The Association Between Low Admission Peak Plasma Creatinine Concentration and In-Hospital Mortality in Patients Admitted to Intensive Care in Australia and New Zealand.

OBJECTIVE: To evaluate the independent association between low peak admission plasma creatinine concentrations and in-hospital mortality in patients requiring critical care in Australia and New Zealand. DESIGN: Multicenter, binational, retrospective cohort study. SETTING: Data were extracted from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database. PATIENTS: All available records for the period 2000 to 2013 were utilized. The following exclusion criteria were applied: all readmission episodes (within the same hospital stay), missing in-hospital mortality, admission post kidney transplantation, chronic renal replacement therapy (hemodialysis or peritoneal dialysis), and missing peak plasma creatinine concentration. Demographic, anthropometric, admission, illness severity, laboratory, and outcome data were then extracted. Patients were categorized on the basis of their peak (maximum) plasma creatinine concentration recorded in the first 24 hours of ICU admission. Illness severity-adjusted associations with in-hospital mortality relative to a reference category of 70-79 µmol/L were then determined using multivariate logistic regression. INTERVENTIONS: Nil. MEASUREMENTS AND MAIN RESULTS: Data pertaining to 1,250,449 admissions were available for the study period. Following exclusions, 1,045,718 patients were included. Regression analysis identified that peak plasma creatinine concentrations less than 60 µmol/L measured in the first 24 hours after ICU admission imply a steadily increasing adjusted in-hospital mortality risk. In cases where this value is markedly low (< 30 µmol/L), the adjusted odds of dying in-hospital is over two-fold higher than the reference category and exceeds the risk implied with elevated (≥ 180 µmol/L) values. This finding was also independent of anthropometric data. CONCLUSIONS: In a large heterogenous cohort of critically ill patients, low admission peak plasma creatinine concentrations are independently associated with increased risk-adjusted in-hospital mortality. Further research should now focus on the potential mechanisms underpinning this finding, such as a low skeletal muscle mass and/or fluid overload.

Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno-arterial-ECMO (SAVE)-score.

RATIONALE: Extracorporeal membrane oxygenation (ECMO) may provide mechanical pulmonary and circulatory support for patients with cardiogenic shock refractory to conventional medical therapy. Prediction of survival in these patients may assist in management of these patients and comparison of results from different centers. AIMS: To identify pre-ECMO factors which predict survival from refractory cardiogenic shock requiring ECMO and create the survival after veno-arterial-ECMO (SAVE)-score. METHODS AND RESULTS: Patients with refractory cardiogenic shock treated with veno-arterial ECMO between January 2003 and December 2013 were extracted from the international Extracorporeal Life Support Organization registry. Multivariable logistic regression was performed using bootstrapping methodology with internal and external validation to identify factors independently associated with in-hospital survival. Of 3846 patients with cardiogenic shock treated with ECMO, 1601 (42%) patients were alive at hospital discharge. Chronic renal failure, longer duration of ventilation prior to ECMO initiation, pre-ECMO organ failures, pre-ECMO cardiac arrest, congenital heart disease, lower pulse pressure, and lower serum bicarbonate (HCO3) were risk factors associated with mortality. Younger age, lower weight, acute myocarditis, heart transplant, refractory ventricular tachycardia or fibrillation, higher diastolic blood pressure, and lower peak inspiratory pressure were protective. The SAVE-score (area under the receiver operating characteristics [ROC] curve [AUROC] 0.68 [95%CI 0.64-0.71]) was created. External validation of the SAVE-score in an Australian population of 161 patients showed excellent discrimination with AUROC = 0.90 (95%CI 0.85-0.95). CONCLUSIONS: The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock (www.save-score.com).

Mechanical ventilation management during extracorporeal membrane oxygenation for acute respiratory distress syndrome: a retrospective international multicenter study.

