Occurrence Of Brain Death Research Articles

С-РЕАКТИВНЫЙ БЕЛОК КАК ПРЕДИКТОР НЕОБРАТИМОГО ПОВРЕЖДЕНИЯ ГОЛОВНОГО МОЗГА

Background. As for now, the level of C-reactive protein (CRP), which may be present in donors with traumatic and non-traumatic brain injuries, has not been reliably established, and its dynamics in patients upon the occurrence of brain death (BD) have not been studied. Objective of this study is to investigate the dynamics of CRP levels in patients with severe irreversible brain damage, which subsequently led to brain death. Material and methods. The prospective study included 106 patients with severe brain damage who were diagnosed with BD despite treatment. The CRP level was determined for patients on the 1st to 10th days of intensive therapy. Results. The CRP level upon admission to the ICU was 13.3 (3.86; 29.1) mg/l. CRP values were within normal limits only in 14 (13.2%) patients. On the 2nd day of intensive therapy, the level of CRP was higher statistically significant – 85 (45.4; 140.6) mg/l, p =0.00004 vs 1 day. On the 3rd day of intensive therapy, the level of CRP was also higher statistically significant – 135.3 (73.6; 238.2) mg/l, p =0.00001 vs 2 days. The CRP values in all patients were higher than the reference values. On the 4th day, the level of CRP in patients became 219.7 (112.7; 326.4) mg/l (p=0.00006 vs 3 days) and did not significantly change in the following days in terms of statistics. Conclusion. The dynamics of CRP levels in patients with severe brain damage can be used as a predictor of unfavorable outcome of intensive care and brain death.

Abstract 176: Development Of A Novel Score To Predict Brain Death After Out Of Hospital Cardiac Arrest

Introduction: Brain death occurs in 10-15% of successfully resuscitated out-of-hospital cardiac arrest (OHCA) patients. Early identification of potential organ donors is critical to prevent withdrawal of life sustaining therapy (WLST) and ensure adequate organ perfusion. To predict brain death after OHCA, we developed a novel brain death risk (BDR) score. Methods: The BDR score was developed from a retrospective, single center cohort of OHCA patients admitted from 2011-2020. After excluding patients with early WLST (defined as < 72 hours from OHCA), univariate regression models identified independent predictors of brain death, which were used to build the BDR score. We included the following variables: non-shockable rhythm (1 point), drug overdose as etiology of arrest (1 point), evidence of grey-white differentiation loss or sulcal effacement on head computed tomography (CT) within 24 hours of arrest (2 points), Full-Outline-Of-UnResponsiveness (FOUR) score of 0 (2 points), FOUR score 1-5 (1 point), and age < 45 years (1 point). Head CT findings were based on neuroradiology reports. We validated the BDR score in an independent single center OHCA cohort. The primary outcome was occurrence of brain death. Using the area under the receiving operator characteristic curve (AUC), we assessed the score’s prediction of brain death. Results: The development cohort included 256 OHCA patients; 15.6% (40/256) experienced brain death. The AUC (95% CI) of the BDR score was 0.921 (0.870-0.971). In the validation cohort, 24.4% (21/86) experienced brain death. The AUC (95% CI) of the BDR score was 0.830 (0.7266-0.9335). Table 1 shows the rate of brain death at each BDR score. In both cohorts, a BDR score ≥ 5 was the optimal cut off (sensitivity 0.9 and 0.714, specificity 0.843 and 0.831, respectively). Conclusion: Early scoring systems may be able to identify those at highest risk for brain death after OHCA. Our data suggest that a BDR score ≥ 5 could help predict progression to brain death.

Prediction of Brain Death After Out-of-Hospital Cardiac Arrest: Development and Validation of the Brain Death After Cardiac Arrest Score

