Oral preanaesthetic medication for children: double-blind randomized study of a combination of midazolam and ketamine vs midazolam or ketamine alone.

Anxiolysis and sedation with oral midazolam are common practice in paediatric anaesthesia. However, good or excellent results are seen in only 50-80% of cases. For this reason, we investigated if addition of a low dose of oral ketamine (MIKE: ketamine 3 mg kg-1, midazolam 0.5 mg kg-1) resulted in better premedication compared with oral midazolam 0.5 mg kg-1 or ketamine 6 mg kg-1 alone, in a prospective, randomized, double-blind study. We studied 120 children (mean age 5.7 (range 2-10) yr) undergoing surgery of more than 30 min duration. After oral premedication in the ward and transfer, the child's condition in the induction room was evaluated by assigning 1-4 points to the quality of anxiolysis, sedation, behaviour at separation from parent and during venepuncture (transfer score). On days 1 and 7 after operation, parents were interviewed for changes in behaviour (eating, sleep, dreams, toilet training), recollection and satisfaction, using a standardized questionnaire. The groups were similar in age, sex, weight, intervention and duration of anaesthesia. The transfer score was significantly better in the MIKE group (12.5 (95% confidence interval (CI) 11.9-13.1)) than in the ketamine or midazolam groups (10.6 (9.8-11.4) and 11.5 (10.7-12.3), respectively). Success rates for anxiolysis and behaviour at separation were greater than 90% with the combination, approximately 70% with midazolam and only 51% with ketamine alone. The incidence of salivation, excitation and psychotic symptoms was low in all groups. Vertigo and emesis before induction were significantly more frequent after ketamine premedication. During recovery, there were no differences in sedation or time of possible discharge. After 1 week, parents reported nightmares (ketamine five, midazolam three, MIKE one), restless sleep (five/four/four) or negative memories (three/four/one). There were no major or continuing disturbances in behaviour or development. In summary, significantly better anxiolysis and separation were observed with a combination of ketamine and midazolam, even in awake children (sedation was not successful according to the preset criteria), than with midazolam or ketamine alone. Duration of action and side effects of the combination were similar to those of midazolam. The combination of both drugs in strawberry flavoured glucose syrup (pH 4.5 approximately) is chemically stable for 8 weeks.

RCT Entities:   Population Interventions Outcomes