Lorazepam/opioid analgesics
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Various toxicities: case report A 58-year-old man developed worsening of confusion during treatment with lorazepam for anxiety. Additionally, he developed myoclonus following concomitant administration of morphine and hydromorphone. Subsequently, he developed worsening delirium and tachyphylaxis during treatment with fentanyl, hydromorphone, lorazepam and morphine [not all routes stated; outcomes not stated]. The man was diagnosed with metastatic cancer of biliary or pancreatic origin with diverticulitis, peritoneal carcinomatosis and small bowel obstruction. He also had chronic anxiety, treated with oral lorazepam 1mg. He was hospitalised. He complained of a severe pain and received IV hydromorphone patient-controlled analgesic (PCA) pump 4 mg/hour for it. He had been receiving transdermal fentanyl 100 mg/hour, followed by 150 mg/hour, which was continued and later increased to 200 mg/hour prior to discharge. Thereafter, symptoms of cancer showed improvement. His medications at the time of discharge included hydromorphone PCA pump at 2 mg/hour (basal rate) plus 2mg every 20 minutes (demand dose). The fentanyl transdermal 200 mg/hour patch was also continued. He was also receiving various other medications concomitantly. After 3 days, he presented again to the emergency room with complaints of pain. Palliative care was consulted and his PCA settings were increased to 4 mg/hour (basal rate) and 3mg every 20 minutes (demand dose). The fentanyl transdermal patch was continued. Thereafter, his pain improved. He presented to the emergency room again with symptoms of abdominal distension and an acute worsening of his pain and was re-admitted to hospital after 48 hours of the emergency room visit. He also showed dyspnoea with reclining or speaking. His family noted the onset of myoclonic jerks and worsening delirium. He showed numerous myoclonic jerks, which were not bothersome. The dose of hydromorphone setting was increased to 6 mg/hour (basal rate) and 4mg every 15 minutes (demand settings). The development of myoclonus and the lack of effect of high-dose hydromorphone prompted a switch from hydromorphone to morphine, with a basal rate of 25 mg/hour and demand dosing of 15mg every 20 minutes. Lorazepam was discontinued due to worsening of confusion. Thereafter, treatment with dexamethasone, octreotide and haloperidol were added. The palliative team attributed his myoclonus to an interaction between morphine and hydromorphone. Further examination revealed ascites with peritoneal and omental nodularity. At the time, his pain medications included methadone, fentanyl PCA, lidocaine bolus, ketamine, midazolam and dexmedetomidine. By day 16, anxiety and intermittently increased discomfort were noted, and he received midazolam. Subsequently, he showed signs of peripheral cyanosis and apneic pauses. On day 21, he died [cause of death not stated]. Author comment: "Individualized doses of opioids are often needed to relieve the symptoms. Additionally, their analgesic effects are not easily separated from adverse effects s
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