_________________________________________________________________________ Opioid Use Disorder
The common underlying themes in all UROD techniques are a desire to condense the detoxification process into a shorter period to blunt the awareness of physical discomfort and to shorten the time lag between a patient’s last dose of opioid and transfer to naltrexone maintenance [143]. This is accomplished by precipitating withdrawal following the administration of opioid antagonists under deep sedation or anesthesia. A highly specific subgroup of patients may benefit more from UROD. This includes patients unable to abstain with methadone substitution despite adequate motivation, patients unable to stop methadone, and patients who are socially and occupationally active and cannot go through a lengthy detoxi- fication. Patient preference is also an important variable [143]. Absolute contraindications include pregnancy; a history or clinical suspicion of cardiac disease; chronic renal impairment; liver disease; current dependence on benzodiazepines, alcohol, or stimulants; and history of psychotic illness [143]. Relative contraindications include a history of treatment for depression and unstable social circumstances. A comprehensive plan to stabilize such patients should be undertaken before the pro- cedure [143]. Patients with chronic pain syndromes requiring opioid medication are not good candidates unless their pain can be controlled by alternative methods [80]. UROD is best performed in an intensive care unit with full resuscitative equipment and monitoring available [80]. Initia- tion of opioid withdrawal is precipitated by IV injection of a high-dose antagonist, usually naloxone. Antagonists are chosen that have high binding coefficients relative to agonists (naltrexone binds at the mu receptor 34 times more than mor- phine) [80]. Parameters that indicate adequacy of withdrawal include a 20% decrease of ventilation below the maximum minute ventilation, an electrocardiogram (ECG) detection of decreased QQ variability, and electroencephalogram (EEG) normalization [80]. Detoxification and withdrawal are rarely complete following UROD, and residual withdrawal symptoms can include drug craving, sympathetic hyperactivity, muscle pain, bone pain, nausea, vomiting, diarrhea, and insomnia. UROD does little to prevent protracted abstinence syndrome, which can last 3 to 10 weeks. Naltrexone may reduce opioid craving during the post-UROD period, with 50 mg per day recommended for relapse prevention [80]. However, patients undergoing long- term naltrexone therapy can become sensitized to opioid drugs, heightening the risk of fatal overdose if opioid use is resumed. Patients with a history of pre-existing liver dysfunction should undergo naltrexone maintenance therapy only under careful supervision. Clonidine may diminish sympathetic hyperactivity and should be continued through the protracted abstinence syndrome [80]. The withdrawal syndrome observed in many of the published studies on UROD was protracted, as reflected in the duration of inpatient stay, which varied from 24 hours to eight days, with a mean duration of three to four days. Therefore, alterna- tives to UROD are considered to be more cost-effective [143].
Krabbe et al. compared abstinence rates and withdrawal effects of UROD with standard methadone tapering in a prospec- tive three-month trial [144]. They found significantly higher abstinence rates and fewer withdrawal symptoms in UROD patients versus methadone patients at one and two months, with no differences at three months. A major shortcoming of UROD is the lack of evidence that an opioid antagonist can accelerate the restoration of neurobio- logic homeostasis following opioid withdrawal [143]. Although significant drawbacks and questionable long-term efficacy exist with UROD, popular demand has proven difficult to restrain, in part due to the marketing of the procedure as a painless cure for opioid dependence. Marketing and the media have also blurred the fact that the original purpose of the procedure was to induce patients as rapidly as possible onto naltrexone and not to magically and permanently terminate years of opi- oid dependence [142]. There are a number of drawbacks to UROD relative to other detoxification methods. For example, one study found that, when used alone, naloxone has a high relapse rate in the long term [145]. The study included 64 opioid-dependent men 18 years of age and older (mean age: 31.1 years) at the time of UROD. One month after UROD, 48 patients (75%) reported relapse and 16 patients (25%) reported abstinence. There was no significant difference between the two groups regarding marital status, level of education, and family history of opioid dependence. Four patients from the nonrelapsed group reported on episode of opiate use [145]. Another study was conducted to assess UROD efficacy with naltrexone and estimate the relapse rate in a two-year follow- up period [146]. A total of 424 opioid-addicted self-reporting patients were enrolled in the study and entered the UROD program; 400 patients completed the program. Of the total patients, 303 (75.75%) were successful and 97 (24.25%) relapsed. No patients in the relapse group continued naltrex- one maintenance at six-month follow-up. The relapse rate was 14% at the first month visit and 24% at the six-month visit and thereafter. All relapsed patients had discontinued use of naltrexone before relapse occurred [146]. A Canadian review of the evidence for UROD found no significant differences between UROD and control groups in commencement or duration of withdrawal treatment [147]. Serious adverse events related to the anesthetic procedure also have been reported. A randomized, controlled trial directly comparing naltrexone-assisted detoxification with and with- out full anesthesia clearly stated that heavy sedation or full anesthesia should not be used because it does not confer any advantages in withdrawal symptom severity or increased rates of initiation or maintenance and it increases the potential for life-threatening adverse events [77]. A trial comparing naltrexone-induced, anesthesia-assisted detoxification with buprenorphine- or clonidine-assisted detoxification found no difference in withdrawal severity and rates of completion. However, potentially life-threatening adverse events associ- ated with the UROD anesthesia were observed. The authors concluded that the data do not support use of anesthesia for detoxification [148]. Heavy sedation compared to light
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MDRI2026
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