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Effect of the Sedative Combination of Ketamine, Morphine and Midazolam on the Quality-of-Life in the Final Days of Terminally Ill Cancer Patients

Noam Asna, Noa Shemesh, Liat Arbel, Rami Ben Yosef, Ron Batash, Moshe Schaffer

Background: Sedation in terminally-ill cancer patients is typically used to alleviate symptoms of physical distress during the last week of life, in order to allow patients to achieve serenity. These include pain, as well as respiratory, neuropsychiatric, and gastrointestinal symptoms.

The purpose of this study is to investigate the effect of the sedative protocol containing ketamine, midazolam, and morphine (KMM) on symptoms of terminally-ill cancer patients at the end-of-life, as well as on consciousness level, and overall survival.

Methods and Findings: This retrospective study included terminally-ill cancer patients (>18 years) who completed cancer-specific treatment and received KMM upon hospitalization. Medical records were reviewed. The symptoms were classified according to their severity before and during treatment. Control of debilitating symptoms and level of consciousness during the hospitalization was clinically evaluated.

Results: The study included 30 patients (10 males; mean age, 55 years). Range doses were: 0.1-1 mg/kg, 0.05-0.5 mg/kg, and 0.5-5 mg/kg daily, for ketamine, midazolam, and morphine, respectively. The mean survival was 4.6 days (therefore, analyses focused on the first 3 days). A statistically significant decrease in pain was achieved on the first day of treatment (P<0.0001). Further improvement was sustained through the following 2 days (P=0.022). An improvement in respiratory, gastrointestinal, and neuropsychiatric symptoms was reported (P=0.033). A significant decline in consciousness level was observed with time. The initial pain level (before administrating KMM) was negatively associated with survival.

Conclusions: The KMM protocol is an effective method in controlling pain and providing relief from respiratory, neuropsychiatric, and gastrointestinal symptoms. No KMMassociated complications were identified. Further research is warranted.