Adverse Drug Reactions in Japanese Patients with End-Stage Heart Failure Receiving Continuous Morphine Infusion: A Single-Center Retrospective Cohort Study

BACKGROUND: Opioids have been reported to be effective for refractory dyspnea in patients with advanced heart failure (HF) in the palliative care setting. OBJECTIVE: The aim of this study was to evaluate the incidence of adverse drug reactions (ADRs) and their relationship with morphine dose/duration or renal insufficiency in patients with end-stage HF receiving continuous morphine infusion. METHODS: We retrospectively studied 38 patients with end-stage HF receiving continuous intravenous or subcutaneous morphine infusion for the relief of breathlessness between 2014 and 2019 (mean age 78 years). The endpoints were nausea/vomiting, respiratory depression, and drowsiness, which are common morphine-related ADRs. RESULTS: Of 38 patients with end-stage HF receiving continuous intravenous/subcutaneous morphine infusion, 14 (37%) experienced ADRs. The median estimated glomerular filtration rate (eGFR) was lower in patients with than in those without ADRs (16 [range 9–48] vs. 41 [range 8–133], respectively; p = 0.011). The ADRs with the highest incidence were drowsiness (n = 13), nausea/vomiting (n =5), and respiratory depression (n =3). There were no differences in the maintenance dose or duration of morphine administration between patients with and without ADRs. A baseline eGFR of 32 mL/min/1.73 m(2) was a good cutoff value for ADR prediction (sensitivity 86%, specificity 96%). A baseline eGFR < 32 mL/min/1.73 m(2) was significantly associated with the occurrence of morphine-related ADRs (odds ratio 6.63, 95% confidence interval 1.19–37.01). CONCLUSIONS: Our results showed that 37% of patients with end-stage HF receiving continuous intravenous/subcutaneous morphine infusion experienced ADRs, especially drowsiness. Patients with eGFR < 32 mL/min/1.73 m(2) were likely to experience morphine-related ADRs.