Among patients successfully resuscitated after an out-of-hospital cardiac arrest (OHCA), 10%to 15%evolve toward brain death (BD), thus becoming potential organ donors. Is it possible to establish a score for early estimation of BD risk after OHCA? The BD after cardiac arrest (BDCA) score was developed from data available within 24 hours after OHCA from two OHCA trials: Cyclosporine in Cardiac Arrest Resuscitation and Erythropoietin After OHCA. The BDCA score was then validated in another large prospective multicenter data set. The main outcome was the occurrence of BD. Independent prognostic covariates for BD were identified using a binomial two-stage adaptive least absolute shrinkage and selection operator procedure. The development cohort included 569 patients alive 24 hours after OHCA, among whom 84 (14.8%) experienced BD. Independent predictors of BD used to build the BDCA score were being female (4 points), nonshockable rhythm (24 points), cardiac cause of OHCA (-6 points), neurological cause of OHCA (45 points), natremia at 24 hours (natremia in millimoles per liter minus 140 points), and vasoactive drug at admission (4 points) and at 24 hours (6 points). The area under the curve (AUC) of the BDCA score was 0.82 (95%CI, 0.77-0.86), and the discrimination value in the validation cohort (n= 487) was consistent (AUC, 0.81; 95%CI, 0.76-0.86). In the validation cohort, BD occurred in 4.0%, 20.4%, and 67.7%of patients with scores of< 20, 20 to 50, and > 50, respectively. The BDCA score allows early detection of patients with a high probability of experiencing BD, which may help increase organ donation after OHCA. ClinicalTrials.gov; No.: NCT01595958, and ClinicalTrials.gov; No.: NCT00999583; URL: www.clinicaltrials.gov.

Abstract TP166: Frequency of Brain Death in Acute Cerebrovascular Disease Related Mortality

Background: Despite the frequent occurrence of brain death in intensive care unit, the prevalence rate of brain death in ischemic stroke (IS), intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is not known at national level. In addition the prevalence of cardiac arrest in these patients is not established. Methods: From 2012, ICD-9-CM includes a specific code for brain death (348.82). Brain death patients were identified from the nationwide in-patient sample database for the years 2012 to 2014. Associated in-hospital cardiac arrest patients were also identified under each category. Demographics, medical comorbidities, in-hospital complications, procedures, length of stay and hospital charges were compared. Results: Rate of brain death was highest in SAH related mortality (22%, 3255 brain deaths/ 14620 in-hospital mortality), followed by ICH, (12.5%, 5760 brain deaths/ 45945 in-hospital mortality) and ischemic stroke (3%, 1840 brain death/62285 in-hospital mortality). Majority of the patients had brain death secondary to neurological insult (ICH n=5260, 91.3%; SAH n= 2625 (80.6%) and IS n=1640, 89.1%) without any secondary diagnosis of in-hospital cardiac arrest. Length of stay was shorter in patients with SAH and ICH (mean 2.92±4.13 days and 2.53±3.56 days respectively) compared to IS patients (mean 4.93 ± 10.2 days, p &lt; 0.001) suggesting brain death is an early event in hemorrhagic stroke. Conclusion: Brain death in the majority of cerebrovascular patients occurs as a result of primary neurological insult without associated cardiac arrest. It occurs much earlier in hemorrhagic stroke compared to ischemic stroke.

The rate of brain death and organ donation in patients resuscitated from cardiac arrest: a systematic review and meta-analysis.

BackgroundThe occurrence of brain death in patients with hypoxic-ischaemic brain injury after resuscitation from cardiac arrest creates opportunities for organ donation. However, its prevalence is currently unknown.MethodsSystematic review. MEDLINE via PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews were searched for eligible studies (2002–2016). The prevalence of brain death in adult patients resuscitated from cardiac arrest and the rate of organ donation among brain dead patients were summarised using a random effect model with double-arcsine transformation. The quality of evidence (QOE) was evaluated according to the GRADE guidelines.Results26 studies [16 on conventional cardiopulmonary resuscitation (c-CPR), 10 on extracorporeal CPR (e-CPR)] included a total of 23,388 patients, 1830 of whom developed brain death at a mean time of 3.2 ± 0.4 days after recovery of circulation. The overall prevalence of brain death among patients who died before hospital discharge was 12.6 [10.2–15.2] %. Prevalence was significantly higher in e-CPR vs. c-CPR patients (27.9 [19.7–36.6] vs. 8.3 [6.5–10.4] %; p < 0.0001). The overall rate of organ donation among brain dead patients was 41.8 [20.2–51.0] % (9/26 studies, 1264 patients; range 0–100 %). The QOE was very low for both outcomes.ConclusionsIn patients with hypoxic-ischaemic brain injury following CPR, more than 10 % of deaths were due to brain death. More than 40 % of brain-dead patients could donate organs. Patients who are unconscious after resuscitation from cardiac arrest, especially when resuscitated using e-CPR, should be carefully screened for signs of brain death.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-016-4549-3) contains supplementary material, which is available to authorized users.

Gray Matter–White Matter De-Differentiation on Brain Computed Tomography Predicts Brain Death Occurrence

Previous studies have shown that a loss of distinction between gray matter (GM) and white matter (WM) on unenhanced CT scans was predictive of poor outcome after cardiac arrest. The aim of this study was to identify a marker/predictor of imminent brain death. In this retrospective study, 15 brain-dead patients after anoxia and cardiac arrest were included. Patients were paired (1:1) with normal control subjects. Only patients' unenhanced CT scans performed before brain death and during the 24 hours after initial signs were analyzed. WM and GM densities were measured in predefined regions of interest (basal ganglia level, centrum semi-ovale level, high convexity level, brainstem level). At each level, GM and WM density and GM/WM ratio for brain-dead patients and normal control subjects were compared using the Wilcoxon signed-rank test. At each level, a lower GM/WM ratio and decreased GM and WM densities were observed in brain-dead patients' CT scans when compared with normal control subject CT scans. A cut-off value of 1.21at the basal ganglia level was identified, below which brain death systematically occurred. GM/WM dedifferentiation on unenhanced CT scan is measurable before the occurrence of brain death, highlighting its importance in brain death prediction. The mechanism of GM/WM differentiation loss could be explained by the lack of oxygen caused by ischemia initially affecting the mitochondrial system.

Establishment of a stable mouse model of brain death by the method of the gradually increasing intracranial pressure.

To establish a stable and modified mouse model of brain death (BD) and to share our experiences in BD induction and maintenance. Totally 35 C57BL/6 male mice were randomized into BD group (n=25) or sham control group (n=10). BD was induced by inserting a 2F Fogarty catheter connected to a syringe pump after trepanation of the left frontoparietal area and injecting volume at the speed of 6 μl/min until spontaneous respiration ceased. BD was diagnosed by electroencephalogram, apnea testing,as well as testing of brain stem reflexes. Mechanical ventilation was performed by orotracheal intubation. Right carotid artery was intubated by a PE-10 cannula for the continuous monitoring of mean blood pressure (MAP) and heart rate (HR). The right external jugular vein was catheterized for volume resuscitation.The sham control group underwent the same procedure with catheter insertion but without balloon inflation.Livers were removed and fixed in paraffin to evaluate the histological alterations with the light microscopy. Mouse models of BD were successfully established about 20 minutes after balloon inflation, and the mean balloon volume at the time of BD was (105.77 ± 21.57)μl. The MAP and HR rapidly increased on occurrence of BD and the peak value was (128.28 ± 17.16) mmHg and (434.16 ± 55.75) beat/min, respectively, which were significant higher than those in the sham control group at the same time point (P=0.000). During the 4-hour follow-up time, MAP and HR in 72% (18/25) of BD animals remained haemodynamically stable. No animal died due to anesthesia and surgical operation.Hepatic tissues in BD mice showed mild focal ischemic damages (cellular edema, congestion, and inflammatory infiltration), which were slighter and fewer in sham control group. The mouse model of BD was successfully established with lower surgical difficulty and can be performed in a standardized, reproducible and successful way.

Establishing a Brain-Death Donor Model in Pigs

IntroductionAn animal model that imitates human conditions might be useful not only to monitor pathomechanisms of brain death and biochemical cascades but also to investigate novel strategies to ameliorate organ quality and functionality after multiorgan donation. MethodsBrain death was induced in 15 pigs by inserting a catheter into the intracranial space after trephination of the skull and augmenting intracranial pressure until brain stem herniation. Intracranial pressure was monitored continuously; after 60 minutes, brain death diagnostics were performed by a neurologist including electroencephalogram (EEG) and clinical examinations. Clinical examinations included testing of brain stem reflexes as well as apnoe testing; then intensive donor care was performed according to standard guidelines until 24 hours after confirmation of brain death. Intensive donor care was performed according to standard guidelines for 24 hours after brain death. ResultsSixty minutes after brain-death induction, neurological examination and EEG examination confirmed brain death. Intracranial pressure increased continuously, remaining stable after the occurrence of brain death. All 15 animals showed typical signs of brain death such as diabetes insipidus, hypertensive and hypotensive periods, as well as tachycardia. All symptoms were treated with standard medications. After 24 hours of brain death we performed successful multiorgan retrieval. DiscussionBrain death can be induced in a pig model by inserting a catheter after trephination of the skull. According to standard guidelines the brain-death diagnosis was established by a flat-line EEG, which occurred in all animals at 60 minutes after induction.

