ORCID Profile
0000-0002-0385-6731
Current Organisations
Royal College of Physicians
,
College of Intensive Care Medicine
,
University of New South Wales
,
Bankstown Lidcombe Hospital
,
George Institute for Global Health
,
Royal Australasian College of Physicians
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Publications
Acupuncture for neuropathic pain in adults
Publisher: John Wiley & Sons, Ltd
Date: 30-04-2013
Incorporating real-world evidence into the development of patient blood glucose prediction algorithms for the ICU
Publisher: Oxford University Press (OUP)
Date: 19-04-2021
Abstract: Glycemic control is an important component of critical care. We present a data-driven method for predicting intensive care unit (ICU) patient response to glycemic control protocols while accounting for patient heterogeneity and variations in care. Using electronic medical records (EMRs) of 18 961 ICU admissions from the MIMIC-III dataset, including 318 574 blood glucose measurements, we train and validate a gradient boosted tree machine learning (ML) algorithm to forecast patient blood glucose and a 95% prediction interval at 2-hour intervals. The model uses as inputs irregular multivariate time series data relating to recent in-patient medical history and glycemic control, including previous blood glucose, nutrition, and insulin dosing. Our forecasting model using routinely collected EMRs achieves performance comparable to previous models developed in planned research studies using continuous blood glucose monitoring. Model error, expressed as mean absolute percentage error is 16.5%–16.8%, with Clarke error grid analysis demonstrating that 97% of predictions would be clinically acceptable. The 95% prediction intervals achieve near intended coverage at 93%–94%. ML algorithms built on observational data sources, such as EMRs, present a promising approach for personalization and automation of glycemic control in critical care. Future research may benefit from applying a combination of methodologies and data sources to develop robust methodologies that account for the variations seen in ICU patients and difficultly in detecting the extremes of observed blood glucose values. We demonstrate that EMRs can be used to train ML algorithms that may be suitable for incorporation into ICU decision support systems.
Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults
Publisher: Massachusetts Medical Society
Date: 03-03-2022
An international comparison of the cost of fluid resuscitation therapies.
Publisher: Elsevier BV
Date: 2020
The authors reply
Publisher: Massachusetts Medical Society
Date: 31-03-2016
DOI: 10.1056/NEJMC1601361
Early peak temperature and mortality in critically ill patients with or without infection
Publisher: Springer Science and Business Media LLC
Date: 31-01-2012
DOI: 10.1007/S00134-012-2478-3
Abstract: PURPOSE: To determine whether fever is associated with an increased or decreased risk of death in patients admitted to an intensive care unit (ICU) with infection. METHODS: We evaluated the independent association between peak temperature in the first 24 h after ICU admission and in-hospital mortality according to whether there was an admission diagnosis of infection using a database of admissions to 129 ICUs in Australia and New Zealand (ANZ) (n = 269,078). Subsequently, we sought to confirm or refute the ANZ database findings using a validation cohort of admissions to 201 ICUs in the UK (n = 366,973). RESULTS: A total of 29,083/269,078 (10.8%) ANZ patients and 103,191/366,973 (28.1%) of UK patients were categorised as having an infection. In the ANZ cohort, adjusted in-hospital mortality risk progressively decreased with increasing peak temperature in patients with infection. Relative to the risk at 36.5-36.9°C, the lowest risk was at 39-39.4°C (adjusted OR 0.56 95% CI 0.48-0.66). In patients without infection, the adjusted mortality risk progressively increased above 39.0°C (adjusted OR 2.07 at 40.0°C or above 95% CI 1.68-2.55). In the UK cohort, findings were similar with adjusted odds ratios at corresponding temperatures of 0.77 (95% CI 0.71-0.85) and 1.94 (95% CI 1.60-2.34) for infection and non-infection groups, respectively. CONCLUSIONS: Elevated peak temperature in the first 24 h in ICU is associated with decreased in-hospital mortality in critically ill patients with an infection randomised trials are needed to determine whether controlling fever increases mortality in such patients.
Cooling therapies after neuronal injury: Direct brain cooling and systemic hypothermia
Publisher: Springer New York
Date: 2007
Fever management in intensive care patients with infections
Publisher: Springer Science and Business Media LLC
Date: 2014
DOI: 10.1186/CC13773
Changes in Temperature Management of Cardiac Arrest Patients Following Publication of the Target Temperature Management Trial.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2018
DOI: 10.1097/CCM.0000000000003339
Abstract: To evaluate knowledge translation after publication of the target temperature management 33°C versus 36°C after out-of-hospital cardiac arrest trial and associated patient outcomes. Our primary hypothesis was that target temperature management at 36°C was rapidly adopted in Australian and New Zealand ICUs. Secondary hypotheses were that temporal reductions in mortality would be seen and would have accelerated after publication of the target temperature management trial. Retrospective cohort study (January 2005 to December 2016). The Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation adult patient database containing greater than 2 million admission episodes from 186 Australian and New Zealand ICUs. Sixteen-thousand two-hundred fifty-two adults from 140 hospitals admitted to ICU after out-of-hospital cardiac arrest. The primary exposure of interest was admission before versus after publication of the target temperature management trial. The primary outcome variable to evaluate changes in temperature management was lowest temperature in the first 24 hours in ICU. The primary clinical outcome variable of interest was inhospital mortality. Secondary outcomes included proportion of patients with fever in the first 24 hours in ICU. Mean ± sd lowest temperature in the first 24 hours in ICU in pre- and posttarget temperature management trial patients was 33.80 ± 1.71°C and 34.70 ± 1.39°C, respectively (absolute difference, 0.98°C [99% CI, 0.89–1.06°C]). Inhospital mortality rate decreased by 1.3 (99% CI, –1.8 to –0.9) percentage points per year from January 2005 until December 2013 and increased by 0.6 (99% CI, –1.4 to 2.6) percentage points per year from January 2014 until December 2016 (change in slope 1.9 percentage points per year [99% CI, –0.6 to 4.4]). Fever occurred in 568 (12.8%) of 4,450 pretarget temperature management trial patients and 853 (16.5%) of 5,184 posttarget temperature management trial patients (odds ratio, 1.35 [99% CI, 1.16–1.57]). The average lowest temperature of postcardiac arrest patients in the first 24 hours in ICU rose after publication of the target temperature management trial. This change was associated with an increased frequency of fever not seen in the target temperature management trial.
Analysis of blood glucose measurements using capillary and arterial blood samples in intensive care patients
Publisher: Springer Science and Business Media LLC
Date: 23-11-2005
DOI: 10.1007/S00134-004-2500-5
Abstract: To analyse agreement between two methods for blood glucose measurement in intensive care patients: capillary blood using a reagent strip and glucometer with arterial blood using a blood gas analyser. Prospective, single-centre, observational study in a 12-bed tertiary referral intensive care unit. Blood glucose levels were measured in consecutive patients using simultaneous measurements of capillary blood s les using glucometry and from a multi-electrode arterial blood gas analyser. An a priori subgroup of patients with tissue hypoperfusion was identified (defined as systolic blood pressure <90 mmHg or vasopressor dependency). A total of 493 paired measurements were obtained 75 of these were from patients with systemic hypoperfusion. Overall, the mean difference (bias) was 0.12 mmol/l (2.15 mg/dl) and precision 0.77 mmol/l (13.8 mg/dl) 95% limits of agreement were -0.14 and 1.66 mmol/l (-2.5 and 29.8 mg/dl). In patients with systemic hypoperfusion the bias was 0.24 mmol/l (4.0 mg/dl) and precision 0.9 mmol/l (16.2 mg/dl) 95% limits of agreement -2.05 and 1.58 mmol/l (36.8 and 28.4 mg/dl). In a general population of intensive care patients, there is statistical agreement between blood glucose measured from capillary blood glucometry and arterial blood gas analysis. However, in patients with systemic hypoperfusion, the accuracy of agreement between these two measurement techniques may be such that that biochemical hypoglycaemia (<2.5 mmol/l, 44.9 mg/dl) may go undetected if used interchangeably.
Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation
Publisher: American Medical Association (AMA)
Date: 18-02-2020
Target temperature management after out-of-hospital cardiac arrest—a randomized, parallel-group, assessor-blinded clinical trial—rationale and design
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.AHJ.2012.01.013
Abstract: Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32°C to 34°C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33°C or 36°C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
Intensive care discharge delay is associated with increased hospital length of stay: A multicentre prospective observational study
Publisher: Public Library of Science (PLoS)
Date: 27-07-2017
Fever and antipyresis in infection
Publisher: AMPCo
Date: 10-2011
DOI: 10.5694/MJA11.10502
Abstract: Fever is an important mechanism of intrinsic resistance against infectious disease. A variety of studies point to a potential detrimental effect of temperature lowering in infectious disorders, but high-quality evidence from randomised controlled trials is lacking. In ambulatory care settings, we need to know whether antipyretics influence the severity and duration of illnesses and, in critically ill patients, whether antipyretics affect mortality.
