Dexamethasone and Surgical-Site Infection.

BACKGROUND: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection. METHODS: In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points. RESULTS: A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group. CONCLUSIONS: Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).

Long-Term Echocardiographic and Clinical Outcomes After Invasive and Non-Invasive Therapies for Sub-Massive and Massive Acute Pulmonary Embolism.

AIM: Acute pulmonary embolism (PE) is a significant cause of mortality in the hospital setting. The objective of this study was to outline the long-term outcomes after surgical and non-surgical management for patients with massive and submassive PE. METHODS: Population cohort observational study evaluating all patients who presented to three tertiary hospitals in the state of Western Australia with access to cardiothoracic services over 5 years (2013-2018). Reviewed notes of all patients as well as radiology, linked mortality data and all available echocardiography studies at the primary hospital. RESULTS: In total, 245 patients were identified, of which 41 received surgical management and 204 non-surgical management; demographic data was similar. Clinically, the surgical group had higher rates of shock requiring vasopressors, severe bradycardia, or cardiopulmonary resuscitation prior to intervention. The 28-day mortality was not statistically significantly different between the surgical embolectomy group (2/41 [4.2%]) and the non-surgical group (17/201 [8.3%]) (p=0.382). There was no difference in 12-month mortality, including when this was adjusted for vasopressors, right ventricular (RV) strain, troponin, and brain natriuretic peptide. In the massive PE sub-group, 28-day mortality was not significantly different: 2/29 (6.9%) surgical group vs 7/34 (20.2%) non-surgical group (p=0.064). Higher rates of severe RV impairment and dilatation were present in the surgical group. All patients with available echocardiography studies at outpatient follow-up returned to normal or mild RV impairment. CONCLUSION: Patients who presented with massive or submassive PE had similar outcomes whether treated with surgical or non-surgical management. Surgical embolectomy is a safe option in a cardiothoracic centre setting.

Correct dosing of Prothrombinex-VF in normalising elevated international normalised ratio in critically ill patients: a prospective cohort pilot study.

BACKGROUND: Prothrombinex-VF is being increasingly used as an off-label therapy to correct non-warfarin-related elevations in international normalised ratio (INR) in the critically ill. Currently there are no dosing guidelines for such use. AIMS: To validate a prediction equation, embedded in a smartphone application (app), to guide dosing of Prothrombinex-VF in critically ill patients. METHODS: A prospective pilot cohort study of critically ill adult patients with elevated INRs who were treated with Prothrombinex-VF. The main outcome measured was INR following Prothrombinex-VF administration. RESULTS: Of the 31 patients included, five (16%) were taking warfarin prior to admission and 14 (45%) had chronic liver disease. There was a significant decrease in INR after Prothrombinex-VF treatment (P < 0.001) and a significant correlation between the app's predicted INRs and the measured INRs (r = 0.63 and P < 0.001). The app's predicted INRs were less accurate for patients with chronic liver disease than for those without. Overall, the app's recommendations achieved an INR either similar to (29.6%) or better than (55.6%) what would have been achieved had the warfarin reversal guidelines been applied to dose the Prothrombinex-VF. CONCLUSION: The app appeared to be reasonably accurate at predicting normalisation of elevated INRs after administration of Prothrombinex-VF, especially among patients without liver disease. Its dosing recommendations were similar to or possibly better than preexisting warfarin reversal guidelines in over 85% of the situations analysed, if we assume a higher dose of Prothrombinex-VF would achieve a greater reduction in INR than a lower dose.

The association between intraoperative cardiopulmonary bypass power and complications after cardiac surgery.

