Critical Care - Research Publications

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    The psychometric properties and minimal clinically important difference for disability assessment using WHODAS 2.0 in critically ill patients
    Higgins, AM ; Neto, AS ; Bailey, M ; Barrett, J ; Bellomo, R ; Cooper, DJ ; Gabbe, B ; Linke, N ; Myles, PS ; Paton, M ; Philpot, S ; Shulman, M ; Young, M ; Hodgson, CL (AUSTRALASIAN MED PUBL CO LTD, 2021-03)
    Objectives: The 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) provides a standardised method for measuring health and disability. This study aimed to determine its reliability, validity and responsiveness and to establish the minimum clinically important difference (MCID) in critically ill patients. Design: Prospective, multicentre cohort study. Setting: Intensive care units of six metropolitan hospitals. Participants: Adults mechanically ventilated for > 24 hours. Main outcome measures: Reliability was assessed by measuring internal consistency. Construct validity was assessed by comparing WHODAS 2.0 scores at 6 months with the EuroQoL visual analogue scale (EQ VAS) and Lawton Instrumental Activities of Daily Living (IADL) scale scores. Responsiveness was evaluated by assessing change over time, effect sizes, and percentage of patients showing no change. The MCID was calculated using both anchor and distribution-based methods with triangulation of results. Main results: A baseline and 6-month WHODAS 2.0 score were available for 448 patients. The WHODAS 2.0 demonstrated good correlation between items with no evidence of item redundancy. Cronbach α coefficient was 0.91 and average split-half coefficient was 0.91. There was a moderate correlation between the WHODAS 2.0 and the EQ VAS scores (r = -0.72; P < 0.001) and between the WHODAS 2.0 and the Lawton IADL scores (r = -0.66; P < 0.001) at 6 months. The effect sizes for change in the WHODAS 2.0 score from baseline to 3 months and from 3 to 6 months were low. Ceiling effects were not present and floor effects were present at baseline only. The final MCID estimate was 10%. Conclusion: The 12-item WHODAS 2.0 is a reliable, valid and responsive measure of disability in critically ill patients. A change in the total WHODAS 2.0 score of 10% represents the MCID.
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    A multicentre point prevalence study of delirium assessment and management in patients admitted to Australian and New Zealand intensive care units
    Ankravs, MJ ; Udy, AA ; Byrne, K ; Knowles, S ; Hammond, N ; Saxena, MK ; Reade, MC ; Bailey, M ; Bellomo, R ; Deane, AM (AUSTRALASIAN MED PUBL CO LTD, 2020-12)
    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.
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    Practice patterns and predictors of outpatient care following acute kidney injury in an Australian healthcare setting
    See, EJ ; Ransley, DG ; Polkinghorne, KR ; Toussaint, ND ; Bailey, M ; Johnson, DW ; Robbins, R ; Bellomo, R (WILEY, 2022-01)
    BACKGROUND: Survivors of acute kidney injury (AKI) are at increased risk of major adverse kidney events and international guidelines recommend individuals be evaluated 3 months following AKI. AIM: We describe practice patterns and predictors of post-AKI care in an Australian tertiary hospital. METHODS: A retrospective analysis was undertaken of adults with AKI (defined by KDIGO criteria) admitted to a single centre between 2012 and 2016. The primary outcome was outpatient nephrology review at 3 months. Secondary outcomes included inpatient nephrology review, and outpatient serum creatinine and urinary protein measurements. Data were analysed using multivariable logistic and competing risk regression. RESULTS: Only 117 of 2111 (6%) patients with AKI were reviewed by a nephrologist at 3 months. Reviewed patients were more likely to have a higher discharge serum creatinine (odds ratio (OR) 1.20 per 10 μmol/L increase; 95% confidence interval (CI) 1.16-1.25) or a history of peripheral vascular disease (OR 1.77; 95% CI 1.00-3.14). They were less likely to be older (OR 0.66 per decade; 95% CI 0.57-0.76) or to have a history of liver (OR 0.47; 95% CI 0.26-0.87) or ischaemic heart (OR 0.50; 95% CI 0.27-0.94) disease. AKI stage did not predict follow up. The median time from discharge to outpatient serum creatinine testing was 12 days (interquartile range 4-47) and proteinuria was measured in 538 (25%) patients. CONCLUSIONS: A minority of admitted AKI patients receive recommended post-AKI care. Studies in other Australian institutions are required to confirm or refute these concerning findings.
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    Sex Differences in Mortality of ICU Patients According to Diagnosis-related Sex Balance
    Modra, LJ ; Higgins, AM ; Pilcher, DV ; Bailey, MJ ; Bellomo, R (AMER THORACIC SOC, 2022-12-01)
    Rationale: Women have worse outcomes than men in several conditions more common in men, including cardiac surgery and burns. Objectives: To describe the relationship between sex balance within each diagnostic group of ICU admissions, defined as the percentage of patients who were women, and hospital mortality of women compared with men with that same diagnosis. Methods: We studied ICU patients in the Australian and New Zealand Intensive Care Society's Adult Patient Database (2011-2020). We performed mixed effects logistic regression for hospital mortality adjusted for sex, illness severity, ICU lead time, admission year, and hospital site. We compared sex balance with the adjusted hospital mortality of women compared with men for each diagnosis using weighted linear regression. Measurements and Main Results: There were 1,450,782 admissions (42.1% women), with no difference in the adjusted hospital mortality of women compared with men overall (odds ratio, 0.99; 99% confidence interval [CI], 0.97 to 1). As the percentage of women within each diagnosis increased, the adjusted mortality of women compared with men with that same diagnosis decreased (regression coefficient, -0.015; 99% CI; -0.020 to -0.011; P < 0.001), and the illness severity of women compared with men at ICU admission decreased (regression coefficient, -0.0026; 99% CI, -0.0035 to -0.0018; P < 0.001). Conclusions: Sex balance in diagnostic groups was inversely associated with both the adjusted mortality and illness severity of women compared with men. In diagnoses with relatively few women, women were more likely than men to die. In diagnoses with fewer men, men were more likely than women to die.
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    Comparing the Clinical Frailty Scale and an International Classification of Diseases-10 Modified Frailty Index in Predicting Long-Term Survival in Critically Ill Patients.
    Subramaniam, A ; Ueno, R ; Tiruvoipati, R ; Darvall, J ; Srikanth, V ; Bailey, M ; Pilcher, D ; Bellomo, R (Ovid Technologies (Wolters Kluwer Health), 2022-10)
    UNLABELLED: The Clinical Frailty Scale (CFS) is the most used frailty measure in intensive care unit (ICU) patients. Recently, the modified frailty index (mFI), derived from 11 comorbidities has also been used. It is unclear to what degree the mFI is a true measure of frailty rather than comorbidity. Furthermore, the mFI cannot be freely obtained outside of specific proprietary databases. OBJECTIVE: To compare the performance of CFS and a recently developed International Classification of Diseases-10 (ICD-10) mFI (ICD-10mFI) as frailty-based predictors of long-term survival for up to 1 year. DESIGN: A retrospective multicentric observational study. SETTING AND PARTICIPANTS: All adult (≥16 yr) critically ill patients with documented CFS scores admitted to sixteen Australian ICUs in the state of Victoria between April 1, 2017 to June 30, 2018 were included. We used probabilistic methods to match de-identified ICU admission episodes listed in the Australia and New Zealand Intensive Care Society Adult Patient Database with the Victorian Admission Episode Dataset and the Victorian Death Index via the Victorian Data Linkage Centre. MAIN OUTCOMES AND MEASURES: The primary outcome was the longest available survival following ICU admission. We compared CFS and ICD-10mFI as primary outcome predictors, after adjusting for key confounders. RESULTS: The CFS and ICD-10mFI were compared in 7,001 ICU patients. The proportion of patients categorized as frail was greater with the CFS than with the ICD-10mFI (18.9% [n = 1,323] vs. 8.8% [n = 616]; p < 0.001). The median (IQR) follow-up time was 165 (82-276) days. The CFS predicted long-term survival up to 6 months after adjusting for confounders (hazard ratio [HR] = 1.26, 95% CI, 1.21-1.31), whereas ICD-10mFI did not (HR = 1.04, 95% CI, 0.98-1.10). The ICD-10mFI weakly correlated with the CFS (Spearman's rho = 0.22) but had a poor agreement (kappa = 0.06). The ICD-10mFI more strongly correlated with the Charlson comorbidity index (Spearman's rho 0.30) than CFS (Spearman's rho = 0.25) (p < 0.001). CONCLUSIONS: CFS, but not ICD-10mFI, predicted long-term survival in ICU patients. ICD-10mFI correlated with co-morbidities more than CFS. These findings suggest that CFS and ICD-10mFI are not equivalent. RELEVANCE: CFS and ICD-10mFI are not equivalent in screening for frailty in critically ill patients and therefore ICD-10mFI in its current form should not be used.
