By Monique Findlay, Zheng Cheng Zhu
Article Reference: Whately, Y. and Stead, M. (2023) ‘Perioperative management of patients on naltrexone’, Australasian anaesthesia 2023. Edited by B. Cheung. doi:https://doi.org/10.60115/11055/1180.
Key Points
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Naltrexone is a long-acting opioid receptor antagonist, used commonly to manage alcohol use disorder.
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Due to its opioid receptor antagonism, naltrexone presents challenges for managing pain in the perioperative period – making patients both resistant to, and have increased sensitivity to the respiratory side effects of opioids.
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It is recommended to discontinue naltrexone 3 days before surgery to ensure effective and safe use of opioid analgesia.
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In emergency cases, additional post op monitoring may be needed, as higher doses of opioid are required to overcome the naltrexone blockade, making patients vulnerable to respiratory side effects.
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In all cases, an individualised and multi-disciplinary approach is recommended for optimal care.
Case
You are an anaesthetic trainee working in a pre-assessment clinic. You see a 45-year-old male patient scheduled for an elective laparoscopic cholecystectomy. The patient has no significant past medical history besides a history of alcohol use disorder, for which he has been on naltrexone 50mg daily for the past 6 months.
He reports good compliance with his medication and has maintained sobriety.
You remember learning that some extra planning and consideration is required with naltrexone but you can’t remember why.
What is Naltrexone
Naltrexone is a competitive opioid receptor antagonist most commonly used in the treatment of alcohol use disorder. It has high mu opioid receptor affinity but does not activate them and blocks opioids from attaching and mediating their effects.
In the treatment of alcohol use disorder, it works by blunting the opioid receptor-mediated reward pathway and blocking the pleasurable effects of endogenous opioids that are released with alcohol consumption. It is also used in opioid abstinence programmes. In other drug combinations and dose formulation, it can be used in weight loss, chronic pain, and severe constipation.
The most common formulation is the daily oral 50mg tablet, which is used in alcohol and opioid dependence. Other formulations of naltrexone include a long-acting surgical implant, monthly depo injection, a combination drug with bupropion, and a low-dose tablet form.
Relevance for the Anaesthetist
Patients taking naltrexone present a significant challenge in managing perioperative pain because of their competitive blockade of opioid analgesics. It reduces the effectiveness of opioids, often necessitating higher doses to achieve adequate pain relief. However, the increased opioid requirement in turn heightens the risk of opioid-related side effects, such as respiratory depression and sedation.
Due to the homeostatic upregulation of opioid receptors that can occur after long-term naltrexone use, patients who have stopped taking naltrexone pre-op remain at increased risk of opioid-induced adverse effects with conventional analgesic doses.
Careful consideration is needed for these cases and planning between the anaesthetist, surgical team, patient, and naltrexone prescriber is essential to ensure the best outcome. As such, timely detection and referral of these patients to multidisciplinary perioperative teams would allow streamlined optimisation, increase team preparedness, prevent unnecessary delays and improve patient outcomes.
Management of Patients for Elective Procedures
If the patient is presenting for a minor procedure with minimal expected postoperative pain, then it is reasonable to continue naltrexone and use non-opioid analgesia. Examples include minor plastics and general surgical cases where combination of local anaesthetic and simple analgesia may be sufficient.
In most cases, where there is an expected need for opioids, oral naltrexone should be stopped at least 24 hours, and ideally 72 hours, prior to surgery. A longer period may be required in renal or hepatic insufficiency and for long-acting formulations. While naltrexone therapy is temporarily discontinued, extra support is recommended as it is a vulnerable time for potential relapse.
Management in Acute or Emergency Cases
In emergency cases, where discontinuation is not feasible, careful planning and implementing an opioid-sparing strategy is essential.
These patients are prone to variability in their response to opioids and must be monitored in a space with a capacity for airway and ventilation support due to the high risk of respiratory depression. If the last dose of naltrexone was taken within 72 hours of surgery, higher doses of opioids will be required for effective pain management. Prioritising alternative pain management techniques through neuraxial or regional anaesthesia, and non-opioid analgesia is favoured in these cases to minimise unpredictable and harmful effects.
Post-operative planning
In the post-op period, the Acute Pain Service, in liaison with the Addiction Medicine service, should be involved to guide the analgesic regime . Determining the optimal time to resume naltrexone requires an individualised, multi-disciplinary approach. The decision must carefully balance the need for effective pain management with the potential risks of restarting naltrexone too soon, as well as the risks of delaying its use, which could hinder the therapeutic benefits it was initially prescribed for. Once the acute pain has resolved and opioids have been discontinued, it is recommended to have at least a 5 day opioid free interval before restarting naltrexone. If there are any doubts or concerns regarding opioid dependence, a naltrexone challenge can be performed to avoid any precipitated withdrawal.
Conclusion
You sit down with your supervisor to discuss the case. You correctly flag your patient with your institution’s Acute Pain service. They agree with your plan for the patient to discontinue naltrexone 3 days before surgery, and adopt an opioid-sparing anaesthetic and to minimise their use post-operatively. You coordinate with the patient, surgeon, and naltrexone prescriber who are all on board..
The case goes well. The Acute Pain Service are involved post-operatively and manage to avoid excess use of opioids following surgery. The patient experiences no opioid-induced sedation or ventilatory impairment.
The patient is safely restarted on his regular medication.
References
Beauchamp GA, Hanisak JL, Amaducci AM, Koons AL, Laskosky J, Maron BM, McLoughlin TM. Perioperative Management of Patients on Maintenance Medication for Addiction Treatment: The Development of an Institutional Guideline. AANA J. 2022;90(1):50-57. PMID: 35076384.
Lane O, Ambai V, Bakshi A, et al Alcohol use disorder in the perioperative period: a summary and recommendations for anesthesiologists and pain physicians. Regional Anesthesia & Pain Medicine 2024;49:621-627.
Whately, Y. and Stead, M. ‘Perioperative management of patients on naltrexone’, Australasian anaesthesia 2023. Edited by B. Cheung. doi:https://doi.org/10.60115/11055/1180.
