Medicine (Austin & Northern Health) - Research Publications

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    Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest
    Eastwood, G ; Nichol, AD ; Hodgson, C ; Parke, RL ; McGuinness, S ; Nielsen, N ; Bernard, S ; Skrifvars, MB ; Stub, D ; Taccone, FS ; Archer, J ; Kutsogiannis, D ; Dankiewicz, J ; Lilja, G ; Cronberg, T ; Kirkegaard, H ; Capellier, G ; Landoni, G ; Horn, J ; Olasveengen, T ; Arabi, Y ; Chia, YW ; Markota, A ; Haenggi, M ; Wise, MP ; Grejs, AM ; Christensen, S ; Munk-Andersen, H ; Granfeldt, A ; Andersen, GO ; Qvigstad, E ; Flaa, A ; Thomas, M ; Sweet, K ; Bewley, J ; Backlund, M ; Tiainen, M ; Iten, M ; Levis, A ; Peck, L ; Walsham, J ; Deane, A ; Ghosh, A ; Annoni, F ; Chen, Y ; Knight, D ; Lesona, E ; Tlayjeh, H ; Svensek, F ; McGuigan, PJ ; Cole, J ; Pogson, D ; Hilty, MP ; During, JP ; Bailey, MJ ; Paul, E ; Ady, B ; Ainscough, K ; Hunt, A ; Monahan, S ; Trapani, T ; Fahey, C ; Bellomo, R (MASSACHUSETTS MEDICAL SOC, 2023-07-06)
    BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).
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    Reduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients
    Bitker, L ; Patel, SK ; Bittar, I ; Eastwood, GM ; Bellomo, R ; Burrell, LM (AUSTRALASIAN MED PUBL CO LTD, 2020-12)
    Objective: Angiotensin-converting enzyme 2 activity reflects non-classical renin-angiotensin system upregulation. We assessed the association of urinary angiotensin-converting enzyme 2 (uACE2) activity with acute kidney injury (AKI). Design, setting and participants: A prospective observational study in which we measured uACE2 activity in 105 critically ill patients at risk of AKI. We report AKI stage 2 or 3 at 12 hours of urine collection (AKI12h) and AKI stage 2 or 3 at any time during intensive care unit stay in patients free from any stage of AKI at inclusion (AKIICU). AKI prediction was assessed using area under the receiver-operating characteristics curve (AUROC) and net reclassification indices (NRIs). Main outcome measure: AKI stage 2 or 3 at 12 hours of urine collection. Results: Within 12 hours of inclusion, 32 of 105 patients (30%) had developed AKI12h. Corrected uACE2 activity was significantly higher in patients without AKI12h compared with those with AKI12h (median [interquartile range], 13 [6-24] v 7 [4-10] pmol/min/mL per mmol/L of urine creatinine; P < 0.01). A 10-unit increase in uACE2 was associated with a 28% decrease in AKI12h risk (odds ratio [95% CI], 0.72 [0.46-0.97]). During intensive care unit admission, 39 of 76 patients (51%) developed AKIICU. uACE2 had an AUROC for the prediction of AKI12h of 0.68 (95% CI, 0.57-0.79), and correctly reclassified 28% of patients (positive NRI) to AKI12h. Patients with uACE2 > 8.7 pmol/min/mL per mmol/L of urine creatinine had a significantly lower risk of AKIICU on log-rank analysis (52% v 84%; P < 0.01). Conclusions: Higher uACE2 activity was associated with a decreased risk of AKI stage 2 or 3. Our findings support future evaluations of the role of the non-classical renin-angiotensin system during AKI.
