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Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment., SCOPUS: ar.j, info:eu-repo/semantics/published

Introduction: The aim of this study was to describe the population pharmacokinetics of vancomycin in critically ill patients treated with and without extracorporeal membrane oxygenation (ECMO).Methods: We retrospectively reviewed data from critically ill patients treated with ECMO and matched controls who received a continuous infusion of vancomycin (35 mg/kg loading dose over 4 hours followed by a daily infusion adapted to creatinine clearance, CrCl)). The pharmacokinetics of vancomycin were described using non-linear mixed effects modeling.Results: We compared 11 patients treated with ECMO with 11 well-matched controls. Drug dosing was similar between groups. The median interquartile range (IQR) vancomycin concentrations in ECMO and non-ECMO patients were 51 (28 to 71) versus 45 (37 to 71) mg/L at 4 hours; 23 (16 to 38) versus 29 (21 to 35) mg/L at 12 hours; 20 (12 to 36) versus 23 (17-28) mg/L at 24 hours (ANOVA, P =0.53). Median (ranges) volume of distribution (Vd) was 99.3 (49.1 to 212.3) and 92.3 (22.4 to 149.4) L in ECMO and non-ECMO patients, respectively, and clearance 2.4 (1.7 to 4.9) versus 2.3 (1.8 to 3.6) L/h (not significant). Insufficient drug concentrations (that is drug levels <20 mg/dL) were more common in the ECMO group. The pharmacokinetic model (non-linear mixed effects modeling) was prospectively validated in five additional ECMO-treated patients over a 6-month period. Linear regression analysis comparing the observed concentrations and those predicted using the model showed good correlation (r2 of 0.67; P <0.001).Conclusions: Vancomycin concentrations were similar between ECMO and non-ECMO patients in the early phase of therapy. ECMO treatment was not associated with significant changes in Vd and drug clearance compared with the control patients., SCOPUS: ar.j, info:eu-repo/semantics/published

INTRODUCTION. Infection is frequent in patients treated by extracorporeal membrane oxygenation (ECMO) and yet pharmacokinetics (PKs) of beta-lactams during ECMO have not been well studied. In critically ill patients, antimicrobial PKs are significantly altered and may result in subtherapeutic drug concentrations [1,2]. ECMO introduces additional confounding factors, which may further alter antibiotic concentrations.OBJECTIVES. We hypothezised that meropenem (MERO) and piperacillin (PIP) PKs parameters are altered in critically ill patients treated with ECMO.METHODS. We reviewed all patients in whom drug levels were measured during MERO or PIP therapy while on ECMO support (from January 2010 to December 2012). Drug concentrations were measured after 2 hours from the onset of a 30-min perfusion and just before (trough, C0) the next dose; PKs were estimated using a one-compartment model. Using a database of all patients having b-lactams level measurements, ECMO patients were matched with non-ECMO patients according to: 1) drug regimen; 2) renal function (i.e. similar measured creatinine clearance or similar intensity of therapy if on continuous renal replacement therapy); 3) total body weight; 4) Sequential Organ Failure Assessment (SOFA) score on the day of drug levels measurement. Drug concentrations were considered as adequate if drug levels remained between 4 and 8 times the clinical breakpoint of the minimal inhibitory concentration (MIC) for Pseudomonas aeruginosa during 50% (PIP) or 40% (MERO) of the dose interval.RESULTS. A total of 41 drug levels (MERO=27; PIP = 14) were obtained in 26 patients treated with ECMO (16 veno-venous and 9 veno-arterial) and 41 matched controls. Patients' characteristics are shown in the table. ECMO patients had higher ICU mortality (58% vs. 26%), longer ICU stay and greater need of mechanical ventilation (93% vs. 66%), but similar need for vasopressors (66% vs. 63%) No significant differences were found between ECMO and non-ECMO pa, info:eu-repo/semantics/published

info:eu-repo/semantics/published

Introduction: Early prognostication of neurological outcome after cardiopulmonary resuscitation (CPR) is extremely important as it can help to reassess therapeutic intensity or select high-risk patients for specific interventionsHypothesis: Age and biological variables obtained from initial simple blood tests could predict poor neurological outcome (PNO) after CPRMethods: Data from all patients admitted after CPR (in and out-of-hospital) from January 2008 to December 2011 in a mixed 35-bed ICU were assessed. Therapeutic hypothermia was used in all patients. We identified those who had a complete blood gas/electrolyte panel within the first hour after ICU admission. PNO was defined as a cerebral performance category (CPC) score of 4-5 at hospital discharge. We calculated areas under the receiver operating characteristic curve (AUROC) for each variable and derived the score from those having the highest AUROCs. We identified the best cut-off point (the best combination of sensitivity and specificity) which was used as a dichotomic value (0 or 1), with 1 representing PNO. We constructed 20 different models with combinations of the variables to identify the best model according to the highest AUROC. All analyses were performed with SPSS 19.0Results: A total of 127 patients (mean age 61 years, male gender 76%) were included in the analysis; 69% had out-of-hospital CPR and 57% had shockable rhythms. Overall mortality was 58%. Individual AUROCs (CI 95%) used in the model were: Hemoglobin (Hb) 0.65 (0.55-0.74), blood glucose (Gly) 0.63 (0.53-0.73), lactate (Lac) 0.62 (0.52-0.72), total CO2 (TCO2) 0.59 (0.49-0.69), and age 0.62 (0.52-0.71). The model with the best AUROC (0.772 (0.69-0.85)) included Hb < 12.5 g/dl, Gly > 180 mg/dl, Lac > 2 mEq/L, TCO2 < 20 mEq/L and age? 60 years. Scores of 0-1, 2-3, and 4-5 resulted in predicted PNOs of 30% (7/23), 51% (30/58) and 91% (42/46), and in predicted good neurological outcomes of 69% (16/23), 48% (28/58) and 8% (4/46), respectively, info:eu-repo/semantics/published, Communication at the 42st SCCM Congress (19-23 January 2013 – San Juan, USA).