Neurological injury after extracorporeal membrane oxygenation use to aid pediatric cardiopulmonary resuscitation

Extracorporeal membrane oxygenation (ECMO) to aid failed cardiopulmonary resuscitation (CPR) in children is associated with a high incidence of neurologic injury. We sought to identify risk factors for acute neurologic injury in children undergoing ECMO to aid CPR (E-CPR). Retrospective cohort study using data reported to the Extracorporeal Life Support Organization registry. Multi-institutional data. Patients <18 years of age undergoing E-CPR during 1992-2005. None. We defined acute neurologic injury as the occurrence of brain death, brain infarction, or intracranial hemorrhage identified by ultrasound or computerized tomography imaging. Of 682 E-CPR patients, 147 (22%) patients had acute neurologic injury. Brain death occurred in 74 (11%), cerebral infarction in 45 (7%), and intracranial hemorrhage in 45 (7%). The in-hospital mortality rate in patients with acute neurologic injury was 89%. In a multivariable logistic regression model, pre-ECMO factors including cardiac disease (odds ratio [OR] 0.46 [95% confidence interval {CI} 0.28-0.76]) and pre-ECMO blood pH > or =6.865 (> or =6.865-7.120; OR 0.49 [95% CI 0.25-0.94]; pH >7.120; OR 0.47 [95% CI 0.26-0.85]) compared with pH <6.865 were associated with decreased odds of neurologic injury. During ECMO, neurologic injury was associated with ECMO complications including pulmonary hemorrhage (OR 1.93, 95% CI 1.1-3.4), dialysis use (OR 2.36, 95% CI 1.4-4.0), and CPR during ECMO support (OR 2.08, 95% CI 1.6-3.8). Neurologic injury is a frequent complication in children undergoing E-CPR. Children with cardiac disease, less severe metabolic acidosis before ECMO, and an uncomplicated ECMO course have decreased odds of sustaining neurologic injury. Providing effective CPR and inclusion of brain protective therapies on ECMO should be considered in the future to improve neurologic outcomes for patients undergoing E-CPR.

Organ donations and unused potential donations in traumatic brain injury, subarachnoid haemorrhage and intracerebral haemorrhage

To obtain insight into the occurrence of brain death and the potential for brain dead and controlled non-heart-beating organ donors (CNHB) in patients with traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) in a large neurosurgical serving area (2.1 million inhabitants). Retrospective analysis of data concerning patients with TBI, SAH and ICH who died during the course of ICU treatment during 1999-2003. A 16-bed neuro-intensive care unit. Patients with TBI, SAH or ICH who died during the course of ICU treatment. The number of ICU deaths in patients with TBI, SAH and ICH declined from 111 in 1999 to 64 in 2003. In total, 476 deaths occurred. Of these, 177 patients were not included in the analysis. Two hundred ninety-nine (299) ventilated patients had two or more absent brainstem reflexes (ABSR) and a Glasgow Coma Score of 3-4 at the moment of treatment withdrawal and formed the potential for organ donation; 61 of these patients were treated until full brain death. Organs of 57 patients could be harvested. We analysed the reasons that organs were not procured in the 242 remaining patients. The most important reasons were family refusal (32%), medical contraindications (14%), and the treating physician not considering potential organ donation (20%). The missed potential is 162/299 (54%). The number of actual and potential organ donors is declining, but a considerable number of potential CNHB donors exists. Refusal by relatives is the most important reason for failure to procure organs.

High prevalence of decreased cortisol reserve in brain-dead potential organ donors.

To investigate the adrenocortical function in brain-dead patients, potential organ donors. Prospective study. Intensive care units in two teaching hospitals. A total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 +/- 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. In all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 microg of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 microg/dL after the administration of adrenocorticotropic hormone were defined as responders. After the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 +/- 6.2 vs. 17.0 +/- 6.6 microg/dL, p <.001) and stimulated (16.9 +/- 6.3 vs. 23.9 +/- 5.7 microg/dL, p =.001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p <.001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r =.71, p =.001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = -.37, p =.15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 +/- 11.4 vs. 6.8 +/- 4.2 microg/dL, p =.003) and stimulated serum cortisol (28.8 +/- 9.9 vs. 16.3 +/- 4.3 microg/dL, p =.008). Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.

High incidence of decreased cortisol reserve in brain-dead potential organ-donors

To investigate the adrenocortical function in brain-dead, potential organ donors, 36 patients (27 men, 9 women) with severe brain injury (BI), having a mean age of 42 ± 18 years were studied. Group A, consisted of 20 BI patients who did not develop brain-death (BD), and group B, was comprised of 16 BI patients who became brain-dead. Of these, seven patients were admitted in the hospital after clinical BD. In all patients (group A and group B), a morning blood sample was obtained upon admission in the ICU to determine baseline plasma cortisol levels. Subsequently, 1 μg of corticotropin (ACTH, synacthen) was administered intravenously and a second blood sample was drawn 30 min following the injection. In group B patients, the same procedure was repeated the morning following the confirmation of BD. Patients having a cortisol level of at least 18 μg/dl following the administration of ACTH were defined as responders. After the occurrence of BD, group B patients had significantly lower values for baseline (8.8 ± 6.3 vs 17.0 ± 6.6 μg/dl, P < 0.001) and stimulated (16.8 ± 6.5 vs. 23.9 ± 5.7 μg/dl, P = 0.001) plasma cortisol levels compared to group A patients. Hormonal data of the nine brain-dead patients studied upon admission in the ICU and after the occurrence of BD were the following: baseline plasma cortisol 23.8 ± 12.0 vs 7.1 ± 4.3 μg/dl, P = 0.008, and stimulated plasma cortisol 28.9 ± 10.5 vs 16.0 ± 4.4 μg/dl, P = 0.01. Thirteen group B patients (81%) and two group A patients (10%) were non-responders to synacthen (P < 0.0001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r = 0.72, P = 0.002), whereas there was no correlation between baseline cortisol and the increment in cortisol (r =-0.33, P = 0.21). In conclusion, adrenal cortisol secretion following dynamic stimulation is deficient in a substantial proportion of brain-dead patients. This finding calls for reconsideration of corticosteroid replacement therapy, at least in a subset, of brain-dead potential organ donors.

Changes in spinal reflex excitability in brain-dead humans

The excitability of proprio- and exteroceptive spinal reflexes was monitored electrophysiologically and clinically during the occurrence of brain death (BD) in 8 patients. After a period of total reflex unresponsiveness, the soleus H reflex attained a steady-state excitability level in 2–6 h. The recovery cycle of this response regained its normal shape at 10–20 h. The threshold of the cutaneous reflex evoked in the biceps femoris by electrical stimulation of the sural nerve had become normal in 4–13 h, although the response displayed an abnormal multi-component pattern. Digital responses to mechanical stimulation of the foot sole were evident after 6–8 h. Knee and ankle jerks were never evoked during the time of monitoring. The time-courses of the changes in excitability were not directly correlated with the fall in the blood pressure which may occur during BD. It is concluded that the human spinal cord reacts to BD with a spinal shock, characterized by sequential recovery of reflex transmission. The overall timing of this process appears to be much shorter than that previously described for the spinal shock following traumatic transection of the cord, but the latter was never studied in the earliest phases.

Elaboration of a cognitive model in a visuomanual tracking task

The excitability of proprio- and exteroceptive spinal reflexes was monitored electrophysiologically and clinically during the occurrence of brain death (BD) in 8 patients.After a period of total reflex unresponsiveness, the soleus H reflex attained a steady-state excitability level in 2–6 h. The recovery cycle of this response regained its normal shape at 10–20 h. The threshold of the cutaneous reflex evoked in the biceps femoris by electrical stimulation of the sural nerve had become normal in 4–13 h, although the response displayed an abnormal multi-component pattern. Digital responses to mechanical stimulation of the foot sole were evident after 6–8 h. Knee and ankle jerks were never evoked during the time of monitoring.The time-courses of the changes in excitability were not directly correlated with the fall in the blood pressure which may occur during BD.It is concluded that the human spinal cord reacts to BD with a spinal shock, characterized by sequential recovery of reflex transmission. The overall timing of this process appears to be much shorter than that previously described for the spinal shock following traumatic transection of the cord, but the latter was never studied in the earliest phases.

The brain-life theory: towards a consistent biological definition of humanness.

This paper suggests that medically the term a 'human being' should be defined by the presence of an active human brain. The brain is the only unique and irreplaceable organ in the human body, as the orchestrator of all organ systems and the seat of personality. Thus, the presence or absence of brain life truly defines the presence or absence of human life in the medical sense. When viewed in this way, human life may be seen as a continuous spectrum between the onset of brain life in utero (eight weeks gestation), until the occurrence of brain death. At any point human tissue or organ systems may be present, but without the presence of a functional human brain, these do not constitute a 'human being', at least in a medical sense. The implications of this theory for various ethical concerns such as in vitro fertilisation and abortion are discussed. This theory is the most consistent possible for the definition of a human being with no contradictions inherent. However, having a good theory of definition of a 'human being' does not necessarily solve the ethical problems discussed herein.