Zusammenfassung.
Kompetitive Rezeptorantagonisten wie Naloxon und Naltrexon werden seit den frühen
siebziger Jahren zur Behandlung der Opioidabhängigkeit eingesetzt. Durch die Anwendung
dieser Substanzen wird der körperliche Entzug zwar beschleunigt, es kommt andererseits
jedoch zu einer erheblichen Verstärkung der Entzugssymptomatik. Ursache dafür ist
die sympatho-adrenerge Hyperaktivität, die mit einer gesteigerten Noradrenalinfreisetzung
einhergeht. Das Risiko des Antagonisten-induzierten Opioidentzuges ist gegenüber konventionellen
Entzugsverfahren erhöht. Mit Hilfe der Allgemeinanästhesie gelingt es, Ungleichgewichte
des vegetativen Nervensystems einzudämmen und Organfunktionsstörungen zu verhindern.
In diesem Artikel wird die klinische Relevanz forcierter Opioidentzugsverfahren in
Narkose auf der Basis der verfügbaren Literatur sowie unter Berücksichtigung eigener
Erfahrungen diskutiert. Wir schlußfolgern, daß diese Methode besonders bei abstinenzmotivierten
und sozial integrierten Patienten, die jedoch wegen der starken körperlichen Entzugssymptomatik
wiederholt Therapien abgebrochen haben, geeignet ist.
Treatment of opioid addicts by means of competitive opioid receptor antagonists was
developed at the University of Vienna in 1987 by Loimer and co-workers. They compared
two withdrawal regimens: The short Opiate withdrawal using a staggered naloxone regimen
and the rapid opiate detoxification during general anesthesia by means of high doses
of naloxone. Based on the latter concept, various modifications have been developed
world-wide using either naloxone or as an alternative, naltrexone, an antagonist available
for oral administration only. However, there are considerable objections to opioid
detoxification during general anesthesia. The main criticism is based an the supposedly
unacceptable high risk : benefit-ratio, the higher costs, the lack of psycho-social
support, and the lack of prospective studies. However, first results suggest that
rapid detoxification procedures are more successful in decreasing relapse than methods
which are based on psychiatric treatment alone. As sympathetic hyperfunction is common
in rapid detoxification procedures using high doses of opioid receptor antagonists,
it is essential to avoid severe autonomic imbalance with possible subsequent impairment
of organ functions. To prevent those disturbances, general anesthesia plays an important
role. So far, there is almost no information about such methods in the anesthesiological
literature. In this article the clinical relevance of such methods is discussed summarizing
both the available literature and our own experience and we conclude that rapid opioid
detoxification under general anesthesia is a safe and efficient method to suppress
withdrawal symptoms. This treatment may be of benefit in patients who particularly
suffer from severe withdrawal symptoms and who have failed repeatedly to complete
conventional withdrawal.
Schlüsselwörter:
Opioide - Narkose - Entzug - Naltrexon
Key words:
Opioids - Anesthesia - Withdrawal - Naltrexone
Literatur
- 1
Brewer C.
Blood pressure monitoring at home for rapid opioid withdrawal with clonidine and naltrexone.
The Lancet.
1987;
1
621
- 2
Brewer C.
Ultra-rapid, antagonist-precipitated opiate detoxification under general aenesthesia
or sedation.
Addict. Biol..
1997;
2/3
291-302
- 3 Brewer C, Laban M, Schmulian C, Gooberman L, Kasvikis Y, Maksoud NA. Rapid opiate
detoxification and naltrexone induction under general anesthesia and assisted ventilation:
Experience with 510 patients in four countries. Aufsatz für das Royal College of Psychiatrists,
London, England. July/1996: 1-5
- 4
Charney DS, Henninger GR, Kleber HD.
The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment
of abrupt withdrawal from methadone.
Am. J. Psychiatry.
1986;
143
831-837
- 5
Dettling M, Tretter F.
Der Opiatentzug in Narkose (forcierter Narkoseentzug, „Turboentzug”) bei Opiatabhängigkeit.
Nervenarzt..
1996;
67
805-810
- 6
Deutschman CS, Harris AP, Fleisher LA.
Changes in heart rate variability under propofol anesthesia: a possible explanation
for propofol-induced bradycardia.
Anesth. Analg..
1994;
79
373-377
- 7
Dinh-Xuan AT, Regnard J, Matran R, Mantrand P, Advenier C, Lockhart A.
Effects of Clonidine an bronchial responses to histamine in normal and asthmatic subjects.
Eur. Respir. J..
1988;
1
345-350
- 8
Eklund C, Melin L, Hiltunen A, Borg S.
Detoxification from methadone maintenance treatment in Sweden: long-term outcome and
effects on quality of life and life situation.
Int. J. Addict..
1994;
29
627-645
- 9
Fishbain DA, Rosomoff HL, Cutier R, Rosomoff RS.
Opiate detoxification. A clinical manual.
Ann. Clin. Psychiatry.
1993;
5
53-65
- 10
Freye E.
Der opioidabhängige Patient - Der Konsum nimmt zu.
Anästhesiologie & Intensivmedizin.
1998;
2
73-86
- 11
Freye E.
Medikamenteninteraktion bei der Methadontherapie.
Z. ärztl. Fortbild..
1992;
86
731-736
- 12
Galletly DC, Short TG.
Total intravenous anaesthesia using propofol infusion - 50 consecutive cases.
Anaesth. Intensive Care.
1988;
16
150-157
- 13
Gerra G, Marcato A, Caccavari R, Fontanesi B, Delsignore R, Fertonani G, Avanzini
P, Rustichelli P, Passeri M.
Clonidine and opiate receptor antagonists in the treatment of heroin addiction.
J. Subst. Abuse Treat..
1995;
12
35-41
- 14
Gold MS.
Opiate addiction and the locus coeruleus. The clinical utility of clonidine, naltrexone,
methadone, and buprenorphine.
Psychiatr. Clin. North. Am..
1993;
16
61-73
- 15
Goldstein A, Herrera J.
Heroin addicts and methadone treatment in Albuquerque: a 22-year follow-up.
Drug Alcohol Depend..
1995;
40
139-150
- 16
Gossop M, Griffiths P, Bradley B, Strang J.
Opiate withdrawal symptoms in response to 10-day and 21-day methadone withdrawal.
Br.J.Psychiatry .
1989;
154
360-363
- 17
Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD.
Two new rating scales for opiate withdrawal.
Am. J. Drug. Alcohol. Abuse.
1987;
13
293-308
- 18
Herman BH, 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.
American National Institute an Drug Abuse (NIDA) Report.
1996;
Februar 23
1-8
- 19
Jaffe H.
Pharmacological treatment of opioid dependence: current techniques and new findings.
Psychiat. Ann..
1995;
25
369-375
- 20
Kanto JH.
Propofol, the newest induction agent of anesthesia.
Int. J. Clin. Pharmacol. Ther. Toxicol..
1988;
26
41-57
- 21
Kienbaum P, Thürauf N, Michel MC, Scherbaum N, Gastpar M, Peters J.
Profound increase in epinephrine concentration in plasma and cardiovascular stimulation
after µ-opioid receptor blockade in opioid-addicted patients during barbiturate-induced
anesthesia for acute detoxification.
Anesthesiology..
1998;
88
1154-1161
- 22
Koob GF, Bloom FE.
Cellular and molecular mechanisms of drug dependence.
Science..
1988;
242
715-723
- 23
Kosten TR, Morgan C, Kleber HD.
Phase II clinical trials of buprenorphine: Detoxification and inducation onto naltrexone.
NIDA Research Monograph.
1992;
121
101-119
- 24
Langley MS, Heel RC.
Propofol. A review of its pharmacodynamic and pharmacokinetic properties and use as
an intravenous anaesthetic.
Drugs.
1988;
35
334-372
- 25
Legarda JJ, Gossop M.
A 24-h detoxification treatment for heroin addicts: a preliminary investigation.
Drug. Alcohol. Depend..
1994;
35
91-93
- 26 Leitlinien der Bundesärztekammer zur Substitutionstherapie Opiatabhängiger. Deutsch.
Ärzteblatt 1997: 7
- 27
Loimer N, Linzmayer L, Grünberger J.
Comparison between observer assessment and self rating of withdrawal distress during
opiate detoxification.
Drug. Alcohol. Depend..
1991;
28
265-268
- 28
Loimer N, Schmid RW, Presslich O, Lenz K.
Naloxone treatment for opiate withdrawal syndrome.
Br. J. Psychiatry.
1988;
153
851-852
- 29
Mackenzie N, Grant IS.
Propofol for continuous intravenous anaesthesia. A comparison with methohexitone.
Postgrad. Med. J..
1985;
61
70-75
- 30
Maldonado R, Stinus L, Gold LH, Koob GF.
Role of different brain structures in the expression of the physical morphine withdrawal
syndrome.
J. Pharmacol. Exp. Ther..
1992;
261
669-677
- 31
Mason ST, King RA, Banks P, Angel A.
Brain noradrenaline and anaesthesia: behavioural and electrophysiological evidence.
Neuroscience.
1983;
10
177-185
- 32
Ness R, Handelsman L, Aronson MJ, Hershkowitz A, Kanof PD.
The acute effects of a rapid medical detoxification upon dysphoria and other psychopathology
experienced by heroin abusers.
J. Nerv. Ment. Dis..
1994;
182
353-359
- 33
Nestler EJ.
Molecular mechanisms of drug addiction.
The Journal of Neuroscience.
1992;
12
2439-2450
- 34
O‘Connor PG, Waugh ME, Carrol KM, Rounsaville BJ, Diagkogiannis IA, Schottenfeld RS.
Primary Care - Based ambulatory opioid detoxification:.
The results of a clinical trial..
1995;
10
255-260
- 35
Partridge BL, Ward CF.
Pulmonary edema following low-dose naloxone administration.
Anesthesiology.
1986;
65
709-710
- 36
Pfab T, Hirtl C, Hibler A, Felgenheuer N, Chlistalla J, Zilker TH.
Der Antagonist-induzierte, Narkose-gestützte Opiat-Schnellentzug (AINOS).
Münch. med. Wschr..
1996;
138
781-786
- 37
Presslich O, Loimer N.
Opiate detoxification under general anesthesia by large doses of naloxone.
Clinical Toxicology.
1989;
27
263-270
- 38
Rabinowitz J, Cohen H, Tarrasch R, Kotler M.
Compliance to naltrexone treatment after Ultra Rapid Opiate Detoxification: An open
label naturalistic study.
Drug Alcohol Depend..
1997;
47
77-86
- 39
Rasmussen K, Beitner-Johnson D, Aghajanian GK, Nestler EJ.
Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and
biochemical correlates.
J. Neurosci..
1990;
10
2308-2317
- 40
San L, Puig M, Bulbena A, Farre M.
High risk of ultrashort noninvasive opiate detoxification.
Am. J. Psychiatry.
1995;
152
956
- 41 Sawicki T. The miracle cure? A revolutionary and highly controversial treatment
for heroin addiction is achieving astounding success in Israel, and is now set to
go overseas. The Jerusalem Report. July: 1995: 20-21
- 42
Schäfer A, Eck M, Bell U, Heckmann W, Schwartlander B.
Der Einsatz von Methadon bei der geburtshilflichen und gynäkologischen Versorgung
von drogenabhängigen Frauen mit und ohne HIV-Infektion.
Geburtshilfe Frauenheilkd. .
1991;
51
595-601
- 43
Senft RA.
Experience with clonidine-naltrexone for rapid opiate detoxification.
J. Subst. Abuse Treat..
1991;
8
257-259
- 44
Seoane A, Carrasco G, Cabré L, Puiggrós A, Hernández E, Álvarez M, Costa J, Molina
R, Sobrepere G.
Efficacy and safety of two new methods of rapid intravenous detoxification in heroin
addicts previously treated without success.
Br. J. Psychiatry.
1997;
171
340-345
- 45
Stephenson J.
Experts debate merits of 1-day opiate detoxification under anesthesia.
JAMA.
1997;
277
363-364
- 46
Stine SM, Kosten TR.
Use of drug combinations in treatment of opioid withdrawal.
J. Clin. Psychopharm..
1992;
12
203-209
- 47
Suzuki T, Koike Y, Yanaura S, George FR, Meisch RA.
Genetic differences in the development of physical dependence on pentobarbital in
four inbred strains of rats.
Jpn. J. Pharmacol..
1987;
45
479-486
- 48
Taff RH.
Pulmonary edema following naloxone administration in a patient without heart disease.
Anesthesiology.
1983;
59
576-577
- 49
Tretter F.
Von der Phantasie, die Sucht auszuschlafen.
Münch. med. Wschr..
1996;
138
76-77
- 50
Vining E, Kosten TR, Kleber HD.
Clinical Utility of rapid clonidine-naltrexone detoxification for opioid abusers.
Br. J. Addict..
1988;
83
567-575
- 51
Wang RIH, Wiesen RL, Lamid S, Roh BL.
Rating the presence and severity of opiate dependence.
Clin. Pharmacol. Ther..
1974;
16
653-658
- 52
Wise RA.
The neurobiology of craving: Implications for the understanding and treatment of addiction.
J. Abnormal Psychology..
1988;
97
118-132
Dr. med. Mario Hensel
Klinik für Anästhesiologie und operative Intensivmedizin der Charité Humboldt-Universität
zu Berlin
Schumannstr. 20/21
D-10117 Berlin