A randomized-controlled, double-blind study to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine on postoperative analgesic in children undergoing lower abdominal surgery.


Shirmohammadie et al (Acta Biomed 2018;89(4):513-518) report a double-blind RCT to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine in children. The authors studied 80 children aged 1-3 years undergoing elective inguinal hernia repair and/or urethroplasty for hypospadias for 24 hours where caudal block was the only pre-emptive analgesia given. It is essentially a replica of a study by Kumar et al. (Anesth Analg 2005;101:69-73) who studied children aged 5-10 years, and arrived at remarkably similar results. They found that the time to first supplementary analgesia was extended from 7.2+/-1 hrs with no adjuvant drug to 12.8+/-2 hrs with ketamine 0.5mg/kg, to 18.2+/-2 hrs with midazolam 50mcg/kg and to 20.9+/-3 hrs with neostigmine 2mcg/kg. In all cases 1ml/kg of 0.25% bupivacaine was used. At face value this study looks reasonable, although there are some shortcomings in the level of detail provided for the methods. While the results are clinically substantial and add support to existing literature, increased nausea and sedation have been reported elsewhere but were not addressed in the paper. As comprehensive dose response curves for each adjuvant drug do not exist, it is also possible that the observed differences are not comparisons of equipotent doses of each adjuvant drug. Safety data for neuraxial use of preservative containing formulations of neostigmine are also lacking.

Take home message

This paper adds to evidence that midazolam and neostigmine are effective adjuvants to bupivacaine for caudal analgesia in children. Adverse effect profiles and safety data are still lacklustre for routine use. Furthermore, in practice when supplemental analgesia is required in these cases, oral paracetamol alone is usually sufficient.

Reviewed by: Dr Bae Corlette