by mouth) naltrexone. Standard premedication included carbamazepine and clonidine PO and phenobarbital IM (intramuscularly). After initial sedation, the patients were given a dose of PO naltrexone. Sedation was then continued on a PRN (as needed) basis in an attempt to control withdrawal symptoms. Detoxification was successful in all cases, with a mean of 1.8 days in the hospital. The method was effective, but despite the premedication, medications were being used to “catch up” with withdrawal symptoms throughout withdrawal, which was inexorable once naltrexone had been administered. It was also difficult to use PO medications for breakthrough symptoms in partially sedated patients. Thus, the medical regimen was changed.
Group 2 patients were treated initially with subcutaneous naloxone instead of naltrexone. Group 2 consisted of 12 detoxifications. The standard therapy involved PO clonidine and carbamazepine, IM phenobarbital, and then subcutaneous naloxone, 0.4 mg in an initial dose followed by intermittent doses. Phenobarbital dosing was tailored to the individual, with a goal of somnolence with arousability. After detoxification was deemed to be complete, the patients were allowed to wake up and were given a dose of PO naltrexone. The regimen was generally well tolerated; 11 of the 12 patients were detoxified in a mean of 2.0 days. One patient could not be sedated adequately, and had to be converted from rapid detoxification to a more gradual detoxification.
Despite its efficacy, the technique noted above was problematic. It required close monitoring in order to maintain the proper balance of sedation. Undersedated patients were agitated and combative, while oversedated patients needed close monitoring. In addition, appropriate sedation was difficult with only PO and subcutaneous routes of administration available. Because of these difficulties, Group 3 consisted of three detoxifications using more traditional means. Initial withdrawal occurred under the cover of carbamazepine, clonidine, and phenobarbital without using opiate antagonists. The three patients were allowed to complete a mean of 2.7 days of withdrawal and were then discharged. Withdrawal was initiated with this approach, but was not complete by the time of discharge; the patients were not given opiate antagonists during hospital stay or at the time of discharge. Thus, naltrexone maintenance could not be established.
After discussion with hospital administration, it was agreed that patients for ROD would be admitted into the intermediate intensive care unit, where the five patients in Group 4 were detoxified. The move to the intermediate intensive-care unit increased the nurse-patient ratio, such that patients were observed more closely. Use of this unit allowed the intravenous administration of sedating drugs, so that sedative effect could be attained more rapidly than is possible with oral or subcutaneous administration. It also allowed mechanical ventilation. After one patient was detoxified using IV (intravenous) phenobarbital and diazepam followed by intravenous naloxone, the decision to take more direct control was made. The last four patients in Group 4 were induced with propofol, intubated, and ventilated. They were maintained on a propofol drip. Norcuron was given as needed to control muscle movement for a 4-hour period, after which the propofol was stopped, allowing the patients to wake up rapidly. All four of these patients had been completely detoxified by hour 4, as demonstrated by a lack of abstinence syndrome when they were given 50 mg of naltrexone PO immediately upon awakening. A period of vomiting did occur with discontinuation of sedation and paralysis, but airway control was maintained until the patients were fully awake and vomiting had ceased; patients were fully functional by the time of extubation. They were watched over night, and no adverse events occurred over that interval.
What we have described is clinical experience with a series of patients, not a prospective clinical study. Nevertheless, we feel that the experience bears several lessons, all of which are relevant to the issue of opiate detoxification.
First, we have reconfirmed the validity of rapid detoxification using opiate antagonists to block opiate receptors and sedative-hypnotics to subdue symptoms during the conversion. Our experience parallels that of the literature; ROD is possible in as little as 4 hours. The mechanism appears to be active displacement of opiates from opiate receptors when the receptors are flooded with the antagonists, as opposed to the gradual loss of bound opiate with “supported” withdrawal. Not only is the time span for withdrawal reduced by many days; in addition, the opiate receptor blockade achieved by ROD means that a dose of narcotics given to a patient having completed ROD would have no physiologic effects. While this cannot be mistaken as a guarantee of abstinence, it does provide a window of time for addicts to be symptom-free and refractory to drugs and to be engaged in programs with the goal of long-term abstinence. The ability to continue taking naltrexone orally (either alone or in a program involving observed administration) also provides the opportunity to extend that window.
We wish to stress that ROD is a technique for detoxification, not a cure for addiction. ROD avoids much of the physical comfort of withdrawal and may avoid attrition caused by the pain of withdrawal, but it cannot be expected to suffice or to offer long-term efficacy unless clients are treated within a psychosocial context. We strongly advocate lifelong participation in a 12-step program as indispensable in maintaining abstinence.
Second, we have described for the first time an aggressive regimen using propofol, mechanical ventilation, and norcuron to control the withdrawal period. Propofol’s short half-life, coupled with short-acting paralysis, allowed an unparalleled degree of control. Thus our clinical experience has shown efficacy within a full range of approaches from “catching up” to naltrexone-induced withdrawal with sedatives to controlling the patient completely before beginning antagonists. What remains to be shown is which approach offers the best combination of safety, efficacy, and efficiency. Perhaps the optimal treatment plan would involve some intermediate point in the continuum.
Third, our experience has shown us that ROD is a technique without a home. If patients are to be sedated optimally, they should be monitored more closely than is possible on a routine hospital floor. On the other hand, the intermediate intensive-care unit is a step-down unit for the intensive-care unit and also receives subacute cases from the emergency room; it is not designed and was sometimes unable to accept scheduled admissions that were nonurgent but required monitoring. In addition, our experience demonstrated that patients who were stable when given a large dose of naltrexone after ROD required no subsequent intervention; no significant adverse effects occurred during overnight observation. Thus, the overnight stay is not needed. ROD does not have to be a hospital procedure. We would argue that opiate detoxification should ideally be accomplished in a unit designed specifically for detoxification. Medical models include outpatient surgicenters and dialysis units.
In conclusion, ROD is humane, fast, and efficient. It is also cost-effective, and would allow more of the health-care dollars spent on opiate addiction to go to programs that alter the social milieu and encourage sustained abstinence. The techniques involved in ROD require expertise and monitoring, but the patients are not critically ill and are detoxified electively; this detoxification would be best effected in centers for ROD and not in beds borrowed from the critical-care system.
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