Stability conditions and phase transition for Kalman filtering over Markovian channels
Publisher: IEEE
Date: 07-2015
Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan
Publisher: Springer Science and Business Media LLC
Date: 07-10-2020
DOI: 10.1186/S13063-020-04654-Y
Abstract: To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear. The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4–6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan. This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
Randomised evaluation of active control of temperature versus ordinary temperature management (REACTOR) trial.
Publisher: Springer Science and Business Media LLC
Date: 10-2019
Physical restraint of patients in Australia and New Zealand intensive care units
Publisher: Springer Science and Business Media LLC
Date: 12-11-2020
The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial
Publisher: Public Library of Science (PLoS)
Date: 17-12-2015
Acetaminophen for Fever in Critically Ill Patients with Suspected Infection
Publisher: Massachusetts Medical Society
Date: 03-12-2015
Health-related quality of life in survivors of septic shock: 6-month follow-up from the ADRENAL trial
Publisher: Springer Science and Business Media LLC
Date: 16-07-2020
Patience and change: A conflict of interests?
Publisher: Springer Science and Business Media LLC
Date: 2006
DOI: 10.1186/CC5034
Paracetamol therapy and outcome of critically ill patients: a multicenter retrospective observational study
Publisher: Springer Science and Business Media LLC
Date: 12-2015
DOI: 10.1186/S13054-015-0865-1
Abstract: In this study, we aimed to examine the association between paracetamol administration in the intensive care unit (ICU) and mortality in critically ill patients. We conducted a multicenter retrospective observational study in four ICUs. We obtained information on paracetamol use, body temperature, demographic, clinical and outcome data from each hospital’s clinical information system and admissions and discharges database. We performed statistical analysis to assess the association between paracetamol administration and hospital mortality. We studied 15,818 patients with 691,348 temperature measurements at 4 ICUs. Of these patients, 10,046 (64%) received at least 1 g of paracetamol. Patients who received paracetamol had lower in-hospital mortality (10% vs. 20%, P .001), and survivors were more likely to have received paracetamol (66% vs. 46% P .001). However, patients treated with paracetamol were also more likely to be admitted to the ICU after surgery (70% vs. 51% P .001) and/or after elective surgery (55% vs. 37% P .001). In multivariate logistic regression analysis including a propensity score for paracetamol treatment, we found a significant and independent association between the use of paracetamol and reduced in-hospital mortality (adjusted odds ratio =0.60 (95% confidence interval (CI), 0.53 to 0.68), P .001). Cox proportional hazards analysis showed that patients who received paracetamol also had a significantly longer time to death (adjusted hazard ratio =0.51 (95% CI, 0.46 to 0.56), P .001). The association between paracetamol and decreased mortality and/or time to death was broadly consistent across surgical and medical patients. It remained present after adjusting for paracetamol administration as a time-dependent variable. However, when such time-dependent analysis was performed, the association of paracetamol with outcome lost statistical significance in the presence of fever and suspected infection and in patients in the lower tertiles of Acute Physiology and Chronic Health Evaluation II scores. Paracetamol administration is common in the ICU and appears to be independently associated with reduced in-hospital mortality and time to death after adjustment for multiple potential confounders and propensity score. This association, however, was modified by the presence of fever, suspected infection and lesser illness severity and may represent the effect of indication bias.
Adjunctive Glucocorticoid Therapy in Patients with Septic Shock
Publisher: Massachusetts Medical Society
Date: 03-2018
Association between early peak temperature and mortality in neutropenic sepsis
Publisher: Springer Science and Business Media LLC
Date: 18-12-2015
DOI: 10.1007/S00277-014-2273-Z
Abstract: Fever is often the first sign of neutropenic infection, but its prognostic impact has not been established. We aimed to determine whether early peak temperature is associated with mortality in patients with neutropenic sepsis admitted to intensive care units (ICUs). We used a database of admissions to 157 ICUs in Australia and New Zealand between 2005 and 2013 to seek an association between peak temperature within the first 24 h in ICU and in-hospital mortality in neutropenic and non-neutropenic sepsis. Odds ratios for in-hospital death were calculated for four temperature bands, adjusting for illness severity. Two patient cohorts were identified: neutropenic sepsis (N = 4027) and non-neutropenic sepsis (N = 114,040). In-hospital mortality was higher in neutropenic sepsis than non-neutropenic sepsis. In both cohorts, early peak temperature below 36.5 °C was associated with significantly increased mortality compared to normothermia. Among non-neutropenic patients, an early peak temperature of 37.5 °C or higher was associated with reduced mortality compared to normothermia. In contrast, in patients with neutropenic sepsis, fever was not associated with reduced mortality compared to normothermia. Similar findings were seen in a subgroup of the neutropenic sepsis cohort with a documented haematological malignancy. In neutropenic sepsis patients admitted to ICU, a temperature below 36.5 °C is associated with increased mortality compared with normothermia. In contrast to non-neutropenic sepsis, fever was not associated with a significant reduction in mortality in neutropenic patients. Interventional studies are needed to determine whether physical or pharmacological measures to reduce fever influence outcomes during neutropenic infections.
What's new with fever control in the ICU
Publisher: Springer Science and Business Media LLC
Date: 02-04-2014
Frailty, delirium and hospital mortality of older adults admitted to intensive care: the Delirium (Deli) in ICU study
Publisher: Springer Science and Business Media LLC
Date: 15-10-2020
DOI: 10.1186/S13054-020-03318-2
Abstract: Clinical frailty among older adults admitted to intensive care has been proposed as an important determinant of patient outcomes. Among this group of patients, an acute episode of delirium is also common, but its relationship to frailty and increased risk of mortality has not been extensively explored. Therefore, the aim of this study was to explore the relationship between clinical frailty, delirium and hospital mortality of older adults admitted to intensive care. This study is part of a Delirium in Intensive Care (Deli) Study. During the initial 6-month baseline period, clinical frailty status on admission to intensive care, among adults aged 50 years or more acute episodes of delirium and the outcomes of intensive care and hospital stay were explored. During the 6-month baseline period, 997 patients, aged 50 years or more, were included in this study. The average age was 71 years (IQR, 63–79) 55% were male ( n = 537). Among these patients, 39.2% (95% CI 36.1–42.3%, n = 396) had a Clinical Frailty Score (CFS) of 5 or more, and 13.0% ( n = 127) had at least one acute episode of delirium. Frail patients were at greater risk of an episode of delirium (17% versus 10%, adjusted rate ratio ( adj RR) = 1.71, 95% confidence interval (CI) 1.20–2.43, p = 0.003), had a longer hospital stay (2.6 days, 95% CI 1–7 days, p = 0.009) and had a higher risk of hospital mortality (19% versus 7%, adj RR = 2.54, 95% CI 1.72–3.75, p 0.001), when compared to non-frail patients. Patients who were frail and experienced an acute episode of delirium in the intensive care had a 35% rate of hospital mortality versus 10% among non-frail patients who also experienced delirium in the ICU. Frailty and delirium significantly increase the risk of hospital mortality. Therefore, it is important to identify patients who are frail and institute measures to reduce the risk of adverse events in the ICU such as delirium and, importantly, to discuss these issues in an open and empathetic way with the patient and their families.
Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
Publisher: Massachusetts Medical Society
Date: 17-06-2021
Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study
Publisher: Springer Science and Business Media LLC
Date: 12-2015
DOI: 10.1186/S13054-015-0765-4
Abstract: The aim of this study was to investigate current mobilization practice, strength at ICU discharge and functional recovery at 6 months among mechanically ventilated ICU patients. This was a prospective, multi-centre, cohort study conducted in twelve ICUs in Australia and New Zealand. Patients were previously functionally independent and expected to be ventilated for hours. We measured mobilization during invasive ventilation, sedation depth using the Richmond Agitation and Sedation Scale (RASS), co-interventions, duration of mechanical ventilation, ICU-acquired weakness (ICUAW) at ICU discharge, mortality at day 90, and 6-month functional recovery including return to work. We studied 192 patients (mean age 58.1 ± 15.8 years mean Acute Physiology and Chronic Health Evaluation (APACHE) (IQR) II score, 18.0 (14 to 24)). Mortality at day 90 was 26.6% (51/192). Over 1,351 study days, we collected information during 1,288 planned early mobilization episodes in patients on mechanical ventilation for the first 14 days or until extubation (whichever occurred first). We recorded the highest level of early mobilization. Despite the presence of dedicated physical therapy staff, no mobilization occurred in 1,079 (84%) of these episodes. Where mobilization occurred, the maximum levels of mobilization were exercises in bed (N = 94, 7%), standing at the bed side (N = 11, 0.9%) or walking (N = 26, 2%). On day three, all patients who were mobilized were mechanically ventilated via an endotracheal tube (N = 10), whereas by day five 50% of the patients mobilized were mechanically ventilated via a tracheostomy tube (N = 18). In 94 of the 156 ICU survivors, strength was assessed at ICU discharge and 48 (52%) had ICU-acquired weakness (Medical Research Council Manual Muscle Test Sum Score (MRC-SS) score /60). The MRC-SS score was higher in those patients who mobilized while mechanically ventilated (50.0 ± 11.2 versus 42.0 ± 10.8, P = 0.003). Patients who survived to ICU discharge but who had died by day 90 had a mean MRC score of 28.9 ± 13.2 compared with 44.9 ± 11.4 for day-90 survivors ( P .0001). Early mobilization of patients receiving mechanical ventilation was uncommon. More than 50% of patients discharged from the ICU had developed ICU-acquired weakness, which was associated with death between ICU discharge and day-90. ClinicalTrials.gov NCT01674608 . Registered 14 August 2012.
Early temperature and mortality in critically ill patients with acute neurological diseases: trauma and stroke differ from infection
Publisher: Springer Science and Business Media LLC
Date: 03-02-2015
Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013
Publisher: Springer Science and Business Media LLC
Date: 03-06-2015
DOI: 10.1007/S00134-015-3878-Y
Abstract: Recent evidence indicates that the choice of intravenous fluids may affect outcomes in critically ill patients. We recorded the administration of resuscitation fluids in patients admitted to Australian and New Zealand adult intensive care units (ICUs) for a 24-h period at 6 time points between 2007 and 2013. Changes in patterns of fluid use over this period were determined using regression analyses. Of the 2825 patients admitted to the 61 ICUs on the 6 study days, 754 (26.7%) patients received fluid resuscitation. Of those receiving fluid resuscitation, the proportion of patients receiving crystalloid significantly increased from 28.9% (41/142) in 2007 to 50.5% (48/95) in 2013 (adjusted odds ratio (OR) 2.93 95% confidence intervals (CI) 1.35-6.33 p = 0.006) of these, the proportion of patients receiving buffered salt solutions significantly increased from 4.9% (7/142) in 2007 to 31.6% (30/95) in 2013 (OR 7.00 95% CI 2.14-22.92 p = 0.001). The use of colloids significantly decreased from 59.9% (85/142) in 2007 to 42.1% (40/95) in 2013 (adjusted OR 0.34 95% CI 0.16-0.74 p = 0.007) due to a significant decrease in the proportion of patients receiving gelatin 28.9% (41/142) to 2.1% (2/95) (OR 0.10 95% CI 0.03-0.29 p ≤ 0.001). Fluid resuscitation practice in Australia and New Zealand adult ICUs has changed over the 6-year study period. Crystalloid use increased primarily due to an increase in the use of buffered salt solutions while overall the use of colloid has decreased.
Modest temperature reduction for traumatic brain injury
Publisher: John Wiley & Sons, Ltd
Date: 17-10-2007
The Plasma-Lyte 148 versus Saline (PLUS) statistical analysis plan: a multicentre, randomised controlled trial of the effect of intensive care fluid therapy on mortality
Publisher: Elsevier BV
Date: 03-2021
DOI: 10.51893/2021.1.OA2
Abstract: BACKGROUND AND OBJECTIVE:The Plasma-Lyte 148 versus Saline (PLUS) study is a prospective, multicentre, parallel-group, concealed, blinded, randomised controlled trial comparing the effect of Plasma-Lyte 148 versus 0.9% sodium chloride (saline) for fluid resuscitation and other fluid therapy on 90-day mortality among critically ill adults requiring fluid resuscitation. The original target for recruitment was 8800 participants, which was reduced to 5000 participants following the onset of the coronavirus disease 2019 (COVID-19) pandemic in 2020. This article describes the statistical analysis plan for the PLUS study. METHODS: The statistical analysis plan was developed by the study statistician, chief investigator, and project manager, and was approved by the Management Committee before unblinding. The plan describes in detail the analysis of baseline characteristics, process measures, and outcomes, including covariate adjustments, subgroup analyses, missing data handling, and sensitivity analyses. RESULTS AND CONCLUSIONS: A statistical analysis plan for the PLUS study was developed. This pre-specified plan accords with high quality standards of internal validity and should minimise future analysis bias.
Population pharmacokinetics of intravenous paracetamol in critically ill patients with traumatic brain injury.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JCRC.2018.05.016
Abstract: High-dose paracetamol (6 g/day) is a low-cost intervention that may prevent pyrexia. The purpose of this study was to describe the pharmacokinetics of high-dose intravenous paracetamol, in patients with traumatic brain injury (TBI). A clinical pharmacokinetic study in adult patients with TBI was performed as a sub-study to a prospective, phase 2B, randomized placebo-controlled study (PARITY). Patients received 1 g of intravenous paracetamol or 0.9% sodium chloride every 4 h for 72 h. All patients were included in the pharmacokinetic sub-study. The mean age, weight and area under the concentration-time curve for the s led dosing interval were 34.5 yr, 82.3 kg and 39.9 ± 19.8 mg.h/L, respectively. The concentrations observed in the study patients were well below the threshold of toxicity and there was no evidence of accumulation of paracetamol. Paracetamol clearance was found to be high and variable (25.7 L.h Due to altered pharmacokinetics, patients experiencing severe TBI may require a higher dose of paracetamol to achieve drug exposure that results in preventing pyrexia.
Intensive care unit acquired weakness
Publisher: Elsevier BV
Date: 04-2012
Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: An international cross-sectional study
Publisher: Public Library of Science (PLoS)
Date: 12-05-2017
Plasma Cortisol, Aldosterone, and Ascorbic Acid Concentrations in Patients with Septic Shock Do Not Predict Treatment Effect of Hydrocortisone on Mortality. A Nested Cohort Study.
Publisher: American Thoracic Society
Date: 09-2020
Temporal Trends in Functional Outcomes after Severe Traumatic Brain Injury: 2006-2015
Publisher: Mary Ann Liebert Inc
Date: 15-04-2018
Abstract: Severe traumatic brain injury (TBI) is associated with poor outcomes however, little is known about whether these outcomes are improving over time. This study examined temporal trends in functional outcomes of severe TBI at six months post-injury. We conducted a retrospective cohort study (January 1, 2006 to December 31, 2015) of hospitalized adult (≥16 years) patients with severe TBI using data from the population-based Victorian State Trauma Registry. The primary outcome was the Glasgow Outcome Scale-Extended (GOS-E) at six months post-injury, dichotomized as upper severe disability or worse (GOS-E ≤4, termed "unfavorable outcome") and lower moderate disability or better (GOS-E ≥5 termed "favorable outcome"). Multivariable logistic regression was used to investigate temporal trends in functional outcomes at six months post-injury. Of the 1966 patients with severe TBI who were followed up at six months post-injury (median age, 42 years (interquartile range [IQR]: 25-68) male, 73%), a majority of patients had an unfavorable outcome (GOS-E ≤4 n = 1372, 70%). After adjusting for confounders, there was no change in functional outcomes over time (adjusted odds ratio [AOR] = 1.02, 95% confidence interval [CI]: 0.98,1.06 p = 0.35). Similarly, there was no change in the adjusted odds of death (GOS-E = 1) at six months post-injury (AOR = 1.04, 95% CI: 1.00,1.08 p = 0.08). Using a population-wide, high quality, comprehensive registry, we demonstrated no change in death or functional outcomes after severe TBI between 2006 and 2015 in a mature trauma system. There is a clear need to identify targeted improvements in the treatment of these patients with the aim of reducing in-hospital death and improving long-term outcomes.
Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial—Rationale and design
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.AHJ.2019.06.012
Abstract: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4-6) at 180 days after arrest. The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest.
