Clinical Determination Of Brain Death Research Articles

Outcomes, Time-Trends, and Factors Associated With Ancillary Study Use for the Determination of Brain Death.

Brain death determination often requires ancillary studies when clinical determination cannot be fully or safely completed. We aimed to analyze the results of ancillary studies, the factors associated with ancillary study performance, and the changes over time in number of studies performed at an academic health system. Retrospective cohort. Multihospital academic health system. Consecutive adult patients declared brain dead between 2010 and 2020. None. Of 140 brain death patients, ancillary studies were performed in 84 (60%). The false negative rate of all ancillary studies was 4% (5% of transcranial Doppler ultrasounds, 4% of nuclear studies, 0% of electroencephalograms, and 17% of CT angiography). In univariate analysis, ancillary study use was associated with female sex (odds ratio, 2.4; 95% CI, 1.21-5.01; p = 0.013) and the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 2.9; 95% CI, 1.43-5.88; p = 0.003), nontraumatic intracranial hemorrhage (odds ratio, 0.45; 95% CI, 0.21-0.96; p = 0.039), or traumatic brain injury (odds ratio, 0.22; 95% CI, 0.04-0.8; p = 0.031). In multivariable analysis, female sex (odds ratio, 5.7; 95% CI, 2.56-15.86; p = 0.004), the etiology of brain death being hypoxic-ischemic brain injury (odds ratio, 3.2; 95% CI, 1.3-8.8; p = 0.015), and the neurologists performing brain death declaration (odds ratio, 0.08; 95% CI, 0.004-0.64; p = 0.034) were factors independently associated with use of ancillary studies. Over the study period, the total number of ancillary studies performed each year did not significantly change; however, the number of electroencephalograms significantly decreased with time (odds ratio per 1-yr increase, 0.67; 95% CI, 0.49-0.90; p = 0.014). A large number of ancillary studies were performed despite a clinical determination of brain death; patients with hypoxic-ischemic brain injury are more likely to undergo ancillary studies for brain death determination, and neurologists were less likely to use ancillary studies for brain death. Recently, the use of electroencephalograms for brain death determination has decreased, likely reflecting significant concerns regarding its validity and reliability.

Clinical Determination of Brain Death in Children Supported by Extracorporeal Membrane Oxygenation.

Children supported by extracorporeal membrane oxygenation (ECMO) are at risk of catastrophic neurologic injury and brain death. Timely determination of brain death is important for minimizing psychological distress for families, resource allocation, and organ donation. Reports of successful determination of brain death in pediatric patients supported by ECMO are limited. The determination of brain death by clinical criteria requires apnea testing, which has historically been viewed as challenging in patients supported by ECMO. We report eight pediatric patients who underwent a total of 14 brain death examinations, including apnea testing, while supported by veno-arterial ECMO (VA-ECMO), resulting in six cases of clinical determination of brain death. We performed a retrospective review of the medical records of pediatric patients who underwent brain death examination while supported by VA-ECMO between 2010 and 2018 at a single tertiary care children's hospital. Eight patients underwent brain death examination, including apnea testing, while supported by VA-ECMO. Six patients met criteria for brain death, while two had withdrawal of technical support after the first examination. During the majority of apnea tests (n=13/14), the ECMO circuit was modified to achieve hypercarbia while maintaining oxygenation and hemodynamic stability. The sweep flow was decreased prior to apnea testing in ten brain death examinations, carbon dioxide was added to the circuit during three examinations, and ECMO pump flows were increased in response to hypotension during two examinations. Clinical determination of brain death, including apnea testing, can be performed in pediatric patients supported by ECMO. The ECMO circuit can be effectively modified during apnea testing to achieve a timely rise in carbon dioxide while maintaining oxygenation and hemodynamic stability.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

Predisposing Hemodynamic Factors Associated with a Failed Apnea Test during Brain Death Determination

Background: The apnea test is an essential component in the clinical determination of brain death, however it may incur a significant risk of complications such as hypotension, hypoxia and even cardiac arrest. We analyzed the risk factors associated with a failed apnea test during brain death assessment in order to predict and avoid these adverse events. Methods: Medical records on apnea tests performed for brain-dead donors at our institution between January 2009 and January 2016 were retrospectively reviewed. Age, gender, etiology of brain death, use of catecholamines and results of arterial blood gas analysis (ABGA), systolic/diastolic blood pressure (SBP/DBP), mean arterial pressure and central venous pressure prior to apnea test initiation were collected as variables. A-a gradient and PaO2/FiO2 were calculated for more precise assessment of the respiratory system. In total, 267 cases were divided into two groups based on those who completed the apnea test and those who failed the test. Results: 13 cases failed the apnea test. Among them, seven cases failed due to severe hypotension (SBP < 60 mmHg) and the others failed due to refractory hypoxia. In terms of hemodynamic state, SBP was significantly higher in the completed test group than the failed group (126.5 ± 23.9 vs. 103 ± 15.2, respectively; p = 0.001). In ABGA, the completed test group showed significantly higher PaO2/ FiO2 (313.6 ± 229.8 vs. 141.5 ± 131.0, respectively; p = 0.008) and a lower A-a gradient (278.2 ± 209.5 vs. 506.2 ± 173.1, respectively; p = 0.000). In multivariable analysis, low SBP (p = 0.003) and high A-a gradient (p = 0.044) were independent risk factors associated with a failed apnea test. Conclusions: Although the unexpected adverse events during the apnea test for brain death determination do not occur frequently, they can be fatal. If a brain-dead patient has low SBP and a high A-a gradient, clinicians should pay more attention and prepare for potential complications prior to the apnea test.

The clinical determination of brain death: rational and reliable.

The clinical determination of brain death: rational and reliable.

Computed tomographic angiography as a useful adjunct in the diagnosis of brain death

Because of its widespread accessibly, computed tomographic angiography (CT-A) is a promising technique in the detection of intracranial circulatory arrest in brain death (BD). Several studies assessed this tool, but neither have standardized evaluation parameters been developed nor has information about specificity become available. We conducted a prospective study between January 2008 and April 2012. Thirty patients were admitted to our University Hospital (16 men and 14 women; age, 18-88 years) and underwent CT-A scanning at two occasions: immediately after the first signs of loss of brain stem reflexes and after definitive determination of brain. The results of CT-A were compared with transcranial Doppler ultrasonography and electroencephalogram. In 3 of 30 patients, we observed a termination of contrast flow at the level of the skull base and foramen magnum in arterial scanning series before the clinical determination of BD. After the clinical determination of BD, the opacification of all vascular territories in arterial phase scanning was found in one case, but venous phase scanning revealed no blood return in internal cerebral veins. In all other cases, contrast filling ceased at level of skull base or below. The specificity of CT-A in the detection of intracranial circulatory arrest was 90%, and sensitivity was 97%. CT-A is reliable and appropriate technical investigation to detect intracranial circulatory arrest in BD. The evaluation of contrast enhancement in arterial phase scanning seems to be more reliable than that in venous phase. An international consensus about a uniformly applied CT-A protocol for the evaluation of BD should be established.

Computed tomographic angiography as a useful adjunct in the diagnosis of brain death

BACKGROUND: Because of its widespread accessibly, computed tomographic angiography (CT-A) is a promising technique in the detection of intracranial circulatory arrest in brain death (BD). Several studies assessed this tool, but neither have standardized evaluation parameters been developed nor has information about specificity become available. METHODS: We conducted a prospective study between January 2008 and April 2012. Thirty patients were admitted to our University Hospital (16 men and 14 women; age, 18–88 years) and underwent CT-A scanning at two occasions: immediately after the first signs of loss of brain stem reflexes and after definitive determination of brain. The results of CT-A were compared with transcranial Doppler ultrasonography and electroencephalogram. RESULTS: In 3 of 30 patients, we observed a termination of contrast flow at the level of the skull base and foramen magnum in arterial scanning series before the clinical determination of BD. After the clinical determination of BD, the opacification of all vascular territories in arterial phase scanning was found in one case, but venous phase scanning revealed no blood return in internal cerebral veins. In all other cases, contrast filling ceased at level of skull base or below. The specificity of CT-A in the detection of intracranial circulatory arrest was 90%, and sensitivity was 97%. CONCLUSION: CT-A is reliable and appropriate technical investigation to detect intracranial circulatory arrest in BD. The evaluation of contrast enhancement in arterial phase scanning seems to be more reliable than that in venous phase. An international consensus about a uniformly applied CT-A protocol for the evaluation of BD should be established. LEVEL OF EVIDENCE: Diagnostic study, level V.

Brain Death Dilemmas and the Use of Ancillary Testing

The Uniform Determination of Death Act indicates that "an individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem, is dead," with brain death being determined based on "accepted medical standards." The AAN has published practice guidelines providing medical standards for the determination of brain death. The most recent AAN guideline update notes that "because of the deficiencies in the evidence base, clinicians must exercise considerable judgment when applying the criteria in specific circumstances" and that "ancillary tests can be used when uncertainty exists about the reliability of parts of the neurologic examination or when the apnea test cannot be performed. This article presents two cases commonly encountered in clinical practice in which the findings of the guideline-specified clinical neurologic assessment may be difficult to interpret, hampering the clinical determination of brain death. In these circumstances, ancillary testing specifically assessing for cerebral circulatory arrest may be helpful.

Clinical Determination of Brain Death

In 2010 an article in the Canadian Journal of Anesthesia1 presented case reports of two patients who appeared to regain spontaneous respiration after they had been determined to be brain dead. The criteria used were those described in the recommendations from the Canadian Council for Donation and Transplantation2. The article was accompanied by an editorial3 that acknowledged the challenges faced by the physicians who determined that brain death had occurred, but concludes that in both cases several of the criteria were either misinterpreted or overlooked. However, it is clearly pertinent to ask if these reports have any implications for the clinical determination of brain death in Australia and New Zealand as described in the Australian and New Zealand Intensive Care Society (ANZICS) Statement on Death and Organ Donation4.

Pronouncing brain death

Little is known of hospital practice in brain death determination, specialty involvement, and followed procedures, including the apnea test. We reviewed 228 patients pronounced brain dead at Mayo Clinic from 1996 to 2007. We performed a detailed review of clinical determination of brain death, intensive care support, apnea test procedure, and complications. There were 228 patients who were pronounced brain dead, mostly after traumatic brain injury, cerebral hematoma, or aneurysmal subarachnoid hemorrhage. Brain death was declared within 24 hours of ictus in 30% of the patients and within 3 days in 62%. All patients were using one or more vasopressors, and 61% of the patients received vasopressin for diabetes insipidus. An apnea test could not be performed in 7% of the patients because of hemodynamic instability or poor oxygenation at baseline. In 3% of the patients, the apnea test procedure was aborted because of hypoxemia or hypotension. No major complications (cardiac arrest or pneumothorax) occurred during the apnea test. Polytrauma resulting in brain death was significantly more common in patients with aborted or not attempted apnea tests than in patients with completed apnea tests (p = 0.0004). During the study epoch, we found a shift toward determination of the tests by neurointensivists, pediatric neurologists, and neurosurgeons. Brain death declaration is frequent within the first 3 days of admission. It is usually performed in hemodynamically unstable patients requiring vasopressors and vasopressin. If preconditions are met, apnea testing using an oxygen-diffusion technique is safe. However, in 1 of 10 patients, an apnea test could not be completed and confirmatory tests were needed.

Complications associated with the apnea test in the determination of the brain death

An apnea test is essential in the clinical determination of brain death. This study was conducted to analyse complications associated with the apnea test in the determination of the brain death. On 93 adult patients in coma in Zhejiang Province of China from January 2003 to December 2006, 179 apnea tests were performed as a part of the determination of brain death. Potential risk conditions and complications were analysed during apnea tests. During apnea, serious cardiac arrhythmia did not occur in all patients. Complications occurred in 37 of 179 (21%) apnea tests. Hypotension occurred in 30 patients (17%) and it was observed in 8/94 (9%) tests with baseline value of systolic arterial blood pressure not less than 120 mmHg, and 22/85 (26%) less than 120 mmHg (P < 0.05). Severe hypoxaemia occurred in 10 patients (6%) of which 3/138 (2%) tests with baseline value of arterial oxygen pressure not less than 200 mmHg, and 7/41 (17%) less than 200 mmHg (P < 0.05). This study demonstrated that complications occurred mostly in patients with inadequate baseline systolic arterial blood pressure and preoxygenation. Adequate precautions during the apnea tests may reduce the risk of cardiovascular and oxygenation complication.

10 Questions About the Clinical Determination of Brain Death

From the Department of Neurology and Division of Critical Care Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota. Reprints: Eelco F. M. Wijdicks, MD, Mayo Clinic College of Medicine, Department of Neurology and Division of Critical Care Neurology, 200 First St. SW, Rochester, MN 55905. E-mail: [email protected].

Continuous multivariable monitoring in neurological intensive care patients-preliminary reports on four cases

Evoked potential monitoring is a standard examination method in neurological intensive therapy units. Previously, multimodality observation was only possible in follow-up examinations. First experience with a new bed-side system continuously monitoring 12 neurophysiological and clinical parameters is reported. It consists of a personal computer and various stimulation units. EEG activity, median nerve somatosensory evoked potentials (SEPs) and brainstem auditory evoked potential (BAEPs) are recorded. Additionally, EEG spectral band power, heart rate, heart rate variability, intracranial pressure, body temperature, expiratory PCO2, blood pressure and transcutaneously measured oxygenation can be monitored. This paper reports on 4 exemplary cases of the 33 patients we have monitored to date, illustrating the principles and main advantages of the system. The system was developed to support the observation of ICU patients as well as to aid therapeutic decisions. It supports the clinical determination of brain death by specifying the deterioration of various neurological systems.

Anencephaly: Clinical determination of brain death and neuropathologic studies

Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (P co 2 > 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation.