Publications

Introduction: Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum β-lactam concentrations when standard dosages are administered. Previous studies on β-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock. Methods: Open, prospective, multicenter study in four Belgian intensive care units. All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom treatment with the study drugs was indicated, were included. Serum concentrations of the antibiotics were determined by high-pressure liquid chromatography (HPLC) before and 1, 1.5, 4.5 and 6 or 8 hours after administration. Results: 80 patients were treated with piperacillin-tazobactam (n = 27), ceftazidime (n = 18), cefepime (n = 19) or meropenem (n = 16). Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 × MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 μg/mL), 45% for ceftazidime (MIC = 32 μg/mL), 34% for cefepime (MIC = 32 μg/mL), and 33% for piperacillin-tazobactam (MIC = 64 μg/mL). The number of patients who attained the target PK profile was 12/16 for meropenem (75%), 5/18 for ceftazidime (28%), 3/19 (16%) for cefepime, and 12/27 (44%) for piperacillin-tazobactam. Conclusions: Serum concentrations of the antibiotic after the first dose were acceptable only for meropenem. Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock.

Introduction: A recent study has shown that fever control during septic shock was associated with decreased vasopressor requirements and reduced mortality. Thus, fever control may improve vascular tone during critically illness. The aim of this study was to evaluate the effect of fever control on peripheral vascular reactivity, assessed by near-infrared spectroscopy (NIRS). Methods: We prospectively included patients admitted to the intensive care unit (ICU) during a 6-month period who presented with core temperature ≥ 38.3°C and in whom attending physician had decided for fever control. Thenar tissue oxygen saturation (StO2) and muscle tissue hemoglobin index (THI) were measured using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology Inc., Hutchinson, MN, USA). A vaso-occlusive test was performed at baseline (T0) and then 1 hour (T1) and 4 hours (T2) after initiation of fever control by rapid inflation of a pneumatic cuff around the upper arm. The following variables were recorded: THI, the StO2 desaturation slope during the occlusion (dSlope, %/sec) and the StO2 upslope of the reperfusion phase following the ischemic period (ascSlope, %/sec). Muscle oxygen consumption (NIR VO2; arbitrary units) was calculated as the product of the inverse StO2 desaturation slope and the mean THI over the first minute of arterial occlusion. Results: Thirty-one patients were included (16 male gender; age 56 [50-66] years); median temperature on TO was 38.7 [38.4-39.0]°C and most of them (25/31) were cooled using pharmacological intervention (IV paracetamol). Temperature at T1 and T2 were 38.0 [37.7-38.3] and 37.5 [37.0-37.8]°C. Values of StO2, THI, nirVO2, dSlope and ascSlope did not significantly change over time. Also, similar StO2, THI, nirVO2, dSlope and ascSlope time course was found when we compared patients on vasopressors (n=13) to the others. Nevertheless, among patients on vasopressors, we observed a significant increase in the dSlope (from 1.85 ± 0.84%/sec at T0 to 2.23 ± 0.68%/sec at T2, p =0.02) and decrease in the ascSlope (from -0.20 ± 0.04%/sec at T0 to -0.28 ± 0.08%/sec at T2, p =0.002). Also, we found a trend toward an increased nirVO2 (from 122 ± 46 at T0 to 153 ± 57 at T2, p =0.11). Conclusions: Fever control was associated with an improvement in peripheral vascular reactivity in critically ill patients on vasopressor therapy.

Automated pupillometry can contribute to the assessment of cerebral dysfunction in critically ill patients.