Department of Anaesthesia and Intensive Care, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK
*Corresponding author. E-mail: dominic.bell@leedsth.nhs.uk This article is accompanied by Editorial I.
Accepted for publication: December 5, 2003
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Abstract |
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Methods. A questionnaire in five sections concerning clinician details, initiation of support, criteria for testing, conduct of the tests, and the process of organ donation, was sent to all members of the Neuroanaesthesia Society.
Results. The survey reveals evidence of failure to apply existing guidelines accurately and a wide variation in practice where the recommendations are not specific.
Conclusions. In an era of scrutiny of medical process, it is timely to consider whether the current guidelines should be revisited. Clarification of the approach to biochemical derangement, and the role of confirmatory tests when the residual effect of sedative agents cannot be excluded, are two areas worthy of debate.
Br J Anaesth 2004; 92: 63340
Keywords: complications, brainstem death; guidelines, confirmatory tests
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Introduction |
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Some 35 years after the original meeting of the Harvard medical committee, there is neither universal recognition of the concept of brainstem death,12 13 nor standardization of the method of diagnosis.14 Even where accepted, questions have been raised as to the medical understanding of the concept of brain death,15 standards of documentation,16 the ability to determine conventional death,17 and diagnostic accuracy in profound neurological deficit.18 Against this background, it is timely to consider whether UK clinicians conduct brainstem death testing in line with the current standards, which were updated with a Code of Practice in 1998.19 Certain elements such as establishing the aetiology are not problematic, although errors in diagnosis are possible with certain conditions that mimic brain death.20 21 Areas where interpretation may differ include: the elimination of confounding variables, the conduct of the tests of brainstem reflexes, the apnoea test, and the repetition of testing.
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Methods |
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Results |
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Initiation of support
Thirty-five per cent of respondents initiate ventilatory support where there is no chance of survival or a meaningful recovery, and 74% where there is little chance of the same. Forty-seven per cent would be more likely to initiate support in patients with trauma or haemorrhage than cerebral hypoxia, but 20% would not differentiate between pathologies. Only 21% would change their attitude to initiation of support if they knew the patient/familys views on organ donation. Twenty-three per cent seek the familys consent to maintain support if there is little or no chance of recovery. Forty-seven per cent would have a different attitude to maintenance of support if they knew unequivocally that the patient/family were either in favour of or opposed to organ donation.
Criteria for testing
Limits for preconditions accepted by respondents are given in Table 1. Thirty per cent of respondents would manipulate a high plasma sodium concentration for the purpose of testing with rapid infusions of 5% dextrose. Over 25% would accept a blood glucose concentration equal to or greater than 20 mmol litre1, with only 3% of respondents requiring that it be within the normal range.
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Nineteen per cent of correspondents did not assess whether there was any endocrine disturbance. Thirty-two per cent considered it excluded if there was no relevant past medical history, 31% if the basic biochemical results were normal, and 14% if the clinical observations were normal. Only 4% of respondents considered hormonal assays relevant. Forty per cent assessed neuromuscular function with a nerve stimulator even if relaxants had not been prescribed or not administered for some time previously.
Twenty per cent of respondents considered it appropriate to test for brainstem death immediately after the clinical diagnosis was made, regardless of triggering pathology. Fifteen per cent always waited 24 h. Thirty per cent maintained a differential delay based on the pathology but there was no clear consensus, with a range between 6 and 72 h, after a hypoxic brain injury. Thirteen per cent of respondents believed that brainstem death should equate with electrical silence on the EEG or cerebral functoin monitor (CFM), and 19% would not carry out tests to confirm brainstem death if there was residual electrical activity.
