Publications

Objectives: A recent prospective study on beta-lactams levels in septic patients receiving continuous renal replacement therapy (CRRT) recommended the following dosage regimens: 2gq8h for ceftazidime or cefepime (CEF), 4gq6h for piperacillin-tazobactam (TZP), and 1gq8h for meropenem (MEM).1 We applied these regimens in our hospital since December 2009. The aim of our study was to evaluate the adequacy of this dosage strategy in a cohort of septic patients undergoing CRRT.Methods: Retrospective observational study from 01/01/2010 to 31/05/2011. Inclusion criteria were: a) sepsis, b) CRRT; c) treatment with CEF, TZP or MEM, and d) at least one measure of beta-lactam levels. Serum concentrations were measured by high-performance liquid chromatography (HPLC-UV). Blood samples were taken twice during the elimination phase after a 30-min intravenous administration of the drug. The two samples were used to calculate the time spent above the minimal inhibitory concentration (MIC), which was empirically considered as the clinical breakpoint for "difficult-to-treat" bacteria, such as Pseudomonas aeruginosa. Adequate therapy was defined as serum concentrations between 4 to 8 times the MIC during optimal periods of time for each drug: > 70% for CEF, > 50% for TZP, and > 40% for MEM. Underdosing and overdosing were defined as drug concentrations that were respectively < 4 times or > 8 times the MIC during optimal periods of time. Early and late phases of therapy were considered if drug levels measurement was performed within 48 hours or later on, respectively.Results: Fifty drugs levels were obtained from 36 patients; 15 during the early and 35 during the late septic phase. Drug levels obtained for each antibiotic are shown in Figure 1.Conclusions: Administering a higher beta-lactam dosage regimen for septic patients receiving CRRT avoided insufficient drug concentrations in most patients. Nevertheless, therapeutic drug monitoring should be performed routinely in order to adapt beta-lactam doses and to avoid drug accumulation .References: 1. Seyler L, Cotton F, Taccone FS, De Backer D, Macours P, Vincent JL, Jacobs F. Recommended beta-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy. Critical Care 2011, 15: R137.

Dysregulation of the renin-angiotensin-aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with a likely significant contribution to organ failure and patient outcomes. A better understanding of the pathophysiology and intricacies of the RAAS in septic shock has led to the use of exogenous angiotensin II as a new therapeutic agent. In this review, we report a multinational and multi-disciplinary expert panel discussion on the role and implications of RAAS modulation in sepsis and the use of exogenous angiotensin II. The panel proposed guidance regarding patient selection and treatment options with exogenous angiotensin II which should trigger further research.

Low dose of HES together with LRS is more effective than only high dose of HES or LRS in the resuscitation for shock induced by ischemia/reperfusion injury of the intestine in rabbits, resulting in better hemodynamic parameters and tissue oxygenation.

Introduction: The aim of our study was to determine the degree of edema in the organs of patients who died with severe sepsis. Hypothesis: In severe sepsis, alterations in vascular permeability result in organ edema. The increase in weight may vary according to the organ considered. Methods: Autopsies are still routinely performed in patients who die in our 35 bed Multidisciplinary Department of Intensive Care. We reviewed the data and the organ weights of all patients who had a postmortem examination in the years 2008- 2011. We extracted a group (n=171) of patients with severe sepsis and a control group of patients who died without evidence of infection (n=54). Results: Total lung weight was significantly greater in septic than in non-infected patients (1591 ± 541 vs. 1306 ± 417 g, p<.001). These differences remained when only septic patients without pulmonary infection (n=74) were kept in the analysis (1509 ± 570 g, p=.028). The spleens were heavier in the sepsis group than in the control group (262 ± 175 vs. 180 ± 83 g, p<0.001) and changes in kidney weight almost reached statistical significance (346 ± 116 vs. 312 ± 100 g, p=.058). No significant difference was found in the weight of heart, liver, brain and thyroid gland. Septic patients with cirrhosis (n=59) had particularly heavy lung, spleen and kidney weight. Conclusions: Among non-survivors, septic patients have more edema in their lungs and spleen and perhaps kidneys than non-infected patients. However, their heart, liver, and brain are not heavier than in other ICU patients.

INTRODUCTION. Elevated ammonium levels (EAL) are one of the side effects of valproic acid (VPA) treatment. This complication has been described during long-term VPA treatment, but less in critically ill patients.OBJECTIVES. The aim of this study was to evaluate the incidence and the factors associated with EAL in those patients.METHODS. A retrospective study in a mixed 35-bed ICU care of a tertiary university hospital was conducted over a 4-year period (2007-2010). Inclusion criteria were; a) VPA therapy for more than 72 hours; b) age > 18 years; c) at least one measurement of ammonium levels during the ICU stay; d) Child C liver cirrhosis. EAL was defined as ammonium levels above 50 mcg/dL. Demographic data, comorbidities, reason for VPA treatment, biological data, concomitant therapies, presence of infection and ICU mortality were collected.RESULTS. A total of 168 patients met the inclusion criteria (median age 64 years, 95 male gender). Most of them (137/168) were admitted for neurological reasons. Overall ICU mortality was 23%. Median ammonium levels were 88 [55-121] mcg/dL. EAL was found in 121 (72%) patients; of those, 38 (31%) had ammonium levels between 100-150 mcg/dL, 11 (9%) between 150-200 mcg/dL and 13 (11%) above 250 mcg/dL. Median time from start of VPA therapy to EAL was 4 [3-5] days. Median maximum VPA level during therapy was 72 [51-88] and was significantly higher in EAL patients than in the others (76 [58-92] mcg/mL vs. 56 [39-81] mcg/mL, p< 0.01). EAL were more frequently observed in patients with sepsis (p< 0.01) and in those treated with mechanical ventilation (p< 0.01), vasopressors (p=0.05) and at least one other antiepileptic drug (p=0.02); these patients tended to have a higher ICU mortality (28% vs. 13%, p = 0.06).CONCLUSIONS. Ammonium levels are often elevated during treatment with valproic acid in ICU patients, especially in those with the greatest severity. This alteration may contribute to their alteration in brain function.