Pharmacokinetics of Midazolam in Anesthetized Cirrhotic Patients

Chauvin, M.; Haberer, J.-P.; Ferrier, Claudia; Trouvin, Jean‐Hugues; Farinotti, Robert; Duvaldestin, P.

doi:10.1097/00000542-198709001-00290

Cited by 5 publications

(1 citation statement)

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“…Although prolonged sedation has been observed in patients with liver disease, 11,49 others have reported reduced clearance of midazolam in patients with cirrhosis. 50,51 Park and colleagues found a wide range in the metabolism of midazolam in patients with end-stage liver disease 52 and liver tissue affected by cirrhotic disease showed greater preservation of enzyme function than that affected by hepatocellular disease. Because midazolam has a high hepatic extraction, the rate of its metabolism is dependent on hepatic blood flow and any reduction in liver perfusion could reduce the rate of its metabolism.…”

Section: Anticipating a Poor Responsementioning

confidence: 99%

When Midazolam Fails

Cheng

Roemer-Bécuwe

Pereira

2002

Journal of Pain and Symptom Management

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Significant distress is experienced by patients, families, and caregivers when a symptom or disorder, such as an agitated delirium, becomes an intractable, or a catastrophic event, such as irreversible stridor. When palliative sedation is indicated for these patients, midazolam is usually the preferred drug. In some cases, however, midazolam fails to provide adequate sedation. Two cases are presented to illustrate this phenomenon and explore the possible mechanisms underlying this lack of response. These mechanisms appear to be multifaceted. The heterogeneity of the GABA(A) receptor complex and the alterations that this complex can undergo functionally can explain, to some degree, the diversity of the physiological and pharmacological outcomes. Other factors responsible for the diversity in response may include concomitant medications, age, concurrent disease, overall health status, alcohol use, liver disease, renal disease, smoking and hormonal status. Evidence-based guidelines on alternative treatment options should midazolam fail are required. In the interim, a lower threshold for adding an alternative drug, such as phenobarbital, or substituting midazolam with another drug, such as propofol, should be considered in these circumstances.

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Section: Anticipating a Poor Responsementioning

confidence: 99%

When Midazolam Fails

Cheng

Roemer-Bécuwe

Pereira

2002

Journal of Pain and Symptom Management

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Pharmacokinetics of midazolam administered concurrently with ketamine after intravenous bolus or infusion in dogs

Brown

Jacobson

Hartsfield

1993

Vet Pharm & Therapeutics

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Midazolam, a water-soluble benzodiazepine tranquilizer, has been considered by some veterinary anaesthesiologists to be suitable as a combination anaesthetic agent when administered concurrently with ketamine because of its water solubility and miscibility with ketamine. However, the pharmacokinetics of midazolam have not been extensively described in the dog. Twelve clinically healthy mixed breed dogs (22.2-33.4 kg) were divided into two groups at random and were administered ketamine (10 mg/kg) and midazolam (0.5 mg/kg) either as an intravenous bolus over 30 s (group 1) or as an i.v. infusion in 0.9% NaCl (2 ml/kg) over 15 min. Blood samples were obtained immediately before the drugs were injected and periodically for 6 h afterwards. Serum concentrations were determined using gas chromatography with electron-capture detection. Serum concentrations were best described using a two-compartment open model and indicated a t1/2-alpha of 1.8 min and t1/2-beta of 27.8 min after i.v. bolus, and t1/2-alpha of 1.35 min and t1/2-beta of 31.6 min after i.v. infusion. The calculated pharmacokinetic coefficient B was significantly smaller after i.v. infusion (429 +/- 244 ng/ml) than after i.v. bolus (888 +/- 130 ng/ml, P = 0.004). Furthermore, AUC was significantly smaller after i.v. infusion (29,800 +/- 6120 ng/h/ml) than after i.v. bolus (42,500 +/- 8460 ng/h/ml, P < 0.05), resulting in a larger ClB after i.v. infusion (17.4 +/- 4.00 ml/min/kg than after i.v. bolus (12.1 +/- 2.24 ml/min/kg, P < 0.05). No other pharmacokinetic value was significantly affected by rate of intravenous administration.

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