OBJECTIVE: To describe mechanical ventilation settings in adult patients treated for an acute respiratory distress syndrome with extracorporeal membrane oxygenation and assess the potential impact of mechanical ventilation settings on ICU mortality. DESIGN: Retrospective observational study. SETTING: Three international high-volume extracorporeal membrane oxygenation centers. PATIENTS: A total of 168 patients treated with extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from January 2007 to January 2013. INTERVENTIONS: We analyzed the association between mechanical ventilation settings (i.e. plateau pressure, tidal volume, and positive end-expiratory pressure) on ICU mortality using multivariable logistic regression model and Cox-proportional hazards model. MEASUREMENT AND MAIN RESULTS: We obtained detailed demographic, clinical, daily mechanical ventilation settings and ICU outcome data. One hundred sixty-eight patients (41 ± 14 years old; PaO2/FIO2 67 ± 19 mm Hg) fulfilled our inclusion criteria. Median duration of extracorporeal membrane oxygenation and ICU stay were 10 days (6-18 d) and 28 days (16-42 d), respectively. Lower positive end-expiratory pressure levels and significantly lower plateau pressures during extracorporeal membrane oxygenation were used in the French center than in both Australian centers (23.9 ± 1.4 vs 27.6 ± 3.7 and 27.8 ± 3.6; p < 0.0001). Overall ICU mortality was 29%. Lower positive end-expiratory pressure levels (until day 7) and lower delivered tidal volume after 3 days on extracorporeal membrane oxygenation were associated with significantly higher mortality (p < 0.05). In multivariate analysis, higher positive end-expiratory pressure levels during the first 3 days of extracorporeal membrane oxygenation support were associated with lower mortality (odds ratio, 0.75; 95% CI, 0.64-0.88; p = 0.0006). Other independent predictors of ICU mortality included time between ICU admission and extracorporeal membrane oxygenation initiation, plateau pressure greater than 30 cm H2O before extracorporeal membrane oxygenation initiation, and lactate level on day 3 of extracorporeal membrane oxygenation support. CONCLUSIONS: Protective mechanical ventilation strategies were routinely used in high-volume extracorporeal membrane oxygenation centers. However, higher positive end-expiratory pressure levels during the first 3 days on extracorporeal membrane oxygenation support were independently associated with improved survival. Further prospective trials on the optimal mechanical ventilation strategy during extracorporeal membrane oxygenation support are warranted.

Predicting survival after extracorporeal membrane oxygenation for severe acute respiratory failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score.

RATIONALE: Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. OBJECTIVES: To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. METHODS: Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction (RESP) score using bootstrapping methodology with internal and external validation. MEASUREMENTS AND MAIN RESULTS: Of the 2,355 patients included in the study, 1,338 patients (57%) were discharged alive from hospital. The RESP score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression, which included age, immunocompromised status, duration of mechanical ventilation before ECMO, diagnosis, central nervous system dysfunction, acute associated nonpulmonary infection, neuromuscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2, and peak inspiratory pressure. The receiver operating characteristics curve analysis of the RESP score was c = 0.74 (95% confidence interval, 0.72-0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c = 0.92; 95% confidence interval, 0.89-0.97). CONCLUSIONS: The RESP score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure.

Mechanical ventilation during extracorporeal membrane oxygenation.

The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.

Calorie intake and patient outcomes in severe acute kidney injury: findings from The Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study trial.

INTRODUCTION: Current practice in the delivery of caloric intake (DCI) in patients with severe acute kidney injury (AKI) receiving renal replacement therapy (RRT) is unknown. We aimed to describe calorie administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study and to assess the association between DCI and clinical outcomes. METHODS: We performed a secondary analysis in 1456 patients from the RENAL trial. We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression, Cox proportional hazards models, and time adjusted models. RESULTS: Overall, mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors. Among patients with a lower DCI (below the median) 334 of 729 (45.8%) had died at 90-days after randomization compared with 316 of 727 (43.3%) patients with a higher DCI (above the median) (P = 0.34). On multivariable logistic regression analysis, mean DCI carried an odds ratio of 0.95 (95% confidence interval (CI): 0.91-1.00; P = 0.06) per 100 Kcal increase for 90-day mortality. DCI was not associated with significant differences in renal replacement (RRT) free days, mechanical ventilation free days, ICU free days and hospital free days. These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling. CONCLUSIONS: In the RENAL study, mean DCI was low. Within the limits of such low caloric intake, greater DCI was not associated with improved clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00221013.

Factors associated with outcomes of patients on extracorporeal membrane oxygenation support: a 5-year cohort study.

INTRODUCTION: Mortality of patients on extracorporeal membrane oxygenation (ECMO) remains high. The objectives of this study were to assess the factors associated with outcome of patients undergoing ECMO in a large ECMO referral centre and to compare veno-arterial ECMO (VA ECMO) with veno-venous ECMO (VV ECMO). METHODS: We reviewed a prospectively obtained ECMO database and patients' medical records between January 2005 and June 2011. Demographic characteristics, illness severity at admission, ECMO indication, organ failure scores before ECMO and the ECMO mode and configuration were recorded. Bleeding, neurological, vascular and infectious complications that occurred on ECMO were also collected. Demographic, illness, ECMO support descriptors and complications associated with hospital mortality were analysed. RESULTS: ECMO was initiated 158 times in 151 patients. VA ECMO (66.5%) was twice as common as VV ECMO (33.5%) with a median duration significantly shorter than for VV ECMO (7 days (first and third quartiles: 5; 10 days) versus 10 days (first and third quartiles: 6; 16 days)). The most frequent complications during ECMO support were bleeding and bloodstream infections regardless of ECMO type. More than 70% of the ECMO episodes were successfully weaned in each ECMO group. The overall mortality was 37.3% (37.1% for the patients who underwent VA ECMO, and 37.7% for the patients who underwent VV ECMO). Haemorrhagic events, assessed by the total of red blood cell units received during ECMO, were associated with hospital mortality for both ECMO types. CONCLUSIONS: Among neurologic, vascular, infectious and bleeding events that occurred on ECMO, bleeding was the most frequent and had a significant impact on mortality. Further studies are needed to better investigate bleeding and coagulopathy in these patients. Interventions that reduce these complications may improve outcome.

Aspergillus sp. isolated in critically ill patients with extracorporeal membrane oxygenation support.

This study reports Aspergillus isolation in critically ill patients who underwent extracorporeal membrane oxygenation (ECMO) and highlights the difficulty in establishing a diagnosis of aspergillosis in this population. The diagnosis of Aspergillus infection or colonization was retrospectively performed using the proposed modified criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) adapted to critically ill patients. Between 2005 and 2011, 11 of 151 patients (7.2%) who underwent ECMO had Aspergillus sp. isolates, 10 in a pulmonary sample and 1 in a mediastinal wound sample. Five patients did not have any classical risk factors for aspergillosis. One patient had a proven invasive pulmonary aspergillosis (IPA), 2 had a putative IPA, and 1 patient had a possible Aspergillus mediastinitis, whilst in 7 patients this was considered colonization. However, the clinical relevance of Aspergillus isolation was based on an algorithm not validated in patients undergoing ECMO. Our data support the need to implement non-invasive diagnostic procedures for aspergillosis in this population.

Intensity of continuous renal-replacement therapy in critically ill patients.

BACKGROUND: The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. METHODS: We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. RESULTS: Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001). CONCLUSIONS: In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.)

An observational study fluid balance and patient outcomes in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy trial.

OBJECTIVE: To examine associations between mean daily fluid balance during intensive care unit study enrollment and clinical outcomes in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement therapy study. DESIGN: Statistical analysis of data from multicenter, randomized, controlled trials. SETTING: Thirty-five intensive care units in Australia and New Zealand. PATIENTS: Cohort of 1453 patients enrolled in the RENAL study. INTERVENTIONS: We analyzed the association between daily fluid balance on clinical outcomes using multivariable logistic regression, Cox proportional hazards, time-dependent analysis, and repeated measure analysis models. MEASUREMENTS AND MAIN RESULTS: During intensive care unit stay, mean daily fluid balance among survivors was -234 mL/day compared with +560 mL/day among nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was -1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study treatment was independently associated with a decreased risk of death at 90 days (odds ratio 0.318; 95% confidence interval 0.24-0.43; p < .000.1) and with increased survival time (p < .0001). In addition, a negative mean daily fluid balance was associated with significantly increased renal replacement-free days (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p = .01). These findings were unaltered after the application of different statistical models. CONCLUSIONS: In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes. Fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.

Measured Energy Expenditure Compared With Best-Practice Recommendations for Obese, Critically Ill Patients-A Prospective Observational Study.

BACKGROUND: This study aimed to compare recommendations in the American Society for Parenteral and Enteral Nutrition (ASPEN) Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient with measured energy expenditure in obese, critically ill adults. METHODS: After enrollment, measured energy expenditure was attempted at baseline and twice weekly to extubation or day 14. Data are reported as median [interquartile range]. RESULTS: Twenty patients were included. The median baseline and subsequent measured energy expenditures were 2438 [1807-2703] kcal and 2919 [2318-3362] kcal, respectively. Baseline measured energy expenditures were -491 [-788 to -323] kcal lower than subsequent measurements, and week 1 measurements were lower than those of week 2. The median bias between the guideline recommendation of 11-14 kcal/kg of actual body weight and measured expenditure at baseline was -950 [-1254 to -595] kcal/d and -1618 [-1820 to -866] kcal/d at subsequent measurements. CONCLUSION: Clinically significant variation was observed between measured expenditure and guideline recommendations at all time points.

Screening and study enrolment in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) Replacement Therapy Trial.

BACKGROUND AND OBJECTIVES: Aspects of trial design, screening and study efficiency can affect recruitment and the findings of the trial itself. A clear understanding of the screening and study inclusion process will assist clinicians in interpreting trial results. DESIGN: Prospective observational data collection on all patients screened for possible inclusion in a randomized controlled trial of normal vs. augmented renal replacement therapy in critically ill patients (the RENAL Trial). SETTING: 35 hospitals in Australia and New Zealand. PARTICIPANTS: All patients screened for the RENAL Trial. RESULTS: We screened 4,551 patients. Of these patients, 767 were ineligible because of lack of inclusion criteria and 2,085 because of exclusion criteria. Of the remaining 1,699, 1,508 (88.7%) were enrolled. The three most common exclusion criteria which prevented recruitment of potentially eligible patients were that the patient had end-stage kidney failure and was already on chronic dialysis (484; 23.2%), the patient's body weight was either <60 or >120 kg (456; 21.8%), and the fact that the patient had already received renal replacement therapy during the index admission. Important modifiable impediments to recruitment were inability to obtain consent in 191 cases, unavailability of research staff in 124 cases, physician objection in 89 cases, and inability to deliver the trial protocol in 78 cases. CONCLUSION: The RENAL Trial's enrolment efficiency was high and compared favourably with previous large intensive care units trials and with that of trials in patients with acute renal failure. The high rate of enrolment suggests that the results can be applied with confidence to most patients with de novo acute renal failure. The loss of close to 1.5% of patients due to consent issues highlights a common problem in critical care trials. The low rate of physician objection suggests clinical equipoise.

Design and challenges of the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy (RENAL) Trial: high-dose versus standard-dose hemofiltration in acute renal failure.

BACKGROUND/AIMS: The optimal dose of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. METHODS: The Randomized Evaluation of Normal versus Augmented Level Replacement Therapy Trial tests the hypothesis that higher dose continuous veno-venous hemodiafiltration (CVVHDF) at an effluent rate of 40 ml/kg/h will increase survival compared to CVVHDF at 25 ml/kg/h of effluent dose. RESULTS: This trial is currently randomizing critically ill patients in 35 intensive care units in Australia and New Zealand with a planned sample size of 1,500 patients. This trial will be the largest trial ever conducted on acute blood purification in critically ill patients. CONCLUSION: A trial of this magnitude and with demanding technical requirements poses design difficulties and challenges in the logistics, conduct, data collection, data analysis and monitoring. Our report will assist in the development of future trials of blood purification in intensive care.

Does Propofol Sedation Contribute to Overall Energy Provision in Mechanically Ventilated Critically Ill Adults? A Retrospective Observational Study.

BACKGROUND: Propofol sedation is common in critically ill patients, providing energy of 1.1 kcal/mL when administered as a 1% solution. We aimed to determine the proportion of energy administered as propofol on days 1-5 in the intensive care unit (ICU) and any association with outcomes. METHODS: Retrospective observational study in a quaternary ICU from January-December 2012. Inclusion criteria were length of stay (LOS) ≥5 days, age ≥18 years, and provision of mechanical ventilation (MV) for ≥5 days. Outcome measures included proportion of total daily energy provided as propofol, overall energy balance, hospital mortality, duration of MV, and ICU LOS. RESULTS: Data from 370 patients were analyzed, 87.8% (n = 325) of whom received propofol during days 1-5 in ICU. A median [interquartile range (IQR)] of 119 [50-730] kcal was provided as propofol per patient-day. Proportion of energy provided by propofol as a percentage of total energy delivered was 55.4%, 15.4%, 9.3%, 7.9%, and 9.9% days 1-5, respectively. Patients administered propofol received a greater proportion of their total daily energy prescription compared with those who were not (P < .01). Proportion of energy provided as propofol was not significantly different based on hospital mortality (P = .62), duration of MV (P = .50), or ICU LOS (P = .15). CONCLUSION: Propofol contributes to overall energy intake on days 1-5 of ICU admission. Energy balance was higher in those receiving propofol. No association was found between the proportion of energy delivered as propofol and outcomes.

