Clinical Diagnosis Of Brain Death Research Articles

Diagnóstico clínico de muerte encefálica y empleo del Doppler transcraneal, con ecografía de las arterias cerebrales medias y el segmento intracraneal de las arterias vertebrales. Concordancia con los hallazgos de la gammagrafía cerebral

The Real Ordinance 2070/1999 meant an important modification in the legislation, when including transcranial Doppler (TCD) in explorations to confirm the clinical diagnosis of brain death (BD). Habitually for their employment in the diagnosis of BD, we look for blood flow signal from the middle cerebral arteries (MCA) and the basilar artery (BA).To check the effectiveness of the TCD like test of BD, looking for both middle cerebral arteries (MCA) and both intracranial vertebral arteries (VA), instead of the BA, and taking as Gold Standard cerebral scintigraphic techniques.. We present 25 patients diagnosed clinically with BD; on these TCD was carried out to confirm BD. Later on we proceeded to carry out cerebral scintigraphic techniques in all these cases. As statistical tool the test of c2 is used with confidence interval of 95%.In 24 of the 25 cases, the TCD was effective in confirming the diagnosis of BD. In the remaining patient, a false positive result was obtained, since the TCD didn't reveal flow in the infratentorial compartment, as contrary to the cerebral scintigraphic techniques which showed the presence of residual flow at this level; this residual flow disappeared in 36 hours. This patient was hemodynamically unstable during TCD exploration.In our results the TCD obtains a reliability of 100% when confirming the absence of blood flow in the supratentorial compartment; nevertheless the false positive result obtained at the infratentorial level, warns us to be cautious in accepting the flow from the VA as a test of absence of flow at the infratentorial compartment, especially in those patients with hemodynamic instability.

Cerebral vasomotor reactivity in brain dead patients

P61 Background: Cerebral vasomotor reactivity (CVMR) is a measure of the changes in arteriolar resistance in response to changes in arterial C0 2 concentration. CMVR is easily performed at the bedside using transcranial Doppler ultrasound (TCD). CVMR has not been studied in brain death. Methods: Patients with a clinical diagnosis of brain death, confirmed by a neurointensivist, were studied. CVMR was determined at the time of the apnea test. An experienced sonographer used a Pioneer TC 2020 (Nicolette) with a 2 MHz probe to insonate a middle cerebral artery of these patients. Continuous middle cerebral artery blood flow velocity (MCAV), systolic blood pressure (SBP), heart rate (HR), body temperature, oxygen saturation, and end-tidal C0 2 was performed during the procedure.A confirmatory arterial blood gas was obtained at baseline, five and ten minutes into the apnea test, and three minutes after hyperventilation. CMVR was calculated as follows: (MCAV at hypercapnia/MCAV at baseline)x100 - (MCAV at hypocapnia/MCAV at baseline)x100.(Normal in adults: 86±16%) CMVR was then divided by the absolute change in C0 2 to yield the percentage change (%Δ) in MCAV per mmHg C0 2 (Normal in adults: 2–4%). Results: Ten patients were studied (8 men) with a mean age 47±16 years.Their underlying disease varied: 3 ischemic strokes, 3 ICH, 2 SAH and 2 anoxic encephalopathy. Values of parameters monitored during the apnea test for this population: SBP:140±25 mmHg, HR:90.6±31/min, temperature: 35.8±2, PC0 2 at baseline: 40.6±9, at end of test: 74.6±13, at hyperventilation: 33.3±5. CMVR was 43.5±20% and %Δ was 1.3±0.4. All these patients had MCAV patterns compatible with brain death. Conclusion: CMVR is severely reduced or exhausted in brain dead patients. This test should be considered when TCD is used as a confirmatory tool in clinically brain dead patients.

Could Heart Rate Variability Analysis Become an Early Predictor of Imminent Brain Death? A Pilot Study

