Brain Death Group Research Articles

Contribution of MRI and MR angiography in early diagnosis of brain death.

The objective of this study was to investigate whether the findings of MR imaging and MR angiography could accurately and early diagnose brain death in comatose patients. Thirty comatose patients were studied with MRI and MR arteriography. In 20 patients (group A) presenting with a Glasgow coma scale (GCS) 3-6, the final clinical diagnosis was brain death. In ten comatose patients with a GCS 4-6 and no clinical signs of brain death (group B), the clinical follow-up did not reveal brain death in a period of 12 months. The MRI examination consisted of turbo fluid-attenuated inversion recovery and T2 turbo spin-echo pulse sequences. The MR arteriography was performed with a 3D inflow pulse sequence. In 12 patients with brain death and 5 patients with no signs of brain death, a 3D phase contrast MR venography was also applied. Magnetic resonance imaging in all patients showed variable edema with swelling of the cerebral gyri, small ventricular system, and basilar subarachnoid spaces. In group A, MRI in addition showed tonsillar herniation. In group A, MR arteriography revealed no arterial flow in the intracranial circulation, whereas MR venography showed in 9 patients no opacification of the sagittal and straight sinuses or visualization of intracranial veins. In contrast, MR angiography showed intact intracranial vessels in patients of group B. In conclusion, MR imaging and MR angiography may be reliable ancillary tests for use in early diagnosis of brain death and further work is required to validate its utility.

Brain death-related energetic failure of the donor heart becomes apparent only during storage and reperfusion: an ex vivo phosphorus-31 magnetic resonance spectroscopy study on the feline heart

Background and Objective: Recently, we have shown, by using localized in vivo phosphorus-31 magnetic resonance spectroscopy ( 31P MRS) of the anterior left ventricular wall, that brain death (BD) is not associated with reduced myocardial energy status. In this study, we applied ex vivo 31P MRS of the entire heart to study the effects of BD on the energy status of the feline donor heart following explantation. Methods: We used cats (6 BD and 6 controls [C]) in a 26-hour protocol. After 2 hours of preparation, we induced BD by filling an intracranial balloon at t = 0 hour. At t = 6 hours, the hearts were arrested with St. Thomas’ Hospital cardioplegic solution, explanted, and stored in the same solution at 4°C in a 4.7 Tesla magnet for 17 hours. Subsequently, the hearts were reperfused in the Langendorff mode at 38°C for 1 hour. The first 5-minute 31P MRS spectrum was obtained 1 hour after crossclamping the aorta; we obtained subsequent spectra every hour during storage and every 5 minutes during reperfusion. At the end, the hearts were dried and weighed. Phosphocreatine (PCr), γ-adenosine triphosphate (γ-ATP), inorganic phosphate (Pi), and phosphomonoesters (PME), were expressed per g dry heart weight. The intracellular pH (pH i) and the PCr/ATP ratio were calculated. Results: During storage, we identified a significant but similar decrease of pH i, PCr/ATP ratio, and PCr in both groups. During reperfusion, pH i and PCr/ATP ratio recovered similarly in both groups, whereas the recovery of PCr in the BD group was significantly lower ( p < 0.05). The Pi and PME increased in both groups during storage but to a lesser extent in the BD group ( p < 0.05). This difference disappeared during reperfusion. The γ-ATP was already significantly lower in the BD group at the onset of storage, and this remained so throughout storage and reperfusion ( p < 0.05 vs C). Contractile capacity was lost in all hearts, except for 1 heart in the BD group. Conclusion: Brain death-related failure of the energetic integrity of the feline donor heart becomes apparent only when using 31P MRS during ischemic preservation and subsequent reperfusion.

Hyperthermia: is it an ominous sign after cardiac arrest?

Objective: To clarify the clinical characteristics of hyperthermia at an early stage after resuscitation from cardiac arrest (CA). Materials and methods: We reviewed the medical records of 43 adult patients with non-traumatic out-of-hospital CA, who survived for longer than 24 h after admission to our intensive care unit (ICU) between January, 1995, and December, 1998. The patients were divided into two groups: a clinical brain death (CBD) group ( n=23) and a non-CBD group ( n=20), and various factors relating to hyperthermia were compared between the two groups. Results: The mean value of peak axillary temperatures within 72 h of admission was 39.8±0.9°C for the CBD group, which was significantly greater than 38.3±0.6°C for the non-CBD group ( P<0.0001). The time of occurrence of the peak axillary temperature was at 19±16 h of admission in the CBD group and 20±18 h in the non-CBD group (not significantly different). There were no significant differences in risk factors relating to the occurrence of hyperthermia between the two groups, except for the number of patients who received epinephrine at ICU. In 23 patients with a peak axillary temperature of ≧39°C during the first 72 h of hospitalization, brain death was diagnosed in 20 patients, whereas only 3 of 20 patients having a peak axillary temperature of <39°C developed brain death (odds ratio, 37.8; 95% confidence interval, 6.72–212.2). Conclusion: Hyperthermia at an early stage after resuscitation from CA may be associated with the outcome of brain death.

Biphasic response after brain death induction: prominent part of catecholamines release in this phenomenon

Background: The physiopathology of hemodynamic instability that occurs after brain death remains unknown. The aim of this study was to examine the initial response to brain death induction. Methods After anesthesia and monitoring, 16 pigs were randomized into a control group (C, n = 8) and a brain death group (BD, n = 8). We inflated a subdural catheter balloon to induce brain death. We analyzed hemodynamic and plasmatic biochemical data for 180 minutes after brain death induction. Energetic compounds were measured. We expressed the results in comparison with the C group. Results The C group remained stable. One minute after brain death, the Cushing reflex appeared, with a hyperdynamic response to plasma catecholamines levels increasing (norepinephrine and epinephrine, 3.1-fold, p = 0.02, and 3.8-fold, p = 0.07, respectively). After a return to baseline, we recorded a second hyperdynamic profile 120 minutes later. At this time, a second peak of catecholamines appeared (6.3-fold, p = 0.04, and 9.1-fold, p = 0.02, concerning norepinephrine and epinephrine). At the same time, we observed brief myocardial lactate production (+175%, p < 0.01), with a rise of troponine I (+64%, p = 0.03). The energetic index was similar in both groups: 0.85 (±0.02) in the C group vs 0.87 (±0.02) in the BD group. Conclusions In this model, biphasic plasmatic catecholamine release appears to primarily explain the physiopathology of the hemodynamic response to brain death induction.

Pretreatment of brain dead rabbits with pinacidil before prolonged cold-storage with an extracellular solution alters aortic endothelial function

Objective: Endothelial injury occurs during heart transplantation and contributes to the development of cardiac allograft vasculopathy. We have evaluated in a brain death model in the rabbit whether pre-treatment with the potassium channel opener (PCO) pinacidil before prolonged hypothermic storage with an extracellular solution would improve vascular endothelial recovery. Methods Rabbits were randomized into 4 experimental groups ( n = 8 per group). In the control group (CTRL), abdominal aortic rings were assessed immediately after 90 minutes of anesthesia. In the brain death group (BD), aortic rings were assessed immediately after 90 minutes of brain death. In the STH group, aortic rings taken from brain dead rabbits were stored for 24 hours at 4°C with the extracellular preservation solution of St. Thomas Hospital (STH) before assessment. In the STH + PCO group, the potassium channel opener pinacidil, 1 mg/kg, was administered intravenously to brain dead rabbits 10 minutes before explantation. Aortic rings were then stored for 24 hours at 4°C with the STH solution before evaluation. Brain death was induced by rapid inflation of a sub-durally placed balloon and validated by clinical and electroencephalographic data. Concentration-response curves to acetylcholine (ACH, 10 -9 to 10 -4 mol/liter) and nitroglycerin (NGL, 10 -9 to 10 -5 mol/liter) were constructed in phenylephrinepre-contracted rings. Results ACH evoked a similar concentration-dependent relaxation in the CTRL (E max: 95.8 ± 2.9%; EC 50: -6.86 ± 0.13 log M) and BD groups (E max: 90.8 ± 3.8%; EC 50: -6.75 ± 0.15 log M). The concentration-relaxation curve was shifted rightward in the STH group (E max: 76.7 ± 7.1%; EC 50: -6.75 ± 0.16 log M) in comparison with the CTRL and BD groups, but there were no significant differences in either E max or EC 50 values. After pinacidil pre-treatment, there was a further significant shift to the right of the concentration-relaxation curve to ACH (E max: 77.4 ± 5.0%; EC 50: -6.14 ± 0.19 log M, p < 0.05 vs CTRL, BD and STH). There were no significant differences between groups in the concentration-relaxation curves to NGL in endothelium-intact and endothelium-denuded vascular rings (either E max or EC 50). Conclusion Pre-treatment of brain dead rabbits with pinacidil before prolonged cold-storage with STH solution significantly impaired endothelium-dependent vasorelaxation in comparison to storage with STH solution. The role of PCO pre-treatment in the context of cardiac transplantation needs to be reconsidered.

Bio-energetic response of the heart to dopamine following brain death–related reduced myocardial workload: A phosphorus-31 magnetic resonance spectroscopy study in the cat

Objective: Long-term exposure of the donor heart to high dosages of dopamine in the treatment of brain death–related hemodynamic deterioration has been shown to reduce myocardial phosphocreatine (PCr) and adenosine triphosphate (ATP) in myocardial biopsy specimens and may preclude heart donation for transplantation. Short-term exposure to the acute catecholamine release during the onset of brain death has shown an unchanged PCr/ATP ratio using in vivo phosphorus-31 magnetic resonance spectroscopy ( 31P MRS). In this study 31P MRS was used to evaluate in vivo myocardial energy metabolism during long-term dopamine treatment. Methods Twelve cats were studied in a 4.7 Tesla magnet for 360 minutes. At t = 0 minutes, brain death was induced ( n = 6). At 210 minutes, when myocardial workload in the brain-death group was reduced significantly, dopamine was infused ( n = 12) at 5 μg/kg/min and its dose was consecutively doubled every 30 minutes and was withheld during the last 30 minutes of the experiment. Phosphorus-31 magnetic resonance spectra were obtained from the left ventricular wall during 5-minute time frames, and PCr/ATP ratios were calculated. The hearts were histologically examined. Results Although significant changes in myocardial workload were observed after the induction of brain death and during support and withdrawal of dopamine in both groups, the initial PCr/ATP ratio of 2.00 ± 0.12 and the contents of PCr and ATP did not vary significantly. Histologically identified sub-endocardial hemorrhage was observed in 3 of 6 of the brain-dead animals and in 1 of 6 of the control animals. Conclusions High dosages of dopamine in the treatment of brain death–related reduced myocardial workload do not alter PCr/ATP ratios and the contents of PCr and ATP of the potential donor heart despite histologic damage.

Investigation of Graft Function-Determining Factor in Cadaveric Renal Transplantations.

343 〈AIM〉 This study was conducted to identify the graft function -determining factors in cadaveric renal transplantations (RTx). 〈PATIENTS〉 One hundred fifty three patients treated by RTx in our center participated in this study. They were grouped by the type of donor and the mode of graft preservation as follows (HP: hypothermic continuous perfusion preservation, CS: simple cold storage): (Table)TableFor each group, multiple regression analysis was performed on donor age (D-Ag), recipient age (R-Ag), donor serum creatinine level (DS-Cr), warm ischemic time (WIT) and total ischemic time (TIT) against post-transplant graft function. 〈RESULTS〉 1) In the brain death group, even though D-Ag was significantly younger (p<0.01) and DS-Cr significantly lower (p<.01) for US kidney than for domestic kidney, ATN was significantly longer (p<.05) for US kidney, which may be attributed to a significantly longer TIT (p<.01). In domestic kidneys, ATN was significantly shorter for HP+CS group than for CS group (p<.05). 2) In the cardiac death group, even though D-Ag was significantly younger (p<.05) and DS-Cr significantly lower (p<.05) for NIS than for IS, ATN duration was significantly shorter (p<.01) for IS than for NIS. In IS cases, in spite of significantly longer WIT for HP+CS group than for CS group (p<.01), there was no difference in ATN between groups. 〈CONCLUSION〉 The function-determining factors were TIT for transplants from brain death donors and WIT for transplants from non-heart beating donors. In both the brain dead and cardiac dead groups, the presence or absence of HP was a factor for determining the graft function (whether or not the graft was treated by IS).

