What are some of the signs of opioid dependence

Opioid Addiction: The Ultra Short Withdrawal

MEDICINE: For further training

State of the literature and own investigations

SUMMARY
With ultra-short withdrawal (UKE) during anesthesia, high-dose administration of opioid receptor antagonists abruptly displaces the opioids consumed by the addict from the receptors of the endorphin system. Compared to conventional withdrawal methods, this procedure is intended to shorten the duration of the withdrawal syndrome to a maximum of a few days, alleviate its intensity and thus lead to a higher frequency of successfully completed withdrawals. Ultra-short withdrawal is only indicated for exclusively opioid addicts. These patients can be detoxified by UKE within a week. The frequency of successfully completed withdrawals is 90 to 100 percent. There are no fundamental safety concerns with precise indications, intensive medical care during acute antagonization and internistically competent treatment in the first days after anesthesia. The competence and interdisciplinary cooperation of psychiatrists and intensive care physicians required for implementation restrict the use of ultra-short withdrawal to a few specialized centers.
Keywords: opioid addiction, opioid withdrawal, ultra-short withdrawal, opioid antagonist, anesthesia
SUMMARY
Opioid Dependence: Ultra-Rapid Detoxification
Ultra-rapid detoxification (URD) ​​of opioid addicts involves abrupt discontinuation of opioid intake and displacement of opioid agonists from the receptor of the endorphin system by administration of large doses of opioid antagonists during sedation or general anesthesia. The following advantages of URD have been proposed: decreased intensity and duration of withdrawal symptoms to at most a few days and increased frequency of completed withdrawal treatment. URD is only indicated for patients solely addicted to opioids. In these patients, withdrawal symptoms after URD last about a week and the rate of completed detoxification is 90 to 100 per cent. Patients with comorbid disorders associated with increased anesthetic risk should be excluded. URD treatment should be performed in an intensive care unit during acute administration of opioid receptor antagonists. Following these preliminary guidelines, there are no fundamental safety objections to this method. Due to the small number of patients suitable for URD and the required cooperation between psychiatrists and anesthesiologists application of URD should be limited to a few specialized centers.
Key words: Opioid dependence, opioid detoxification, ultra-rapid detoxification, opioid antagonist, general anesthesia
Withdrawal or detox is the process of removing an addictive substance from the body. In the case of opioid dependence, withdrawal as a result of physical dependence is associated with the occurrence of withdrawal symptoms (text box). Pharmacological factors, such as the dose and half-life of the opioid consumed, and psychological factors, such as the fear of withdrawal symptoms, influence the intensity of the withdrawal.
Withdrawal treatment means medical help in coping with the withdrawal syndrome. Successful withdrawal, in turn, is an essential prerequisite for commencing weaning therapy, the therapeutic aid to building a drug-free life. Criteria for the quality of a withdrawal treatment (14) are the alleviation of the duration and intensity of the withdrawal symptoms, the safety of the procedure, the frequency of successfully completed withdrawals and the frequency with which addicts are placed in withdrawal treatment. In view of the high prevalence of somatic and psychiatric comorbidities, other tasks include precise diagnosis and the initiation of appropriate therapeutic measures. In view of the widespread polytoxicomania among opioid addicts, withdrawal usually affects other addictive substances in addition to opioids (8).
At the moment, the so-called "warm" withdrawal is the standard treatment: If the patient is not already on substitution therapy, he receives an opioid with a longer half-life, namely methadone, instead of the previously consumed heroin. The methadone dose is then reduced in small steps. In addition, withdrawal symptoms are treated symptomatically. The α-2 agonist clonidine is particularly effective in relieving symptoms of sympathetic hyperactivity (3). The so-called warm withdrawal can take a few weeks, depending on the starting methadone dose. Because of this long duration and a dropout rate of around 30 percent (14), alternative methods of withdrawal treatment are being scientifically examined. !
Principle of
Ultra short withdrawal
The ultra-short withdrawal (UKE), also called "turbo" or "anesthesia withdrawal", consists of a fundamentally different procedure: After abrupt discontinuation of the opioids, high-dose administration of opioid receptor antagonists such as naloxone or naltrexone removes the consumed opioids from the Receptors of the endorphin system displaced. The addict does not consciously experience the withdrawal symptoms provoked by this in sedation or anesthesia. Specific medication, for example clonidine, before the administration of the opioid antagonist or for several days during the course, alleviates the intensity of withdrawal symptoms. Long-term naltrexone therapy can be followed by administration of antagonists for several days during the withdrawal phase. Proponents of ultra-short withdrawal postulate that the frequency of successfully completed withdrawals increases by alleviating the intensity, but especially also the duration of withdrawal from a few hours to at most a few days.
State of the literature
So far, only a few scientific studies on the UKE have been published. Loimer in Vienna administered 270 mg morphine / day for three days to six exclusively opioid dependent, regardless of previous opioid consumption (10). On the fourth day, during 30 to 50 minutes of anesthesia with the barbiturate methohexital (dose: 0.5 to 1 g), the intubated patients were given 10 mg of naloxone i.v. within ten minutes. administered. The receptor blockade was maintained by a continuous naloxone infusion (dose: 0.4 mg / h) over the next 72 hours. All six patients successfully completed withdrawal treatment. According to the authors, the naloxone bolus administration and the subsequent course of the drug gave rise to at most minor withdrawal symptoms. The observation was ended on the sixth day after anesthesia.
