Reviewing Ethical Guidelines for the Care of Patients with Do-Not-Resuscitate Orders after 30 Years: Rethinking Our Approach at a Time of Transition.

The American Society of Anesthesiologists (ASA) opposes automatic reversal of do-not-resuscitate orders during the perioperative period, instead advocating for a goal-directed approach that aligns decision-making with patients' priorities and clinical circumstances. Implementation of ASA guidelines continues to face significant barriers including time constraints, lack of longitudinal relationships with patients, and difficulty translating goal-focused discussion into concrete clinical plans. These challenges mirror those of advance care planning more generally, suggesting a need for novel frameworks for serious illness communication and patient-centered decision-making. This review considers ASA guidelines in the context of ongoing transitions to serious illness communication and increasingly multidisciplinary perioperative care. It aims to provide practical guidance for the practicing anesthesiologist while also acknowledging the complexity of decision-making, considering limitations inherent to anesthesiologists' role, and outlining a need to conceptualize delivery of ethically informed care as a collaborative, multidisciplinary endeavor.

Identifying Variation in Intraoperative Management of Brain-Dead Organ Donors and Opportunities for Improvement: A Multicenter Perioperative Outcomes Group Analysis.

BACKGROUND: Intraoperative events and clinical management of deceased organ donors after brain death are poorly characterized and may consequently vary between hospitals and organ procurement organization (OPO) regions. In a multicenter cohort, we sought to estimate the incidence of hypotension and anesthetic and nonanesthetic medication use during organ recovery procedures. METHODS: We used data from electronic anesthetic records generated during organ recovery procedures from brain-dead adults across a Multicenter Perioperative Outcomes Group (MPOG) cohort of 14 US hospitals and 4 OPO regions (2014-2020). Hypotension, defined as mean arterial pressure or MAP <60 mm Hg for at least 10 cumulative minutes was the primary outcome of interest. The associations between hypotension and age, sex, race, anesthesia time, OPOs, and OPO case volume were examined using multivariable mixed-effects Poisson regression analyses with robust standard error estimates. We calculated intraclass correlation coefficients (ICCs) to describe the variation between-MPOG centers and the OPO regions in the use of medications, time of the operation, and duration of the operation. RESULTS: We examined 1338 brain-dead adult donors, with a mean age of 42± (standard deviation [SD] 15) years; 60% (n = 801) were males and 67% (n = 891) non-Hispanic White. During the entire intraoperative monitoring period, 321 donors (24%, 95% confidence interval [CI], 22%-26%) had hypotension for a median of 13.8% [quartile1-quartile 3: 9.4%-21%] of the monitoring period and a minimum of 10 minutes to a maximum of 96 minutes [(median: 17, quartile1-quartile 3: 12-24]). The probability having hypotension in donors 35 to 64 years and 65 years and older were approximately 30% less than in donors 18 to 34 years of age (adjusted relative risk ratios, aRR, 0.68, 95% CI, 0.55-0.82, aRR, 0.63, 95% CI, 0.42-0.94, respectively). Donors received intravenous heparin (96.4%, n = 1291), neuromuscular blockers (89.5%, n = 1198), vasoactive medications (82.7%, n = 1108), crystalloids (76.2%, n = 1020), halogenated anesthetic gases (63.5%, n = 850), diuretics (43.8%, n = 587), steroids (16.7%, n = 224), and opioids (23.2%, n = 310). The largest practice heterogeneity observed between the MPOG center and OPO regions was steroids (between-center ICCs = 0.65, 95% CI, 0.62-0.75, between-region ICCs = 0.39, 95% CI, 0.27-0.63) and diuretics (between-center ICCs = 0.44, 95% CI, 0.36-0.6, between-region ICCs = 0.30, 95% CI, 0.22-0.49). CONCLUSIONS: Despite guidelines recommending maintenance of MAP >60 mm Hg in adult brain-dead organ donors, hypotension during recovery procedures was common. Future research is needed to clarify the relationship between intraoperative events with donation and transplantation outcomes and to identify best practices for the anesthetic management of brain-dead donors in the operating room.

