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Traumatic brain injury (TBI) can initiate a very complex disease of the central nervous system (CNS), starting with the primary pathology of the inciting trauma and subsequent inflammatory and CNS tissue response. Delirium has long been regarded as an almost inevitable consequence of moderate to severe TBI, but more recently has been recognized as an organ dysfunction syndrome with potentially mitigating interventions. The diagnosis of delirium is independently associated with prolonged hospitalization, increased mortality and worse cognitive outcome across critically ill populations. Investigation of the unique problems and management challenges of TBI patients is needed to reduce the burden of delirium in this population. : In this narrative review, possible etiologic mechanisms behind post-traumatic delirium are discussed, including primary injury to structures mediating arousal and attention and secondary injury due to progressive inflammatory destruction of the brain parenchyma. Other potential etiologic contributors include dysregulation of neurotransmission due to intravenous sedatives, seizures, organ failure, sleep cycle disruption or other delirium risk factors. Delirium screening can be accomplished in TBI patients and the presence of delirium portends worse outcomes. : There is evidence that multi-component care bundles including an analgesia-prioritized sedation algorithm, regular spontaneous awakening and breathing trials, protocolized delirium assessment, early mobility and family engagement can reduce the burden of ICU delirium. The aim of this review is to summarize the approach to delirium in TBI patients with an emphasis on pathogenesis and management. Emerging CNS-active drug therapies that show promise in preclinical studies are highlighted.

Objectives Adult ICU survivors that experience delirium are at high risk for developing new functional disabilities and mental health disorders. We sought to determine if individual motoric subtypes of delirium are associated with worse disability, depression, and/or post-traumatic stress disorder in ICU survivors. Design Secondary analysis of a prospective multicenter cohort study. Setting Academic, community, and Veteran Affairs hospitals. Patients Adult ICU survivors of respiratory failure and/or shock. Interventions We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation and Sedation Scale daily during hospitalization. We classified delirium as hypoactive (Richmond Agitation and Sedation Scale ≤ 0) or hyperactive (Richmond Agitation and Sedation Scale > 0). At 3- and 12-month postdischarge, we assessed for dependence in activities of daily living and instrumental activities of daily living, symptoms of depression, and symptoms of post-traumatic stress disorder. Adjusting for baseline and inhospital covariates, multivariable regression examined the association of exposure to delirium motoric subtype and long-term outcomes. Measurements and main results In our cohort of 556 adults with a median age of 62 years, hypoactive delirium was more common than hyperactive (68.9% vs 16.8%). Dependence on the activities of daily living was present in 37% at 3 months and 31% at 12 months, whereas dependence on instrumental activities of daily living was present in 63% at 3 months and 56% at 12 months. At both time points, depression and post-traumatic stress disorder rates were constant at 36% and 5%, respectively. Each additional day of hypoactive delirium was associated with higher instrumental activities of daily living dependence at 3 months only (0.24 points [95% CI, 0.07-0.41; p = 0.006]). There were no associations between the motoric delirium subtype and activities of daily living dependence, depression, or post-traumatic stress disorder. Conclusions Longer duration of hypoactive delirium, but not hyperactive, was associated with a minimal increase in early instrumental activities of daily living dependence scores in adult survivors of critical illness. Motoric delirium subtype was neither associated with early or late activities of daily living functional dependence or mental health outcomes, nor late instrumental activities of daily living functional dependence.

Objectives Little is known about frailty that develops following critical illness. We sought to describe the prevalence of newly acquired frailty, its clinical course, and the co-occurrence of frailty with disability and cognitive impairment in survivors of critical illness. Design Longitudinal prospective cohort study. Setting Medical and surgical ICUs at five U.S. centers. Patients Adult patients treated for respiratory failure and/or shock. Measurements and main results We measured frailty with the Clinical Frailty Scale at baseline (i.e., study enrollment) and at 3 and 12 months postdischarge. We constructed alluvial diagrams to describe the course of frailty and Venn diagrams to describe the overlap of frailty with disability in activities of daily living and cognitive impairment. We included 567 participants a median (interquartile range) of 61 years old (51-70 yr old) with a high severity of illness (Acute Physiology and Chronic Health Evaluation II of 23). Frailty (Clinical Frailty Scale scores ≥ 5) was present in 135 of 567 (24%) at baseline, 239 of 530 (45%) at 3 months, and 163 of 445 (37%) at 12 months. Of those with frailty at 3- or 12-month follow-up, 61% were not frail at baseline. Transition to a worse frailty state occurred in 242 of 530 of patients (46%) between baseline and 3 months and in 179 of 445 of patients (40%) between baseline and 12 months. There were 376 patients with frailty, disability, or cognitive impairment at 3-month follow-up. Of these, 53 (14%) had frailty alone. At 12 months, 276 patients had frailty, disability, or cognitive impairment, 37 (13%) of whom had frailty alone. Conclusions Frailty is common among survivors of critical illness. In the majority, frailty is newly acquired. Roughly one in seven had frailty without co-occurring disability or cognitive impairment. Studies to understand outcomes of frailty that develops as the result of a critical illness and to identify modifiable risk factors for this potentially reversible syndrome are needed.

OBJECTIVES: Delirium, a heterogenous syndrome, is associated with worse long-term cognition after critical illness. We sought to determine if duration of motoric subtypes of delirium are associated with worse cognition. DESIGN: Secondary analysis of prospective multicenter cohort study. SETTING: Academic, community, and Veteran Affairs hospitals. Patients: Five-hundred eighty-two survivors of respiratory failure or shock. PATIENTS: Five-hundred eighty-two survivors of respiratory failure or shock. INTERVENTIONS: We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale daily during hospitalization. We defined a day with hypoactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score less than or equal to 0 and a day with hyperactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score greater than 0. At 3 and 12 months, we assessed global cognition with the Repeatable Battery for the Assessment of Neurologic Status and executive function with the Trail Making Test Part B. We used multivariable regression to examine the associations between days of hypoactive and hyperactive delirium with cognition outcomes. We allowed for interaction between days of hypoactive and hyperactive delirium and adjusted for baseline and in-hospital covariates. MEASUREMENTS AND RESULTS: Hypoactive delirium was more common and persistent than hyperactive delirium (71% vs 17%; median 3 vs 1 d). Longer duration of hypoactive delirium was associated with worse global cognition at 3 (−5.13 [−8.75 to −1.51]; p = 0.03) but not 12 (−5.76 [−9.99 to −1.53]; p = 0.08) months and with worse executive functioning at 3 (−3.61 [−7.48 to 0.26]; p = 0.03) and 12 (−6.22 [−10.12 to −2.33]; p = 0.004) months; these associations were not modified by hyperactive delirium. Hyperactive delirium was not associated with global cognition or executive function in this cohort. CONCLUSIONS: Longer duration of hypoactive delirium was independently associated with worse long-term cognition. Assessing motoric subtypes of delirium in the ICU might aid in prognosis and intervention allocation. Future studies should consider delineating motoric subtypes of delirium. (Crit Care Med 2020; 48:e480–e488)

Objective The aim of this study was to determine the health utility states of the most commonly used traumatic brain injury (TBI) clinical trial endpoint, the Extended Glasgow Outcome Scale (GOSE). Summary background data Health utilities represent the strength of one's preferences under conditions of uncertainty. There are insufficient data to indicate how an individual would value levels of disability after a TBI. Methods This was a cross-sectional web-based online convenience sampling adaptive survey. Using a standard gamble approach, participants evaluated their preferences for GOSE health states 1 year after a hypothetical TBI. The categorical GOSE was studied from vegetative state (GOSE2) to upper good recovery (GOSE8). Median (25th percentile, 75th percentile) health utility values for different GOSE states after TBI, ranging from -1 (worse than death) to 1 (full health), with 0 as reference (death). Results Of 3508 eligible participants, 3235 (92.22%) completed the survey. Participants rated lower GOSE states as having lower utility, with some states rated as worse than death, though the relationship was nonlinear and intervals were unequal between health states. Over 75% of participants rated a vegetative state (GOSE2, absence of awareness and bedridden) and about 50% rated lower severe disability (GOSE3, housebound needing all-day assistance) as conditions worse than death. Conclusions In the largest investigation of public perceptions about post-TBI disability, we demonstrate unequally rated health states, with some states perceived as worse than death. Although limited by selection bias, these results may guide future comparative-effectiveness research and shared medical decision-making after neurologic injury.

Background The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year. Methods We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium. Results Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2-7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2-7) days and 1 (1-2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year. Conclusions Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Background Civilian penetrating traumatic brain injury (pTBI) is a serious public health problem in the United States, but predictors of outcome remain largely understudied. We previously developed the Survival After Acute Civilian Penetrating Brain Injuries (SPIN) score, a logistic, regression-based risk stratification scale for estimating in-hospital and 6-mo survival after civilian pTBI with excellent discrimination (area under the receiver operating curve [AUC-ROC = 0.96]) and calibration, but it has not been validated. Objective To validate the SPIN score in a multicenter cohort. Methods We identified pTBI patients from 3 United States level-1 trauma centers. The SPIN score variables (motor Glasgow Coma Scale [mGCS], sex, admission pupillary reactivity, self-inflicted pTBI, transfer status, injury severity score, and admission international normalized ratio [INR]) were retrospectively collected from local trauma registries and chart review. Using the original SPIN score multivariable logistic regression model, AUC-ROC analysis and Hosmer-Lemeshow goodness of fit testing were performed to determine discrimination and calibration. Results Of 362 pTBI patients available for analysis, 105 patients were lacking INR, leaving 257 patients for the full SPIN model validation. Discrimination (AUC-ROC = 0.88) and calibration (Hosmer-Lemeshow goodness of fit, P value = .58) were excellent. In a post hoc sensitivity analysis, we removed INR from the SPIN model to include all 362 patients (SPINNo-INR), still resulting in very good discrimination (AUC-ROC = 0.82), but reduced calibration (Hosmer-Lemeshow goodness of fit, P value = .04). Conclusion This multicenter pTBI study confirmed that the full SPIN score predicts survival after civilian pTBI with excellent discrimination and calibration. Admission INR significantly adds to the prediction model discrimination and should be routinely measured in pTBI patients.

Frailty is a predominant predictor of poor outcomes in older populations. This article presents a review of the concept of frailty and its role for prognostication among geriatric trauma and surgery patients. We discuss models of frailty defined in the scientific literature, emphasizing that frailty is a process of biologic aging. We emphasize the importance of screening, assessment, and inclusion of frailty indices for the development and use of prognostication instruments/tools in the population of interest. Finally, we discuss best practices for the delivery of prognostic information in acute care settings and specific recommendations for trauma and surgical care settings.

Objective In intensive care units (ICUs), a patient’s brain function status can shift from a state of acute brain dysfunction (ABD) to one that is ABD-free and vice versa, which is challenging to forecast and, in turn, hampers the allocation of hospital resources. We aim to develop a machine learning model to predict next-day brain function status changes. Materials and Methods Using multicenter prospective adult cohorts involving medical and surgical ICU patients from 2 civilian and 3 Veteran Affairs hospitals, we trained and externally validated a light gradient boosting machine to predict brain function status changes. We compared the performances of the boosting model against state-of-the-art models—an ABD predictive model and its variants. We applied Shapley additive explanations to identify influential factors to develop a compact model. Results There were 1026 critically ill patients without evidence of prior major dementia, or structural brain diseases, from whom 12 295 daily transitions (ABD: 5847 days; ABD-free: 6448 days) were observed. The boosting model achieved an area under the receiver-operating characteristic curve (AUROC) of 0.824 (95% confidence interval [CI], 0.821-0.827), compared with the state-of-the-art models of 0.697 (95% CI, 0.693-0.701) with P Conclusion The inputs of the compact model are based on several simple questions that clinicians can quickly answer in practice, which demonstrates the model has direct prospective deployment potential into clinical practice, aiding in critical hospital resource allocation.

Study objective To determine the association between postoperative delirium (POD) and cognitive outcomes at least 1 month after surgery in elderly patients, and synthesize the dynamic risk trajectory of cognition impairment after POD. Design Meta-analysis searching PubMed, Cochrane and EMBASE from inception to November 1, 2020. The terms postoperative delirium, delirium after surgery, postsurgical delirium, postoperative cogniti*, postoperative cognitive dysfunction, postoperative cognition decline, cognitive decline, cognitive impair* and dement* were searched alone or in combination. Measurements Inclusion criteria were prospective cohort studies investigating the association between POD and cognitive outcomes in patients aged ≥60 years underwent surgery. The primary outcome was the association between POD and cognitive outcomes at 1 or more months after surgery. We considered cognitive outcomes measured up to 12 months after surgery as short-term and beyond 12 months as long-term. Two authors performed the study screening, data extraction and quality assessments. Effect sizes were calculated as Hedges g or Odds ratio (OR) based on random- and fixed-effects models. Meta-regression was conducted to analyze the role of potential contributors to heterogeneity. Main results Eighteen studies were included. Our result showed a significant and medium association between POD and cognitive outcomes after at least 1 month postoperatively (g = 0.61 95% CI 0.43–0.79; I2 = 65.1%), indicating that patients with POD were associated with worse cognitive outcomes. The association of POD with short- and long-term cognitive impairment were also both significant (short-term: g = 0.46 95% CI 0.24–0.68; I2 = 53.1%; and long-term: g = 0.82 95% CI 0.57–1.06; I2 = 57.1%). A multivariate meta-regression suggested that age and measure of delirium were significant sources of heterogeneity. POD was also associated with the significant risk for dementia (OR = 6.08 95% CI 3.80–9.72; I2 = 0) as well as attention (OR = 1.74 95% CI 1.13–2.68; I2 = 0), executive (OR = 1.33 95% CI 1.00–1.80; I2 = 0) and memory impairment (OR = 1.59 95% CI 1.20–2.10; I2 = 43.0%). Additionally, our results showed that the risk trajectory for cognitive decline associated with POD within five years after surgery revealed exponential growth. Conclusions This is the first meta-analysis quantifying the association between POD and cognitive outcomes. Our results showed that POD was significantly associated with worse cognitive outcomes, including short- and long-term cognitive outcomes following surgery.

Introduction: Catatonia, characterized by motor, behavioral and affective abnormalities, frequently co-occurs with delirium during critical illness. Advanced age is a known risk factor for development of delirium. However, the association between age and catatonia has not been described. We aim to describe the occurrence of catatonia, delirium, and coma by age group in a critically ill, adult population.Design: Convenience cohort, nested within two clinical trials and two observational cohort studies.Setting: Intensive care units in an academic medical center in Nashville, TN.Patients: 378 critically ill adult patients on mechanical ventilation and/or vasopressors.Measurements and Main Results: Patients were assessed for catatonia, delirium, and coma by independent and blinded personnel, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method for the Intensive Care Unit (ICU) and the Richmond Agitation and Sedation Scale. Of 378 patients, 23% met diagnostic criteria for catatonia, 66% experienced delirium, and 52% experienced coma during the period of observation. There was no relationship found between age and catatonia severity or age and presence of specific catatonia items. The prevalence of catatonia was strongly associated with age in the setting of critical illness (p < 0.05). Delirium and comas' association with age was limited to the setting of catatonia.Conclusion: Given the significant relationship between age and catatonia independent of coma and delirium status, these data demonstrate catatonia's association with advanced age in the setting of critical illness. Future studies can explore the causative factors for this association and further elucidate the risk factors for acute brain dysfunction across the age spectrum.

BACKGROUND: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown. METHODS: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation–Sedation Scale (RASS, on which scores range from −5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months. RESULTS: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses — 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups. CONCLUSIONS: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.)

Background Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. Research Question Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? Study Design and Methods This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. Results Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). Interpretation In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. Trial Registry ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov

Objective We aimed to identify socioeconomic and clinical risk factors for post-intensive care unit (ICU)-related long-term cognitive impairment (LTCI). Summary background data After delirium during ICU stay, LTCI has been increasingly recognized, but without attention to socioeconomic factors. Methods We enrolled a prospective, multicenter cohort of ICU survivors with shock or respiratory failure from surgical and medical ICUs across 5 civilian and Veteran Affairs (VA) hospitals from 2010 to 2016. Our primary outcome was LTCI at 3- and 12 months post-hospital discharge defined by the Repeatable Battery for Assessment of Neuropsychological Symptoms (RBANS) global score. Covariates adjusted using multivariable linear regression included age, sex, race, AHRQ socioeconomic index, Charlson comorbidity, Framingham stroke risk, Sequential Organ Failure Assessment, duration of coma, delirium, hypoxemia, sepsis, education level, hospital type, insurance status, discharge disposition, and ICU drug exposures. Results Of 1040 patients, 71% experienced delirium, and 47% and 41% of survivors had RBANS scores >1 standard deviation below normal at 3- and 12 months, respectively. Adjusted analysis indicated that delirium, non-White race, lower education, and civilian hospitals (as opposed to VA), were associated with at least a half standard deviation lower RBANS scores at 3- and 12 months (P ≤ 0.03). Sex, AHRQ socioeconomic index, insurance status, and discharge disposition were not associated with RBANS scores. Conclusions Socioeconomic and clinical risk factors, such as race, education, hospital type, and delirium duration, were linked to worse PICS ICU-related, LTCI. Further efforts may focus on improved identification of higher-risk groups to promote survivorship through emerging improvements in cognitive rehabilitation.

Background Trauma patients may present with nonsurvivable injuries, which could be resuscitated for future organ transplantation. Trauma surgeons face an ethical dilemma of deciding whether, when, and how to resuscitate a patient who will not directly benefit from it. As there are no established guidelines to follow, we aimed to describe resuscitation practices for organ transplantation; we hypothesized that resuscitation practices vary regionally. Method Over a 3-month period, we surveyed trauma surgeons practicing in Levels I and II trauma centers within a single state using an instrument to measure resuscitation attitudes and practices for organ preservation. Descriptive statistics were calculated for practice patterns. Results The survey response rate was 51% (31/60). Many (81%) had experience with resuscitations where the primary goal was to preserve potential for organ transplantation. Many (90%) said they encountered this dilemma at least monthly. All respondents were willing to intubate; most were willing to start vasopressors (94%) and to transfuse blood (84%) (range, 1 unit to >10 units). Of respondents, 29% would resuscitate for ≥24 hours, and 6% would perform a resuscitative thoracotomy. Respect for patients’ dying process and future organ quality were the factors most frequently considered very important or important when deciding to stop or forgo resuscitation, followed closely by concerns about excessive resource use. Conclusion Trauma surgeons’ regional resuscitation practices vary widely for this patient population. This variation implies a lack of professional consensus regarding initiation and extent of resuscitations in this setting. These data suggest this is a common clinical challenge, which would benefit from further study to determine national variability, areas of equipoise, and features amenable to practice guidelines.

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients, and can be classified into mild, moderate, and severe by the Glasgow coma scale (GCS). Prehospital, initial emergency department, and subsequent intensive care unit (ICU) management of severe TBI should focus on avoiding secondary brain injury from hypotension and hypoxia, with appropriate reversal of anticoagulation and surgical evacuation of mass lesions as indicated. Utilizing principles based on the Monro–Kellie doctrine and cerebral perfusion pressure (CPP), a surrogate for cerebral blood flow (CBF) should be maintained by optimizing mean arterial pressure (MAP), through fluids and vasopressors, and/or decreasing intracranial pressure (ICP), through bedside maneuvers, sedation, hyperosmolar therapy, cerebrospinal fluid (CSF) drainage, and, in refractory cases, barbiturate coma or decompressive craniectomy (DC). While controversial, direct ICP monitoring, in conjunction with clinical examination and imaging as indicated, should help guide severe TBI therapy, although new modalities, such as brain tissue oxygen (PbtO2) monitoring, show great promise in providing strategies to optimize CBF. Optimization of the acute care of severe TBI should include recognition and treatment of paroxysmal sympathetic hyperactivity (PSH), early seizure prophylaxis, venous thromboembolism (VTE) prophylaxis, and nutrition optimization. Despite this, severe TBI remains a devastating injury and palliative care principles should be applied early. To better affect the challenging long-term outcomes of severe TBI, more and continued high quality research is required.

Background Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place. Methods Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting. Results We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms. Conclusions These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference. Electronic supplementary material The online version of this article (10.1007/s00134-019-05900-x) contains supplementary material, which is available to authorized users.

Multiple instance learning (MIL) is a supervised learning methodology that aims to allow models to learn instance class labels from bag class labels, where a bag is defined to contain multiple instances. MIL is gaining traction for learning from weak labels but has not been widely applied to 3D medical imaging. MIL is well-suited to clinical CT acquisitions since (1) the highly anisotropic voxels hinder application of traditional 3D networks and (2) patch-based networks have limited ability to learn whole volume labels. In this work, we apply MIL with a deep convolutional neural network to identify whether clinical CT head image volumes possess one or more large hemorrhages (> 20cm$^3$), resulting in a learned 2D model without the need for 2D slice annotations. Individual image volumes are considered separate bags, and the slices in each volume are instances. Such a framework sets the stage for incorporating information obtained in clinical reports to help train a 2D segmentation approach. Within this context, we evaluate the data requirements to enable generalization of MIL by varying the amount of training data. Our results show that a training size of at least 400 patient image volumes was needed to achieve accurate per-slice hemorrhage detection. Over a five-fold cross-validation, the leading model, which made use of the maximum number of training volumes, had an average true positive rate of 98.10%, an average true negative rate of 99.36%, and an average precision of 0.9698. The models have been made available along with source code to enabled continued exploration and adaption of MIL in CT neuroimaging.

The current literature available on delirium after primary neurologic injury (PNI) is not as robust as that for other critically ill patients, but the emerging literature suggests similar findings to non-neurologically injured delirium cohorts hailing from medical and/or surgical intensive care units (ICUs). Delirium is measurable after PNI with reasonable test characteristics for a number of existing delirium assessment tools. After PNI, there is a significant impact of delirium on hospital and ICU length of stay, as well as cognitive and functional outcomes, but delirium’s impact on mortality in PNI is uncertain. The best data are in poststroke delirium, with a significant paucity of large prospective studies in patients with traumatic brain injury. Further work needs to be done both on confirming the outcomes of delirium and potentially different subsets of risk factors in patients with PNI, as well as the development of delirium assessment methods tailored to patients with altered language processing and visuospatial deficits from their underlying brain injury.

Intensive care unit (ICU) delirium is highly prevalent and a potentially avoidable hospital complication. The current cost of ICU delirium is unknown.To specify the association between the daily occurrence of delirium in the ICU with costs of ICU care accounting for time-varying illness severity and death.We performed a prospective cohort study within medical and surgical ICUs in a large academic medical center.We analyzed critically ill patients (N=479) with respiratory failure and/or shock.Covariates included baseline factors (age, insurance, cognitive impairment, comorbidities, Acute Physiology and Chronic Health Evaluation II Score) and time-varying factors (sequential organ failure assessment score, mechanical ventilation, and severe sepsis). The primary analysis used a novel 3-stage regression method: first, estimation of the cumulative cost of delirium over 30 ICU days and then costs separated into those attributable to increased resource utilization among survivors and those that were avoided on the account of delirium's association with early mortality in the ICU.The patient-level 30-day cumulative cost of ICU delirium attributable to increased resource utilization was $17,838 (95% confidence interval, $11,132-$23,497). A combination of professional, dialysis, and bed costs accounted for the largest percentage of the incremental costs associated with ICU delirium. The 30-day cumulative incremental costs of ICU delirium that were avoided due to delirium-associated early mortality was $4654 (95% confidence interval, $2056-7869).Delirium is associated with substantial costs after accounting for time-varying illness severity and could be 20% higher (∼$22,500) if not for its association with early ICU mortality.

OBJECTIVES To describe the frequency of co-occurring newly acquired cognitive impairment, disability in activities of daily livings, and depression among survivors of a critical illness and to evaluate predictors of being free of post-intensive care syndrome problems. DESIGN Prospective cohort study. SETTING Medical and surgical ICUs from five U.S. centers. PATIENTS Patients with respiratory failure or shock, excluding those with preexisting cognitive impairment or disability in activities of daily livings. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS At 3 and 12 months after hospital discharge, we assessed patients for cognitive impairment, disability, and depression. We categorized patients into eight groups reflecting combinations of cognitive, disability, and mental health problems. Using multivariable logistic regression, we modeled the association between age, education, frailty, durations of mechanical ventilation, delirium, and severe sepsis with the odds of being post-intensive care syndrome free. We analyzed 406 patients with a median age of 61 years and an Acute Physiology and Chronic Health Evaluation II of 23. At 3 and 12 months, one or more post-intensive care syndrome problems were present in 64% and 56%, respectively. Nevertheless, co-occurring post-intensive care syndrome problems (i.e., in two or more domains) were present in 25% at 3 months and 21% at 12 months. Post-intensive care syndrome problems in all three domains were present in only 6% at 3 months and 4% at 12 months. More years of education was associated with greater odds of being post-intensive care syndrome free (p < 0.001 at 3 and 12 mo). More severe frailty was associated with lower odds of being post-intensive care syndrome free (p = 0.005 at 3 mo and p = 0.048 at 12 mo). CONCLUSIONS In this multicenter cohort study, one or more post-intensive care syndrome problems were present in the majority of survivors, but co-occurring problems were present in only one out of four. Education was protective from post-intensive care syndrome problems and frailty predictive of the development of post-intensive care syndrome problems. Future studies are needed to understand better the heterogeneous subtypes of post-intensive care syndrome and to identify modifiable risk factors.

BackgroundTrauma-related hospitalizations drive a high percentage of health care expenditure and inpatient resource consumption, which is directly related to length of stay (LOS). Robust and reliable interactions among health care employees can reduce LOS. However, there is little known about whether certain patterns of interactions exist and how they relate to LOS and its variability. The objective of this study is to learn interaction patterns and quantify the relationship to LOS within a mature trauma system and long-standing electronic medical record (EMR).MethodsWe adapted a spectral co-clustering methodology to infer the interaction patterns of health care employees based on the EMR of 5588 hospitalized adult trauma survivors. The relationship between interaction patterns and LOS was assessed via a negative binomial regression model. We further assessed the influence of potential confounders by age, number of health care encounters to date, number of access action types care providers committed to patient EMRs, month of admission, phenome-wide association study codes, procedure codes, and insurance status.ResultsThree types of interaction patterns were discovered. The first pattern exhibited the most collaboration between employees and was associated with the shortest LOS. Compared to this pattern, LOS for the second and third patterns was 0.61 days (P = 0.014) and 0.43 days (P = 0.037) longer, respectively. Although the 3 interaction patterns dealt with different numbers of patients in each admission month, our results suggest that care was provided for similar patients.DiscussionThe results of this study indicate there is an association between LOS and the extent to which health care employees interact in the care of an injured patient. The findings further suggest that there is merit in ascertaining the content of these interactions and the factors that induce these differences in interaction patterns within a trauma system.

Introduction: Platelet dysfunction following traumatic brain injury (TBI) is associated with worse outcomes. The efficacy of platelet transfusion to reverse antiplatelet medication (APM) remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve outcomes following TBI.Methods: An observational study at six US trauma centres was performed. Adult patients on APM with CT evident TBI after blunt injury were enrolled. Demographics, brain CT and TEG-PM results before/after platelet transfusion, length of stay (LOS), and injury severity score (ISS) were abstracted.Results: Sixty six patients were enrolled (89% aspirin, 50% clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion. Transfused patients had significantly higher ISS and admission CT scores. Platelet transfusion significantly reduced platelet inhibition due to aspirin (76.0 ± 30.2% to 52.7 ± 31.5%, p

Background: The relationship between plasma concentration of sedatives and delirium is unknown. Objective: We hypothesized that higher plasma concentrations of lorazepam are associated with increased delirium risk, whereas higher plasma concentrations of dexmedetomidine are associated with reduced delirium risk. Methods: This prospective cohort study was embedded in a double-blind randomized clinical trial, where ventilated patients received infusions of lorazepam and dexmedetomidine. Plasma concentrations of these drugs and delirium assessments were measured at least daily. A multivariable logistic regression model accounting for repeated measures was used to analyze associations between same-day plasma concentrations of lorazepam and dexmedetomidine (exposures) and the likelihood of next-day delirium (outcome), adjusting for same-day mental status (delirium, coma, or normal) and same-day fentanyl doses. Results: This critically ill cohort (n = 103) had a median age of 60 years (IQR: 48-66) with APACHE II score of 28 (interquartile range [IQR] = 24-32), where randomization resulted in assignment to lorazepam (n = 51) or dexmedetomidine (n = 52). After adjusting for same-day fentanyl dose and mental status, higher plasma concentrations of lorazepam were associated with increased probability of next-day delirium (comparing 500 vs 0 ng/mL; odds ratio [OR] = 13.2; 95% CI = 1.4-120.1; P = 0.02). Plasma concentrations of dexmedetomidine were not associated with next-day delirium (comparing 1 vs 0 ng/mL; OR = 1.1; 95% CI = 0.9-1.3; P = 0.45). Conclusions: In critically ill patients, higher lorazepam plasma concentrations were associated with delirium, whereas dexmedetomidine plasma concentrations were not. This implies that the reduced delirium risk seen in patients sedated with dexmedetomidine may be a result of avoidance of benzodiazepines, rather than a dose-dependent protective effect of dexmedetomidine.

To determine if beta-(β)-blockers improve outcomes after acute traumatic brain injury (TBI).There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with β-blockers offers a potentially beneficial approach.Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was β-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I).Data were extracted from 9 included studies encompassing 2005 unique TBI patients with β-blocker treatment and 6240 unique controls. Exposure to β-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified.In adults with acute TBI, observational studies reveal a significant mortality advantage with β-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital β-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after β-blocker use for TBI.

Delirium is one of the most common behavioral manifestations of acute brain dysfunction in the intensive care unit (ICU) and is a strong predictor of worse outcome. Routine monitoring for delirium is recommended for all ICU patients using validated tools. In delirious patients, a search for all reversible precipitants is the first line of action and pharmacologic treatment should be considered when all causes have been ruled out, and it is not contraindicated. Long-term morbidity has significant consequences for survivors of critical illness and for their caregivers. ICU patients may develop posttraumatic stress disorder related to their critical illness experience.

Traumatic brain injury (TBI) is a leading cause of death and disability in trauma patients. As the primary injury cannot be undone, management strategies must therefore focus on preventing secondary injury by avoiding hypotension and hypoxia and maintaining appropriate cerebral perfusion pressure (CPP), which is a surrogate for cerebral blood flow (CBF). Cerebral perfusion pressure can be maintained by increasing mean arterial pressure (MAP), decreasing intracranial pressure (ICP), or both. MAP can be increased through a combination of pressors in the euvolemic state, although the ideal fluid in TBI patients is unknown. The goal should be euvolemia and avoidance of hypotension. Elevated intracranial pressure can be treated through an algorithmic approach utilization simple bedside maneuvers, hyperosmolar therapy, cerebral spinal fluid (CSF) drainage as well as pentobarbital coma and decompressive craniectomy in refractory cases. Mass lesions may require operative evacuation depending on size, exam findings, and ICP measurements. Although CPP may not be an ideal surrogate for cerebral blood flow and metabolic delivery, other modalities have not gained widespread use due to paucity of strong data. Other factors that deserve important consideration in the acute management of TBI patients are venous thromboembolism, stress ulcer, and seizure prophylaxis as well as nutritional and metabolic optimization.

Surgeons perceive that some surgical transfers are futile, but the incidence and risk factors of futile transfer are not quantified. Identifying futile interfacility transfers could save cost and undue burdens to patients and families. We sought to describe the incidence and factors associated with futile transfers. We conducted a retrospective cohort study from 2009 to 2013 including patients transferred to a tertiary referral center for general or vascular surgical care. Futile transfers were defined as resulting in death or hospice discharge within 72 hours of transfer without operative, endoscopic, or radiologic intervention. One per cent of patient transfers were futile (27/ 1696). Characteristics of futile transfers included older age, higher comorbidity burden and illness severity, vascular surgery admission, Medicare insurance, and surgeon documentation of end-stage disease as a factor in initial decision-making. Among futile transfers, 82 per cent were designated as do not resuscitate (vs 9% of nonfutile, P < 0.01), and 59 per cent received a palliative care consult (vs 7%, P < 0.01). A small but salient proportion of transferred patients undergo deliberate care de-escalation and early death or hospice discharge without intervention. Efforts to identify such patients before transfer through improved communication between referring and accepting surgeons may mitigate burdens of transfer and facilitate more comfortable deaths in patients’ local communities.

Background Mentorship programs in surgery are used to overcome barriers to clinical and academic productivity, research success, and work-life balance. We sought to determine if the Eastern Association for the Surgery of Trauma (EAST) Mentoring Program has met its goals of fostering academic and personal growth in young acute care surgeons. Methods We conducted a systematic program evaluation of EAST Mentoring Program's first 4 years. Demographic information was collected from EAST records, mentorship program applications, and mentee-mentor career development plans. We reviewed the career development plans for thematic commonalities and results of a structured, online questionnaire distributed since program inception. A mixed methods approach was used to better understand the program goals from both mentee and mentor perspectives, as well as attitudes and barriers regarding the perceived success of this career development program. Results During 2012 to 2015, 65 mentoring dyads were paired and 60 completed the program. Of 184 surveys distributed, 108 were returned (57% response rate). Respondents were evenly distributed between mentees and mentors (53 vs. 55, p = 0.768). In participant surveys, mentoring relationships were viewed to focus on research (45%), "sticky situations" (e.g., communication, work-life balance) (27%), education (18%), or administrative issues (10%). Mentees were more focused on research and education versus mentors (74% vs. 50%; p = 0.040). Mentees felt that goals were "always" or "usually" met versus mentors (89% vs. 77%; p = 0.096). Two barriers to successful mentorship included time and communication, with most pairs communicating by email. Most respondents (91%) planned to continue the relationship beyond the EAST Mentoring Program and recommended the experience to colleagues. Conclusion Mentee satisfaction with the EAST Mentoring Program was high. Mentoring is a beneficial tool to promote success among EAST's young members, but differences exist between mentee and mentor perceptions. Revising communication expectations and time commitment to improve career development may help our young acute care surgeons.

The ABCDEF bundle represents an evidence-based guide for clinicians to approach the organizational changes needed for optimizing ICU patient recovery and outcomes. The ABCDEF bundle includes: Assess, Prevent, and Manage Pain, Both Spontaneous Awakening Trials (SAT) and Spontaneous Breathing Trials (SBT), Choice of analgesia and sedation, Delirium: Assess, Prevent, and Manage, Early mobility and Exercise, and Family engagement and empowerment. In this chapter, we will review the core evidence and features behind the ABCDEF bundle. The bundle has individual components that are clearly defined, flexible to implement, and help empower multidisciplinary clinicians and families in the shared care of the critically ill. The ABCDEF bundle helps guide well-rounded patient care and optimal resource utilization resulting in more interactive ICU patients with better controlled pain, who can safely participate in higher-order physical and cognitive activities at the earliest point in their critical illness.

Rib fractures are identified in 10% of all injury victims and are associated with significant morbidity (33%) and mortality (12%). Significant progress has been made in the management of rib fractures over the past few decades, including operative reduction and internal fixation (rib ORIF); however, the subset of patients that would benefit most from this procedure remains ill-defined. The aim of this project was to develop evidence-based recommendations.Population, intervention, comparison, and outcome (PICO) questions were formulated for patients with and without flail chest. Outcomes of interest included mortality, duration of mechanical ventilation (DMV), hospital and intensive care unit (ICU) length of stay (LOS), incidence of pneumonia, need for tracheostomy, and pain control. A systematic review and meta-analysis of currently available evidence was performed per the Grading of Recommendations Assessment, Development, and Evaluation methodology.Twenty-two studies were identified and analyzed. These included 986 patients with flail chest, of whom 334 underwent rib ORIF. Rib ORIF afforded lower mortality; shorter DMV, hospital LOS, and ICU LOS; and lower incidence of pneumonia and need for tracheostomy. The data quality was deemed very low, with only three prospective randomized trials available. Analyses for pain in patients with flail chest and all outcomes in patients with nonflail chest were not feasible due to inadequate data.In adult patients with flail chest, we conditionally recommend rib ORIF to decrease mortality; shorten DMV, hospital LOS, and ICU LOS; and decrease incidence of pneumonia and need for tracheostomy. We cannot offer a recommendation for pain control, or any of the outcomes in patients with nonflail chest with currently available data.Systematic review/meta-analysis, level III.

Brain injury; Head trauma; Algorithm Daño cerebral; Trauma en la cabeza; Algoritmo Lesió cerebral; Trauma al cap; Algoritme Background: Management algorithms for adult severe traumatic brain injury (sTBI) were omitted in later editions of the Brain Trauma Foundation’s sTBI Management Guidelines, as they were not evidence-based. Methods: We used a Delphi-method-based consensus approach to address management of sTBI patients undergoing intracranial pressure (ICP) monitoring. Forty-two experienced, clinically active sTBI specialists from six continents comprised the panel. Eight surveys iterated queries and comments. An in-person meeting included whole- and small-group discussions and blinded voting. Consensus required 80% agreement. We developed heatmaps based on a traffic-light model where panelists’ decision tendencies were the focus of recommendations. Results: We provide comprehensive algorithms for ICP-monitor-based adult sTBI management. Consensus established 18 interventions as fundamental and ten treatments not to be used. We provide a three-tier algorithm for treating elevated ICP. Treatments within a tier are considered empirically equivalent. Higher tiers involve higher risk therapies. Tiers 1, 2, and 3 include 10, 4, and 3 interventions, respectively. We include inter-tier considerations, and recommendations for critical neuroworsening to assist the recognition and treatment of declining patients. Novel elements include guidance for autoregulation-based ICP treatment based on MAP Challenge results, and two heatmaps to guide (1) ICP-monitor removal and (2) consideration of sedation holidays for neurological examination. Conclusions: Our modern and comprehensive sTBI-management protocol is designed to assist clinicians managing sTBI patients monitored with ICP-monitors alone. Consensus-based (class III evidence), it provides management recommendations based on combined expert opinion. It reflects neither a standard-of-care nor a substitute for thoughtful individualized management. We thank our financial supporters who include Adler/Geirsch Attorney at Law, the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Neurotrauma and Critical Care, Bard, the Brain Trauma Foundation, DePuy, Hemedex, Integra, the Neurointensive Care Section of the European Society of Intensive Care Medicine, Neurosurgical Society of Australasia, Medtronic, Moberg Research, Natus, Neuroptics, Raumedic, Sophysa, Stryker, and Zoll.

Purpose Delirium is prevalent but with unclear pathogenesis. Neuronal injury repair pathways may be protective. We hypothesized that higher concentrations of neuronal repair biomarkers would be associated with decreased delirium in critically ill patients. Materials and methods We performed a nested study of hospital survivors within a prospective cohort that enrolled patients within 72 h of respiratory failure or shock. We measured plasma concentrations of ubiquitin carboxyl-terminal-esterase-L1 (UCHL1) and brain-derived neurotrophic factor (BDNF) from blood collected at enrollment. Delirium was assessed twice daily using the CAM-ICU. Multivariable regression was used to examine the associations between biomarkers and delirium prevalence/duration, adjusting for covariates and interactions with age and IL-6 plasma concentration. Results We included 427 patients with a median age of 59 years (IQR 48–69) and APACHE II score of 25 (IQR 19–30). Higher plasma concentration of UCHL1 on admission was independently associated with lower prevalence of delirium (p = .04) but not associated with duration of delirium (p = .06). BDNF plasma concentration was not associated with prevalence (p = .26) or duration of delirium (p = .36). Conclusions During critical illness, higher UCHL1 plasma concentration is associated with lower prevalence of delirium; BDNF plasma concentration is not associated with delirium. Clinical trial number: NCT00392795 ; https://clinicaltrials.gov/ct2/show/NCT00392795

Background While understanding of critical illness and delirium continue to evolve, the impact on clinical practice is often unknown and delayed. Our purpose was to provide insight into practice changes by characterizing analgesia and sedation usage and occurrence of delirium in different years and international regions. Methods We performed a retrospective analysis of two multicenter, international, prospective cohort studies. Mechanically ventilated adults were followed for up to 28 days in 2010 and 2016. Proportion of days utilizing sedation, analgesia, and performance of a spontaneous awakening trial (SAT), and occurrence of delirium were described for each year and region and compared between years. Results A total of 14,281 patients from 6 international regions were analyzed. Proportion of days utilizing analgesia and sedation increased from 2010 to 2016 (p

Brain imaging analysis on clinically acquired computed tomography (CT) is essential for the diagnosis, risk prediction of progression, and treatment of the structural phenotypes of traumatic brain injury (TBI). However, in real clinical imaging scenarios, entire body CT images (e.g., neck, abdomen, chest, pelvis) are typically captured along with whole brain CT scans. For instance, in a typical sample of clinical TBI imaging cohort, only ~15% of CT scans actually contain whole brain CT images suitable for volumetric brain analyses; the remaining are partial brain or non-brain images. Therefore, a manual image retrieval process is typically required to isolate the whole brain CT scans from the entire cohort. However, the manual image retrieval is time and resource consuming and even more difficult for the larger cohorts. To alleviate the manual efforts, in this paper we propose an automated 3D medical image retrieval pipeline, called deep montage-based image retrieval (dMIR), which performs classification on 2D montage images via a deep convolutional neural network. The novelty of the proposed method for image processing is to characterize the medical image retrieval task based on the montage images. In a cohort of 2000 clinically acquired TBI scans, 794 scans were used as training data, 206 scans were used as validation data, and the remaining 1000 scans were used as testing data. The proposed achieved accuracy=1.0, recall=1.0, precision=1.0, f1=1.0 for validation data, while achieved accuracy=0.988, recall=0.962, precision=0.962, f1=0.962 for testing data. Thus, the proposed dMIR is able to perform accurate CT whole brain image retrieval from large-scale clinical cohorts., Accepted for SPIE: Medical Imaging 2019

PURPOSE: As deep neural networks achieve more success in the wide field of computer vision, greater emphasis is being placed on the generalizations of these models for production deployment. With sufficiently large training datasets, models can typically avoid overfitting their data; however, for medical imaging it is often difficult to obtain enough data from a single site. Sharing data between institutions is also frequently nonviable or prohibited due to security measures and research compliance constraints, enforced to guard protected health information (PHI) and patient anonymity. METHODS: In this paper, we implement cyclic weight transfer with independent datasets from multiple geographically disparate sites without compromising PHI. We compare results between single-site learning (SSL) and multi-site learning models (MSL) on testing data drawn from each of the training sites as well as two other institutions. RESULTS: The MSL model attains an average Dice Similarity Coefficient (DSC) of 0.690 on the holdout institution datasets with a volume correlation of 0.914, respectively corresponding to a 7% and 5% statistically significant improvement over the average of both SSL models, which attained an average DSC of 0.646 and average correlation of 0.871. CONCLUSIONS: We show that a neural network can be efficiently trained on data from two physically remote sites without consolidating patient data to a single location. The resulting network improves model generalization and achieves higher average DSCs on external datasets than neural networks trained on data from a single source.

Machine learning models are becoming commonplace in the domain of medical imaging, and with these methods comes an ever-increasing need for more data. However, to preserve patient anonymity it is frequently impractical or prohibited to transfer protected health information (PHI) between institutions. Additionally, due to the nature of some studies, there may not be a large public dataset available on which to train models. To address this conundrum, we analyze the efficacy of transferring the model itself in lieu of data between different sites. By doing so we accomplish two goals: 1) the model gains access to training on a larger dataset that it could not normally obtain and 2) the model better generalizes, having trained on data from separate locations. In this paper, we implement multi-site learning with disparate datasets from the National Institutes of Health (NIH) and Vanderbilt University Medical Center (VUMC) without compromising PHI. Three neural networks are trained to convergence on a computed tomography (CT) brain hematoma segmentation task: one only with NIH data, one only with VUMC data, and one multi-site model alternating between NIH and VUMC data. Resultant lesion masks with the multi-site model attain an average Dice similarity coefficient of 0.64 and the automatically segmented hematoma volumes correlate to those done manually with a Pearson correlation coefficient of 0.87, corresponding to an 8% and 5% improvement, respectively, over the single-site model counterparts.

The ABCDEF bundle (i.e., Assess, Prevent and Manage Pain; Both Spontaneous Awakening/Breathing Trials; Choice of analgesia and sedation; Delirium: Assess, Prevent, Manage; Early Mobility; Family engagement) is a popular topic in critical care and cardiac surgery. There are several special considerations depending on the patient population prior to embarking on these efforts. Patients requiring circulatory support for either respiratory and/or cardiac dysfunction via extracorporeal membrane oxygenation (ECMO) may have pulmonary and/or hemodynamic instability. This severity of illness may elevate uncertainty about the implementation of the ABCDEF bundle in ECMO patients, and herein lays the current evidence about using these elements in patients with severe cardiopulmonary dysfunction requiring this advanced life support.

To comprehensively describe the use of dexmedetomidine in a single institutional series of adult ICU patients with severe TBI. This study describes the dexmedetomidine dosage and infusion times, as well as the physiological parameters, neurological status and daily narcotic requirements before, during and after dexmedetomidine infusion.This study identified 85 adult patients with severe TBI who received dexmedetomidine infusions in the Trauma ICU at Vanderbilt University Medical Center between 2006-2010. Demographic, haemodynamic, narcotic use and sedative use data were systematically obtained from the medical record and analysed for changes associated with dexmedetomidine infusion.During infusion with dexmedetomidine, narcotic and sedative use decreased significantly (p0.001 and p0.05). Median MAP, SBP, DBP and HR also decreased significantly during infusion when compared to pre-infusion values (p0.001). Despite the use of dexmedetomidine, RASS and GCS scores improved from pre-infusion to infusion time periods.The findings demonstrate that initiation of dexmedetomidine infusion is not associated with a decline in neurological functioning in adults with severe TBI. Although there was an observed decrease in haemodynamic parameters during infusion with dexmedetomidine, the change was not clinically significant and the requirements for narcotics and additional sedatives were minimized.

Colonic obstruction is a surgical emergency, and delay in decompression results in added morbidity and mortality. Advances have led to less invasive procedures such as stenting as a bridge for definitive surgery. The aim of this article was to perform a systematic review regarding colon obstruction (malignant or benign) and to provide recommendations following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework.A systematic literature review was conducted using the PubMed, EMBASE, and the Cochrane Library databases of published studies. The search was last performed on January 2, 2015. Two independent reviewers extracted the desired variables from the studies. For our meta-analysis, we used Review Manager X.6 (RevMan). Recommendations are provided using GRADE methodology. A single POPULATION, Intervention, Comparator, Outcome (PICO) question with two outcomes was addressed as follows:in adult patients with a colonic obstruction (malignant or benign).should surgery be performed.Comparator: versus endoscopic stenting.decreased mortality and decreased emergency, nonplanned procedures?The search yielded 210 results. Screening of the titles excluded 102 articles, leaving 108 for review. After abstract review, 71 additional articles were excluded because of failure to address the PICO questions of this guideline. Thirty-seven articles were reviewed in their entirety, of those six randomized control trials that evaluated the use of stents versus emergency surgery in colonic obstruction caused by malignant disease were included in the final qualitative review.We conditionally recommend endoscopic, colonic stenting (if available) as initial therapy for colonic obstruction. In our review, stent use was associated with decreased mortality and rates for emergency, nonplanned procedures to include reoperations. This conditional recommendation is limited to those with malignancy because of the lack of literature supporting this practice in benign colonic disease.

Background Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for. Methods Our study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with daily follow-up to 30 days. Our independent variable was exposure to previous-day antimicrobial class: beta-lactams (subclasses: penicillins, first- to third-generation cephalosporins, fourth-generation cephalosporins, and carbapenems), macrolides, fluoroquinolones, and other. We adjusted for baseline covariates (age, comorbidities, cognition scores, sepsis, and mechanical ventilation), previous-day covariates (delirium, doses of analgesics/sedatives, and antipsychotic use), and same-day covariates (illness severity). Our primary outcome of delirium was measured by using the Confusion Assessment Method for the ICU. A daily delirium logistic regression model was used with an ICU time-restricted sensitivity analysis including daily adjustment for sepsis and mechanical ventilation. Results Of 418 ICU patients, delirium occurred in 308 (74%) with a median of 3 days (interquartile range 2–6) among those affected and 318 (76%) were exposed to antimicrobials. When covariates and ICU type were adjusted for, only first- to third-generation cephalosporins were associated with delirium (logistic regression model odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.28–3.79, P = 0.004; sensitivity analysis OR = 2.13, 95% CI 1.10–4.10, P = 0.024). Conclusions First-, second-, and third-generation cephalosporins doubled the odds of delirium after baseline co-morbidities, ICU type, the course of critical care, and other competing antimicrobial and psychotropic medication risks were adjusted for. We did not find an association between delirium and cefepime, penicillins, carbapenems, fluoroquinolones, or macrolides.

BackgroundThere are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU).MethodsIn a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation.ResultsWritten informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms.ConclusionsThe use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .).