Pharmacokinetics Alterations of Midazolam Infusion versus Bolus Administration in Mechanically Ventilated Critically Ill Patients

Document Type : Research article


1 General ICU Department, Imam Khomeini University Hospital, Tehran University of Medical Sciences, Tehran, Iran.

2 Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Pharmaceutics, Pharmaceutical Sciences Research Center. School of Pharmacy, Tehran University of Medical Science, Tehran, Iran.


There is no randomized study carried out in order to compare their pharmacokinetic parameters although midazolam, as a sedative, has been widely administered via continuous infusion as well as intermittent bolus doses in mechanically ventilated critically ill patients. We prospectively investigated the effect of these two principal methods on pharmacokinetic parameters in 23 of mentioned patients (16 males, 7 females) with the mean (± SD) age of 41.22 ± 17.5. All patients received total dose of 72 mg throughout the test days, 9 of whom received 1 mg/h (continuous infusion) and the rest obtained 4 mg / 4 h (intermittent bolus doses). Blood samples were collected at 8 and 4 h prior to the end time of drug administration (zero time), zero time and 4, 8, 12, 20 and 30 h after it. APACHE (Acute Physiology and Chronic Health Evaluation) II required data was recorded daily and the patients’ mean score was 16.26 ± 4.38. The mean (± SD) value of pharmacokinetic parameters of Midazolam in continuous infusion and intermittent bolus doses methods were as follows: (t½ = 17.88 ± 14.65 h, Cl = 21.80 ± 14.95 L/h) vs. (t½ = 19.74 ± 12.45 h, Cl = 29.43 ± 19.45 L/h). Volume of distribution (Vd) was measured in continuous infusion group which was 612.58 ± 582.93 L. The calculated clearance and half-life were found not to be significantly different (p < 0.05). The patients might be exposed to similar undesired effects due to the large volumes of distribution following the administration methods studied.


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