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.