The utility of the clinical pulmonary infection score.

The most common infectious complication in critically ill patients is ventilator-associated pneumonia. Ventilator-associated pneumonia has significant morbidity and mortality, prolongs mechanical ventilation, and extends length of hospitalization. Despite its prevalence and impact, uniform diagnostic standards are lacking. The Centers for Disease Control, American Thoracic Society, and Infectious Diseases Society of America have recommended focus on improving preventive measures, establishing widely available and accurate diagnostic tools, and improving ventilator-associated pneumonia management with length of therapy guidelines. The purpose of this article is to review the evidence supporting the clinical pulmonary infection score as an adjunct to distinguish and detect clinically relevant ventilator-associated pneumonia and its use to guide length of therapy. This score combines clinical diagnostic criteria (tracheal secretion quantification and body temperature) with routinely obtained laboratory data (white blood cell count and oxygenation parameters), radiographic data, and bacteriological culture results. Limitations of clinical pulmonary infection score will be discussed.

Cyclosporin A disposition following acute traumatic brain injury.

Although the precise mechanism of action remains to be defined, Cyclosporin A (CsA) has demonstrated potential for neuroprotection in animal models. Predictive dosing strategies for CsA in acute traumatic brain injured (TBI) patients must account for the influence of the acute phase response on drug disposition. To characterize CsA pharmacokinetic parameters early following acute TBI, serial blood samples from patients enrolled into a Phase II dose-escalation trial were analyzed. Within eight hours of injury, thirty patients admitted with acute severe TBI were prospectively randomized into three cohorts (n = 8 CsA; n = 2 placebo per cohort) in this dose-escalation trial. Patients received one of three doses (I = 0.625 mg/kg/dose; II = 1.25 mg/kg/dose; III = 2.5 mg/kg/dose) or placebo intravenously every 12 h for 72 h. Serial blood collection began prior to dose 1 and continued for 72 h following the completion of six doses. Whole blood concentrations were determined by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Pharmacokinetic parameters were determined for each patient by fitting the concentration-time profile to a two-compartmental model with first order elimination. Mean area under the curve and predicted maximal blood concentration increased with each dosing cohort (I = 9840 h*microg/L, 398 microg/L; II = 18300 h*microg/L, 645 microg/L; III = 32500 h*microg/L, 1300 microg/L). Whole blood clearance, steady state volume of distribution, and beta half-life were independent of dose and higher than published reports from other populations: 0.420 L/h/kg, 5.91 L/kg, and 17.3 h, respectively. These data show patients with acute severe TBI demonstrate a more rapid clearance and a larger distribution volume of CsA. Pharmacokinetic parameters derived from this study will guide dosing strategies for future prospective clinical trials evaluating CsA therapy following acute TBI.