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    Subsegmental pulmonary embolism and anticoagulant therapy: the impact of clinical context
    Dahan, A ; Farina, S ; Holmes, NE ; Kachel, S ; McDonald, CF ; Lewis, JE ; Marhoon, N ; Yanase, F ; Yang, N ; Bellomo, R (WILEY, 2023-08)
    BACKGROUND: Anticoagulation for subsegmental pulmonary embolism (SSPE) is controversial. AIM: To assess the impact of clinical context on anticoagulation and outcomes of SSPE. METHODS: We electronically searched computed tomography pulmonary angiogram reports to identify SSPE. We extracted demographic, risk factor, investigations and outcome data from the electronic medical record. We stratified patients according to anticoagulation and no anticoagulation. RESULTS: From 1 January 2017 to 31 December 2019, we identified 166 patients with SSPE in 5827 pulmonary angiogram reports. Of these, 123 (74%) received anticoagulation. Compared with non-anticoagulated patients, such patients had a different clinical context: higher rates of previous venous thromboembolism (11% vs 0%; P = 0.019), more recent surgery (26% vs 9%; P = 0.015), more elevated serum D-dimer (22% vs 5%; P = 0.004), more lung parenchymal abnormalities (76% vs 61%; P = 0.037) and were almost twice as likely to require inpatient care (76% vs 42%; P < 0.001). Such patients also had twice the all-cause mortality at 1 year (32% vs 16%). CONCLUSIONS: SSPE is diagnosed in almost 3% of pulmonary angiograms and is associated with high mortality, regardless of anticoagulation, due to coexistent disease processes rather than SSPE. Anticoagulation appears dominant but markedly affected by the clinical context of risk factors, alternative indications and illness severity. Thus, the controversy is partly artificial because anticoagulation after SSPE is clinically contextual with SSPE as only one of several factors.
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    Estimating baseline kidney function in hospitalized adults with acute kidney injury
    Larsen, T ; See, EJ ; Holmes, N ; Bellomo, R (WILEY, 2022-07)
    AIM: Baseline serum creatinine values are required to diagnose acute kidney injury but are often unavailable. We evaluated four conventional equations to estimate creatinine. We then developed and validated a new equation corrected by age and gender. METHODS: We retrospectively examined adults who, at first hospital admission, had available baseline creatinine data and developed acute kidney injury ≥24 h after admission. We split the study population: 50% (derivation) to develop a new linear equation and 50% (validation) to compare against conventional equations for bias, precision, and accuracy. We stratified analyses by age and gender. RESULTS: We studied 3139 hospitalized adults (58% male, median age 71). Conventional equations performed poorly in bias and accuracy in patients aged <60 or ≥75 (68% of the study population). The new linear equation had less bias and more accuracy. There were no clinically significant differences in precision. The median (95% confidence interval) difference in creatinine values estimated via the new equation minus measured baselines was 0.9 (-3.0, 5.9) and -0.5 (-7.0, 3.7) μmol/L in female patients 18-60 and 75-100, and -1.5 (-4.2, 2.2) and -7.8 (-12.7, -3.6) μmol/L in male patients 18-60 and 75-100, respectively. The new equation improved reclassification of KDIGO AKI stages compared to the MDRD II equation by 5.0%. CONCLUSION: Equations adjusted for age and gender are less biased and more accurate than unadjusted equations. Our new equation performed well in terms of bias, precision, accuracy, and reclassification.
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    Natural language processing diagnosed behavioral disturbance vs confusion assessment method for the intensive care unit: prevalence, patient characteristics, overlap, and association with treatment and outcome
    Young, M ; Holmes, N ; Kishore, K ; Marhoon, N ; Amjad, S ; Serpa-Neto, A ; Bellomo, R (SPRINGER, 2022-05)
    PURPOSE: To compare the prevalence, characteristics, drug treatment for delirium, and outcomes of patients with Natural Language Processing (NLP) diagnosed behavioral disturbance (NLP-Dx-BD) vs Confusion Assessment Method for intensive care unit (CAM-ICU) positivity. METHODS: In three combined medical-surgical ICUs, we obtained data on demographics, treatment with antipsychotic medications, and outcomes. We applied NLP to caregiver progress notes to diagnose behavioral disturbance and analyzed simultaneous CAM-ICU. RESULTS: We assessed 2313 patients with a median lowest Richmond Agitation-Sedation Scale (RASS) score of - 2 (- 4.0 to - 1.0) and median highest RASS score of 1 (0 to 1). Overall, 1246 (53.9%) patients were NLP-Dx-BD positive (NLP-Dx-BDpos) and 578 (25%) were CAM-ICU positive (CAM-ICUpos). Among NLP-Dx-BDpos patients, 539 (43.3%) were also CAM-ICUpos. In contrast, among CAM-ICUpos patients, 539 (93.3%) were also NLP-Dx-BDpos. The use of antipsychotic medications was highest in patients in the CAM-ICUpos and NLP-Dx-BDpos group (24.3%) followed by the CAM-ICUneg and NLP-Dx-BDpos group (10.5%). In NLP-Dx-BDneg patients, antipsychotic medication use was lower at 5.1% for CAM-ICUpos and NLP-Dx-BDneg patients and 2.3% for CAM-ICUneg and NLP-Dx-BDneg patients (overall P < 0.001). Regardless of CAM-ICU status, after adjustment and on time-dependent Cox modelling, NLP-Dx-BD was associated with greater antipsychotic medication use. Finally, regardless of CAM-ICU status, NLP-Dx-BDpos patients had longer duration of ICU and hospital stay and greater hospital mortality (all P < 0.001). CONCLUSION: More patients were NLP-Dx-BD positive than CAM-ICU positive. NLP-Dx-BD and CAM-ICU assessment describe partly overlapping populations. However, NLP-Dx-BD identifies more patients likely to receive antipsychotic medications. In the absence of NLP-Dx-BD, treatment with antipsychotic medications is rare.
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    Prevalence, severity, duration and resolution of cholestasis after acute liver failure
    Warming, S ; Michel, C ; Serpa Neto, A ; Kishore, K ; Marhoon, N ; Holmes, N ; Bellomo, R ; Testro, A ; Sinclair, M ; Gow, P ; Warrillow, S (BMJ PUBLISHING GROUP, 2022-04)
    OBJECTIVE: Persistent cholestasis may follow acute liver failure (ALF), but its course remains unknown. We aimed to describe the prevalence, onset, severity, duration and resolution of post-ALF cholestasis. DESIGN: Cohort of 127 adult patients with ALF at a liver transplantation centre identified using electronic databases. We obtained laboratory data every 6 hours for the first week, daily until day 30 and weekly, when documented, until day 180. RESULTS: Median age was 40.7 (IQR 31.0-52.4) years, median peak alanine aminotransferase level was 5494 (2521-8819) U/L and 87 (68.5%) cases had paracetamol toxicity. Overall, 12.6% underwent transplantation (3.4% for paracetamol vs 32.5% for non-paracetamol; p<0.001). Ninety-day mortality was 20.7% for paracetamol versus 30.0% for non-paracetamol patients. All non-transplanted survivors reached a bilirubin level>50 µmol/L, which peaked 3.5 (1.0-10.1) days after admission at 169.0 (80.0-302.0) µmol/L. At hospital discharge, 18.8% of patients had normal bilirubin levels and, at a median follow-up time from admission to last measurement of 16 (10-30) days, 46.9% had normal levels. Similarly, there was an increase in alkaline phosphatase (ALP) (207.0 (148.0-292.5) U/L) and gamma-glutamyl transferase (GGT) (336.0 (209.5-554.5) U/L) peaking at 4.5 days, with normalised values in 40.3% and 8.3% at hospital discharge. CONCLUSION: Post-ALF cholestasis is ubiquitous. Bilirubin, ALP and GGT peak at 3 to 5 days and, return to baseline in the minority of patients at median follow-up of 16 days. These data inform clinical expectations of the natural course of this condition.
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    Renal effects of an emergency department chloride-restrictive intravenous fluid strategy in patients admitted to hospital for more than 48 hours
    Yunos, NM ; Bellomo, R ; Taylor, DM ; Judkins, S ; Kerr, F ; Sutcliffe, H ; Hegarty, C ; Bailey, M (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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    Duration of platelet storage and outcomes of critically ill patients
    Flint, A ; Aubron, C ; Bailey, M ; Bellomo, R ; Pilcher, D ; Cheng, AC ; Hegarty, C ; Reade, MC ; McQuilten, Z (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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    Characteristics, incidence and outcome of patients admitted to intensive care because of pulmonary embolism
    Winterton, D ; Bailey, M ; Pilcher, D ; Landoni, G ; Bellomo, R (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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    The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial
    Chiam, E ; Weinberg, L ; Bailey, M ; McNicol, L ; Bellomo, R (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.