A Randomized Pharmacokinetic and Pharmacodynamic Evaluation of Every 8-Hour and 12-Hour Dosing Strategies of Vancomycin and Cefepime in Neurocritically ill Patients.

PURPOSE: Neurocritically ill patients have clinically significant alterations in pharmacokinetic parameters of renally eliminated medications that may result in subtherapeutic plasma and cerebrospinal fluid antibiotic concentrations. METHODS: We conducted a prospective randomized open-label study of adult neurocritically ill patients treated with vancomycin and cefepime. Vancomycin 15 mg/kg and cefepime 2 g were dosed at every-8- or 12-hour intervals. The primary outcomes were the achievement of pharmacodynamic (PD) targets related to time of unbound drug above minimum inhibitory concentrations (MIC) for 60% or more of the dosing interval (fT > MIC ≥ 60%) for ß-lactams and ratio of 24-hour area under the curve (AUC):MIC of 400 or greater for vancomycin. RESULTS: Twenty patients were included in the study. They were divided equally between the every-12-hour and every-8-hour dosing groups. Patients (mean age 51.8 ± 11 yrs) were primarily male (60%) and white (95%), and most had an admission diagnosis of intracranial hemorrhage (80%). Compared with the every-12-hour group, the every-8-hour vancomycin group achieved target trough concentrations (higher than 15 µg/ml) significantly more frequently at initial measurement (0% vs 80%, p<0.01) and at 7-10 days (0% vs 90%, p=0.045) and achieved PD targets more frequently at increasing MICs. Similarly, compared with every-12-hour dosing, the every-8-hour cefepime dosing strategy significantly increased PD target attainment (fT > MIC ≥ 60%) at an MIC of 8 µg/ml (20% vs 70%, p=0.02). CONCLUSIONS: This study demonstrated that more frequent dosing of vancomycin and cefepime is required to achieve optimal PD targets in adult neurocritically ill patients. The need for increased total daily doses is potentially secondary to the development of augmented renal clearance.

Management of intracerebral hemorrhage--use of statins.

Intracerebral hemorrhage (ICH) is a neurologic injury resulting in significant morbidity and mortality. Statins play a significant role in primary and secondary prevention of cardiovascular and cerebrovascular ischemic events. Despite clear benefits of statins in ischemic stroke, post hoc analyses of some studies suggest there may be a link between statin therapy and development of ICH. Direct pharmacologic effects of decreased serum levels of total cholesterol and low-density lipoproteins in conjunction with pleiotropic effects are thought to be linked to this possible increase in ICH risk. In the face of the potential of statins to increase the risk of ICH, recent evidence suggests that statins may also have beneficial effects on patient outcomes when continued or initiated following an ICH. This discordance in findings and the overall lack of well-designed prospective clinical trials increase the complexity of clinical decision making when utilizing statin therapy in patients with, or at risk for, ICH. This review evaluates the pharmacologic effects of statin therapy and describes how these effects translate to both risks and benefits in ICH. The current literature regarding the effects of statin therapy on clinical outcomes in ICH is evaluated to help guide clinicians with decisions regarding initiation, continuation, or discontinuation of statin therapy in patients with ICH.

Assessing renal function in cirrhotic patients: problems and pitfalls.

Assessment of glomerular filtration rate (GFR) by common creatinine-based methods potentially is very inaccurate in patients with cirrhosis. Cirrhotic patients have several underlying conditions that contribute to falsely low serum creatinine concentrations, even in the presence of moderate to severe renal impairment, and often cause creatinine-based methods to overestimate true GFR. Such underlying conditions include decreased creatinine production secondary to decreased hepatic creatine synthesis, increased tubular creatinine secretion, and decreased skeletal muscle mass. These factors all contribute to serum creatinine concentrations that often do not accurately reflect renal function. Serum creatinine level, measured creatinine clearance, and calculated creatinine clearance may all significantly overestimate GFR; the degree of GFR overestimation was a median of 95% in published studies. Until more accurate methods of estimating GFR in cirrhotic patients are adequately validated, care should be exercised in the management of these patients because of the potential for severely impaired renal function, even in the face of normal serum creatinine concentrations.

The critical care pharmacist: an essential intensive care practitioner.

Clinical pharmacy services in the critical care setting have expanded dramatically and include assisting physicians in pharmacotherapy decision making, providing pharmacokinetic consultations, monitoring patients for drug efficacy and safety, providing drug information, and offering medical education to physicians, nurses, and patients. Measurable clinical effects of these services include reduced drug errors and adverse drug events, decreased morbidity and mortality rates, and a positive pharmacoeconomic impact by decreasing overall health care costs.