Propofol sedation substantially increases the caloric and lipid intake in critically ill patients.

OBJECTIVE: The amount of lipid delivered to patients varies considerably depending on the non-nutritional intake from sedation, and on the feeding solution. The aim of this study was to quantify the magnitude and proportion of lipids and energy provided from propofol sedation in intensive care unit (ICU) patients. METHODS: This was a retrospective analysis of prospectively collected data in consecutive patients admitted to the ICUs of two university hospitals. Inclusion criterion included an ICU stay >5 d. Data were collected for a maximum of 10 d. Propofol sedation using 1% or 2% propofol solutions was defined as >100 mg/d. Nutritional management was per protocol in both centers, recommending enteral feeding. Data are shown as means ± standard deviation. RESULTS: In all, 701 admissions (687 patients, ages 59 ± 16 y, SAPS II 51 ± 17) and 6485 d, including 3484 propofol sedation days were analyzed. Energy targets were 1987 ± 411 kcal/d; mean energy delivery was 1362 ± 811 kcal/d (70% ± 38% of prescription) including propofol and dextrose. Enteral feeding dominated (75% of days) and progressed similarly in both ICUs. Mean propofol sedation dose was 2045 ± 1650 mg/d, resulting in 146 ± 117 kcal/d. Fat from propofol constituted 17% of total energy (up to 100% during the first days). Fat delivery (40 ± 23 g/d: maximum 310 g/d) was significantly increased by the combination of propofol sedation, the 1% solution, and high-fat-containing feeds. In survivors, high-fat proportion was associated with prolonged ventilation time (P < 0.0001). CONCLUSION: Propofol sedation resulted in large doses of lipids being delivered to patients, some receiving pure lipids during the first days. As the metabolic effects of high proportions of fat are unknown, further research is warranted.

Predictive factors of bleeding events in adults undergoing extracorporeal membrane oxygenation.

BACKGROUND: Bleeding is the most frequent complication associated with extracorporeal membrane oxygenation (ECMO) support in critically ill patients. Nonetheless, risk factors for bleeding have been poorly described especially those associated with coagulation anomalies and anticoagulant therapy during ECMO support. The aim of this study is to describe bleeding complications in critically ill patients undergoing ECMO and to identify risk factors for bleeding events. METHODS: We retrospectively analysed ICU charts of adults who received either veno-venous (VV) or veno-arterial (VA) ECMO support in two participating ICUs between 2010 and 2013. Characteristics of patients with and without bleeding complications, as per the Extracorporeal Life Support Organisation (ELSO) definition, were compared, and the impact of bleeding complications on patient outcomes was assessed using survival analysis. Variables that were independently associated with bleeding, including daily clinical and biological variables during ECMO courses, were modelled. RESULTS: Of the 149 ECMO episodes (111 VA ECMO and 38 VV ECMO) performed in 147 adults, 89 episodes (60 %) were complicated by at least one bleeding event. The most common bleeding sources were: ECMO cannula (37 %), haemothorax or cardiac tamponade (17 %) and ear-nose and throat (16 %). Intra-cranial haemorrhage occurred in five (2.2 %) patients. Bleeding complications were independently associated with worse survival [adjusted hazard ratio (HR) 2.17, 95 % confidence interval (CI) 1.07-4.41, P = 0.03]. Higher activated partial thromboplastin time (aPTT) [adjusted odds ratio (OR) 3.00, 95 % CI 1.64-5.47, P < 0.01], APACHE III score [adjusted OR 1.01, 95 % CI 1.01-1.02, P = 0.01] and ECMO following surgery [adjusted OR 3.04, 95 % CI 1.62-5.69, P < 0.01] were independently associated with greater risk of bleeding occurrence. A similar association between bleeding and higher aPTT was found when non-post-surgical VA ECMO was considered separately. CONCLUSIONS: Bleeding events based on the ELSO bleeding definition occurred in more than 60 % of ECMO episodes and were associated with hospital mortality. We identified higher aPTT prior bleeding as an independent risk factor for bleeding event, suggesting that better control of the aPTT (through a better control of either coagulopathy or anticoagulation) may improve patients' outcome.

