Critical Care - Research Publications
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ItemThe association between peri-operative acute risk change (ARC) and long-term survival after cardiac surgery(WILEY, 2017-12)Acute risk change has been described as the difference in calculated mortality risk between the pre-operative and postoperative periods of cardiac surgery. We aimed to assess whether this was associated with long-term survival after cardiac surgery. We retrospectively analysed 22,570 cardiac surgical patients, with minimum and maximum follow-up of 1.0 and 6.7 years. Acute risk change was calculated as the arithmetic difference between pre- and postoperative mortality risk. 'Rising risk' represented an increase in risk from pre- to postoperative phase. The primary outcome was one-year mortality. Secondary outcomes included mortality at 3 and 5 years and time to death. Univariable and multivariable analyses were undertaken to examine the relationship between acute risk change and outcomes. Rising risk was associated with higher mortality (5.6% vs. 3.5%, p < 0.001). After adjusting for baseline risk, rising risk was independently associated with increased 1-year mortality (OR 2.6, 95%CI 2.2-3.0, p < 0.001). The association of rising risk with long-term survival was greatest in patients with highest baseline risk. Cox regression confirmed rising risk was associated with shorter time to death (HR 1.86, 1.68-2.05, p < 0.001). Acute risk change may represent peri-operative clinical events in combination with unmeasured patient risk and noise. Measuring risk change could potentially identify patterns of events that may be amenable to investigation and intervention. Further work with case review, and risk scoring with shared variables, may identify mechanisms, including the interaction between miscalibration of risk and true differences in peri-operative care.
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ItemRenal effects of an emergency department chloride-restrictive intravenous fluid strategy in patients admitted to hospital for more than 48 hours(WILEY, 2017-12)OBJECTIVE: Patients commonly receive i.v. fluids in the ED. It is still unclear whether the choice of i.v. fluids in this setting influences renal or patient outcomes. We aimed to assess the effects of restricting i.v. chloride administration in the ED on the incidence of acute kidney injury (AKI). METHODS: We conducted a before-and-after trial with 5008 consecutive ED-treated hospital admissions in the control period and 5146 consecutive admissions in the intervention period. During the control period (18 February 2008 to 17 August 2008), patients received standard i.v. fluids. During the intervention period (18 February 2009 to 17 August 2009), we restricted all chloride-rich fluids. We used the Kidney Disease: Improving Global Outcomes (KDIGO) staging to define AKI. RESULTS: Stage 3 of KDIGO-defined AKI decreased from 54 (1.1%; 95% confidence interval [CI] 0.8-1.4) to 30 (0.6%; 95% CI 0.4-0.8) (P = 0.006). The rate of renal replacement therapy did not change, from 13 (0.3%; 95% CI 0.2-0.4) to 8 (0.2%; 95% CI 0.1-0.3) (P = 0.25). After adjustment for relevant covariates, liberal chloride therapy remained associated with a greater risk of KDIGO stage 3 (hazard ratio 1.82; 95% CI 1.13-2.95; P = 0.01). On sensitivity assessment after removing repeat admissions, KDIGO stage 3 remained significantly lower in the intervention period compared with the control period (P = 0.01). CONCLUSION: In a before-and-after trial, a chloride-restrictive strategy in an ED was associated with a significant decrease in the incidence of stage 3 of KDIGO-defined AKI.
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ItemDuration of platelet storage and outcomes of critically ill patients(WILEY, 2017-03)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.
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ItemCharacteristics, incidence and outcome of patients admitted to intensive care because of pulmonary embolism(WILEY, 2017-02)BACKGROUND AND OBJECTIVE: Despite the clinical significance of major pulmonary embolism (PE), little is known about patients with a presentation severe enough to lead to intensive care unit (ICU) admission and nothing is known about PE requiring mechanical ventilation (MV). We aimed to examine the characteristics, incidence and outcome of patients with PE as their reason for ICU admission. METHODS: We performed a retrospective, cross-sectional study of patients admitted to Australia's and New Zealand's ICUs because of PE from 2005 to 2013. We compared survivors with non-survivors and mechanically ventilated with non-ventilated patients. We analysed variations in incidence and mortality over time. RESULTS: We studied 2797 patients. PE accounted for 0.3% of all ICU admissions and had a population incidence of 11 cases/million people/year, which increased significantly during the study period (P < 0.0001). Co-morbidities were common (24.1%) and the emergency department was the most common admission source (49.1%). However, patients who died were more commonly admitted from the wards (P < 0.0001). Overall mortality was 14.1% but reached 41.0% in patients requiring MV (P < 0.0001). Illness severity-adjusted mortality rate did not change during the study period. CONCLUSION: The incidence of PE requiring admission to ICU has increased over time; its mortality rate remains high, especially in mechanically ventilated patients, and its prognosis has not improved over time. Our findings imply the need for focused research in this high-risk patient group.
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ItemThe haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial(WILEY, 2016-04)AIM: The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. METHODS: We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. RESULTS: Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). CONCLUSIONS: I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.
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ItemNo Preview AvailableCost-Effectiveness of Erythropoietin in Traumatic Brain Injury: A Multinational Trial-Based Economic Analysis(MARY ANN LIEBERT, INC, 2019-09-01)The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p < 0.001) higher in the EPO group, with an adjusted QALY increment of 0.014 (0.000-0.028; p = 0.04). Mean unadjusted costs (95% CI) were $US5668 (-9191 to -2144; p = 0.002) lower in the treatment group; controlling for baseline IMPACT-TBI score and regional heterogeneity reduced this difference to $2377 (-12,446 to 7693; p = 0.64). For a willingness-to-pay threshold of $US50,000 per QALY, 71.8% of replications were considered cost-effective. Therefore, we did not find evidence that EPO was significantly cost-effective in the treatment of moderate or severe TBI at 6-month follow-up.
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ItemNo Preview AvailableVenous thromboembolic events in critically ill traumatic brain injury patients(SPRINGER, 2017-03)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.
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ItemCharacteristics and outcomes of patients with acute liver failure admitted to Australian and New Zealand intensive care units(WILEY, 2019-07)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.
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ItemThe Australasian Resuscitation In Sepsis Evaluation: FLUid or vasopressors In Emergency Department Sepsis, a multicentre observational study (ARISE FLUIDS observational study): Rationale, methods and analysis plan(WILEY, 2019-02)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.
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ItemTrauma-related admissions to intensive care units in Australia: the influence of Indigenous status on outcomes(WILEY, 2019-06)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.