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Meta-analysis is a technique for combining evidence from multiple trials. However, meta-analyses of studies with substantial heterogeneity among patients within trials-common in intensive care-can lead to incorrect conclusions if performed using aggregate data. Use of individual patient data (IPD) can avoid this concern, increase the power of a meta-analysis, and is useful for exploring subgroup effects. Barriers exist to IPD meta-analysis, most of which are overcome if clinical trials are designed to prospectively facilitate the incorporation of their results with other trials. We review the features of prospective IPD meta-analysis and identify those of relevance to intensive care research. We identify three clinical questions, which are the subject of recent or planned randomised controlled trials where IPD MA offers advantages over approaches using aggregate data.

Objective: Catecholamines have been the mainstay of pharmacological treatment of cardiogenic shock (CS). Recently, use of epinephrine has been associated with detrimental outcomes. In the present study we aimed to evaluate the association between epinephrine use and short-term mortality in all-cause CS patients.Design: We performed a meta-analysis of individual data with prespecified inclusion criteria: (1) patients in non-surgical CS treated with inotropes and/or vasopressors and (2) at least 15% of patients treated with epinephrine administrated alone or in association with other inotropes/vasopressors. The primary outcome was short-term mortality.Measurements and Results: Fourteen published cohorts and two unpublished data sets were included. We studied 2583 patients. Across all cohorts of patients, the incidence of epinephrine use was 37% (17-76%) and short-term mortality rate was 49% (21-69%). A positive correlation was found between percentages of epinephrine use and short-term mortality in the CS cohort. The risk of death was higher in epinephrine-treated CS patients (OR [CI] = 3.3 [2.8-3.9]) compared to patients treated with other drug regimens. Adjusted mortality risk remained striking in epinephrine-treated patients (n = 1227) (adjusted OR = 4.7 [3.4-6.4]). After propensity score matching, two sets of 338 matched patients were identified and epinephrine use remained associated with a strong detrimental impact on short-term mortality (OR = 4.2 [3.0-6.0]).Conclusions: In this very large cohort, epinephrine use for hemodynamic management of CS patients is associated with a threefold increase of risk of death. [ABSTRACT FROM AUTHOR]

Purpose: The Sepsis-3 consensus task force defined sepsis as life-threatening organ dysfunction caused by dysregulated host response to infection. However, the clinical criteria for this definition were neither designed for nor validated in children. We validated the performance of SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores as predictors of outcome in children.Methods: We performed a multicentre binational cohort study of patients < 18 years admitted with infection to ICUs in Australia and New Zealand. The primary outcome was ICU mortality. SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores were compared using crude and adjusted area under the receiver operating characteristic curve (AUROC) analysis.Results: Of 2594 paediatric ICU admissions due to infection, 151 (5.8%) children died, and 949/2594 (36.6%) patients died or experienced an ICU length of stay ≥ 3 days. A ≥ 2-point increase in the individual score was associated with a crude mortality increase from 3.1 to 6.8% for SIRS, from 1.9 to 7.6% for age-adapted SOFA, from 1.7 to 7.3% for PELOD-2, and from 3.9 to 8.1% for qSOFA (p < 0.001). The discrimination of outcomes was significantly higher for SOFA (adjusted AUROC 0.829; 0.791-0.868) and PELOD-2 (0.816; 0.777-0.854) than for qSOFA (0.739; 0.695-0.784) and SIRS (0.710; 0.664-0.756).Conclusions: SIRS criteria lack specificity to identify children with infection at substantially higher risk of mortality. We demonstrate that adapting Sepsis-3 to age-specific criteria performs better than Sepsis-2-based criteria. Our findings support the translation of Sepsis-3 into paediatric-specific sepsis definitions and highlight the importance of robust paediatric organ dysfunction characterization. [ABSTRACT FROM AUTHOR]

Purpose: To use the World Health Organisation's International Classification of Functioning to measure disability following critical illness using patient-reported outcomes.Methods: A prospective, multicentre cohort study conducted in five metropolitan intensive care units (ICU). Participants were adults who had been admitted to the ICU, received more than 24 h of mechanical ventilation and survived to hospital discharge. The primary outcome was measurement of disability using the World Health Organisation's Disability Assessment Schedule 2.0. The secondary outcomes included the limitation of activities and changes to health-related quality of life comparing survivors with and without disability at 6 months after ICU.Results: We followed 262 patients to 6 months, with a mean age of 59 ± 16 years, and of whom 175 (67%) were men. Moderate or severe disability was reported in 65 of 262 (25%). Predictors of disability included a history of anxiety/depression [odds ratio (OR) 1.65 (95% confidence interval (CI) 1.22, 2.23), P = 0.001]; being separated or divorced [OR 2.87 (CI 1.35, 6.08), P = 0.006]; increased duration of mechanical ventilation [OR 1.04 (CI 1.01, 1.08), P = 0.03 per day]; and not being discharged to home from the acute hospital [OR 1.96 (CI 1.01, 3.70) P = 0.04]. Moderate or severe disability at 6 months was associated with limitation in activities, e.g. not returning to work or studies due to health (P < 0.002), and reduced health-related quality of life (P < 0.001).Conclusion: Disability measured using patient-reported outcomes was prevalent at 6 months after critical illness in survivors and was associated with reduced health-related quality of life. Predictors of moderate or severe disability included a prior history of anxiety or depression, separation or divorce and a longer duration of mechanical ventilation.Trial Registration: NCT02225938. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit.Methods: A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death.Results: Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2-11) and to PE diagnosis 6.5 days (IQR 2-16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01-1.03), patient weight (HR per kg 1.01, 95% CI 1-1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01-1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51-1.65).Conclusions: Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality. [ABSTRACT FROM AUTHOR]

The authors highlight the side effects of hydroxyethyl starch (HES), an artificial colloid solution used in treating hypovolemia. Topics covered include link of HES in the increased risk of acute kidney injury (AKI), trials showing increased risk of bleeding with the use of HES as compared with crystalloid solutions in patients with sepsis, and increased mortality with HES in critically ill patients.

The article presents updates on the development of research and supportive care protocols for Ebola virus disease (EVD) patients as of January 2015. Topics discussed include the overall EVD case fatality rate in West Africa, characteristics of the disease, and treatment uncertainties that should be resolved. The authors suggest the need to deploy and evaluate specific supportive care for EVD patients.

Purpose: To determine whether fever is associated with an increased or decreased risk of death in patients admitted to an intensive care unit (ICU) with infection. Methods: We evaluated the independent association between peak temperature in the first 24 h after ICU admission and in-hospital mortality according to whether there was an admission diagnosis of infection using a database of admissions to 129 ICUs in Australia and New Zealand (ANZ) ( n = 269,078). Subsequently, we sought to confirm or refute the ANZ database findings using a validation cohort of admissions to 201 ICUs in the UK ( n = 366,973). Results: A total of 29,083/269,078 (10.8%) ANZ patients and 103,191/366,973 (28.1%) of UK patients were categorised as having an infection. In the ANZ cohort, adjusted in-hospital mortality risk progressively decreased with increasing peak temperature in patients with infection. Relative to the risk at 36.5-36.9°C, the lowest risk was at 39-39.4°C (adjusted OR 0.56; 95% CI 0.48-0.66). In patients without infection, the adjusted mortality risk progressively increased above 39.0°C (adjusted OR 2.07 at 40.0°C or above; 95% CI 1.68-2.55). In the UK cohort, findings were similar with adjusted odds ratios at corresponding temperatures of 0.77 (95% CI 0.71-0.85) and 1.94 (95% CI 1.60-2.34) for infection and non-infection groups, respectively. Conclusions: Elevated peak temperature in the first 24 h in ICU is associated with decreased in-hospital mortality in critically ill patients with an infection; randomised trials are needed to determine whether controlling fever increases mortality in such patients. [ABSTRACT FROM AUTHOR]

Objective: We aim to evaluate the incidence and outcome of acute kidney injury (AKI) among critically ill adult patients with H1N1 2009 infection. Design and patients: From a prospectively collected influenza A (H1N1) 2009 bi-national, we identified 671 adult patients admitted to intensive care unit (ICU) from June 1 to August 31, 2009. Of these, 628 (93.6%) had admission and/or peak serum creatinine values during ICU stay. We defined AKI according to the creatinine criteria of the RIFLE classification. Results: Of 628 adult patients, 211 [33.6%, 95% confidence interval (CI) 29.8-37.4%] had AKI: 41 (6.5%) risk, 56 (8.9%) injury and 114 (18.2%) failure. Of all 211 AKI patients, 76 [36.0% (29.4-42.6%)] died in hospital (36.6% in risk, 25.0% in injury and 41.3% in failure group) compared with 33 of 408 (8.1%) patients without AKI. Among the 33 AKI patients treated with renal replacement therapy, 13 died (39.4%). Mechanical ventilation [odds ratio (OR) 3.62 (2.07-6.34)], any severe co-morbidity (OR 2.36, 95% CI 1.15-3.71), age (OR 1.02, 95% CI 1.01-1.03 per 1 year increase), and AKI (OR 6.69, 95% CI 4.25-10.55) were independently associated with hospital mortality. Conclusions: Acute kidney injury appears common in H1N1 2009 infected patients and is independently associated with an increased risk of hospital mortality. [ABSTRACT FROM AUTHOR]

Objective: To document current management of blood glucose in Australian and New Zealand intensive care units (ICUs) and to investigate the association between insulin administration, blood glucose concentration and hospital outcome.Design and Setting: Practice survey and inception cohort study in closed multi-disciplinary ICUs in Australia and New Zealand.Patients: Twenty-nine ICU directors and 939 consecutive admissions to 29 ICUs during a 2-week period.Measurement and Results: Data collected included unit approaches to blood glucose management, patient characteristics, blood glucose concentrations, insulin administration and patient outcomes. Ten percent of the ICU directors reported using an intensive insulin regimen in all their patients. In 861 patients (91.7%) blood glucose concentration was greater than 6.1[Symbol: see text]mmol/l, 287 (31.1%) received insulin, and the median blood glucose concentration triggering insulin administration was 11.5 (IQR 9.4-14) mmol/l. Univariate analysis demonstrated that non-survivors had a higher maximum daily blood glucose concentration (12 mmol/l, 9.4-14.8, vs. 9.5, 7.6-12.2) and were more likely to receive insulin (47% vs. 28%). Multiple logistic regression analysis showed age (OR per 5-year decrease 0.93, 95% CI 0.87-1.00) and APACHE II (OR per point decrease 0.87, 95% CI 0.84-0.90) to be independently associated with hospital mortality. After controlling for age and APACHE II both daily highest blood glucose (OR 0.95, 95% CI 0.90-1.00) and administration of insulin (OR 0.62, 95% CI 0.39-1.00) were independently associated when added to the model alone; neither was independently associated when they were simultaneously included in the model.Conclusion: Few Australian and New Zealand ICUs have adopted intensive insulin therapy. In this study, insulin administration and highest daily blood glucose concentration could not be separated in their association with hospital mortality. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of early short-term, isovolaemic haemofiltration at 45 ml/kg/h on physiological and clinical outcomes in patients with septic shock.Design: Retrospective study before and after a change of unit protocol (study period 8 years).Setting: Intensive care unit of metropolitan hospital.Patients: Eighty patients with septic shock.Interventions: Introduction of a new septic shock protocol based on early isovolaemic haemofiltration (EIHF). In the pre-EIHF period (before), 40 patients received conventional supportive therapy. In the post-EIHF period (after), 40 patients received EIHF at 45 ml/kg/h of plasma-water exchange over 6 h followed by conventional continuous venovenous haemofiltration (CVVH). Anticoagulation policy remained unchanged.Measurements and Main Results: The two groups were comparable for age, gender and baseline APACHE II score. Delivered haemofiltration dose was above 85% of prescription in all patients. PaO2/FiO2 ratio increased from 117+/-59 to 240+/-50 in EIHF, while it changed from 125+/-55 to 160+/-50 in the control group (p<0.05). In EIHF patients, mean arterial pressure increased (95+/-10 vs 60+/-12 mmHg; p<0.05), and norepinephrine dose decreased (0.20+/-2 vs 0.02+/-0.2 microg/kg/min; p<0.05). Among EIHF patients, 28 (70%) were successfully weaned from the ventilator compared with 15 (37%) in the control group (p<0.01). Similarly, 28-day survival was 55% compared with 27.5% (p<0.05). Length of stay in the ICU was 9+/-5 days compared with 16+/-4 days (p<0.002).Conclusions: In patients with septic shock, EIHF was associated with improved gas exchange, haemodynamics, greater likelihood of successful weaning and greater 28-day survival compared with conventional therapy. [ABSTRACT FROM AUTHOR]