Conduct of the tests
The practice of 12% of respondents was to conduct just one set of tests and 27% would always test independently (Table 2). Of those that carried out the tests with a colleague, 15% would always directly conduct two sets of tests, 50% followed a practice whereby one conducted the tests with the other observing, followed by role reversal, and the remainder would follow either practice depending on the approach of the colleague. Twenty-five per cent of clinicians carried out each set of tests sequentially, with the remainder either deliberately imposing or accepting a delay of between 20 min and 24 h. Fifteen per cent of practitioners routinely spoke to the family between tests and others sought to normalize the PaCO2 before embarking on the second tests. Five per cent considered a wait between sets of tests obligatory with certain pathologies such as hypoxia. The apnoea test was run simultaneously with the other tests by 50% of respondents, 40% always carrying this out independently, invariably following the other tests. The remainder would follow either practice dependent on colleagues preferences. The minimum PaCO2 considered acceptable ranged from 4.5 to 13 kPa, with 15% accepting less than 6 kPa and 29% demanding more than 7 kPa. Only 12% adopted the recommended threshold of 6.65 kPa. Thirty per cent reported allowing the PaCO2 to increase before testing by reducing tidal volume and ventilatory frequency whilst administering oxygen 100%. Capnography was used as the endpoint by 40% of respondents, aiming for a minimum end-tidal carbon dioxide concentration of 6%.
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The process of organ donation
Seventy-five per cent of respondents would use anaesthetic agents to control cardiovascular surges during organ donation, the remainder using specific vasoactive agents. Thirty-five per cent of those who used anaesthetic agents aimed to provide anaesthesia as opposed to cardiovascular control and recommended that trainees also provide anaesthesia. If intending to provide anaesthesia, 7% would inform the family and 2% would seek their consent for anaesthesia. Twenty-two per cent of respondents allow the family to observe the tests if asked. The family was most commonly approached with regard to organ donation by a nurse (42%) or anaesthetist/intensivist (37%), and less commonly by a member of the transplant team (12%) or a surgeon (9%). The family was approached with regard to organ donation before testing by 29% of respondents, between both sets of tests by 46%, and after the tests were concluded by 25%. The most common perception of why a brainstem dead patient may not become an organ donor was relatives refusal in 65% of respondents. Other reasons stated in the following order of frequency were: patient dying before testing despite full support, failure to meet the criteria for testing, refusal of organs by transplant team, patient dying before testing because of failure to provide full support, non-availability of personnel to carry out the tests, and refusal of consent from the coroner or procurator fiscal. The commonest reasons for relatives refusal were: mutilation of the body (21%), patient had had enough (14%), the very idea of organ donation (12%), ethical/religious/cultural (9%), did not know patients views (8%), could not cope with decision (5%), recent scandals (4%), family disagreement (2%), and not enough time (2%). Eleven per cent of respondents did not feel comfortable with withdrawing support in severely brain-injured but not brainstem dead patients. Twenty-nine per cent would feel less comfortable with the decision to withdraw support if the patient was to be viewed as a potential non-beating-heart donor.
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Discussion |
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A completed reply rate of 47% appears less than ideal, but many of those who were sent questionnaires had no involvement in neurointensive care or brainstem death testing. Despite this, every UK neurosurgical unit was represented in these results. This was a comprehensive and, therefore, challenging questionnaire, with many sections requiring comment rather than yes or no answers. It is possible that questions may have been misunderstood and freehand replies are additionally prone to errors of interpretation. The finding that 30% of respondents considered that anaesthesia should be performed for organ retrieval, for reasons other than suppressing cardiovascular responses, may reflect misunderstanding rather than concern that sensory pathways potentially remain intact.22 Similarly, the respondents interpretation may have differed from that of the investigators on the questions regarding confirmatory tests.
UK guidelines and the Code of Practice allow clinical interpretation as to whether the patients state of unresponsiveness is contributed to, or caused by, depressant drugs, hypothermia, or reversible metabolic and endocrine disturbance, but set no absolute criteria. If a patient on a sedative regime displays: the cardiovascular changes of brainstem death; dilated and unreactive pupils; loss of gag and cough reflexes; no response to painful stimuli; and additional markers such as diabetes insipidus, there is no theoretical restriction on testing the patient immediately. There is no absolute indication to wait for drug clearance or indeed normalization of temperature or biochemistry as clinically the patient is brainstem dead rather than unresponsive as a result of sedatives.
