Effects of Intra-operative Cardiopulmonary Variability On Post-operative Pulmonary Complications in Major Non-cardiac Surgery: A Retrospective Cohort Study.

Intraoperative cardiopulmonary variables are well-known predictors of postoperative pulmonary complications (PPC), traditionally quantified by median values over the duration of surgery. However, it is unknown whether cardiopulmonary instability, or wider intra-operative variability of the same metrics, is distinctly associated with PPC risk and severity. We leveraged a retrospective cohort of adults (n = 1202) undergoing major non-cardiothoracic surgery. We used multivariable logistic regression to evaluate the association of two outcomes (1)moderate-or-severe PPC and (2)any PPC with two sets of exposure variables- (a)variability of cardiopulmonary metrics (inter-quartile range, IQR) and (b)median intraoperative cardiopulmonary metrics. We compared predictive ability (receiver operating curve analysis, ROC) and parsimony (information criteria) of three models evaluating different aspects of the intra-operative cardiopulmonary metrics: Median-based: Median cardiopulmonary metrics alone, Variability-based: IQR of cardiopulmonary metrics alone, and Combined: Medians and IQR. Models controlled for peri-operative/surgical factors, demographics, and comorbidities. PPC occurred in 400(33%) of patients, and 91(8%) experienced moderate-or-severe PPC. Variability in multiple intra-operative cardiopulmonary metrics was independently associated with risk of moderate-or-severe, but not any, PPC. For moderate-or-severe PPC, the best-fit predictive model was the Variability-based model by both information criteria and ROC analysis (area under the curve, AUCVariability-based = 0.74 vs AUCMedian-based = 0.65, p = 0.0015; AUCVariability-based = 0.74 vs AUCCombined = 0.68, p = 0.012). For any PPC, the Median-based model yielded the best fit by information criteria. Predictive accuracy was marginally but not significantly higher for the Combined model (AUCCombined = 0.661) than for the Median-based (AUCMedian-based = 0.657, p = 0.60) or Variability-based (AUCVariability-based = 0.649, p = 0.29) models. Variability of cardiopulmonary metrics, distinct from median intra-operative values, is an important predictor of moderate-or-severe PPC.

Thrombosis-Related Loss of Arterial Lines in the First Wave of COVID-19 and Non-COVID-19 Intensive Care Unit Patients.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can present with severe respiratory distress requiring intensive care unit (ICU)-level care. Such care often requires placement of an arterial line for monitoring of pulmonary disease progression, hemodynamics, and laboratory tests. During the first wave of the COVID-19 pandemic in March 2020, experienced physicians anecdotally reported multiple attempts, decreased insertion durations, and greater need for replacement of arterial lines in patients with COVID-19 due to persistent thrombosis. Because invasive procedures in patients with COVID-19 may increase the risk for caregiver infection, better defining difficulties in maintaining arterial lines in COVID-19 patients is important. We sought to explore the association between COVID-19 infection and arterial line thrombosis in critically ill patients. METHODS: In this primary exploratory analysis, a multivariable Fine-Gray subdistribution hazard model was used to retrospectively estimate the association between critically ill COVID-19 (versus sepsis/acute respiratory distress syndrome [ARDS]) patients and the risk of arterial line removal for thrombosis (with arterial line removal for any other reason treated as a competing risk). As a sensitivity analysis, we compared the number of arterial line clots per 1000 arterial line days between critically ill COVID-19 and sepsis/ARDS patients using multivariable negative binomial regression. RESULTS: We retrospectively identified 119 patients and 200 arterial line insertions in patients with COVID-19 and 54 patients and 68 arterial line insertions with non-COVID ARDS. Using a Fine-Gray subdistribution hazard model, we found the adjusted subdistribution hazard ratio (95% confidence interval [CI]) for arterial line clot to be 2.18 (1.06-4.46) for arterial lines placed in COVID-19 patients versus non-COVID-19 sepsis/ARDS patients ( P = .034). Patients with COVID-19 had 36.3 arterial line clots per 1000 arterial line days compared to 19.1 arterial line clots per 1000 arterial line days in patients without COVID-19 (adjusted incidence rate ratio [IRR] [95% CI], 1.78 [0.94-3.39]; P = .078). CONCLUSIONS: Our study suggests that arterial line complications due to thrombosis are more likely in COVID-19 patients and supports the need for further research on the association between COVID-19 and arterial line dysfunction requiring replacement.

