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Effect of mechanical ventilation on hepatic drug pharmacokinetics
Abstract:
Mechanical ventilation was able to induce a decrease in cardiac output and regional blood flow, especially hepatic flow. Thus, hepatic elimination of drugs with a high hepatic-extraction ratio, which was linked to alteration in hepatic blood flow, could be reduced during mechanical ventilation. The aim of this work was to determine the effect of mechanical ventilation on pharmacokinetic parameters of lidocaine, which is a well-known nonrestrictive elimination drug at the hepatic level. Five patients (mean age, 58 years) with normal hepatic function and quite similar gasometric parameters before and after weaning from mechanical ventilation were studied. With a washout period of 48 hours between mechanical ventilation and spontaneous ventilation, each patient was submitted to the following protocol: lidocaine in a bolus (1.5 mg/kg intravenously), followed by infusion (1.0 to 1.7 mg/min for 120 minutes). The results were that the peak plasma concentration after the bolus during mechanical ventilation was 3.22 +/- 0.37 mg/L (mean +/- SE) vs 2.40 +/- 0.35 mg/L during spontaneous ventilation (p less than 0.02). Steady-state plasma concentration during mechanical ventilation was 2.10 +/- 0.20 mg/L vs 1.64 +/- 0.16 mg/L during spontaneous ventilation (p less than 0.01). Total clearance was 604.2 +/- 87.0 ml/min during mechanical ventilation vs 775.0 +/- 112.1 ml/min during spontaneous ventilation (p less than 0.01). Elimination half-life was 245.2 +/- 50.6 minutes during mechanical ventilation vs 160.0 +/- 40.6 minutes during spontaneous ventilation (p less than 0.05). Distribution volume was 188.6 +/- 50.2 L during mechanical ventilation and 183.0 +/- 50.8 L during spontaneous ventilation (not significant). These preliminary data clearly demonstrated a decrease in lidocaine elimination in patients submitted to mechanical ventilation, but the magnitude of dosage adjustment of such a highly hepatic-extracted drug in patients submitted to mechanical ventilation remains to be investigated.