The efficacy and safety of midazolam with fentanyl versus midazolam with ketamine for bedside invasive procedural sedation in pediatric oncology patients: A randomized, double-blinded, crossover trial

Children with cancer often require sedation before undergoing invasive procedures. Fentanyl, ketamine, and midazolam are effective drugs widely used for procedural sedation. This study aimed to investigate the efficacy and safety of midazolam-fentanyl (M-F) compared with midazolam-ketamine (M-K) for bedside procedural sedation among pediatric oncology patients. A randomized, double-blinded, crossover trial was conducted among children with cancer requiring procedural sedation for invasive procedures. Patients were randomly assigned either intravenous M-F or M-K and subsequently received the alternate regimens following the crossover design of the study. The efficacy and safety of the sedations including sedation time intervals, nausea score, vomiting episodes, pain score, adverse effects, and parent's satisfaction were evaluated. In all, 58 patients with 116 procedural sedations were enrolled. M-K provided a shorter induction time (0:58 vs. 1:23 min) (p = 0.005), but longer sedation (9:02 vs. 5:50 min) (p = 0.019) and emergence time (4:26 vs. 0:56 min) (p = 0.011) compared with M-F. Sedation routes affected the sedation time intervals. Patients had higher rates of vomiting (0, range 0-8 vs. 0, range 0-2) (p = 0.033) but experienced less pain (0 vs. 2) (p = 0.008) in the M-K group. Overall satisfaction and other adverse effects were comparable among both sedation regimens. Combined sedative drugs are recommended to improve the effectiveness of bedside procedural sedation. M-K provided shorter induction, but longer sedation and emergence time compared with M-F. These findings correlated with sedative routes. Patients receiving M-K experienced a higher rate of vomiting, but less painfulness compared with M-F. Overall satisfaction and tolerable side effects were comparable among both sedative regimens.