Individualised positive end-expiratory pressure in abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) may optimise pulmonary compliance, thereby potentially mitigating lung injury. This meta-analysis aimed to determine the impact of individualised PEEP vs fixed PEEP during abdominal surgery on postoperative pulmonary outcomes. METHODS: Medical databases (PubMed, Embase, Web of Science, ScienceDirect, Google Scholar, and the China National Knowledge Infrastructure) were searched for RCTs comparing fixed vs individualised PEEP. The composite primary outcome of pulmonary complications comprised hypoxaemia, atelectasis, pneumonia, and acute respiratory distress syndrome. Secondary outcomes included oxygenation (PaO2/FiO2) and systemic inflammatory markers (interleukin-6 [IL-6] and club cell protein-16 [CC16]). We calculated risk ratios (RRs) and mean differences (MDs) with 95% confidence interval (CI) using DerSimonian and Laird random effects models. Cochrane risk-of-bias tool was applied. RESULTS: Ten RCTs (n=1117 patients) met the criteria for inclusion, with six reporting the primary endpoint. Individualised PEEP reduced the incidence of overall pulmonary complications (141/412 [34.2%]) compared with 183/415 (44.1%) receiving fixed PEEP (RR 0.69 [95% CI: 0.51-0.93]; P=0.016; I2=43%). Risk-of-bias analysis did not alter these findings. Individualised PEEP reduced postoperative hypoxaemia (74/392 [18.9%]) compared with 110/395 (27.8%) participants receiving fixed PEEP (RR 0.68 [0.52-0.88]; P=0.003; I2=0%) but not postoperative atelectasis (RR 0.93 [0.81-1.07]; P=0.297; I2=0%). Individualised PEEP resulted in higher PaO2/FiO2 (MD 20.8 mm Hg [4.6-36.9]; P=0.012; I2=80%) and reduced systemic inflammation (lower plasma IL-6 [MD -6.8 pg ml-1; -11.9 to -1.7]; P=0.009; I2=6%; and CC16 levels [MD -6.2 ng ml-1; -8.8 to -3.5]; P<0.001; I2=0%) at the end of surgery. CONCLUSIONS: Individualised PEEP may reduce pulmonary complications, improve oxygenation, and reduce systemic inflammation after abdominal surgery. CLINICAL TRIAL REGISTRATION: CRD42021277973.

Postoperative pulmonary complications with adjuvant regional anesthesia versus general anesthesia alone: a sub-analysis of the Perioperative Research Network study.

BACKGROUND: Adjuvant regional anesthesia is often selected for patients or procedures with high risk of pulmonary complications after general anesthesia. The benefit of adjuvant regional anesthesia to reduce postoperative pulmonary complications remains uncertain. In a prospective observational multicenter study, patients scheduled for non-cardiothoracic surgery with at least one postoperative pulmonary complication surprisingly received adjuvant regional anesthesia more frequently than those with no complications. We hypothesized that, after adjusting for surgical and patient complexity variables, the incidence of postoperative pulmonary complications would not be associated with adjuvant regional anesthesia. METHODS: We performed a secondary analysis of a prospective observational multicenter study including 1202 American Society of Anesthesiologists physical status 3 patients undergoing non-cardiothoracic surgery. Patients were classified as receiving either adjuvant regional anesthesia or general anesthesia alone. Predefined pulmonary complications within the first seven postoperative days were prospectively identified. Groups were compared using bivariable and multivariable hierarchical logistic regression analyses for the outcome of at least one postoperative pulmonary complication. RESULTS: Adjuvant regional anesthesia was performed in 266 (22.1%) patients and not performed in 936 (77.9%). The incidence of postoperative pulmonary complications was greater in patients receiving adjuvant regional anesthesia (42.1%) than in patients without it (30.9%) (site adjusted p = 0.007), but this association was not confirmed after adjusting for covariates (adjusted OR 1.37; 95% CI, 0.83-2.25; p = 0.165). CONCLUSION: After adjusting for surgical and patient complexity, adjuvant regional anesthesia versus general anesthesia alone was not associated with a greater incidence of postoperative pulmonary complications in this multicenter cohort of non-cardiothoracic surgery patients.

