[Use of midazolam in postoperative sedation of patients with multiple organ failure treated with hemodiafiltration. Clinical study and pharmacokinetics].
OBJECTIVE
Evaluate the risk of accumulation of midazolam and conjugated 1-hydroxy-midazolam in high-risk ICU patients treated by continuous veno-venous haemofiltration.


METHODS
A prospective pharmocokinetic and clinical evaluation in 11 patients, with hepatic and renal failure.


METHODS
Midazolam and metabolites were dosed in plasma and ultratiltration liquid by chromatography. Sedation was assessed by a simplified Ramsay score (EDS) with 4 levels.


RESULTS
The 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).


CONCLUSIONS
OH-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.
Bastien
O
O
Service d'anesthésie-réanimation, hôpital cardiovasculaire et pneumologique L. Pradel, boulevard Pinel, 69394 Lyon, France. olivier.bastien@chu-lyon.fr
Bolon
M
M
Flamens
C
C
Lehot
J J
JJ
Boulieu
R
R
D000759:Adjuvants, Anesthesia / Q000009:adverse effects / Q000493:pharmacokinetics*; D000368:Aged; D001711:Biotransformation; D002853:Chromatography, Liquid; D005260:Female; D006207:Half-Life; D006440:Hemofiltration; D006801:Humans; D017093:Liver Failure / Q000378:metabolism; D008297:Male; D008874:Midazolam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000378:metabolism*; D051437:Renal Insufficiency / Q000378:metabolism
D000759:Adjuvants, Anesthesia; C040081:1-hydroxymethylmidazolam; D008874:Midazolam