Right ventricular function after brain death: response to an increased afterload.

A major cause of early postoperative morbidity and mortality after cardiac transplantation is right ventricular (RV) failure which is attributed to the inability of the donor's RV to acutely compensate for the recipient's elevated pulmonary vascular resistance. This study was performed to determine: (1) the acute effects of brain death on the RV function; and (2) the adaptation potential of the RV to a progressive increase in RV afterload. In 13 anesthetized, open-chest dogs (eight with brain death vs. five control with sham operation), brain death was induced by inflation of a subdural balloon catheter. Heart rate, RV systolic and end-diastolic pressure (RVSP, RVEDP), pulmonary arterial pressure (PAP), and cardiac output (CO), and pressure-length loops (sonomicrometry) were recorded. Afterload increase was induced 2 h after brain death induction by constriction of the pulmonary artery with an increase in RVP from 25 to 50 mmHg in 5 mmHg steps. Cushing phenomenon occurred within a few minutes after brain death induction, with a significant increase of HR (229 +/- 10 vs. 89 +/- 6 min(-1), P < 0.001), CO (3.2 +/- 0.2 vs. 1.7 +/- 0.1 l/min, P < 0.001), PAP (30.4 +/- 2.5 vs. 15.5 +/- 1.3 mmHg, P < 0.01) RVSP (55 +/- 5 vs. 23 +/- 2 mmHg, P < 0.001) and RVEDP (7.4 +/- 0.9 vs. 3.3 +/- 0.6 mmHg, P < 0.001). All these values were also significantly (P < 0.01) higher than the time corresponding values of the control group. The analysis of the pressure-length loops showed a hypercontractile state. Within 15-60 min, all parameters turned to baseline and remained stable for up to 2 h. When afterload was increased progressively, RVEDP increased markedly in the brain death and slightly in the control group (9.4 +/- 0.7 vs. 4.2 +/- 1.1 mmHg, P < 0.01, at RVSP = 50 mmHg). On the other hand, the increase of peak positive dP/dt was significantly higher in the control group (430 +/- 37 vs. 644 +/- 55 mmHg/s, P < 0.01, at RVP = 50 mmHg). However, global RV pump function characterized by CO and stroke work was similar in both groups. While regional RV contractility remained unchanged in the brain death group in terms of pressure-length relationships, RV contractility significantly increased in the control group. (1) Brain death per se does not result in an acute impairment of RV function. (2) While control animals adapt to an increased afterload by the homeometric, as well as the heterometric regulation, after brain death, an increase in RV preload follows elevations in RV afterload by the Frank-Starling mechanism subserving the increased stroke work required to ensure unchanged pump function.

Brain Death Further Promotes Ischemic Reperfusion Injury of the Rabbit Myocardium

Background. Little is known about preload-dependent cardiac function after brain death (BD) and subsequent graft preservation. Methods. A validated model of BD in rabbits was developed and myocardial performance was studied after BD induction and 1 hour of subsequent global hypothermic ischemia using a validated rabbit model and an isolated work-performing heart preparation. Results. Significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed 2 hours after BD. After global hypothermic ischemia, significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed in the BD group compared with controls. Cardiac output and coronary flow were also significantly decreased in BD hearts compared with controls. Creatine kinase release was increased by 32.5% in BD hearts compared with controls. Conclusions. In a rabbit model, BD combined with global hypothermic ischemia causes a significant decrease in left ventricular function compared with global hypothermic ischemia. This dysfunction may be attributed to a significant decrease in coronary flows in BD hearts.

