[Determination of brain death in organ donation: is EEG required?]. / Vaststellen van hersendood bij orgaandonatie: is een eeg noodzakelijk?

The determination of brain death is a prerequisite of multiple organ donation in ventilated patients in the ICU. The criteria for brain death differ internationally. In some countries, brain stem death is equivalent to brain death. In others, including the Netherlands, in addition to the determination of brain stem death, an EEG must also be carried out to rule out cortex activity according to the criteria of "whole brain death". However, this does not prove that there is complete failure of all brain functions; indeed, EEG does not examine the subcortical brain. The Dutch Health Board has established that brain death is ruled out by rest activity in the cortex, but not by persistent subcortical activity. This is conceptually incorrect. The criteria for brain stem death fit better in practice than the criteria for whole brain death. Taking an EEG should therefore no longer be an obligation in establishing brain death, as is the case in many other countries.

Imprecise definitions of starting points in retrospectively reviewing potential organ donors causes confusion: call for a reproducible method like 'imminent brain death'.

Low donor supply and the high demand for transplantable organs is an international problem. The efficiency of organ procurement is often expressed by donor conversion rates (DCRs). These rates differ among countries, but a uniform starting point for defining a potential heart-beating donor is lacking. Imprecise definitions cause confusion; therefore, we call for a reproducible method like imminent brain death (IBD), which contains criteria in detail to determine potential heart-beating donors. Medical charts of 4814 patients who died on an ICU in Dutch university hospitals between January 2007 and December 2009 were reviewed for potential heart-beating donors. We compared two starting points: 'Severe Brain Damage' (SBD) (old definition) and IBD (new definition), which differ in the number of absent brainstem reflexes. Of the potential donors defined by IBD 45.6% fulfilled the formal brain death criteria, compared with 33.6% in the larger SBD group. This results in a higher DCR in the IBD group (40% vs. 29.5%). We illustrated important differences in DCRs when using two different definitions, even within one country. To allow comparison among countries and hospitals, one universal definition of a potential heart-beating donor should be used. Therefore, we propose the use of IBD.

Prediction of potential for organ donation after cardiac death in patients in neurocritical state: a prospective observational study.

BACKGROUND: Successful donation of organs after cardiac death (DCD) requires identification of patients who will die within 60 min of withdrawal of life-sustaining treatment (WLST). We aimed to validate a straightforward model to predict the likelihood of death within 60 min of WLST in patients with irreversible brain injury. METHODS: In this multicentre, observational study, we prospectively enrolled consecutive comatose patients with irreversible brain injury undergoing WLST at six medical centres in the USA and the Netherlands. We assessed four clinical characteristics (corneal reflex, cough reflex, best motor response, and oxygenation index) as predictor variables, which were selected on the basis of previous findings. We excluded patients who had brain death or were not intubated. The primary endpoint was death within 60 min of WLST. We used univariate and multivariable logistic regression analyses to assess associations with predictor variables. Points attributed to each variable were summed to create a predictive score for cardiac death in patients in neurocritical state (the DCD-N score). We assessed performance of the score using area under the curve analysis. FINDINGS: We included 178 patients, 82 (46%) of whom died within 60 min of WLST. Absent corneal reflexes (odds ratio [OR] 2·67, 95% CI 1·19-6·01; p=0·0173; 1 point), absent cough reflex (4·16, 1·79-9·70; p=0·0009; 2 points), extensor or absent motor responses (2·99, 1·22-7·34; p=0·0168; 1 point), and an oxygenation index score of more than 3·0 (2·31, 1·10-4·88; p=0·0276; 1 point) were predictive of death within 60 min of WLST. 59 of 82 patients who died within 60 min of WLST had DCD-N scores of 3 or more (72% sensitivity), and 75 of 96 of those who did not die within this interval had scores of 0-2 (78% specificity); taking into account the prevalence of death within 60 min in this population, a score of 3 or more was translated into a 74% chance of death within 60 min (positive predictive value) and a score of 0-2 translated into a 77% chance of survival beyond 60 min (negative predictive value). INTERPRETATION: The DCD-N score can be used to predict potential candidates for DCD in patients with non-survivable brain injury. However, this score needs to be tested specifically in a cohort of potential donors participating in DCD protocols. FUNDING: None.

