Twenty percent human albumin solution fluid bolus administration therapy in patients after cardiac surgery-II: a multicentre randomised controlled trial.

PURPOSE: After cardiac surgery, fluid bolus therapy (FBT) with 20% human albumin may facilitate less fluid and vasopressor administration than FBT with crystalloids. We aimed to determine whether, after cardiac surgery, FBT with 20% albumin reduces the duration of vasopressor therapy compared with crystalloid FBT. METHODS: We conducted a multicentre, parallel-group, open-label, randomised clinical trial in six intensive care units (ICUs) involving cardiac surgery patients deemed to require FBT. We randomised 240 patients to receive up to 400 mL of 20% albumin/day as FBT, followed by 4% albumin for any subsequent FBT on that day, or to crystalloid FBT for at least the first 1000 mL, with use of crystalloid or 4% albumin FBT thereafter. The primary outcome was the cumulative duration of vasopressor therapy. Secondary outcomes included fluid balance. RESULTS: Of 480 randomised patients, 466 provided consent and contributed to the primary outcome (mean age 65 years; median EuroSCORE II 1.4). The cumulative median duration of vasopressor therapy was 7 (interquartile range [IQR] 0-19.6) hours with 20% albumin and 10.8 (IQR 0-22.8) hours with crystalloids (difference - 3.8 h, 95% confidence interval [CI] - 8 to 0.4; P = 0.08). Day one fluid balance was less with 20% albumin FBT (mean difference - 701 mL, 95% CI - 872 to - 530). CONCLUSIONS: In patients after cardiac surgery, when compared to a crystalloid-based FBT, 20% albumin FBT was associated with a reduced positive fluid balance but did not significantly reduce the duration of vasopressor therapy.

PRECISION-TBI: a study protocol for a vanguard prospective cohort study to enhance understanding and management of moderate to severe traumatic brain injury in Australia.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, cohort study that will establish a clinical research network across major neurotrauma centres in Australia. This network will enable the ongoing collection of injury and clinical management data from patients with msTBI, to quantify variations in processes of care between sites. It will also pilot high-frequency data collection and analysis techniques, novel clinical interventions, and comparative effectiveness methodology. METHODS AND ANALYSIS: PRECISION-TBI will initially enrol 300 patients with msTBI with Glasgow Coma Scale (GCS) <13 requiring intensive care unit (ICU) admission for invasive neuromonitoring from 10 Australian neurotrauma centres. Demographic data and process of care data (eg, prehospital, emergency and surgical intervention variables) will be collected. Clinical data will include prehospital and emergency department vital signs, and ICU physiological variables in the form of high frequency neuromonitoring data. ICU treatment data will also be collected for specific aspects of msTBI care. Six-month extended Glasgow Outcome Scores (GOSE) will be collected as the key outcome. Statistical analysis will focus on measures of between and within-site variation. Reports documenting performance on selected key quality indicators will be provided to participating sites. ETHICS AND DISSEMINATION: Ethics approval has been obtained from The Alfred Human Research Ethics Committee (Alfred Health, Melbourne, Australia). All eligible participants will be included in the study under a waiver of consent (hospital data collection) and opt-out (6 months follow-up). Brochures explaining the rationale of the study will be provided to all participants and/or an appropriate medical treatment decision-maker, who can act on the patient's behalf if they lack capacity. Study findings will be disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: NCT05855252.

Magnitude and time to peak oxygenation effect of prone positioning in ventilated adults with COVID-19 related acute hypoxemic respiratory failure.