A multicentre point prevalence study of delirium assessment and management in patients admitted to Australian and New Zealand intensive care units
Publisher: Elsevier BV
Date: 12-2020
DOI: 10.51893/2020.4.OA8
Abstract: Objective: To characterise the assessment and management of delirium in patients admitted to intensive care units (ICUs) in Australia and New Zealand. Methods: We conducted a multicentre observational point prevalence study across 44 adult Australian and New Zealand ICUs. Data were extracted for all patients in the ICU in terms of assessment and treatment of delirium. ICU-level data were collected regarding the use of explicit protocols related to delirium. Results: We studied 627 patients, with 54% (336/627) having at least one delirium screening assessment performed. The Confusion Assessment Method for the ICU (CAM-ICU) was the most frequently used tool (88%, 296/336). Of patients assessed, 20% (68) were identified to have delirium. Eighteen per cent (111) of patients were administered a drug to manage delirium, with 41% (46) of those receiving a drug having no recorded assessment for delirium on that day. Of the drugs used to treat delirium, quetiapine was the most frequently administered. Physical restraints were applied to 8% (48/626) of patients, but only 17% (8/48) of such patients had been diagnosed with delirium. Most physically restrained patients either did not have delirium diagnosed (31%, 15/48) or had no formal assessment recorded (52%, 25/48) on that day. Conclusions: On the study day, more than 50% of patients had a delirium screening assessment performed, with 20% of screened patients deemed to have delirium. Drugs that are prescribed to treat delirium and physical restraints were frequently used in the absence of delirium or the formal assessment for its presence.
Modest cooling therapies (35°C to 37.5°C) for traumatic brain injury
Publisher: Wiley
Date: 19-08-2014
The ICU Mobility Scale Has Construct and Predictive Validity and Is Responsive. A Multicenter Observational Study
Publisher: American Thoracic Society
Date: 06-2016
Interventions to reduce body temperature to 35 ⁰C to 37 ⁰C in adults and children with traumatic brain injury.
Publisher: Wiley
Date: 31-10-2020
Clinical review: Early patient mobilization in the ICU
Publisher: Springer Science and Business Media LLC
Date: 2012
DOI: 10.1186/CC11820
Modest cooling therapies (35°C to 37.5°C) for traumatic brain injury
Publisher: John Wiley & Sons, Ltd
Date: 16-07-2008
Fever control in critically ill adults. An individual patient data meta-analysis of randomised controlled trials
Publisher: Springer Science and Business Media LLC
Date: 11-02-2019
DOI: 10.1007/S00134-019-05553-W
Abstract: One potential way to protect patients from the physiological demands that are a consequence of fever is to aim to prevent fever and to treat it assiduously when it occurs. Our primary hypothesis was that more active fever management would increase survival among patient subgroups with limited physiological reserves such as older patients, patients with higher illness acuity, and those requiring organ support. We conducted an in idual-level patient data meta-analysis of randomised controlled trials to compare the outcomes of ICU patients who received more active fever management with the outcomes of patients who received less active fever management. The primary outcome variable of interest was the unadjusted time to death after randomisation. Of 1413 trial participants, 707 were assigned to more active fever management and 706 were assigned to less active fever management. There was no statistically significant heterogeneity in the effect of more active compared with less active fever management on survival in any of the pre-specified subgroups that were chosen to identify patients with limited physiological reserves. Overall, more active fever management did not result in a statistically significant difference in survival time compared with less active fever management [hazard ratio 0.91 (95% CI 0.75-1.10), P = 0.32]. Our findings do not support the hypothesis that more active fever management increases survival compared with less active fever management overall or in patients with limited physiological reserves.
Health-related outcomes of critically ill patients with and without sepsis.
Publisher: Springer Science and Business Media LLC
Date: 27-06-2018
DOI: 10.1007/S00134-018-5274-X
Abstract: To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis. We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years. We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p = 0.86), self-care (24.7% vs. 26.0%, p = 0.44), usual activities (44.5% vs. 46.8%, p = 0.28), pain/discomfort (42.4% vs. 41.6%, p = 0.54) and anxiety/depression (36.9% vs. 37.7%, p = 0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86-1.18, p = 0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1 ± 11.9 vs. 8.0 ± 9.8 days (p < 0.0001) and 22.8 ± 21.2 vs. 19.1 ± 19.0 days, (p = 0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345 ± 46,263 (€35,109 ± 35,043) versus 34,844 ± 38,281 (€28,223 ± 31,007), mean difference $8501 (€6885), 95% CI $4342-12,660 (€3517 ± 10,254), p < 0.001 as was the total cost of hospital treatment to 2 years: A$74,120 ± 60,750 (€60,037 ± 49,207) versus A$65,806 ± 59,856 (€53,302 ± 48,483), p = 0.005. Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.