Heart rate variability in brain death.

The sensitivity and specificity of heart rate variability (HRV) in the corroboration of brain death diagnosis in patients with acute traumatic intracranial lesions was evaluated in 20 patients with clinical criteria of brain death, nine patients in deep coma (Glasgow scale < 7) and 18 normal controls, all age matched. The electrocardiogram was sampled at 650 Hz and several parameters of HRV were calculated, in both time and frequency domains. The HRV parameters were significantly lower in the brain death group compared with the deep coma group. Linear discriminant analysis between brain death and deep coma patients was performed on a data set made of nine randomly selected patients with clinical criteria of brain death and nine patients in deep coma. Cross-validation was performed on the remaining 11 patients with clinical criteria of brain death. All patients in the data set were correctly classified (sensitivity and specificity of 100%). All patients in the cross-validation set were correctly classified (sensitivity of 100%). Further studies are necessary to evaluate the specificity of the method in the independent set of deep coma patients and in the follow-up of comatose and vegetative patients to identify irreversibility of HRV. Nevertheless, these results suggest that HRV analysis constitutes a fully sensitive and specific method for assessing brain death in potential organ donors with acute traumatic lesions of the brain. This fast, quantitative and bedside method seems very promising for the early confirmation of brain death, which is an important factor for the success of transplantation procedures and could have a high predictive value of brain death in comatose patients with brain injuries without fully diagnostic criteria.

Modalités et causes de 259 décès dans un service de réanimation pédiatrique

Background. — There are few data available from European pediatric intensive care units (PICU) regarding the modes of death and their causes.Population and methods. — Two hundred and fifty nine children, not including neonates, died in the PICU over a 7-year period (1987–1993). Data were obtained from a computerized data base and the retrospective review of medical records by two intensivists. Deaths were classified into three groups according to the terminal event: brain death (BD), unsuccessful resuscitation (UR), do-not-resuscitate order and limitation and/or withdrawal of therapy (LWT).Results. — BD was the most common mode of death (38%); GR accounted for 34% and LWT for 28% of deaths. There was no significant annual vacation in the proportion of BD. UR and LWT. Age and sex were similar in the three groups. The predominant organ system failure involved upon admission was the central nervous system (52%) in the LWT group, and the cardiovascular system (54%) in the UR group. Severe chronic disease (37%) and immunosuppression (19%) were more prevalent in the LWT group than in the BD group. Time from admission to death was longer in the LWT group (median = 119 hours) as compared to the UR group (10 hours) and the BD group (54 hours). Ten percent of the BD patients became organ transplant donors. Sixty-seven per cent of BD patients had medical contraindication for organ donation: parents did not accept organ donation in 61% of potential cases. Thirty deaths (12%) seemed to be avoidable; dehydration from acute infectious gastroenteritis (n = 7) was the most common cause of avoidable death.Conclusions. — The modes of death in our PICU were statistically not different from those seen in two of four North-American PICUs; LWT was less prevalent than in the two other PICUs, but the patient populations were very different (presence of neonates and many cardiovascular surgery patients). Assessment of the severity of illness at admission and of functional outcome in the survivors are mandatory in future studies.

Hyperthermia following cardiopulmonary resuscitation

To clarify the clinical nature of post-resuscitation hyperthermia, we reviewed the charts of 18 patients who had cardiac arrest on arrival and regained cardiovascular stability for a study period of sufficient length. Patients with trauma, burns, poisoning and cerebrovascular accidents were excluded. We analyzed the hyperthermia (above 38 degrees C) occurring in the initial 48 h after resuscitation. After resuscitation, most patients showed a rapid rise in body temperature. Patients with later brain death showed significantly earlier appearance of hyperthermia (6.2 h after cardiac resuscitation; median) and a higher peak temperature (39.8 degrees C; median) compared with patients showing prolonged coma (12.7 h and 38.3 degrees C, respectively). Hyperthermia above 39 degrees C was associated with subsequent brain death. The incidence of factors influencing body temperature did not differ between the brain death and prolonged coma groups. Patients achieving full recovery did not show hyperthermia. In conclusion, hyperthermia is an early indicator of brain damage after resuscitation.

Ｔｒａｎｓｃｒａｎｉａｌ Ｄｏｐｐｌｅｒ法による脳血流動態の研究 特にｐｕｌｓａｔｉｌｉｔｙ ｉｎｄｅｘの意義について

Transcranial Doppler Ultrasonography (TCD) is now commonly used to evaluate the cerebral hemodynamics. However, the blood velocity measured with TCD is not always accurate, because as a rule the direction of the blood flow does not completely coincide with that of the ultrasonic beam. The error in the measurement could be as large as 15%. This could be eliminated by calculating pulsatility index (PI) from the Doppler ultrasonography. This study evaluates the reliability of the PI as an index of cerebral hemodynamics. In total, 164 measurements were made in patients with various cerebrovascular diseases (CVD), including 14 of brain death patients (group B) and 14 of inpending herniation patients (group I). Of CVD, 46 were persistent vegetative state patients (group V), and 43 were in relatively good conditions (group A). Other including 15 of hydrocephalus patients (group H) and 19 of cerebral vasospasm after subarachnoid hemorrhages (group S) were also investigated. Nineteen normal young volunteers (group N) were used as controls. The mean level of PI in group N shows 0.82. PI in group A was increased to 1.04, and in group V, 1.27. Furthermore in the brain death group, the mean level of PI was increased to 3.86, which was statistically significant. It was concluded that measurement of PI was very useful to evaluate the changes of cerebral hemodynamics, and the levels of PI was affected more with the changes in diastolic than in systolic flow velocity.

Prevention of Myocardial Injury During Brain Death by Total Cardiac Sympathectomy in the Chacma Baboon

In a previous study, structural myocardial damage was found to occur in 60% of baboons after brain death had been induced by a rapid increase in intracranial pressure. In the present study, we attempt to clarify the causative mechanisms involved in the development of such injury. Three groups of baboons were subjected to brain death: group A, the control; group B, those with previous surgical or pharmacological cardiac sympathectomy or cardiac denervation; and group C, those with bilateral vagotomy, incomplete sympathectomy, or bilateral adrenalectomy. Electrocardiographic and hemodynamic responses to brain death were greatly modified in group B baboons compared with responses in groups A and C. Groups A and C showed a high incidence of myocardial necrosis, whereas no myocyte damage was seen in the hearts of group B baboons. The histological appearance of innervated hearts following brain death (groups A and C) may closely resemble that seen during an acute rejection episode following cardiac transplantation. We suggest that myocardial damage occurring during the process of dying may be related to endogenous catecholamine release (possibly resulting in increased calcium uptake by the myocardial cells), inducing various forms of myocyte necrosis. This may result in early failure in a donor heart following cardiac transplantation.

Hyperoxia of internal jugular venous blood in brain death.

✓ The oxygen tension and acid-base values of internal jugular venous blood were compared to those of arterial and systemic mixed venous blood in 40 patients suffering from severe head injury. The results were divided into “brain death” and “coma groups” according to the clinical status when the sample was obtained. Hyperoxia of the jugular venous blood was a common finding in both groups, especially in the brain death group. The mean value of the arteriojugular venous oxygen content difference was 1.86 vol % in the brain death group, and 4.41 vol % in the coma group. Although most of the oxygen content differences in the brain death group were below 3 vol %, there was an overlap with the coma group at the low level of arteriojugular O2 difference. For definitive assessment of brain death, the fact that jugular pO2 was higher than that in systemic mixed venous pO2 was more valuable than the decrease of arteriojugular oxygen difference. The extreme hyperoxia of the jugular venous blood is possibly a sign of brain death, but should not be interpreted as the result of decreased oxygen consumption in the brain, because most of the jugular venous blood is returned from the extracerebral tissues. The causes of jugular hyperoxia in the state of brain death are discussed.