BACKGROUND: Prone positioning may improve oxygenation in acute hypoxemic respiratory failure and was widely adopted in COVID-19 patients. However, the magnitude and timing of its peak oxygenation effect remain uncertain with the optimum dosage unknown. Therefore, we aimed to investigate the magnitude of the peak effect of prone positioning on the PaO2 :FiO2 ratio during prone and secondly, the time to peak oxygenation. METHODS: Multi-centre, observational study of invasively ventilated adults with acute hypoxemic respiratory failure secondary to COVID-19 treated with prone positioning. Baseline characteristics, prone positioning and patient outcome data were collected. All arterial blood gas (ABG) data during supine, prone and after return to supine position were analysed. The magnitude of peak PaO2 :FiO2 ratio effect and time to peak PaO2 :FIO2 ratio effect was measured. RESULTS: We studied 220 patients (mean age 54 years) and 548 prone episodes. Prone positioning was applied for a mean (±SD) 3 (±2) times and 16 (±3) hours per episode. Pre-proning PaO2 :FIO2 ratio was 137 (±49) for all prone episodes. During the first episode. the mean PaO2 :FIO2 ratio increased from 125 to a peak of 196 (p < .001). Peak effect was achieved during the first episode, after 9 (±5) hours in prone position and maintained until return to supine position. CONCLUSIONS: In ventilated adults with COVID-19 acute hypoxemic respiratory failure, peak PaO2 :FIO2 ratio effect occurred during the first prone positioning episode and after 9 h. Subsequent episodes also improved oxygenation but with diminished effect on PaO2 :FIO2 ratio. This information can help guide the number and duration of prone positioning episodes.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

The Impact of Sedative Choice on Intracranial and Systemic Physiology in Moderate to Severe Traumatic Brain Injury: A Scoping Review.

Although sedative use is near-ubiquitous in the acute management of moderate to severe traumatic brain injury (m-sTBI), the evidence base for these agents is undefined. This review summarizes the evidence for analgosedative agent use in the intensive care unit management of m-sTBI. Clinical studies of sedative and analgosedative agents currently utilized in adult m-sTBI management (propofol, ketamine, benzodiazepines, opioids, and alpha-2 agonists) were identified and assessed for relevance and methodological quality. The primary outcome was the effect of the analgosedative agent on intracranial pressure (ICP). Secondary outcomes included intracranial hemodynamic and metabolic parameters, systemic hemodynamic parameters, measures of therapeutic intensity, and clinical outcomes. Of 594 articles identified, 61 met methodological review criteria, and 40 were included in the qualitative summary; of these, 33 were prospective studies, 18 were randomized controlled trials, and 8 were blinded. There was consistent evidence for the efficacy of sedative agents in the management of m-sTBI and raised ICP, but the overall quality of the evidence was poor, consisting of small studies (median sample size, 23.5) of variable methodological quality. Propofol and midazolam achieve the goals of sedation without notable differences in efficacy or safety, although high-dose propofol may disrupt cerebral autoregulation. Dexmedetomidine and propofol/ dexmedetomidine combination may cause clinically significant hypotension. Dexmedetomidine was effective to achieve a target sedation score. De novo opioid boluses were associated with increased ICP and reduced cerebral perfusion pressure. Ketamine bolus and infusions were not associated with increased ICP and may reduce the incidence of cortical spreading depolarization events. In conclusion, there is a paucity of high-quality evidence to inform the optimal use of analgosedative agents in the management of m-sTBI, inferring significant scope for further research.

Development of Traumatic Brain Injury Associated Intracranial Hypertension Prediction Algorithms: A Narrative Review.

Traumatic intracranial hypertension (tIH) is a common and potentially lethal complication of moderate to severe traumatic brain injury (m-sTBI). It often develops with little warning and is managed reactively with the tiered application of intracranial pressure (ICP)-lowering interventions administered in response to an ICP rising above a set threshold. For over 45 years, a variety of research groups have worked toward the development of technology to allow for the preemptive management of tIH in the hope of improving patient outcomes. In 2022, the first operationalizable tIH prediction system became a reality. With such a system, ICP lowering interventions could be administered prior to the rise in ICP, thus protecting the patient from potentially damaging tIH episodes and limiting the overall ICP burden experienced. In this review, we discuss related approaches to ICP forecasting and IH prediction algorithms, which collectively provide the foundation for the successful development of an operational tIH prediction system. We also discuss operationalization and the statistical assessment of tIH algorithms. This review will be of relevance to clinicians and researchers interested in development of this technology as well as those with a general interest in the bedside application of machine learning (ML) technology.