A Comparison of Web-Based with Traditional Classroom-Based Training of Lung Ultrasound for the Exclusion of Pneumothorax.

BACKGROUND: Lung ultrasound (LUS) is a well-established method that can exclude pneumothorax by demonstration of pleural sliding and the associated ultrasound artifacts. The positive diagnosis of pneumothorax is more difficult to obtain and relies on detection of the edge of a pneumothorax, called the "lung point." Yet, anesthesiologists are not widely taught these techniques, even though their patients are susceptible to pneumothorax either through trauma or as a result of central line placement or regional anesthesia techniques performed near the thorax. In anticipation of an increased training demand for LUS, efficient and scalable teaching methods should be developed. In this study, we compared the improvement in LUS skills after either Web-based or classroom-based training. We hypothesized that Web-based training would not be inferior to "traditional" classroom-based training beyond a noninferiority limit of 10% and that both would be superior to no training. Furthermore, we hypothesized that this short training session would lead to LUS skills that are similar to those of ultrasound-trained emergency medicine (EM) physicians. METHODS: After a pretest, anesthesiologists from 4 academic teaching hospitals were randomized to Web-based (group Web), classroom-based (group class), or no training (group control) and then completed a posttest. Groups Web and class returned for a retention test 4 weeks later. All 3 tests were similar, testing both practical and theoretical knowledge. EM physicians (group EM) performed the pretest only. Teaching for group class consisted of a standardized PowerPoint lecture conforming to the Consensus Conference on LUS followed by hands-on training. Group Web received a narrated video of the same PowerPoint presentation, followed by an online demonstration of LUS that also instructs the viewer to perform an LUS on himself using a clinically available ultrasound machine and submit smartphone snapshots of the resulting images as part of a portfolio system. Group Web received no other hands-on training. RESULTS: Groups Web, class, control, and EM contained 59, 59, 20, and 42 subjects. After training, overall test results of groups Web and class improved by a mean of 42.9% (±18.1% SD) and 39.2% (±19.2% SD), whereas the score of group control did not improve significantly. The test improvement of group Web was not inferior to group class. The posttest scores of groups Web and class were not significantly different from group EM. In comparison with the posttests, the retention test scores did not change significantly in either group. CONCLUSIONS: When training anesthesiologists to perform LUS for the exclusion of pneumothorax, we found that Web-based training was not inferior to traditional classroom-based training and was effective, leading to test scores that were similar to a group of clinicians experienced in LUS.

Increased plasma catalytic iron in patients may mediate acute kidney injury and death following cardiac surgery.

Catalytic iron, the chemical form of iron capable of participating in redox cycling, is a key mediator of acute kidney injury (AKI) in multiple animal models, but its role in human AKI has not been studied. Here we tested in a prospective cohort of 250 patients undergoing cardiac surgery whether plasma catalytic iron levels are elevated and associated with the composite outcome of AKI requiring renal replacement therapy or in-hospital mortality. Plasma catalytic iron, free hemoglobin, and other iron parameters were measured preoperatively, at the end of cardiopulmonary bypass, and on postoperative days 1 and 3. Plasma catalytic iron levels, but not other iron parameters, rose significantly at the end of cardiopulmonary bypass and were directly associated with bypass time and number of packed red blood cell transfusions. In multivariate analyses adjusting for age and preoperative eGFR, patients in the highest compared with the lowest quartile of catalytic iron on postoperative day 1 had a 6.71 greater odds of experiencing the primary outcome, and also had greater odds of AKI, hospital mortality, and postoperative myocardial injury. Thus, our data are consistent with and expand on findings from animal models demonstrating a pathologic role of catalytic iron in mediating adverse postoperative outcomes. Interventions aimed at reducing plasma catalytic iron levels as a strategy for preventing AKI in humans are warranted.

