Beyond the Final Heartbeat: Neurological Perspectives on Normothermic Regional Perfusion for Organ Donation after Circulatory Death.

Normothermic regional perfusion (NRP) has recently been used to augment organ donation after circulatory death (DCD) to improve the quantity and quality of transplantable organs. In DCD-NRP, after withdrawal of life-sustaining therapies and cardiopulmonary arrest, patients are cannulated onto extracorporeal membrane oxygenation to reestablish blood flow to targeted organs including the heart. During this process, aortic arch vessels are ligated to restrict cerebral blood flow. We review ethical challenges including whether the brain is sufficiently reperfused through collateral circulation to allow reemergence of consciousness or pain perception, whether resumption of cardiac activity nullifies the patient's prior death determination, and whether specific authorization for DCD-NRP is required. ANN NEUROL 2024;95:1035-1039.

Guidelines for Neuroprognostication in Critically Ill Adults with Moderate-Severe Traumatic Brain Injury.

BACKGROUND: Moderate-severe traumatic brain injury (msTBI) carries high morbidity and mortality worldwide. Accurate neuroprognostication is essential in guiding clinical decisions, including patient triage and transition to comfort measures. Here we provide recommendations regarding the reliability of major clinical predictors and prediction models commonly used in msTBI neuroprognostication, guiding clinicians in counseling surrogate decision-makers. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, we conducted a systematic narrative review of the most clinically relevant predictors and prediction models cited in the literature. The review involved framing specific population/intervention/comparator/outcome/timing/setting (PICOTS) questions and employing stringent full-text screening criteria to examine the literature, focusing on four GRADE criteria: quality of evidence, desirability of outcomes, values and preferences, and resource use. Moreover, good practice recommendations addressing the key principles of neuroprognostication were drafted. RESULTS: After screening 8125 articles, 41 met our eligibility criteria. Ten clinical variables and nine grading scales were selected. Many articles varied in defining "poor" functional outcomes. For consistency, we treated "poor" as "unfavorable". Although many clinical variables are associated with poor outcome in msTBI, only the presence of bilateral pupillary nonreactivity on admission, conditional on accurate assessment without confounding from medications or injuries, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. In terms of prediction models, the Corticosteroid Randomization After Significant Head Injury (CRASH)-basic, CRASH-CT (CRASH-basic extended by computed tomography features), International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-core, IMPACT-extended, and IMPACT-lab models were recommended as moderately reliable in predicting 14-day to 6-month mortality and functional outcomes at 6 months and beyond. When using "moderately reliable" predictors or prediction models, the clinician must acknowledge "substantial" uncertainty in the prognosis. CONCLUSIONS: These guidelines provide recommendations to clinicians on the formal reliability of individual predictors and prediction models of poor outcome when counseling surrogates of patients with msTBI and suggest broad principles of neuroprognostication.

Guidelines for neuroprognostication in adults with traumatic spinal cord injury.

BACKGROUND: Traumatic spinal cord injury (tSCI) impacts patients and their families acutely and often for the long term. The ability of clinicians to share prognostic information about mortality and functional outcomes allows patients and their surrogates to engage in decision-making and plan for the future. These guidelines provide recommendations on the reliability of acute-phase clinical predictors to inform neuroprognostication and guide clinicians in counseling adult patients with tSCI or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of an appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Timing/Setting question was framed as "When counseling patients or surrogates of critically ill patients with traumatic spinal cord injury, should < predictor, with time of assessment if appropriate > be considered a reliable predictor of < outcome, with time frame of assessment >?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four Grading of Recommendations Assessment, Development, and Evaluation criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. Good practice recommendations addressed essential principles of neuroprognostication that could not be framed in the Population/Intervention/Comparator/Outcome/Timing/Setting format. Throughout the guideline development process, an individual living with tSCI provided perspective on patient-centered priorities. RESULTS: Six candidate clinical variables and one prediction model were selected. Out of 11,132 articles screened, 369 met inclusion criteria for full-text review and 35 articles met eligibility criteria to guide recommendations. We recommend pathologic findings on magnetic resonance imaging, neurological level of injury, and severity of injury as moderately reliable predictors of American Spinal Cord Injury Impairment Scale improvement and the Dutch Clinical Prediction Rule as a moderately reliable prediction model of independent ambulation at 1 year after injury. No other reliable or moderately reliable predictors of mortality or functional outcome were identified. Good practice recommendations include considering the complete clinical condition as opposed to a single variable and communicating the challenges of likely functional deficits as well as potential for improvement and for long-term quality of life with SCI-related deficits to patients and surrogates. CONCLUSIONS: These guidelines provide recommendations about the reliability of acute-phase predictors of mortality, functional outcome, American Spinal Injury Association Impairment Scale grade conversion, and recovery of independent ambulation for consideration when counseling patients with tSCI or their surrogates and suggest broad principles of neuroprognostication in this context.