In practice, the changes may be less well defined creating difficulties as to whether a temperature of 34°C, in association with a sodium level of 120 mmol litre1, a glucose of 20 mmol litre1, and no tests of endocrine function, would invalidate the diagnosis of brainstem death. These criteria are no better defined in other jurisdictions, American guidelines23 simply stating that there should be no severe electrolyte, acidbase, or endocrine disturbance, but somewhat arbitrarily setting 32°C as the lower level for testing of brainstem reflexes and 36.5°C for apnoea testing. UK practice could not accommodate the former level and would not routinely meet the latter threshold, but otherwise there is commonality. A logical solution to this problem is not obvious. If permissible upper and lower limits were set for temperature, sodium, and other biochemical markers such as urea and creatinine, practitioners would have an explicit template to work within. However, the limits would be arbitrary, and lend themselves to short-term manipulation as described in relation to sodium levels.
The guidelines state that endocrine disturbance should be eliminated but are not specific about how this should be undertaken. Whilst failure of corticosteroid production is associated with shock, the impact of this on brain function is unknown but probably limited. Tests of thyroid function are also notoriously difficult to interpret in the context of critical illness. Even if the circumstances in which specific tests should be conducted were defined, difficulties would still arise with interpretation and recommendations for correction of any deficit. Given however that the tests revolve around the absence of a motor response, and that muscle relaxants may be slowly cleared,24 or have been administered inadvertently, there is a strong argument for making testing of the neuromuscular junction compulsory.
The elimination of depressant drugs as a confounding factor warrants scrutiny because there are no directives as to whether the drug should have been cleared completely, reached minimal levels with regard to impact in the normal population, or reached a level incompatible with the picture of brainstem death. Within the guidelines, there is no reference to the use of opioid and benzodiazepine antagonists to either validate or expedite testing. The conduct of the tests after administration of thiopental is particularly difficult as the half-life of this agent is long, there is no antagonist, analysis of blood levels is restricted to a limited number of laboratories, and there is a long wait for results. Furthermore, there is no consensus as to an appropriate minimum level. The reported practice of empirically waiting for up to 5 days is arbitrary, is not an efficient use of intensive care resources, and does little for the well-being of the patients family or morale of attendant staff. Potential donation is lost because of destabilization of the patient or unwillingness on the part of family or staff to continue support for a protracted period. When donation is delayed, organ function may deteriorate because of systemic changes, infection, and the use of chemical and mechanical support. There is also emerging evidence of graft dysfunction as a result of immunological activation of the donor organ.25 This is clearly one area where confirmatory tests of brain as opposed to brainstem death could be conducted to consolidate a diagnosis. Over 50% of respondents stated that absence of flow on cerebral angiography, the original gold standard for brain death, would be satisfactory in this regard, but 20% of these believed that under current UK guidelines this could not be used to legitimize organ donation. There is no basis for these concerns, as the brainstem death criteria evolved to avoid the need for such technically demanding interventions, not because of inherent error in the technique.
Angiography is clearly not a bedside investigation but TCD is gaining validity as a confirmatory test for brain death, 2628 particularly in the presence of residual sedative drugs.29 Although certain countries are introducing legislation to accommodate the technique,30 only 8% of respondents would consider this an appropriate method of consolidating the diagnosis, but this may reflect a lack of familiarity. Another alternative to angiography involves single photon emission computed tomography (SPECT).31 Although this technique has other uses,32 and has been validated,33 it is difficult to envisage the introduction of such new technology solely for this purpose.
Serial absence of activity on the EEG is mandatory in certain jurisdictions, but this would be an inappropriate test in the presence of residual sedatives. Evoked potentials have been promoted,34 and refined,35 as a confirmatory technique even in the presence of depressant drugs, but it would be unrealistic to rely on a tool that is vulnerable to errors of interpretation in inexperienced hands. Measurement of intracranial pressure (ICP) is routinely undertaken on neurosurgical ICUs and at first sight it is difficult to understand why only 12% of respondents would consider a sustained increase in ICP, equal to or greater than mean arterial pressure, satisfactory as a confirmatory test of brain death on the basis of absent cerebral perfusion. However, this test is only applicable when ICP monitoring is indicated clinically as in the management of traumatic brain injury and, in common with any clinical monitoring technique or investigation, is vulnerable to measurement error. As failure to meet criteria for testing as a result of the prolonged effects of agents such as thiopental was cited as the third commonest cause of lost donors, the issue of confirmatory tests does need to be revisited. Use of thiopental will predictably be in the context of ICP control within neurosurgical units, where angiography and TCD expertise should be available.
The conceptual diagnosis of brainstem death should stand independently of triggering pathology, and there is no logic in delaying either the first or second set of tests after cerebral hypoxia as the guidelines suggest. A significant number of practitioners, in testing immediately (20%) or with no time delay between testing (25%), clearly question the guidelines.
The guidelines do not define clearly what constitutes two sets of tests, this being interpreted by 12% as two practitioners each conducting one set of tests independently and the majority of the remainder each conducting one set of tests but rotating the conductor/observer role with a colleague. The value of repeated testing has been questioned, but the suggestion that there is a place when confounding factors such as drug therapy are present,36 offers little reassurance about the validity of the first set of tests. The guidelines would therefore benefit from clarification regarding the timing, repetition of, and intervals between tests.
There was significant variability in the conduct of the tests themselves, particularly in areas where the Code of Practice is quite specific. The Code19 specifies the injection of at least 50 ml of ice cold water over 1 min and practice was at variance with this. The Code requires that no motor responses within the cranial nerve distribution can be elicited by adequate stimulation of any somatic area. This was only carried out by 65% of practitioners. Given that false negatives may occur in the presence of a cord injury, the role of this test as a measure of brainstem function is questionable and the failure of full compliance may reflect a need to reconsider its value. Peripheral painful stimulation is not included in recommendations from other countries because it is only an indirect test of brainstem function.
There are no precise recommendations as to whether the apnoea test should be conducted independently of the other tests as in other jurisdictions,37 so it is not surprising that individual practice varies. The observation that clinicians are prepared to accept less than recommended thresholds for PaCO2 is worrying particularly in view of observations that in certain patient groups much higher levels may be needed to stimulate respiratory effort,38 39 and that the UK figure is already lower than other countries.40 The practice of allowing an arbitrary increase in PaCO2 before testing with eventual levels higher than 13 kPa also generates potential criticism. Regardless of the potential for aggravating incomplete brain injury,41 primary carbon dioxide narcosis may confound the clinical picture, particularly if the tests are conducted sequentially without normalization of PaCO2 before the second set. There are, therefore, arguments for a more prescriptive approach to these tests and the setting of a higher PaCO2 level equivalent to the 8 kPa used in other countries.
In summary, this survey demonstrates a wide variation in interpretation of the UK guidelines for certification of brainstem death. The elimination of confounding factors, the timing and repetition of testing and the conduct of the tests themselves, particularly the apnoea test, would benefit from refinement and clearer definition. The results also indicate that specific recommendations in the existing guidelines are not accurately followed and although this is unlikely to invalidate the determination of death,42 reinforcement is warranted. Confirmatory tests, as performed in other European countries, should be considered, particularly when clinical testing could be delayed by the presence of long-acting sedative agents. Despite medical opinion questioning the concept of brainstem death, most practising doctors have confidence in the process of testing, at least as an end-point for determining futility of treatment. However, in view of the significant implications of the diagnosis of brainstem death, the profession should be proactive in defining and applying more stringent criteria in the areas where uncertainty exists, to maintain public confidence and ensure protection of both patients and practitioners. We would recommend that the current guidelines in the UK be reviewed.
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Appendix |
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Clinician details
1. How long have you held a consultant post in neuro-anaesthesia?
05 yr 510 yr 1020 yr >20 yr
2. Do you carry out BSDT (brainstem death tests)?
If yes; <2/yr 25/yr 510/yr >10/yr
Initiation of support
3. Do you initiate ventilatory and cardiovascular support in cases where there is no chance of survival or a meaningful recovery?
4. If yes, is this because of:
a. pressure from the parent specialty to provide support,
b. failure of the parent specialty to endorse your decision not to initiate support,
c. a wish to give the patient every opportunity,
d. the potential for organ donation?
5. Do you initiate ventilatory and cardiovascular support in cases where there is little chance of survival or a meaningful recovery?
6. If yes, is this a result of:
a. pressure from the parent specialty to provide support,
b. failure of the parent specialty to endorse your decision not to initiate support,
c. a wish to give the patient every opportunity,
d. the potential for organ donation?
7. If yes, are you more likely to initiate support for certain pathologies?
If yes please number; cerebral hypoxia, trauma, haemorrhage 1, 2, and 3 where 1 represents most likely and 3 least likely to initiate support.
8. Once support is initiated and there is little or no chance of recovery do you seek the familys consent to maintain support?
9. Would your attitude to initiation of support in the above circumstances differ if you knew unequivocally that the patient/family were either in favour or opposed to organ donation?
10. Would your attitude to maintenance of support in the above circumstances differ if you knew unequivocally that the patient/family were either in favour or opposed to organ donation?
Criteria for testing
11.What is the minimum temperature at which you would consider testing?
12. What is the minimum Na at which you would consider testing?
13a. What is the maximum Na at which you would consider testing?
13b. Would you rapidly infuse large volumes of 5% dextrose to bring the Na down?
14. What is the maximum glucose at which you would consider testing?
15. What criteria do you use to determine that the following drugs do not invalidate the tests?
a. opioids
b. benzodiazepines
c. thiopentone
16. Would you consider using the following agents where opiates and benzodiazepines had been administered recently or could be considered to still be present within the body?
a. naloxone
b. flumazenil
17. If the patient had been receiving thiopentone recently enough to invalidate the tests, would you consider the following investigations sufficient to diagnose brainstem death?
a. cerebral angiography and absence of flow?
b. Doppler evidence of absence of flow?
c. A sustained ICP = or >MAP
18. How do you assess whether there is any endocrine disturbance that can invalidate the tests?
19. Do you assess neuromuscular function with a nerve stimulator even if relaxants have either not been used, or not used for some time?
20. If the patient was clinically brainstem dead, how soon after initiation of support for the following conditions would you consider it appropriate to test?
a. trauma
b. haemorrhage
c. hypoxic injury
d. infection
21. Do you believe that brainstem death should equate with electrical silence on the EEG or CFM?
22. Would you carry out the tests and confirm BSD if there was residual electrical activity on the relevant monitors?
Conduct of the tests
23. Do you always carry out two sets of tests?
24. If no, in which circumstances would you only conduct one set?
25. Do you carry out the tests
a. with a colleague?
b. independently?
c. either, depending on circumstance?
26. If with a colleague
a. each carrying out two sets of tests?
b. one conducting the tests with one observing, followed by role reversal?
c. either, depending on the wishes or practice of the colleague?
27. Do you carry out each set of tests
a. sequentially?
b. after an interval?
28. If after an interval
a. how long?
b. what factors determine this interval?
29. With regard to the apnoea test, do you
a. conduct this independently of the other tests?
b. if yes, i. before or ii. following the other tests?
c. run it simultaneously with the other tests?
d. either, depending on colleagues preference/practice?
30. What minimum PaCO2 would you accept?
31. Do you use peripheral painful stimulation?
32. What volume of iced water do you use for caloric testing?
33. Over how long do you inject the fluid?
34. How do you assess the gag reflex?
Process of organ donation
35. Do you allow the family to observe the tests?
36. Who routinely approaches the family with regard to donation?
a. anaesthetist/intensivist?
b. surgeon?
c. nurse?
d. member of transplant team?
37. When do you approach the family with regard to organ donation?
a. before testing?
b. between both sets of tests?
c. after the tests are concluded?
38. Do you use anaesthetic agents to control cardiovascular surges during organ donation?
39. Do you provide anaesthesia for the patient undergoing organ harvest, as opposed to the above?
40. Do you recommend that trainees provide anaesthesia?
41. If intending to provide anaesthesia do you
a. inform the family?
b. seek their consent?
42. Could you number the following in the order 17 according to your perception of why a brainstem dead patient may not become an organ donor (1 being the commonest cause) failure to meet criteria for testing (e.g. thiopentone infusion)
failure to carry out tests (non-availability of personnel)
patient dying before testing despite full support
patient dying before testing because of a failure to provide full support
relatives refusal
transplant teams refusal of organs
otherplease specify
43. Could you give the commonest cause of relatives refusal?
44. Do you feel comfortable withdrawing support on a severely brain-injured but not brainstem dead BSD patient?
45. Would you feel less comfortable with the decision to withdraw support and liaison with the family if the patient was viewed as a potential non-beating-heart organ donor?
46. Is there any other element of this process that creates problems that has not been addressed here?
Many, many thanks for your patience.
If you wish to be included in the draw for the digital camera please write your name and hospital here with any additional comments.
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References |
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