Search

Patient sex affects treatment and outcomes in critical illness. Previous studies of sex differences in critical illness compared female and male patients. In this study, we describe the group of patients classified as a third sex admitted to ICUs in Australia and New Zealand. What are the admission characteristics and outcomes of ICU patients classified as belonging to a third sex group compared with patients classified as female or male? Retrospective observational study of admissions to 200 ICUs, recorded in the Australian and New Zealand Intensive Care Society's Adult Patient Database from 2018 to 2022. We undertook mixed effect logistic regression to compare hospital mortality across the sex groups, adjusted for illness severity, diagnosis, treatment limitation, year, and hospital. We examined 892,161 admissions, of whom 525 (0.06%) were classified as third sex. Patients classified as third sex were represented across all diagnostic categories, jurisdictions, and hospital types. On average, they were younger than the groups classified as female (59.2 ± 20.0 vs 61.3 ± 18.4 years; P =.02) or male (63.2 ± 16.7 years; P <.001), respectively. Patients classified as third sex were more likely to be admitted after orthopedic surgery (10.1% third sex admissions [95% CI, 7.7%-13.0%]; 6.2% female [95% CI, 6.1%-6.3%]; 4.8% male [95% CI, 4.7%-4.9%]) and drug overdose (8.8% third sex admissions [95% CI, 6.5%-11.5%]; 4.2% female [95% CI, 4.1%-4.2%]; 3.1% male [95% CI, 3.0%-3.1%]). There was no difference in the adjusted hospital mortality of patients classified as third sex compared with the other groups. Patients classified as third sex composed a small minority group of adult ICU patients. This group had a different diagnostic case mix but similar outcomes to the groups classified as female or male. Further characterizing a third sex group will require improved processes for recording sex and gender in health records. [Display omitted] [ABSTRACT FROM AUTHOR]

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404). [ABSTRACT FROM AUTHOR]

Introduction: The contribution of fluid temperature to the effect of crystalloid fluid bolus therapy (FBT) in post-cardiac surgery patients is unknown. We evaluated the hemodynamic effects of FBT with fluid warmed to 40°C (warm FBT) versus room-temperature fluid. Methods: In this single centre prospective before-and-after study, we evaluated the effects of 500 ml of warm versus room-temperature compound sodium lactate administered over <30 minutes, in 50 cardiac surgery patients admitted to ICU. We recorded hemodynamics continuous before and for 30 minutes after the first FBT. We defined CI responsiveness (CI-R) as an CI increase >15% of baseline immediately after FBT and effect dissipation if the CI returned to <5% of baseline and MAP responsiveness as >10% increase and dissipation as return to <3 mmHg of baseline. Results: Hypotension (56%) and low CI (40%) typically triggered FBT. Temperature decreased >0.3°C in 13 (52%) patients after room-temperature FBT versus 0 (0%) after warm FBT (p < 0.01). CI and MAP responsiveness was similar (16 [64%] versus 11 [44%], p = 0.15 and 15 [60%] versus 17 [68%], p = 0.77, respectively). Among CI responders, CI increased more with room-temperature FBT (+0.6 [IQR, 0.5–1.1] versus +0.5 [IQR, 0.4–0.6] L/min/m2, p = 0.01). However, dissipation was more common after room-temperature versus warm FBT (9/16 [56%] versus 1/11 [9%], p = 0.02). Conclusion: In postoperative cardiac surgery patients, warm FBT preserved core temperature and induced smaller but more sustained CI increases among responders. Fluid temperature appears to impact both core temperature and the duration of CI response. [ABSTRACT FROM AUTHOR]

Introduction: Higher net ultrafiltration (UFNET) rates are associated with mortality among critically ill patients with acute kidney injury (AKI) and treated with continuous renal replacement therapy (CRRT). Objective: The aim of the study was to discover whether UFNET rates are associated with renal recovery and independence from renal replacement therapy (RRT). Methods: Retrospective cohort study using data from the Randomized Evaluation of Normal versus Augmented Level of Renal Replacement Therapy trial that enrolled 1,433 critically ill patients with AKI and treated with CRRT between December 2005 and November 2008 across 35 intensive care units in Australia and New Zealand. We examined the association between UFNET rate and time to independence from RRT by day 90 using competing risk regression after accounting for mortality. The UFNET rate was defined as the volume of fluid removed per hour adjusted for patient body weight. Results and Conclusions: Median age was 67.3 (interquartile range [IQR], 57–76.3) years, 64.4% were male, median Acute Physiology and Chronic Health Evaluation-III score was 100 (IQR, 84–118), and 634 (44.2%) died by day 90. Kidney recovery occurred in 755 patients (52.7%). Using tertiles of UFNET rates, 3 groups were defined: high, >1.75; middle, 1.01–1.75; and low, <1.01 mL/kg/h. Proportion of patients alive and independent of RRT among the groups were 47.8 versus 57.2 versus 53.0%; p = 0.01. Using competing risk regression, higher UFNET rate tertile compared with middle (cause-specific hazard ratio [csHR], 0.79, 95% CI, 0.66–0.95; subdistribution hazard ratio [sHR], 0.80, 95% CI, 0.67–0.97) and lower (csHR, 0.69, 95% CI, 0.56–0.85; sHR, 0.78, 95% CI 0.64–0.95) tertiles were associated with a longer time to independence from RRT. Every 1.0 mL/kg/h increase in rate was associated with a lower probability of kidney recovery (csHR, 0.81, 95% CI, 0.74–0.89; and sHR, 0.87, 95% CI, 0.80–0.95). Using the joint model, longitudinal increases in UFNET rates were also associated with a lower renal recovery (β = −0.29, p < 0.001). UFNET rates >1.75 mL/kg/h compared with rates 1.01–1.75 and <1.01 mL/kg/h were associated with a longer duration of dependence on RRT. Randomized clinical trials are required to confirm this UFNET rate-outcome relationship. [ABSTRACT FROM AUTHOR]

Background: Low tidal volume (VT) ventilation and its associated increase in arterial carbon dioxide (PaCO2) may affect postoperative neurologic function. We aimed to test the hypothesis that intraoperative low VT ventilation affect the incidence of postoperative ICD-10 coded delirium and/or the need for antipsychotic medications. Methods: This is a post-hoc analysis of a large randomized controlled trial evaluating low vs. conventional VT ventilation during major non-cardiothoracic, non-intracranial surgery. The primary outcome was the incidence of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay, and the absolute difference with its 95% confidence interval (CI) was calculated. Results: We studied 1206 patients (median age of 64 [55–72] years, 59.0% males, median ARISCAT of 26 [19–37], and 47.6% of ASA 3). ICD-10 coded delirium and /or antipsychotic medication use was diagnosed in 11.2% with similar incidence between low and conventional VT ventilation (11.1% vs. 11.3%; absolute difference, -0.24 [95%CI, -3.82 to 3.32]; p = 0.894). There was no interaction between allocation group and type of surgery. Conclusion: In adult patients undergoing major surgery, low VT ventilation was not associated with increased risk of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay. Trial registration: ANZCTR Identifier: ACTRN12614000790640. [ABSTRACT FROM AUTHOR]

Purpose: Acute illness severity predicts mortality in intensive care unit (ICU) patients, however, its predictive value decreases over time in ICU. Typically after 10 days, pre-ICU (antecedent) characteristics become more predictive of mortality, defining the onset of persistent critical illness (PerCI). How patient frailty affects development and death from PerCI is unknown. Methods: We conducted a secondary analysis of data from a prospective binational cohort study including 269,785 critically ill adults from 168 ICUs in Australia and New Zealand, investigating whether frailty measured with the Clinical Frailty Scale (CFS) changes the timing of onset and risk of developing PerCI and of subsequent in-hospital mortality. We assessed associations between frailty (CFS ≥ 5) and mortality prediction using logistic regression and area under the receiver operating characteristics (AUROC) curves. Results: 2190 of 50,814 (4.3%) patients with frailty (CFS ≥ 5) versus 6624 of 218,971 (3%) patients without frailty (CFS ≤ 4) developed PerCI (P < 0.001). Among patients with PerCI, 669 of 2190 (30.5%) with frailty and 1194 of 6624 without frailty (18%) died in hospital (P < 0.001). The time point defining PerCI onset did not vary with frailty degree; however, with increasing length of ICU stay, inclusion of frailty progressively improved mortality discrimination (0.1% AUROC improvement on ICU day one versus 3.6% on ICU day 17). Conclusion: Compared to patients without frailty, those with frailty have a higher chance of developing and dying from PerCI. Moreover the importance of frailty as a predictor of mortality increases with ICU length of stay. Future work should explore incorporation of frailty in prognostic models, particularly for long-staying patients. [ABSTRACT FROM AUTHOR]

Title: Low blood flow continuous veno-venous haemodialysis (CVVHD) compared with higher blood flow continuous veno-venous haemodiafiltration (CVVHDF): effect on alarm rates, filter life, and azotaemic control. Introduction: Continuous renal replacement therapy (CRRT) can be delivered via convective, diffusive, or mixed approaches. Higher blood flows have been advocated for convective clearance efficiency and promotion of filter life. It is unclear whether a lower blood flow predominantly diffusive approach may benefit filter life and alarm rates. Materials and Methods: Sequential cohort study of 284 patients undergoing 874 CRRT circuits from January 2015 to August 2018 in a single university-associated tertiary referral hospital in Australia. Patients underwent a protocol of either CVVHDF at blood flow 200–250 mL/min or CVVHD at blood flow 100–130 mL/min. Machine and patient data were analysed. Outcomes of azotaemic control, filter life, and warning alarm rates were log transformed and analysed with mixed linear modelling with patient as a random effect. Results: Both groups had similar azotaemic control (effect estimate on log creatinine CVVHD vs. CVVHDF 1.04 [0.87–1.25], p = 0.68) and median filter life (CVVHDF 16.8 [8.4–90.5] h and CVVHD 16.4 [9.4–82.3] h, p = 0.97). However, circuit pressures were less extreme with a narrower distribution during CVVHD. Multivariate analysis showed CVVHD had a reduced risk of warning alarms (incidence risk ratio [IRR] 0.51 [0.38–0.70]) and femoral access placement also had a reduced risk of alarms (IRR 0.55 [0.41–0.73]). Conclusion: Low blood flow CVVHD and femoral vascular access reduce alarms while maintaining azotaemic control and circuit patency thus minimizing bedside clinician workload. [ABSTRACT FROM AUTHOR]

Background: Survivors of acute kidney injury (AKI) are at increased risk of major adverse kidney events and international guidelines recommend individuals be evaluated 3 months following AKI. Aim: We describe practice patterns and predictors of post‐AKI care in an Australian tertiary hospital. Methods: A retrospective analysis was undertaken of adults with AKI (defined by KDIGO criteria) admitted to a single centre between 2012 and 2016. The primary outcome was outpatient nephrology review at 3 months. Secondary outcomes included inpatient nephrology review, and outpatient serum creatinine and urinary protein measurements. Data were analysed using multivariable logistic and competing risk regression. Results: Only 117 of 2111 (6%) patients with AKI were reviewed by a nephrologist at 3 months. Reviewed patients were more likely to have a higher discharge serum creatinine (odds ratio (OR) 1.20 per 10 μmol/L increase; 95% confidence interval (CI) 1.16–1.25) or a history of peripheral vascular disease (OR 1.77; 95% CI 1.00–3.14). They were less likely to be older (OR 0.66 per decade; 95% CI 0.57–0.76) or to have a history of liver (OR 0.47; 95% CI 0.26–0.87) or ischaemic heart (OR 0.50; 95% CI 0.27–0.94) disease. AKI stage did not predict follow up. The median time from discharge to outpatient serum creatinine testing was 12 days (interquartile range 4–47) and proteinuria was measured in 538 (25%) patients. Conclusions: A minority of admitted AKI patients receive recommended post‐AKI care. Studies in other Australian institutions are required to confirm or refute these concerning findings. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with poor outcomes in critical illness. However, it is unclear whether frailty screening on admission to the ICU can be conducted routinely at the population level and whether it has prognostic importance.Research Question: Can population-scale frailty screening with the Clinical Frailty Scale (CFS) be implemented for critically ill adults in Australia and New Zealand (ANZ) and can it identify patients at risk of negative outcomes?Study Design and Methods: We conducted a binational prospective cohort study of critically ill adult patients admitted between July 1, 2018, and June 30, 2020, in 175 ICUs in ANZ. We classified frailty with the CFS on admission to the ICU. The primary outcome was in-hospital mortality; secondary outcomes were length of stay (LOS), discharge destination, complications (delirium, pressure injury), and duration of survival.Results: We included 234,568 critically ill patients; 45,245 (19%) were diagnosed as living with frailty before ICU admission. Patients with vs without frailty had higher in-hospital mortality (16% vs 5%; P < .001), delirium (10% vs 4%; P < .001), longer LOS in the ICU and hospital, and increased new chronic care discharge (3% vs 1%; P < .001), with worse outcomes associated with increasing CFS category. Of patients with very severe frailty (CFS score, 8), 39% died in hospital vs 2% of very fit patients (CFS score, 1; multivariate categorical CFS score, 8 [reference, 1]; OR, 7.83 [95% CI, 6.39-9.59]; P < .001). After adjustment for illness severity, frailty remained highly significantly predictive of mortality, including among patients younger than 50 years, with improvement in the area under the receiver operating characteristic curve of the Acute Physiology and Chronic Health Evaluation III-j score to 0.882 (95% CI, 0.879-0.885) from 0.868 (95% CI, 0.866-0.871) with the addition of frailty (P < .001).Interpretation: Large-scale population screening for frailty degree in critical illness was possible and prognostically important, with greater frailty (especially CFS score of ≥ 6) associated with worse outcomes, including among younger patients. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence indicates a relationship between glycemic variability during intensive care unit (ICU) admission and death. We assessed whether mean glucose, hypoglycemia occurrence, or premorbid glycemic control modified this relationship. Methods: In this retrospective, multicenter cohort study, we included adult patients admitted to five ICUs in Australia and Sweden with available preadmission glycated hemoglobin A1c (HbA1c) and three or more glucose readings. We calculated the glycemic lability index (GLI), a measure of glycemic variability, and the time‐weighted average blood glucose (TWA‐BG) from all glucose readings. We used logistic regression analysis with adjustment for hypoglycemia and admission characteristics to assess the independent association of GLI (above vs. below cohort median) and TWA‐BG (above vs. below cohort median) with hospital mortality. Results: Among 2305 patients, 859 (37%) had diabetes, median GLI was 40 [mmol/L]2/h/week, median TWA‐BG was 8.2 mmol/L, 171 (7%) developed hypoglycemia, and 371 (16%) died. The adjusted odds ratio for death was 1.61 (95% CI, 1.19‐2.15; P =.002) for GLI above versus below median and 1.06 (95% CI, 0.80‐1.41; P =.67) for TWA‐BG above versus below median. The relationship between GLI and mortality was not modified by TWA‐BG (P [interaction] = 0.66), a history of diabetes (P [interaction] = 0.89) or by HbA1c ≥52 mmol/mol (vs. <52 mmol/mol) (P [interaction] = 0.29). Conclusion: In adult patients admitted to an ICU in Sweden and Australia, a high GLI was associated with increased hospital mortality irrespective of the level of mean glycemia, hypoglycemia occurrence, or premorbid glycemic control. These findings support the assessment of interventions to reduce glycemic variability during critical illness. [ABSTRACT FROM AUTHOR]

