Marked and sustained reduction of opioid requirements after administration of intravenous naloxone for respiratory depression

Naloxone is a mu-opioid antagonist used to reverse opioid-induced sedation and respiratory depression. When administered at the low subtherapeutic doses concurrently with opioids, it has been observed to improve opioid analgesia in chronic but not acute pain. We present a case of a 33 year-old man with widely metastatic stage IV diffuse large B-cell lymphoma and a long history of intermittent exposure to hydromorphone. He required up to 18 mg intravenous boluses of hydromorphone during prior pain exacerbations. On this occasion, he had excruciating abdominal pain due to bowel prolapsed through his ileostomy. He was started on intravenous hydromorphone that was rapidly titrated to 19 mg/hr. At this dose, he experienced some improvement in analgesia and no sedation. He was changed to methadone over the next 2 days, and good analgesia was achieved 36 hours later at a dose of 8 mg/hr of intravenous methadone. Twelve hours later, the patient developed sedation and respiratory depression and was electively intubated for 12 hours. During that time naloxone 1.2 mg was administered intravenously in divided doses. Upon extubation the patient's opioid requirements markedly dropped to 1.3 mg/hr hydromorphone (a 15-fold decrease). This effect was sustained for over 6 weeks. This case report demonstrates a marked (15-fold) and sustained decrease in opioid requirements after an episode of opioid-induced sedation and respiratory depression which were reversed by naloxone administration. Possible explanations of this unusual response are: 1) decreased opioid tolerance by naloxone; 2) resolution of hydromorphone-induced hyperalgesia while on methadone; 3) resolution of an acute pain crisis that incidentally coincided with the administration of a large dose of naloxone. However, none of these explanations adequately explains this patient's profound and sustained reduction in opioid requirements.