Critical Care - Research Publications
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ItemA fixed dose approach to thrombosis chemoprophylaxis may be inadequate in heavier critically ill patients(AUSTRALASIAN MED PUBL CO LTD, 2021-03)Objectives: Overweight patients are at greater risk of venous thromboembolism. We aimed to describe prescribing patterns of thrombosis chemoprophylaxis in critically ill patients weighing ≥ 100 kg and quantify the effectiveness of these regimens using the surrogate biomarker of plasma anti-Xa level. Design, setting and patients: A prospective single-centre cohort study was conducted over a 6-month period. Patients weighing ≥ 100 kg who were prescribed enoxaparin for chemoprophylaxis and expected to remain in the intensive care unit for > 48 hours were eligible. Anti-Xa levels were measured once a patient had received at least three consecutive doses of enoxaparin. Peak levels were measured 4-6 hours after the third dose and trough levels were measured before the fourth dose. Anti-Xa levels were compared with established target ranges for peak and trough anti-Xa levels (0.2-0.5 IU/mL and > 0.1 IU/mL, respectively). Results: Eighty-eight patients met the eligibility criteria, and anti-Xa levels for 42 patients were obtained. Fixed dose chemoprophylaxis approaches varied considerably, with 40 mg once daily (54/88 [61%]) and 40 mg twice daily (20/88 [23%]) being the most frequently prescribed regimens. No patient had a peak anti-Xa level > 0.5 IU/mL. When comparing 40 mg once daily versus twice daily, the once daily regimen had lower median trough levels (0.01 IU/mL [interquartile range (IQR), 0.00-0.04] v 0.09 IU/mL [IQR, 0.05-0.13]; P < 0.001) and greater proportions of patients with levels below the established range (< 0.1 IU/mL) (15/16 [95%] v 7/14 [50%]; P = 0.002) and levels that were undetectable (0.00 IU/mL) (8/16 [50%] v 1/14 [7%]; P = 0.01). Conclusions: At a single centre, thrombosis chemoprophylaxis prescribing patterns for heavier critically ill patients varied considerably. Current fixed dose approaches may be inadequate in this cohort.
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ItemNo Preview AvailableA multicentre point prevalence study of delirium assessment and management in patients admitted to Australian and New Zealand intensive care units(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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ItemNo Preview AvailableStudy protocol and statistical analysis plan for the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial(AUSTRALASIAN MED PUBL CO LTD, 2020-06)BACKGROUND: Contemporary glucose management of intensive care unit (ICU) patients with type 2 diabetes is based on trial data derived predominantly from patients without type 2 diabetes. This is despite the recognition that patients with type 2 diabetes may be relatively more tolerant of hyperglycaemia and more susceptible to hypoglycaemia. It is uncertain whether glucose targets should be more liberal in patients with type 2 diabetes. OBJECTIVE: To detail the protocol, analysis and reporting plans for a randomised clinical trial - the Liberal Glucose Control in Critically Ill Patients with Pre-existing Type 2 Diabetes (LUCID) trial - which will evaluate the risks and benefits of targeting a higher blood glucose range in patients with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: A multicentre, parallel group, open label phase 2B randomised controlled clinical trial of 450 critically ill patients with type 2 diabetes. Patients will be randomised 1:1 to liberal blood glucose (target 10.0-14.0 mmol/L) or usual care (target 6.0-10.0 mmol/L). MAIN OUTCOME MEASURES: The primary endpoint is incident hypoglycaemia (< 4.0 mmol/L) during the study intervention. Secondary endpoints include biochemical and feasibility outcomes. RESULTS AND CONCLUSION: The study protocol and statistical analysis plan described will delineate conduct and analysis of the trial, such that analytical and reporting bias are minimised. TRIAL REGISTRATION: This trial has been registered on the Australian New Zealand Clinical Trials Registry (ACTRN No. 12616001135404) and has been endorsed by the Australian and New Zealand Intensive Care Society Clinical Trials Group.
