Publications

Introduction: Infection is a frequent complication in patients undergoing lung transplantation (LTx). Moreover, some of these patients are already colonized by Pseudomonas aeruginosa (PA) before surgery and need an adequate antibiotic prophylaxis to avoid further infection. Although acute, critically illness induce large changes in antibiotic pharmacokinetics and may result in inadequate drug concentrations to treat PA, no data are available on β-lactams levels after LTx. We hypothesized that β-lactams concentrations could be inadequate to treat PA in the early phase after LTx. Methods: We reviewed all patients in whom broad-spectrum β-lactams levels (ceftzidime or cefepime, CEF; meropenem, MEM; piperacillin; TZP) were measured after LTx from April 2010 to November 2012. Drug concentrations were measured after 2 hours from the onset of a 30-min perfusion and just before (trough, C0) the next dose. Drug regimens were adapted in case of cystic fibrosis. Creatinine clearance (CrCl) was calculated on the 24-hour urine collection on the day of the drug dosing. β-lactams concentrations were considered as insufficient if drug levels remained below 4 times the clinical breakpoint of the minimal inhibitory concentration (MIC) for PA at 70% (CEF), 40% (MEM) or 50% (TZP) of the dose interval. Clinical breakpoints were defined according to EUCAST guidelines and were as follows: 8 mg/L for CEF, 2 mg/L for MEM and 16 mg/L for TZP. Results: A total of 44 drug levels (7=CEF; 18=MEM; 19=TZP) were obtained in 22 patients (median age 48 [36-62] years; 8/22 male gender; median APACHE II score on ICU admission 15 [11-18]); 6 of them had cystic fibrosis. Median time from antibiotic initiation to drug dosing was 2 [1-5] days. Insufficient drug concentrations were found in 2/7 (29%) dosing for CEF, 7/18 (38%) for MEM and 12/19 (63%) for TZP (p=0.18). Only 1/10 drug dosing was found to be insufficient in patients with cystic fibrosis when compared to others (20/34, p=0.006). The proportion of patients with insufficient drug concentrations increased from 7/19 if CrCl < 40 ml/min to 4/10 if CrCl 40-120 and 10/12 if CrCl >120 ml/min (p=0.03). Conclusions: β-lactams levels are often insufficient to treat PA after LTx. Augmented renal clearance is an important determinant of insufficient drug levels.

Graf, Jürgen MD; Doig, Gordon S. DVM, PhD; Cook, Deborah J. MD, FRCPC, MSc(Epid); Vincent, Jean-Louis- MD, PhD, FCCM; Sibbald, William J. MD, FCCM Author Information

Although physicians and pharmacists were the most active users of EHR searches, search volume and frequently searched terms varied considerably by and within user role. Further customization of the EHR interface may help leverage users' search content and patterns to improve targeted information retrieval.

SCOPUS: no.j

ECPR after CA may be associated with improved long-term neurological outcome.

Introduction: Brain dysfunction is common during sepsis and is associated with increased mortality. These observations have been limited by potential confounding factors and the lack of evaluation over time. Hypothesis: To investigate the prognostic value of brain dysfunction as well as changes in neurological status over time in septic patients. Methods: Analysis of the Sepsis Occurrence in Acutely Ill Patients (SOAP) database. All data were collected until death, hospital discharge or for 60 days. Central nervous system (CNS) status was assessed using the neurological SOFA sub-score (nSOFA): CNS failure was defined as nSOFA > 2. Early failure was considered if occurred within 2 days since admission. Changes in nSOFA (?nSOFA) were calculated as the difference in nSOFA on day 3 (or day 2 if data on day 3 were not available) and nSOFA on admission. Brain improvement (BI) was defined as?nSOFA < 0 for initial nSOFA of 1 and 2, and nSOFA < 3 on day 3 for those with initial nSOFA 3 and 4. Patients without brain dysfunction had nSOFA of 0 during the first 3 ICU days. All the others were considered as having brain deterioration (BD). Results: After exclusion of 776 patients who presented with primary brain injury, we analysed the data of 2371 patients (904 with sepsis). In septic patients, ICU mortality was associated with a higher nSOFA score and early CNS failure; however, in a multivariable analysis, these factors were not independently predictors of poor outcome. When analyzing septic and non-septic patients, sepsis had an increased odds ratio (OR) for mortality of 1.21 [1.18-1.25], CNS failure of 1.45 [1.24-1.68] and sepsis with CNS failure of 1.76 [1.46-2.12]. nSOFA changes yielded 213 patients with BI and 278 with BD. After adjustment for confounding factors, sepsis had an increased odds ratio (OR) for ICU mortality of 1.42 [1.34-1.59], BD of 1.98 [1.79-2.18]. The presence of sepsis and BD increased the OR for ICU mortality to 2.80 [2.56-3.06]. Conclusions: Brain dysfunction is not independently associated with mortality in septic patients, but it has a greater impact on outcome in septic than in non-septic patients, even after correction for confounding factors.

Through a methodologically robust development process, the SOFA-2 score offers updated definitions to describe organ dysfunction in adult patients requiring critical care and readily quantifiable criteria to grade the degree of dysfunction in individual organ systems. This score considers contemporaneous changes in patient management and outcomes.