Low-dose Ketamine and Midazolam as an Adjuvant to IV Morphine for Control of Pain in Cancer Terminal Life Care

Joo, Jin Deok; Kim, Dae Woo; Kang, Yoo Jin

Abstract

BACKGROUND
It is demanding to find a new, or any other effective, method to control the pain in patients with far-advanced cancer, who are experiencing excruciating and intractable pain that responds poorly to rapidly escalating doses of morphine, and who refuse a continuous epidural procedure, or cases involving inadequate regional block due to generalized pain or a previous wide spine operation. This study was conducted to evaluate the effect of a low dose ketamine and midazolam infusion, as an adjuvant to intravenous morphine, to control the intractable pain in these patients. METHODS: Thirty cancer patients, who had not responded to an ordinary morphine infusion, were randomly allocated into 3 groups (n = 10 each). The patients in each group only received initial morphine (Group 1, control group), ketamine 0.1 mg/kg/h in addition to the initial morphine (Group 2), or ketamine 0.1 mg/kg/h and midazolam 0.01 mg/kg/h in addition to the initial morphine (Group 3). If the pain was not decreased to half the initial pain, the continuous IV morphine was escalated to 50% of the previous dosage. In each group, the degree of sedation by the OAA/S's scale, refractory delirium and other side effects were evaluated. RESULTS: Treatment with both ketamine and midazolam (group 3) eliminated the need for any further opioid use, diminished the refractory delirium and provided profound analgesia, with no severe side effects, during the last hours and days of these patients' lives. CONCLUSIONS: The adjuvants, low dose ketamine and midazolam, may have a significant role in the care of patients with pain that respond poorly to opioids, or who experience dose limiting adverse effects, near the end of their lives.