Anesthetic selection and disease-free survival following optimal primary cytoreductive surgery for stage III epithelial ovarian cancer.

BACKGROUND: Previous studies have offered conflicting results regarding an association between perioperative epidural analgesia and disease-free survival (DFS) following optimal primary cytoreductive surgery for stage III epithelial ovarian cancer. A possible separate role for inhalational anesthetics has not been assessed. METHODS: We conducted a historical cohort study of all women undergoing optimal primary cytoreduction (<1 cm residual disease) for Stage III epithelial ovarian cancer between January 1, 2007, and December 31, 2011, at Brigham and Women's Hospital. Cohorts were defined by exposure to perioperative epidural analgesia or exposure to specific volatile anesthetics. The primary outcome was DFS. RESULTS: A total of 194 patients met study inclusion criteria. Addition of epidural analgesia was associated with a lower overall rate of ovarian cancer recurrence compared with general anesthesia alone (72 vs. 85 %, p = 0.028). Longer median DFS was associated with more than 48 h of epidural use (14.9 months) compared with fewer than 24 h (10.9 months) or 24-48 h of epidural use (10.0 months; p = 0.025). Use of desflurane was associated with a lower overall rate of ovarian cancer recurrence compared with sevoflurane (63 vs. 84 %, p = 0.01). In multivariate analysis, use of desflurane was independently associated with improved DFS (hazards ratio 0.563; 95% confidence interval 0.33-0.962). CONCLUSIONS: For patients with Stage III ovarian cancer, use of desflurane is associated with improved DFS following primary cytoreductive surgery compared with other volatile anesthetics. If epidural analgesia offers additional benefit, this effect appears limited to patients with more than 48 h of postoperative epidural use.

Providing initial transthoracic echocardiography training for anesthesiologists: simulator training is not inferior to live training.

OBJECTIVE: Transthoracic echocardiography (TTE) is finding increased use in anesthesia and critical care. Efficient options for training anesthesiologists should be explored. Simulator mannequins allow for training of manual acquisition and image recognition skills and may be suitable due to ease of scheduling. The authors tested the hypothesis that training with a simulator would not be inferior to training using a live volunteer. DESIGN: Prospective, randomized trial. SETTING: University hospital. PARTICIPANTS: Forty-six anesthesia residents, fellows, and faculty. INTERVENTIONS: After preparation with a written and video tutorial, study subjects received 80 minutes of TTE training using either a simulator or live volunteer. Practical and written tests were completed before and after training to assess improvement in manual image acquisition skills and theoretic knowledge. The written test was repeated 4 weeks later. MEASUREMENTS AND MAIN RESULTS: Performance in the practical image-acquisition test improved significantly after training using both the live volunteer and the simulator, improving by 4.0 and 4.3 points out of 15, respectively. Simulator training was found not to be inferior to live training, with a mean difference of -0.30 points and 95% confidence intervals that did not cross the predefined non-inferiority margin. Performance in the written retention test also improved significantly immediately after training for both groups but declined similarly upon repeat testing 4 weeks later. CONCLUSIONS: When providing initial TTE training to anesthesiologists, training using a simulator was not inferior to using live volunteers.

Impaired oxygenation after lung resection: Incidence and perioperative risk factors.