BACKGROUND: Low cardiac power (product of flow and pressure) has been shown to be associated with mortality in patients with cardiogenic shock after acute myocardial infarction, but has not been studied in cardiac surgical patients. This study's hypothesis was that cardiac power during cardiopulmonary bypass for cardiac surgery would have a greater association with adverse events than either flow or MAP (mean arterial pressure) alone. METHODS: We undertook a retrospective observational study using patient data from February 2015 to March 2022 undergoing cardiac surgery at Fiona Stanley Hospital in Perth Australia. Excluded were patient age less than 18 years old, patients undergoing thoracic transplantation, ventricular assist devices, off pump cardiac surgery and aortic surgery. The primary outcome was a composite outcome of 30-days mortality, stroke or new-onset renal insufficiency. RESULTS: Overall, 1984 cardiac surgeries were included in the analysis. Neither duration nor area below thresholds tested for power, MAP or flow was associated with the primary composite outcome. However, we found that an area below MAP thresholds 35-50 mmHg was associated with new renal insufficiency (adjusted odds ratio 1.17 [95% CI 1.02 to 1.35] for patients spending 10 min at 10 mmHg below 50 mmHg MAP compared to those who did not). CONCLUSIONS: This study suggests that MAP during cardiopulmonary bypass, but not power or flow, was an independent risk factor for adverse renal outcomes for cardiac surgical patients.

A Multicenter Trial of Vena Cava Filters in Severely Injured Patients.

BACKGROUND: Whether early placement of an inferior vena cava filter reduces the risk of pulmonary embolism or death in severely injured patients who have a contraindication to prophylactic anticoagulation is not known. METHODS: In this multicenter, randomized, controlled trial, we assigned 240 severely injured patients (Injury Severity Score >15 [scores range from 0 to 75, with higher scores indicating more severe injury]) who had a contraindication to anticoagulant agents to have a vena cava filter placed within the first 72 hours after admission for the injury or to have no filter placed. The primary end point was a composite of symptomatic pulmonary embolism or death from any cause at 90 days after enrollment; a secondary end point was symptomatic pulmonary embolism between day 8 and day 90 in the subgroup of patients who survived at least 7 days and did not receive prophylactic anticoagulation within 7 days after injury. All patients underwent ultrasonography of the legs at 2 weeks; patients also underwent mandatory computed tomographic pulmonary angiography when prespecified criteria were met. RESULTS: The median age of the patients was 39 years, and the median Injury Severity Score was 27. Early placement of a vena cava filter did not result in a significantly lower incidence of symptomatic pulmonary embolism or death than no placement of a filter (13.9% in the vena cava filter group and 14.4% in the control group; hazard ratio, 0.99; 95% confidence interval [CI], 0.51 to 1.94; P = 0.98). Among the 46 patients in the vena cava filter group and the 34 patients in the control group who did not receive prophylactic anticoagulation within 7 days after injury, pulmonary embolism developed in none of those in the vena cava filter group and in 5 (14.7%) in the control group, including 1 patient who died (relative risk of pulmonary embolism, 0; 95% CI, 0.00 to 0.55). An entrapped thrombus was found in the filter in 6 patients. CONCLUSIONS: Early prophylactic placement of a vena cava filter after major trauma did not result in a lower incidence of symptomatic pulmonary embolism or death at 90 days than no placement of a filter. (Funded by the Medical Research Foundation of Royal Perth Hospital and others; Australian New Zealand Clinical Trials Registry number, ACTRN12614000963628.).

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.

BACKGROUND: Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. METHODS: In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. RESULTS: A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56-1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37-0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20-202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. CONCLUSIONS: Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

Incremental cost of venous thromboembolism in trauma patients with contraindications to prophylactic anticoagulation: a prospective economic study.

Venous thromboembolism (VTE) is common in patients after major trauma. Attributable cost of VTE and whether this is related to the severity of injury have not been thoroughly investigated. We aimed to define the hospitalization costs of VTE and assess whether the costs were related to the severity of injury in this prospective economic study. Cost data of each patient enrolled in the da Vinci trial were drawn from hospital finance departments and standardized to 2020 Australian dollars (A$); and Injury Severity Score and Trauma Embolic Scoring System were used to quantify the severity of injury. Of the 223 patients who had complete financial cost data available until day-90 follow-up, 37 (16.6%) developed VTE, including upper limb (n = 3) and lower limb deep vein thrombosis (n = 25), pulmonary embolism (n = 7) and clots entrapped in a vena cava filter. The median total radiology (A$4307) as well as the hospitalization costs (A$138,526) of those who had VTE were significantly higher than those without VTE (A$1210; p < 0.001 and A$105,842; p = 0.023, respectively). The incremental hospitalization cost attributable to VTE was most apparent among those who had sustained extremely severe injuries, and estimated to be between A$43,292 (95% confidence interval [CI] 12,624-73,961, p = 0.006) and 41,680 (95%CI 7766-75,594, p = 0.016) after adjusted for Trauma Embolic Scoring System and Injury Severity Scores, respectively. VTE was common after major trauma and incurred a substantial incremental financial cost to the healthcare system, especially among those who had extremely severe injuries.

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs.

OBJECTIVES: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs. STUDY DESIGN: Experimental, repeated measures, prospective study. ANIMALS: A group of six male adult Greyhound dogs. METHODS: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05. RESULTS: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL-1 CysC (p = 0.009) and 2043 (790-5458) U L-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.

Cost-effectiveness of early placement of vena cava filters to prevent symptomatic pulmonary embolism in patients with contraindications to prophylactic anticoagulant.

INTRODUCTION: Vena cava filters have been used as a primary means to prevent symptomatic pulmonary embolism (PE) in trauma patients who cannot be anticoagulated after severe injury, but the economic implications for this practice remain unclear. METHODS: Using a healthcare system perspective to analyze the a priori primary outcome of the da Vinci trial, we report the cost-effectiveness of using vena cava filters as a primary means to prevent PE in patients who have contraindications to prophylactic anticoagulation after major trauma. RESULTS: Of the 240 patients enrolled, complete, prospectively collected, hospital cost data during the entire hospital stay - including costs for the filter, medical/nursing/allied health staff, medical supplies, pathology tests, and radiological imaging - were available in 223 patients (93%). Patients allocated to the filter group (n = 114) were associated with a reduced risk of PE (0.9%) compared to those in the control group (n = 109, 5.5%; p = 0.048); and the filter's benefit was more pronounced among those who could not be anticoagulated within 7 days (filter: 0% vs control: 16%, Bonferroni-corrected p = 0.02). Overall, the cost needed to prevent one PE was high (AUD $379,760), but among those who could not be anticoagulated within 7 days, the costs to prevent one PE (AUD $36,156; ~ USD $26,032) and gain one quality-adjusted life-year (AUD $30,903; ~ USD $22,250) were substantially lower. CONCLUSION: The cost of using a vena cava filter to prevent PE for those who have contraindications to prophylactic anticoagulation within 3 days of injury is prohibitive, unless such contraindications remain for longer than 7 days. (Australian New Zealand Clinical Trials Registry no.: ACTRN12614000963628).

Intensive care doctors and nurses personal preferences for Intensive Care, as compared to the general population: a discrete choice experiment.

BACKGROUND: To test the hypothesis that Intensive Care Unit (ICU) doctors and nurses differ in their personal preferences for treatment from the general population, and whether doctors and nurses make different choices when thinking about themselves, as compared to when they are treating a patient. METHODS: Cross sectional, observational study conducted in 13 ICUs in Australia in 2017 using a discrete choice experiment survey. Respondents completed a series of choice sets, based on hypothetical situations which varied in the severity or likelihood of: death, cognitive impairment, need for prolonged treatment, need for assistance with care or requiring residential care. RESULTS: A total of 980 ICU staff (233 doctors and 747 nurses) participated in the study. ICU staff place the highest value on avoiding ending up in a dependent state. The ICU staff were more likely to choose to discontinue therapy when the prognosis was worse, compared with the general population. There was consensus between ICU staff personal views and the treatment pathway likely to be followed in 69% of the choices considered by nurses and 70% of those faced by doctors. In 27% (1614/5945 responses) of the nurses and 23% of the doctors (435/1870 responses), they felt that aggressive treatment would be continued for the hypothetical patient but they would not want that for themselves. CONCLUSION: The likelihood of returning to independence (or not requiring care assistance) was reported as the most important factor for ICU staff (and the general population) in deciding whether to receive ongoing treatments. Goals of care discussions should focus on this, over likelihood of survival.