In a further communication from this working group, a largely similar method was used in 15 exclusively opioid-dependent patients and the course of withdrawal (with non-randomized allocation) compared with that of 29 patients who were detoxified by gradually reducing the methadone dose (13). Four of the 29 patients in methadone-assisted withdrawal stopped treatment prematurely, but none of the 15 patients in UKE. In the patients after UKE, the intensity of the withdrawal symptoms was already reduced after six days to the level that patients only reached after three weeks after tapering off methadone.
When the procedure was modified, further examinations confirmed the findings of only brief and mild withdrawal. Instead of the supposedly time-consuming general anesthesia, sedation was carried out with the benzodiazepine midazolam (9, 2) or a combination of propofol and midazolam (20). Instead of naloxone, naltrexone was also used as an antagonist and the administration of withdrawal-relieving drugs, such as the α-2 agonists, was started even before the antagonization (9).
In contrast to the cited studies that assessed the UKE as positive, one working group (17) prematurely discontinued its investigation after one case of respiratory failure requiring weeks of ventilation and two cases with acute kidney failure after the treatment of twelve patients. After a study of 300 heroin addicts who were administered the antagonist in sedation, other authors (20) refer to the supposed safety of the procedure: only six patients required endotracheal intubation, one of which also required mechanical ventilation. Tretter et al. (24) observed no complications in 88 patients.
Why the administration of opioid antagonists under anesthesia should lead to a shortened, but above all only mild, course of withdrawal has not yet been adequately investigated. It seems trivial that the withdrawal process is shorter after abrupt discontinuation of an opioid than when methadone is tapered off. Animal experiments could not confirm the superiority of ultra-short withdrawal with regard to the duration and intensity of withdrawal symptoms even compared to placebo treatment (21).
Overall, however, the available scientific studies (Table 1) do not allow a conclusive evaluation of the method due to various methodological deficiencies (15, 22). Most studies report only a small number of cases. Information that is important for assessing the duration and intensity of withdrawal symptoms, such as the type and dose of opioids consumed or the use of other addictive substances, is inadequate. Furthermore, the duration of the follow-up examination with regard to withdrawal symptoms was sometimes only a few hours, at most a few days. In addition, only partially standardized scales were used to assess the intensity of the withdrawal symptoms. The effectiveness of ultra-short withdrawal claimed by a commercial provider (2), especially with regard to the shortening of the withdrawal period to a few hours, received a lot of attention in the media, but has not yet been proven by scientific studies. This made it necessary to conduct a systematic investigation of our own.
Own research
The target group of our own study (7, 19) were patients with pure opioid addiction. Exclusion criteria were the dependent consumption of another addictive substance or polytoxicomania. Further exclusion criteria were florid viral hepatitis, HIV infection and diseases with an increased risk of anesthesia, such as pulmonary infections. During the preliminary outpatient phase, which lasted several weeks, extensive psychiatric diagnostics were carried out, the indications and contraindications to the UKE were checked, and follow-up treatment was specifically planned. In order to compare the course of withdrawal, all patients, provided they were not already on methadone substitution treatment, were substituted with methadone racemate for at least the last two weeks before admission.
On the day of admission to the psychiatric admission ward, in addition to a urine test for addictive substances, tests of the current physical condition to assess the anesthetic risk were carried out (anamnesis, physical examination, EKG, routine laboratory, chest X-ray). The next day the patients were transferred to the intensive care unit in the morning. The short-term withdrawal was carried out there during general anesthesia with endotracheal intubation, controlled ventilation and invasive hemodynamic monitoring. This elaborate procedure appeared to be justified, since case reports of respiratory and cardiovascular complications - even fatal - are available after perioperative administration of even small doses of naloxone for the treatment of opioid-induced respiratory depression (1, 16). Propofol or methohexital were used as anesthetics. !
The opioid receptor blockade was carried out with naloxone; after an initial bolus dose of 0.4 mg, the naloxone dose every quarter-hour increased to 0.8 mg, 1.6 mg, 3.2 mg, 6.4 mg up to a total dose of 12 , 4 mg was doubled in each case within one hour. This was followed by a naloxone infusion at 0.8 mg / h until the next morning. A considerable cardiovascular activation (increase in cardiac output by 80 percent) was observed as a reaction to the opioid receptor blockade, which could only be estimated poorly from changes in arterial blood pressure, since the systemic vascular resistance fell in parallel. This was due to massive sympathetic activation with a 30-fold increase in adrenaline and a three-fold increase in noradrenaline concentration in plasma (7).
As a rule, the anesthesia could be withdrawn after about six hours and the patient extubated. However, all patients remained under intensive care surveillance until the morning of the next day. In this phase, severe withdrawal symptoms were alleviated by intravenous administration of clonidine. On the evening of the day in the intensive care unit and the following morning, 50 mg naltrexone was given each time. At least until the end of the inpatient treatment, naltrexone therapy was continued with a morning dose of 50 mg.
