Critical Care - Research Publications

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    "We are a unique breed": strategies to enhance physical activity participation for preschool-aged children born extremely preterm, a mixed-methods study
    Coulston, F ; Spittle, A ; McDonald, C ; Remedios, L ; Toovey, R ; Cheong, J ; Sellick, K (TAYLOR & FRANCIS LTD, 2023-12)
    PURPOSE: Preschool-aged children (three to five years old) born preterm participate in less physical activity (PA) than term-born children. Circus activities (a type of recreational PA) are a potential avenue to increase PA rates, but further insight into how to tailor these to address the participation gap is needed. This study investigated barriers and facilitators informing participation in recreational PA for preschool-aged children born extremely preterm and explored strategies to enhance participation in circus activities. MATERIALS AND METHODS: Sequential mixed-methods study utilizing surveys (n = 217), interviews (n = 43), and a focus group (n = 6) with key stakeholder groups (parents, coaches, and clinicians). Qualitative data (Framework Method) and quantitative data (descriptive statistics) were mixed during preliminary and final analyses. RESULTS: Five themes were developed from the mixed data: the crucial role of the coach and the need for specific training, the therapeutic role of PA and promoting outcomes beyond the physical, the impact of communication and class planning, consideration of convenience and cost, and finally, the role of clinicians. CONCLUSIONS: Barriers, facilitators, and strategies were identified which may be used to modify or co-design circus-based PA interventions to enhance participation and improve rates of PA for preschool-aged children born extremely preterm.IMPLICATIONS FOR REHABILITATIONFamilies consider recreational physical activities to be part of the therapeutic agenda for their preschool-aged children born extremely preterm.Key stakeholders feel that recreational physical activity should target outcomes beyond the physical.Coach attributes and capability impact participation of children born preterm and their families, and may be enhanced with specific training.Clinicians should be engaged in design of recreational physical activities for children born preterm.
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    Atherosclerosis on CT coronary angiography and the risk of long-term cardiovascular events after liver transplantation.
    Sampaio Rodrigues, T ; Koshy, AN ; Gow, PJ ; Weinberg, L ; Cailes, B ; Testro, A ; Smith, G ; Lim, HS ; Teh, AW ; Lim, RP ; Farouque, O (Ovid Technologies (Wolters Kluwer Health), 2024-02-01)
    Computed tomography coronary angiography (CTCA) is increasingly utilized for preoperative risk stratification before liver transplantation (LT). We sought to assess the predictors of advanced atherosclerosis on CTCA using the recently developed Coronary Artery Disease-Reporting and Data System (CAD-RADS) score and its impact on the prediction of long-term major adverse cardiovascular events (MACE) following LT. We conducted a retrospective cohort study of consecutive patients who underwent CTCA for LT work-up between 2011 and 2018. Advanced atherosclerosis was defined as coronary artery calcium scores > 400 or CAD-RADS score ≥ 3 (≥50% coronary artery stenosis). MACE was defined as myocardial infarction, heart failure, stroke, or resuscitated cardiac arrest. Overall, 229 patients underwent CTCA (mean age 66 ± 5 y, 82% male). Of these, 157 (68.5%) proceeded with LT. The leading etiology of cirrhosis was hepatitis (47%), and 53% of patients had diabetes before transplant. On adjusted analysis, male sex (OR 4.6, 95% CI 1.5-13.8, p = 0.006), diabetes (OR 2.2, 95% CI 1.2-4.2, p = 0.01) and dyslipidemia (OR 3.1, 95% CI 1.3-6.9, p = 0.005) were predictors of advanced atherosclerosis on CTCA. Thirty-two patients (20%) experienced MACE. At a median follow-up of 4 years, CAD-RADS ≥ 3, but not coronary artery calcium scores, was associated with a heightened risk of MACE (HR 5.8, 95% CI 1.6-20.6, p = 0.006). Based on CTCA results, 71 patients (31%) commenced statin therapy which was associated with a lower risk of all-cause mortality (HR 0.48, 95% CI 0.24-0.97, p = 0.04). The standardized CAD-RADS classification on CTCA predicted the occurrence of cardiovascular outcomes following LT, with a potential to increase the utilization of preventive cardiovascular therapies.
