Background

Medical benefits of peripherally-acting mu-opioid receptor antagonists other than improving opioid-induced constipation remain unclear. Our aim was to evaluate the association between the use of naldemedine and incidence of hyperactive delirium in cancer patients receiving chemotherapy and opioid therapy.

Methods

We conducted a propensity score-matched analysis using a nationwide inpatient database in Japan. Cancer patients receiving both inpatient chemotherapy and opioid therapy from June 1, 2017 to March 31, 2018 were included. Patients receiving naldemedine were matched to control patients by propensity score. Our primary outcome was the incidence of hyperactive delirium during hospitalization, and secondary outcomes were the length of hospital stay, hospital costs, in-hospital mortality, and incidence of ileus.

Results

Of 34,031 patients receiving inpatient chemotherapy and opioid therapy, 1905 (5.6%) were included in the naldemedine group. After one-to-four propensity score matching, 1904 patients were included in the naldemedine group and 7616 in the control group. Naldemedine users had significantly reduced incidence of hyperactive delirium compared with the control patients (19.4% vs 23.3%; risk difference, -3.9 [95% confidence interval, -5.9 – -1.9]; risk ratio, 0.83 [0.75–0.92]; P<0.001; subdistribution hazard ratio, 0.85 [0.75–0.97]; P=0.015). The median length of hospital stay was significantly shorter in the naldemedine group compared with the control group (12 days [interquartile range, 6–23] vs 14 days [6–26]; P=0.001). The median hospital costs were also significantly lower in the naldemedine group compared with the control group (US $6179 [3351–10,026] vs US $6576 [3436–11,107]; P<0.001). No significant differences were found for in-hospital mortality or incidence of ileus between the groups.

Conclusions

Our findings suggest that the use of naldemedine may have benefits in preventing hyperactive delirium, shortening hospital stay, and decreasing hospital costs in cancer patients receiving chemotherapy and opioid therapy.