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: a secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study.

BACKGROUND: Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. METHODS: In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg-1 min-1 and peak oxygen consumption (VO2 peak) >16 ml kg-1 min-1, cut-points that represent a reduced risk of postoperative complications. RESULTS: Five questions were identified to have dominance in predicting AT>11 ml kg-1 min-1 and VO2 peak>16 ml.kg-1min-1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg-1.min-1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO2 peak>16 ml.kg-1.min-1 and VO2 peak<16 ml.kg-1.min-1. CONCLUSIONS: The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management.

Incidence of Antithrombin Deficiency and Anti-Cardiolipin Antibodies After Severe Traumatic Brain Injury: A Prospective Cohort Study.

BACKGROUND: Animal studies suggested that cerebral mitochondrial cardiolipin phospholipids were released after severe traumatic brain injury (TBI), contributing to the pathogenesis of thromboembolism. OBJECTIVES: To determine the incidence of anti-cardiolipin antibodies after severe TBI and whether this was related to the severity of TBI and development of venous thromboembolism. METHODS: Serial anti-cardiolipin antibodies, antithrombin levels, viscoelastic testing, and coagulation parameters were measured on admission, day-1, and between day-5 and day-7 in patients with severe TBI requiring intracranial pressure monitoring. RESULTS: Of the 40 patients included (85% male and median age 42 years), 7 (18%) had a raised Ig-G or Ig-M anti-cardiolipin antibody titer after TBI. Antithrombin levels were below the normal level-especially on day-0 and day-1-in 15 patients (38%), and 14 patients (38%) developed an increase in maximum clot firmness on the viscoelastic test in conjunction with elevations in fibrinogen concentration and platelet count. Four patients (10%) developed deep vein thrombosis, and 10 patients (25%) died, both of which were not significantly related to the presence of anti-cardiolipin antibodies (P = 0.619 and P = 0.638, respectively). CONCLUSIONS: A reduction in antithrombin level and development of anti-cardiolipin antibodies were not rare immediately after severe TBI; these abnormalities were followed by an increase in in vitro clot strength due to elevations in fibrinogen concentration and platelet count. The quantitative relationships between the development of anti-cardiolipin antibodies and severity of TBI or clinical thromboembolic events deserve further investigation.

Perioperative ADministration of Dexamethasone And blood Glucose concentrations in patients undergoing elective non-cardiac surgery - the randomised controlled PADDAG trial.

BACKGROUND: The hyperglycaemic effect of dexamethasone in diabetic and nondiabetic patients in the peri-operative period is unknown. OBJECTIVE: To assess the effect of a single dose of intra-operative dexamethasone on peri-operative blood glucose. DESIGN: Multicentre, stratified, randomised trial. SETTING: University hospitals in Australia and Hong Kong. PATIENTS: A total of 302 adults scheduled for elective, noncardiac and nonobstetric surgical procedures under general anaesthesia, stratified by diabetes mellitus status, were randomised to receive placebo, 4 or 8 mg dexamethasone administered intravenously after induction of anaesthesia. MAIN OUTCOME MEASURES: Maximum blood glucose within 24 h of surgery, and the interaction between glycated haemoglobin (HbA1c) and dexamethasone were the primary and secondary outcomes. RESULTS: The median [IQR] baseline blood glucose in the nondiabetes stratum in the placebo (n=81), 4 mg (n=81) and 8 mg dexamethasone (n=77) trial arms were respectively 5.3 [4.6 to 5.8], 5.0 [4.7 to 5.4] and 5.0 [4.2 to 5.9] mmol l-1. In the diabetes stratum these values were 6.6 [6.0 to 8.3]; (n=22), 6.1 [5.5 to 10.4]; (n=22) and 6.7 [5.6 to 8.3]; (n=19) mmol l-1. The median [IQR] maximum peri-operative blood glucose values in the nondiabetes stratum were 6.0 [5.3 to 6.8], 6.3 [5.5 to 7.3] and 6.3 [5.8 to 7.4] mmol l-1 in the control, dexamethasone 4 mg and dexamethasone 8 mg arms, respectively. In the diabetes stratum these values were 10.3 [8.1 to 12.4], 12.6 [10.3 to 18.3] and 13.6 [11.2 to 20.1] mmol l-1. There was a significant interaction between pre-operative HbA1c value and 8 mg dexamethasone: every 1% increment in HbA1c produced a 4.0 mmol l-1 elevation in maximal peri-operative glucose concentration. CONCLUSION: Dexamethasone 4 mg or 8 mg did not induce greater hyperglycaemia compared with placebo for nondiabetic and well controlled diabetic patients. Maximal peri-operative blood glucose concentrations in patients with diabetes were related to baseline HbA1c values in a concentration-dependent fashion after 8 mg of dexamethasone. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry (ACTRN12614001145695): URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367272.

