ORAL MIDAZOLAM WITH AN ANTACID INCREASES THE SPEED OF ONSET OF SEDATION IN CHILDREN PRIOR TO GENERAL ANESTHESIA

Abstract

S300 INTRODUCTION: This study was designed to determine if the inclusion of an antacid with oral midazolam increases the speed of onset of sedation in children prior to general anesthesia. METHODS: A randomized, double-blinded, controlled study was carried out in 40 pre-surgical ASA 1 & 2 patients (ages 2-6 years) at Lucile Salter Packard Children's Hospital, Stanford University. Human Studies Committee approval and parent/guardian consent were obtained. Children with gastrointestinal pathology were excluded. Patients were randomly divided into two groups. Group 1 received midazolam 0.5 mg/kg mixed with sodium citrate 1 ml/kg up to 20 ml (pH 4.5). Group 2 (control) received midazolam 0.5 mg/kg mixed with Hawaiian Fruit Punch 1ml/kg up to 20 ml (pH 3). Each patient was evaluated prior to premedication and again at 5 minute intervals for up to 30 minutes by a blinded observer. The evaluator scored the patient for anxiety (1 to 4) and sedation (1 to 5). Separation of child from parent was scaled as easy separation (1) to crying and clinging to parents (4). With the standard anesthetic monitors in place, a routine mask induction proceeded and the induction was scored as excellent (1) to poor (4). The times to first change in sedation and anxiety scores were analyzed using the unpaired Student t-test. The final sedation, final anxiety, separation, and induction scores were analyzed using the Mann-Whitney U test. Age, weight, pre-op anxiety score, and pre-op sedation score were comparable in the two groups. RESULTS: After premedication, the onset of sedation (mean +/- SD), measured by the first change in sedation score, was determined to be significantly faster in Group 1 (17.8 mins +/- 7.11) as compared to Control Group 2 (21.9 mins +/- 5.34) p<0.05 (Figure 1), There was no difference of onset in anxiety, final sedation/anxiety, separation, or induction scores.Figure 1DISCUSSION: Commercially available midazolam has a pH of 3.5 and is more water soluble than at its physiologic pH. At a pH of 4.5, midazolam undergoes a conformational change such that its imidazole ring closes, making it more lipophilic. We propose that the decreased onset time observed in our study is a result of increasing the pH of the oral premedicant mixture. The higher pH enhances its lipid solubility and speeds its absorption across the gastric mucosal membrane.