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    Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients
    Moore, JPR ; Shehabi, Y ; Reade, MC ; Bailey, M ; Fraser, JF ; Murray, L ; Anstey, C ; Singer, M (BMC, 2022-11-22)
    BACKGROUND: Sedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults. METHODS: This was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis. RESULTS: One hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20-0.93] vs 0.14 [0.08-0.38] mg/kg/day; p < 0.01). The geometric mean (95% CI) plasma level of the stress hormones, adrenaline (0.32 [0.26-0.4] vs 0.38 [0.31-0.48]), noradrenaline (4.27 [3.12-5.85] vs 6.2 [4.6-8.5]), adrenocorticotropic hormone (17.1 [15.1-19.5] vs 18.1 [15.9-20.5]) and cortisol (515 [409-648] vs 618 [491-776)] did not differ between dexmedetomidine and usual-care groups, respectively. There were no significant differences in any other assayed biomarkers or physiological parameters Sensitivity analyses showed no effect of age or sepsis. CONCLUSIONS: Early sedation with dexmedetomidine as the primary sedative agent in mechanically ventilated critically ill adults resulted in comparable changes in physiological and blood-borne parameters associated with the stress-response as with usual-care sedation.
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    Comparison of 6-month outcomes of sepsis versus non-sepsis critically ill patients receiving mechanical ventilation
    Hodgson, CL ; Higgins, AM ; Bailey, M ; Barrett, J ; Bellomo, R ; Cooper, DJ ; Gabbe, BJ ; Iwashyna, T ; Linke, N ; Myles, PS ; Paton, M ; Philpot, S ; Shulman, M ; Young, M ; Serpa Neto, A (BMC, 2022-06-13)
    BACKGROUND: Data on long-term outcomes after sepsis-associated critical illness have mostly come from small cohort studies, with no information about the incidence of new disability. We investigated whether sepsis-associated critical illness was independently associated with new disability at 6 months after ICU admission compared with other types of critical illness. METHODS: We conducted a secondary analysis of a multicenter, prospective cohort study in six metropolitan intensive care units in Australia. Adult patients were eligible if they had been admitted to the ICU and received more than 24 h of mechanical ventilation. There was no intervention. RESULTS: The primary outcome was new disability measured with the WHO Disability Assessment Schedule 2.0 (WHODAS) 12 level score compared between baseline and 6 months. Between enrollment and follow-up at 6 months, 222/888 (25%) patients died, 100 (35.5%) with sepsis and 122 (20.1%) without sepsis (P < 0.001). Among survivors, there was no difference for the incidence of new disability at 6 months with or without sepsis, 42/106 (39.6%) and 106/300 (35.3%) (RD, 0.00 (- 10.29 to 10.40), P = 0.995), respectively. In addition, there was no difference in the severity of disability, health-related quality of life, anxiety and depression, post-traumatic stress, return to work, financial distress or cognitive function. CONCLUSIONS: Compared to mechanically ventilated patients of similar acuity and length of stay without sepsis, patients with sepsis admitted to ICU have an increased risk of death, but survivors have a similar risk of new disability at 6 months. Trial registration NCT03226912, registered July 24, 2017.
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    Comparison of 6-Month Outcomes of Survivors of COVID-19 versus Non-COVID-19 Critical Illness
    Hodgson, CL ; Higgins, AM ; Bailey, MJ ; Mather, AM ; Beach, L ; Bellomo, R ; Bissett, B ; Boden, IJ ; Bradley, S ; Burrell, A ; Cooper, DJ ; Fulcher, BJ ; Haines, KJ ; Hodgson, IT ; Hopkins, J ; Jones, AYM ; Lane, S ; Lawrence, D ; van der Lee, L ; Liacos, J ; Linke, NJ ; Gomes, LM ; Nickels, M ; Ntoumenopoulos, G ; Myles, PS ; Patman, S ; Paton, M ; Pound, G ; Rai, S ; Rix, A ; Rollinson, TC ; Tipping, CJ ; Thomas, P ; Trapani, T ; Udy, AA ; Whitehead, C ; Anderson, S ; Neto, AS (AMER THORACIC SOC, 2022-05-15)