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    Acute Severe Behavioral Disturbance Requiring Parenteral Sedation in Pediatric Mental Health Presentations to Emergency Medical Services: A Retrospective Chart Review
    Bourke, EM ; Douglas, N ; Wilson, CL ; Anderson, D ; Nehme, Z (MOSBY-ELSEVIER, 2023-11)
    STUDY OBJECTIVES: To describe the epidemiological factors of mental health presentations in young people to emergency medical services (EMS) and define those experiencing acute severe behavioral disturbance by reviewing parenteral sedation use. METHODS: We performed a retrospective review of records of EMS attendance for young people (aged <18 years) with mental health presentations between July 2018 and June 2019 to a statewide EMS system in Australia of a population of 6.5 million persons. In addition, epidemiological data and information about parenteral sedation for acute severe behavioral disturbance and any adverse events were extracted from the records and analyzed. RESULTS: A total of 7,816 patients had mental health presentations with a median age of 15 years (IQR 14-17). The majority (60%) were female. These presentations accounted for 14% of all pediatric presentations to EMS. Out of them, 612 (8%) received parenteral sedation for acute severe behavioral disturbance. A number of factors were associated with increased odds of parenteral sedative medication being used, including autism spectrum disorder (odds ratio [OR] 3.3; confidence interval [CI], 2.7 to 3.9), posttraumatic stress disorder (OR 2.8; CI, 2.2 to 3.5) and intellectual disability (OR 3.6; CI, 2.6 to 4.8). The majority (460, 75%) of young people received midazolam as their first-line medication, with the remaining patients being provided ketamine (152, 25%). No serious adverse events were noted. CONCLUSION: Mental health conditions were a common presentation to EMS. A history of autism spectrum disorder, posttraumatic stress disorder, or an intellectual disability increased the odds of receiving parenteral sedation for acute severe behavioral disturbance. Sedation appears generally safe in the out-of-hospital setting.
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    A Real-Time Neurophysiologic Stress Test for the Aging Brain: Novel Perioperative and ICU Applications of EEG in Older Surgical Patients
    Berger, M ; Ryu, D ; Reese, M ; McGuigan, S ; Evered, LA ; Price, CC ; Scott, DA ; Westover, MB ; Eckenhoff, R ; Bonanni, L ; Sweeney, A ; Babiloni, C (SPRINGER, 2023-07)
    As of 2022, individuals age 65 and older represent approximately 10% of the global population [1], and older adults make up more than one third of anesthesia and surgical cases in developed countries [2, 3]. With approximately > 234 million major surgical procedures performed annually worldwide [4], this suggests that > 70 million surgeries are performed on older adults across the globe each year. The most common postoperative complications seen in these older surgical patients are perioperative neurocognitive disorders including postoperative delirium, which are associated with an increased risk for mortality [5], greater economic burden [6, 7], and greater risk for developing long-term cognitive decline [8] such as Alzheimer's disease and/or related dementias (ADRD). Thus, anesthesia, surgery, and postoperative hospitalization have been viewed as a biological "stress test" for the aging brain, in which postoperative delirium indicates a failed stress test and consequent risk for later cognitive decline (see Fig. 3). Further, it has been hypothesized that interventions that prevent postoperative delirium might reduce the risk of long-term cognitive decline. Recent advances suggest that rather than waiting for the development of postoperative delirium to indicate whether a patient "passed" or "failed" this stress test, the status of the brain can be monitored in real-time via electroencephalography (EEG) in the perioperative period. Beyond the traditional intraoperative use of EEG monitoring for anesthetic titration, perioperative EEG may be a viable tool for identifying waveforms indicative of reduced brain integrity and potential risk for postoperative delirium and long-term cognitive decline. In principle, research incorporating routine perioperative EEG monitoring may provide insight into neuronal patterns of dysfunction associated with risk of postoperative delirium, long-term cognitive decline, or even specific types of aging-related neurodegenerative disease pathology. This research would accelerate our understanding of which waveforms or neuronal patterns necessitate diagnostic workup and intervention in the perioperative period, which could potentially reduce postoperative delirium and/or dementia risk. Thus, here we present recommendations for the use of perioperative EEG as a "predictor" of delirium and perioperative cognitive decline in older surgical patients.
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    Outcomes following severe septic shock in a cohort of Aboriginal and Torres Strait Islander people: a nested cohort study from the ADRENAL trial
    Donaldson, LH ; Hammond, NE ; Agarwal, S ; Taylor, S ; Bompoint, S ; Coombes, J ; Bennett-Brook, K ; Bellomo, R ; Myburgh, J ; Venkatesh, B (AUSTRALASIAN MED PUBL CO LTD, 2022-03)
    Objective: To describe the pattern of acute illness and 6-month mortality and health-related quality-of-life outcomes for a cohort of Aboriginal and Torres Strait Islander patients presenting with septic shock. Design: Nested cohort study of Aboriginal and Torres Strait Islander participants recruited to a large randomised controlled trial of corticosteroid treatment in patients with septic shock. Setting: Royal Darwin Hospital, Northern Territory. Participants: All Aboriginal and Torres Strait Islander patients recruited to the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial at Royal Darwin Hospital were compared with a non-Indigenous cohort drawn from the same site, and a cohort matched for age, sex and severity of disease. Main outcome measures: Mortality at 90 days and 6 months, time to shock resolution, mechanical ventilation requirement, renal replacement therapy requirement, and five-domain, five-level EuroQol questionnaire (EQ-5D-5L) score at 6 months. Results: Aboriginal and Torres Strait Islander patients had significantly reduced risk of death at 90 days when compared with non-Indigenous patients recruited to ADRENAL at Royal Darwin Hospital (12/60 v 23/62; adjusted odds ratio, 0.40 [95% CI, 0.17 to 0.94]) which was robust to additional adjustment for baseline covariates (odds ratio, 0.35 [95% CI, 0.14 to 0.90]). When compared with the matched population drawn from the broader ADRENAL cohort, there was no significant difference in 90-day mortality (12/60 v 16/61; adjusted odds ratio, 1.43 [95% CI, 0.60 to 3.39]; P = 0.42). Only nine Aboriginal and Torres Strait Islander patients provided 6-month health-related quality-of-life data. Conclusions: Aboriginal and Torres Strait Islander patients had reduced risk of death at 90 days when compared with non- Indigenous patients recruited to the ADRENAL trial at Royal Darwin Hospital, which was robust to adjustment for covariates, but similar outcomes when compared with a cohort matched for age, sex and severity of disease.
