The medical literature relevant to naltrexone induced heroin detoxification under general anesthesia consists of six studies with a total of 63 patients.
The following discussion focuses on issues of patient population, anesthetic agent, airway management, duration of anesthesia, antagonist use, withdrawal symptoms, changes in vital signs, complications, and follow-up.
| Study No. | 1 | 2 | 3 | 4 | 5 | 6 |
| No. of patients | 6 | 6 | 18 | 15 | 7 | 11 |
| Sex | Unknown | All male | 15 male 3 female |
13 male 2 female |
4 male 3 female |
11 male |
| Age | 21-28 yr. | 25-35 yr. | 20-35 yr. | Unknown | 20-36 yr. | 22-30 yr. |
| Opiate abused | Unknown | Unknown | Unknown | Unknown | Unknown | Heroin |
| Duration of abuse | Unknown | 8-10 yr. | 2-18 yr. | 1-14 yr. | 3-13 yr. | 1.5-11.5 yr. |
All patients met DSM III-R criteria for opiate addiction. Only Study no.6 included patients using substances other than opiates. The authors of the first five studies did not mention if patients used heroin or methadone as their standard opiate source. Any significance regarding the type of opiate addiction or concurrent use of other substances prior to naltrexone induced heroin detoxification under general anesthesia remains to be evaluated.
Anesthetic, airway management, and duration of anesthesia
| Study | 1 | 2 | 3 | 4 | 5 | 6 |
| Pre-med | None | None | None | None | None | Guanfacine Odansetron Loperamide |
| Induction | Brevital 500-1000mg |
Thiopentone 1000mg |
Brevital 100 mg |
Brevital 100 mg |
Midazolam 30 mg |
Midazolam 0.5-0.7mg/kg |
| Intubation | Yes | Yes | Yes | Yes | No | No |
| Maintenance | None | Thiopentone 5000mg |
Brevital 400 mg |
Brevital 400 mg |
Midazolam repeated 50-75mg |
Midazolam ? dose |
| Duration | 30-50 min | 3 hr | 30-40 min | Unknown | Unknown | 4 hr |
These studies can be separated into two major groups. In
Studies no.1-4, barbiturates were used for induction and
maintenance of anesthesia. All patients were intubated (tube in
the wind pipe to protect the lungs in case the patient vomits).
In Studies no.5&6, midazolam (like valium) was used for
induction and maintenance of anesthesia. No patients were
intubated. The duration of anesthesia lasted from thirty minutes
to four hours.
One may consider whether the anesthetic or naltrexone was
responsible for reducing the duration of withdrawal to within
four hours. Results of Study #3 suggests that naltrexone was the
responsible agent. Loimer divided 18 patients into two groups.
Group A patients received the standard antagonist (naltrexone
type of drug) induced detoxification procedure under general
anesthesia. Group B patients, a control group, were placed under
general anesthesia but were not treated with an opiate
antagonist. Upon emergence from anesthesia (wake up), only
patients in group B showed evidence of opiate dependence. These
patients were subsequently re-anesthetized and received the
standard antagonist treatment.
What is the best anesthetic for this procedure? Barbiturate and
midazolam were used successfully in these studies. Propofol (an
IV anesthetic) has been utilized successfully in one preliminary
study (personal communication). The use of inhalation agents
(newer, ether type of anesthetics) has not been reported. Any
anesthetic, except of course narcotics, may be adequate. Further
studies will be needed.
Should all patients be intubated? Patients in Studies no.5&6
were not intubated and experienced no complications. However, San et al described a patient who vomited and
became hypoxemic (low oxygen in the blood) while anesthetized for
detoxification. This was probably due to aspiration (contents
from the stomach entering the lungs). Since opiates reduce
intestinal motility, and detoxification is associated with nausea
and vomiting, all patients should have a protected airway
(windpipe) with an endotracheal tube.
What is the optimal duration of anesthesia? The above six studies
suggest that 30 minutes to four hours is adequate. In another
study, Resnick obtained detoxification
within 24 hr. in 13 awake patients (Fig 1). 
