Midazolam is widely used as a preanesthetic medication for children. Prior studies have used extemporaneous formulations to disguise the bitter taste of IV midazolam and to improve patient acceptance, but with unknown bioavailability. In this prospective, randomized, double-blinded study we examined

A comparison of three doses of a commercially prepared oral midazolam syrup in children

Rectal route in the 21st Century to treat children

The effect of aging on the pharmacodynamics of midazolam was investigated in a double-blinded study involving 39 consenting patients ranging in age from 39 to 77 yr. Midazolam was infused intravenously (i.v.) using a pharmacokinetic model-driven drug infusion device to achieve a plasma midazolam concentration that was held constant for the 10-min duration of the study. Blood samples were obtained from the radial artery at 5 and 10 min for subsequent measurement of the plasma midazolam concentrations. With the 10-min sample, the patients were also assessed for the presence or absence of responsiveness to verbal command. To ensure that the pharmacodynamic end-point was assessed under the condition of a relative steady-state effect-site midazolam concentration, only those patients (n = 33) in whom the plasma midazolam concentration at 10 min was within 30% of the measured concentration at 5 min were included in the subsequent data analyses. Logistic regression was used to fit the verbal command response/no response data to a mathematical model that included patient age and the plasma midazolam concentration measured at 10 min. Cp50, the steady-state plasma midazolam concentration at which 50% of patients would be expected not to respond to a specific stimulus (e.g., verbal command), was calculated as a function of age from the parameterized logistic model. The midazolam Cp50 for response to verbal command decreased significantly (P = 0.034) with increasing patient age, demonstrating that aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam independent of pharmacokinetic factors.

Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam.

Preanesthetic medication with rectal midazolam in children undergoing dental extractions.

Rectal ketamine and midazolam for premedication in pediatric dentistry.

The present study aimed to assess the pharmaco-clinical profile of infants premedicated with rectal midazolam. The results were compared with those of a reference drug, flunitrazepam. Infants undergoing minor surgery were divided into three groups : group A (n=30), with a mean age of 15.8±13.2 months and a mean weight of 8.6±3.3 kg, receiving 0.33 mg · kg−1 flunitrazepam; group B (n=15), with a mean age of 11.2±10.7 months and a mean weight of 9.3±3.1 kg, receiving 0.3 mg · kg−1 midazolam; and group C (n=30), with a mean age of 15.5±9.1 months and a mean weight of 10.7 ±2.5 kg, receiving 0.4 mg · kg−1 midazolam. An aqueous solution of each drug was administered with atropine sulfate (0.02 mg · kg−1) 20 min prior to induction of anaesthesia. The drug was well tolerated in 84 % of cases. Statistically significant haemodynamic changes consisted of: a 9 c · min−1 decrease in heart rate (p <0.05) and a 12 mmHg decrease in systolic and diastolic blood pressures (p <0.05) in group C; a 6 mmHg decrease in systolic blood pressure (p <0.05) in groupe B. The tranquillizer action was either excellent or good in 93 % of groups B and C compared with only 40 % in group A (p <0.001 in both cases). Somnolence was attained in 60 % of group A, 26.6 % of group B and 30 % of group C. A mask was much better accepted in group C (86.6 %) than in group B (66.6 %; p <0.05) or in group A (36.6 %; p <0.01). Therefore, midazolam given rectally at 0.4 mg · kg−1 was better than flunitrazepam, because of a greater therapeutic effect for an equivalent rate of side effects.

Comparaison du midazolam et du flunitrazépam en prémédication par voie rectale chez le nourrisson

The useful intramuscular premedication dose of midazolam was determined in 100 children divided up in three age groups: one month to three years, 3 to 10 years, 10 to 15 years. All biometric parameters were normal for the age, and comparable between similar age groups. Haemodynamic and respiratory parameters were not altered by the premedication. The reduction in anxiety, as assessed by the child's behaviour, was good or excellent in more than 85% of cases from all age groups; it was proportional to the dose used. The doses that had, for equivalent reductions in anxiety as assessed by the chi-square test, the least hypnotic effect, were: 0.5 mg X kg-1 before three years of age, 0.4 mg X kg-1 for the 3 to 10 yr olds, and 0.25 mg X kg-1 for the 10 to 15 yr olds. This fall in dose with age, quite usual in paediatrics, was not unexpected. The level of consciousness, one hour after surgery, was always normal. No undesirable side-effect was observed. These results, together with its physical, chemical and pharmacodynamic characteristics, make midazolam a choice drug for intramuscular premedication in children, with a foreseeable use in day-care anaesthesia. The unexpected finding of an age-dependent dissociation between the reduction in anxiety and the hypnotic effect is discussed in the light of a study carried out in the adult and recent data from the literature.

La prémédication intramusculaire au midazolam chez le nourrisson et l'enfant

The material included two groups of 10 women undergoing diagnostic laparoscopy. General anesthesia was administered by injection of 0.1 mg fentanyl followed by infusion of propanidide-succinylcholine. The control group received no medication prior to surgery, whereas patients in the experimental group were given 5 mg bromocriptine per os. Blood samples for prolactin determinations were drawn as the patients were placed on the operating table and immediately following surgery. The association of anesthesia and surgery caused prolactin levels to rise from 10.9 +/- 3.5 to 168 +/- 18.7 ng . ml-1 in the control group (p much less than 0.001) and from 3.5 +/- 0.5 to 7.5 +/- 1.1 ng . ml-1 in the test group (p less than 0.001). A significant difference was noted between the two groups for their pre- and postoperative levels and prolactin response (p less than 0.05, p much less than 0.001 and p much less than 0.001, respectively). The proposed protocol successfully suppresses prolactin increase during surgery and constitutes a useful tool for investigating hyperprolactinemia and its consequences during this same time. Possible applications include in vitro fertilization and studies on prolactin receptor-bearing tumors.

Bromocriptine Inhibition of Hyperprolactinemia during Surgery

Unbound bupivacaine and lidocaine after epidural anesthesia in newborns

42 patients are given, before any neuroleptanalgesia mixture, 0.2 mg · kg−1 of IV midazolam. Pain during the injection is reported in two cases. The loss of conversation onset is 38 ± 18 seconds and of the lid reflex is 75 ± 43 seconds. The only clinical variation is a drop of the systolic blood pressure from 121.4 ± 19.5 mmHg to 114.8 ± 19.6 mmHg, p <0.005. Apnea occurs in nine patients (21 per cent). It lasts 29 ± 35 seconds. But in a steady ventilatory state, the minute ventilation, the tidal volume and the respiratory rate are unchanged from the control values. At the end of the procedure, the answer to simple orders and the space and time orientation come back after 10 ± 13 minutes and 33 ± 28 minutes. The punctured vein is free of any reaction up to the third day.

In conclusion, midazolam is a useful hypnotic drug mainly in the debilitated patient.

Le midazolam intraveineux comme agent hynotique d'une neuroleptanalgésie

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