From the Guidelines
Narcotics should be used with extreme caution in patients with mitochondrial deficiency, prioritizing careful monitoring for respiratory depression and metabolic decompensation, and considering alternative analgesic strategies whenever possible. When narcotics are necessary, it is recommended to start with reduced doses (approximately 25-50% of standard dosing) of shorter-acting opioids like fentanyl (0.5-1 mcg/kg) or hydromorphone (0.01-0.02 mg/kg), rather than longer-acting agents like morphine or methadone 1.
Key Considerations
- Avoid propofol completely due to the risk of propofol infusion syndrome, and use caution with benzodiazepines which may worsen respiratory depression.
- Multimodal analgesia is preferred, incorporating non-opioid options like acetaminophen (10-15 mg/kg every 4-6 hours, not exceeding 4g daily in adults) and regional anesthesia techniques when possible.
- Patients should be closely monitored for lactic acidosis, respiratory compromise, and neurological deterioration during narcotic administration.
- The use of lactate-free i.v. fluids, such as 5% dextrose –0.9% saline, is recommended to maintain normoglycaemia and prevent lactic acidosis, especially during preoperative fasting periods 1.
Rationale
Mitochondrial dysfunction impairs cellular energy production, making these patients particularly vulnerable to the metabolic and respiratory effects of narcotics, which can trigger metabolic crises by further compromising ATP production and cellular respiration 1. Given the diverse nature of mitochondrial disease, meticulous individual assessment is crucial, and careful attention to fluid management is essential to prevent adverse events such as hypovolaemia, acute on chronic renal failure, and metabolic decompensation 1.
Clinical Approach
Given the limited and inconclusive evidence base for the use of general anesthesia in patients with mitochondrial disease, a cautious approach is warranted, with careful consideration of the potential risks and benefits of narcotic use in each individual case 1. By prioritizing careful monitoring, reduced dosing, and alternative analgesic strategies, clinicians can minimize the risks associated with narcotic use in patients with mitochondrial deficiency.
From the Research
Guidelines for Using Narcotics in Patients with Mitochondrial Deficiency
- There is currently no clear evidence supporting any pharmacological interventions for most mitochondrial disorders, except for coenzyme Q10 deficiencies, Leber hereditary optic neuropathy, and mitochondrial neurogastrointestinal encephalomyopathy 2.
- Some drugs, including narcotics, may potentially have detrimental effects on mitochondrial dysfunction, and should be avoided whenever possible 2, 3.
- Mitochondrial patients needing treatment with narcotics should be carefully monitored, clinically and by laboratory exams, including creatine kinase and lactate 2.
Narcotics and Mitochondrial Toxicity
- Certain opioids, such as methadone and fentanyl, have been shown to negatively impact mitochondrial morphology, which may be associated with neuronal cell death 4.
- Morphine, on the other hand, did not appear to have any significant effects on mitochondrial morphology in one study 4.
- The use of narcotics in patients with mitochondrial deficiency should be approached with caution, and alternative treatments should be considered whenever possible 3, 5.
Treatment Considerations
- Treatment of mitochondrial disorders is based on five main columns, including symptomatic measures, application of supportive agents, dietary measures, physiotherapy, and the avoidance of drugs known to be toxic for mitochondrial functions 3.
- Nutritional supplements, pharmacological agents, and physical therapies have been used in different clinical trials, but the efficacy of these interventions needs to be further evaluated 6.
- Lifestyle changes, such as weight loss, exercise, and nutrition, may also help improve mitochondrial function in patients with mitochondrial deficiency 5.