Purpose: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.Methods: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.Results: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.Conclusions: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified. [ABSTRACT FROM AUTHOR]

Background: General medical wards admit a varied cohort of patients from the emergency department, some of whom deteriorate during their hospital stay. Currently, we use vital signs based warning scores to predict patients at risk of imminent deterioration, but there is now a growing body of literature that commonly available laboratory results may also help to identify those at risk. Aim: To assess whether a laboratory‐based admission score can predict in hospital mortality, intensive care unit (ICU) admission, medical emergency team (MET) activation or cardiac arrest in a cohort of Australian general medical patients admitted through the emergency department (ED). Methods: We performed a retrospective observational study of all general medical admissions to hospital through the ED in 2015. Admission pathology was used to calculate a risk score. In‐patient outcomes of death, ICU transfer, MET call activation or cardiac arrest were collected from hospital records. Results: We studied 2942 admissions derived from 2521 patients, with a median age of 81 years. There were 143 in‐patient deaths, 82 ICU admissions, 277 MET calls and 14 cardiac arrest calls. The laboratory‐based admission score had an area under the receiver operating characteristic curve (AUC‐ROC) of 0.76 (95% confidence interval (CI): 0.72–0.80) for inpatient death, an AUC‐ROC of 0.79 (95% CI: 0.66–0.93) for inpatient cardiac arrest, an AUC‐ROC of 0.64 (95% CI: 0.58–0.70) for ICU transfer and an AUC‐ROC of 0.59 (95% CI: 0.55–0.62) for MET call activation. When patients aged over 75 were analysed separately, the AUC‐ROC for prediction of in‐patient death was 0.74 (95% CI: 0.70–0.78) and increased to 0.86 (95% CI: 0.73–0.98) for the prediction of in‐patient cardiac arrest. Conclusion: A simple laboratory‐derived score obtained at patient admission is a fair to good predictor of subsequent in‐patient death or cardiac arrest in general medical patients and in the older patient cohort. Prospective interventional studies are required to ascertain the clinical utility of this admission score. [ABSTRACT FROM AUTHOR]

Rationale: There are no prospective observational studies exploring the relationship between relative hypotension and adverse kidney-related outcomes among critically ill patients with shock.Objectives: To investigate the magnitude of relative hypotension during vasopressor support among critically ill patients with shock and to determine whether such relative hypotension is associated with new significant acute kidney injury (AKI) or major adverse kidney events (MAKE) within 14 days of vasopressor initiation.Methods: At seven multidisciplinary ICUs, 302 patients, aged ≥40 years and requiring ≥4 hours of vasopressor support for nonhemorrhagic shock, were prospectively enrolled. We assessed the time-weighted average of the mean perfusion pressure (MPP) deficit (i.e., the percentage difference between patients' preillness basal MPP and achieved MPP) during vasopressor support and the percentage of time points with an MPP deficit > 20% as key exposure variables. New significant AKI was defined as an AKI-stage increase of two or more (Kidney Disease: Improving Global Outcome creatinine-based criteria).Measurements and Main Results: The median MPP deficit was 19% (interquartile range, 13-25), and 54% (interquartile range, 19-82) of time points were spent with an MPP deficit > 20%. Seventy-three (24%) patients developed new significant AKI; 86 (29%) patients developed MAKE. For every percentage increase in the time-weighted average MPP deficit, multivariable-adjusted odds of developing new significant AKI and MAKE increased by 5.6% (95% confidence interval, 2.2-9.1; P = 0.001) and 5.9% (95% confidence interval, 2.2-9.8; P = 0.002), respectively. Likewise, for every one-unit increase in the percentage of time points with an MPP deficit > 20%, multivariable-adjusted odds of developing new significant AKI and MAKE increased by 1.2% (0.3-2.2; P = 0.008) and 1.4% (0.4-2.4; P = 0.004), respectively.Conclusions: Vasopressor-treated patients with shock are often exposed to a significant degree and duration of relative hypotension, which is associated with new-onset, adverse kidney-related outcomes.Study registered with Australian New Zealand Clinical Trial Registry (ACTRN 12613001368729). [ABSTRACT FROM AUTHOR]

Background: A threshold Clinical Frailty Scale (CFS) of 5 (indicating mild frailty) has been proposed to guide ICU admission for UK patients with coronavirus disease 2019 (COVID-19) pneumonia. However, the impact of frailty on mortality with (non-COVID-19) pneumonia in critical illness is unknown. We examined the triage utility of the CFS in patients with pneumonia requiring ICU.Methods: We conducted a retrospective cohort study of adult patients admitted with pneumonia to 170 ICUs in Australia and New Zealand from January 1, 2018 to September 31, 2019. We classified patients as: non-frail (CFS 1-4) frail (CFS 5-8), mild/moderately frail (CFS 5-6),and severe/very severely frail (CFS 7-8). We evaluated mortality (primary outcome) adjusting for site, age, sex, mechanical ventilation, pneumonia type and illness severity. We also compared the proportion of ICU bed-days occupied between frailty categories.Results: 1852/5607 (33%) patients were classified as frail, including1291/3056 (42%) of patients aged >65 yr, who would potentially be excluded from ICU admission under UK-based COVID-19 triage guidelines. Only severe/very severe frailty scores were associated with mortality (adjusted odds ratio [aOR] for CFS=7: 3.2; 95% confidence interval [CI]: 1.3-7.8; CFS=8 [aOR: 7.2; 95% CI: 2.6-20.0]). These patients accounted for 7% of ICU bed days. Vulnerability (CFS=4) and mild frailty (CFS=5) were associated with a similar mortality risk (CFS=4 [OR: 1.6; 95% CI: 0.7-3.8]; CFS=5 [OR: 1.6; 95% CI: 0.7-3.9]).Conclusions: Patients with severe and very severe frailty account for relatively few ICU bed days as a result of pneumonia, whilst adjusted mortality analysis indicated little difference in risk between patients in vulnerable, mild, and moderate frailty categories. These data do not support CFS ≥5 to guide ICU admission for pneumonia. [ABSTRACT FROM AUTHOR]

Rationale: Whether biomarkers can identify subgroups of patients with septic shock with differential treatment responses to hydrocortisone is unknown.Objectives: To determine if there is heterogeneity in effect for hydrocortisone on mortality, shock resolution, and other clinical outcomes based on baseline cortisol, aldosterone, and ascorbic acid concentrations.Methods: From May 2014 to April 2017, we obtained serum samples from 529 patients with septic shock from 22 ICUs in Australia and New Zealand.Measurements and Main Results: There were no significant interactions between the association with 90-day mortality and treatment with either hydrocortisone or placebo for total cortisol (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.16 vs. OR, 1.07; 95% CI, 1.00-1.13; P = 0.70), free cortisol (OR, 1.20; 95% CI, 1.04-1.38 vs. OR, 1.16; 95% CI, 1.02-1.32; P = 0.75), aldosterone (OR, 1.01; 95% CI, 0.97-1.05 vs. OR, 1.01; 95% CI, 0.98-1.04; P = 0.99), or ascorbic acid (OR, 1.11; 95% CI, 0.89-1.39 vs. OR, 1.05; 95% CI, 0.91-1.22; P = 0.70), respectively. Similar results were observed for the association with shock resolution. Elevated free cortisol was significantly associated with 90-day mortality (OR, 1.13; 95% CI, 1.00-1.27; P = 0.04), but total cortisol, aldosterone, and ascorbic acid were not.Conclusions: In patients with septic shock, there was no heterogeneity in effect of adjunctive hydrocortisone on mortality, shock resolution, or other clinical outcomes based on cortisol, aldosterone, and ascorbic acid concentrations. Plasma aldosterone and ascorbic acid concentrations are not associated with outcome. [ABSTRACT FROM AUTHOR]