STUDY OBJECTIVE: To estimate the incidence of postoperative oxygenation impairment after lung resection in the era of lung-protective management, and to identify perioperative factors associated with that impairment. DESIGN: Registry-based retrospective cohort study. SETTING: Two large academic hospitals in the United States. PATIENTS: 3081 ASA I-IV patients undergoing lung resection. MEASUREMENTS: 79 pre- and intraoperative variables, selected for inclusion based on a causal inference framework. The primary outcome of impaired oxygenation, an early marker of lung injury, was defined as at least one of the following within seven postoperative days: (1) SpO2 < 92%; (2) imputed PaO2/FiO2 < 300 mmHg [(1) or (2) occurring at least twice within 24 h]; (3) intensive oxygen therapy (mechanical ventilation or > 50% oxygen or high-flow oxygen). MAIN RESULTS: Oxygenation was impaired within seven postoperative days in 70.8% of patients (26.6% with PaO2/FiO2 < 200 mmHg or intensive oxygen therapy). In multivariable analysis, each additional cmH2O of intraoperative median driving pressure was associated with a 7% higher risk of impaired oxygenation (OR 1.07; 95%CI 1.04 to 1.10). Higher median intraoperative FiO2 (OR 1.23; 95%CI 1.14 to 1.31 per 0.1) and PEEP (OR 1.12; 95%CI 1.04 to 1.21 per 1 cm H2O) were also associated with increased risk. History of COPD (OR 2.55; 95%CI 1.95 to 3.35) and intraoperative albuterol administration (OR 2.07; 95%CI 1.17 to 3.67) also showed reliable effects. CONCLUSIONS: Impaired postoperative oxygenation is common after lung resection and is associated with potentially modifiable pre- and intraoperative respiratory factors.

Fibrinogen excretion in the urine and immunoreactivity in the kidney serves as a translational biomarker for acute kidney injury.

Fibrinogen (Fg) is significantly up-regulated in the kidney after acute kidney injury (AKI). We evaluated the performance of Fg as a biomarker for early detection of AKI. In rats and mice with kidney tubular damage induced by ischemia/reperfusion (I/R) or cisplatin administration, respectively; kidney tissue and urinary Fg increased significantly and correlated with histopathological injury, urinary kidney injury molecule-1 (KIM-1) and N-acetyl glucosaminidase (NAG) corresponding to the progression and regression of injury temporally. In a longitudinal follow-up of 31 patients who underwent surgical repair of abdominal aortic aneurysm, urinary Fg increased earlier than SCr in patients who developed postoperative AKI (AUC-ROC = 0.72). Furthermore, in a cohort of patients with biopsy-proven AKI (n = 53), Fg immunoreactivity in the tubules and interstitium increased remarkably and was able to distinguish patients with AKI from those without AKI (n = 59). These results suggest that immunoreactivity of Fg in the kidney, as well as urinary excretion of Fg, serves as a sensitive and early diagnostic translational biomarker for detection of AKI.

Feasibility Assessment of a Biomarker-Guided Kidney-Sparing Sepsis Bundle: The Limiting Acute Kidney Injury Progression In Sepsis Trial.