The Relationship Between Manifestation of Diabetes Insipidus and Estimated Glomerular Filtration Rate in Brain Death.

OBJECTIVES: Systematic reviews have revealed that up to 50% of patients with brain death have residual hypothalamic/pituitary activity based on the absence of central diabetes insipidus (DI). We hypothesized that different degrees of renal dysfunction may impact the presence of DI in patients with brain death. DESIGN: Single-center prospective data collection. SETTING: ICUs in a tertiary academic hospital. PATIENTS: All adult patients declared brain dead over 12 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: DI was diagnosed by polyuria, low urine specific gravity, and increasing serum sodium, measured in close proximity. Renal function was assessed by the estimated glomerular filtration rate (eGFR), calculated using the simplified modification of diet in renal disease equation. Analysis was completed in 192 of 234 patients with brain death after excluding those with missing data, those younger than 18 years and those on vasopressin infusions. One hundred twenty-two patients (63.5%) developed DI and 70 patients (36.5%) did not. The proportion of DI decreased significantly with decreasing eGFR: for eGFR greater than 60 mL/min, DI was present in 77.2%; for eGFR 15-60 mL/min, DI was present in 54.5%; for eGFR 14.9-9.8 mL/min, DI was present in 32%; none of the 14 patients with eGFR less than or equal to 9.7 mL/min ever experienced DI ( p < 0.001). Using logistic regression, for every 10 mL/min decrease in eGFR, the odds of DI decreased 0.83 times (95% CI, 0.76-0.90, p < 0.001). CONCLUSIONS: Renal dysfunction significantly impacts DI's clinical manifestation in brain death. We report that patients who experience brain death with severe renal dysfunction may not develop clinical signs of DI.

Guidelines for Neuroprognostication in Critically Ill Adults with Intracerebral Hemorrhage.

BACKGROUND: The objective of this document is to provide recommendations on the formal reliability of major clinical predictors often associated with intracerebral hemorrhage (ICH) neuroprognostication. METHODS: A narrative systematic review was completed using the Grading of Recommendations Assessment, Development, and Evaluation methodology and the Population, Intervention, Comparator, Outcome, Timing, Setting questions. Predictors, which included both individual clinical variables and prediction models, were selected based on clinical relevance and attention in the literature. Following construction of the evidence profile and summary of findings, recommendations were based on Grading of Recommendations Assessment, Development, and Evaluation criteria. Good practice statements addressed essential principles of neuroprognostication that could not be framed in the Population, Intervention, Comparator, Outcome, Timing, Setting format. RESULTS: Six candidate clinical variables and two clinical grading scales (the original ICH score and maximally treated ICH score) were selected for recommendation creation. A total of 347 articles out of 10,751 articles screened met our eligibility criteria. Consensus statements of good practice included deferring neuroprognostication-aside from the most clinically devastated patients-for at least the first 48-72 h of intensive care unit admission; understanding what outcomes would have been most valued by the patient; and counseling of patients and surrogates whose ultimate neurological recovery may occur over a variable period of time. Although many clinical variables and grading scales are associated with ICH poor outcome, no clinical variable alone or sole clinical grading scale was suggested by the panel as currently being reliable by itself for use in counseling patients with ICH and their surrogates, regarding functional outcome at 3 months and beyond or 30-day mortality. CONCLUSIONS: These guidelines provide recommendations on the formal reliability of predictors of poor outcome in the context of counseling patients with ICH and surrogates and suggest broad principles of neuroprognostication. Clinicians formulating their judgments of prognosis for patients with ICH should avoid anchoring bias based solely on any one clinical variable or published clinical grading scale.