Physiology of brain death is characterized by major disturbances of autonomic nervous system (ANS) activity which can lead to graft dysfunction. These findings exhibit the importance of early diagnosis of brain death to improve transplantation outcome. The aim of this prospective study was to assess whether heart rate variability (HRV) analysis, a noninvasive method to investigate ANS activity in comatose patients, could achieve this goal. A total of 14 brain-injured patients were included in the study as soon as they exhibited the clinical signs of imminent brain death. The electrocardiogram was then recorded from two leads with a Holter digital monitor. The clinical diagnosis of brain death was considered after an autonomic storm had occurred. HRV was assessed from 6 h before to 6 h after brain death in both time domain and spectral analysis, estimating either global ANS activity (index of variability, total power), parasympathetic activity (percentage of δ of R-R interval >50 ms, root mean square for successive interval differences, LnHF) or sympathetic activity (LnLF). Hourly averages of these variables were compared by using one-way analysis of variance. To assess whether HRV could per se diagnose brain death, receiver operating characteristic curves were generated for total power, root mean square for successive interval differences, and LnHF. We observed, for 6 h before brain death, a progressive extinction of the influence of the ANS on cardiovascular regulation. There was no activity in the two components of the ANS as soon as brain death occurred. HRV analysis appeared to be a very sensitive but a less specific method of diagnosing brain death. Implications A total of 14 brain-injured patients with the clinical criteria of imminent brain death were enrolled for electrocardiogram recording and heart rate variability analysis (a noninvasive method to investigate autonomic nervous system activity). For 6 h before brain death, we observed a progressive extinction of autonomic nervous system activity which was not present as soon as brain death was clinically evoked.

Could heart rate variability analysis become an early predictor of imminent brain death? A pilot study.

Physiology of brain death is characterized by major disturbances of autonomic nervous system (ANS) activity which can lead to graft dysfunction. These findings exhibit the importance of early diagnosis of brain death to improve transplantation outcome. The aim of this prospective study was to assess whether heart rate variability (HRV) analysis, a noninvasive method to investigate ANS activity in comatose patients, could achieve this goal. A total of 14 brain-injured patients were included in the study as soon as they exhibited the clinical signs of imminent brain death. The electrocardiogram was then recorded from two leads with a Holter digital monitor. The clinical diagnosis of brain death was considered after an autonomic storm had occurred. HRV was assessed from 6 h before to 6 h after brain death in both time domain and spectral analysis, estimating either global ANS activity (index of variability, total power), parasympathetic activity (percentage of delta of R-R interval >50 ms, root mean square for successive interval differences, LnHF) or sympathetic activity (LnLF). Hourly averages of these variables were compared by using one-way analysis of variance. To assess whether HRV could per se diagnose brain death, receiver operating characteristic curves were generated for total power, root mean square for successive interval differences, and LnHF. We observed, for 6 h before brain death, a progressive extinction of the influence of the ANS on cardiovascular regulation. There was no activity in the two components of the ANS as soon as brain death occurred. HRV analysis appeared to be a very sensitive but a less specific method of diagnosing brain death. A total of 14 brain-injured patients with the clinical criteria of imminent brain death were enrolled for electrocardiogram recording and heart rate variability analysis (a noninvasive method to investigate autonomic nervous system activity). For 6 h before brain death, we observed a progressive extinction of autonomic nervous system activity which was not present as soon as brain death was clinically evoked.

Accuracy of Clinical Evaluation in the Determination of Brain Death

The accuracy of the clinical diagnosis of brain death has never been established. Seventy-one consecutive clinically brain dead patients were studied retrospectively. Inclusion criteria were complete cessation of brain function with profound coma of known cause, complete absence of brain stem reflexes, and apnea, all persisting for a least 6 hours. A formal apnea test with a documented Pco2 of > 60 mm Hg was required. All evaluations were done by experienced neurosurgery or neurology resident or staff physicians. The clinical diagnosis was compared with the results of radionuclide angiography and with the clinical course and final outcome. Seventy patients had no arterial blood flow on radionuclide angiography. One blood flow study was considered to have yielded a false-negative result. No patient recovered or survived. The clinical diagnosis of brain death is highly reliable when made by experienced examiners using established criteria. In this study, the accuracy was 100%.

European brain death codes: a comparison of national guidelines.

The majority of European countries have published recommendations for the diagnosis of brain death as a necessary prerequisite for organ donation. The concept of brain death as defining the death of the individual is accepted in all European countries; however, the guidelines for determining the total and irreversible loss of all brain functions differ somewhat in the various countries. While the clinical examination and documentation of the clinical signs of brain death are very uniform, there are significant differences in the guidelines for using technical confirmatory tests to corroborate the clinical signs. These range from rejecting all technical tests to accepting of multiple neurophysiological tests alone or in combination. The present study examined the similarities and differences in current concepts of brain death in the various European countries and their recommendations for the diagnosis of brain death. The diagnosis of brain death is based on a number of prerequisites, on the clinical diagnosis of deep coma, loss of all brainstem reflexes, and the demonstration of apnea. Neurophysiological tests are recommended by a number of national professional societies as confirmatory tests to confirm the clinical diagnosis of brain death and shorten otherwise necessary waiting periods of 6-12 h. Most brain death codes allow the use of electroencephalography, which must demonstrate electrocortical silence over a certain period. Evoked cerebral potentials can demonstrate the successive loss of activity of various afferent pathways and are accepted in some countries as a confirmatory test. Other neurophysiological tests which demonstrate the loss of cerebral perfusion can be implemented. Brain scintigraphy can confirm the loss of isotope uptake into the brain. Doppler sonography also demonstrates cessation of brain perfusion. Cerebral panangiography may also be used to demonstrate the loss of brain perfusion but is less desirable since it might endanger the patient.

