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 inpaediatric anaesthesia. However, good or excellent results are seen in only50-80% of cases. For this reason, we investigated if addition of a low doseof oral ketamine (MIKE: ketamine 3 mg kg-1, midazolam 0.5 mg kg-1) resultedin better premedication compared with oral midazolam 0.5 mg kg-1 orketamine 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 surgeryof more than 30 min duration. After oral premedication in the ward andtransfer, the child's condition in the induction room was evaluated byassigning 1-4 points to the quality of anxiolysis, sedation, behaviour atseparation from parent and during venepuncture (transfer score). On days 1and 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 wassignificantly 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) and11.5 (10.7-12.3), respectively). Success rates for anxiolysis and behaviourat separation were greater than 90% with the combination, approximately 70%with midazolam and only 51% with ketamine alone. The incidence ofsalivation, excitation and psychotic symptoms was low in all groups.Vertigo and emesis before induction were significantly more frequent afterketamine premedication. During recovery, there were no differences insedation or time of possible discharge. After 1 week, parents reportednightmares (ketamine five, midazolam three, MIKE one), restless sleep(five/four/four) or negative memories (three/four/one). There were no majoror continuing disturbances in behaviour or development. In summary,significantly better anxiolysis and separation were observed with acombination of ketamine and midazolam, even in awake children (sedation wasnot successful according to the preset criteria), than with midazolam orketamine alone. Duration of action and side effects of the combination weresimilar to those of midazolam. The combination of both drugs in strawberryflavoured glucose syrup (pH 4.5 approximately) is chemically stable for 8weeks.