After staying in the intensive care unit for a day, she was transferred back to the psychiatric clinic. If withdrawal symptoms persist, symptom-oriented drug therapy by oral administration of clonidine, trimipramine or diclofenac was possible. The intensity of the withdrawal symptoms was assessed by the patients using established clinical scales (4, 5).
With large interindividual differences, the 22 patients examined so far (Table 2) experienced on average moderate withdrawal symptoms in the first week after UKE (graphic). Over seven days, the intensity of the withdrawal symptoms was significantly higher than in the control surveys before withdrawal treatment. On average, the patients could be discharged after an inpatient stay of around eight days. Treatment complications were temporary and manageable or had no causal connection with the withdrawal method. In the further inpatient course after being readmitted from the intensive care unit, sinus bradycardia and hypokalemia developed in almost all patients, which required monitoring and treatment. One patient prematurely discontinued inpatient withdrawal treatment. Five of the 22 patients did not start any further therapy after UKE after discharge, despite an agreement to the contrary. 13 patients started naltrexone therapy.
Résumé
Contrary to the scientific reports mentioned, the majority of our patients complained of moderate withdrawal symptoms for over a week. No patient was symptom-free immediately after anesthesia. There are several possible explanations for this discrepancy. The most important differences between the studies are likely to be in patient selection. In our study, methadone was withdrawn, the half-life of which is much longer than that of heroin or morphine (8). In addition, users of benzodiazepines, which in turn can alleviate opioid withdrawal, were excluded from our study.
The advantages of ultra-short withdrawal in our study as well as in the literature are the high frequency of completed withdrawals of 90 to 100 percent and the shortening of the withdrawal period compared to the so-called warm withdrawal. The dropout rate of conventional withdrawal treatments is given as around 30 percent (14). It can vary considerably between different samples, for example when comparing electively admitted patients for withdrawal therapy with unmotivated, severely intoxicated addicts treated as emergency cases. Due to the inclusion criteria and procedures, patients with a rather good prognosis for the course of withdrawal were certainly included in this study. With regard to some studies on the UKE, it should also be noted critically that with in some cases only a very short observation time of in some cases only 24 hours, a possible intensification of withdrawal symptoms in the following days with a rapid resumption of opioid consumption could not be recorded.
Few reports have been made of complications from the procedure. In our experience, there are no fundamental safety concerns with intensive medical monitoring and treatment for a few hours. However, in our opinion, the UKE definitely requires intensive medical monitoring. This includes at least one endotracheal intubation to keep the airways clear and the creation of a central venous access to control volume therapy (in the case of massive diarrhea and gastrointestinal reflux) and for the application of medication. It must be doubted whether avoiding intubation is an advantage: Sedation alone without intubation leaves the airway of these aspiration-endangered patients completely unprotected. In view of persistent withdrawal symptoms, the high volume turnover and the frequently accompanying hypokalaemia (effect of the endogenous catecholamine secretion) as well as the high prevalence of clonidine-related ECG changes (QT prolongations), which predispose to cardiac arrhythmias, close monitoring of the patient is also necessary on a psychiatric Station necessary. In our opinion, these recommendations on the safety standard should apply in principle. However, details of the implementation of the ultra-short withdrawal shown here are definitely debatable. This applies, for example, to the choice of the opioid antagonist and its dose or the administration of withdrawal-relieving substances, such as clonidine, even before the start of the receptor blockade. Our detailed presentation of the medication serves to make the procedure we have chosen comprehensible and should not be misunderstood as an empirically proven therapy regime.
The high frequency of referral of 75 percent of our patients to further treatments is high compared to an unread sample of opioid addicts (6) and can be explained, for example, by the exclusion of polytoxicomaniac patients. Most studies on the UKE do not provide any information on referral. The use of naltrexone in withdrawal treatment facilitates the initiation of naltrexone therapy as a long-term weaning strategy. So far it has not been clarified whether this advantage will be eroded by high drop-out rates in the further course.
Overall, the UKE is only indicated for a minority of opioid addicts. Above all, polyvalent addicts and patients with anesthesia-related diseases are to be excluded. A priori, there is no plausible reason to assume a shortening of the withdrawal duration even with withdrawal from alcohol and benzodiazepines in polytoxicomania. At the moment, patients stabilized in methadone substitution appear to be most suitable for the UKE. The indication should be made by an addiction therapist. In view of the short inpatient stay at UKE, further treatment must be specifically planned in a preliminary outpatient phase. To avoid "detox tourism" (23), the UKE should be organizationally and conceptually integrated into the local addiction help network. In view of the necessary professional competence and close cooperation between psychiatrists and intensive care physicians, the use of this method is limited to a few specialized centers.


