• O Bastien, M Bolon, C Flamens, J J Lehot, and R Boulieu.
• Service d'anesthésie-réanimation, hôpital cardiovasculaire et pneumologique L. Pradel, boulevard Pinel, 69394 Lyon, France. olivier.bastien@chu-lyon.fr
• Ann Fr Anesth Reanim. 2002 Nov 1; 21 (9): 692-7.

ObjectivesEvaluate the risk of accumulation of midazolam and conjugated 1-hydroxy-midazolam in high-risk ICU patients treated by continuous veno-venous haemofiltration.Study DesignA prospective pharmocokinetic and clinical evaluation in 11 patients, with hepatic and renal failure.MethodsMidazolam and metabolites were dosed in plasma and ultratiltration liquid by chromatography. Sedation was assessed by a simplified Ramsay score (EDS) with 4 levels.ResultsThe mean duration of continuous infusion was 11 +/- 6 days. Peak plasma levels were over 150 ng ml-1 during the first 3 days, but normalized after that, only by drug adjustment based on scoring and clinical observation. There was no progressive accumulation of OH-midazolam, in spite of high levels (> 1000 ng ml-1). The Sieving coefficient (S) was 0.11 +/- 0.10 and 0.44 +/- 0.15 for midazolam and conjugated OH-midazolam respectively. A significant clearance (9.6 +/- 1.9 ml min-1) was observed for the conjugated products. T 1/2 beta was 11 h and was correlated with the mean time of recovery. A significant correlation was found between sedation score and both midazolam (r = 0.47) and OH-midazolam (r = 0.32).ConclusionOH-midazolam risk of accumulation and significant clearance by haemodiafiltration should be taken into account in the drug adjustment in patients treated by continuous veno-venous haemofiltration.

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