Medicine (Austin & Northern Health) - Research Publications
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ItemNo Preview AvailableMild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest(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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ItemNo Preview AvailableReduced urinary levels of angiotensin-converting enzyme 2 activity predict acute kidney injury in critically ill patients(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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ItemSubsegmental pulmonary embolism and anticoagulant therapy: the impact of clinical context(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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ItemEstimating baseline kidney function in hospitalized adults with acute kidney injury(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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ItemNatural language processing diagnosed behavioral disturbance vs confusion assessment method for the intensive care unit: prevalence, patient characteristics, overlap, and association with treatment and outcome(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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ItemPrevalence, severity, duration and resolution of cholestasis after acute liver failure(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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ItemCoagulation abnormalities, bleeding, thrombosis, and management of patients with acute liver failure in Australia and New Zealand(WILEY, 2020-05)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.
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ItemContinuous renal replacement therapy and its impact on hyperammonaemia in acute liver failure(AUSTRALASIAN MED PUBL CO LTD, 2020-06)OBJECTIVE: Hyperammonaemia contributes to complications in acute liver failure (ALF) and may be treated with continuous renal replacement therapy (CRRT), but current practice is poorly understood. DESIGN: We retrospectively analysed data for baseline characteristics, ammonia concentration, CRRT use, and outcomes in a cohort of Australian and New Zealand patients with ALF. SETTING: All liver transplant ICUs across Australia and New Zealand. PARTICIPANTS: Sixty-two patients with ALF. MAIN OUTCOME MEASURES: Impact of CRRT on hyperammonaemia and patient outcomes. RESULTS: We studied 62 patients with ALF. The median initial (first 24 h) peak ammonia was 132 μmol/L (interquartile range [IQR], 91-172), median creatinine was 165 μmol/L (IQR, 92-263) and median urea was 6.9 mmol/L (IQR, 3.1-12.0). Most patients (43/62, 69%) received CRRT within a median of 6 hours (IQR, 2-12) of ICU admission. At CRRT commencement, three-quarters of such patients did not have Stage 3 acute kidney injury (AKI): ten patients (23%) had no KDIGO creatinine criteria for AKI, 12 (28%) only had Stage 1, and ten patients (23%) had Stage 2 AKI. Compared with non-CRRT patients, those treated with CRRT had higher ammonia concentrations (median, 141 μmol/L [IQR, 102-198] v 91 μmol/L [IQR, 54-115]; P = 0.02), but a nadir Day 1 pH of only 7.25 (standard deviation, 0.16). Prevention of extreme hyperammonaemia (> 140 μmol/L) after Day 1 was achieved in 36 of CRRT-treated patients (84%) and was associated with transplant-free survival (55% v 13%; P = 0.05). CONCLUSION: In Australian and New Zealand patients with ALF, CRRT is typically started early, before Stage 3 AKI or severe acidaemia, and in the presence hyperammonaemia. In these more severely ill patients, CRRT use was associated with prevention of extreme hyperammonaemia, which in turn, was associated with increased transplant-free survival.
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ItemThe effects of 0.9% saline versus Plasma-Lyte 148 on renal function as assessed by creatinine concentration in patients undergoing major surgery: A single-centre double-blinded cluster crossover trial(PUBLIC LIBRARY SCIENCE, 2021-05-19)OBJECTIVES: Saline and Plasma-Lyte have different physiochemical contents; consequently, they may differently affect patients' renal function. We compared the effects of fluid therapy with 0.9% saline and with Plasma-Lyte 148 on renal function as assessed by creatinine concentration among patients undergoing major surgery. METHODS: We conducted a prospective, double-blinded cluster crossover trial comparing the effects of the two fluids on major surgery patients. The primary aim was to establish the pilot feasibility, safety and preliminary efficacy evidence base for a large interventional trial to establish whether saline or Plasma-Lyte is the preferred crystalloid fluid for managing major surgery patients. The primary efficacy outcome was the proportion of patients with changes in renal function as assessed by creatinine concentration during their index hospital admission. We used changes in creatinine to define acute kidney injury (AKI) according to the RIFLE criteria. RESULTS: The study was feasible with 100% patient and clinician acceptance. There were no deviations from the trial protocol. After screening, we allocated 602 patients to saline and 458 to Plasma-Lyte. The median (IQR) volume of intraoperative fluid received was 2000 mL (1000:2000) in both groups. Forty-nine saline patients (8.1%) and 49 Plasma-Lyte patients (10.7%) developed a postoperative AKI (adjusted incidence rate ratio [aIRR]: 1.34; 95% CI: 0.93-1.95; p = 0.120). No differences were observed in the development of postoperative complications (aIRR: 0.98; 95% CI: 0.89-1.08) or the severity of the worst complication (aIRR: 1.00; 95% CI: 0.78-1.30). The median (IQR) length of hospital stay was six days (3:11) for the saline group and five days (3:10) for the Plasma-Lyte group (aIRR: 0.85; 95% CI: 0.73-0.98). There were no serious adverse events relating to the trial fluids, nor were there fluid crossover or contamination events. CONCLUSIONS: The study design was feasible to support a future follow-up larger clinical trial. Patients treated with saline did not demonstrate an increased incidence of postoperative AKI (defined as changes in creatinine) compared to those treated with Plasma-Lyte. Our findings imply that clinicians can reasonably use either solution intraoperatively for adult patients undergoing major surgery. TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; ACTRN12613001042730; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364988.
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ItemPrognostic performance of qSOFA in oncology patients admitted to the emergency department with suspected infection(WILEY, 2021-02)Aim We aimed to test the performance of the quick Sequential Organ Failure Assessment score (qSOFA) in predicting the outcomes of oncology patients admitted to the emergency department (ED) with suspected infection. Methods Retrospective cohort analysis of all oncology patients presenting to the ED of a tertiary hospital with suspected infection from 1 December 2014 to 1 June 2017. Patients were identified by cross‐linkage of ED and Oncology electronic health records. The primary outcome was in‐hospital mortality and/or ICU stay ≥ 3 days. Results A total of 1655 patients were included in this study––1267 (76.6%) with solid tumor and 388 (23.4%) with hematological malignancies. At presentation, 495 patients had chemotherapy, and 140 had radiotherapy within the preceding 6 months. Four hundred patients received chemotherapy and/or radiotherapy in the previous 4 weeks. Overall, 371 (22.4%) patients had qSOFA ≥ 2. Such patients had a higher likelihood of respiratory infections compared to patients with a qSOFA < 2 (43.9% vs 29%) and were more likely to be admitted to ICU or require mechanical ventilation. In‐hospital mortality or in‐hospital mortality and/or ICU stay ≥ 3 days were 17.3% and 21%, for qSOFA ≥ 2 patients versus 4.7% and 6.9% for qSOFA < 2 patients (P < .001). qSOFA ≥ 2 had a negative predictive value of 95% for in‐hospital mortality and 93% for in‐hospital mortality or ICU stay ≥ 3 days. Conclusion Among oncology patients presenting to the ED with suspected infection, a qSOFA ≥ 2 is associated with a threefold risk of hospital mortality/prolonged ICU stay. Its absence helps identify low‐risk patients.