BackgroundUnderstanding how clinicians prognosticate is important for creating interventions that improve current practice and clinical trials. We compared clinicians' reported approaches to prognostication with traumatic brain injury (TBI) and comatose cardiac arrest (CA) for patients enrolled in a multicenter clinical trial.MethodsWe conducted semi-structured interviews with clinicians who treated patients with severe traumatic brain injury (TBI) enrolled in the Brain Oxygen Optimization in Severe TBI Phase-3 (BOOST-3) trial (NCT03754114). We compared these reports with ones in a previous study of patients who were comatose after cardiac arrest (CA) and were enrolled in the Influence of Cooling Duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (NCT04217551). We performed deductive coding using our codebook from CA interviews and then used inductive coding to add new topics raised in the TBI interviews. We looked specifically for reported reliance on initial "clinical gestalt" as observed in the CA interviews.ResultsWe interviewed 18 clinicians at 13 hospitals. Predicting poor outcomes was less common with TBI cases than in the CA study, consistent with records showing that final prognostication was determined later in the TBI cases (7 [interquartile range (IQR) 2-18.5] vs. 3 [IQR 2-7] days). Similar percentages of clinicians reported high confidence in their initial prognostic assessments in the two settings (TBI, 33%; CA, 40%). Fewer clinicians reported relying on initial clinical gestalt predictions with patients with TBI (22%) than with patients who had experienced CA (70%). With patients with TBI, more clinicians reported having used later subjective assessments to revise their initial uncertain prognostication.ConclusionsIn interviews with clinicians practicing at multiple institutes, we found that clinicians were less likely to report relying on initial gestalt impressions with patients with TBI than with patients who had experienced CA and were more likely to report relying on later subjective assessments to refine uncertain initial prognostic judgments. Fewer clinicians reported high confidence in initial assessments of patients with TBI.

Brain death, or death by neurologic criteria (BD/DNC), is the permanent loss of brain function, defined by coma with loss of capacity for consciousness and complete brainstem areflexia, including the inability to breathe spontaneously. The 2023 American Academy of Neurology/American Academy of Pediatrics/Child Neurology Society (CNS)/Society for Critical Care Medicine guidelines state that pregnancy is not a contraindication for BD/DNC evaluation. Clinical evaluation of BD/DNC includes an apnea test to demonstrate the absence of spontaneous respiratory effort in response to hypercapnia and acidosis. The safety of apnea testing to the fetus in pregnant patients remains uncertain.We convened a panel of experts in BD/DNC, neurocritical care, maternal-fetal medicine, neonatology, fetal/neonatal/child neurology, and pediatric/fetal anesthesiology to perform a scoping review of apnea testing in pregnant persons. We found no studies directly assessing safety of apnea testing on the fetus. Apnea testing consists of fetal exposure to parental hyperoxia and hypercapnia; therefore, we searched for evidence related to these conditions in pregnancy. Case reports, series, and literature on physiologic changes induced during apnea testing and their potential effects on placental, fetal systemic, and fetal cerebral circulations were identified. In reported cases of BD/DNC in pregnant persons, some authors described explicitly avoiding apnea testing because of safety concerns, but whether apnea testing was performed at all was inconsistently reported. Evidence from studies evaluating hyperoxia and hypercapnia in healthy pregnant persons and in other animal models suggested possible adverse effects caused by reduced uteroplacental blood flow, fetal metabolic acidosis, and hypercapnia-induced cerebral hyperperfusion. Further possible complications of apnea testing, such as hypotension or hypoxemia in pregnant persons, could also contribute to fetal injury. These potential detrimental risks to the fetus raise the question as to whether apnea testing should be deferred if a fetus may be viable. Ancillary tests, such as radionuclide cerebral blood flow imaging or transcranial Doppler ultrasonography, can be used if the remainder of the BD/DNC evaluation and neurologic examination is otherwise consistent with BD/DNC. Further research is essential to assess the physiologic consequences of apnea testing in pregnant persons and potential risks to the fetus.

BACKGROUND:Accrual of participants into clinical trials is a fundamental and important aspect for the management of trial progress. Monitoring of trial accrual often provides insight into the potential timing of key study events, such as interim analysis, as well as the feasibility of the overall trial to enroll the projected sample size in the original estimated timeline. METHODS:A Bayesian first order simple dynamic linear model with weakly informative priors is utilized to characterize enrollment rates temporally within pre-defined time windows (quarterly) for the duration of a trial. RESULTS:Application of the model to three ongoing clinical trials demonstrates the utility of the model to characterize the observed accrual patterns. Additionally, the applications demonstrate the flexibility of the model to react to variable accrual patterns without overreacting to the variability of accrual within a trial due to expected causes, such as seasonal variability in disease incidence, or unexpected causes, such as a global pandemic. CONCLUSIONS:Much statistical literature has been dedicated to predicting when key study events are likely to occur by utilizing current estimated rates of participant accrual; however, study teams, sponsors, and funding agencies have interest in the previous trends in participant accrual. This work presents an addition to the literature which allows parties interested in assessing trial progress to do so by providing a flexible framework for the standardized characterization of trial accrual which is not overly sensitive to the expected variability of trial accrual.

Introduction: Cerebral vasospasm is a serious complication after aneurysmal subarachnoid hemorrhage (aSAH) leading to secondary neurologic injury. Nimodipine is the only FDA approved medication to reduce poor neurological outcomes after aSAH. Mild systemic hypotension is frequently seen with nimodipine, although severe refractory shock is rare. We present a case of refractory vasoplegia and severe shock after first dose of enteral nimodipine (60 mg), which responded only to hydroxocobalamin (B12) administration. Description: 59 yo F presented with a sudden onset severe headache. CTH/ CTA showed aSAH due to ruptured Posterior Communicating (PCOMM) artery aneurysm. Worsening hydrocephalus prompted placement of an external ventricular drain. She underwent a frontal craniotomy and L PCOMM clipping. After stabilization in the Neuro-ICU, oral nimodipine (60 mg) was started per aSAH management. Within 30 minutes of the first dose, MAP dropped to 47 mmHg. Fluids and norepinephrine were started. Her MAP remained low (50s) despite escalating doses of norepinephrine and addition of epinephrine and vasopressin. Bedside POCUS showed no cardiac abnormalities or other etiologies of shock. Despite maximum doses of 3 vasopressors, her MAP remained low. She was administered IV B12 as reversal for suspected nitric oxide vasodilation. Within an hour, vasoactive medications were quickly weaned off. A rechallenge of nimodipine was attempted the next day (30 mg) which again precipitated severe vasoplegia. B12 was administered again with almost instantaneous improvement in her MAP. Nimodipine was discontinued and no additional episodes of severe vasoplegia occurred. Discussion: There is little evidence to guide management of severe vasoplegia due to nimodipine. We describe the first case of nimodipine induced refractory vasoplegia that recurred upon rechallenge with lower dose of nimodipine. Although other etiologies of shock must be ruled out, Intensivists should consider B12 as a lifesaving reversal agent for suspected vasoplegia due to nimodipine.

Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies. The incidence of PTE after traumatic brain injury (TBI) depends on the severity of injury, approaching one in three in groups with the most severe injuries. The repeated seizures that characterize PTE impair neurological recovery and increase the risk of poor outcomes after TBI. Given this high risk of recurrent seizures and the relatively short latency period for their development after injury, PTE serves as a model disease to understand human epileptogenesis and trial novel anti-epileptogenic therapies. Epileptogenesis is the process whereby previously normal brain tissue becomes prone to recurrent abnormal electrical activity, ultimately resulting in seizures. In this Review, we describe the clinical course of PTE and highlight promising research into epileptogenesis and treatment using animal models of PTE. Clinical, imaging, EEG and fluid biomarkers are being developed to aid the identification of patients at high risk of PTE who might benefit from anti-epileptogenic therapies. Studies in preclinical models of PTE have identified tractable pathways and novel therapeutic strategies that can potentially prevent epilepsy, which remain to be validated in humans. In addition to improving outcomes after TBI, advances in PTE research are likely to provide therapeutic insights that are relevant to all epilepsies. Post-traumatic epilepsy is a major driver of disability associated with traumatic brain injury. This article reviews the epidemiology and clinical features of post-traumatic epilepsy and discusses how an understanding of the underlying epileptogenic mechanisms might inform the development of anti-epileptogenic medications. Post-traumatic epilepsy (PTE) is highly prevalent after traumatic brain injury, impairing neurological recovery and leading to worse functional outcomes.Current epilepsy therapeutics symptomatically treat seizures but do not modify epileptogenesis, the process by which brain tissue becomes prone to seizures.The unique nature of PTE, occurring after a well-defined epileptogenic insult, makes it a promising model system for understanding epileptogenesis.Future research in individuals with PTE populations might not only reveal novel mechanisms of epileptogenesis but also enable anti-epileptogenic therapies to be tested.

Background The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. Methods A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. Results A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). Conclusions This consensus provides practical recommendations to support a clinician’s decision making in the management of tSCI polytrauma patients.

OBJECTIVES:Neurocritically ill patients are at high risk for developing delirium, which can worsen the long-term outcomes of this vulnerable population. However, existing delirium assessment tools do not account for neurologic deficits that often interfere with conventional testing and are therefore unreliable in neurocritically ill patients. We aimed to determine the accuracy and predictive validity of the Fluctuating Mental Status Evaluation (FMSE), a novel delirium screening tool developed specifically for neurocritically ill patients. DESIGN:Prospective validation study. SETTING:Neurocritical care unit at an academic medical center. PATIENTS:One hundred thirty-nine neurocritically ill stroke patients (mean age, 63.9 [ sd , 15.9], median National Institutes of Health Stroke Scale score 11 [interquartile range, 2-17]). INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Expert raters performed daily Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based delirium assessments, while paired FMSE assessments were performed by trained clinicians. We analyzed 717 total noncomatose days of paired assessments, of which 52% ( n = 373) were rated by experts as days with delirium; 53% of subjects were delirious during one or more days. Compared with expert ratings, the overall accuracy of the FMSE was high (area under the curve [AUC], 0.85; 95% CI, 0.82-0.87). FMSE scores greater than or equal to 1 had 86% sensitivity and 74% specificity on a per-assessment basis, while scores greater than or equal to 2 had 70% sensitivity and 88% specificity. Accuracy remained high in patients with aphasia (FMSE ≥ 1: 82% sensitivity, 64% specificity; FMSE ≥ 2: 64% sensitivity, 84% specificity) and those with decreased arousal (FMSE ≥ 1: 87% sensitivity, 77% specificity; FMSE ≥ 2: 71% sensitivity, 90% specificity). Positive FMSE assessments also had excellent accuracy when predicting functional outcomes at discharge (AUC, 0.86 [95% CI, 0.79-0.93]) and 3 months (AUC, 0.85 [95% CI, 0.78-0.92]). CONCLUSIONS:In this validation study, we found that the FMSE was an accurate delirium screening tool in neurocritically ill stroke patients. FMSE scores greater than or equal to 1 indicate "possible" delirium and should be used when prioritizing sensitivity, whereas scores greater than or equal to 2 indicate "probable" delirium and should be used when prioritizing specificity.

Intracranial multimodal monitoring (iMMM) is increasingly used in neurocritical care, but a lack of standardization hinders its evidence-based development. Here, we devised core outcome sets (COS) and reporting guidelines to harmonize iMMM practices and research. An open, decentralized, three-round Delphi consensus study involved experts between December 2023 and June 2024. Items—spanning three domains: (i) patient characteristics, (ii) practices, and (iii) outcomes—with ≥ 75

OBJECTIVES:The prehospital prediction of the radiographic diagnosis of traumatic brain injury (TBI) in hemorrhagic shock patients has the potential to promote early therapeutic interventions. However, the identification of TBI is often challenging and prehospital tools remain limited. While the Glasgow Coma Scale (GCS) score is frequently used to assess the extent of impaired consciousness after injury, the utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is poorly understood. METHODS:We performed a post-hoc, secondary analysis utilizing data derived from three randomized prehospital clinical trials: the Prehospital Air Medical Plasma trial (PAMPER), the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport trial (STAAMP), and the Pragmatic Prehospital Type O Whole Blood Early Resuscitation (PPOWER) trial. Patients were dichotomized into two cohorts based on the presence of TBI and then further stratified into three groups based on prehospital GCS score: GCS 3, GCS 4-12, and GCS 13-15. The association between prehospital GCS score and clinical documentation of TBI was assessed. RESULTS:A total of 1,490 enrolled patients were included in this analysis. The percentage of patients with documented TBI in those with a GCS 3 was 59.5, 42.4% in those with a GCS 4-12, and 11.8% in those with a GCS 13-15. The positive predictive value (PPV) of the prehospital GCS score for the diagnosis of TBI is low, with a GCS of 3 having only a 60% PPV. Hypotension and prehospital intubation are independent predictors of a low prehospital GCS. Decreasing prehospital GCS is strongly associated with higher incidence or mortality over time, irrespective of the diagnosis of TBI. CONCLUSIONS:The ability to accurately predict the presence of TBI in the prehospital phase of care is essential. The utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is limited. The use of novel scoring systems and improved technology are needed to promote the accurate early diagnosis of TBI.

Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3

BACKGROUND:Clinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs. METHODS:The Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms. RESULTS:Among hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpoint CDE measures for adults and 5 for children. CONCLUSIONS:The DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges.

Wang, Fajun1; Reimer, James2; Ramiro, Joanna3; Welch, Emily2; Christopher, Kara3; Shutter, Lori4; Barun, James2 Author Information

OBJECTIVES:Clinical practice guidelines are essential for promoting evidence-based healthcare. While diversification of panel members can reduce disparities in care, processes for panel selection lack transparency. We aim to share our approach in forming a diverse expert panel for the updated Adult Critical Care Ultrasound Guidelines. DESIGN:This process evaluation aims to understand whether the implementation of a transparent and intentional approach to guideline panel selection would result in the creation of a diverse expert guideline panel. SETTING:This study was conducted in the setting of creating a guideline panel for the updated Adult Critical Care Ultrasound Guidelines. PATIENTS:Understanding that family/patient advocacy in guideline creations can promote the impact of a clinical practice guideline, patient representation on the expert panel was prioritized. INTERVENTIONS:Interventions included creation of a clear definition of expertise, an open invitation to the Society of Critical Care Medicine membership to apply for the panel, additional panel nomination by guideline leadership, voluntary disclosure of pre-identified diversity criteria by potential candidates, and independent review of applications including diversity criteria. This resulted in an overall score per candidate per reviewer and an open forum for discussion and final consensus. MEASUREMENTS AND MAIN RESULTS:The variables of diversity were collected and analyzed after panel selection. These were compared with historical data on panel composition. The final guideline panel comprised of 33 panelists from six countries: 45% women and 79% historically excluded people and groups. The panel has representation from nonphysician professionals and patients advocates. Of the healthcare professionals, there is representation from early, mid, and late career stages. CONCLUSIONS:Our intentional and transparent approach resulted in a panel with improved gender parity and robust diversity along ethnic, racial, and professional lines. We hope it can serve as a starting point as we strive to become a more inclusive and diverse discipline that creates globally representative guidelines.

Purpose of review The A2F intensive care unit (ICU) liberation bundle is a multi-component management strategy that has been shown to improve hospital survival and reduce rates of delirium and ICU readmission. In this review, we aim to highlight the potential role of the A2F bundle in neurocritical care settings while further delineating its individual components. Recent findings The A2F bundle and its components are supported by a robust evidence base that continues to develop regarding the management of critically ill patients. Recent additions include the DEXACET trial, which found that scheduled intravenous acetaminophen reduced delirium, breakthrough analgesia, and ICU length of stay for post-operative patients. Meanwhile, although previous trials indicated that dexmedetomidine for light sedation reduces delirium when compared with benzodiazepine sedation, the MENDS2 and SPICE-III trials did not find that dexmedetomidine as a first-line sedative for mechanically ventilated ICU patients improved outcomes compared with propofol. Trials of family engagement support more frequent goals of care discussions and improvements in quality of communication and patient-centered care. However, evidence specific to neurocritically ill patients remains limited. A small trial found utility for goals of care decision aids to support shared decision-making in patients with severe acute brain injury. Recent studies have also suggested that delirium may have a unique impact on outcomes in neurocritically ill patients, and new tools may have utility in delirium identification in patients with acute neurological injury. Finally, there is accumulating evidence to suggest that early mobilization is safe and feasible in neurocritically ill patients, even those with external ventricular drains, and that it may improve outcomes. Summary Although the A2F bundle in its entirety has not been specifically studied in neurocritically ill patients, many of its goals overlap with contemporary neurocritical care practices. Future studies are needed to determine optimal ICU liberation strategies that can be safely and effectively implemented in patients with acute neurological injury.

CRITICAL CARE CLINICS www.criticalcare.theclinics.com Consulting Editor GREGORY S. MARTIN January 2023 • Volume 39 • Number 1

In this issue, we have attempted to portray the evolution of both the science and the field of Neurocritical Care from its organic origins out of the polio epidemic to its reemergence as one of the burgeoning subspecialities in the landscape of modern critical care. Despite the remarkable growth in number of board-certified neurointensivists, specialty trained advanced practice providers, pharmacists, nurses, respiratory therapists, and other allied health care professionals, there continues to be a severe shortage of neurocritical care programs throughout the world.