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    Interhospital transport of children with bronchiolitis by a statewide emergency transport service
    Fahey, KP ; Gelbart, B ; Oberender, F ; Thompson, J ; Rozen, T ; James, C ; McLaren, C ; Sniderman, J ; Uahwatanasakul, W (AUSTRALASIAN MED PUBL CO LTD, 2021-09)
    Objective: To investigate the rate of interhospital emergency transport for bronchiolitis and intensive care admission following the introduction of high flow nasal cannula and standardised paediatric observation and response charts. Design: Retrospective cohort study. Setting: A statewide paediatric intensive care transport service and its two referral paediatric intensive care units (PICUs) in Victoria, Australia. Participants: Children less than 2 years old emergently transported with bronchiolitis during two time periods: 2008-2012 and 2015-2019. Main outcome measures: Incidence rates of bronchiolitis transport episodes, PICU admissions and respiratory support. Results: 802 children with bronchiolitis were transported during the study period, 233 in the first period (2008-2012) and 569 in the second period (2015-2019). The rate of interhospital transport for bronchiolitis increased from 32.9 to 71.8 per 100 000 children aged 0-2 years. The population-adjusted rate of PICU admission increased from 16.2 to 36.6 per 100 000 children aged 0-2 years. Metropolitan hospitals were the predominant referral source and this increased from 60.1% of transports to 78.6% (P < 0.001). In children admitted to a PICU, the administration of high flow nasal cannula during transport increased significantly from 1.7% to 75.9% (P < 0.001) and a concomitant reduction in continuous positive airway pressure and mechanical ventilation occurred (40-12.4% and 27-6.9% respectively; P < 0.001). The proportion of mechanical ventilation as well as PICU and hospital length of stay decreased over time. Conclusions: The population-adjusted rate of interhospital transport and admission to the PICU for bronchiolitis increased over time. This occurred despite a lower rate of non-invasive and invasive mechanical ventilation during transport and in the PICU.
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    Rapid 500 mL albumin bolus versus rapid 200 mL bolus followed by slower continuous infusion in post-cardiac surgery patients: a pilot before-and-after study
    Yanase, F ; Naorungroj, T ; Cutuli, SL ; Eastwood, GM ; Bellomo, R (AUSTRALASIAN MED PUBL CO LTD, 2021-09)
    Objective: To evaluate the haemodynamic effects of rapid fluid bolus therapy (FBT) (500 mL of 4% albumin over several minutes) versus combined FBT (rapid 200 mL FBT followed by a 300 mL infusion over 30 minutes). Design: Single centre, prospective, before-and-after trial. Setting: A tertiary intensive care unit in Australia. Participants: Fifty mechanically ventilated post-cardiac surgery patients. Interventions: Rapid 4% albumin FBT versus combined FBT. Main outcome measures: We recorded haemodynamic parameters from before FBT to 30 minutes after FBT. A mean arterial pressure (MAP) response was defined by a MAP increase > 10%, and a cardiac index (CI) response was defined by a CI increase > 15%. Results: Immediately after rapid FBT versus combined FBT, there was a CI response in 13 patients (52%) compared with five patients (20%) respectively (P = 0.038), and a MAP response in 11 patients (44%) in each group. However, from FBT administration to 30 minutes, there was a time and group interaction such that MAP was higher in the rapid FBT group (P = 0.003), as was the case for central venous pressure (P = 0.002) and mean pulmonary artery pressure (P < 0.001). Body temperature fell immediately and was lower with rapid FBT but became warmer than with combined FBT later (P < 0.001). At 30 minutes, a MAP response was seen in ten patients (40%) compared with nine patients (36%) (P < 0.99) and a CI response was present in eight patients (32%) compared with 11 patients (44%) (P = 0.56) in the rapid versus combined FBT groups respectively. Conclusion: Rapid FBT was superior to combined FBT in terms of mean MAP levels and immediate CI response. However, the number of MAP responders or CI responders was similar at 30 minutes.
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    Protocol and statistical analysis plan for the phase 3 randomised controlled Treatment of Invasively Ventilated Adults with Early Activity and Mobilisation (TEAM III) trial
    Presneill, JJ ; Bellomo, R ; Brickell, K ; Buhr, H ; Gabbe, BJ ; Gould, DW ; Harrold, M ; Higgins, AM ; Hurford, S ; Iwashyna, T ; Neto, AS ; Nichol, A ; Schaller, SJ ; Sivasuthan, J ; Tipping, C ; Webb, S ; Young, P ; Hodgson, CL (AUSTRALASIAN MED PUBL CO LTD, 2021-09)
    Objective: To describe the protocol and statistical analysis plan for the Treatment of Invasively Ventilated Adults with Early Activity and Mobilisation (TEAM III) trial. Design: An international, multicentre, parallel-group, randomised controlled phase 3 trial. Setting: Intensive care units (ICUs) in Australia, New Zealand, Germany, Ireland, the United Kingdom and Brazil. Patients: 750 adult patients expected to receive mechanical ventilation for more than 48 hours. Interventions: Early activity and mobilisation delivered to critically ill patients in an ICU for up to 28 days compared with standard care. Main outcome measures: The primary outcome is the number of days alive and out of hospital at 180 days after randomisation. Secondary outcomes include ICU-free days, ventilator-free days, delirium-free days, all-cause mortality at 28 and 180 days after randomisation, and functional outcome at 180 days after randomisation. Results: Recruitment at 46 research sites passed 576 patients in March 2021. Final collection of all 180-day outcome data for the target of 750 patients is anticipated by May 2022. Conclusions: Consistent with international guidelines, a detailed protocol and prospective analysis plan has been developed for the TEAM III trial. This plan specifies the statistical models for evaluating primary and secondary outcomes, defines covariates for adjusted analyses, and defines methods for exploratory analyses. Application of this protocol and statistical analysis plan to the forthcoming TEAM III trial will facilitate unbiased analyses of the clinical data collected. Trial registration:ClinicalTrials.gov identifier NCT03133377.
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    Characteristics and outcomes of children receiving intensive care therapy within 12 hours following a medical emergency team event
    Gelbart, B ; Vidmar, S ; Stephens, D ; Cheng, D ; Thompson, J ; Segal, A ; Gadish, T ; Carlin, J (AUSTRALASIAN MED PUBL CO LTD, 2021-09)
    Objectives: To describe characteristics and outcomes of children requiring intensive care therapy (ICT) within 12 hours following a medical emergency team (MET) event. Design: Retrospective cohort study. Setting: Quaternary paediatric hospital. Patients: Children experiencing a MET event. Measurements and main results: Between July 2017 and March 2019, 890 MET events occurred in 566 patients over 631 admissions. Admission to intensive care followed 183/890 (21%) MET events. 76/183 (42%) patients required ICT, defined as positive pressure ventilation or vasoactive support in intensive care, within 12 hours. Older children had a lower risk of requiring ICT than infants aged < 1 year (age 1-5 years [risk difference, -6.4%; 95% CI, -11% to -1.6%; P = 0.01] v age > 5 years [risk difference, -8.0%; 95% CI, -12% to -3.8%; P < 0.001]), while experiencing a critical event increased this risk (risk difference, 16%; 95% CI, 3.3-29%; P = 0.01). The duration of respiratory support and intensive care length of stay was approximately double in patients requiring ICT (ratio of geometric means, 2.0 [95% CI, 1.4-3.0] v 2.1 [95% CI, 1.5-2.8]; P < 0.001) and the intensive care mortality increased (risk difference, 9.6%; 95% CI, 2.4-17%; P = 0.01). Heart rate, oxygen saturation and respiratory rate were the most commonly measured vital signs in the 6 hours before the MET event. Conclusions: Approximately one-fifth of MET events resulted in intensive care admission and nearly half of these required ICT within 12 hours. This group had greater duration of respiratory support, intensive care and hospital length of stay, and higher mortality. Age < 1 year and a critical event increased the risk of ICT.
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    Statistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial
    Gibbons, KS ; Schlapbach, LJ ; Horton, SB ; Long, DA ; Beca, J ; Erickson, S ; Festa, M ; d'Udekem, Y ; Alphonso, N ; Winlaw, D ; Johnson, K ; Delzoppo, C ; van Loon, K ; Gannon, B ; Fooken, J ; Blumenthal, A ; Young, PJ ; Butt, W ; Schibler, A (ELSEVIER, 2021-03)
    Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses.