Ketamine-Midazolam versus Morphine-Midazolam for continuous sedation of critically ill patients in intensive care units in Uganda. A randomized controlled trial.
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Introduction: Critically ill patients experience pain, discomfort and anxiety, which require sedation to facilitate life-saving procedures such as mechanical ventilation. Ketamine poses an attractive and readily available alternative for continuous analgo-sedation of critically ill patients to usual care of opioids. It may provide better clinical outcomes in terms of incidence of delirium, incidence of hypotension requiring vasopressor support and duration of mechanical ventilation compared to Morphine in combination with Midazolam. Objective: The aim of this study was to compare duration of mechanical ventilation, incidence of delirium and use of vasopressor therapy among patients on continuous sedation with Ketamine-Midazolam with those under Morphine-Midazolam in intensive care units in Uganda. Methodology: We conducted a prospective, double-blinded, superiority, multicenter randomized control trial. Critically ill patients above 12 years of age requiring continuous sedation for at least 24 hours in the ICU were screened, and those meeting selection criteria were enrolled into the study. Participants were consecutively randomized to receive either Ketamine-Midazolam or Morphine-Midazolam using a block sequence technique. Blinding was done at patient/next of kin level as well as investigator/data collector level. Enrolled subjects were followed up for incidence of delirium, duration of mechanical ventilation and vasopressor requirements for 14 days or until discharge/death. Patient demographics, admission diagnosis, co-morbidities and related data were collected and results analyzed. Results: At study termination due to futility, 124 patients were enrolled from the 6 intensive care units involved in the study; 60 patients were randomized to Morphine-Midazolam group and 64 to Ketamine-Midazolam. There was no statistically significant difference between the Morphine-Midazolam group and Ketamine-Midazolam group in terms of duration of mechanical ventilation, incidence of delirium and incidence of vasopressor therapy by days 3, 7 or 14 of follow up. However, trends towards increased delirium incidence in the Ketamine group by day 3 (12.5% vs 22.2%, 0.199) and increased vasopressor use in the Ketamine-Midazolam were noted by day 7 of follow up (7.1% vs 18.8%, 0.187).The ICU length of stay(9.3±8.2 vs 9.1±7.2, 0.892) daily intravenous fluid therapy, and mortality rates(43.6% vs 46.3%, 0.768) were comparable between the two treatment arms. Conclusion: This study shows that Ketamine-Midazolam is not superior to Morphine-Midazolam for continuous patient sedation in the intensive care unit as far as duration of mechanical ventilation, incidence of delirium and incidence of vasopressor therapy are concerned. The study also affirms the safety of ketamine use for analgo-sedation without increase in incidence of adverse events, ICU length of stay or mortality rate.