Radionuclide angiography as a confirmatory test for brain death: a review of 229 studies in 219 patients.

Radionuclide angiography (RA) has been used for many years to confirm the clinical diagnosis of brain death, but quantitative data regarding the technique are unavailable. We conducted a retrospective review of 229 RA procedures done in 219 patients. Of 206 patients who had interpretable studies and met clinical criteria for brain death (profound coma, absent brain stem reflexes, and apnea), including 10 patients who had repeated studies, 203 (98.5% sensitivity) had positive studies, and 6 (2.9%) had negative studies. Of nine patients who had interpretable studies and did not meet the clinical criteria for brain death, five (56% specificity) had positive studies and four (44%) had negative studies. Radionuclide angiography is a sensitive confirmatory test of brain death. The study does not evaluate the posterior fossa circulation, and an occasional patient may have residual brain stem function. The examination is most reliable when the patient is in a deep coma, has no brain stem reflexes, and has failed a formal apnea test.

Evaluating Brain Death with Positron Emission Tomography: Case Report on Dynamic Imaging of 18F‐Fluorodeoxyglucose Activity after Intravenous Bolus Injection

A dynamic positron emission tomography (PET) study of the head was performed over 1 hour after the intravenous bolus administration of 18F-fluorodeoxyglucose (18F-FDG) to a 18-year-old patient with the clinical diagnosis of brain death. This dynamic PET study was performed on the seventh day after a severe posttraumatic closed-head injury. No intracerebral uptake or retention of tracer was noted, consistent with a diffuse absence of brain metabolism. A small amount of tracer was noted to slowly rise over time within the sagittal sinus, indicating that visualization of sagittal sinuses on technetium 99m-diethylene-triaminepentaacetic acid planar images could provide a falsely negative scintigraphic evaluation for the presence of brain death. It is concluded that PET FDG imaging may be a useful technique in evaluating patients for brain death.

Magnetic resonance imaging of brain death : Lee DH, Nathanson JA, Fox AJ, et al. (Department of Diagnostic Radiology and Nuclear Medicine, University Hospital, 339 Windermere Road, London, Ontario N6A 5A5, Canada). Can Assoc Radiol J 1995;46:174–178

To demonstrate the magnetic resonance imaging (MRI) appearance of the brain in patients with clinical brain death.High-field (1.5-T) MRI was performed on five patients who were subsequently proven clinically brain dead. Conventional T1-weighted and T2-weighted imaging was performed.MRI exhibited similar features for all of the patients: loss of the subarachnoid spaces of the brain; slow flow in the intracavernous and cervical internal carotid arteries; and loss of flow void in the small and large intracranial arteries, as well as in the major intracranial venous sinuses. The differentiation between grey and white matter in the brain was preserved, although the brain had a "supernormal" appearance due to the absence of cerebrospinal fluid and arterial pulsations. These findings have not been observed in MRI of comatose patients who were not clinically brain dead.With the advent of MRI-compatible ventilators and noninvasive monitoring, which facilitate imaging of patients under intensive care, MRI may offer another method of confirming the clinical diagnosis of brain death.

Reliability in diagnosis of brain death

To compare some of the confirmatory investigations of brain death with clinical criteria in order to achieve the most sensitive and accurate diagnosis of brain death. All patients with isolated brain lesions and Glasgow Coma Scale (GCS) = 3 were subjected to neurological examination after ruling out hypothermia, metabolic disorders and drug intoxications and diagnosed as clinically brain-dead when the brainstem reflexes were absent and the apnea test positive. 15 patients with clinical diagnosis of brain death entered this study. The patients were submitted to the following investigations: electroencephalogram (EEG), transcranial Doppler (TCD) of the middle cerebral arteries (MCA), cerebral blood flow measurements with the i.v. Xe-133 method (CBF) and selective cerebral angiography (CA). EEG was isoelectric in 8 patients while the remaining 7 patients showed persistence of electrical activity. TCD was compatible with intracranial circulatory arrest in 18 MCA districts, compatible with normal flow in 2 and undetectable in 10 out of 30 districts insonated. In CBF examinations, however, all the patients showed a characteristic "plateau" of the desaturation curves lasting through the whole investigation and suggestive of absent cortical flow. CA showed circulatory arrest in both carotid and vertebral arteries. Our study suggests that cerebral angiography and CBF studies are the most reliable investigations whereas the role of EEG and TCD remains to be determined because of the presence of false negatives and positives.

Determining brain death in adults [RETIRED

Overview. The Quality Standards Subcommittee of the American Academy of Neurology (AAN) is charged with developing guidelines for neurologists for diagnostic procedures, treatment modalities, and clinical disorders. The present document is intended to provide background for the report “Practice Parameters for Determining Brain Death in Adults” (in this issue), which has been produced by the Quality Standards Subcommittee of the AAN and approved by the AAN Executive Board. This document outlines diagnostic criteria for the chical diagnosis of brain death in patients older than 18 years. The recommendations for diagnosis in neonates and children have been published as a position paper by the American Academy of Pediatrics’; in addition, a review paper can be consulted.‘ The sensitivity and specificity of laboratory tests that confirm the clinical diagnosis of brain death are discussed. Justification. Brain death is seen frequently as a result of severe head injury, aneurysmal subarachnoid hemorrhage, and intracerebral hem~rrhage.~.~ In medical and surgical intensive care units, large ischemic strokes associated with brain swelling and herniation, hypoxic-ischemic encephalopathy after prolonged cardiac resuscitation or asphyxia, and massive brain edema in patients with fulminant hepatic necrosis are the most common causes of brain death.7-9 In large referral hospitals, neurologists or neurosurgeons may diagnose brain death

Intracerebral temperature in neurosurgical patients: Intracerebral temperature gradients and relationships to consciousness level

Information regarding human brain temperature is still rather sparse, which is surprising giving the no longer recent findings that the mammalian brain is very sensitive to minor variations in temperature. We therefore report the results of intracranial temperature monitoring in thirty neurosurgical patients. Intraventricular temperature was monitored with a thermocouple specifically designed for the purpose, and introduced through a plastic catheter used for monitoring of intracranial pressure, with simultaneous measurements of rectal and epidural temperature with commercially available thermocouples. Human intraventricular temperature is higher than central core temperature, and there is also a temperature gradient within the brain, with the central parts being warmer than the surface. The presence of an intracerebral temperature gradient was confirmed in two patients undergoing stereotactic thalatomy. We found no clear evidence for a correlation between consciousness level and brain temperature. Observations of brain temperature changes after clinical diagnosis of brain death are also reported.

Brain death: neuropathological findings and forensic implications

‘Brain death’ is defined pathophysiologically as intracranial circulatory arrest. The morphological features of brain death include cerebral edema, absence of reactive changes, and — after an interval of 15–36 h — the morphological hallmarks of respirator brain: edema, global softening of the brain, dusky discoloration of the gray matter, and often necrotic and sloughing tonsillar herniations. The following implications of brain death for forensic medicine are discussed: discriminating between respirator and autolytic brain, declaration of death, determining the time of brain death versus the time of the traumatic event leading to brain death, and neuropathological control of the clinical diagnosis of brain death. These issues are elucidated and their bearing on forensic practice is illustrated by several real-life situations. Thus, neuropathological examination in the case of clinically diagnosed brain death is — without doubt — necessary in order to answer several questions often or regularly expected.

Transcranial Doppler Ultrasonography: Clinical Applications in Cerebrovascular Disease

Transcranial Doppler ultrasonography was introduced in 1982 as a noninvasive procedure for assessment of the intracranial cerebral circulation. The lightweight and portable equipment used for transcranial Doppler examination facilitates its use in the bedside assessment of critically ill hospitalized patients and outpatients. Clinical applications include the diagnosis of vasospasm in patients with subarachnoid hemorrhage, assessment of intracranial collateral flow in patients with extracranial arterial occlusive disease, detection of intracranial arterial stenosis, identification of the feeding arteries of arteriovenous malformations and monitoring the hemodynamic effects of their treatment, confirmation of the clinical diagnosis of brain death, intensive-care unit monitoring of brain-injured patients, and intraoperative and postoperative monitoring of neurosurgical patients. Transcranial Doppler technology is also providing new insights into the pathophysiologic mechanisms of a variety of cerebrovascular conditions. Clinicians will find transcranial Doppler technology most helpful if they have a specific question about the status of the intracranial circulation. Further investigations may expand the clinical and research utility of this technology.

Use of brainstem auditory evoked potentials in pediatric brain death.

Brainstem auditory evoked potentials (BAEPs) were examined prospectively in ten clinically brain-dead and 13 comatose nonbrain-dead children. All clinically brain-dead children failed to demonstrate brainstem impulse transmission, displaying no waves or only wave I. The comatose, nonbrain-dead children maintained evidence of brainstem electrical activity, manifested by at least two waveforms. This suggests that BAEPs are a useful noninvasive method of supporting the clinical diagnosis of brain death in children.

