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.

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).

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.

Variability in Serum Sodium Concentration and Prognostic Significance in Severe Traumatic Brain Injury: A Multicenter Observational Study.

BACKGROUND/OBJECTIVE: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality. METHODS: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNaSD), an index of variability, and 28-day mortality. RESULTS: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4-8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0-3.9] mmol/L. Maximum daily serum sodium standard deviation (dNaSD) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNaSD over the first 7 days (coefficient - 0.15 95% CI [- 0.18 to - 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNaSD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01-1.61), p = 0.048). CONCLUSIONS: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients.

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.

Routine Intraoperative Inhaled Milrinone and Iloprost Reduces Inotrope Use in Patients Undergoing Cardiac Surgery: A Retrospective Cohort Pilot Study.

BACKGROUND: Catecholamine inotropes are frequently used after cardiopulmonary bypass (CPB) but may have undesirable effects. The aim was to identify whether the routine use of inhaled pulmonary vasodilators might reduce the requirement for inotrope drugs after cardiac surgery. METHODS: Retrospective cohort study of sequential patients undergoing cardiac surgery at the Royal Melbourne Hospital performed by a single surgeon and anesthesia care team, within 14 months before and after routine implementation of inhaled pulmonary vasodilators, August 2017. Milrinone 4 mg and iloprost 20 µg were inhaled using a vibrating mesh nebulizer (Aerogen) before initiation of CPB and at chest closure. Other aspects of clinical management were unaltered over the time period. Two investigators blinded to each other extracted data from electronic and written medical records. The primary outcome was any use of inotropes in the perioperative period; a Fisher exact test was used to analyze any differences between the 2 groups. Demographic data, hemodynamic data, and use of inotropes and vasopressors were collected from induction of anesthesia to 36 hours postoperative in the intensive care unit (ICU). Hospital and ICU length of stay, cost, and complications were collected. RESULTS: Any use of inotropes was significantly lower with inhaled pulmonary dilators (62.5% vs 86.8%, odds ratio [95% confidence interval {CI}], 0.253 (0.083-0.764); P = .011), including intraoperative inotrope use (37.5% vs 86.8%, odds ratio [95% CI], 0.091 (0.03-0.275); P < .001). ICU length of stay was significantly lower with inhaled pulmonary dilators (45 hours, interquartile range [IQR], 27-65 vs 50 hours, IQR, 45-74; P = .026). There were no significant differences among major postoperative complications or costs between groups. CONCLUSIONS: Routine use of inhaled milrinone 4 mg and iloprost 20 µg before and after CPB is associated with reduced postoperative inotrope use.

Outcome and potentially modifiable risk factors for candidemia in critically ill burns patients: A matched cohort study.

BACKGROUND: Patients with extensive burns are at risk of developing candidemia. OBJECTIVES: To identify potentially modifiable risk factors and outcomes of candidemia in critically ill burns patients. PATIENTS AND METHODS: Retrospective matched cohort study including adult burns patients. Patients who developed candidemia were matched with burns patients with Candida spp colonisation and sepsis or septic shock without candidemia in a ratio of 1:3 (same severity scores and colonisation index). Univariate and multiple regression analyses were performed. RESULTS: Of 130 severely burned patients with Candida spp colonisation and at least one episode of sepsis or septic shock, 14 were diagnosed with candidemia. In the candidemia group, patients had a median (IQR) total burns surface area (TBSA) of 57 (38-68)%, SAPSII of 43 (36-58) and ABSI of 11 (8-13). Multiple regression analysis showed that only duration of prior antibiotic therapy was independently associated with candidemia. ICU mortality was higher in the candidemia group (71% vs 35% [P = 0.02]). The log-rank test for 28-day mortality comparing patients with candidemia treated with an empirical strategy vs a curative strategy did not reach significance (P = 0.056). CONCLUSIONS: Burns patients having received recent antibiotherapy have a higher risk of candidemia. Antifungal strategies did not influence outcome in this series.

20% Human Albumin Solution Fluid Bolus Administration Therapy in Patients After Cardiac Surgery (the HAS FLAIR Study).

OBJECTIVE: To compare the effects of fluid bolus therapy using 20% albumin versus crystalloid on fluid balance, hemodynamic parameters, and intensive care unit (ICU) treatment effects in post-cardiac surgery patients. DESIGN: Sequential period open-label pilot study. SETTING: University teaching hospital. PARTICIPANTS: One hundred adult cardiac surgery patients who were prescribed fluid bolus therapy to correct hypotension or perceived hypovolemia or to optimize cardiac index during the first 24 hours in the ICU. INTERVENTIONS: The first 50 patients were treated with crystalloid fluid bolus therapy in the first period (control), and 50 patients with up to 2 treatments of 100 mL of 20% albumin fluid bolus therapy in the second period (intervention), followed by crystalloid therapy if needed. MEASUREMENTS AND MAIN RESULTS: Demographic characteristics were similar at baseline. The intervention was associated with a less positive median fluid balance in the first 24 hours (albumin: 1,100 [650-1,960] v crystalloid: 1,970 [1,430-2,550] p = 0.001), fewer episodes of fluid bolus therapy (3 [2-5] v 5 [4-7]; p < 0.0001) and a lesser volume of fluid bolus therapy (700 [200-1,450] v 1,500 mL/24 h [1,100-2,250]; p < 0.0001). The intervention also was associated with a decreased median overall dose of norepinephrine in the first 24 hours of ICU stay (19 [0-52] v 47 µg/kg/24 hours [0-134]; p = 0.025) and shorter median time to cessation of norepinephrine (17 [5-28] v 28 hours [20-48]; p = 0.002). CONCLUSION: Post-cardiac surgery fluid bolus therapy with 20% albumin when compared with crystalloid fluid resulted in less positive fluid balance as well as several hemodynamic and potential ICU treatment advantages.

Opinions and practices of blood glucose control in critically ill patients with pre-existing type 2 diabetes in Australian and New Zealand intensive care units.

BACKGROUND: Approximately 9000 patients with type-2 diabetes mellitus (T2DM) are admitted to an intensive care unit (ICU) in Australia and New Zealand annually. For these patients, recent exploratory data suggest that targeting a more liberal blood glucose range during ICU admission may be safe and potentially beneficial. However, the current approach to blood glucose management of patients with T2DM in Australia and New Zealand ICUs is not well described, and there is uncertainty about clinician equipoise for trials of liberal glycaemic control in these patients. AIM: The aim is to describe self-reported blood glucose management in patients with T2DM by intensivists working in Australian and New Zealand ICUs and to establish whether equipoise exists for a trial of liberal versus standard glycaemic control in such patients. METHOD: An online questionnaire of Australia and New Zealand intensivists conducted in July-September 2016. RESULTS: Seventy-one intensivists responded. Forty-five (63%) used a basic nomogram to titrate insulin. Sixty-six (93%) reported that insulin was commenced at blood glucose concentrations >10 mmol/L and titrated to achieve a blood glucose concentration between 6.0 and 10.0 mmol/L. A majority of respondents (75%) indicated that there was insufficient evidence to define optimal blood glucose targets in patients with T2DM, and 59 (83%) were prepared to enrol such patients in a clinical trial to evaluate a more liberal approach. CONCLUSION: A majority of respondents were uncertain about the optimal blood glucose target range for patients with T2DM and would enrol such patients in a comparative trial of conventional versus liberal blood glucose control.

Dependence of Present and Future European Temperature Extremes on the Location of Atmospheric Blocking.

The impact of atmospheric blocking on European heat waves (HWs) and cold spells (CSs) is investigated for present and future conditions . A 50-member ensemble of the second generation Canadian Earth System Model is used to quantify the role of internal variability in the response to blocking. We find that the present blocking-extreme temperature link is well represented compared to ERA-Interim, despite a significant underestimation of blocking frequency in most ensemble members. Our results show a strong correlation of blocking with northern European HWs in summer, spring, and fall. However, we also find a strong anticorrelation between blocking and HW occurrence in southern Europe in all seasons. Blocking increases the CS frequency particularly in southern Europe in fall, winter, and spring but reduces it in summer. For the future we find that blocking will continue to play an important role in the development of both CSs and HWs in all seasons.

Point-of-Care Ultrasound Needs Assessment, Curriculum Design, and Curriculum Assessment in a Large Academic Internal Medicine Residency Program.

OBJECTIVES: Internal medicine (IM) residency point-of-care ultrasound (POCUS) curricula are being developed but often are limited in scope or components. In this article, we discuss the demonstration of a need for POCUS training in our large academic IM residency program; the development of a longitudinal curriculum; and the impact of the curriculum on POCUS knowledge, use, and confidence. METHODS: In 2014, we designed a cross-sectional POCUS survey and knowledge test for all IM residents at the University of California, San Francisco. The results of this assessment drove the design of a longitudinal POCUS curriculum that included a 2-hour workshop for all IM interns and a 1-month elective offered to all IM residents. Residents were tested on their POCUS knowledge and image interpretation before the elective and were given the same test 6 months after the elective. The posttest included a survey of self-reported POCUS use and confidence. RESULTS: In the needs assessment, residents scored a mean of 27% on the knowledge test, and across all applications the percentage of residents reporting confidence in their POCUS skills was lower than the percentage reporting use of the application in clinical practice. Residents scored a mean of 37% on the elective pretest and 74% on the posttest, an increase of 37% (95% confidence interval 31.6-42.8, P < 0.001), with improvements seen across all applications. After the elective, self-reported use of POCUS and confidence in POCUS skills were increased for the applications, using the needs assessment as an approximate baseline. For core cardiac and pulmonary applications, 76% to 95% of residents, depending on application, reported "high" or "very high" use and 79% to 100% reported "high" or "very high" confidence in their POCUS skills. CONCLUSIONS: We used a needs assessment to guide the development of a longitudinal, multidisciplinary POCUS curriculum. Residents who completed all components showed substantial long-term gains in knowledge in all major applications and high use of and confidence in cardiac and pulmonary applications.

Altered synaptic dynamics during normal brain aging.

What is the neuroanatomical basis for the decline in brain function that occurs during normal aging? Previous postmortem studies have blamed it on a reduction in spine density, though results remain controversial and spine dynamics were not assessed. We used chronic in vivo two-photon imaging of dendritic spines and axonal boutons in somatosensory cortex for up to 1 year in thy1 GFP mice to test the hypothesis that aging is associated with alterations in synaptic dynamics. We find that the density of spines and en passant boutons (EPBs) in pyramidal cells increases throughout adult life but is stable between mature (8-15 months) and old (>20 months) mice. However, new spines and EPBs are two to three times more likely to be stabilized over 30 d in old mice, although the long-term retention (over months) of stable spines is lower in old animals. In old mice, spines are smaller on average but are still able to make synaptic connections regardless of their size, as assessed by serial section electron microscopy reconstructions of previously imaged dendrites. Thus, our data suggest that age-related deficits in sensory perception are not associated with synapse loss in somatosensory cortex (as might be expected) but with alterations in the size and stability of spines and boutons observed in this brain area. The changes we describe here likely result in weaker synapses that are less capable of short-term plasticity in aged individuals, and therefore to less efficient circuits.

Gonococcal aneurysm of the ascending aorta: case report and review of Neisseria gonorrhoeae endovascular infections.

We present the case of a man with a bicuspid aortic valve who presented with persistent fever. Blood cultures yielded Neisseria gonorrhoeae, and the diagnosis of infected mycotic aneurysm was confirmed by detection of the bacterial genome in the aortic wall. The patient was cured with surgery and intravenous ceftriaxone.

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.

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.

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.

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.

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.