Verification of Death by Neurologic Criteria: A Survey of 12 Organ Procurement Organizations Across the United States.

BACKGROUND: The Center for Medicare and Medicaid Services requires Organ Procurement Organizations (OPOs) to verify and document that any potential organ donor has been pronounced dead per applicable legal requirements of local, state, and federal laws. However, OPO practices regarding death by neurologic criteria (DNC) verification are not standardized, and little is known about their DNC verification processes. This study aimed to explore OPO practices regarding DNC verification in the United States. METHODS: An electronic survey was sent to all 57 OPOs in the United States from June to September 2023 to assess verification of policies and practices versus guidelines, concerns about policies and practices, processes to address concerns about DNC determination, and communication practices. RESULTS: Representatives from 12 OPOs across six US regions completed the entire survey; 8 of 12 reported serving > 50 referral hospitals. Most respondents (11 of 12) reported comparing their referral hospital's DNC policies with the 2010 American Academy of Neurology Practice Parameter and/or other (4 of 12) guidelines. Additionally, most (10 of 12) reported independently reviewing and verifying each DNC determination. Nearly half (5 of 12) reported concerns about guideline-discordant hospital policies, and only 3 of 12 thought all referral hospitals followed the 2010 American Academy of Neurology Practice Parameter in practice. Moreover, 9 of 12 reported concerns about clinician knowledge surrounding DNC determination, and most (10 of 12) reported having received referrals for patients whose DNC declaration was ultimately reversed. All reported experiences in which their OPO requested additional assessments (11 of 12 clinical evaluation, 10 of 12 ancillary testing, 9 of 12 apnea testing) because of concerns about DNC determination validity. CONCLUSIONS: Accurate DNC determination is important to maintain public trust. Nearly all OPO respondents reported a process to verify hospital DNC policies and practices with medical society guidelines. Many reported concerns about clinician knowledge surrounding DNC determination and guideline-discordant policies and practices. Educational and regulatory advocacy efforts are needed to facilitate systematic implementation of guideline-concordant practices across the country.

Delirium and Its Associations with Critical Care Utilizations and Outcomes at the Time of Hospital Discharge in Patients with Acute Brain Injury.

Background and Objectives: We analyzed delirium testing, delirium prevalence, critical care associations outcomes at the time of hospital discharge in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), non-traumatic subarachnoid hemorrhage (SAH), non-traumatic intraparenchymal hemorrhage (IPH), and traumatic brain injury (TBI) admitted to an intensive care unit. Materials and Methods: We examined the frequency of assessment for delirium using the Confusion Assessment Method for the intensive care unit. We assessed delirium testing frequency, associated factors, positive test outcomes, and their correlations with clinical care, including nonpharmacological interventions and pain, agitation, and distress management. Results: Amongst 11,322 patients with ABI, delirium was tested in 8220 (726%). Compared to patients 18-44 years of age, patients 65-79 years (aOR 0.79 [0.69, 0.90]), and those 80 years and older (aOR 0.58 [0.50, 0.68]) were less likely to undergo delirium testing. Compared to English-speaking patients, non-English-speaking patients (aOR 0.73 [0.64, 0.84]) were less likely to undergo delirium testing. Amongst 8220, 2217 (27.2%) tested positive for delirium. For every day in the ICU, the odds of testing positive for delirium increased by 1.11 [0.10, 0.12]. Delirium was highest in those 80 years and older (aOR 3.18 [2.59, 3.90]). Delirium was associated with critical care resource utilization and with significant odds of mortality (aOR 7.26 [6.07, 8.70] at the time of hospital discharge. Conclusions: In conclusion, we find that seven out of ten patients in the neurocritical care unit are tested for delirium, and approximately two out of every five patients test positive for delirium. We demonstrate disparities in delirium testing by age and preferred language, identified high-risk subgroups, and the association between delirium, critical care resource use, complications, discharge GCS, and disposition. Prioritizing equitable testing and diagnosis, especially for elderly and non-English-speaking patients, is crucial for delivering quality care to this vulnerable group.

The balance of interleukin-12 and interleukin-23 determines the bias of MAIT1 versus MAIT17 responses during bacterial infection.

Mucosal-associated invariant T (MAIT) cells are a major subset of innate-like T cells mediating protection against bacterial infection through recognition of microbial metabolites derived from riboflavin biosynthesis. Mouse MAIT cells egress from the thymus as two main subpopulations with distinct functions, namely, T-bet-expressing MAIT1 and RORγt-expressing MAIT17 cells. Previously, we reported that inducible T-cell costimulator and interleukin (IL)-23 provide essential signals for optimal MHC-related protein 1 (MR1)-dependent activation and expansion of MAIT17 cells in vivo. Here, in a model of tularemia, in which MAIT1 responses predominate, we demonstrate that IL-12 and IL-23 promote MAIT1 cell expansion during acute infection and that IL-12 is indispensable for MAIT1 phenotype and function. Furthermore, we showed that the bias toward MAIT1 or MAIT17 responses we observed during different bacterial infections was determined and modulated by the balance between IL-12 and IL-23 and that these responses could be recapitulated by cytokine coadministration with antigen. Our results indicate a potential for tailored immunotherapeutic interventions via MAIT cell manipulation.

Understanding Research Methods: Up-and-down Designs for Dose-finding.

SUMMARY: For the task of estimating a target benchmark dose such as the ED50 (the dose that would be effective for half the population), an adaptive dose-finding design is more effective than the standard approach of treating equal numbers of patients at a set of equally spaced doses. Up-and-down is the most popular family of dose-finding designs and is in common use in anesthesiology. Despite its widespread use, many aspects of up-and-down are not well known, implementation is often misguided, and standard, up-to-date reference material about the design is very limited. This article provides an overview of up-and-down properties, recent methodologic developments, and practical recommendations, illustrated with the help of simulated examples. Additional reference material is offered in the Supplemental Digital Content.

Critical Care Medicine Practice: A Pilot Survey of US Anesthesia Critical Care Medicine-Trained Physicians.

BACKGROUND: This survey assessed satisfaction with the practice environment among physicians who have completed fellowship training in critical care medicine (CCM) as recognized by the American Board of Anesthesiology (and are members of the American Society of Anesthesiology) and evaluated the perceived effectiveness of training programs in preparing fellows for critical care practice. METHODS: A cross-sectional online survey composed of 39 multiple choice and open-ended questions was administered between August and December 2018 to all members of the American Society of Anesthesiologists (ASA) who self-identified as being CCM trained. The survey instrument was developed and revised in an iterative fashion by ASA committee on CCM and the Society for Education in Anesthesia (SEA). Survey results were analyzed using a mixed-method approach. RESULTS: Three hundred fifty-three of the 1400 anesthesiologists who self-identified to the ASA as having CCM training (25.2%) completed the survey. Most were men (72.3%), board certified in CCM (98.7%), and had practiced a median of 5 years. Half of the respondents rated their training as "excellent." A total of 70.6% described currently working in academic centers with 53.6% providing care in open surgical intensive care units (ICUs). Most anesthesiologist intensivists (75%) spend at least 25% of their clinical time providing ICU care (versus clinical anesthesia). A total of 89% of the respondents were involved in educational activities, 60% reported being in administrative leadership roles, and 37% engaged in scholarly activity. Areas of dissatisfaction included fatigue, lack of collegiality or respect, lack of research training, decreased job satisfaction, and burnout. Analysis suggested moderate levels of job satisfaction (49%), work-life balance (52%), and high levels of burnout (74%). A significant contributor to burnout was with a perception of lack of respect (P = .005) in the work environment. Burnout was not significantly associated with gender or duration of practice. Qualitative analysis of the open-ended responses also identified these 3 variables as major themes. CONCLUSIONS: This survey of CCM-trained anesthesiologists described a high rate of board certification, practice in academic settings, and participation in resident education. Areas of dissatisfaction with an anesthesia/critical care practice included burnout, work/life balance, and lack of respect. These results may increase recruitment of anesthesiologists into critical care and inform strategies to improve satisfaction with anesthesia critical care practice, fellowship training.

CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells.

Lyme disease is a common multisystem disease caused by infection with a tick-transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL-II) is a major target of antibodies in sera from infected individuals. Here, we show that CD1b presents BbGL-II to human T cells and that the TCR mediates the recognition. However, we did not detect increased frequency of CD1b-BbGL-II binding T cells in the peripheral blood of Lyme disease patients compared to controls. Unexpectedly, mapping the T cell specificity for BbGL-II-like molecules using tetramers and activation assays revealed a concomitant response to CD1b-expressing APCs in absence of BbGL-II. Further, among all major classes of self-lipid tested, BbGL-II responsive TCRs show strong cross-reactivity to diacylglycerol, a self-lipid antigen with structural similarities to BbGL-II. Extending prior work on MHC and CD1b, CD1c, and CD1d proteins, this study provides evidence for cross-reactive CD1b-restricted T cell responses to bacterial and self-antigens, and identifies chemically defined targets for future discovery of self and foreign antigen cross-reactive T cells.

When it's good to have MAITs.

This article discusses mucosal-associated invariant T-cell prophylactic and therapeutic vaccination schemes tested by Sakai et al. in mouse models of Mycobacterium tuberculosis infection together with the outcomes and observations.

Hypersensitivities following allergen antigen recognition by unconventional T cells.

Conventional T cells recognise protein-derived antigens in the context of major histocompatibility complex (MHC) class Ia and class II molecules and provide anti-microbial and anti-tumour immunity. Conventional T cells have also been implicated in type IV (also termed delayed-type or T cell-mediated) hypersensitivity reactions in response to protein-derived allergen antigens. In addition to conventional T cells, subsets of unconventional T cells exist, which recognise non-protein antigens in the context of monomorphic MHC class I-like molecules. These include T cells that are restricted to the cluster of differentiation 1 (CD1) family members, known as CD1-restricted T cells, and mucosal-associated invariant T cells (MAIT cells) that are restricted to the MHC-related protein 1 (MR1). Compared with conventional T cells, much less is known about the immune functions of unconventional T cells and their role in hypersensitivities. Here, we review allergen antigen presentation by MHC-I-like molecules, their recognition by unconventional T cells, and the potential role of unconventional T cells in hypersensitivities. We also speculate on possible scenarios of allergen antigen presentation by MHC-I-like molecules to unconventional T cells, the hallmarks of such responses, and the expected frequencies of hypersensitivities within the human population.

Brain death: optimizing support of the traumatic brain injury patient awaiting organ procurement.

PURPOSE OF REVIEW: Increasing numbers of deaths on the transplant waiting list is associated with an expanding supply-demand deficit in transplantable organs. There is consequent interest in reviewing both donor eligibility after death from traumatic brain injury, and subsequent management, to minimize perimortem insult to donatable organs. RECENT FINDINGS: Recipient outcomes are not worsened when transplanting organs from donors who were declared dead after traumatic brain injury. Protocolized donor management improves overall organ procurement rates and subsequent organ function. Longer periods of active management (up to 48 h) are associated with improved outcomes in renal, lung, and heart transplantation. Several empirically derived interventions have been shown to be ineffective, but there are increasing numbers of structured trials being performed, offering the possibility of improving transplant numbers and recipient outcomes. SUMMARY: New studies have questioned previous considerations of donor eligibility, demonstrating the ability to use donated organs from a wider pool of possible donors, with less exclusion for associated injury or comorbid conditions. There are identifiable benefits from improved donor resuscitation and bundled treatment approaches, provoking systematic assessments of effect and new clinical trials in previously overlooked areas of clinical intervention.

Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project.

IMPORTANCE: There are inconsistencies in concept, criteria, practice, and documentation of brain death/death by neurologic criteria (BD/DNC) both internationally and within countries. OBJECTIVE: To formulate a consensus statement of recommendations on determination of BD/DNC based on review of the literature and expert opinion of a large multidisciplinary, international panel. PROCESS: Relevant international professional societies were recruited to develop recommendations regarding determination of BD/DNC. Literature searches of the Cochrane, Embase, and MEDLINE databases included January 1, 1992, through April 2020 identified pertinent articles for review. Because of the lack of high-quality data from randomized clinical trials or large observational studies, recommendations were formulated based on consensus of contributors and medical societies that represented relevant disciplines, including critical care, neurology, and neurosurgery. EVIDENCE SYNTHESIS: Based on review of the literature and consensus from a large multidisciplinary, international panel, minimum clinical criteria needed to determine BD/DNC in various circumstances were developed. RECOMMENDATIONS: Prior to evaluating a patient for BD/DNC, the patient should have an established neurologic diagnosis that can lead to the complete and irreversible loss of all brain function, and conditions that may confound the clinical examination and diseases that may mimic BD/DNC should be excluded. Determination of BD/DNC can be done with a clinical examination that demonstrates coma, brainstem areflexia, and apnea. This is seen when (1) there is no evidence of arousal or awareness to maximal external stimulation, including noxious visual, auditory, and tactile stimulation; (2) pupils are fixed in a midsize or dilated position and are nonreactive to light; (3) corneal, oculocephalic, and oculovestibular reflexes are absent; (4) there is no facial movement to noxious stimulation; (5) the gag reflex is absent to bilateral posterior pharyngeal stimulation; (6) the cough reflex is absent to deep tracheal suctioning; (7) there is no brain-mediated motor response to noxious stimulation of the limbs; and (8) spontaneous respirations are not observed when apnea test targets reach pH <7.30 and Paco2 ≥60 mm Hg. If the clinical examination cannot be completed, ancillary testing may be considered with blood flow studies or electrophysiologic testing. Special consideration is needed for children, for persons receiving extracorporeal membrane oxygenation, and for those receiving therapeutic hypothermia, as well as for factors such as religious, societal, and cultural perspectives; legal requirements; and resource availability. CONCLUSIONS AND RELEVANCE: This report provides recommendations for the minimum clinical standards for determination of brain death/death by neurologic criteria in adults and children with clear guidance for various clinical circumstances. The recommendations have widespread international society endorsement and can serve to guide professional societies and countries in the revision or development of protocols and procedures for determination of brain death/death by neurologic criteria, leading to greater consistency within and between countries.

Human blood MAIT cell subsets defined using MR1 tetramers.

Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18Rα and CD26. The development of MR1-Ag tetramers now permits the specific identification of MAIT cells based on T-cell receptor specificity. Here, we compare these approaches for identifying MAIT cells and show that surrogate markers are not always accurate in identifying these cells, particularly the CD4+ fraction. Moreover, while all MAIT cell subsets produced comparable levels of IFNγ, TNF and IL-17A, the CD4+ population produced more IL-2 than the other subsets. In a human ontogeny study, we show that the frequencies of most MR1 tetramer+ MAIT cells, with the exception of CD4+ MAIT cells, increased from birth to about 25 years of age and declined thereafter. We also demonstrate a positive association between the frequency of MAIT cells and other unconventional T cells including Natural Killer T (NKT) cells and Vδ2+ γδ T cells. Accordingly, this study demonstrates that MAIT cells are phenotypically and functionally diverse, that surrogate markers may not reliably identify all of these cells, and that their numbers are regulated in an age-dependent manner and correlate with NKT and Vδ2+ γδ T cells.

Cardiac dysfunction following brain death in children: prevalence, normalization, and transplantation.

OBJECTIVES: Cardiac dysfunction has been reported to occur in as much as 42% of adults with brain death, and may limit cardiac donation after brain death. Knowledge of the prevalence and natural course of cardiac dysfunction after brain death may help to improve screening and transplant practices but adequately sized studies in pediatric brain death are lacking. The aims of our study are to describe the prevalence and course of cardiac dysfunction after pediatric brain death. DESIGN: Cross-sectional study. SETTING/SUBJECTS: We examined an organ procurement organization database (Life Center Northwest) of potential pediatric cardiac donors diagnosed with brain death between January 2011 and November 2013. INTERVENTION: Transthoracic echocardiograms were reviewed for cardiac dysfunction (defined as ejection fraction <50% or the presence of regional wall motion abnormalities). Descriptive statistics were used to analyze clinical characteristics and describe longitudinal echocardiogram findings in a subgroup of patients. We examined for heterogeneity between cardiac dysfunction with respect to cause of brain death. MEASUREMENT AND MAIN RESULTS: We identified 60 potential pediatric cardiac donors (age ≤ 18 yr) with at least one transthoracic echocardiogram following brain death. Cardiac dysfunction was present in 23 patients (38%) with brain death. Mean ejection fraction (37.6% vs 62.2%) and proportion of procured hearts (56.5% vs 83.8%) differed significantly between the groups with and without cardiac dysfunction, respectively. Of the 11 subjects with serial transthoracic echocardiogram data, the majority of patients with cardiac dysfunction (73%) improved over time, leading to organ procurement. No heterogeneity between cardiac dysfunction and particular causes of brain death was observed. CONCLUSION: The frequency of cardiac dysfunction in children with brain death is high. Serial transthoracic echocardiograms in patients with cardiac dysfunction showed improvement of cardiac function in most patients, suggesting that initial decisions to procure should not solely depend on the initial transthoracic echocardiogram examination results.

Temporal Changes in Left Ventricular Systolic Function and Use of Echocardiography in Adult Heart Donors.

BACKGROUND: One reason for refusal of donor hearts is the development of left ventricular systolic dysfunction, a condition reported to occur in up to 42 % of adults with brain death. Prior studies have suggested that appropriate donor management and evaluation of cardiac dysfunction with serial echocardiography (TTE) can improve organ procurement. The aims of our study are to examine the prevalence and describe longitudinal changes in cardiac dysfunction after brain death. METHODS: A cross-sectional study was performed using the Life Center Northwest organ database to identify potential adult heart donors diagnosed with brain death between January 2011 and November 2013. 246 potential donors with at least one TTE following brain death were identified. 58 donors received serial TTEs. Echocardiograms were reviewed for cardiac dysfunction, defined as left ventricular ejection fraction (EF) <50 % and/or presence of regional wall motion abnormalities. RESULTS: Cardiac dysfunction was present in 74 (30 %) patients. Age, body mass index, EF, and proportion of harvested organs differed significantly between the groups with and without cardiac dysfunction. Among patients receiving serial TTEs, 29 patients had cardiac dysfunction on initial TTE, with 15 (52 %) of these patients demonstrating resolved cardiac dysfunction over time leading to organ harvest. CONCLUSIONS: To our knowledge, the present study is the largest study describing the use of serial TTE and its utilization in adult donors. The prevalence of cardiac dysfunction after adult brain death is high, but given enough time and support, many of these donors have improvement in cardiac function, ultimately leading to transplantation.

Recommendations for the Critical Care Management of Devastating Brain Injury: Prognostication, Psychosocial, and Ethical Management : A Position Statement for Healthcare Professionals from the Neurocritical Care Society.

Devastating brain injuries (DBIs) profoundly damage cerebral function and frequently cause death. DBI survivors admitted to critical care will suffer both intracranial and extracranial effects from their brain injury. The indicators of quality care in DBI are not completely defined, and despite best efforts many patients will not survive, although others may have better outcomes than originally anticipated. Inaccuracies in prognostication can result in premature termination of life support, thereby biasing outcomes research and creating a self-fulfilling cycle where the predicted course is almost invariably dismal. Because of the potential complexities and controversies involved in the management of devastating brain injury, the Neurocritical Care Society organized a panel of expert clinicians from neurocritical care, neuroanesthesia, neurology, neurosurgery, emergency medicine, nursing, and pharmacy to develop an evidence-based guideline with practice recommendations. The panel intends for this guideline to be used by critical care physicians, neurologists, emergency physicians, and other health professionals, with specific emphasis on management during the first 72-h post-injury. Following an extensive literature review, the panel used the GRADE methodology to evaluate the robustness of the data. They made actionable recommendations based on the quality of evidence, as well as on considerations of risk: benefit ratios, cost, and user preference. The panel generated recommendations regarding prognostication, psychosocial issues, and ethical considerations.

Alternative clinical trial design in neurocritical care.

Neurocritical care involves the care of highly complex patients with combinations of physiologic derangements in the brain and in extracranial organs. The level of evidence underpinning treatment recommendations remains low due to a multitude of reasons including an incomplete understanding of the involved physiology; lack of good quality, prospective, standardized data; and the limited success of conventional randomized controlled trials. Comparative effectiveness research can provide alternative perspectives and methods to enhance knowledge and evidence within the field of neurocritical care; these include large international collaborations for generation and maintenance of high quality data, statistical methods that incorporate heterogeneity and individualize outcome prediction, and finally advanced bioinformatics that integrate large amounts of variable-source data into patient-specific phenotypes and trajectories.

Brain Death: Medical, Ethical, Cultural, and Legal Aspects.

The development of critical care stimulated brain death criteria formulation in response to concerns on treatment resources and unregulated organ procurement. The diagnosis centered on irreversible loss of brain function and subsequent systemic physiologic collapse and was subsequently codified into law. With improved critical care, physiologic collapse (while predominant) is not inevitable-provoking criticisms of the ethical and legal foundation for brain death. Other criteria have been unsuccessfully proposed, but irreversibility remains the conceptual foundation. Conflicts can arise when families reject the diagnosis-resulting in ethical, cultural, and communication challenges and implications for diversity, equity, and inclusion.

External Ventricular Drain Placement, Critical Care Utilization, Complications, and Clinical Outcomes after Spontaneous Subarachnoid Hemorrhage: A Single-Center Retrospective Cohort Study.

BACKGROUND: To examine the association between external ventricular drain (EVD) placement, critical care utilization, complications, and clinical outcomes in hospitalized adults with spontaneous subarachnoid hemorrhage (SAH). METHODS: A single-center retrospective study included SAH patients 18 years and older, admitted between 1 January 2014 and 31 December 2022. The exposure variable was EVD. The primary outcomes of interest were (1) early mortality (<72 h), (2) overall mortality, (3) improvement in modified-World Federation of Neurological Surgeons (m-WFNSs) grade between admission and discharge, and (4) discharge to home at the end of the hospital stay. We adjusted for admission m-WFNS grade, age, sex, race/ethnicity, intraventricular hemorrhage, aneurysmal cause of SAH, mechanical ventilation, critical care utilization, and complications within a multivariable analysis. We reported adjusted odds ratios (aORs) and 95% confidence intervals (CI). RESULTS: The study sample included 1346 patients: 18% (n = 243) were between the ages of 18 and 44 years, 48% (n = 645) were between the age of 45-64 years, and 34% (n = 458) were 65 years and older, with other statistics of females (56%, n = 756), m-WFNS I-III (57%, n = 762), m-WFNS IV-V (43%, n = 584), 51% mechanically ventilated, 76% White (n = 680), and 86% English-speaking (n = 1158). Early mortality occurred in 11% (n = 142). Overall mortality was 21% (n = 278), 53% (n = 707) were discharged to their home, and 25% (n = 331) improved their m-WFNS between admission and discharge. Altogether, 54% (n = 731) received EVD placement. After adjusting for covariates, the results of the multivariable analysis demonstrated that EVD placement was associated with reduced early mortality (aOR 0.21 [0.14, 0.33]), an improvement in m-WFNS grade (aOR 2.06 [1.42, 2.99]) but not associated with overall mortality (aOR 0.69 [0.47, 1.00]) or being discharged home at the end of the hospital stay (aOR 1.00 [0.74, 1.36]). EVD was associated with a higher rate of ventilator-associated pneumonia (aOR 2.32 [1.03, 5.23]), delirium (aOR 1.56 [1.05, 2.32]), and a longer ICU (aOR 1.33 [1.29;1.36]) and hospital length of stay (aOR 1.09 [1.07;1.10]). Critical care utilization was also higher in patients with EVD compared to those without. CONCLUSIONS: The study suggests that EVD placement in hospitalized adults with spontaneous subarachnoid hemorrhage (SAH) is associated with reduced early mortality and improved neurological recovery, albeit with higher critical care utilization and complications. These findings emphasize the potential clinical benefits of EVD placement in managing SAH. However, further research and prospective studies may be necessary to validate these results and provide a more comprehensive understanding of the factors influencing clinical outcomes in SAH.