Variant flow patterns in radionuclide cerebral imaging performed for brain death.

Radionuclide cerebral imaging (RCI) is a commonly used technique for detection of intracranial blood flow in patients with clinically suspected brain death. In 115 studies performed on 95 patients in a six-year period at the Geisinger Medical Center, a number of variant flow patterns have been observed. Although all have been described previously, there has been no review of these patterns on studies performed for brain death. The significance of normal blood flow, absent blood flow, isolated superior sagittal sinus activity, luxury perfusion, hypoperfusion, hemiperfusion, and jugular venous reflux is discussed. Any demonstrable intracranial blood pool activity is presently considered to counter a diagnosis of brain death, except that jugular reflux renders an examination uninterpretable. Technique must be top quality but, even so, RCI cannot evaluate basilar brain flow. Nonetheless, RCI is a valuable adjunct in helping to establish the clinical diagnosis of brain death.

Confirmation of Brain Death with Portable Isotope Angiography: A Review of 204 Consecutive Cases

Abstract Intravenous isotope angiography is a rapid, safe, and specific bedside test for confirming brain death by demonstrating the lack of critical cerebral perfusion that occurs in this condition, regardless of etiology. A review of 204 consecutive cases of suspected brain death studied with isotope angiography has reaffirmed our confidence in the specificity of the technique and has convinced us to make less stringent our radiographic criteria for confirming brain death by this method. A technically satisfactory single flow study that shows arrest of the carotid circulation at the base of the skull and absence of the intracranial arterial circulation may be considered confirmatory of a carefully established clinical diagnosis of brain death, even though there may be some visualization of the intracranial venous sinuses. Arbitrary waiting periods, withdrawal of sedative drugs, and electrophysiological studies are not needed when this technique is used.

Confirmation of Brain Death with Portable Isotope Angiography: A Review of 204 Consecutive Cases

Intravenous isotope angiography is a rapid, safe, and specific bedside test for confirming brain death by demonstrating the lack of critical cerebral perfusion that occurs in this condition, regardless of etiology. A review of 204 consecutive cases of suspected brain death studied with isotope angiography has reaffirmed our confidence in the specificity of the technique and has convinced us to make less stringent our radiographic criteria for confirming brain death by this method. A technically satisfactory single flow study that shows arrest of the carotid circulation at the base of the skull and absence of the intracranial arterial circulation may be considered confirmatory of a carefully established clinical diagnosis of brain death, even though there may be some visualization of the intracranial venous sinuses. Arbitrary waiting periods, withdrawal of sedative drugs, and electrophysiological studies are not needed when this technique is used.

Failure of electroencephalography to diagnose brain death in comatose children

Two isoelectric electroencephalograms obtained 24 hours apart support a clinical diagnosis of brain death in prolonged coma. Without documentation of electrocerebral silence, physicians are reluctant to discontinue vital support systems. A radionuclide bolus technique has been developed that documents the absence of cerebral blood flow in suspected brain death and supplements the flat EEG. In a recent review of this technique, all 27 adults who had EEG activity maintained the integrity of their cerebral blood flow. This contrasts to our studies of 5 children, all of whom demonstrated persistent EEG activity but had no evidence of cerebral blood flow by either the isotope bolus technique (5 patients) or cerebral angiography (4 patients). These children (mean age, 7 months) lacked cephalic reflexes and were maintained on assisted ventilation for an average of 15 days. Multiple electroencephalographic tracings persistently demonstrated low-voltage cortical activity over this time. Despite the lack of cerebral blood flow, all patients were continued on respiratory support. At autopsy, extensive brain liquefaction necrosis was noted. In comatose children, EEG monitoring may be of limited value while cerebral blood flow measurements can provide more practical and prognostic information.

Bedside procedures in the diagnosis of brain death

Thirteen different tests were performed on 42 patients in the state of brain death. Some of these tests are well known and widely utilized, such as elect roencephalography, carotid and vertebral arteriography, brain scanning and gamma camera, and echoencephalography. More sophisticated tests such as measurement of cerebral blood flow, cerebral oxygen consumption and intracranial pressure are less accurate but may assist in an earlier forecast of brain death. Three new procedures, electronystagmography, intrathecal injection of I-labelled serum albumin and brain temperature tests, are also described. The poor specificity of the caloric test and the high reliability of the atropine test are stressed. It is concluded that a selection of simple, rapid, bedside tests have been shown to be entirely adequate in confirming the clinical diagnosis of brain death.