Intravenous Infusion Of Midazolam Research Articles

Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients.

The pharmacokinetics of midazolam and of its main metabolite, 1-hydroxymidazolam, were investigated in intensive care patients after intravenous bolus of 0.2 mg/kg followed by a 0.1 mg/kg/h intravenous infusion of midazolam over 2 hours. A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found. The mean values of elimination half life and volume of distribution, 4.5 +/- 5.4 h and 1.7 +/- 0.7 l/kg respectively, were higher than those reported in healthy subjects. Total plasma clearance was significantly increased in patients taking drugs that induce hepatic metabolism. Significant concentrations of the unconjugated form of 1-hydroxymidazolam were recovered in plasma. The volume of distribution and the elimination half life of the metabolite were higher than those of the parent drug. These results show that 1-hydroxymidazolam might contribute to the pharmacodynamic effect of midazolam and consequently must be taken into account during pharmacokinetic and pharmacodynamic studies.

Efficacy of Continuous Intravenous Infusion of Midazolam in the Treatment of Status Epilepticus in Children

Efficacy of Continuous Intravenous Infusion of Midazolam in the Treatment of Status Epilepticus in Children

Tolerability profile on continuous intravenous midazolam in critical care patients

This review summarizes the tolerability profile of midazolam administered as a continuous intravenous (IV) infusion to patients in the intensive care unit (ICU) who are receiving mechanical ventilation. Midazolam is a short-acting benzodiazepine indicated for intramuscular administration for preoperative sedation; for IV administration for conscious sedation prior to short diagnostic, therapeutic, or endoscopic procedures; and for IV administration for induction of general anesthesia. The drug can also be used for short surgical procedures as a component of IV supplementation. Because of its favorable properties (short half-life, ease of titration of infusion, and favorable tolerability profile), midazolam is used as a sedative agent for critically ill patients requiring mechanical ventilatory support. No clinically significant differences with respect to laboratory, hemodynamic, respiratory, neurologic, or monitoring variables have been reported between continuous IV midazolam and propofol, lorazepam, or diazepam. No adverse events were reported in association with the administration of midazolam by continuous infusion other than those previously identified in the short-term use of midazolam. Mortality rates for midazolam were no greater than those previously reported for critically ill patients receiving mechanical ventilation. The tolerability profile indicates that the continuous IV infusion of midazolam in critically ill patients who require mechanical ventilation in the ICU will not result in any significant clinical problems.

Sedation during Artificial Ventilation by Continuous Intravenous Infusion of Midazolam: Effects of Hepatocellular or Renal Damage

To evaluate the effects of hepatocellular or renal damage on therapeutic doses of midazolam and emergence time after withdrawal of the drug, 87 patients under continuous sedation with midazolam on artificial ventilation were prospectively studied. They needed continuous sedation for 12 hours or more. They included 55 patients with normal hepatocellular and renal functions (C group), 21 patients with hepatocellular damage (II group), and 11 patients with hepatocellular and renal damage (HR group). Midazolam was initiated with an intravenous dose of 0.1 mg/kg followed by 0.05 mg/kg/hr. Dosage was regulated to maintain a state in which patients responded to verbal command and had bucking responses to endotracheal suctioning. The three groups were compared with respect to midazolam dosage, emergence time, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels and urine volume. The mean doses of midazolam in the C, H, and HR groups were 0.083 ± 0.038 mg/kg/hr, (mean ± standard deviation) 0.073 ± 0.037 mg/kg/hr, and 0.088 ± 0.048 mg/kg/hr, respectively, showing no differences among these groups. Emergence time was significantly longer in the H group (333 ± 263 min; p < 0.005) and the HR group (305 ± 225 min; p < 0.025) than in the C group (171 ± 106 min). No effect of midazolam administration was seen on AST, ALT, BUN, Cr, and urine volume in all groups. In conclusion, presence of hepatocellular or renal damage did not alter required dosage of midazolam. Hepatocellular damage prolonged emergence time, but renal damage had no more additive effect. There was no evidence of hepatocellular and renal damages during treatment.

Comparison of propofol and midazolam for sedation in intensive care unit patients

To evaluate the comparative safety and effectiveness of intravenous infusion of propofol or midazolam when used for 12 to 24 hrs of sedation and to evaluate the quality of sedation during stimulation. An open, comparative, prospective, randomized study. Surgical intensive care unit (ICU) in a university hospital. Postoperative, intubated, general surgical, and orthopedic patients requiring mechanical ventilation (n = 60). None. Assessments were made at baseline (0 time), 5, 10, 15, 30, 45, and 60 mins; at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hrs; and at the end of sedation. The assessments included systolic, mean, and diastolic blood pressures, heart rate, two-lead electrocardiogram, pulse oximetry oxygen saturation, FIO2, end-tidal CO2, respiratory rate, ventilator rate, tidal volume, and sedation scale. Vital signs and the sedation scale were obtained at 30, 60, and 90 mins and at 2, 4, 12, and 24 hrs after the end of sedation. At approximately 8 hrs and 24 hrs (or at the end of sedation), the patient's CO2 production was calculated over a 5-min interval. Every 4 hrs, the nurse would summarize and rate patient response during stimulation as well as the overall rating of the sedation and patient ability to tolerate the ICU setting. There were no significant differences in pulse oximetry, arterial blood gas values, or respiratory measurements during sedation with propofol or midazolam. The mean heart rate was slower in the propofol group throughout the sedation and postsedation periods. The rating of sedation and tolerance of the ICU environment were significantly better for the propofol-treated group. Postsedation, the propofol group woke up faster on discontinuation of the sedative. Propofol was as safe and as efficacious as midazolam for continuous intravenous sedation. The quality of sedation was better in the propofol group.

