Medicine (Austin & Northern Health) - Research Publications
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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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ItemHospital-acquired complications in intensive care unit patients with diabetes: A before-and-after study of a conventional versus liberal glucose control protocol(WILEY, 2019-07)BACKGROUND: Critically ill patients with diabetes mellitus (DM) are at increased risk of in-hospital complications and the optimal glycemic target for such patients remains unclear. A more liberal approach to glucose control has recently been suggested for patients with DM, but uncertainty remains regarding its impact on complications. METHODS: We aimed to test the hypothesis that complications would be more common with a liberal glycemic target in ICU patients with DM. Thus, we compared hospital-acquired complications in the first 400 critically ill patients with DM included in a sequential before-and-after trial of liberal (glucose target: 10-14 mmol/L) vs conventional (glucose target: 6-10 mmol/L) glucose control. RESULTS: Of the 400 patients studied, 165 (82.5%) patients in the liberal and 177 (88.5%) in the conventional-control group were coded for at least one hospital-acquired complication (P = 0.09). When comparing clinically relevant complications diagnosed between ICU admission and hospital discharge, we found no difference in the odds for infectious (adjusted odds ratio [aOR] for liberal-control: 1.15 [95% CI: 0.68-1.96], P = 0.60), cardiovascular (aOR 1.40 [95% CI: 0.63-3.12], P = 0.41) or neurological complications (aOR: 1.07 [95% CI: 0.61-1.86], P = 0.81), acute kidney injury (aOR 0.83 [95% CI: 0.43-1.58], P = 0.56) or hospital mortality (aOR: 1.09 [95% CI: 0.59-2.02], P = 0.77) between the liberal and the conventional-control group. CONCLUSION: In this prospective before-and-after study, liberal glucose control was not associated with an increased risk of hospital-acquired infectious, cardiovascular, renal or neurological complications in critically ill patients with diabetes.
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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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ItemOutcome of Acetaminophen-Induced Acute Liver Failure Managed Without Intracranial Pressure Monitoring or Transplantation(WILEY, 2019-01)Acetaminophen-induced acute liver failure (ALF) may require emergency liver transplantation (LT) in the presence of specific criteria, and its management may also include intracranial pressure (ICP) monitoring in selected patients at high risk of cerebral edema. We aimed to test the hypothesis that management of such patients without ICP monitoring or LT would yield outcomes similar to those reported with conventional management. We interrogated a database of all patients treated in an intensive care unit for acetaminophen-induced ALF between November 2010 and October 2016 and obtained relevant information from electronic medical records. We studied 64 patients (58 females) with a median age of 38 years. Such patients had a high prevalence of depression, substance abuse, or other psychiatric disorders and had ingested a median acetaminophen dose of 25 g. No patient received ICP monitoring or LT. Overall, 51 (79.7%) patients survived. Of the 42 patients who met King's College Hospital (KCH) criteria, 29 (69.0%) survived without transplantation. There were 45 patients who developed severe hepatic encephalopathy, and 32 (71.1%) of these survived. Finally, compared with the KCH criteria, the current UK Registration Criteria for Super-Urgent Liver Transplantation (UKRC) for super-urgent LT had better sensitivity (92.3%) and specificity (80.4%) for hospital mortality. In conclusion, in a center applying a no ICP monitoring and no LT approach to the management of acetaminophen-induced ALF, during a 6-year period, overall survival was 79.7%, and for patients fulfilling KCH criteria, it was 69.0%, which were both higher than for equivalent patients treated with conventional management as reported in the literature. Finally, the current UKRC may be a better predictor of hospital mortality in this patient population.