Would You Rather: Quantifying Traumatic Brain Injury Survivor Perceptions of Functional Status Through Their Surrogates.

OBJECTIVE: To quantify health utilities of the Glasgow Outcome Scale-Extended (GOSE) states after actual traumatic brain injury (TBI). BACKGROUND: Recovery after TBI is measured using the GOSE, a validated clinical trial endpoint. A recent public survey quantified the health utilities of some GOSE states after hypothetical TBI as worse than death. However, no health utilities exist for disability after actual TBI. METHODS: This national computer-adaptive survey followed Enhancing the Quality and Transparency of Health Research-Checklist for Reporting Results of Internet E-Surveys guidelines and recruited adult TBI survivors (injury >1 year prior) through their available surrogates. Using a standard gamble approach in randomized order, participants gave preferences for post-TBI categorical health states ranging from GOSE 2 to GOSE 8. We calculated median (interquartile range) health utilities for each GOSE state, from -1 (worse than death) to 1 (full health), with 0 as reference (death, GOSE 1). RESULTS: Of 515 eligible, 298 surrogates (58%) consented and completed the scenarios on TBI survivors' behalf. TBI survivors had a current median GOSE 5 (3-7). GOSE 2, GOSE 3, and GOSE 4 were rated worse than death by 89%, 64%, and 38%, respectively. The relationship was nonlinear, and intervals were unequal between states, with a bimodal distribution for GOSE 4. CONCLUSIONS: In this index study of actual post-TBI disability, poor neurological outcomes represented by GOSE 2 to GOSE 4 were perceived as worse than death by at least one in 3 survivors. Similar to previously reported public perceptions after a hypothetical TBI, these long-term perceptions may inform earlier post-TBI shared decision-making, as well as help shape value-based research and quality of care. LEVEL OF EVIDENCE: Level II-economic and value-based evaluations.

Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial.

OBJECTIVE: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). BACKGROUND: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. METHODS: This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. RESULTS: Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. CONCLUSION: Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Prevalence and Risk Factors for Intensive Care Unit Delirium After Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Delirium remains understudied after traumatic brain injury (TBI). We sought to identify independent predictors of delirium among intensive care unit (ICU) patients with TBI. METHODS: This single-center retrospective cohort study evaluated adult patients with TBI requiring ICU admission. Outcomes included delirium days within the first 14 days, as assessed by the Confusion Assessment Method-ICU (CAM-ICU). Models were adjusted for age, sex, insurance, Marshall head computed tomography classification, presence of subarachnoid hemorrhage (SAH), Injury Severity Score (ISS), need for cardiopulmonary resuscitation, maximum admission Glasgow Coma motor score, glucose level, hemoglobin level, and pupil reactivity. RESULTS: Delirium prevalence was 60%, with a median duration of 4 days (interquartile range: 2-8) among ICU patients with TBI (n = 2,664). Older age, higher ISS, maximum motor score < 6, Marshall class II-IV, and SAH were associated with risk of increased delirium duration (all p < 0.001). CONCLUSIONS: In this large cohort, ICU delirium after TBI affected three of five patients for a median duration of 4 days. Age, general injury severity, motor score, and features of intracranial hemorrhage were predictive of more TBI-associated delirium days. Given the high prevalence of ICU delirium after TBI and its impact on hospitalization, further work is needed to understand the impact of delirium and TBI on outcomes and to determine whether delirium risk can be minimized.

Worse Than Death: Survey of Public Perceptions of Disability Outcomes After Hypothetical Traumatic Brain Injury.

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.

Management and Challenges of Severe Traumatic Brain Injury.

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.

Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient?

Nivolumab is an immune checkpoint inhibitor (ICI) currently in phase 3 clinical trials for hepatocellular carcinoma. The safety of ICIs in recipients of organ allotransplant is unclear, and several reports of fatal alloimmune injury after posttransplant ICI use have been published. We present the first published case of nivolumab used in the pretransplant setting for HCC resulting in fatal acute hepatic necrosis in the immediate postoperative period from a profound immune reaction likely propagated by nivolumab. Further investigation and significant caution are needed in the evaluation of patients awaiting transplant who are receiving ICI therapy.

Socioeconomic Factors and Intensive Care Unit-Related Cognitive Impairment.

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.

Incidence of Endoscopic Retrograde Cholangiography after Subtotal Fenestrating and Reconstituting Cholecystectomy.

BACKGROUND: Laparoscopic subtotal cholecystectomy (SC) is used for the difficult cholecystectomy, but published experience with resource utilization for SC is limited. We hypothesized that the need for advanced resources are common after SC. STUDY DESIGN: Retrospective review of laparoscopic cholecystectomies between 2017 and 2021 at a large center. SC cases were identified using a medical record tool. Baseline characteristics were assessed with student's t-test and chi-squared. Primary outcome was ERC within 60-days. Secondary outcomes were reconstituted SC on post-op ERC and length of stay (LOS). Uni- and multivariable logistic regression were used for binary outcomes. Multiple linear regression was used for LOS. Covariates included age, sex, BMI, ASA class. RESULTS: A total of 1222 laparoscopic cholecystectomies were performed between 2017 and 2021. Of these, 87 (7%) were SC. Male (p<0.001) and older (p<0.001) patients were more likely to undergo SC. Odds of post-op ERC were higher in the SC group (OR 9.79 95% CI 5.90, 16.23 p<0.001). There was no difference in pre-op ERC (17% vs 21% p=0.38). Reconstituting SC had lower odds of post-op ERC (OR 0.12, 0.023-0.58, p=0.009). LOS was 1.81 times higher in the SC group(p=<0.001). Post-op ERC was not associated with LOS (p=.24). CONCLUSIONS: We present one of the largest single-center series of SC. SC patients are more likely to be male, older, have higher ASA class, and have increased LOS. SC should be performed when access to ERC and interventional radiology is available. Absent these adjuncts, reconstituting SC decreases the need for early ERC, but long-term outcomes are unknown.

Surrogate Perception of Disability after Hospitalization for Traumatic Brain Injury.

BACKGROUND: The Glasgow Outcome Scale Extended (GOSE) is a measure of recovery after traumatic brain injury (TBI). Public surveys rate some GOSE states as worse than death. Direct family experience caring for patients with TBI may impact views of post-TBI disability. STUDY DESIGN: We conducted a national cross-sectional computer-adaptive survey of surrogates of TBI dependents incurring injury more than 1 year earlier. Using a standard gamble approach in randomized order, surrogates evaluated preferences for post-TBI GOSE states from GOSE 2 (bedridden, unaware) to GOSE 8 (good recovery). We calculated median (interquartile range [IQR]) health utilities for each post-TBI state, ranging from -1 to 1, with 0 as reference (death = GOSE 1), and assessed sociodemographic associations using proportional odds logistic regression modeling. RESULTS: Of 515 eligible surrogates, 298 (58%) completed scenarios. Surrogates were median aged 46 (IQR 35 to 60), 54% married, with Santa Clara strength of faith 14 (10 to 18). TBI dependents had a median GOSE5 (3 to 7). Median (IQR) health utility ratings for GOSE 2, GOSE 3, and GOSE 4 were -0.06 (-0.50 to -0.01), -0.01 (-0.30 to 0.45), and 0.30 (-0.01 to 0.80), rated worse than death by 91%, 65%, and 40%, respectively. Surrogates rated GOSE 4 (daily partial help) worse than the general population. Married surrogates rated GOSE 4 higher (p < 0.01). Higher strength of faith was associated with higher utility scores across GOSE states (p = 0.034). CONCLUSIONS: In this index study of surrogate perceptions about disability after TBI, poor neurologic outcomes-vegetative, needing all-day or partial daily assistance-were perceived as worse than death by at least 1 in 3 surrogates. Surrogate perceptions differed from the unexposed public. Long-term perceptions about post-TBI disability may inform earlier, tailored shared decision-making after neurotrauma.

The Safe Cholecystectomy: Evaluating the Use of Laparoscopic Subtotal Cholecystectomy Between Junior and Senior Faculty.

BACKGROUND: Laparoscopic Subtotal Cholecystectomy (SC) is a technique for performing safe cholecystectomy when excessive inflammation prevents exposure of the Critical View of Safety. Studies have evaluated outcomes and complications of laparoscopic cholecystectomy (LC), with mixed results in terms of surgeon experience. It is unclear if the rate of SC is associated with experience. We hypothesized that the rate of SC would decrease as surgical experience increased. METHODS: We performed a retrospective review of LC performed at an academic medical center. Demographics were analyzed using descriptive statistics. We performed a multivariable logistic regression to examine the relationship between years in practice and performance of SC. We performed a sensitivity analysis comparing those in their first year on faculty with all others. RESULTS: Between November 1, 2017, and November 1, 2021, there were 1222 LC performed. 771 patients (63%) were female. 89 patients (7.3%) underwent SC. There were no bile duct injuries requiring reconstruction. Controlling for age, sex, and ASA class, there was no difference in the rate of SC by years of experience (OR .98, 95% CI .94-1.01). In a sensitivity analysis comparing first-year faculty to those beyond their first year, there was also no difference (OR .76, 95% CI 0.42-1.39). DISCUSSION: We find no difference in the rate of performance of SC between junior and senior faculty. This reflects consistency, in keeping with best practice guidelines. This could be confounded by junior faculty requesting assistance during difficult operations. Further investigation into factors affecting decision-making may clarify this.

Dynamic predictors of in-hospital and 3-year mortality after traumatic brain injury: A retrospective cohort study.

BACKGROUND: Mortality risks after Traumatic Brain Injury (TBI) are understudied in critical illness. We sought to identify risks of mortality in critically ill patients with TBI using time-varying covariates. METHODS: This single-center, six-year (2006-2012), retrospective cohort study measured demographics, injury characteristics, and daily data of acute TBI patients in the Intensive Care Unit (ICU). Time-varying Cox proportional hazards models assessed in-hospital and 3-year mortality. RESULTS: Post-TBI ICU patients (n = 2664) experienced 20% in-hospital mortality (n = 529) and 27% (n = 706) 3-year mortality. Glasgow Coma Scale motor subscore (hazard ratio (HR) 0.58, p < 0.001), pupil reactivity (HR 3.17, p < 0.001), minimum glucose (HR 1.44, p < 0.001), mSOFA score (HR 1.81, p < 0.001), coma (HR 2.26, p < 0.001), and benzodiazepines (HR 1.38, p < 0.001) were associated with in-hospital mortality. At three years, public insurance (HR 1.78, p = 0.011) and discharge disposition (HR 4.48, p < 0.001) were associated with death. CONCLUSIONS: Time-varying characteristics influenced in-hospital mortality post-TBI. Socioeconomic factors primarily affect three-year mortality.

Current Perspectives on the Assessment and Management of Pain in the Intensive Care Unit.

Critical illness is often painful, both from the underlying source of illness, as well as necessary procedures performed for the monitoring and care of these patients. Pain is often under-recognized in the critically ill, especially among those who cannot self-report, so accurate assessment and management continue to be major consideration in their care. Pain management in the intensive care unit (ICU) is an evolving practice, with a focus on accurate and frequent pain assessment, and targeted pharmacologic and non-pharmacologic treatment methods to maximize analgesia and minimize sedation. In this review, we will evaluate several validated methods of pain assessment in the ICU and present management options. We will review the evidence-based recommendations put forth by the largest critical care societies and several high-quality studies related to both the in-hospital approach to pain, as well as the short- and long-term consequences of untreated pain in ICU patients. We conclude with future directions.

Multicenter Validation of the Survival After Acute Civilian Penetrating Brain Injuries (SPIN) Score.

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.