4.4 DIAGNOSING BRAIN DEATH

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INTRODUCTION

Throughout mankind’s history, the concept of death has changed constantly in parallel with the scientific, cultural and social evolution of the various eras. Until the nineteenfifties, the interruption of the heart beat or breathing marked the point in time in which an individual was deemed to be dead. With the introduction and dissemination of resuscitation techniques as well as with the availability of total artificial respiratory and cardiocirculatory support, it is no longer sensible to equate the time of death with the time of cardiorespiratory arrest. In fact, externally controlled respiratory and car- diocirculatory techniques have made it possible to consider that a patient who is no longer able to breath autonomously is nevertheless alive.

However, these cardiopulmonary resuscita- tion techniques may also allow a patient to con- tinue to be well oxygenated and maintain suffi- cient haemodynamic stability for limited peri- ods even when all cerebral functions have been completely and irreversibly lost. It therefore follows that the confirmation of death cannot be based on the observation or conservation of autonomous cardiopulmonary activity alone.

Over the past thirty years this observation has led to the introduction of the concept of

“brain death”, intended as a definitive and complete loss of all functions of the CNS. In the 1960’s the French school of medicine pro- posed the term coma depassée to describe this condition, however from a semantic point of view the term is inaccurate because, as it indi- cates a state of brain death, it is no longer pos- sible to speak of coma. Coma in fact implies that brain activity is still present, albeit com- promised to a greater or lesser extent. It is therefore preferable to avoid such expressions as “irreversible coma” but instead use the term

“brain death” (BD) to indicate a subject whose cerebrum is no longer vital but whose car- diopulmonary function is still present.

By BD, we therefore signify the irreversible arrest of all brain function, including that of the brainstem, which is precisely the structure whose loss of function is required for the veri- fication of brain death (14).

PATHOPHYSIOLOGY

The skull, a rigid and inelastic container, contains: brain substance, interstitial fluid, ar- terial and venous blood and the cerebrospinal fluid (CSF). Any variation in the volume of one or more of these components must necessarily

4.4 DIAGNOSING BRAIN DEATH

M.G. Bonetti, F. Menichelli, T. Scarabino, U. Salvolini

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be compensated for by a variation in one of the other components in order to maintain total in- tracranial volume and pressure constant.

With progressive increases in volume, with- in certain limits, a slight and equally gradual in- crease in intracranial pressure (ICP) takes place. A part of this compensation takes place as a consequence of the cranial CSF being dis- placed into the subarachnoid space of the spinal canal (14). If the increases in volume are sufficiently large to exceed so-called cerebral compliance, intracranial hypertension sets in, which if not treated can be life threatening.

The close relationship that exists between ICP and cerebral blood flow (CBF) means that any increase in intracranial pressure must cor- respond to an increase in venous and arterial pressure. This mechanism serves to prevent a collapse of the cerebral blood vessels and there- fore makes it possible to maintain adequate cerebral perfusion pressure (CPP).

There are cases in which this compensation mechanism is inadequate and in such instances the ICP increases beyond the limit required to ensure adequate CPP. This occurs when nonspe- cific cerebral mass effect is not controlled or con- trollable using therapy, resulting in an increase in brain volume within the rigid skull. This in turn causes a consequent compression of the intracra- nial vascular structures in order to gain addition- al intracranial space. In an attempt to compen- sate for this situation, a vicious circle is estab- lished whereby CBF rapidly increases, contribut- ing to further increases ICP and, ultimately, to further reductions in CPP.

At this point ICP, which can increase be- yond 40 mm Hg, prevents adequate CPP with consequent anoxia and death of the brain with- in a very few minutes. The compressive effect of high ICP upon the cerebral vessels with eventual arrest of the blood flow correlates with studies showing an absence of cerebral perfusion.

DIAGNOSIS

The diagnosis of BD is first and foremost a clinical one, the main signs being clinical coma,

together with the absence of brainstem reflexes and apnea. The main pathogenic factor leading to BD is a severe state of brain swelling with a progressive reduction and eventual complete interruption of intracranial blood flow.

The further clinical criteria (16) for the diag- nosis of BD are the absence of spontaneous so- matic movements, total areflexia and an ab- sence of activity on the EEG as well as on the brainstem auditory evoked potentials (BAEP).

However, such findings can be mimicked by various causes such as intoxication from medi- cines, hypothermia and technical problems with the recording equipment (14). For this reason the Italian law (Law n. 578 of 29/12/93;

Italian Ministry of Health Decree n. 582 of 22/8/94) establishes that complementary inves- tigations aimed at highlighting the absence of cerebral blood flow need to be performed in order to prove BD (15, 18). However, ancillary examinations used for the confirmation of BD are only conducted if the usual clinical criteria are unable to provide an unquestionable diag- nosis.

Transcranial Doppler (TCD) examinations can be performed with ease at the patient’s bedside and can demonstrate the interruption of arterial flow with a sensitivity that varies from 90% to 99%, and with a specificity that approaches 100%. In order to confirm a TCD diagnosis of vascular stasis, it is recommended that the examination be repeated 30 minutes following the first determination.

TCD can be used to diagnose BD (3, 8) (al- though it remains decidedly operator-depend- ent) on condition that the examination is car- ried out with both a supra- and subtentorial ap- proach while checks of systemic systolic blood pressure insure that the recorded values do not drop below 70 mmHg.

In cases of brain death, in addition to re-

vealing the potential presence of focal lesions,

computed tomography (CT) enables the detec-

tion (21) of cytotoxic oedema secondary to is-

chaemia- related diffuse cellular necrosis. This

is responsible for the predominant hypodensity

of the grey matter, with the disappearance of

the grey-white grey matter differentiation. This

is also accompanied by a reduction and eventu-

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al disappearance of sulcal, pericerebral and ventricular CSF spaces due to cerebral swelling (Fig. 4.32).

However, CT alone does not allow an un- questionable distinction between diffuse parenchymal insult and frank brain death. The use of spiral CT has been proposed as a method that may overcome this limitation. A demon- stration of the absence of cerebral blood flow (4), as required for the diagnosis of BD, is per- formed by means of the acquisition of images in the arterial and venous phases after the admin- istration of intravenous contrast medium utiliz- ing a rapid bolus injection. This technique en- ables the measurement of blood flow, blood vol- ume, mean transit times and flow peak times of the cerebrum corresponding to the territories of the main arterial vessels, including the anterior, middle and posterior cerebral arteries (13).

CBF measurements can also be obtained by evaluating the distribution of inhaled xenon, which diffuses into the brain to form a variation in tissue density (10, 17).

It is also possible to visualize the arterial ves- sels directly by using the angio-CT technique.

The administration of a bolus of intravenous contrast medium is followed by a high spatial resolution volumetric acquisition, with results that are similar to those obtained by conven- tional selective angiographic catheterization.

However, all the various possibilities of es- tablishing BD diagnosis by CT described above have yet to be validated for use for forensic purposes.

Cerebral angiography by means of selective arterial catheterization (Fig. 4.33), preferably utilizing digital imaging equipment, has limita- tions in that it is invasive and cannot be per- formed in all centres (20). In the past this tech- nique has repeatedly been proposed as a method for diagnosing BD. If this method is utilised, we suggest tailoring the examination to include a study of the supraaortic vessels and the intracranial circulation by a simple catheterization of the ascending aorta, with in- jection of contrast medium at this point using the automatic injector. In order to certify BD, one must be able to demonstrate the absence of filling of the internal carotid arteries and the

Fig. 4.32 - Diffuse cerebral cytotoxic oedema in a patient with subarachnoid haemorrhage. Unenhanced CT shows swelling of the brain with compression of the ventricular and subarachnoid spaces of the supratentorial compartment and posterior fossa. Note also the disappearance of the grey-white matter differentiation indicating diffuse cytotoxic oedema.

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vertebral arteries at the point where they enter the skull together with normal filling of the ex- ternal carotid arteries (2, 5, 9). Being an inva-

sive technique, and given the known potential for the toxic effect of the contrast medium on organs suitable for transplantation, certain

Fig. 4.33 - Brain death. Selective right carotid arteriogram reveals an absence of flow of contrast past the base of the cranium via the internal carotid artery. Similar findings were observed in the left carotid and vertebral arteries (not shown).

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doubts have been voiced concerning the use of conventional cerebral angiography for verifying BD (20).

Magnetic resonance imaging (MRI) easily demonstrates diffuse cerebral oedema, even at an early stage, using T2-weighted or diffusion- weighted imaging sequences; MR spectroscopy can directly show the presence of lactic acid, an early indication of cellular necrosis; MR an- giography can indicate the presence or absence of flow in the cerebral veins and arteries. De-

spite the fact that MRI does present certain dif- ficulties in execution and has some clear limita- tions, the initial results would suggest further future investigation into its potential medico-le- gal use in the evaluation of BD (11, 12).

With regard to nuclear medicine methods, the study of cerebral perfusion with 133-Xenon, which is not readily available, does not enable evaluation of the deep brain structures and is hindered by artefacts caused by increased ex- tracranial flow (19). In addition, cerebral an- gioscintigraphy can be difficult to interpret, and importantly, it is unable to study the vascular structures of the posterior fossa (7, 19).

On the other hand, in our experience and that of others, SPECT with HM-PAO has proved to be simple to perform and interpret (1, 6). Additionally, it has made it possible to diagnose brain death at an early stage.

Using SPECT, the diagnosis of brain death is made by demonstrating an absence of per- fusion throughout the brain. One example of this finding is shown in Fig. 4.34: absence of detection of the radionuclide in the brain; de- tection of radionuclide in the subcutaneous muscular and bony tissues of the skull. In the same case CT demonstrated the presence of a deep intraparencymal haematoma (Fig. 4.35).

In another patient (scintigraphic planar scans in AP: Fig. 4.36; SPECT: Fig. 4.37), CT and MRI studies (Figs. 4.38-4.42) demonstrated the presence of an intraparenchymal haema-

Fig. 4.34 - Brain death. SPECT scans reveal a complete absence of cerebral and cerebellar perfusion. [a) axial a), sagittal b) and c) coronal SPECT].

a

b

c

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Fig. 4.35 - Same case as Fig. 4.34. The CT images show only the presence of a deep intraparenchymal haematoma.

Fig. 4.36 - SPECT, CT and MRI comparison of brain death. See text.

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toma, intraventricular and midbrain haemor- rhage and brain swelling. MRI also demostrat- ed a loss of grey-white matter differentiation and the absence of blood flow in the main in- tracranial vessels, suggested by a high in- travascular MR signal intensity.

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Whichever methodology is embraced, it is recommended that explicitly approved proto- cols are adopted in all hospitals were BD certi- fication is performed taking into account local situations and conditions.

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