External validation of a prognostic model predicting time of death after withdrawal of life support in neurocritical patients.

OBJECTIVE: The ability to predict the time of death after withdrawal of life support is of specific interest for organ donation after cardiac death. We aimed to externally validate a previously developed model to predict the probability of death within the time constraint of 60 mins after withdrawal of life-sustaining measures. DESIGN: The probability to die within 60 mins for each patient in this validation sample was calculated based on the model developed by Yee et al, which includes four variables (absent corneal reflex, absent cough reflex, extensor or absent motor response, and an oxygenation index >4.2). Analyses included logistic regression modeling with bootstrapping to adjust for overoptimism. Performance was assessed by calibration (agreement between observed and predicted outcomes) and discrimination (distinction of those patients who die within 60 mins from those who do not, expressed by the area under the receiver operating characteristic curve). SETTING: Mixed intensive care unit in The Netherlands. PATIENTS: We analyzed data from 152 patients who died as a result of a neurologic condition between 2007 and 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 82 patients had sufficient data. Fifty (61%) died within 60 mins. Univariable and multivariable odds ratios of the predictors were very similar between the development and validation sample. The prediction model showed good discrimination with an area under the receiver operating characteristic curve of 0.75 (95% confidence interval [CI] 0.63-0.87) but calibration was modest. The mean predicted probability was 80%, overestimating the 61% overall observed risk of death within 60 mins. Modeling oxygenation index as a linear term led to an improved version of the Mayo NICU model. (area under the receiver operating characteristic curve [95% CI] = 0.774 [0.69-0.90], bootstrap-validated area under the receiver operating characteristic curve [95% CI] = 0.74 [0.66-0.87]). CONCLUSIONS: The model discriminated well between patients who died within 60 mins after withdrawal of life support and those who did not. Further prospective validation is needed.

A national multicenter trial on family presence during brain death determination: the FABRA study.

PURPOSE: As brain death is a difficult concept for the lay public to understand, we hypothesized that allowing relatives of the patient to be present during brain death determination would improve their understanding of this condition and would eventually lead to an increased consent rate for organ donation. METHODS: A prospective multicenter trial was conducted in five Dutch hospitals. Relatives were given the opportunity to be present during brain death testing. The family consent rate for organ donation was the primary endpoint examined, and the degree of the relatives' understanding of brain death was the secondary endpoint. RESULTS: Between April 2010 and July 2011, we included the relatives of 8 patients in this study. The relatives witnessed brain death testing during this time. This sample size was too small to draw valid statistical conclusions. However, we have documented some noteworthy experiences of the relatives. CONCLUSIONS: Although, the hypothesis behind this study had promise, we were unable to reach our predefined goal. The possible causes for this shortcoming included the rarity of patients with brain death, the common practice in the Netherlands of obtaining consent for organ donation before brain death testing and the uneasiness of the staff in the presence of the patients' relatives during brain death determination. Although, we cannot draw a conclusion from statistical evidence, we would recommend that relatives be given the opportunity to be present during brain death testing and, specifically, during the apnea test.

Remarkable changes in the choice of timing to discuss organ donation with the relatives of a patient: a study in 228 organ donations in 20 years.

INTRODUCTION: We studied whether the choice of timing of discussing organ donation for the first time with the relatives of a patient with catastrophic brain injury in The Netherlands has changed over time and explored its possible consequences. Second, we investigated how thorough the process of brain death determination was over time by studying the number of medical specialists involved. And we studied the possible influence of the Donor Register on the consent rate. METHODS: We performed a retrospective chart review of all effectuated brain dead organ donors between 1987 and 2009 in one Dutch university hospital with a large neurosurgical serving area. RESULTS: A total of 271 medical charts were collected, of which 228 brain dead patients were included. In the first period, organ donation was discussed for the first time after brain death determination (87%). In 13% of the cases, the issue of organ donation was raised before the first EEG. After 1998, we observed a shift in this practice. Discussing organ donation for the first time after brain death determination occurred in only 18% of the cases. In 58% of the cases, the issue of organ donation was discussed before the first EEG but after confirming the absence of all brain stem reflexes, and in 24% of the cases, the issue of organ donation was discussed after the prognosis was deemed catastrophic but before a neurologist or neurosurgeon assessed and determined the absence of all brain stem reflexes as required by the Dutch brain death determination protocol. CONCLUSIONS: The phases in the process of brain death determination and the time at which organ donation is first discussed with relatives have changed over time. Possible causes of this change are the introduction of the Donor Register, the reintroduction of donation after circulatory death and other logistical factors. It is unclear whether the observed shift contributed to the high refusal rate in The Netherlands and the increase in family refusal in our hospital in the second studied period. Taking published literature on this subject into account, it is possible that this may have a counterproductive effect.

[Communication with the relatives of a patient presumed brain dead]. / Communicatie met familieleden van een vermoedelijk hersendode patiënt.

BACKGROUND: The choice of wording in cases of suspected brain death is important. If brain death has not been proven by electrocerebral silence and by absence of spontaneous breathing in an apnoea test in a patient in intensive care, then words like 'brain dead', 'has died' and 'clinical brain death' should be avoided in conversations with the relatives of the patient. This is illustrated by three cases. CASES: The first patient was a 46-year-old woman, with thrombosis of the basilar artery; the second was a 26-year-old man who was resuscitated after a bilateral pneumothorax, but developed severe postanoxic encephalopathy; and the third patient was a 64-year-old man with a large intracerebral haemorrhage. The relatives were informed that the patient was 'brain dead' or 'deceased' based on loss of consciousness (Glasgow Coma score of 3) and absence of brain stem reflexes, but prior to the completion of the brain death protocol by electroencephalography and apnoea testing. In the first and third cases, brain death could not be proven, and the pronouncement that the patient was deceased had to be reversed. The emotional relatives refused organ donation. In the second case, death was pronounced upon loss of consciousness and absence of brain stem reflexes. The relatives refused organ donation, after which mechanical ventilation was withdrawn and the patient was declared dead for a second time based on circulatory arrest. CONCLUSION: A patient is dead after complete brain death determination or after circulatory arrest. Loss of consciousness (Glasgow Coma score of 3) and absence of brain stem reflexes lead to a state of catastrophic cerebral damage, but not to brain death. In such a situation, wording such as 'brain death', 'deceased' and 'clinical brain death' should be avoided in conversations with the relatives.

Historical sources of basilar artery occlusion.

Posterior circulation stroke, which includes basilar artery occlusion (BAO), accounts for approximately 20% of all ischemic strokes. Much is unclear concerning the early historical descriptions of basilar artery occlusion, and some modern authors cite the historical sources incorrectly and incompletely. The case described by the Scottish physician John Abercrombie in 1828 is probably the first description of this form of stroke. The progressive bulbar signs that Abercrombie described in his case were striking, i.e., dysphagia and speech difficulties. Many authors in the 19th century described a waxing and waning clinical course for several days before profound coma and death. They also noticed signs and symptoms such as hemiplegia without loss of sensitivity and bulbar symptoms such as swallowing and speech impairment, vertigo, and altered consciousness. After Virchow's epoch-making work on embolism and thrombosis, all authors correctly described BAO as resulting from emboli and thrombosis based on arteriosclerosis instead of ossification of the arterial walls or inflammation. Around 1880, the clinical symptoms of BAO were obviously well-known to the experienced clinician. In this article we offer a chronological description of historical sources.