Introduction: Antibiotics are often administered in patients treated by extracorporeal membrane oxygenation (ECMO) but pharmacokinetics (PKs) of antibiotics during ECMO have not been well defined.Hypothesis: To evaluate vancomycin concentrations in critically ill patients treated with ECMO.Methods: We reviewed all patients who received a continuous infusion (CI) of vancomycin when on ECMO support from January 2011 to May 2012. Vancomycin was given as a 35 mg/kg loading dose in 4-hr, and the infusion doses were adapted to creatinine clearance, CrCL). Drug concentrations were measured at 4 (T1), 12 (T2) and in the first 24 hours (T3) after the onset of therapy. Using a database reporting all patients having this vancomycin regimen, ECMO patients were matched (1:1) with non-ECMO patients according to four criteria: 1) renal function (i.e. same CrCL or both on continuous renal replacement therapy, CRRT); 2) total body weight; 3) Sequential Organ Failure Assessment (SOFA) score; 4) age. Vancomycin concentrations between 20 and 30 [micro]g/ml were considered as adequate.Results: We compared 11 patients treated with ECMO and 11 well matched controls. Mean vancomycin loading (2500 [1610-2975] mg vs. 2450 [1645-3500] mg) and daily doses (1125 [750-3000] vs. 1200 [750-2500] mg) were similar in the two groups. Drug concentrations in ECMO and non-ECMO patients were: 51 [28-71] mcg/mL vs. 45 [37-71] mcg/mL on T1; 23 [16-38] vs. 29 [21-35] mcg/mL on T2; 20 [12-36] vs. 23 [17-28] mcg/mL on T3 (ANOVA, p=0.53). The number of patients with insufficient drug concentrations in ECMO group was 2 on T2 and 4 on T3 when compared to 0 and 1, respectively, in the control group.Conclusions: Vancomycin concentrations in the early phase of therapy were quite similar in patients treated or not with ECMO. Nevertheless, more patients in the ECMO group tended to have insufficient drug concentrations, so that vancomycin doses should be probably increased somewhay in these patients., info:eu-repo/semantics/published, Communication at the 42st SCCM Congress (19-23 January 2013 – San Juan, USA).

Introduction: Despite the development of new molecules with anti-Gram positive bacteria activity, vancomycin is still the treatment of choice in septic critically ill patients. Because sepsis can alter drug pharmacokinetics, the development of an administration strategy able to promptly provide adequate antimicrobial concentrations is crucial.Hypothesis: The aim of this study was to prospectively validate a new regimen of vancomycin given by continuous infusion (CI)1 in septic patients.Methods: We prospectively included septic patients admitted to a mixed ICU from January 2011 to May 2012, treated with a new regimen of CI vancomycin, including a loading dose (LD) of 35 mg/kg of body weight given as a 4-hr infusion, followed by a daily CI dose adapted on creatinine clearance (CrCL), estimated by the Cockroft-Gault formula. We excluded patients treated by extracorporeal replacement therapies or less than 18 years of age. Serum vancomycin levels were measured at the end of LD, 12, 24 (n=107) and 48 hours (n=56) after the start of therapy. Dose adjustment was decided on drug concentrations at 24 and/or 48 hours. Adequate vancomycin concentrations were considered between 20 and 30 [micro]g/ml.Results: A total of 107 patients were included (77 male, age: 59 [48-71] years; weight: 75 [65-85] kgs; medical admission 69 (64%). Median APACHE II score on admission was 19 [14-23]. Mechanical ventilation was used in 58 (54%) patients and septic shock was present in 54 (53%). Overall ICU mortality was 22%. Median loading and daily doses were 2650 [2288 +/- 2295] mg and 2112 [1500-2838] mg/day, respectively. Vancomycin concentrations were 44 [37-49] [micro]g/mL at the end of LD and then 25 [21-32], 22 [19-28] and 26 [22-29] [micro]g/mL at 12, 24 and 48 hrs, respectively. Insufficient drug concentrations were found in 17 (16%), 29 (27%) and 4 (7%) patients at 12, 24 and 48 hrs, respectively and excessive levels (>30[micro]g/mL) were found in 30 (28%), 19 (17%) and 5 (9%).Conclusions, Communication at the 42st SCCM Congress (19-23 January 2013 – San Juan, USA)., info:eu-repo/semantics/published