special subjects
Opioid Toxicity and Withdrawal
Treatment of Opioid Toxicity or Withdrawal
Supportive therapy For opioid withdrawal, sometimes drug therapy (eg, with an opioid agonist, opioid agonist-antagonist, opioid antagonist, orclonidine) Treatment to maintain the airway and support breathing is the first priority. Naloxone0.4 mg to 2 mg IV Sometimes endotracheal intubation has no agonist activity and a very short half-life (see table Symptoms and Treatment of Specific Poisons ). Because some patients become agitated, delirious, and combative as consciousness returns and becausenaloxoneprecipitates acute withdrawal, soft physical restraints may be indicated if these symptoms occur and should be applied beforenaloxoneis given. To ameliorate withdrawal in long-term users, some experts suggest titrating very small doses ofnaloxone(0.1 mg) when the clinical situation does not require emergency total reversal. Apneic patients can initially be treated withnaloxone2 mg IV if it can be given without delay; note that the dose is higher than for patients who are only somnolent. In some parts of the US and some countries,naloxoneis available without a prescription so apneic patients can be rescued by friends or family. Whennaloxoneis available and given quickly, endotracheal intubation is rarely required. Patients should be observed for several hours after they regain spontaneous respirations. Because the duration of action ofnaloxoneis less than that of some opioids, respiratory depression can recur within several hours of an overdose ofmethadoneor sustained-releasedoxycodoneormorphinetablets. Thus, the duration of observation should vary depending on the half-life of the opioid involved. Typically, patients who took longer-acting opioids should be admitted for observation; patients who took short-acting opioids may be discharged after several hours. If respiratory depression recurs,naloxoneshould be readministered at an appropriate dose. The best dosing regimen is unclear. Many clinicians use repeat bolus doses of the same dose that was effective initially. Others use continuousnaloxoneinfusion; they typically begin with about two thirds of the initially effective dose per hour. In theory, the continuous infusion should allow the dose to be titrated to maintain respiratory rate without triggering withdrawal; however, in practice this can be difficult to do and the patient's life is dependent on the security of the IV line—respiratory depression will quickly recur if the infusion is interrupted (eg, by the patient pulling out the IV). Both regimens require close monitoring, typically in an intensive care unit. Patients should be observed until nonaloxonepharmacologic activity is present and they have no opioid-related symptoms. The serum half-life ofnaloxoneis about 1 hour, so an observation period of 2 to 3 hours after use ofnaloxoneshould clarify disposition. The half-life of IV heroin is relatively short, and recurrent respiratory depression afternaloxonereversal of IV heroin is rare. Acute Pulmonary Edema is treated with supplemental oxygen and often noninvasive or invasive modalities of breathing support (eg, Treatment may involve several strategies: No treatment (“cold turkey”) Substitution withbuprenorphineormethadone Clonidineto relieve symptoms Long-term support and possiblynaltrexone The opioid withdrawal syndrome is self-limited and, although severely uncomfortable, is not life threatening. Minor metabolic and physical withdrawal effects may persist up to 6 months. Withdrawal is typically managed in outpatient settings, unless patients require hospitalization for concurrent medical or mental health problems. Options for management of withdrawal include allowing the process to run its course (“cold turkey”) after the patient’s last opioid dose and giving another opioid (substitution) that can be tapered on a controlled schedule. Medication-assisted treatment withbuprenorphineandnaloxonehas become the primary choice of treatment. Buprenorphine,a partial opioid agonist—usually given sublingually—has been successfully used in treatment of withdrawal.Naloxoneis added tobuprenorphineto reduce abuse potential. When taken sublingually, thebuprenorphine(opioid agonist) effects predominate, reducing withdrawal symptoms. If crushed and injected, thenaloxoneeffects predominate, increasing withdrawal symptoms. The first dose ofbuprenorphineis given sublingually when the first signs of withdrawal appear. The dose needed to effectively control severe symptoms is titrated as quickly as possible; sublingual doses of 8 to 16 mg/day are typically used.Buprenorphineis then tapered over several weeks. The Substance Abuse and Mental Health Services Administration (SAMHSA)provides information onbuprenorphineand the training required to qualify for a waiver to prescribe the drug, as well as protocols for usingbuprenorphinefor detoxification or maintenance therapy (which are available for download). Methadoneis provided only by SAMHSA-certified opioid treatment programs and in acute care settings under limited circumstances.Methadoneis given orally in the smallest amount that prevents severe, but not necessarily all symptoms of withdrawal. The typical initial dose range is 10 to 30 mg. The titration should be individualized. The dose should not be increased by any more than 10 mg every 5 days. Once initial withdrawal is stabilized, the common daily dose is 60 to 120 mg per day. Symptom scales are available for estimating the appropriate dose. Higher doses should be given when evidence of withdrawal is observed. After the appropriate dose has been established, it should be reduced progressively by 10 to 20% each day unless the decision is made to continue the drug at a stable dose ( Maintenance ). During tapering of the drug, patients commonly become anxious and request more of the drug. Methadonewithdrawal for people with opioid use disorder who have been in amethadonemaintenance program may be particularly difficult because their dose ofmethadonemay be as high as 100 mg once/day; in these patients, the dose should be gradually reduced to 60 mg once/day over several weeks before attempting complete detoxification. has been reported to be associated with QTc prolongation and serious arrhythmias including torsades de pointes (see also Torsades de Pointes Ventricular Tachycardia ). Thus, it should be used very carefully with appropriate patient evaluation and monitoring during initiation and dose titration. Clonidine,a centrally acting adrenergic drug, can suppress autonomic symptoms and signs of opioid withdrawal. Starting dosages are 0.1 mg orally every 4 to 6 hours and may be increased to 0.2 mg orally every 4 to 6 hours as tolerated.Clonidinecan cause hypotension and drowsiness, and its withdrawal may precipitate restlessness, insomnia, irritability, tachycardia, and headache. Rapid and ultrarapid protocolshave been evaluated for managing withdrawal and detoxification. In rapid protocols, combinations ofnaloxone,nalmefene, andnaltrexoneare used to induce withdrawal, andclonidineand various adjuvant drugs are used to suppress withdrawal symptoms. Some rapid protocols usebuprenorphineto suppress opioid withdrawal symptoms. Ultrarapid protocols may use large boluses ofnaloxoneand diuretics to enhance excretion of the opioids while patients are under general anesthesia; these ultrarapid protocols are not recommended because they have a high risk of complications and no substantial additional benefit. Clinicians must understand that detoxification is not treatment per se. It is only the first step and must be followed by an ongoing treatment program, which may involve various kinds of counseling and possibly nonopioid antagonists (eg,naltrexone). 