How this article is cited:
Dt Ärztebl 1999; 96: A-2021-2025
[Issue 31-32]
The numbers in brackets refer to the bibliography, which is available from the author in a special print and from the website (at http://www.aerzteblatt.de).


Address for the authors
Dr. med. Norbert Scherbaum
Clinic for Psychiatry and Psychotherapy
Rheinische Kliniken Essen
University of Essen
Virchowstrasse 174
45147 Essen

Symptoms of opioid withdrawal
Symptoms of a "rebound" hyperactivity of the sympathetic nervous system: tears, rhinorrhea, tendency to perspire, tachycardia and pupillary dilation (mydriasis),
Craving for addictive substances (craving),
Hot flashes, "goose bumps" (piloerection),
colicky gastrointestinal pain,
Muscle and bone pain,
Muscle tremors,
Yawning,
inner restlessness and sleep disorders,
Nausea, vomiting, diarrhea.

Table 1
Overview of scientific studies of ultra-short withdrawal
Reference patient opiates polyvalent observational target variables procedure
number of consumption period
Presslich, 1989 6 opiates * 1 unclear 1 hour hemodynamics right heart catheter
Loimer, 1990 18 opiates * 1 no 7 days withdrawal symptoms Wang and after withdrawal scale
Kolb and Himmelsbach
Loimer, 1991 15 opiates * 1 no unclear withdrawal symptoms withdrawal scale according to Kolb and Himmelsbach
Legarda, 1994 11 opiates * 1 yes 12 hours withdrawal symptoms withdrawal scale
after Bradley
Pfab, 1996 12 Methadone no variable, approx. Withdrawal symptoms withdrawal scale according to
Codeine 6-9 days Kolb and Himmelsbach,
Heroin sensitivity scales
Seoane, 1997 300 Heroin yes 1 day withdrawal symptoms withdrawal scale according to
28 days relapse Wang, urine screening
Tretter, 1998 88 Methadone no variable, approx. Withdrawal symptoms no standardized codeine 3-14 days te withdrawal scale
Kienbaum, 10 methadone no 3 hours hemodynamics right heart catheter
1998 Catecholamines HPLC * 2
in the plasma
Scherbaum, 22 methadone no 28 days withdrawal symptoms withdrawal scales
1998 after Gossop and
according to Handelsman
* 1 not specified in more detail
* 2 HPLC = high performance pressure liquid chromatography

Table 2
Description of the sample of our 22 patients
Mean values ​​range
Age 29.4 years 6 8 20 - 47 years
Duration of opiate addiction 84 months 6 64 13 - 280 months
Methadone dose 89 mg / d 6 65 10 - 270 mg
previous at least 19 out of 22 patients
several months of substitution therapy
previous inpatient 17 of 22 patients
Withdrawal treatments


Evaluation of the intensity of the withdrawal symptoms using the Short Opiate Withdrawal Scale (SOWS). In the version modified for this study, this survey instrument comprises 10 items on withdrawal symptoms, the intensity of which the patients rate as 0 or nonexistent, 1 or mild, 2 or moderate, and 3 or severe. With an initial sample of 22 patients, the numbers on the columns indicate the number of patients who were examined at the respective point in time. * p < 0,05="" versus="" tag="" 1="" vor="" der="" entgiftung="" (grafik="" übernommen="" aus="" scherbaum="" et="" al.="">

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Opioid Addiction: The Ultra Short Withdrawal

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