Background: Delirium is a frequent complication in patients with advanced cancer and may result from infection, metabolic abnormalities, central nervous system disease, or medications. Opioid-induced neurotoxicity is an important but often underrecognized cause, particularly in older patients with renal impairment. Current clinical evidence and pharmacologic mechanisms of action will be explained.
Case Presentation: A 72-year-old man with metastatic non-small cell lung cancer involving the spine and liver was admitted with uncontrolled cancer-related pain. His medical history included stage 3 chronic kidney disease, hypertension, type 2 diabetes mellitus, chronic obstructive pulmonary disease, and depression. Regular medications included amlodipine, perindopril , metformin, sertraline, tiotropium, dexamethasone, pantoprazole, coloxyl with senna, and simvastatin. Due to worsening pain and concerns regarding morphine metabolite accumulation, he was rotated from sustained-release morphine to modified-release hydromorphone 8 mg twice daily with immediate-release hydromorphone 2 mg as needed.
Seventy-two hours after commencing hydromorphone, he developed fluctuating confusion, impaired attention, visual hallucinations, agitation, and disorientation. Examination revealed no focal neurological deficits. Investigations, including full blood count, electrolytes, renal and liver function tests, inflammatory markers, urinalysis, chest radiography, and brain computed tomography, showed no acute abnormalities or alternative cause for delirium. Hydromorphone-induced neurotoxicity was suspected based on the temporal relationship and exclusion of other etiologies. Hydromorphone was discontinued, intravenous hydration was commenced, and analgesia was changed to a fentanyl transdermal patch with breakthrough fentanyl. Low-dose haloperidol was administered for agitation. The patient's mental status returned to baseline within 48–72 hours while maintaining satisfactory pain control.
Conclusion: This case highlights hydromorphone as a potential cause of delirium in patients with advanced cancer, particularly those with predisposing risk factors such as chronic kidney disease and advanced age. Recognition of opioid-induced neurotoxicity and timely opioid rotation can rapidly reverse delirium while preserving effective analgesia.