Background and Aims:Prolonged mechanical ventilation after cardiac surgery is associated with serious complications that increase morbidity and mortality. The present study was designed to compare ketamine-propofol (KP) and ketamine-dexmedetomidine (KD) combinations for sedation and analgesia in patients after coronary artery bypass graft (CABG) surgery as regards hemodynamics, total fentanyl dose, time of weaning from mechanical ventilation, time of extubation, and any adverse outcome.Materials and Methods:Seventy post-CABG patients were sedated using ketamine 1 mg/kg IV then 0.25 mg/kg/h infusion combined with either dexmedetomidine or propofol to maintain Ramsay sedation score ≥4 during assisted ventilation. Group KP received ketamine + propofol 1 mg/kg bolus followed by 25–50 μg/kg/min. Group KD received ketamine + dexmedetomidine 1.0 μg/kg over 20 min and then 0.2–0.7 μg/kg/h. Total dose of fentanyl in the first 24 h, time of weaning, time of extubation, mean arterial blood pressure, heart rate, and Intensive Care Unit (ICU) stay time were recorded.Statistics:Sample size of 35 patients was calculated for 90% power, α = 0.05, β = 0.1, and anticipated effect size = 0.40 using sample size software (G*Power version 3.00.10, Germany). Analytic statistics was performed on IBM compatible computer using SPSS version 11.5 (IBM, New York, United States) software package under Windows XP operating system. All results presented in the form of mean ± standard deviation. Data compared using unpaired Student's t-test, P < 0.05 was considered as statistically significant.Results:Group KD showed a significant decrease in mean time of weaning and extubation in group KD in comparison with group KP (374.05 ± 20.25 min vs. 445.23 ± 21.7 min, respectively, P < 0.001) (432.4 ± 19.4 min and 504 ± 28.7 min, respectively, P < 0.0001). Fentanyl consumption showed a significant decrease in group KD in comparison with group KP (41.94 ± 20.43 μg and 152.8 ± 51.2 μg, respectively, with P < 0.0001). There were insignificant difference between both groups as regards hemodynamic stability and length of ICU stay.Conclusion:Using KD combination for sedation, post-CABG surgery provided short duration of mechanical ventilation with less fentanyl dose requirement in comparison with KP with insignificant difference in both groups as regards hemodynamic stability and length of the ICU stay.