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30‐day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6‐ and 24‐h post‐enrolment, time to antimicrobial administration, intensive care admission, organ support and in‐hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre‐enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in‐hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy. [ABSTRACT FROM AUTHOR]

Rationale: The characteristics and outcomes of patients presenting with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) requiring intensive care unit (ICU) admission are poorly understood and there are sparse epidemiological data.Objectives: The objectives were to describe epidemiology and outcomes of patients admitted to an ICU with COPD and to evaluate whether outcomes varied over time.Methods: We studied adult ICU admissions across Australia and New Zealand between 2005 and 2017 with a diagnosis of AECOPD and used an admission diagnosis of asthma as comparator for trends over time. We measured changes in characteristics and outcomes over time using logistic regression, adjusting for illness severity using the Australian New Zealand Risk of Death model.Results: We studied 31,991 admissions with AECOPD and 11,096 with asthma. Mean (standard deviation) age for AECOPD patients was 68.3 (11.2) years, with 35.4% mechanically ventilated. For patients with AECOPD, the percentage of deaths in an ICU was 8.7% and in a hospital was 15.4% of admissions, with the proportion of 69.2% discharged home and 5.6% discharged to a high-level care facility. During the study period, the proportion of ICU admissions with AECOPD per 10,000 admissions decreased at an annual rate of 2.0 (95% confidence interval [CI], 0.8-3.2; P = 0.009) but their admission rate per million population increased annually by 4.5 (95% CI, 3.7-5.3; P < 0.0001). There was a linear reduction in mortality for AECOPD but not for asthma admissions (odds ratio annual decline: AECOPD, 0.94 [0.93-0.95] and asthma, 1.01 [0.97-1.05]; P = 0.001) and an increase in AECOPD admissions discharged to home (odds ratio annual increase, AECOPD, 1.04 [1.03-1.05] and asthma, 1.01 [0.99-1.03]; P = 0.01). The reduction in mortality was sustained after adjusting for illness severity.Conclusions: Across Australia and New Zealand, the rate of ICU admissions due to AECOPD is increasing but mortality rates are decreasing, with a corresponding increase in the home discharge rates. [ABSTRACT FROM AUTHOR]

Background and Aim: To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). Methods: Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. Results: We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter‐quartile range [IQR] 3.8–8.7), median longest activated partial thromboplastin time was 62 s (IQR 44–87), and median lowest fibrinogen was 1.1 (IQR 0.8–1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P < 0.0001). Median initial lowest platelet count was 83 (IQR 41–122) × 109/L. Overall, 58% of patients received fresh frozen plasma, 40% cryoprecipitate, 35% platelets, and 15% prothrombin complex concentrate. Patients with bleeding complications (19%) had more severe overall hypofibrinogenemia and thrombocytopenia. Thrombotic complications were less common (10% of patients), were not associated with consistent patterns of abnormal hemostasis, and were not immediately preceded by clotting factor administration and half occurred only after liver transplantation surgery. Conclusion: In ALF patients admitted to dedicated Australia and New Zealand ICUs, fibrinogen was measured less frequently than other coagulation parameters but, together with platelets, appeared more relevant to bleeding risk. Blood products and procoagulant factors were administered to most patients at variable levels of hemostatic derangement, and bleeding complications were more common than thrombotic complications. This epidemiologic information and practice variability provide baseline data for the design and powering of interventional studies. [ABSTRACT FROM AUTHOR]

The oxygen concentration (FiO2) and arterial oxygen tension (PaO2) delivered in patients undergoing major surgery is poorly understood. We aimed to assess current practice with regard to the delivered FiO2 and the resulting PaO2 in patients undergoing major surgery. We performed a retrospective cohort study in a tertiary hospital. Data were collected prospectively as part of a larger randomised controlled trial but were analysed retrospectively. Patients were included if receiving controlled mandatory ventilation and arterial line monitoring. Anaesthetists determined the FiO2 and the oxygenation saturation (SpO2) targets. An arterial blood gas (ABG) was obtained 15-20 minutes after induction of anaesthesia, immediately before the emergence phase of anaesthesia and 15 minutes after arrival in the post-anaesthesia care unit (PACU). We defined hyperoxaemia as a PaO2 of >150 mmHg and included a further threshold of PaO2 >200 mmHg. We studied 373 patients. The median (interquartile range (IQR)) lowest intraoperative FiO2 and SpO2 values were 0.45 (IQR 0.4-0.5) and 97% (IQR 96-98%), respectively, with a median PaO2 on the first and second ABG of 237 mmHg (IQR 171-291 mmHg) and 189 mmHg (IQR 145-239 mmHg), respectively. In the PACU, the median lowest oxygen flow rate was 6 L/min (IQR 3-6 L/min), and the PaO2 was 158 mmHg (IQR 120-192 mmHg). Hyperoxaemia occurred in 82%, 73% and 54% of participants on the first and second intraoperative and postoperative ABGs respectively. A PaO2 of >200 mmHg occurred in 64%, 41% and 21% of these blood gases, respectively. In an Australian tertiary hospital, a liberal approach to FiO2 and PaO2 was most common and resulted in a high incidence of perioperative hyperoxaemia. [ABSTRACT FROM AUTHOR]

Objective: To compare the characteristics, use of invasive ventilation and outcomes of patients admitted with critical asthma syndrome (CAS) to ICUs in Australia and New Zealand (ANZ), and a large cohort of ICUs in the United States (US). Methods: We examined two large databases of ICU for patients admitted with CAS in 2014 and 2015. We obtained, analyzed, and compared information on demographic and physiological characteristics, use of invasive mechanical ventilation, and clinical outcome and derived predictive models. Results: Overall, 2202 and 762 patients were admitted with a primary diagnosis of CAS in the ANZ and US databases respectively (0.73% vs. 0.46% of all ICU admissions, P < 0.001). A similar percentage of patients received invasive mechanical ventilation in the first 24 h (24.7% vs. 24.4%, P = 0.87) but ANZ patients had lower respiratory rates and higher PaCO2 levels. Overall mortality was low (1.23 for ANZ and 1.71 for USA; P = 0.36) and even among invasively ventilated patients (2.4% for ANZ vs. 1.1% for USA; P = 0.38). However, ANZ patients also had longer length of stay in ICU (43 vs. 37 h, P = 0.001) and hospital (105 vs. 78 h, P = 0.003). Conclusions: Patients admitted to ANZ and USA ICU with CAS are broadly similar and have a low and similar rate of invasive ventilation and mortality. However, ANZ patients made up a greater proportion of ICU patients and had longer ICU and hospital stays. These findings provide a modern invasive ventilation and mortality rates benchmark for future studies of CAS. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the initiation of vasopressor infusions via peripheral venous catheters (PVC) compared to central venous catheters (CVC) in ED patients with early septic shock was associated with differences in processes of care and outcomes. Methods: We conducted a post‐hoc analysis of the ARISE trial. We compared participants who had a vasopressor infusion first commenced via a PVC versus a CVC. The primary outcome was 90 day mortality. Results: We studied 937 participants. Of these, 389 (42%) had early vasopressor infusion commenced via a PVC and 548 (58%) via a CVC. Trial participants who received a vasopressor infusion via a PVC were more severely ill, with higher median (interquartile range [IQR]) Acute Physiology And Chronic Health Evaluation (APACHE II) scores (17 [13–23] versus 16 [12–21], P = 0.003), and higher median (IQR) lactate (mmol/L) (3.6 [1.9–5.8] versus 2.5 [1.5–4.5], P < 0.001). After adjusting for baseline covariates, the estimated odds ratio for mortality for PVC‐treated patients was 1.26 (95% confidence interval 0.95–1.67, P = 0.11). Trial participants who had vasopressors commenced via PVC had a shorter median (IQR) time to commencement of antimicrobials (55 [32–96] versus 71.5 [39–119] min, P < 0.001) and a shorter median (IQR) time to commencement of vasopressors (2.4 [1.3–3.9] versus 4.9 [3.5–6.6] h, P < 0.001). Conclusion: The practice of commencing a vasopressor infusion via a PVC was common in the ARISE trial and more frequent in trial participants with higher severity of illness. Commencement of a vasopressor infusion via a PVC was associated with some improvements in processes of care and, after adjustment, was not associated with an increased risk of death. [ABSTRACT FROM AUTHOR]

Background: Delirium is common in hospitalised patients but its epidemiology remains poorly characterised. Aims: To test the hypothesis that patient demographics, clinical phenotype, management and outcomes of patient with delirium in hospital ward patients differ from intensive care unit (ICU) patients. Methods: Retrospective cohort of patients admitted to an Australian university‐affiliated hospital between March 2013 and April 2017 and coded for delirium at discharge using the International Classification of Diseases System, 10th revision, criteria. Results: Among 61 032 hospitalised patients, 2864 (4.7%) were coded for delirium. From these, we studied a random sample of 100 ward patients and 100 ICU patients. Ward patients were older (median age: 84 vs 65 years; P < 0.0001), more likely to have dementia (38% vs 2% for ICU patients; P < 0.0001) and less likely to have had surgery (24% vs 62%; P < 0.0001). Of ward patients, 74% had hypoactive delirium, while 64% of ICU patients had agitated delirium (P < 0.0001). Persistent delirium at hospital discharge was more common among ward patients (66% vs 17%, P < 0.0001). On multivariable analysis, age and dementia predicted persistent delirium, while surgery predicted recovery. Conclusions: Delirium in ward patients is profoundly different from delirium in ICU patients. It has a dominant hypoactive clinical phenotype, is preceded by dementia and is less likely to recover at hospital discharge. Therefore, delirium prevention, detection and goals of care should be adapted to the environment in which it occurs. [ABSTRACT FROM AUTHOR]

Objective: To explore associations between frailty (Clinical Frailty Scale score of 5 or more) in very old patients in intensive care units (ICUs) and their clinical outcomes (mortality, discharge destination).Design, Setting and Participants: Retrospective population cohort analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data for all patients aged 80 years or more admitted to participating ICUs between 1 January 2017 and 31 December 2018.Main Outcome Measures: Primary outcome: in-hospital mortality; secondary outcomes: length of stay (hospital, ICU), re-admission to ICU during the same hospital admission, discharge destination (including new chronic care or nursing home admission).Results: Frailty status data were available for 15 613 of 45 773 patients aged 80 years or more admitted to 178 ICUs (34%); 6203 of these patients (39.7%) were deemed frail. A smaller proportion of frail than non-frail patients were men (47% v 57%), the mean illness severity scores of frail patients were slightly higher than those of non-frail patients, and they were more frequently admitted from the emergency department (28% v 21%) or with sepsis (12% v 7%) or respiratory complications (16% v 12%). In-hospital mortality was higher for frail patients (17.6% v 8.2%; adjusted odds ratio [OR], 1.87 [95% CI, 1.65-2.11]). Median lengths of ICU and hospital stay were slightly longer for frail patients, and they were more frequently discharged to new nursing home or chronic care (4.9% v 2.8%; adjusted OR, 1.61 [95% CI, 1.34-1.95]).Conclusions: Many very old critically ill patients in Australia and New Zealand are frail, and frailty is associated with considerably poorer health outcomes. Routine screening of older ICU patients for frailty could improve outcome prediction and inform intensive care and community health care planning. [ABSTRACT FROM AUTHOR]

Background: Knowledge about patients with acute liver failure (ALF) in Australia and New Zealand (ANZ) is lacking. Aims: To evaluate whether the pattern of ALF would be similar to previous studies and whether, despite potentially low transplantation rates, mortality would be comparable. Methods: We obtained data from the ANZ Intensive Care Society Adult Patient Database and the ANZ Liver Transplant Registry for 10 years commencing 2005 and analysed for patient outcomes. Results: During the study period, 1 022 698 adults were admitted to intensive care units across ANZ, of which 723 had ALF. The estimated annual incidence of ALF over this period was 3.4/million people and increased over time (P = 0.001). ALF patients had high illness severity (Acute Physiology And Chronic Health Evaluation III 79.8 vs 50.1 in non‐ALF patients; P < 0.0001) and were more likely to be younger, female, pregnant and immunosuppressed. ALF was an independent predictor of mortality (odds ratio 1.5 (1.26–1.79); P < 0.0001). At less than 23%, the use of liver transplantation was low, but the mortality of 39% was similar to previous studies. Conclusions: ALF is a rare but increasing diagnosis in ANZ intensive care units. Low transplantation rates in ANZ for ALF do not appear to be associated with higher mortality rates than reported in the literature. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the admission characteristics and hospital outcomes for Indigenous and non-Indigenous patients admitted to intensive units (ICUs) after major trauma.Design, Setting: Retrospective analysis of Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database data from 92 Australian ICUs for the 6-year period, 2010-2015.Participants: Patients older than 17 years of age admitted to public hospital ICUs with a primary diagnosis of trauma.Main Outcome Measures: ICU and overall hospital lengths of stay, hospital discharge destination, and ICU and overall hospital mortality rates for Indigenous and non-Indigenous patients.Results: 23 804 people were admitted to Australian public hospital ICUs after major trauma; 1754 (7.4%) were Indigenous Australians. The population-standardised incidence of admissions was consistently higher for Indigenous Australians than for non-Indigenous Australians (847 per million v 251 per million population; incidence ratio, 3.37; 95% CI, 3.19-3.57). Overall hospital mortality rates were similar for Indigenous and non-Indigenous patients (adjusted odds ratio [aOR], 1.04; 95% CI, 0.82-1.31). Indigenous patients were more likely than non-Indigenous patients to be discharged to another hospital (non-Indigenous v Indigenous: aOR, 0.84; 95% CI, 0.72-0.96) less likely to be discharged home (non-Indigenous v Indigenous: aOR, 1.17; 95% CI, 1.04-1.31).Conclusion: The population rate of trauma-related ICU admissions was substantially higher for Indigenous than non-Indigenous patients, but hospital mortality rates after ICU admission were similar. Indigenous patients were more likely to be discharged to a another hospital and less likely to be discharged home than non-Indigenous patients. [ABSTRACT FROM AUTHOR]

Objective: There is uncertainty about the optimal i.v. fluid volume and timing of vasopressor commencement in the resuscitation of patients with sepsis and hypotension. We aim to study current resuscitation practices in EDs in Australia and New Zealand (the Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis [ARISE FLUIDS] observational study). Methods: ARISE FLUIDS is a prospective, multicentre observational study in 71 hospitals in Australia and New Zealand. It will include adult patients presenting to the ED during a 30 day period with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation. We will obtain data on baseline demographics, clinical and laboratory variables, all i.v. fluid given in the first 24 h, vasopressor use, time to antimicrobial administration, admission to intensive care, organ failure and in‐hospital mortality. We will specifically describe (i) the volume of fluid administered at the following time points: when meeting eligibility criteria, in the first 6 h, at 24 h and prior to vasopressor commencement and (ii) the frequency and timing of vasopressor use in the first 6 h and at 24 h. Screening logs will provide reliable estimates of the proportion of ED patients meeting eligibility criteria for a subsequent randomised controlled trial. Discussion: This multicentre, observational study will provide insight into current haemodynamic resuscitation practices in patients with sepsis and hypotension as well as estimates of practice variation and patient outcomes. The results will inform the design and feasibility of a multicentre phase III trial of early haemodynamic resuscitation in patients presenting to ED with sepsis and hypotension. [ABSTRACT FROM AUTHOR]

