Midazolam for

Propofol is very lipid soluble, has a large volume of distribution, and has a rapid onset of action. It has comparable efficacy to midazolam for refractory GCSE. It has been associated with metabolic acidosis, hemodynamic instability, and bradyarrhythmias that are refractory to treatment. 

The technique typically involves the use of intravenous midazolam for premedication (to provide anxiolysis, amnesia, and mild sedation) followed by a titrated, variable-rate propofol infusion (to provide moderate to deep levels of sedation), and a potent opioid analgesic or ketamine (to minimize the discomfort associated with the injection of local anesthesia and the surgical manipulations). 

In the case of simvastatin and midazolam, nine shared inhibitors, tested at a comparable dose regimen, are available. The fold increases in the substrates AUC are summarized in Table 2 and show that the AUC ratios are consistently higher with simvastatin than midazolam for all nine inhibitors, suggesting a higher sensitivity to CYP3A inhibition for simvastatin [mean of AUC ratios of 1.67 (1.28-2.60)]. 

When an in vitro evaluation cannot rule out the possibility that an investigational drug is an inducer of a CYP enzyme, an in vivo evaluation can be conducted using the most sensitive substrate (e.g., oral midazolam for CYP3A). 

Benzodiazepines are secreted into the milk in relatively small amounts (28). During lactation, longer-acting agents are relatively contraindicated, particularly with continued administration beyond 3-5 days, owing to the likelihood of infant sedation (122,124). Short-acting benzodiazepines and zopiclone are probably safe, especially if restricted to single doses or for short courses of therapy (28,125). Zopiclone and midazolam, for example, become undetectable in breast milk 4—5 hours after a dose (126). 

Wassner E, Morris B, Fernando L, Rao M, Whitehouse WP. Intranasal midazolam for treating febrile seizures in children. Buccal midazolam for childhood seizures at home preferred to rectal diazepam. BMJ 2001 322(7278) 108. 

The incidence of hypotension with the use of midazolam for pre-hospital rapid-sequence intubation of the trachea has been assessed in a retrospective chart review of two aeromedical crews (19). The rapid-sequence protocols were identical, except for the dose of midazolam. Both crews used 0.1 mg/kg, but one crew had a maximum dose of 5 mg imposed. This meant that patients over 50 kg received lower doses of midazolam they also had a higher incidence of hypotension. This relation was also present in patients with traumatic brain injury, implying that cerebral perfusion could be compromised at a critical time in those without dosage restriction. 

The pharmacology and adverse effects of midazolam in infants and children have been reviewed (4). The optimal dose of intramuscular midazolam for preoperative sedation has been studied in a double-blind prospective study of 600 patients who were age-stratified (51). The patients received intramuscular atropine 0.6 mg and one of five doses of midazolam 15 minutes before induction of anesthesia. For the age groups 20-39, 40-59, and 60-79 years, the optimal sedative and amnesic effects of midazolam were 0.10, 0.08, and 0.04 mg/kg respectively. The frequency with which the undesirable adverse effects of reduced blood pressure, oxygen desaturation, oversedation, loss of eyelash reflex, and tongue root depression occurred increased with age, and optimal doses for a low incidence of adverse effects were 0.08, 0.06, and 0.04 mg/ kg in the same age groups respectively. 

Karl HW, Cote CJ, McCubbin MM, Kelley M, Liebelt E, Kaufman S, Burkhart K, Albers G, Wasserman G. Intravenous midazolam for sedation of children undergoing procedures an analysis of age- and procedure-related factors. Pediatr Emerg Care 1999 15(3) 167-72. 

Hall RI, Sandham D, Cardinal P, Tweeddale M, Moher D, Wang X, Anis AH. Propofol vs midazolam for ICU sedation a Canadian multicenter randomized trial. Chest 2001 119(4) 1151—9. 

Davis DP, Kimbro TA, Vilke GM. The use of midazolam for prehospital rapid-sequence intubation may be associated with a dose-related increase in hypotension. Prehosp Emerg Care 2001 5(2) 163-8. 

Burns R, McCrae AF, Tiplady B. A comparison of target-controlled with patient-controlled administration of propofol combined with midazolam for sedation during dental surgery. Anaesthesia 2003 58 170-6. 

In vivo probe substrates are available to assess the activity of particular enzymes, for example midazolam for CYP3A4/5, caffeine for CYP1A2 and tolbutamide for CYP2C9 [14],... 

Propofol caused marked prolongation of the QTc interval in a 71-year-old woman with an acute myocardial infarction who required ventilatory support (19). Substituting midazolam for propofol was associated with normalization of the QT interval. Rechallenge with propofol was associated with further prolongation. There were no malignant ventricular dysrhythmias. 

LeDuc TJ, Goellner WE, Sanadi NE. Out-of-hospital midazolam for stams epilepticus. Ann Emerg Med 1996 28 377. 

Shih et al. (2003) evaluated the potency and rapidity of action of some anticholinergics, including atropine and two benzodiazepines (diazepam and midazolam), for seizures produced... 

Given the conditions and the requirements for the initial symptomatic treatment of mass casualties, the diazepam derivative avizafone in autoinjectors and/or midazolam for intramuscular injection should be sufficient. In view of lo-razepam s reported efficacy in treatment of status epilepticus, it is recommended that more experimental studies are performed on the efficacy of lorazepam, and also in controlling nerve-agent-induced seizures and convulsions. 

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