Guidelines for Neuroprognostication in Adults with Guillain-Barré Syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) often carries a favorable prognosis. Of adult patients with GBS, 10-30% require mechanical ventilation during the acute phase of the disease. After the acute phase, the focus shifts to restoration of motor strength, ambulation, and neurological function, with variable speed and degree of recovery. The objective of these guidelines is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling adult patients with GBS and/or their surrogates. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and presence of appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Time frame/Setting (PICOTS) question was framed as follows: "When counseling patients or surrogates of critically ill patients with Guillain-Barré syndrome, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome, with time frame of assessment]?" Additional full-text screening criteria were used to exclude small and lower quality studies. Following construction of an evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eight candidate clinical variables and six prediction models were selected. A total of 45 articles met our eligibility criteria to guide recommendations. We recommend bulbar weakness (the degree of motor weakness at disease nadir) and the Erasmus GBS Respiratory Insufficiency Score as moderately reliable for prediction of the need for mechanical ventilation. The Erasmus GBS Outcome Score (EGOS) and modified EGOS were identified as moderately reliable predictors of independent ambulation at 3 months and beyond. Good practice recommendations include consideration of both acute and recovery phases of the disease during prognostication, discussion of the possible need for mechanical ventilation and enteral nutrition during counseling, and consideration of the complete clinical condition as opposed to a single variable during prognostication. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of the need for mechanical ventilation, poor functional outcome, and independent ambulation following GBS in the context of counseling patients and/or surrogates and suggest broad principles of neuroprognostication. Few predictors were considered moderately reliable based on the available body of evidence, and higher quality data are needed.

Guidelines for Neuroprognostication in Comatose Adult Survivors of Cardiac Arrest.

BACKGROUND: Among cardiac arrest survivors, about half remain comatose 72 h following return of spontaneous circulation (ROSC). Prognostication of poor neurological outcome in this population may result in withdrawal of life-sustaining therapy and death. The objective of this article is to provide recommendations on the reliability of select clinical predictors that serve as the basis of neuroprognostication and provide guidance to clinicians counseling surrogates of comatose cardiac arrest survivors. METHODS: A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, which included clinical variables and prediction models, were selected based on clinical relevance and the presence of an appropriate body of evidence. The Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) question was framed as follows: "When counseling surrogates of comatose adult survivors of cardiac arrest, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of poor functional outcome assessed at 3 months or later?" Additional full-text screening criteria were used to exclude small and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four GRADE criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. In addition, good practice recommendations addressed essential principles of neuroprognostication that could not be framed in PICOTS format. RESULTS: Eleven candidate clinical variables and three prediction models were selected based on clinical relevance and the presence of an appropriate body of literature. A total of 72 articles met our eligibility criteria to guide recommendations. Good practice recommendations include waiting 72 h following ROSC/rewarming prior to neuroprognostication, avoiding sedation or other confounders, the use of multimodal assessment, and an extended period of observation for awakening in patients with an indeterminate prognosis, if consistent with goals of care. The bilateral absence of pupillary light response > 72 h from ROSC and the bilateral absence of N20 response on somatosensory evoked potential testing were identified as reliable predictors. Computed tomography or magnetic resonance imaging of the brain > 48 h from ROSC and electroencephalography > 72 h from ROSC were identified as moderately reliable predictors. CONCLUSIONS: These guidelines provide recommendations on the reliability of predictors of poor outcome in the context of counseling surrogates of comatose survivors of cardiac arrest and suggest broad principles of neuroprognostication. Few predictors were considered reliable or moderately reliable based on the available body of evidence.

Metabolic values precluding clinical death by neurologic Criteria/Brain death: Survey of neurocritical care society physicians.

BACKGROUND: There are no established ranges for metabolic values prior to death by neurologic criteria/brain death determination (DNC/BD) and the thresholds required by institutional protocols and accepted by neurointensivists is unknown. METHODS: We designed a survey that addressed 1) the metabolic tests required in institutional guidelines prior to brain death determination, 2) the metabolic tests the respondent reviewed prior to brain death determination, and 3) the metabolic test thresholds for laboratory tests that were perceived to preclude or permit clinical DNC/BD determination. The survey was distributed online to physicians in the Neurocritical Care Society from September to December 2019. Respondents were dichotomized based on the number of brain death evaluations they had performed (≤20 vs. > 20) and responses were compared between groups. RESULTS: The survey was completed by 84 physicians. Nearly half (47.6%) of respondents did not believe their institutions required metabolic testing. The metabolic testing for which institutions most commonly provided a defined threshold were arterial pH (34.5%, 29/84), sodium (28.6%, 24/84), and glucose (15.5%, 13/84). Nearly all (97.6%) respondents routinely reviewed metabolic tests prior to brain death evaluation, the most common of which were: sodium (91.7%, 77/84), arterial pH (83.3%, 70/84), and glucose (79.8%, 67/84). Respondents who had performed > 20 evaluations were less likely to check thyroxine and total bilirubin (3.6%, 2/55 vs. 20.7%, 6/29 (p = 0.011) and 12.7%, 7/55 vs. 31%, 9/29 (p = 0.042), respectively), and had a more liberal upper limit of potassium (6.3 mEq/L vs 6.0 mEq/L, p = 0.045). CONCLUSION: Prior to brain death evaluation, neurocritical care providers commonly review similar metabolic tests and have similar thresholds regarding values that would preclude clinical brain death determination. This finding is independent of experience with brain death determination.