Is organ donation from brain dead donors reaching an inescapable and desirable nadir?

The brain dead patient is the ideal multiorgan donor. Conversely, brain death (BD) is an undesirable outcome of critical care medicine. Conditions that can lead to the state of BD are limited. An analysis showed that a (aneurysmal) subarachnoid hemorrhage, traumatic brain injury, or intracerebral hemorrhage in 83% precede the state of BD. Because of better prevention and treatment options, we should anticipate on an inescapable and desirable decline of BD. In this article, we offer arguments for this statement and discuss alternatives to maintain a necessary level of donor organs for transplantation.

Donor conversion rates depend on the assessment tools used in the evaluation of potential organ donors.

PURPOSE: It is desirable to identify a potential organ donor (POD) as early as possible to achieve a donor conversion rate (DCR) as high as possible which is defined as the actual number of organ donors divided by the number of patients who are regarded as a potential organ donor. The DCR is calculated with different assessment tools to identify a POD. Obviously, with different assessment tools, one may calculate different DCRs, which make comparison difficult. Our aim was to determine which assessment tool can be used for a realistic estimation of a POD pool and how they compare to each other with regard to DCR. METHODS: Retrospective chart review of patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage. We applied three different assessment tools on this cohort of patients. RESULTS: We identified a cohort of 564 patients diagnosed with a subarachnoid haemorrhage, traumatic brain injury or intracerebral haemorrhage of whom 179/564 (31.7%) died. After applying the three different assessment tools the number of patients, before exclusion of medical reasons or age, was 76 for the IBD-FOUR definition, 104 patients for the IBD-GCS definition and 107 patients based on the OPTN definition of imminent neurological death. We noted the highest DCR (36.5%) in the IBD-FOUR definition. CONCLUSION: The definition of imminent brain death based on the FOUR-score is the most practical tool to identify patients with a realistic chance to become brain dead and therefore to identify the patients most likely to become POD.

What to do when a competent ICU patient does not want to live anymore but is dependent on life-sustaining treatment? Experience from The Netherlands.

If patients on the intensive care unit (ICU) are awake and life-sustaining treatment is suspended because of the patients' request, because of recovering from the disease, or because independence from organ function supportive or replacement therapy outside the ICU can no longer be achieved, these patients can suffer before they inevitably die. In The Netherlands, two scenarios are possible for these patients: (1) deep palliative (terminal) sedation through ongoing administration of barbiturates or benzodiazepines before withdrawal of treatment, or (2) deliberate termination of life (euthanasia) before termination of treatment. In this article we describe two awake patients who asked for withdrawal of life-sustaining measures, but who were dependent on mechanical ventilation. We discuss the doctrine of double effect in relation to palliative sedation on the ICU. Administration of sedatives and analgesics before withdrawal of treatment is seen as normal palliative care. We conclude that the doctrine of the double effect is not applicable in this situation, and mentioning it criminalised the practice unnecessarily and wrongfully.

A description and illustration of a necrotizing fasciitis by John Bell in 1801, hypothetically caused by Vibrio vulnificus.

We present an overlooked and noteworthy historical case and illustration of a necrotizing fasciitis, observed and written by John Bell (1763-1820), first published in 1801. Considering the setting and the clinical presentation, we hypothesize that the pathogen responsible was the species Vibrio vulnificus. The typical clinical course of a rapidly progressive illness preceded by saltwater exposure shortly followed by the development of a hemorrhagic skin lesion, with a fatal outcome, should strongly suggest a V. vulnificus infection. To our knowledge, there are few historical case reports with illustrations included describing cases of necrotizing fasciitis, particularly with V. vulnificus as the suggested pathogen.

Imminent brain death: point of departure for potential heart-beating organ donor recognition.

PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. METHODS: We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. RESULTS: A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E(0)M(0)B(0)R(0). CONCLUSION: The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.