The FDA states that clinicians should limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients with inadequate alternative treatment options. Avoid prescribing opioid-containing cough medicines to patients taking benzodiazepines or other CNS depressants, including alcohol. When prescribing medications, limit dosages and the duration of each drug to the least possible while achieving the desired clinical effect. Counseling patients regarding possible adverse severe reactions is critical. Despite the warnings, the use of other sedative medications is not an absolute contraindication when patients are using certain opioid medications. The FDA clarified this warning for patients taking opioid-addiction medications. Specifically, the FDA advised that the opioid-addiction medications buprenorphine and methadone should not be withheld from patients taking benzodiazepines or other drugs that depress the CNS. Although the combined use of these drugs increases the risk of severe side effects, the harm caused by untreated opioid addiction can outweigh these risks. These medications are often used with counseling and behavioral therapies for patients undergoing treatment with medications for opioid use disorder (MOUD), and patients can be treated with them indefinitely. Careful patient monitoring is necessary when prescribing benzodiazepines or other CNS- depressant agents in combination with MOUD and appropriate and continued patient counseling. 122 Tapering of Chronic Opioid Therapy Sometimes, clinicians must decide whether to decrease or discontinue chronic opioid therapy. Many factors may contribute to this decision: Patient request; lack of response; signs of substance abuse disorder, overdose, or other serious adverse events; or early signs of overdose risk. Therefore, any tapering schedule must be patient-specific to minimize withdrawal symptoms while maintaining adequate pain management. A general recommendation is to begin with a 10% decrease of the initial dose per week. Some patients who have taken opioids for a long time may require slower tapers (e.g., 10% per month). Adjust the rate and duration of the taper based on the patient’s response. It is advisable to slow or pause a taper to manage withdrawal symptoms rather than reversing the taper. It is essential to discuss the risk of overdose if a patient quickly returns to a prescribed higher dose. Consider prescribing naloxone to reverse possible overdose symptoms. After achieving the smallest available dose, the interval between opioid doses increases, and opioids stop when taken less than once a day. Patients at high risk of harm, such as pregnant women or those with substance abuse disorder, may require coordination with treatment experts. Withdrawal symptoms are especially concerning in pregnant patients due to the risks to the mother and fetus. It is crucial to ensure patients receive appropriate encouragement and psychosocial support, including consultations with mental health providers and treatment for opioid use disorder as needed. Reassure patients that most people
have improved function, without worse pain, after tapering opioids. In addition, some patients experience less pain after a taper, even though the pain may worsen initially. Nonopioid Pain Treatment Nonopioid pain management is an important tool in the war against both acute and chronic pain. The Alternatives to Opiates (ALTO) program was launched in 2016 at St. Joseph’s Regional Medical Center in Paterson, New Jersey. This program was novel at the time and used targeted nonopioid medications, trigger-point injections, nitrous oxide, and ultrasound-guided nerve blocks to tailor its patients’ pain management needs and avoid opioids when possible. According to their website, the hospital reduced opioid use by 50% since the inception of the program. 113 The ALTO program has matured, and other institutions have implemented similar programs. The Colorado ALTO project has a toolkit with specific recommendations for the treatment of acute and nonacute pain. It is accessible at https://cha.com/wp-content/ uploads/2018/04/Colorado-ALTO-Project-Clinician- Toolkit.pdf. This project, initially designed and tested on patients presenting to the ED, has categories of patients organized by pain type within the toolkit. It can be used by all providers to treat various types of pain in the ED, inpatient, and outpatient setting. Other clinical applications guides are available and include specific recommendations for treatment regimens depending on the acute complaint in the ED. The use of NSAIDs, skeletal muscle relaxants, and topical medications is very common. More recent additions include the use of low dose ketamine and haloperidol in the treatment of acute pain in the Emergency Department setting. 114 The American Academy of Pain Medicine developed a clinical practice guideline for use in the treatment of pain that can be reviewed on their website: https://painmed.org/clinical-guidelines/. A comprehensive report on pain management practices can be found on the U.S. Department of Health and Human Services website: https://www. hhs.gov/opioids/prevention/pain-management- options/index.html. BEFORE MOVING ONTO THE NEXT SECTION, PLEASE COMPLETE CASE STUDY 4 ON THE NEXT PAGE. Acute Treatment of Overdose: Naloxone (Narcan) Overdose involving opioids continues to be common, and acute treatment of opioid overdose typically utilizes naloxone (Narcan) to reverse the dangerous respiratory depression and sedation associated with severe toxicity. Scientists looking to treat constipation caused by chronic opioid use first patented naloxone in New York in 1961. In 1971, the Food and Drug Administration approved naloxone for treating opioid overdoses by intravenous or intramuscular injection. In 1996, piloted use of take-home naloxone kits started in 15 states. Naloxone is a strong opioid antagonist. Dosing of
naloxone in medical settings should start low to reverse severe respiratory depression but with the intent of avoiding full withdrawal. Acute withdrawal results in dysphoria, insomnia, pupillary dilation, piloerection, yawning, muscle aches, lacrimation, rhinorrhea, nausea, fever, sweating, vomiting, and diarrhea. 123 Currently, intranasal (IN) naloxone kits are widely distributed throughout the United States and can be used by laypersons to revive individuals who are unresponsive due to opioid overdose. Naloxone is combined with oral buprenorphine in some formulations like Suboxone (buprenorphine + naloxone) to discourage intravenous injection. When a combination medication like Suboxone is ingested, the buprenorphine gets absorbed in the stomach while the naloxone is inactivated by stomach acid and does not result in opiate withdrawal. Administration of naloxone in the setting of overdose or suspected overdose presents little to no risk to the patient if the overdose or alteration in mental status is not from opiates. It is important to communicate this to families or friends and the public to encourage the use of naloxone. Naloxone distribution campaigns vary between states, with some states providing free naloxone kits from pharmacies, distribution events, and even vending machines. In March 2023, the FDA approved 4 mg naloxone nasal spray for over-the-counter, nonprescription use. Opioid Withdrawal Successful treatment of opioid overdose frequently results in withdrawal symptoms for the patient habituated to opioids. Treatment of opioid withdrawal symptoms can be complex. In the acute care setting the withdrawal can be abrupt and severe following the use of naloxone or due to precipitated withdrawal related to the inappropriate use of buprenorphine. Clinical evaluation of withdrawal should utilize the Clinical Opiate Withdrawal Scale (COWS) score to assist in decisions related to treatment. This 11-item scale can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. A template of this scale can be found at this site: https://www.asam.org/docs/default-source/ education-docs/cows_induction_flow_sheet.pdf. Some adjunct medications can serve to lessen the symptoms and bridge the patient to more definitive therapy, or past the duration of action of the naloxone. It is important to note that the duration of action of naloxone is typically less than 1 hour, while the duration of action of the opioid agent that was responsible for the overdose initially may be multiple hours. This is important when creating a treatment plan for those who are treated in the ED or on the street and refuse to be monitored or evaluated after they wake from their sedation.
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