Note that the severity of withdrawal signs increased
dramatically soon after naloxone administration (Segment A).
Then, symptoms decreased quickly over the next 2-3 hours (Segment
B) with a slower decrease over the rest of the day (Segment C).
The purpose of the anesthetic is to avoid the severely
exacerbated withdrawal signs provoked by naloxone administration
(Top of Segment A). Emergence (wake up from anesthesia), then,
should occur at the latter part of Segment B. The trade-off
includes waking up early with the possibility of significant
withdrawal symptoms vs. waking up later with less symptoms but
longer anesthesia, cost, and risk.
Results from the measurement of pupillary diameter, in Study
no.4, suggests that mild withdrawal signs may be present for up
to six days. Rat models suggest that three days may be necessary
for complete resolution of withdrawal signs.
Antagonist
| 1 | 2 | 3 | 4 | 5 | 6 | |
| Naloxone | 10 mg IV over one hour, infuse 0.4 mg/hr x 24 hr. | 10 mg IV over one hour, infuse 0.4 mg/hr x 24 hr. | 10 mg IV bolus, infuse 0.8 mg/hr x 48 hr. | 10 mg IV bolus, infuse 0.8 mg/hr x 72 hr. | 4.0 mg infusion, ? duration |
None |
| Naltrexone | None | None | None | None | 50 mg PO qd x 30 days, Start when awake | 50 mg PO prior to induction, then 50 mg PO qd x 30d |
A clear progression of antagonist administration is observed.
Initially, 10 mg of naloxone was administered intravenously over
one hour followed by an infusion at 0.4mg/hr x 24 hr. In Study
no. 4, 10 mg of naloxone was administered as an IV bolus and the
infusion was increased to 0.8mg/hr x 72 hr. Oral naltrexone was
utilized in Studies no. 5 & 6. Further studies will be needed
to determine the optimal antagonist regimen.
Opiate antagonist treatment must continue as long as agonist
(heroin or methadone) is present. Resnick
administered naloxone to awake addicts over a two day period. On
the second day, naloxone precipitated an acute exacerbation of
withdrawal symptoms. The author postulated that systemic
antagonist levels decreased overnight, allowing agonist to rebind
to its receptor which re-instituted the dependent state. Long
term antagonist levels can be maintained with oral naltrexone
therapy.
Evidence of Withdrawal After Detoxification
| Study | Signs or Symptoms of Withdrawal |
| 1 | "limited
susceptibility to opiate withdrawal symptoms" "no patient showed severe withdrawal signs" |
| 2 | "no significant
withdrawal signs" 2/6 patients did have nausea, vomiting, or muscle pains for 4 - 6 hr. |
| 3 | "minimal withdrawal signs" |
| 4 | "no significant differences were obtained" when comparing pre-detoxification and post-detoxification withdrawal symptoms |
| 5 | "no objective withdrawal symptoms were recorded" |
| 6 | All patients experienced
slight agitation, piloerection, and sneezing "levels of opiate withdrawal symptomatology were found to be at normal baseline levels after detoxification" |
The majority of these studies offer a poor evaluation of withdrawal signs and symptoms. Most of the post-detoxification evaluations occurred on the day after detoxification. It is not clear if evidence of withdrawal was present immediately after emerging (waking up) from anesthesia. Some studies evaluated signs of withdrawal, i.e. nausea, diarrhea, shakes etc. Other studies evaluated symptoms of withdrawal, i.e. restlessness and anxiety. In general, subjective symptoms, as compared to signs, are more prevalent after detoxification. As mentioned previously in the section, "duration of anesthesia," mild withdrawal signs may be present for up to 6 days.
Vitals, Complications, and Follow-up
Most of these studies suggest that changes in blood pressure
and heart rate are minimal during detoxification. There were no
reported severe hypertensive episodes. Invasive pulmonary and
femoral artery catheters were used in only one study.
No significant complications were reported.
Only one study offered follow-up data for greater than one week.
All patients were still taking naltrexone, and all but two
patients challenged naltrexone with opiate use.
Please see the FAQ and discussion forum sections for an elaboration of issues raised in this review.
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