Fever control
Publisher: Springer Science and Business Media LLC
Date: 22-10-2018
Fluid resuscitation
Publisher: Springer International Publishing
Date: 2016
Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
Publisher: Elsevier BV
Date: 05-2020
A multicentre evaluation of two intensive care unit triage protocols for use in an influenza pandemic
Publisher: Wiley
Date: 08-2012
DOI: 10.5694/MJA11.10926
Abstract: To determine the increase in intensive care unit (ICU) bed availability that would result from the use of the New South Wales and Ontario Health Plan for an Influenza Pandemic (OHPIP) triage protocols. Prospective evaluation study conducted in eight Australian, adult, general ICUs, between September 2009 and May 2010. All patients who were admitted to the ICU, excluding those who had elective surgery, were prospectively evaluated using the two triage protocols, simulating a pandemic situation. Both protocols were originally developed to determine which patients should be excluded from accessing ICU resources during an influenza pandemic. Increase in ICU bed availability. At admission, the increases in ICU bed availability using Tiers 1, 2 and 3 of the NSW triage protocol were 3.5%, 14.7% and 22.7%, respectively, and 52.8% using the OHPIP triage protocol (P < 0.001). Re-evaluation of patients at 12 hours after admission using Tiers 1, 2 and 3 of the NSW triage protocol incrementally increased ICU bed availability by 19.2%, 16.1% and 14.1%, respectively (P < 0.001). The maximal cumulative increases in ICU bed availability using Tiers 1, 2 and 3 of the NSW triage protocol were 23.7%, 31.6% and 37.5%, respectively, at 72 hours (P < 0.001), and 65.0% using the OHPIP triage protocol, at 120 hours (P < 0.001). Both triage protocols resulted in increases in ICU bed availability, but the OHPIP protocol provided the greatest increase overall. With the NSW triage protocol, ICU bed availability increased as the protocol was escalated.
Management of Australian Patients with Severe Traumatic Brain Injury: Are Potentially Harmful Treatments Still Used?
Publisher: Mary Ann Liebert Inc
Date: 15-12-2020
A Binational Multicenter Pilot Feasibility Randomized Controlled Trial of Early Goal-Directed Mobilization in the ICU*
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2016
DOI: 10.1097/CCM.0000000000001643
Abstract: To determine if the early goal-directed mobilization intervention could be delivered to patients receiving mechanical ventilation with increased maximal levels of activity compared with standard care. A pilot randomized controlled trial. Five ICUs in Australia and New Zealand. Fifty critically ill adults mechanically ventilated for greater than 24 hours. Patients were randomly assigned to either early goal-directed mobilization (intervention) or to standard care (control). Early goal-directed mobilization comprised functional rehabilitation treatment conducted at the highest level of activity possible for that patient assessed by the ICU mobility scale while receiving mechanical ventilation. The ICU mobility scale, strength, ventilation duration, ICU and hospital length of stay, and total inpatient (acute and rehabilitation) stay as well as 6-month post-ICU discharge health-related quality of life, activities of daily living, and anxiety and depression were recorded. The mean age was 61 years and 60% were men. The highest level of activity (ICU mobility scale) recorded during the ICU stay between the intervention and control groups was mean (95% CI) 7.3 (6.3–8.3) versus 5.9 (4.9–6.9), p = 0.05. The proportion of patients who walked in ICU was almost doubled with early goal-directed mobilization (intervention n = 19 [66%] vs control n = 8 [38%] p = 0.05). There was no difference in total inpatient stay (d) between the intervention versus control groups (20 [15–35] vs 34 [18–43] p = 0.37). There were no adverse events. Key Practice Points: Delivery of early goal-directed mobilization within a randomized controlled trial was feasible, safe and resulted in increased duration and level of active exercises.
Related Organisations
Royal College Of Physicians
Location: United Kingdom of Great Britain and Northern Ireland
St Thomas' Hospital
Location: United Kingdom of Great Britain and Northern Ireland
University Of Cambridge
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
Plasma-Lyte 148® Versus Saline (PLUS) Trial
Start Date: 2016
End Date: 2019
Funder: National Health and Medical Research Council
View Funded ActivityTherapeutic Thermal Regulation In Critical Illness
Start Date: 2017
End Date: 2020
Funder: National Health and Medical Research Council
View Funded Activity