HEPATIC-FUNCTION AS ASSESSED BY LIDOCAINE METABOLISM IN SICKLE-CELL DISEASE

Objective: To evaluate hepatic drug metabolism, as determined by the f ormation of monoethylglycinexylidide (MEGX) after lidocaine injection and indocyanine green (ICG) clearance, in patients with sickle cell di sease. Study design: A case-control study including 19 patients with h omozygous hemoglobin S, and 13 age- and sex-matched black control subj ects. Serum MEGX concentration was measured after intravenous injectio n of 1 mg/kg (maximum 50 mg) lidocaine. ICG (0.5 mg/kg) was injected c oncomitantly and absorbance (805 nm) of serum was measured over time t o determine its volume of distribution, serum half-life, and hepatic b lood flow. Results: MEGX formation at 15 minutes was decreased in pati ents with sickle cell disease compared with formation in the control s ubjects (39.9 +/- 18.0 vs 65.6 +/- 50.0 mu g/L, respectively, p < 0.02 ). The volume of distribution of ICG was increased in patients with si ckle cell disease compared with that in the control subjects (0.21 +/- 0.09 vs 0.11 +/- 0.03 L/kg, p < 0.01). This partly accounts for the d ecreased MEGX formation. The ICG half-life was similar in both groups (3.8 +/- 1.5 vs 3.1 +/- 1.0 min). Hepatic blood flow, derived from ICG clearance, was increased in sickle cell patients compared with that o f the control subjects (12.2 +/- 4.5 vs 8.1 +/- 2.1 ml/kg/min, p < 0.0 1). Conclusion: Hepatic drug metabolism, as assessed by MEGX formation after lidocaine injection, is impaired in patients with sickle cell d isease. This impairment may have clinical implications when using hepa tically metabolized medications in patients with sickle cell disease.