Sepsis has recently been redefined as acute organ dysfunction due to infection. The ED plays a critical role in identifying patients with sepsis. This is challenging due to the heterogeneity of the syndrome, and the lack of an objective standard diagnostic test. While overall mortality rates from sepsis appear to be falling, there is an increasing burden of morbidity among survivors. This largely reflects the growing proportion of older patients with comorbid illnesses among those treated for sepsis. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified.Methods/design: The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support 'free days' to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups.Discussion: This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium.Trial Registration: Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016. [ABSTRACT FROM AUTHOR]

Background: The storage duration of platelet (PLT) units is limited to 5 to 7 days. This study investigates whether PLT storage duration is associated with patient outcomes in critically ill patients.Study Design and Methods: This study was a retrospective analysis of critically ill patients admitted to the intensive care unit (ICU) of two hospitals in Australia who received one or more PLT transfusions from 2008 to 2014. Storage duration was approached in several different ways. Outcome variables were hospital mortality and ICU-acquired infection. Associations between PLT storage duration and outcomes were evaluated using multiple logistic regression and also by Cox regression.Results: Among 2250 patients who received one or more PLT transfusions while in the ICU, the storage duration of PLTs was available for 64% of patients (1430). In-hospital mortality was 22.1% and ICU infection rate 7.2%. When comparing patients who received PLTs of a maximum storage duration of not more than 3, 4, or 5 days, there were no significant differences in baseline characteristics. After confounders were adjusted for, the storage duration of PLTs was not independently associated with mortality (4 days vs. ≤3 days, odds ratio [OR] 0.88, 95% confidence interval [CI] 0.59-1.30; 5 days vs. ≤3 days, OR 0.97, 95% CI 0.68-1.37) or infection (4 days vs. ≤3 days, OR 0.71, 95% CI 0.39-1.29; 5 days vs. ≤3 days, OR 1.11, 95% CI 0.67-1.83). Similar results were obtained regardless of how storage duration of PLTs was approached.Conclusions: In this large observational study in a heterogeneous ICU population, storage duration of PLTs was not associated with an increased risk of mortality or infection. [ABSTRACT FROM AUTHOR]

Importance: The Sepsis-3 Criteria emphasized the value of a change of 2 or more points in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, introduced quick SOFA (qSOFA), and removed the systemic inflammatory response syndrome (SIRS) criteria from the sepsis definition.Objective: Externally validate and assess the discriminatory capacities of an increase in SOFA score by 2 or more points, 2 or more SIRS criteria, or a qSOFA score of 2 or more points for outcomes among patients who are critically ill with suspected infection.Design, Setting, and Participants: Retrospective cohort analysis of 184 875 patients with an infection-related primary admission diagnosis in 182 Australian and New Zealand intensive care units (ICUs) from 2000 through 2015.Exposures: SOFA, qSOFA, and SIRS criteria applied to data collected within 24 hours of ICU admission.Main Outcomes and Measures: The primary outcome was in-hospital mortality. In-hospital mortality or ICU length of stay (LOS) of 3 days or more was a composite secondary outcome. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). Adjusted analyses were performed using a model of baseline risk determined using variables independent of the scoring systems.Results: Among 184 875 patients (mean age, 62.9 years [SD, 17.4]; women, 82 540 [44.6%]; most common diagnosis bacterial pneumonia, 32 634 [17.7%]), a total of 34 578 patients (18.7%) died in the hospital, and 102 976 patients (55.7%) died or experienced an ICU LOS of 3 days or more. SOFA score increased by 2 or more points in 90.1%; 86.7% manifested 2 or more SIRS criteria, and 54.4% had a qSOFA score of 2 or more points. SOFA demonstrated significantly greater discrimination for in-hospital mortality (crude AUROC, 0.753 [99% CI, 0.750-0.757]) than SIRS criteria (crude AUROC, 0.589 [99% CI, 0.585-0.593]) or qSOFA (crude AUROC, 0.607 [99% CI, 0.603-0.611]). Incremental improvements were 0.164 (99% CI, 0.159-0.169) for SOFA vs SIRS criteria and 0.146 (99% CI, 0.142-0.151) for SOFA vs qSOFA (P <.001). SOFA (AUROC, 0.736 [99% CI, 0.733-0.739]) outperformed the other scores for the secondary end point (SIRS criteria: AUROC, 0.609 [99% CI, 0.606-0.612]; qSOFA: AUROC, 0.606 [99% CI, 0.602-0.609]). Incremental improvements were 0.127 (99% CI, 0.123-0.131) for SOFA vs SIRS criteria and 0.131 (99% CI, 0.127-0.134) for SOFA vs qSOFA (P <.001). Findings were consistent for both outcomes in multiple sensitivity analyses.Conclusions and Relevance: Among adults with suspected infection admitted to an ICU, an increase in SOFA score of 2 or more had greater prognostic accuracy for in-hospital mortality than SIRS criteria or the qSOFA score. These findings suggest that SIRS criteria and qSOFA may have limited utility for predicting mortality in an ICU setting. [ABSTRACT FROM AUTHOR]

Background: Platelets are commonly transfused to critically ill patients. Reports suggest an association between platelet transfusion and infection. However, there is no large study to have determined whether platelet transfusion in critically ill patients is associated with hospital-acquired infection.Methods: We conducted a multi-centre study using prospectively maintained databases of two large academic intensive care units (ICUs) in Australia. Characteristics of patients who received platelets in ICUs between 2008 and 2014 were compared to those of patients who did not receive platelets. Association between platelet administration and infection (bacteraemia and/or bacteriuria) was modelled using multiple logistic regression and Cox regression, with blood components as time-varying covariates. A propensity covariate adjustment was also performed to verify results.Results: Of the 18,965 patients included, 2250 (11.9%) received platelets in ICU with a median number of 1 platelet unit (IQR 1-3) administered. Patients who received platelets were more severely ill at ICU admission (mean Acute Physiology and Chronic Health Evaluation III score 65 (SD 29) vs 52 (SD 25), p < 0.01) and had more comorbidities (31% vs 19%, p < 0.01) than patients without platelet transfusion. Invasive mechanical ventilation (87% vs 57%, p < 0.01) and renal replacement therapy (20% vs 4%, p < 0.01) were more frequently administered in patients receiving platelets than in patients without platelets. On univariate analysis, platelet transfusion was associated with hospital-acquired infection in the ICU (7.7% vs 1.4%, p < 0.01). After adjusting for confounders, including other blood components administered, patient severity, centre, year, and diagnosis category, platelet transfusions were independently associated with infection (adjusted OR 2.56 95% CI 1.98-3.31, p < 0.001). This association was also found in survival analysis with blood components as time-varying covariates (adjusted HR 1.85, 95% CI 1.41-2.41, p < 0.001) and when only bacteraemia was considered (adjusted OR 3.30, 95% CI 2.30-4.74, p <0.001). Platelet transfusions remained associated with infection after propensity covariate adjustment.Conclusions: After adjustment for confounders, including patient severity and other blood components, platelet transfusion was independently associated with ICU-acquired infection. Further research aiming to better understand this association and to prevent this complication is warranted. [ABSTRACT FROM AUTHOR]