Insurance status and mortality in critically ill patients.

OBJECTIVE: The association between insurance status and outcome in critically ill patients is uncertain. We aimed to determine if there was an independent relationship between the presence or absence of compensable insurance status and mortality, after admission to the intensive care unit. METHODS: We performed a retrospective cohort study in five public hospitals in Victoria, comprising adult patients admitted to the ICU between 2007 and 2012. We obtained data on demographics, severity of illness, chronic health status, insurance category, length of stay (LOS) and mortality. We matched socio-economic indices (collected from the Australian Bureau of Statistics) to postcodes. The primary outcome measured was in-hospital mortality. Secondary outcomes were ICU mortality, and ICU and hospital LOS, measured in days. RESULTS: We studied 33 306 patients. Compensable patients comprised 21.2% of the study population (7046). Personal private insurance accounted for 13.4% (4451) and Transport Accident Commission insurance for 5.1% (1701) of compensable patients. Unadjusted in-hospital mortality was higher in publicly insured patients (13.4% v 10.6%, P < 0.0001). After adjusting for age, severity of illness, diagnosis and socio-economic status, being a compensable patient in a public hospital ICU was independently associated with a reduction in mortality (odds ratio, 0.73; 95% CI, 0.65-0.80; P < 0.001). CONCLUSIONS: Among ICU patients treated in public hospitals in Victoria, being a compensable patient appears to be independently associated with a reduction in mortality. Further studies are needed to confirm and validate these findings elsewhere in Australia.

The laparoscopic adjustable gastric band (Lap-Band): a prospective study of medium-term effects on weight, health and quality of life.

BACKGROUND: Obesity is now one of our major public health problems. Effective and acceptable treatment options are needed. The Lap-Band system is placed laparoscopically and allows adjustment of the level of gastric restriction. METHODS: A prospective study of 709 severely obese patients was conducted over a 6-year period at a university-based multidisciplinary referral center. After extensive preoperative evaluation, patients with a body mass index > 35 were treated by Lap-Band placement. Close follow-up with progressive adjustment of gastric restriction continued permanently. Medical co-morbidities were monitored as part of comprehensive prospective data collection. RESULTS: There have been no deaths perioperatively or during follow-up. Significant perioperative adverse events occurred in 1.2% only. Reoperation has been needed for prolapse (slippage) in 12.5%, erosion of the band into the stomach in 2.8% and for tubing breaks in 3.6%. A steady progression of weight loss has occurred through the duration of the study with 52 +/- 19% EWL at 24 months (n = 333), 53 +/- 22% EWL at 36 months (n = 264), 52 +/- 24% EWL at 48 months (n = 108), 54 +/- 24% EWL at 60 months (n = 30), and 57 +/- 15% EWL at 72 months (n = 10). Major improvements have occurred in diabetes, asthma, gastroesophageal reflux, dyslipidemia, sleep apnea and depression. Quality of life as measured by Rand SF-36 shows highly significant improvement. CONCLUSIONS: Placement of the Lap-Band system provides safe and effective control of severe obesity. The effect on weight loss is durable and is associated with major improvement in health and quality of life. It has the potential to provide a broadly acceptable option for this common and serious disease.

Where to now with carbon monoxide poisoning?

The controversy regarding the role of hyperbaric oxygen (HBO) in the treatment of carbon monoxide (CO) poisoning has been re-ignited following the publication of a further randomized controlled trial by Weaver et al., the results of which appear to conflict with our findings. Comparative analysis suggests that the apparent outcome differences may be secondary to the design, analysis and interpretation of the results of the two studies. Following careful analysis of these two papers and further results from a study by Raphael et al on 385 CO-poisoned patients, we can still find no convincing evidence favouring HBO therapy. Pending further research to determine optimal oxygen therapy for CO-poisoning, current therapy should involve stratifying patients for risk of a poor outcome. This stratification may be aided by the evolving availability of biochemical markers of brain injury and the finding that patients with transient loss of consciousness and poor performance on neuropsychological tests of the supervisory attention system are at higher risk of neuropsychological sequelae. We propose that those patients most at risk be admitted and receive more prolonged normobaric oxygen therapy whilst those with more minor CO-poisoning should be provided with normobaric oxygen of no less than 6 h duration and certainly until sign and symptom free.