Medicine (Austin & Northern Health) - Research Publications

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    Comparison of Thromboelastography and Conventional Coagulation Tests in Patients With Severe Liver Disease
    Lloyd-Donald, P ; Vasudevan, A ; Angus, P ; Gow, P ; Martensson, J ; Glassford, N ; Eastwood, GM ; Hart, GK ; Jones, D ; Weinberg, L ; Bellomo, R (SAGE PUBLICATIONS INC, 2020-06-03)
    OBJECTIVE: Thromboelastography (TEG) may provide rapid and clinically important coagulation information in acutely ill patients with chronic liver disease (CLD). Our objective was to describe the relationship between TEG and conventional coagulation tests (CCTs), which has not been previously explored in this population. METHODS: In acutely ill patients with severe CLD (Child-Pugh score > 9, category C), we conducted a prospective observational study investigating coagulation assessment as measured by both CCTs and TEG. We used quantile regression to explore 30 associations between TEG parameters and corresponding CCTs. We compared TEG and CCT measures of coagulation initiation, clot formation, clot strength, and fibrinolysis. RESULTS: We studied 34 patients on a total of 109 occasions. We observed inconsistent associations between TEG and CCT measures of coagulation initiation: TEG (citrated kaolin [CK] assay) standard reaction time and international normalized ratio: R 2 = 0.117 (P = .044). Conversely, there were strong and consistent associations between tests of clot formation: TEG (CK) kinetics time and fibrinogen: R 2 = 0.202 (P < .0001) and TEG (CK) α angle and fibrinogen 0.263 (P < .0001). We also observed strong associations between tests of clot strength, specifically TEG MA and conventional fibrinogen levels, across all TEG assays: MA (CK) and fibrinogen: R 2 = 0.485 (P < .0001). There were no associations between TEG and D-dimer levels. CONCLUSIONS: In acutely ill patients with CLD, there are strong and consistent associations between TEG measures of clot formation and clot strength and conventional fibrinogen levels. There are weak and/or inconsistent associations between TEG and all other conventional measures of coagulation.
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    The nature and discriminatory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury
    Glassford, NJ ; Schneider, AG ; Xu, S ; Eastwood, GM ; Young, H ; Peck, L ; Venge, P ; Bellomo, R (SPRINGER, 2013-10)
    BACKGROUND: Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients. METHODS: We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL(E1) and uNGAL(E2)] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of >25 μmol/L. MEASUREMENTS AND MAIN RESULTS: Bland-Altman analysis demonstrated that, despite correlating well (r = 0.988), uNGAL and uNGAL(E1) were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95% CI 82.03-450.44 ng/mg creatinine; limits of agreement: -1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] ≤0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction. CONCLUSIONS: uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker.
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    Current ventilation practice during general anaesthesia: a prospective audit in Melbourne, Australia
    Karalapillai, D ; Weinberg, L ; Galtieri, J ; Glassford, N ; Eastwood, G ; Darvall, J ; Geertsema, J ; Bangia, R ; Fitzgerald, J ; Tuong, P ; OHallaran, L ; Cocciante, A ; Watson, S ; Story, D ; Bellomo, R (BMC, 2014-10-01)
    BACKGROUND: Recent evidence suggests that the use of low tidal volume ventilation with the application of positive end-expiratory pressure (PEEP) may benefit patients at risk of respiratory complications during general anaesthesia. However current Australian practice in this area is unknown. METHODS: To describe current practice of intraoperative ventilation with regard to tidal volume and application of PEEP, we performed a multicentre audit in patients undergoing general anaesthesia across eight teaching hospitals in Melbourne, Australia. RESULTS: We obtained information including demographic characteristics, type of surgery, tidal volume and the use of PEEP in a consecutive cohort of 272 patients. The median age was 56 (IQR 42-69) years; 150 (55%) were male. Most common diagnostic groups were general surgery (31%), orthopaedic surgery (20%) and neurosurgery (9.6%). Mean FiO2 was 0.6 (IQR 0.5-0.7). Median tidal volume was 500 ml (IQR 450-550). PEEP was used in 54% of patients with a median value of 5.0 cmH2O (IQR 4.0-5.0) and median tidal volume corrected for predicted body weight was 9.5 ml/kg (IQR 8.5-10.4). Median peak inspiratory pressure was 18 cmH2O (IQR 15-22). In a cohort of patients considered at risk for respiratory complications, the median tidal volume was still 9.8 ml/kg (IQR 8.6-10.7) and PEEP was applied in 66% of patients with a median value of 5 cmH20 (IQR 4-5). On multivariate analyses positive predictors of tidal volume size included male sex (p < 0.01), height (p = 0.04) and weight (p < 0.001). Positive predictors of the use of PEEP included surgery in a tertiary hospital (OR = 3.11; 95% CI: 1.05 to 9.23) and expected prolonged duration of surgery (OR = 2.47; 95% CI: 1.04 to 5.84). CONCLUSION: In mechanically ventilated patients under general anaesthesia, tidal volume was high and PEEP was applied to the majority of patients, but at modest levels. The findings of our study suggest that the control groups of previous randomized controlled trials do not closely reflect the practice of mechanical ventilation in Australia.
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    Liberal Versus Conventional Glucose Targets in Critically III Diabetic Patients: An Exploratory Safety Cohort Assessment
    Di Muzio, F ; Presello, B ; Glassford, NJ ; Tsuji, IY ; Eastwood, GM ; Deane, AM ; Ekinci, EI ; Bellomo, R ; Martensson, J (LIPPINCOTT WILLIAMS & WILKINS, 2016-09)
    OBJECTIVES: To assess the feasibility, safety, and impact on relative hypoglycemia of liberal versus conventional blood glucose concentration targets in critically ill diabetic patients. DESIGN: Prospective, open-label, sequential-period exploratory study. SETTING: A 22-bed multidisciplinary ICU of a tertiary care hospital in Australia. PATIENTS: Eighty adult diabetic patients, 40 from the conventional before period and 40 from the liberal after period. INTERVENTIONS: Blood glucose concentration targets were 6-10 mmol/L during the before period and 10-14 mmol/L during the after period. MEASUREMENTS AND MAIN RESULTS: We used admission glycated hemoglobin to estimate premorbid baseline blood glucose concentration. We defined glycemic distance as the difference between blood glucose concentration in ICU and baseline blood glucose concentration. During the first 48 ICU hours, we recorded absolute (blood glucose concentration, < 3.9 mmol/L) and relative (glycemic distance, > 30% below baseline) hypoglycemia rates, insulin administration, and outcomes. The groups had similar baseline characteristics. We observed a negative glycemic distance in 248 of 488 blood glucose concentrations (50.8%) during the before period and 164 of 485 (33.8%) during the after period (p < 0.001). We detected relative hypoglycemia in 20 (50.0%) and nine (22.5%) patients in the before and after periods, respectively (p = 0.01). On day 1, 50.0% and 16.7% received insulin in the before and after periods (p = 0.007). ICU and hospital length of stay and mortality were similar between groups. CONCLUSIONS: In a safety cohort of critically ill diabetic patients, a blood glucose concentration target of 10-14 mmol/L resulted in fewer episodes of negative glycemic distance or relative hypoglycemia and reduced insulin administration compared with a target of 6-10 mmol/L.