The use of midazolam for persistent postoperative nausea and vomiting.

The effect of intravenous midazolam on persistent postoperative nausea and vomiting (PONV) was compared to placebo in a prospective randomized double-blind study. Twenty patients aged 18 to 82 years with persistent PONV resistant to standard anti-emetics and present for greater than six hours were randomized to receive either an intravenous infusion of midazolam 1.0 mg/h or placebo. Nausea (P = 0.04), vomiting (P = 0.02) and the use of rescue anti-emetics (P = 0.003) were significantly less in the midazolam group. We conclude that low-dose intravenous infusion of midazolam significantly reduces persistent PONV.

Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit

Twenty-four patients in a paediatric intensive care unit mostly undergoing cardiac surgery, received a midazolam dosage between 50-400 micrograms/kg per hour as a continuous intravenous infusion partly in combination with fentanyl [0,5-2,5 micrograms/kg per hour] for analgesia and sedation. The mean duration of midazolam infusion was 11.6 days (range 38 h-40 days). Blood samples for the HPLC assay of serum midazolam concentration were taken and the clearance estimated. The efficiency of sedation in correlation to the midazolam concentration was evaluated by a clinical sedation score. Serum midazolam concentrations between 100-400 micrograms/l were sufficient for sedation. Dosage had to be increased during therapy according to an increased midazolam clearance. The evaluation of the sedation score showed that sedation of artificially ventilated infants and young children can be established by continuous intravenous infusion of midazolam.

COMPARISON OF PROPOFOL AND MIDAZOLAM FOR SEDATION IN CRITICALLY ILL PATIENTS

101 critically ill patients admitted to five intensive-care units were allocated randomly to receive a continuous intravenous infusion of either propofol or midazolam for sedation for up to 24 h. In addition, morphine was given to provide analgesia. The mean duration of infusion was 20-2 h (range 3·0-24·5) in the propofol group and 21·3 h (4·0-47·0) in the midazolam group and infusion rates were 1·77 mg/kg/h (range 0·40 -5·00) and 0·10 mg/kg/h (0·01-0·26), respectively. The infasion rates were adjusted as necessary, and the desired level of sedation was achieved easily in most patients in both groups. There were slight falls in arterial pressure, but there were no significant differences between the groups. Heart rate was lower in patients who received propofol. Some small changes occurred in biochemical and haematological variables in both groups, but they were not clinically significant. There was no indication that either drug substantially impaired adrenal steroidogenesis. When the infusion was discontinued, there was less variability in recovery of consciousness in patients who had received propofol. In a subgroup of patients, weaning from mechanical ventilation was achieved significantly faster after discontinuation of propofol than of midazolam. Propofol proved to be a satisfactory agent for sedation of these critically ill patients and compared favourably with midazolam.

Isoflurane compared with midazolam for sedation in the intensive care unit.

To compare isoflurane with midazolam for sedation of ventilated patients. Randomised control study. Setting--Intensive care unit in university teaching hospital. Sixty patients aged 18-76 who required mechanical ventilation. Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). Achievement of a predetermined level of sedation for as much of the time as possible. Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit.

Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability?

The pharmacokinetics of midazolam and its metabolites were studied in 17 patients on mechanical ventilation in a general intensive care unit who were receiving a continuous intravenous infusion of midazolam, adjusted according to the level of induced sedation. Three patients were studied twice. Serum midazolam and alpha-hydroxymidazolamglucuronide levels were determined during and after infusion. The sedation level was scored on a four-point scale. Half of the observed patients were still drowsy or asleep 10 hours after termination of midazolam infusion. In only one patient was midazolam serum elimination half-life less than 2 hours and in six patients the half-life was greater than 10 hours. A wide range of midazolam serum levels was associated with adequate sedation, and similarly the midazolam levels at the moment of awakening were highly variable. The serum concentration ratio of midazolam/alpha-hydroxymidazolamglucuronide at the end of the infusion varied from 0.03 to 15.6. Renal function could account for only a part of this variation.

Continuous Intravenous Midazolam Infusion for Sedation in the Pediatric Intensive Care Unit

Continuous Intravenous Midazolam Infusion for Sedation in the Pediatric Intensive Care Unit

Failure of critically ill patients to metabolise midazolam.

The pharmacokinetics of midazolam and its metabolite, 1-OH midazolam, were studied in six critically ill patients during and after a continuous intravenous infusion of midazolam. Four patients had an increased elimination half-life of midazolam; two were associated with a reduction in plasma clearance with low plasma concentrations of the metabolite, and two with normal metabolite levels and increased volume of distribution. The two patients with reduced clearance suffered from septic shock and were studied over a longer period. Their altered clearance was due to a reduced capability to form the 1-OH metabolite. As their condition improved, plasma concentrations of 1-OH midazolam increased and midazolam clearance returned towards normal. The impaired ability of critically ill patients with septic shock to metabolise midazolam, may be due to reduced organ perfusion and may lead to cumulation of midazolam in these patients.

The Effects of Midazolam on Cerebral Blood Flow and Oxygen Consumption and Its Interaction with Nitrous Oxide

The effects of the intravenous infusion of midazolam on cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO2) were measured in rats in the presence and absence of nitrous oxide. Midazolam produced 40-45% decreases in CBF with no difference in response between nitrous oxide and nitrogen-ventilated rats. CMRO2 decreased 55% during midazolam infusion in rats ventilated with nitrogen, significantly more (P less than 0.05) than in rats ventilated with nitrous oxide (35%). We conclude that cerebrovascular responses to midazolam infusion were not altered by nitrous oxide and suggest that nitrous oxide may slightly but significantly stimulate brain metabolism during midazolam infusion.