Summary Background Critical care physicians recognise persistent critical illness as a specific syndrome, yet few data exist for the timing of the transition from acute to persistent critical illness. Defining the onset of persistent critical illness as the time at which diagnosis and illness severity at intensive care unit (ICU) arrival no longer predict outcome better than do simple pre-ICU patient characteristics, we measured the timing of this onset at a population level in Australia and New Zealand, and the variation therein, and assessed the characteristics, burden of care, and hospital outcomes of patients with persistent critical illness. Methods In this retrospective, population-based, observational study, we used data for ICU admission in Australia and New Zealand from the Australian and New Zealand Intensive Care Society Adult Patient Database. We included all patients older than 16 years of age admitted to a participating ICU. We excluded patients transferred from another hospital and those admitted to an ICU for palliative care or awaiting organ donation. The primary outcome was in-hospital mortality. Using statistical methods in evenly split development and validation samples for risk score development, we examined the ability of characteristics to predict in-hospital mortality. Findings Between Jan, 2000, and Dec, 2014, we studied 1 028 235 critically ill patients from 182 ICUs across Australia and New Zealand. Among patients still in an ICU, admission diagnosis and physiological derangements, which accurately predicted outcome on admission (area under the receiver operating characteristics curve 0·898 [95% CI 0·897–0·899] in the validation cohort), progressively lost their predictive ability and no longer predicted outcome more accurately than did simple antecedent patient characteristics (eg, age, sex, or chronic health status) after 10 days in the ICU, thus empirically defining the onset of persistent critical illness. This transition occurred between day 7 and day 22 across diagnosis-based subgroups and between day 6 and day 15 across risk-of-death-based subgroups. Cases of persistent critical illness accounted for only 51 509 (5·0%) of the 1 028 235 patients admitted to an ICU, but for 1 029 345 (32·8%) of 3 138 432 ICU bed-days and 2 197 108 (14·7%) of 14 961 693 hospital bed-days. Overall, 12 625 (24·5%) of 51 509 patients with persistent critical illness died and only 23 968 (46·5%) of 51 509 were discharged home. Interpretation Onset of persistent critical illness can be empirically measured at a population level. Patients with this condition consume vast resources, have high mortality, have much less chance of returning home than do typical ICU patients, and require dedicated future research. ICU clinicians should be aware that the risk of in-hospital mortality can change quickly over the first 2 weeks of an ICU course and be sure to incorporate such changes in their decision making and prognostication. Funding None. [ABSTRACT FROM AUTHOR]

Rationale: The ICU Mobility Scale (IMS) is a measure of mobility milestones in critically ill patients.Objectives: This study aimed to determine the validity and responsiveness of the IMS from a prospective cohort study of adults admitted to the intensive care unit (ICU).Methods: Construct and predictive validity were assessed by comparing IMS values at ICU discharge in 192 patients to other variables using Spearman rank correlation coefficient, Mann-Whitney U tests, and logistic regression. Responsiveness was assessed using change over time, effect size, floor and ceiling effects, and percentage of patients showing change.Measurements and Main Results: The IMS at ICU discharge demonstrated a moderate correlation with muscle strength (r = 0.64, P < 0.001). There was a significant difference between the IMS at ICU discharge in patients with ICU-acquired weakness (median, 4.0; interquartile range, 3.0-5.0) compared with patients without (median, 8.0; interquartile range, 5.0-8.0; P < 0.001). Increasing IMS values at ICU discharge were associated with survival to 90 days (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14-1.66) and discharge home (OR, 1.16; 95% CI, 1.02-1.32) but not with return to work at 6 months (OR, 1.09; 95% CI, 0.92-1.28). The IMS was responsive with a significant change from study enrollment to ICU discharge (d = 0.8, P < 0.001), with IMS values increasing in 86% of survivors during ICU admission. No substantial floor (14% scored 0) or ceiling (4% scored 10) effects were present at ICU discharge.Conclusions: Our findings support the validity and responsiveness of the IMS as a measure of mobility in the ICU. [ABSTRACT FROM AUTHOR]

Importance: Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation.Objective: To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation.Design, Setting, and Participants: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded.Interventions: Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician.Main Outcomes and Measures: Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori.Results: Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P < .001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P = .01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P = .007).Conclusions and Relevance: Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.Trial Registration: clinicaltrials.gov Identifier: NCT01151865. [ABSTRACT FROM AUTHOR]

Background: Over the last two decades, there have been several improvements in the management of diabetes. Whether this has impacted on the epidemiology and outcome of diabetic ketoacidosis (DKA) requiring intensive care unit (ICU) admission is unknown.Method: This was a retrospective study of 8533 patients with the diagnosis of DKA admitted to 171 ICUs in Australia and New Zealand between 2000-2013 with separate independent analysis of those on established insulin (Group I) or not on insulin (Group NI) at the time of hospitalisation.Results: Of the 8553 patients, 2344 (27%) were identified as NI. The incidence of ICU admission with DKA progressively increased fivefold from 0.97/100,000 (95% CI 0.84-1.10) in 2000 to 5.3/100,000 (95% CI 4.98-5.53) in 2013 (P<0.0001), with the proportions between I and NI remaining stable. Rising incidences were observed mainly in rural and metropolitan hospitals (P<0.01). In the first 24 hours in the ICU, mean worst pH increased over the study period from 7.20±0.02 to 7.24±0.01 (P<0.0001), and mean lowest plasma bicarbonate from 12.1±6.6 to 13.8±6.6 mmol/L (P<0.0001). In contrast, mean highest plasma glucose decreased from 26.3±14 to 23.2±13.1 mmol/L (P<0.0001). Hospital mortality was significantly greater in NI as compared to I (2.4% vs 1.1%, P>0.0001). Elevated plasma urea in the first 24 hours (≥25 mmol/L, adjusted odds ratio 20.6 (6.54-65.7), P<0.0001) was the strongest individual predictor of mortality.Conclusions: The incidence of ICU admission of patients with DKA in Australia and New Zealand has increased fivefold over the last decade, with a significant proportion of patients not on insulin at presentation. Overall physiological status in the first 24 hours of ICU admission has progressively improved and mortality rates have remained stable. However, DKA patients not on established insulin therapy at presentation had significantly worse outcomes. This notion has epidemiologic, diagnostic and management implications. [ABSTRACT FROM AUTHOR]

RATIONALE: Previous studies suggested an association between after-hours intensive care unit (ICU) discharge and increased hospital mortality. Their retrospective design and lack of correction for patient factors present at the time of discharge make this association problematic. OBJECTIVES: To determine factors independently associated with mortality after ICU discharge. METHODS: This was a prospective, multicenter, binational observational study involving 40 ICUs in Australia and New Zealand. Participants were consecutive adult patients discharged alive from the ICU between September 2009 and February 2010. MEASUREMENTS AND MAIN RESULTS: We studied 10,211 patients discharged alive from the ICU. Median age was 63 years (interquartile range, 49-74), 6,224 (61%) were male, 5,707 (56%) required mechanical ventilation, and their median Acute Physiology and Chronic Health Evaluation III risk of death was 9% (interquartile range, 3-25%). A total of 8,539 (83.6%) patients were discharged in-hours (06:00-18:00) and 1,672 (16.4%) after-hours (18:00-06:00). Of these, 408 (4.8%) and 124 (7.4%), respectively, subsequently died in hospital (P < 0.001). After risk adjustment for markers of illness severity at time of ICU discharge including limitations of medical therapy (LOMT) orders, the time of discharge was no longer a significant predictor of mortality. The presence of a LOMT order was the strongest predictor of death (odds ratio, 35.4; 95% confidence interval, 27.5-45.6). CONCLUSIONS: In this large, prospective, multicenter, binational observational study, we found that patient status at ICU discharge, particularly the presence of LOMT orders, was the chief predictor of hospital survival. In contrast to previous studies, the timing of discharge did not have an independent association with mortality. [ABSTRACT FROM AUTHOR]

