Parenteral Opioids Effective, Safe for Relieving Terminal Dyspnea

In patients with cancer, parenteral opioids relieved terminal dyspnea at 24 hours in most patients using morphine (70%) and oxycodone (61%) and all patients using of hydromorphone.

Parenteral morphine, oxycodone, and hydromorphone are effective and safe for the treatment of terminal dyspnea resulting from cancer, according to a study published in the Journal of Pain and Symptom Management.

Terminal dyspnea can be one of the most distressing symptoms patients with cancer experience in their final days of life, when many such patients are unable to take oral medications. Investigators therefore explored the effectiveness and safety of parenteral morphine, oxycodone, and hydromorphone to treat terminal dyspnea in these patients.

The researchers conducted a secondary analysis of data from a multicenter, prospective cohort study of 108 inpatients with advanced cancer who were recruited at 5 sites in Japan between 2020 and 2021. Patients received parenteral morphine (n=66), oxycodone (n=34), or hydromorphone (n=8) at an opioid dose of 6-12 mg/day for opioid-naïve patients or a 20%-50% increase in prior dosage for opioid-experienced patients. The intensity of dyspnea symptoms was assessed using the Integrated Palliative Care Outcome Scale (IPOS) at 24 and 48 hours. Dyspnea relief was defined as an IPOS score of 0 or 1.

Our preliminary findings justify future RCTs and/or larger cohort studies with comparison arms to confirm the effects of various opioids for terminal dyspnea.

Among the study participants (mean [SD] age, 72 years; 46% female; 87% receiving supplemental oxygen), dyspnea was caused by lung tumors (39%), pleural effusions (36%), lymphangitis carcinomatosis (18%), and cachexia (12%). Overall, 60 patients were opioid-experienced and were receiving an average dose of 63 (88) mg/day.

The opioid-naïve group received a median parenteral morphine-equivalent daily dose (MEDD) of 6.0 mg/day at baseline. The dose was increased to 12, 6.0, and 6.8 mg/day at 24 hours and 12 mg/day at 48 hours among the morphine, oxycodone, and hydromorphone groups, respectively. The opioid-experienced patients received a morphine, oxycodone, and hydromorphone dose of 18, 15, and 12 mg/day at baseline which increased to 24, 16, and 18 mg/day at 24 hours and 24, 20, and 18 mg/day at 48 hours, respectively.

Mean IPOS scores decreased by 1.4 points among morphine recipients (P <.001), 0.9 points among oxycodone recipients (P <.001), and 2.2 points among hydromorphone recipients (P =.011) at 24 hours compared with baseline. The improvement in IPOS scores were maintained at 48 hours. No significant group differences in IPOS scores were observed at 24 (P =.080) or 48 (P =.322) hours.

Overall, dyspnea relief at 24 hours was achieved by 70% of morphine, 61% of oxycodone, and 100% of hydromorphone recipients (P =.210) and 78%, 63%, and 100% at 48 hours (P =.303), respectively.

Most adverse events were mild to moderate. The most common events were nausea and delirium. No group differences in adverse events were observed.

This study may have been limited by the imbalanced cohorts.

The study authors concluded, “Our preliminary findings justify future RCTs and/or larger cohort studies with comparison arms to confirm the effects of various opioids for terminal dyspnea.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Mori M, Yamaguchi T, Suzuki K, et al. Do types of opioids matter for terminal cancer dyspnea? A preliminary multicenter cohort study. J Pain Symptom Manage. 2023;S0885-3924(23)00461-X. doi:10.1016/j.jpainsymman.2023.04.009