Evaluation of a combination of low-dose ketamine and low-dose midazolam in terminal dyspnea-attenuation of "double-effect"

Abstract

Aim: Of all symptoms in palliative medicine those concerning respiration are most excruciating and difficult to treat. Reticence about the use of morphine for palliation of dyspnea is common, especially in nonmalignant diseases, as there is a fear of causing respiratory depression, particularly where Chronic Obstructive Pulmonary Disease (COPD) exists. This factor is also compounded by the lack of availability of morphine in parts of developing countries. Ketamine has excellent anesthetic and analgesic effects in addition to being easily available. It produces bronchodilatation and does not produce respiratory or cardiovascular depression. The author seeks to evaluate the role of low-dose (0.2 mg/kg) ketamine and midazolam (0.02 mg/kg) in the attenuation of terminal dyspnea. Methods: Sixteen patients with terminal dyspnea, admitted to the Critical Care Unit (CCU) with cancer and other noncancer diagnoses were recruited. The subjective component of dyspnea was assessed using the Graphic Rating Scale (GRS), which has values from 0 - 10, 10 being maximum dyspnea. Each patient received a low-dose of ketamine and midazolam for relief of dyspnea. All the patients received low-flow (2 L/min.) oxygen therapy via nasal cannula. Immediately after admission, all the patients were reassured and nursed in a decubitus position of their choice. The GRS was recorded at the point of admission, 10 minutes after starting oxygen therapy, and ten minutes after administration of low-dose ketamine and midazolam. Hemodynamic parameters were also recorded at these three points. Result: All the patients who enrolled in our study had significant dyspnea at admission, as was evident from the GRS scores of 8.250 (SD 0.91), respiratory rate of 28.56 (SD 5.0), mean arterial blood pressure (MABP) of 102.7 (SD 14.63), pulse rate of 115.62 (SD 23.3), and SpO2 of 92.43 (SD 2.38). All the patients benefited from the combination of ketamine and midazolam, as evidenced by the statistically significant ( P < 0.01) improvement in all monitored parameters. Conclusion: The author concludes that a combination of low-dose ketamine and midazolam can be safely used in the palliation of terminal dyspnea, with excellent results. The duration of action of this combination in providing symptomatic relief is however short-lived, being 36.7 minutes on an average (SD 5.23), thus necessitating intermittent IV top-ups. No adverse reports were obtained in the study.