Defining persistent critical illness based on growth trajectories in patients with sepsis.

BACKGROUND: Persistent critical illness is common in critically ill patients and is associated with vast medical resource use and poor clinical outcomes. This study aimed to define when patients with sepsis would be stabilized and transitioned to persistent critical illness, and whether such transition time varies between latent classes of patients. METHODS: This was a retrospective cohort study involving sepsis patients in the eICU Collaborative Research Database. Persistent critical illness was defined at the time when acute physiological characteristics were no longer more predictive of in-hospital mortality (i.e., vital status at hospital discharge) than antecedent characteristics. Latent growth mixture modeling was used to identify distinct trajectory classes by using Sequential Organ Failure Assessment score measured during intensive care unit stay as the outcome, and persistent critical illness transition time was explored in each latent class. RESULTS: The mortality was 16.7% (3828/22,868) in the study cohort. Acute physiological model was no longer more predictive of in-hospital mortality than antecedent characteristics at 15 days after intensive care unit admission in the overall population. Only a minority of the study subjects (n = 643, 2.8%) developed persistent critical illness, but they accounted for 19% (15,834/83,125) and 10% (19,975/198,833) of the total intensive care unit and hospital bed-days, respectively. Five latent classes were identified. Classes 1 and 2 showed increasing Sequential Organ Failure Assessment score over time and transition to persistent critical illness occurred at 16 and 27 days, respectively. The remaining classes showed a steady decline in Sequential Organ Failure Assessment scores and the transition to persistent critical illness occurred between 6 and 8 days. Elevated urea-to-creatinine ratio was a good biochemical signature of persistent critical illness. CONCLUSIONS: While persistent critical illness occurred in a minority of patients with sepsis, it consumed vast medical resources. The transition time differs substantially across latent classes, indicating that the allocation of medical resources should be tailored to different classes of patients.

Association Between the Use of Sodium Bicarbonate and Mortality in Acute Kidney Injury Using Marginal Structural Cox Model.

OBJECTIVE: Acute kidney injury with metabolic acidosis is common in critically ill patients. This study assessed the associations between the use of IV sodium bicarbonate and mortality of patients with acute kidney injury and acidosis. DESIGN: The study was conducted by using data from Beth Israel Deaconess Medical Center, which included several ICUs such as coronary care unit, cardiac surgery recovery unit, medical ICU, surgical ICU, and trauma-neuro ICU. Marginal structural Cox model was used to assess the relationship between receipt of sodium bicarbonate and hospital mortality, allowing pH, PaCO2, creatinine, and bicarbonate concentration as time-varying predictors of sodium bicarbonate exposure while adjusting for baseline characteristics of age, gender, Sequential Organ Failure Assessment score, acute kidney injury stage, Elixhauser score, quick Sequential Organ Failure Assessment, and Simplified Acute Physiology Score II. SETTING: A large U.S.-based critical care database named Medical Information Mart for Intensive Care. PATIENTS: Patients with Kidney Disease: Improving Global Outcomes acute kidney injury stage greater than or equal to 1 (> 1.5 (Equation is included in full-text article.)baseline creatinine) and one measurement of acidosis (pH ≤ 7.2). Baseline creatinine was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 3,406 eligible patients, 836 (24.5%) had received sodium bicarbonate treatment. Patients who received sodium bicarbonate treatment had a higher Sequential Organ Failure Assessment (9 vs 7; p < 0.001), lower pH (7.16 vs 7.18; p < 0.001), and bicarbonate concentration (16.51 ± 7.04 vs 20.57 ± 6.29 mmol/L; p < 0.001) compared with those who did not receive sodium bicarbonate. In the marginal structural Cox model by weighing observations with inverse probability of receiving sodium bicarbonate, sodium bicarbonate treatment was not associated with mortality in the overall population (hazard ratio, 1.16; 95% CI, 0.98-1.42; p = 0.132), but it appeared to be beneficial in subgroups of pancreatitis (hazard ratio, 0.53; 95% CI, 0.28-0.98; p = 0.044) and severe acidosis (pH < 7.15; hazard ratio, 0.75; 95% CI, 0.58-0.96; p = 0.024). Furthermore, sodium bicarbonate appeared to be beneficial in patients with severe bicarbonate deficit (< -50 kg·mmol/L). CONCLUSIONS: In the analysis by adjusting for potential confounders, there is no evidence that IV sodium bicarbonate is beneficial for patients with acute kidney injury and acidosis. Although the study suggested potential beneficial effects in some highly selected subgroups, the results need to be validated in experimental trials.

Thromboelastography Predicts Thromboembolism in Critically Ill Coagulopathic Patients.

OBJECTIVES: Critically ill patients with deranged conventional coagulation tests are often perceived to have an increased bleeding risk. Whether anticoagulant prophylaxis for these patients should be withheld is contentious. This study assessed the ability of using in vitro clot strength, as measured by thromboelastography, to predict thromboembolism in patients with abnormal coagulation profiles. DESIGN: Prospective cohort study. SETTING: A tertiary ICU. PATIENTS: Two-hundred and fifteen critically ill coagulopathic patients with thrombocytopenia and/or a derangement in at least one conventional coagulation test (international normalized ratio or activated partial thromboplastin time) within 48 hours of ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thromboelastography was performed for all study patients, and plasma thrombotic biomarkers were measured in a nested cohort (n = 40). Of the 215 patients included, 34 patients (16%) developed subsequent thromboembolism-predominantly among those with a normal (maximum amplitude, 54-72 mm) or increased (maximum amplitude, > 72 mm) in vitro clot strength on thromboelastography (91%; area under the receiver-operating characteristic curve, 0.74; 95% CI, 0.64-0.83). The ability of the maximum amplitude to predict thromboembolism was comparable to plasma P-selectin concentrations (thromboembolism, 78.3 ng/mL vs no thromboembolism, 59.5 ng/mL; p = 0.031; area under the receiver-operating characteristic curve, 0.73; 95% CI, 0.52-0.95). In addition, patients with an increased maximum amplitude were also less likely to receive blood product transfusions within 24 hours of testing compared with those with a subnormal maximum amplitude (12.8% vs 69.2%, respectively; area under the receiver-operating characteristic curve, 0.74; 95% CI, 0.67-0.80). CONCLUSIONS: In patients with abnormal coagulation profiles, an increased in vitro clot strength on thromboelastography was associated with an increased risk of thromboembolism, and a reduced risk of requiring transfusion compared with those with a normal or reduced in vitro clot strength.

Machine learning for the prediction of volume responsiveness in patients with oliguric acute kidney injury in critical care.

