Publications

Abstract BACKGROUND : Acute kidney injury (AKI) occurs frequently after liver transplant surgery and is associated with significant morbidity and mortality. While the impact of intraoperative hypotension (IOH) on postoperative AKI has been well demonstrated in patients undergoing a wide variety of non-cardiac surgeries, it remains poorly studied in liver transplant surgery. We tested the hypothesis that IOH is associated with AKI following liver transplant surgery. METHODS : This historical cohort study included all consecutive patients who underwent liver transplant surgery between 2014 and 2019 except those with a preoperative creatinine > 1.5 mg/dl and/or who had combined transplantation surgery. IOH was defined as any mean arterial pressure (MAP) < 65 mmHg and was classified according to the percentage of case time during which the MAP was < 65 mmHg into three groups, based on the interquartile range of the study cohort: “short” (Quartile 1, < 8.6% of case time), “ intermediate” (Quartiles 2-3, 8.6-39.5%) and “ long” (Quartile 4, > 39.5%) duration. AKI stages were classified according to a “modified” “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria. Logistic regression modelling was conducted to assess the association between IOH and postoperative AKI. The model was run both as a univariate and with multiple perioperative covariates to test for robustness to confounders. RESULTS : Of the 205 patients who met our inclusion criteria, 117 (57.1%) developed AKI. Fifty-two (25%), 102 (50%) and 51 (25%) patients had short, intermediate and long duration of IOH respectively. In multivariate analysis, IOH was independently associated with an increased risk of AKI (adjusted odds ratio [OR] 1.05; 95%CI 1.02-1.09; P < 0.001). Compared to “ short duration ” of IOH, “ intermediate duration” was associated with a 10-fold increased risk of developing AKI (OR 9.7; 95%CI 4.1-22.7; P < 0.001). “ Long duration” was associated with an even greater risk of AKI compared to “ short duration ” (OR 34.6; 95%CI 11.5-108.6; P < 0.001). CONCLUSION : Intraoperative hypotension is independently associated with the development of AKI after liver transplant surgery. The longer the MAP stays < 65 mmHg, the higher the risk the patient will develop AKI in the immediate postoperative period, and the greater the likely severity. Trial Registration: Not Applicable

We describe the molecular characterization of a multiresistant Pseudomonas aeruginosa clone causing an outbreak in the intensive care unit (ICU) of a tertiary-care university hospital. Analysis included antimicrobial susceptibility profile, O-serotyping, pulsed-field gel electrophoresis, and amplified fragment length polymorphism. Resistance mechanisms were characterized, including production of naturally occurring and acquired beta-lactamases, porin expression, and efflux pump systems. Eighteen patients were colonized or infected with multiresistant P. aeruginosa. Multiresistant P. aeruginosa was panresistant to penicillins, cephalosporins, carbapenems, aminoglycosides, and fluoroquinolones and remained susceptible only to colistin. Sixteen isolates (89%) belonged to serotype O:11, pulsed-field gel electrophoresis type A1, and amplified fragment length polymorphism type A. Resistance characterization of this epidemic clone showed an overexpression of the chromosomal cephalosporinase AmpC combined with decreased expression of porin OprD and the absence of metallo-beta-lactamase or extended-spectrum beta-lactamase. An upregulation of the MexXY efflux system due to an agrZ mutation in the mexZ repressor was detected. This epidemic clone was restricted to the ICU and was not found elsewhere in hospital. Contamination of the ICU environment and the hands of an ICU nurse with this clone suggests possible hand-borne transmission. Implementation of contact precautions effectively controlled transmission of the epidemic clone. This study illustrates the ability of multiresistant P. aeruginosa to cause an outbreak with significant morbidity and mortality and underscores the need to identify clonal outbreaks, which require targeted infection control measures.

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 µg/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.

In this sheep model of renal ischemia/reperfusion, BH4 pretreatment reduced renal microvascular injury and improved renal metabolism and function. Further work is needed to clarify the potential role of BH4 in ischemia/reperfusion injury.