OBJECTIVES: To determine the feasibility, safety, and efficacy of a biomarker-guided implementation of a kidney-sparing sepsis bundle (KSSB) of care in comparison with standard of care (SOC) on clinical outcomes in patients with sepsis. DESIGN: Adaptive, multicenter, randomized clinical trial. SETTING: Five University Hospitals in Europe and North America. PATIENTS: Adult patients, admitted to the ICU with an indwelling urinary catheter and diagnosis of sepsis or septic shock, without acute kidney injury (acute kidney injury) stage 2 or 3 or chronic kidney disease. INTERVENTIONS: A three-level KSSB based on Kidney Disease: Improving Global Outcomes (KDIGOs) recommendations guided by serial measurements of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 used as a combined biomarker [TIMP2]•[IGFBP7]. MEASUREMENTS AND MAIN RESULTS: The trial was stopped for low enrollment related to the COVID-19 pandemic. Nineteen patients enrolled in five sites over 12 months were randomized to the SOC (n = 8, 42.0%) or intervention (n = 11, 58.0%). The primary outcome was feasibility, and key secondary outcomes were safety and efficacy. Adherence to protocol in patients assigned to the first two levels of KSSB was 15 of 19 (81.8%) and 19 of 19 (100%) but was 1 of 4 (25%) for level 3 KSSB. Serious adverse events were more frequent in the intervention arm (4/11, 36.4%) than in the control arm (1/8, 12.5%), but none were related to study interventions. The secondary efficacy outcome was a composite of death, dialysis, or progression of greater than or equal to 2 stages of acute kidney injury within 72 hours after enrollment and was reached by 3 of 8 (37.5%) patients in the control arm, and 0 of 11 (0%) patients in the intervention arm. In the control arm, two patients experienced progression of acute kidney injury, and one patient died. CONCLUSIONS: Although the COVID-19 pandemic impeded recruitment, the actual implementation of a therapeutic strategy that deploys a KDIGO-based KSSB of care guided by risk stratification using urinary [TIMP2]•[IGFBP7] seems feasible and appears to be safe in patients with sepsis.

An evaluation of the diagnostic accuracy of the 1991 American College of Chest Physicians/Society of Critical Care Medicine and the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine/American College of Chest Physicians/American Thoracic Society/Surgical Infection Society sepsis definition.

OBJECTIVES: Limited research has been conducted to compare the test characteristics of the 1991 and 2001 sepsis consensus definitions. This study assessed the accuracy of the two sepsis consensus definitions among adult critically ill patients compared to sepsis case adjudication by three senior clinicians. DESIGN: Observational study of patients admitted to intensive care units. SETTING: Seven intensive care units of an academic medical center. PATIENTS: A random sample of 960 patients from all adult intensive care unit patients between October 2007 and December 2008. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sensitivity, specificity, and the area under the receiver operating characteristic curve for the two consensus definitions were calculated by comparing the number of patients who met or did not meet consensus definitions vs. the number of patients who were or were not diagnosed with sepsis by adjudication. The 1991 sepsis definition had a high sensitivity of 94.6%, but a low specificity of 61.0%. The 2001 sepsis definition had a slightly increased sensitivity but a decreased specificity, which were 96.9% and 58.3%, respectively. The areas under the receiver operating characteristic curve for the two definitions were not statistically different (0.778 and 0.776, respectively). The sensitivities and areas under the receiver operating characteristic curve of both definitions were lower at the 24-hr time window level than those of the intensive care unit stay level, though their specificities increased slightly. Fever, high white blood cell count or immature forms, low Glasgow coma score, edema, positive fluid balance, high cardiac index, low PaO2/FIO2 ratio, and high levels of creatinine and lactate were significantly associated with sepsis by both definitions and adjudication. CONCLUSIONS: Both the 1991 and the 2001 sepsis definition have a high sensitivity but low specificity; the 2001 definition has a slightly increased sensitivity but a decreased specificity compared to the 1991 definition. The diagnostic performances of both definitions were suboptimal. A parsimonious set of significant predictors for sepsis diagnosis is likely to improve current sepsis case definitions.

Voltage-Gated Sodium Channels as Potential Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer.

Abnormal ion channel expression distinguishes several types of carcinoma. Here, we explore the relationship between voltage-gated sodium channels (VGSC) and epithelial ovarian cancer (EOC). We find that EOC cell lines express most VGSC, but at lower levels than fallopian tube secretory epithelial cells (the cells of origin for most EOC) or control fibroblasts. Among patient tumor samples, lower SCN8A expression was associated with improved overall survival (OS) (median 111 vs. 52 months; HR 2.04 95% CI: 1.21-3.44; p = 0.007), while lower SCN1B expression was associated with poorer OS (median 45 vs. 56 months; HR 0.69 95% CI 0.54-0.87; p = 0.002). VGSC blockade using either anti-epileptic drugs or local anesthetics (LA) decreased the proliferation of cancer cells. LA increased cell line sensitivity to platinum and taxane chemotherapies. While lidocaine had similar additive effects with chemotherapy among EOC cells and fibroblasts, bupivacaine showed a more pronounced impact on EOC than fibroblasts when combined with either carboplatin (ΔAUC -37% vs. -16%, p = 0.003) or paclitaxel (ΔAUC -37% vs. -22%, p = 0.02). Together, these data suggest VGSC are prognostic biomarkers in EOC and may inform new targets for therapy.

Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma.

OBJECTIVES: Cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin has been used successfully to treat malignant pleural mesothelioma, a highly aggressive malignancy that is rapidly fatal in most cases. We hypothesized that the combination of ischemic injury with nephrotoxic injury from cisplatin would result in high rates of acute kidney injury. METHODS: We conducted an observational study in 503 patients to study the risks and outcomes of acute kidney injury after surgical resection of malignant pleural mesothelioma. Eligible subjects underwent extrapleural pneumonectomy or pleurectomy/decortication with or without hyperthermic intraoperative chemotherapy. Acute kidney injury was defined as an increase in creatinine of 26.5 µmol/L or greater within 48 hours of surgery or a 50% or greater increase over 7 days. RESULTS: Acute kidney injury developed in 243 patients (48.3%). Severe acute kidney injury requiring renal replacement therapy developed in 16 patients (3.2%). Major significant predictors for acute kidney injury included male sex (odds ratio, 2.98; P < .001), intraoperative cisplatin administration (odds ratio, 3.12; P < .001), previous cisplatin exposure (odds ratio, 1.96; P = .02), hypertension (odds ratio, 1.57; P = .02), and longer surgical time (odds ratio, 1.15 per hour; P = .02). Compared with patients without acute kidney injury, those with severe acute kidney injury had longer length of stay (26 vs 13 days) and a 2.71-fold increased risk of death in multivariable-adjusted models. CONCLUSIONS: Acute kidney injury is common after cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin and is associated with poor long-term outcomes. Strategies to prevent postoperative acute kidney injury are needed to improve multimodal treatment of malignant pleural mesothelioma.

Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern?

BACKGROUND: Candidaemia is often treated with fluconazole in the absence of susceptibility testing. We examined factors associated with candidaemia caused by Candida isolates with reduced susceptibility to fluconazole. METHODS: We identified consecutive episodes of candidaemia at two hospitals from 2001 to 2007. Species identification followed CLSI methodology and fluconazole susceptibility was determined by Etest or broth microdilution. Susceptibility to fluconazole was defined as: full susceptibility (MIC < or = 8 mg/L); and reduced susceptibility (MIC > or = 32 mg/L). Complete resistance was defined as an MIC > 32 mg/L. RESULTS: Of 243 episodes of candidaemia, 190 (78%) were fully susceptible to fluconazole and 45 (19%) had reduced susceptibility (of which 27 were fully resistant). Of Candida krusei and Candida glabrata isolates, 100% and 51%, respectively, had reduced susceptibility. Despite the small proportion of Candida albicans (8%), Candida tropicalis (4%) and Candida parapsilosis (4%) with reduced fluconazole susceptibility, these species composed 36% of the reduced-susceptibility group and 48% of the fully resistant group. In multivariate analysis, independent factors associated with reduced fluconazole susceptibility included male sex [odds ratio (OR) 3.2, P < 0.01], chronic lung disease (OR 2.7, P = 0.01), the presence of a central vascular catheter (OR 4.0, P < 0.01) and prior exposure to antifungal agents (OR 2.2, P = 0.04). CONCLUSIONS: A significant proportion of candidaemia with reduced fluconazole susceptibility may be caused by C. albicans, C. tropicalis and C. parapsilosis, species usually considered fully susceptible to fluconazole. Thus, identification of these species may not be predictive of fluconazole susceptibility. Other factors that are associated with reduced fluconazole susceptibility may help clinicians choose adequate empirical anti-Candida therapy.