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ItemEffects of Standard vs Energy-Dense Formulae on Gastric Retention, Energy Delivery, and Glycemia in Critically Ill Patients(WILEY, 2021-05)BACKGROUND: Energy-dense formulae are often provided to critically ill patients with enteral feed intolerance with the aim of increasing energy delivery, yet the effect on gastric emptying is unknown. The rate of gastric emptying of a standard compared with an energy-dense formula was quantified in critically ill patients. METHODS: Mechanically ventilated adults were randomized to receive radiolabeled intragastric infusions of 200 mL standard (1 kcal/mL) or 100 mL energy-dense (2 kcal/mL) enteral formulae on consecutive days in this noninferiority, blinded, crossover trial. The primary outcome was scintigraphic measurement of gastric retention (percentage at 120 minutes). Other measures included area under the curve (AUC) for gastric retention and intestinal energy delivery (calculated from gastric retention of formulae over time), blood glucose (peak and AUC), and intestinal glucose absorption (using 3-O-methyl-D-gluco-pyranose [3-OMG] concentrations). Comparisons were undertaken using paired mixed-effects models. Data presented are mean ± SE. RESULTS: Eighteen patients were studied (male/female, 14:4; age, 55.2 ± 5.3 years). Gastric retention at 120 minutes was greater with the energy-dense formula (standard, 17.0 ± 5.9 vs energy-dense, 32.5 ± 7.1; difference, 12.7% [90% confidence interval, 0.8%-30.1%]). Energy delivery (AUC120 , 13,038 ± 1119 vs 9763 ± 1346 kcal/120 minutes; P = 0.057), glucose control (peak glucose, 10.1 ± 0.3 vs 9.7 ± 0.3 mmol/L, P = 0.362; and glucose AUC120 8.7 ± 0.3 vs 8.5 ± 0.3 mmol/L.120 minutes, P = 0.661), and absorption (3-OMG AUC120 , 38.5 ± 4.0 vs 35.7 ± 4.0 mmol/L.120 minutes; P = .508) were not improved with the energy-dense formula. CONCLUSION: In critical illness, administration of an energy-dense formula does not reduce gastric retention, increase energy delivery to the small intestine, or improve glucose absorption or glucose control; instead, there is a signal for delayed gastric emptying.
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ItemAdministration of pharmacological sleep aids prior to, during and following critical illness(WILEY, 2022-11)BACKGROUND: Sleep in the intensive care unit (ICU) is frequently disturbed and this may have a detrimental effect on recovery. AIM: To determine the use of pharmacological sleep aids in critically ill patients prior to, during and after ICU admission. METHODS: We conducted a single-centre period prevalence study of all adult patients admitted to a university-associated adult medical-surgical ICU for more than two nights in a 3-month period ending September 2019. The major outcome of interest was the proportion of ICU patients who had a pharmacological sleep aid administered prior to, during and after ICU admission. Associations of selected patient variables with sleep aid prescription in the ICU were summarised both as unadjusted univariable comparisons and as adjusted effect estimates returned by a multivariable logistic regression model. RESULTS: During the study period, 370 patients met all eligibility criteria. A pharmacological sleep aid was identified prior to hospital admission in 34 (9%) patients and in 62 (17%) patients during ICU admission. Of the 340 ICU survivors, 292 remained in the same hospital. Of these, 96 (33%) received a pharmacological sleep aid at least once during their post-ICU general hospital ward stay. Pre-hospital sleep aid use, male sex, longer ICU admission and higher APACHE (Acute Physiology and Chronic Health Evaluation) III scores were associated with sleep aid prescription in the ICU. CONCLUSIONS: Pharmacological sleep aids are administered frequently in the ICU with administration increasing substantially after ICU discharge.
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ItemMachine learning predicts the short-term requirement for invasive ventilation among Australian critically ill COVID-19 patients(PUBLIC LIBRARY SCIENCE, 2022-10-26)OBJECTIVE(S): To use machine learning (ML) to predict short-term requirements for invasive ventilation in patients with COVID-19 admitted to Australian intensive care units (ICUs). DESIGN: A machine learning study within a national ICU COVID-19 registry in Australia. PARTICIPANTS: Adult patients who were spontaneously breathing and admitted to participating ICUs with laboratory-confirmed COVID-19 from 20 February 2020 to 7 March 2021. Patients intubated on day one of their ICU admission were excluded. MAIN OUTCOME MEASURES: Six machine learning models predicted the requirement for invasive ventilation by day three of ICU admission from variables recorded on the first calendar day of ICU admission; (1) random forest classifier (RF), (2) decision tree classifier (DT), (3) logistic regression (LR), (4) K neighbours classifier (KNN), (5) support vector machine (SVM), and (6) gradient boosted machine (GBM). Cross-validation was used to assess the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of machine learning models. RESULTS: 300 ICU admissions collected from 53 ICUs across Australia were included. The median [IQR] age of patients was 59 [50-69] years, 109 (36%) were female and 60 (20%) required invasive ventilation on day two or three. Random forest and Gradient boosted machine were the best performing algorithms, achieving mean (SD) AUCs of 0.69 (0.06) and 0.68 (0.07), and mean sensitivities of 77 (19%) and 81 (17%), respectively. CONCLUSION: Machine learning can be used to predict subsequent ventilation in patients with COVID-19 who were spontaneously breathing and admitted to Australian ICUs.
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ItemNo Preview AvailableMuscle Protein Synthesis after Protein Administration in Critical Illness(AMER THORACIC SOC, 2022-09-15)Rationale: Dietary protein may attenuate the muscle atrophy experienced by patients in the ICU, yet protein handling is poorly understood. Objectives: To quantify protein digestion and amino acid absorption and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods: Fifteen mechanically ventilated adults (12 male; aged 50 ± 17 yr; body mass index, 27 ± 5 kg⋅m-2) and 10 healthy control subjects (6 male; 54 ± 23 yr; body mass index, 27 ± 4 kg⋅m-2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5 hours and a duodenal bolus of intrinsically labeled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20 g protein) over 60 minutes. Arterial blood and muscle samples were taken at baseline (fasting) and for 6 hours following duodenal protein administration. Data are mean ± SD, analyzed with two-way repeated measures ANOVA and independent samples t test. Measurements and Main Results: Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy control subjects (0.023 ± 0.013% h-1 vs. 0.034 ± 0.016% h-1; P = 0.077). After protein administration, plasma amino acid availability did not differ between groups (ICU patients, 54.2 ± 9.1%, vs. healthy control subjects, 61.8 ± 13.1%; P = 0.12), and myofibrillar protein synthesis rates increased in both groups (0.028 ± 0.010% h-1 vs. 0.043 ± 0.018% h-1; main time effect P = 0.046; P-interaction = 0.584) with lower rates in ICU patients than in healthy control subjects (main group effect P = 0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ∼60% lower in ICU patients (0.007 ± 0.007 mol percent excess vs. 0.017 ± 0.009 mol percent excess; P = 0.007). Conclusions: The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption.
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ItemMethodological Rigor and Transparency in Clinical Practice Guidelines for Nutrition Care in Critically Ill Adults: A Systematic Review Using the AGREE II and AGREE-REX Tools(MDPI, 2022-07)Background: To evaluate the methodological quality of (1) clinical practice guidelines (CPGs) that inform nutrition care in critically ill adults using the AGREE II tool and (2) CPG recommendations for determining energy expenditure using the AGREE-REX tool. Methods: CPGs by a professional society or academic group, intended to guide nutrition care in critically ill adults, that used a systematic literature search and rated the evidence were included. Four databases and grey literature were searched from January 2011 to 19 January 2022. Five investigators assessed the methodological quality of CPGs and recommendations specific to energy expenditure determination. Scaled domain scores were calculated for AGREE II and a scaled total score for AGREE-REX. Data are presented as medians (interquartile range). Results: Eleven CPGs were included. Highest scoring domains for AGREE II were clarity of presentation (82% [76-87%]) and scope and purpose (78% [66-83%]). Lowest scoring domains were applicability (37% [32-42%]) and stakeholder involvement (46% [33-51%]). Eight (73%) CPGs provided recommendations relating to energy expenditure determination; scores were low overall (37% [36-40%]) and across individual domains. Conclusions: Nutrition CPGs for critically ill patients are developed using systematic methods but lack engagement with key stakeholders and guidance to support application. The quality of energy expenditure determination recommendations is low.
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Itemβ-Hydroxy-β-methylbutyrate (HMB) supplementation and functional outcomes in multi-trauma patients: a study protocol for a pilot randomised clinical trial (BOOST trial)(BMC, 2022-01-31)BACKGROUND: There are no therapies proven to diminish the muscle wasting that occurs in patients after major trauma who are admitted to the intensive care unit (ICU). β-Hydroxy-β-methylbutyrate (HMB) is a nutrition intervention that may attenuate muscle loss and, thereby, improve recovery. The primary aim of this study is to determine the feasibility of a blinded randomised clinical trial of HMB supplementation to patients after major trauma who are admitted to the ICU. Secondary aims are to establish estimates for the impact of HMB when compared to placebo on muscle mass and nutrition-related patient outcomes. METHODS: This prospective, single-centre, blinded, randomised, placebo-controlled, parallel-group, feasibility trial with allocation concealment will recruit 50 participants over 18 months. After informed consent, participants will be randomised [1:1] to receive either the intervention (three grams of HMB dissolved in either 150 ml of orange juice for those allowed oral intake or 150 ml of water for those being enterally fed) or placebo (150 ml of orange juice for those allowed oral intake or 150 ml of water for those being enterally fed). The intervention will be commenced in ICU, continued after ICU discharge and ceased at hospital discharge or day 28 post randomisation, whichever occurs first. The primary outcome is the feasibility of administering the intervention. Secondary outcomes include change in muscle thickness using ultrasound and other nutritional and patient-centred outcomes. DISCUSSION: This study aims to determine the feasibility of administering HMB to critically ill multi-trauma patients throughout ICU admission until hospital discharge. Results will inform design of a larger randomised clinical trial. TRIAL REGISTRATION: The protocol is registered with Australian New Zealand Clinical Trials Registry (ANZCTR) ANZCTR: 12620001305910 . UTN: U1111-1259-5534.