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

Abstract

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.

Keywords:

• Fentanyl
• ketamine
• midazolam
• pediatric oncology
• procedural sedation

Acknowledgments

The authors gratefully acknowledged Mrs. Supak Cae-Ngow, Office of Research and Development, Phramongkutklao Hospital, and Phramongkutklao College of Medicine for statistical analysis. The authors also thank the physicians, nurses, patients, and families for participating in this study.

Disclosure statement

The authors declare that they have no competing interests.

Funding

The funding to conduct the study, analyze and submit the study for publication was provided by the Phramongkutklao College of Medicine.

Availability of data and material

The datasets generated during the current study are not publicly available due to privacy and ethics restrictions.

Authors’ contributions

CM contributed to patients’ care, conceptualized and designed the study, managed the program overall, collected, analyzed, and interpreted data and was a major contributor in writing the manuscript. NL, AP, PR, and CT were involved in patients’ care and analyzed and interpreted the patient’s data. All authors critically reviewed and approved the final manuscript.

Ethics approval, consent to participate and for publication

Written informed consent and assent forms were obtained from all participants. This study was approved by the Institutional Review Board, Royal Thai Army Medical Department (IRBRTA 1602/2561) following the ethical principles of the Declaration of Helsinki (1964), including revisions.