    Rationale: The outcomes of survivors of critical illness due to coronavirus disease (COVID-19) compared with non-COVID-19 are yet to be established. Objectives: We aimed to investigate new disability at 6 months in mechanically ventilated patients admitted to Australian ICUs with COVID-19 compared with non-COVID-19. Methods: We included critically ill patients with COVID-19 and non-COVID-19 from two prospective observational studies. Patients were eligible if they were adult (age ⩾ 8 yr) and received ⩾24 hours of mechanical ventilation. In addition, patients with COVID-19 were eligible with a positive laboratory PCR test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Measurements and Main Results: Demographic, intervention, and hospital outcome data were obtained from electronic medical records. Survivors were contacted by telephone for functional outcomes with trained outcome assessors using the World Health Organization Disability Assessment Schedule 2.0. Between March 6, 2020, and April 21, 2021, 120 critically ill patients with COVID-19, and between August 2017 and January 2019, 199 critically ill patients without COVID-19, fulfilled the inclusion criteria. Patients with COVID-19 were older (median [interquartile range], 62 [55-71] vs. 58 [44-69] yr; P = 0.019) with a lower Acute Physiology and Chronic Health Evaluation II score (17 [13-20] vs. 19 [15-23]; P = 0.011). Although duration of ventilation was longer in patients with COVID-19 than in those without COVID-19 (12 [5-19] vs. 4.8 [2.3-8.8] d; P < 0.001), 180-day mortality was similar between the groups (39/120 [32.5%] vs. 70/199 [35.2%]; P = 0.715). The incidence of death or new disability at 180 days was similar (58/93 [62.4%] vs. 99/150 [66/0%]; P = 0.583). Conclusions: At 6 months, there was no difference in new disability for patients requiring mechanical ventilation for acute respiratory failure due to COVID-19 compared with non-COVID-19. Clinical trial registered with www.clinicaltrials.gov (NCT04401254).
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    Impact of frailty on persistent critical illness: a population-based cohort study
    Darvall, JN ; Bellomo, R ; Bailey, M ; Young, PJ ; Rockwood, K ; Pilcher, D (SPRINGER, 2022-03)
    PURPOSE: Acute illness severity predicts mortality in intensive care unit (ICU) patients, however, its predictive value decreases over time in ICU. Typically after 10 days, pre-ICU (antecedent) characteristics become more predictive of mortality, defining the onset of persistent critical illness (PerCI). How patient frailty affects development and death from PerCI is unknown. METHODS: We conducted a secondary analysis of data from a prospective binational cohort study including 269,785 critically ill adults from 168 ICUs in Australia and New Zealand, investigating whether frailty measured with the Clinical Frailty Scale (CFS) changes the timing of onset and risk of developing PerCI and of subsequent in-hospital mortality. We assessed associations between frailty (CFS ≥ 5) and mortality prediction using logistic regression and area under the receiver operating characteristics (AUROC) curves. RESULTS: 2190 of 50,814 (4.3%) patients with frailty (CFS ≥ 5) versus 6624 of 218,971 (3%) patients without frailty (CFS ≤ 4) developed PerCI (P < 0.001). Among patients with PerCI, 669 of 2190 (30.5%) with frailty and 1194 of 6624 without frailty (18%) died in hospital (P < 0.001). The time point defining PerCI onset did not vary with frailty degree; however, with increasing length of ICU stay, inclusion of frailty progressively improved mortality discrimination (0.1% AUROC improvement on ICU day one versus 3.6% on ICU day 17). CONCLUSION: Compared to patients without frailty, those with frailty have a higher chance of developing and dying from PerCI. Moreover the importance of frailty as a predictor of mortality increases with ICU length of stay. Future work should explore incorporation of frailty in prognostic models, particularly for long-staying patients.
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    The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study
    Hodgson, CL ; Higgins, AM ; Bailey, MJ ; Mather, AM ; Beach, L ; Bellomo, R ; Bissett, B ; Boden, IJ ; Bradley, S ; Burrell, A ; Cooper, DJ ; Fulcher, BJ ; Haines, KJ ; Hopkins, J ; Jones, AYM ; Lane, S ; Lawrence, D ; van der Lee, L ; Liacos, J ; Linke, NJ ; Gomes, LM ; Nickels, M ; Ntoumenopoulos, G ; Myles, PS ; Patman, S ; Paton, M ; Pound, G ; Rai, S ; Rix, A ; Rollinson, TC ; Sivasuthan, J ; Tipping, CJ ; Thomas, P ; Trapani, T ; Udy, AA ; Whitehead, C ; Hodgson, IT ; Anderson, S ; Neto, AS (BMC, 2021-11-08)
    BACKGROUND: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months. METHODS: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM. RESULTS: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51-70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06-13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, - 0.19 [- 0.28 to - 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty. CONCLUSIONS: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning. Clinical trial registration NCT04401254 May 26, 2020.