Determinants of early inadequate vancomycin concentrations during continuous infusion in septic patients.

Vancomycin is frequently administered to critically ill patients by continuous infusion in order to optimise drug efficacy; however, there are few data available on the efficacy of this strategy in septic patients. In this retrospective analysis, 261 patients treated with continuous infusion of vancomycin in the Department of Intensive Care at Hôpital Erasme (Brussels, Belgium) were evaluated. Creatinine clearance (CL(Cr)) was calculated from 24-h urine collection and normalised to body surface area. During the study period, 139 patients (53%) had insufficient vancomycin concentrations (<20 µg/mL) on Day 1 and 87 patients (33%) on Day 2. Patients who had insufficient drug concentrations on Day 1 of therapy were more likely to be men, to have a higher CL(Cr) and to have received lower loading and daily vancomycin doses than other patients, who received greater vasopressor support and had higher Sepsis-related Organ Failure Assessment scores. In multivariate regression analysis, high CL(Cr) and male sex independently predicted the presence of insufficient vancomycin concentrations on Days 1 and 2 of therapy. Receiver operating characteristic curve analysis for CL(Cr) showed an area under the concentration-time curve of 0.75 (95% confidence interval 0.69-0.81) to predict insufficient drug concentrations on Day 1 of therapy. A CL(Cr)>120 mL/min/1.73 m(2) had a sensitivity of 26%, a specificity of 94% and an 84% positive predictive value of 84% for vancomycin concentrations <20 µg/mL. In conclusion, approximately one-half of the septic Intensive Care Unit patients treated with continuous infusion of vancomycin at currently recommended doses had insufficient drug concentrations in the early phase of therapy. A high CL(Cr) was the variable most strongly associated with insufficient drug concentrations.

Increased blood glucose variability during therapeutic hypothermia and outcome after cardiac arrest.

OBJECTIVE: Hypothermia impairs blood glucose homeostasis and insulin sensitivity. However, the impact of therapeutic hypothermia on blood glucose levels and insulin requirements is unknown. We analyzed blood glucose variability during therapeutic hypothermia in patients with coma after cardiac arrest and examined its impact on outcome. DESIGN: Prospective observational study. SETTING: Two university hospital medical/surgical intensive care units. PATIENTS: Comatose cardiac arrest patients treated with therapeutic hypothermia (33°C, 24 hrs). INTERVENTIONS: Insulin therapy (blood glucose target 6-8 mmol/L [110-150 mg/dL]), according to a written algorithm, with nurse-driven adjustment of insulin dose. MEASUREMENTS AND MAIN RESULTS: Two-hundred and twenty patients (median age 61 yrs, median time to return of spontaneous circulation 20 min) were studied. Two time periods, comparable in duration, were categorized: therapeutic hypothermia (stable maintenance phase) and normothermia (after rewarming). Blood glucose variability was defined as the difference between maximum and minimum blood glucose concentration during each time period. Mean blood glucose (8.3±2.3 vs. 7.1±1.3 mmol/L), blood glucose variability (5.7±3.9 vs. 3.7±3.6 mmol/L), and insulin dose (2±2 vs. 1±1 U/h) were higher during therapeutic hypothermia compared to normothermia (all p<.001). Higher mean blood glucose (7.9±1.8 mmol/L in survivors vs. 8.7±2.6 mmol/L in nonsurvivors, p=.02) and increased blood glucose variability (4.9±3.5 vs. 6.5±4.1 mmol/L, p=.003) during therapeutic hypothermia were associated with mortality. After adjusting for time to return of spontaneous circulation, initial arrest rhythm, and cardiac arrest etiology, increased blood glucose variability during therapeutic hypothermia, but not mean blood glucose level, was an independent predictor of inhospital mortality (odds ratio for death 1.10 [confidence interval 1.02-1.19], p=.016). CONCLUSIONS: Mild therapeutic hypothermia is associated with higher blood glucose levels, increased blood glucose variability, and greater insulin requirements compared to the postrewarming normothermic phase. Increased blood glucose variability during therapeutic hypothermia is a predictor of inhospital mortality after cardiac arrest, independent of injury severity and mean blood glucose levels.

Diagnosis, management and prevention of ventilator-associated pneumonia: an update.

Ventilator-associated pneumonia (VAP) affects 10-20% of mechanically ventilated patients and is associated with increased morbidity and mortality and high costs. Early diagnosis is crucial for rapid appropriate antimicrobial therapy to be instituted, but debate remains as to the optimal diagnostic strategy. Noninvasive clinical-based diagnosis is rapid but may not be as accurate as invasive techniques. Increased use of biomarkers and advances in genomics and proteomics may help speed up diagnosis. Management of VAP relies principally on appropriate antimicrobial therapy, which should be selected according to individual patient factors, such as previous antibacterial therapy and length of hospitalization or mechanical ventilation, and local infection and resistance patterns. In addition, once bacterial culture and sensitivity results are available, broad-spectrum therapy should be de-escalated to provide a more specific, narrower-spectrum cover. Optimum duration of antibacterial therapy is difficult to define and should be tailored to clinical response. Biomarker levels may be useful to monitor response to therapy. With the high morbidity and mortality, prevention of VAP is important and several strategies have been shown to reduce the rates of VAP in mechanically ventilated patients, including using noninvasive ventilation where possible, and semi-recumbent positioning. Other potentially beneficial preventive techniques include subglottal suctioning, oral decontamination strategies and antimicrobial-coated endotracheal tubes, although further study is needed to confirm the cost effectiveness of these strategies.