Teaching the Teachers: A Flexible, Cognitive-Focused Curriculum in Point-of-Care Ultrasound Education for Hospital Medicine Faculty.

OBJECTIVES: We aimed to decrease barriers to acquiring Point-of-Care Ultrasound (POCUS) knowledge among attending physicians and improve the safety of trainee POCUS use through a novel flexible and cognitive based curriculum. METHODS: We developed three educational pathways using varied approaches to educational delivery: a novel and asynchronous cognitive curriculum to allow Educational Supervision, a hands-on pathway for Limited Practice, and a more robust pathway for Independent Practice and credentialing. RESULTS: From November 2018 through June 2021, 102 of 116 hospitalists engaged in some portion of the curriculum. Twenty-four completed the Educational Supervision pathway, 31 completed the Limited Practice pathway, and 17 enrolled in the Independent Practice pathway with three achieving independent practice. Faculty who completed the Educational Supervision pathway had improved scores on a comprehensive POCUS knowledge assessment, 43.5% [95% Confidence Interval (CI) 38.2-48.8] versus 72.0% [95% CI 65.2-78.8], P < .001. Junior faculty were more likely to engage in the supervision pathway and senior faculty were more likely to complete an intensive course to complete the Limited Practice pathway. CONCLUSIONS: A flexible, cognitive focused POCUS curriculum was effective in creating high levels of engagement, and a cognitive only curriculum resulted in significant improvement in hospitalists' POCUS knowledge without hands on training. Finally, we found that hospitalist engagement in the curriculum did not follow the lowest barrier to entry or time commitment and engagement varied by time in practice. Training faculty to independent practice remains a substantial challenge.

The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma.

The Monitoring with Advanced Sensors, Transmission and E-Resuscitation in Traumatic Brain Injury (MASTER-TBI) collaborative: bringing data science to the ICU bedside.

Background: With the adoption of multimodal neuromonitoring techniques, a large amount of high resolution neurophysiological data is generated during the treatment of patients with moderate to severe traumatic brain injury (m-sTBI) that is available for further analysis. The Monitoring with Advanced Sensors, Transmission and E-Resuscitation in Traumatic Brain Injury (MASTER-TBI) collaborative was formed in 2020 to facilitate analysis of these data. Objective: The MASTER-TBI collaborative curates m-sTBI patient data for the purposes of comparative effectiveness research, machine learning algorithm development, and neuropathophysiological phenomena analysis. Design, setting and participants: The MASTER-TBI collaborative is a multicentre longitudinal cohort study which utilises a novel hybrid cloud platform and other data science-informed techniques to collect and analyse data from patients with m-sTBI in whom both intracranial pressure monitoring and ICM+ (Cambridge Enterprise, Cambridge, UK) neuromonitoring software are utilised. MASTER-TBI enrols patients with m-sTBI from three participating Australian trauma intensive care units (ICUs). Main outcome measures: Captured outcome measures available for analysis include pathophysiological events (intracranial hypertension, cerebral perfusion pressure variations etc), surgical interventions, ICU and hospital length of stay, patient discharge status, and, where available, Glasgow Outcome Score-Extended (GOS-E) at 6 months. Results and conclusion: MASTER-TBI continues to develop data science-informed systems and techniques to maximise the use of captured high resolution m-sTBI patient neuromonitoring data. The highly innovative systems provide a world-class platform which aims to enhance the search for improved m-sTBI care and outcomes. This article provides an overview of the MASTER-TBI project's developed systems and techniques as well as a rationale for the approaches taken.

Early sedation in traumatic brain injury: a multicentre international observational study.

Objectives: We aimed to investigate the use of sedation in patients with severe traumatic brain injury (TBI), focusing on the choice of sedative agent, dose, duration, and their association with clinical outcomes. Design: Multinational, multicentre, retrospective observational study. Settings: 14 trauma centres in Europe, Australia and the United Kingdom. Participants: A total of 262 adult patients with severe TBI and intracranial pressure monitoring. Main outcome measures: We described how sedative agents were used in this population. The primary outcome was 60-day mortality according to the use of different sedative agents. Secondary outcomes included intensive care unit and hospital length of stay, and the Extended Glasgow Outcome Scale at hospital discharge. Results: Propofol and midazolam were the most commonly used sedatives. Propofol was more common than midazolam as first line therapy (35.4% v 25.6% respectively). Patients treated with propofol had similar Acute Physiology and Chronic Health Evaluation (APACHE) II and International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) scores to patients treated with midazolam, but lower Injury Severity Score (ISS) (median, 26 [IQR, 22-38] v 34 [IQR, 26-44]; P = 0.001). The use of propofol was more common in heavier patients, and midazolam use was strongly associated with opioid co-administration (OR, 12.9; 95% CI, 3.47-47.95; P < 0.001). Sixty-day mortality and hospital mortality were predicted by a higher IMPACT score (P < 0.001) and a higher ISS (P < 0.001), but, after adjustment, were not related to the choice of sedative agent. Conclusions: Propofol was used more often than midazolam, and large doses were common for both sedatives. The first choice was highly variable, was affected by injury severity, and was not independently associated with 60-day mortality.

Study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-ll (HAS FLAIR-II) trial.

Background: Fluid bolus therapy with 20% albumin may shorten the duration of vasopressor therapy in patients after cardiac surgery. Objective: To describe the study protocol and statistical analysis plan for the 20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients after Cardiac Surgery-II (HAS FLAIR-II) trial. Design, setting, participants and intervention: HAS FLAIR-II is a phase 2b, multicentre, parallel group, openlabel, randomised controlled trial that will be conducted at six Australian intensive care units. Patients requiring fluid bolus therapy after cardiac surgery will be randomly assigned in a 1:1 ratio to the intervention of fluid bolus therapy with 20% albumin or a comparator of fluid bolus therapy with a crystalloid solution. Main outcome measures: The primary outcome measure is the cumulative duration of vasopressor therapy. Secondary outcomes include vasopressor use, service utilisation, and mortality. All analyses will be conducted on an intention-to-treat basis. Results and conclusion: The study protocol and statistical analysis plan will guide the conduct and analysis of the HAS FLAIR-II trial, such that analytical and reporting biases are minimised. Trial registration: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN No. 12620000137998).

Dysnatremia and 6-Month Functional Outcomes in Critically Ill Patients With Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

OBJECTIVES: To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. DESIGN: Prospective cohort study. SETTING: Eleven ICUs in Australia and New Zealand. PARTICIPANTS: Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05-1.29), and greater overall variability-as measured by the sd (odds ratio, 1.53; 95% CI, 1.17-1.99)-were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07-1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01-1.15). CONCLUSIONS: In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

Rethinking PICO in the Machine Learning Era: ML-PICO.

BACKGROUND: Machine learning (ML) has captured the attention of many clinicians who may not have formal training in this area but are otherwise increasingly exposed to ML literature that may be relevant to their clinical specialties. ML papers that follow an outcomes-based research format can be assessed using clinical research appraisal frameworks such as PICO (Population, Intervention, Comparison, Outcome). However, the PICO frameworks strain when applied to ML papers that create new ML models, which are akin to diagnostic tests. There is a need for a new framework to help assess such papers. OBJECTIVE: We propose a new framework to help clinicians systematically read and evaluate medical ML papers whose aim is to create a new ML model: ML-PICO (Machine Learning, Population, Identification, Crosscheck, Outcomes). We describe how the ML-PICO framework can be applied toward appraising literature describing ML models for health care. CONCLUSION: The relevance of ML to practitioners of clinical medicine is steadily increasing with a growing body of literature. Therefore, it is increasingly important for clinicians to be familiar with how to assess and best utilize these tools. In this paper we have described a practical framework on how to read ML papers that create a new ML model (or diagnostic test): ML-PICO. We hope that this can be used by clinicians to better evaluate the quality and utility of ML papers.

Long-term Survival of Critically Ill Patients Stratified According to Pandemic Triage Categories: A Retrospective Cohort Study.

BACKGROUND: The COVID-19 pandemic has led to unprecedented demand for ICUs, with the need to triage admissions along with the development of ICU triage criteria. However, how these criteria relate to outcomes in patients already admitted to the ICU is unknown, as is the incremental ICU capacity that triage of these patients might create given existing admission practices. RESEARCH QUESTION: What is the short- and long-term survival of low- vs high-priority patients for ICU admission according to current pandemic triage criteria? STUDY DESIGN AND METHODS: This study analyzed prospectively collected registry data (2007-2018) in 23 ICUs in Victoria, Australia, with probabilistic linkage with death registries. After excluding elective surgery, admissions were stratified according to existing ICU triage protocol prioritization as low (age ≥ 85 years, or severe chronic illness, or Sequential Organ Failure Assessment [SOFA] score = 0 or ≥ 12), medium (SOFA score = 8-11) or high (SOFA score = 1-7) priority. The primary outcome was long-term survival. Secondary outcomes were in-hospital mortality, ICU length of stay (LOS) and bed-day usage. RESULTS: This study examined 126,687 ICU admissions. After 5 years of follow-up, 1,093 of 3,296 (33%; 95% CI, 32-34) of "low-priority" patients aged ≥ 85 years or with severe chronic illness and 86 of 332 (26%; 95% CI, 24-28) with a SOFA score ≥ 12 were still alive. Sixty-three of 290 (22%; 95% CI, 17-27) of patients in these groups followed up for 10 years were still alive. Together, low-priority patients accounted for 27% of all ICU bed-days and had lower in-hospital mortality (22%) than the high-priority patients (28%). Among nonsurvivors, low-priority admissions had shorter ICU LOS than medium- or high-priority admissions. INTERPRETATION: Current SOFA score or age or severe comorbidity-based ICU pandemic triage protocols exclude patients with a close to 80% hospital survival, a > 30% five-year survival, and 27% of ICU bed-day use. These findings imply the need for stronger evidence-based ICU triage protocols.

Optimising a targeted test reduction intervention for patients admitted to the intensive care unit: The Targeted Intensive Care Test Ordering Cluster Trial intervention.

BACKGROUND: Approaches to routine diagnostic testing in the intensive care unit include time-scheduled testing and targeted testing. Blood tests and chest radiographs requested on a routine, time-scheduled basis may reduce the risk of missing important findings. Targeted testing, considering individual patient needs, may reduce unnecessary testing, wasted clinician time, and costs. However, existing evidence of targeted testing interventions is generally of low quality, and the optimal testing approach is uncertain. OBJECTIVES: The aim of the study was to describe the development of an intervention to reduce unnecessary diagnostic test ordering by clinicians working in intensive care, with the aim of informing the design of a pivotal clinical trial. METHODS: The Capability, Opportunity, Motivation-Behaviour model was used as a theoretical framework for change. The intervention components were informed by systematically identifying, assessing, and classifying targeted testing interventions in behavioural terms. Feedback from intensive care clinicians and patients was sought using surveys and a consumer reference group. RESULTS: The mean percentage of routine tests considered unnecessary by 201 intensive care clinicians was 33 (standard deviation = 16). When presented with a statement of the pros and cons for targeted versus liberal testing (n = 154), 93 (60%) consumer survey respondents preferred a more liberal approach, 33 (21%) preferred a more restrictive approach, and 28 (18%) were unsure. There were 24 behavioural interventions identified and incorporated into the final intervention. This had five major components: (i) a management committee to acquire, disseminate, and coordinate intervention-related information, (ii) a targeted testing guideline for sites, (iii) educational material for sites, (iv) site medical and nursing champions, and (v) site audit and feedback. CONCLUSIONS: Although surveyed intensive care clinicians report substantial unnecessary routine diagnostic testing, on the basis of currently available evidence, consumers prefer a more liberal approach. This feedback, and a framework to identify behavioural interventions, has been used to inform the design of a proposed targeted testing clinical trial.

A fixed dose approach to thrombosis chemoprophylaxis may be inadequate in heavier critically ill patients.

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.