Predicting unbound phenytoin concentrations in the critically ill neurosurgical patient.

OBJECTIVE: To assess the correlation of measured unbound phenytoin concentration (dphF) to estimated unbound concentration (dphEF) using the Sheiner-Tozer equation in critically ill patients in the neurosurgical intensive care unit. DESIGN: The dphF and total phenytoin (dphT) trough serum concentrations were measured during the first week of therapy in 17 consecutive patients with albumin concentrations less than 3.5 g/dL. Serum albumin concentrations were measured within 24 hours of serum phenytoin concentration measurement. SETTING: A university-affiliated urban teaching hospital. PARTICIPANTS: The study population consisted of 17 neurosurgical patients who were at least 18 years old. MAIN OUTCOME MEASURES: The predictability of the Sheiner-Tozer equation was tested by measuring dphF, dphT, and serum albumin concentrations. Measured phenytoin concentrations were compared with phenytoin concentrations calculated from the Sheiner-Tozer equation. To estimate correlation between variables linear regression was calculated. Mean absolute value of error and mean error were estimated to assess precision and bias between measures, respectively. RESULT: The mean +/- SD dphT was 13.05 +/- 5.15 mu g/mL. The measured dphF was 1.89 +/- 0.80 compared with 2.00 +/- 0.8 mu g/mL for the dphEF (NS). Regression analysis for dphEF versus dphF revealed a significant correlation (r2 = 0.94, p = 0.001). The mean absolute value of error for the Sheiner-Tozer equation to predict dphEF was 0.167, which was 9% of the mean value of dphEF (1.89). CONCLUSIONS: These results indicate that, in this population, the Sheiner-Tozer estimate of dphEF provides an unbiased, precise clinical estimate of dphF in patients for whom measured dphF is unavailable or impractical.

Labetalol: response and safety in critically ill hemorrhagic stroke patients.

OBJECTIVE: To observe and characterize the blood pressure (BP)-lowering and adverse hemodynamic and/or central nervous system effects of intravenous bolus doses of labetalol in hemorrhagic stroke patients. DESIGN: Observational, prospective, pilot survey conducted over an eight-week period. SETTING: Surgical intensive care unit. PARTICIPANTS: Patients admitted with an intracerebral or subarachnoid hemorrhage. MAIN OUTCOME PARAMETERS: Absolute decline in systolic BP (SBP) and diastolic BP (DBP), time to peak reduction in SBP and DBP, and adverse hemodynamic and mental status changes. RESULTS: Labetalol at doses between 5 and 25 mg lowered SBP by 6-19 percent (baseline 152-184 mm Hg) and DBP by 3-26 percent (baseline 50-99 mm Hg). Adverse hemodynamic or mental status changes were not detected following labetalol administration. CONCLUSIONS: Small (< or = 25 mg) intravenous bolus doses of labetalol produce mild decreases in BP in hemorrhagic stroke patients.