Comparison of 1 vs 2 Brain Death Examinations on Time to Death Pronouncement and Organ Donation: A 12-Year Single Center Experience.

OBJECTIVE: To fill the evidence gap on the value of a single brain death (SBD) or dual brain death (DBD) examination by providing data on irreversibility of brain function, organ donation consent, and transplantation. METHODS: Twelve-year tertiary hospital and organ procurement organization data on brain death (BD) were combined and outcomes, including consent rate for organ donation and organs recovered and transplanted after SBD and DBD, were compared after multiple adjustments for covariates. RESULTS: A total of 266 patients were declared BD, 122 after SBD and 144 after DBD. Time from event to BD declaration was longer by an average of 20.9 hours after DBD (p = 0.003). Seventy-five (73%) families of patients with SBD and 86 (72%) with DBD consented for organ donation (p = 0.79). The number of BD examinations was not a predictor for consent. No patient regained brain function during the periods following BD. Patients with SBD were more likely to have at least 1 lung transplanted (p = 0.031). The number of organs transplanted was associated with the number of examinations (ß coefficient [95% confidence interval] -0.5 [-0.97 to -0.02]; p = 0.044), along with age (for 5-year increase, -0.36 [-0.43 to -0.29]; p < 0.001) and PaO2 level (for 10 mm Hg increase, 0.026 [0.008-0.044]; p = 0.005) and decreased as the elapsed time to BD declaration increased (p = 0.019). CONCLUSIONS: A single neurologic examination to determine BD is sufficient in patients with nonanoxic catastrophic brain injuries. A second examination is without additional yield in this group and its delay reduces the number of organs transplanted.

Apnea Testing for the Determination of Brain Death: A Systematic Scoping Review.

Apnea is one of the three cardinal findings in brain death (BD). Apnea testing (AT) is physiologically and practically complex. We sought to review described modifications of AT, safety and complication rates, monitoring techniques, performance of AT on extracorporeal membrane oxygenation (ECMO), and other relevant considerations regarding AT. We conducted a systematic scoping review to answer these questions by searching the literature on AT in English language available in PubMed or EMBASE since 1980. Pediatric or animal studies were excluded. A total of 87 articles matched our inclusion criteria and were qualitatively synthesized in this review. A large body of the literature on AT since its inception addresses a variety of modifications, monitoring techniques, complication rates, ways to perform AT on ECMO, and other considerations such as variability in protocols, lack of uniform awareness, and legal considerations. Only some modifications are widely used, especially methods to maintain oxygenation, and most are not standardized or endorsed by brain death guidelines. Future updates to AT protocols and strive for unification of such protocols are desirable.

Factors that affect consent rate for organ donation after brain death: A 12-year registry.

OBJECTIVE: To account for factors affecting family approach and consent for organ donation after brain death (BD). MATERIAL AND METHODS: A prospective cohort study in a large, tertiary, urban hospital, where we reviewed the database of all brain-dead patients between January 2006 and December 2017 cross-matched with local organ procurement organization (OPO) records. RESULTS: Two-hundred sixty-six brain-dead patients were included (55% African Americans (AAs)). Two-hundred twenty-two were approached for donation. The reason for not approaching families was medical exclusion due to cancer or multi-organ failure. Patient demographics or religion were not associated with approaching families. Lower creatinine level was the only independent factor associated with higher approach. Consent rate for organ donation was 72.5%. Consent was significantly higher in Caucasians (89% vs 62% for AAs), younger patients (46.7 vs 52.5 years old), in patients with lower creatinine at time of death (1.7 vs 2.4 mg/dL), patients for whom apnea testing was completed (92% vs 80%) and patients with diabetes insipidus (DI) (72% vs 54%). There was no significant relationship between consent and patient gender, admission diagnosis, number of examinations or completion of a confirmatory test. In a logistic regression model, only AA race independently predicted consent for donation (odds, 95% CI, 0.27, 0.12-0.57 p < .001). In a different model, apnea test completion was an additional independent predictor (3.66, 1.28-10.5 p = .015). CONCLUSIONS: Approaching families for organ donation consent was associated with medical suitability only and not with demographic or religious characteristics. AAs were 3.7 times less likely to consent for organ donation than non-AAs. Completion of apnea testing was associated with higher consent rates, an observation that needs to be explored in future studies documenting the effect on bedside family presence during this test.

Gap Analysis Regarding Prognostication in Neurocritical Care: A Joint Statement from the German Neurocritical Care Society and the Neurocritical Care Society.

BACKGROUND/OBJECTIVE: Prognostication is a routine part of the delivery of neurocritical care for most patients with acute neurocritical illnesses. Numerous prognostic models exist for many different conditions. However, there are concerns about significant gaps in knowledge regarding optimal methods of prognostication. METHODS: As part of the Arbeitstagung NeuroIntensivMedizin meeting in February 2018 in Würzburg, Germany, a joint session on prognostication was held between the German NeuroIntensive Care Society and the Neurocritical Care Society. The purpose of this session was to provide presentations and open discussion regarding existing prognostic models for eight common neurocritical care conditions (aneurysmal subarachnoid hemorrhage, intracerebral hemorrhage, acute ischemic stroke, traumatic brain injury, traumatic spinal cord injury, status epilepticus, Guillain-Barré Syndrome, and global cerebral ischemia from cardiac arrest). The goal was to develop a qualitative gap analysis regarding prognostication that could help inform a future framework for clinical studies and guidelines. RESULTS: Prognostic models exist for all of the conditions presented. However, there are significant gaps in prognostication in each condition. Furthermore, several themes emerged that crossed across several or all diseases presented. Specifically, the self-fulfilling prophecy, lack of accounting for medical comorbidities, and absence of integration of in-hospital care parameters were identified as major gaps in most prognostic models. CONCLUSIONS: Prognostication in neurocritical care is important, and current prognostic models are limited. This gap analysis provides a summary assessment of issues that could be addressed in future studies and evidence-based guidelines in order to improve the process of prognostication.

Correction to: Gap Analysis Regarding Prognostication in Neurocritical Care: A Joint Statement from the German Neurocritical Care Society and the Neurocritical Care Society.

This article was updated to correct the spelling of Karl Georg Haeusler.

Neurocritical Care Outcomes, Research, and Technology: A Review.

Importance: Neurocritical care has grown into an organized specialty that may have consequences for patient care, outcomes, research, and neurointensive care (neuroICU) technology. Observations: Neurocritical care improves care and outcomes of the patients who are neurocritically ill, and neuroICUs positively affect the financial state of health care systems. The development of neurocritical care as a recognized subspecialty has fostered multidisciplinary research, neuromonitoring, and neurocritical care information technology, with advances and innovations in practice and progress. Conclusions and Relevance: Neurocritical care has become an important part of health systems and an established subspecialty of neurology. Understanding its structure, scope of practice, consequences for care, and research are important.

Status Epilepticus, Refractory Status Epilepticus, and Super-refractory Status Epilepticus.

PURPOSE OF REVIEW: Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus can be life-threatening conditions. This article presents an overview of the three conditions and discusses their management and outcomes. RECENT FINDINGS: Status epilepticus was previously defined as lasting for 30 minutes or longer but now is more often defined as lasting 5 minutes or longer. A variety of potential causes exist for status epilepticus, refractory status epilepticus, and super-refractory status epilepticus, but all three ultimately involve changes at the cellular and molecular level. Management of patients with status epilepticus generally requires several studies, with EEG of utmost importance given the pathophysiologic changes that can occur during the course of status epilepticus. Status epilepticus is treated with benzodiazepines as first-line antiepileptic drugs, followed by phenytoin, valproic acid, or levetiracetam. If status epilepticus does not resolve, these are followed by an IV anesthetic and then alternative therapies based on limited data/evidence, such as repetitive transcranial magnetic stimulation, therapeutic hypothermia, immunomodulatory agents, and the ketogenic diet. Scores have been developed to help predict the outcome of status epilepticus. Neurologic injury and outcome seem to worsen as the duration of status epilepticus increases, with outcomes generally worse in super-refractory status epilepticus compared to status epilepticus and sometimes also to refractory status epilepticus. SUMMARY: Status epilepticus can be a life-threatening condition associated with multiple complications, including death, and can progress to refractory status epilepticus and super-refractory status epilepticus. More studies are needed to delineate the best management of these three entities.