BACKGROUND AND OBJECTIVES: Excess fluid balance in acute kidney injury (AKI) may be harmful, and conversely, some patients may respond to fluid challenges. This study aimed to develop a prediction model that can be used to differentiate between volume-responsive (VR) and volume-unresponsive (VU) AKI. METHODS: AKI patients with urine output < 0.5 ml/kg/h for the first 6 h after ICU admission and fluid intake > 5 l in the following 6 h in the US-based critical care database (Medical Information Mart for Intensive Care (MIMIC-III)) were considered. Patients who received diuretics and renal replacement on day 1 were excluded. Two predictive models, using either machine learning extreme gradient boosting (XGBoost) or logistic regression, were developed to predict urine output > 0.65 ml/kg/h during 18 h succeeding the initial 6 h for assessing oliguria. Established models were assessed by using out-of-sample validation. The whole sample was split into training and testing samples by the ratio of 3:1. MAIN RESULTS: Of the 6682 patients included in the analysis, 2456 (36.8%) patients were volume responsive with an increase in urine output after receiving > 5 l fluid. Urinary creatinine, blood urea nitrogen (BUN), age, and albumin were the important predictors of VR. The machine learning XGBoost model outperformed the traditional logistic regression model in differentiating between the VR and VU groups (AU-ROC, 0.860; 95% CI, 0.842 to 0.878 vs. 0.728; 95% CI 0.703 to 0.753, respectively). CONCLUSIONS: The XGBoost model was able to differentiate between patients who would and would not respond to fluid intake in urine output better than a traditional logistic regression model. This result suggests that machine learning techniques have the potential to improve the development and validation of predictive modeling in critical care research.

A cross-sectional survey of Australian anesthetists' and surgeons' perceptions of preoperative risk stratification and prehabilitation.

PURPOSE: Preoperative fitness training has been listed as a top ten research priority in anesthesia. We aimed to capture the current practice patterns and perspectives of anesthetists and colorectal surgeons in Australia and New Zealand regarding preoperative risk stratification and prehabilitation to provide a basis for implementation research. METHODS: During 2016, we separately surveyed fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) and members of the Colorectal Society of Surgeons in Australia and New Zealand (CSSANZ). Our outcome measures investigated the responders' demographics, practice patterns, and perspectives. Practice patterns examined preoperative assessment and prehabilitation utilizing exercise, hematinic, and nutrition optimization. RESULTS: We received 155 responses from anesthetists and 71 responses from colorectal surgeons. We found that both specialty groups recognized that functional capacity was linked to postoperative outcome; however, fewer agreed that robust evidence exists for prehabilitation. Prehabilitation in routine practice remains low, with significant potential for expansion. The majority of anesthetists do not believe their patients are adequately risk stratified before surgery, and most of their colorectal colleagues are amenable to delaying surgery for at least an additional two weeks. Two-thirds of anesthetists did not use cardiopulmonary exercise testing as they lacked access. Hematinic and nutritional assessment and optimization is less frequently performed by anesthetists compared with their colorectal colleagues. CONCLUSIONS: An unrecognized potential window for prehabilitation exists in the two to four weeks following cancer diagnosis. Early referral, larger multi-centre studies focusing on long-term outcomes, and further implementation research are required.

RéSUMé: OBJECTIF: Le conditionnement physique préopératoire a été cité dans les dix priorités de recherche les plus importantes en anesthésie. Notre objectif était de déterminer quels étaient les habitudes actuelles de pratique ainsi que les perspectives des anesthésistes et des chirurgiens colorectaux en Australie et en Nouvelle-Zélande concernant la stratification préopératoire du risque et la préhabilitation afin de proposer un point de départ pour la recherche sur sa mise en œuvre. MéTHODE: Au cours de l'année 2016, nous avons soumis un questionnaire séparé aux membres du Collège australien et néozélandais des anesthésistes (ANZCA - Australian and New Zealand College of Anaesthetists) et aux membres de la Société colorectale des chirurgiens australiens et néozélandais (CSSANZ - Colorectal Society of Surgeons in Australia and New Zealand). Nos critères d'évaluation portaient sur les données démographiques, les habitudes de pratique et les perspectives des répondants. Les questions sur les habitudes de pratique touchaient à l'évaluation préopératoire et la préhabilitation fondée sur l'exercice physique et l'optimisation antianémique et nutritionnelle. RéSULTATS: Nous avons reçu 155 réponses d'anesthésistes et 71 réponses de chirurgiens colorectaux. Notre questionnaire a révélé que les deux spécialités reconnaissaient que la capacité fonctionnelle est liée au pronostic postopératoire; toutefois, moins de répondants étaient d'avis qu'il existe des données probantes fiables concernant la préhabilitation. Dans la pratique de routine, la préhabilitation demeure peu courante mais a le potentiel de prendre plus d'ampleur. La plupart des anesthésistes estiment que leurs patients ne sont pas stratifiés adéquatement en fonction de leur risque avant leur chirurgie, et la plupart de leurs collègues colorectaux sont ouverts à l'idée de retarder la chirurgie d'au moins deux semaines supplémentaires. Deux tiers des anesthésiologistes n'ont pas eu recours à un test d'effort cardiopulmonaire par manque d'accès à ce type d'examen. L'évaluation et l'optimisation antianémique et nutritionnelle sont moins fréquemment réalisées par les anesthésistes comparativement à leurs collègues colorectaux. CONCLUSION: Il existe une fenêtre potentielle mais non reconnue pour la mise en œuvre d'une préhabilitation au cours des deux à quatre semaines suivant l'annonce d'un diagnostic de cancer. Une prise en charge précoce par des spécialistes, des études multicentriques plus importantes s'intéressant aux pronostics à long terme et des travaux de recherche supplémentaires sur la mise en œuvre sont nécessaires.

Use of viscoelastic tests to predict clinical thromboembolic events: A systematic review and meta-analysis.

We aimed to assess whether whole-blood viscoelastic tests are useful to identify patients who are hypercoagulable and at increased risk of thromboembolism. Two investigators independently analyzed studies in the MEDLINE, EMBASE, and Cochrane controlled trial register databases to determine the ability of viscoelastic tests to identify a hypercoagulable state that is predictive of objectively proven thromboembolic events. Forty-one eligible studies, including 10,818 patients, were identified and subject to meta-analysis. The majority of the studies (n = 36, 88%) used the maximum clot strength to identify a hypercoagulable state which had a moderate ability to differentiate between patients who developed thromboembolic events and those who did not (area under the summary receiver operating characteristic [sROC] curve = 0.70, 95% confidence interval [CI]: 0.65-0.75). The pooled sensitivity, specificity, and diagnostic odds ratio to predict thromboembolism were 56% (95%CI: 44-67), 76% (95%CI: 67-83), and 3.6 (95%CI: 2.6-4.9), respectively. The predictive performance did not vary substantially between patient populations, and publication bias was not observed. Current evidence suggests that whole-blood viscoelastic tests have a moderate ability to identify a variety of patient populations with an increased risk of thromboembolic events and can be considered as a useful adjunct to clinical judgment to stratify a patient's risk of developing thromboembolism.

Long-term outcome following decompressive craniectomy: an inconvenient truth?

PURPOSE OF REVIEW: There is little doubt that decompressive craniectomy can reduce mortality following malignant middle cerebral infarction or severe traumatic brain injury. However, the concern has always been that the reduction in mortality comes at the cost of an increase in the number of survivors with severe neurological disability. RECENT FINDINGS: There has been a number of large multicentre randomized trials investigating surgical efficacy of the procedure. These trials have clearly demonstrated a survival benefit in those patients randomized to surgical decompression. However, it is only possible to demonstrate an improvement in outcome if the definition of favourable is changed such that it includes patients with either a modified Rankin score of 4 or upper severe disability. Without this recategorization, the results of these trials have confirmed the 'Inconvenient truth' that surgery reduces mortality at the expense of survival with severe disability. SUMMARY: Given these results, the time may have come for a nuanced examination of the value society places on an individual life, and the acceptability or otherwise of performing a procedure that converts death into survival with severe disability.