IMPORTANCE Severe sepsis and septic shock are major causes of mortality in intensive care unit (ICU) patients. It is unknown whether progress has been made in decreasing their mortality rate. OBJECTIVE To describe changes in mortality for severe sepsis with and without shock in ICU patients. DESIGN, SETTING, AND PARTICIPANTS Retrospective, observational study from 2000 to 2012 including 101 064 patients with severe sepsis from 171 ICUs with various patient case mix in Australia and New Zealand. MAIN OUTCOMES AND MEASURES Hospital outcome (mortality and discharge to home, to other hospital, or to rehabilitation). RESULTS Absolute mortality in severe sepsis decreased from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12 512; P < .001), representing an overall decrease of 16.7% (95% CI, 14.8%-18.6%), an annual rate of absolute decrease of 1.3%, and a relative risk reduction of 47.5% (95% CI, 44.1%-50.8%). After adjusted analysis, mortality decreased throughout the study period with an odds ratio (OR) of 0.49 (95% CI, 0.46-0.52) in 2012, using the year 2000 as the reference (P < .001). The annual decline in mortality did not differ significantly between patients with severe sepsis and those with all other diagnoses (OR, 0.94 [95% CI, 0.94-0.95] vs 0.94 [95% CI, 0.94-0.94]; P = .37). The annual increase in rates of discharge to home was significantly greater in patients with severe sepsis compared with all other diagnoses (OR, 1.03 [95% CI, 1.02-1.03] vs 1.01 [95% CI, 1.01-1.01]; P < .001). Conversely, the annual increase in the rate of patients discharged to rehabilitation facilities was significantly less in severe sepsis compared with all other diagnoses (OR, 1.08 [95% CI, 1.07-1.09] vs 1.09 [95% CI, 1.09-1.10]; P < .001). In the absence of comorbidities and older age, mortality was less than 5%. CONCLUSIONS AND RELEVANCE In critically ill patients in Australia and New Zealand with severe sepsis with and without shock, there was a decrease in mortality from 2000 to 2012. These findings were accompanied by changes in the patterns of discharge to home, rehabilitation, and other hospitals. [ABSTRACT FROM AUTHOR]

Purpose: It is unclear if blood pressure targets for patients with shock should be adjusted to pre-morbid levels. We aimed to investigate mean deficit between the achieved mean perfusion pressure (MPP) in vasopressor-treated patients and their estimated basal (resting) MPP, and assess whether MPP deficit has any association with subsequent acute kidney injury (AKI). Materials and Methods: Fifty-one consecutive, non-trauma patients, aged ⩾40 years, with ⩾2 organ dysfunction and requiring vasopressor ⩾4 hours were observed at an academic intensive care unit. Mean MPP deficit [=%(basal MPP - achieved MPP)/basal MPP] and % time spent with >20% MPP deficit were assessed during initial 72 vasopressor hours (T0-T72) for each patient. Results: Achieved MPP was unrelated to basal MPP (P = .99). Mean MPP deficit was 18%(95%CI 15-21). Patients spent 48% (95% CI 39-57) time with >20% MPP deficit. Despite similar risk scores at T0, subsequent AKI (⩾2 RIFLE class increase from T0) occurred more frequently in patients with higher (Nmedian) MPP deficit compared to patients with lower MPP deficit (56% vs 28%; P = .045). Incidence of subsequent AKI was also higher among patients who spent greater % time with >20% MPP deficit (P = .04). Conclusions: Achieved blood pressure during vasopressor therapy had no relationship to the pre-morbid basal level. This resulted in significant and varying degree of relative hypotension (MPP deficit), which could be a modifiable risk factor for AKI in patients with shock. [ABSTRACT FROM AUTHOR]

Purpose: Comparison of illness severity for intensive care unit populations assessed according to different scoring systems should increase our ability to compare and meta-analyze past and future trials but is currently not possible. Accordingly, we aimed to establish a methodology to translate illness severity scores obtained from one system into another. Materials and methods: Using the Australian and New-Zealand intensive care adult patient database, we obtained simultaneous admission Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores and Simplified Acute Physiology Score (SAPS) II in 634428 patients admitted to 153 units between 2001 and 2010. We applied linear regression analyses to create models enabling translation of one score into another. Sensitivity analyses were performed after removal of diagnostic categories excluded from the original APACHE database, after matching for similar risk of death, after splitting data according to country of origin (Australia or New Zealand) and after splitting admissions occurring before or after 2006. Results: The translational models were APACHE III = 3.08 × APACHE II + 5.75; APACHE III = 1.47 × SAPS II + 8.6; and APACHE II = 0.36 × SAPS II + 4.4. The area under the receiver operating curve for mortality prediction was 0.853 (95% confidence interval, 0.851-0.855) for the "APACHE II derived APACHE III" score and 0.854 (0.852-0.855) for the "SAPS II derived APACHE III" vs 0.854 (0.852- 0.855) for the original APACHE III score. Similarly, it was 0.841 (0.839-0.843) for the "SAPS II derived APACHE II score" vs 0.842 (0.840-0.843) for the original APACHE II score. Correlation coefficients as well as intercepts remained very similar in all subgroups analyses. Conclusions: Simple and robust translational formulas can be developed to allow clinicians to compare illness severity between studies involving critically ill patients. Further studies in other countries and health care systems are needed to confirm the generalizability of these results. [ABSTRACT FROM AUTHOR]

Objective To estimate the ability of commonly measured laboratory variables to predict imminent (within the same or next calendar day) medical emergency team ( MET) calls, ICU admission or death. Methods We performed a retrospective observational study of ED patients. We estimated the ability of each laboratory variable or combination of variables together with patient age to predict imminent MET calls, ICU admission or death. We externally validated our findings in patients from a different hospital. Results We studied 160 341 batches in 71 453 ED patients (average age: 59.9 ± 22.1 years) for a total of 1 million individual measurements. There were 341 MET calls, 160 ICU admissions from the wards and 858 deaths. Multivariable modelling achieved a receiver operating characteristic area under the curve (ROC-AUC) of 0.69 (95% CI 0.63-0.74) for imminent MET call with prediction occurring a mean of 11.9 h before the call. Additionally, it achieved a ROC-AUC of 0.82 (95% CI 0.73-0.87) for imminent ICU admission. Finally, it achieved a ROC-AUC of 0.90 (95% CI 0.87-0.91) for imminent death. When tested using an additional 37 367 batches from a cohort of 21 430 ED patients from a second teaching hospital, the multivariate model achieved a ROC-AUC of 0.70 (95% CI 0.66-0.73) for imminent MET call, a ROC-AUC of 0.84 (95% CI 0.78-0.90) for imminent ICU admission. Finally, it achieved a ROC-AUC of 0.89 (95% CI 0.86-0.91) for imminent death. Conclusions Commonly performed laboratory tests can help predict imminent MET calls, ICU admission or death in ED patients. Prospective investigations of the clinical utility of such predictions appear desirable. [ABSTRACT FROM AUTHOR]

The article discusses in-hospital cardiac arrests and the medical emergency team (MET) model. An overview of the MET model and its use in Australian hospitals in identifying potential ward patients for cardiac arrest is presented. It discusses findings on the efficacy of the MET approach in responding to care for deteriorating patients and highlights the need for improvements through audit of the clinical causes of MET calls.

Background: There is limited information on changes in the epidemiology and outcome of patients with asthma admitted to intensive care units (ICUs) in the last decade. A database sampling intensive care activity in hospitals throughout Australia offers the opportunity to examine these changes. Methods: The Australian and New Zealand Intensive Care Society Adult Patient Database was examined for all patients with asthma admitted to ICUs from 1996 to 2003. Demographic, physiological and outcome information was obtained and analysed from 22 hospitals which had submitted data continuously over this period. Results: ICU admissions with the primary diagnosis of asthma represented 1899 (1.5%) of 126 906 admissions during the 8-year period. 36.1% received mechanical ventilation during the First 24 h. The overall incidence of admission to CU fell from 1 .9% in 1996 to 1 .1% in 2003 (p<0.001). Overall hospital mortality was 3.2%. There was a significant decline in mortality from a peak of 4.7% in 1 997 to 1 .1% in 2003 (p=0.014). This was despite increasing severity of illness (as evidenced by an increasing predicted risk of death derived from the APACHE II score) over the 8-year period (p=0.002). Conclusions: There has been a significant decline in the incidence of asthma requiring ICU admission between 1996 and 2003 among units sampled by the Australian and New Zealand Intensive Care Society Adult Patient Database. The mortality of these patients has also decreased over time and is lower than reported in other studies. [ABSTRACT FROM AUTHOR]