Diagnosis
Of Death And Its Physiology
Diagnosing death
Circulatory death
Traditionally, death has been certified by the absence of a circulation,
usually taken as the point at which the heart stops beating. In the UK, current
guidance suggests that death may be confirmed after 5 minutes of observation
following cessation of cardiac function (e.g. absence of heart sounds, absence
of palpable central pulse or asystole on a continuous electrocardiogram). Organ
donation after circulatory death (DCD) may occur following confirmation that
death has occurred (also called non-heart-beating donation). There are two sorts of DCD donation, controlled and uncontrolled.
Controlled DCD donation occurs when life-sustaining
treatment is withdrawn on an intensive therapy unit (ITU). This usually
involves discontinuing inotropes and other medicines, and stopping ventilation.
This is done with the transplant team ready in the operating theatre able to
proceed with organ retrieval as soon as death is confirmed.
Uncontrolled DCD donation occurs when a patient is brought
into hospital and, in spite of attempts at resuscitation, dies. Since such
events are unpredictable a surgical team is seldom present or prepared, and
longer periods of warm ischaemia occur (see later).
Brainstem death
Brainstem death (often termed simply brain death) evolved not for the
purposes of transplantation, but following technological advances in the 1960s
and 1970s that enabled patients to be supported for long periods on a
ventilator while deep in coma. There was a requirement to diagnose death in
such patients whose cardiorespiratory function was supported artificially.
Before brain-stem death can be diagnosed, five pre-requisites must be met.
Pre-requisites before brainstem death testing can occur
1 The patient’s condition should be due to
irreversible brain damage of known aetiology.
2 There should be no evidence that the comatose
state is due to depressant drugs – drug levels should be measured if doubt
exists.
3 Hypothermia as a cause of coma has been excluded – the temperature
should be >34°C before testing.
4 Potentially reversible circulatory,
metabolic and endocrine causes have
been excluded. The commonest confounding problem is hypernatraemia, which
develops as a consequence of diabetes insipidus, itself induced by failure of
hypothalamic antidiuretic hormone (ADH) production.
5 Potentially reversible causes of apnoea have
been excluded, such as neuromuscular blocking drugs or cervical cord injury.
Tests of brainstem function
1 Pupils
are fixed and unresponsive to sharp changes in the intensity of incident light.
2 The
corneal reflex is absent.
3 There
is no motor response within the cranial nerve distribution to adequate
stimulation of any somatic area, such as elicited by supra-orbital pressure.
4 The
oculo-vestibular reflexes are absent: at least 50 ml of ice-cold water is
injected into each external auditory meatus. In life, the gaze moves to the
side of injection; in death, there is no movement.
5 There
is no cough reflex to bronchial stimulation, e.g. to a suction catheter passed
down the trachea to the carina, or gag response to stimulation of the posterior
pharynx with a spatula.
6 The
apnoea test: following pre-oxygenation with 100% oxygen, the respiratory rate is lowered until the pCO2 rises
above 6.0 kPa (with a pH less than 7.4). The patient is then disconnected from
the ventilator and observed for 5 minutes for a respiratory response. Following
brainstem death spinal reflexes may still be intact, resulting in movements of
the limbs and torso.
These criteria are used in the UK; different criteria exist else- where
in the world, some countries requiring an unresponsive electroencephalogram
(EEG) or demonstration of no flow in the cerebral arteries on angiography. The
UK criteria assess brainstem function without which independent life is not
possible.
Causes of death
Most organ donors have died from an intracranial catastrophe of some
sort, be it haemorrhage, thrombosis, hypoxia, trauma or tumour. The past decade
has seen a change in the types of brain injury suffered by deceased organ
donors; deaths due to trauma are much less common, and have been replaced by an
increased prevalence of deaths from stroke. This is also a reflection of the
increased age of organ donors today.
Physiology of brainstem death
Cushing’s reflex and the catecholamine storm
Because the skull is a rigid container of fixed volume, the swelling that
follows a brain injury results in increased intracranial pressure (ICP). The
perfusion pressure of the brain is the mean arterial pressure (MAP) minus the
ICP, hence as ICP rises, MAP must rise to maintain perfusion. This is triggered
by baroreceptors in the brain-stem that activate the autonomic nervous system,
resulting in catecholamine release. Catecholamine levels may reach 20-fold
those of normal, with systemic blood pressure rising dramatically.
The ‘catecholamine storm’ has deleterious effects on other organs: the
left ventricle is placed under significant strain with subendocardial
haemorrhage, and subintimal haemorrhage occur in arteries, particularly at the
points of bifurcation, predisposing to thrombosis of the organ following
transplantation; perfusion of the abdominal organs suffers in response to the
high catecholamine levels. Eventually the swollen brain forces the brainstem to
herniate down through the foramen magnum (coning), an occurrence that is marked
by its compression of the oculomotor nerve and resultant pupillary dilatation. Once
coning has occurred circulatory collapse follows with hypotension, secondary
myocardial depression and vasodilatation, with failure of hormonal and neural
regulators of vascular tone.
Decompressive craniectomy
Modern neurosurgical practices include craniectomy (removal of parts of
the skull) to allow the injured brain to swell, reducing ICP and so maintaining
cerebral perfusion. While such practices may protect the brainstem, the
catastrophic nature of the brain injury may be such that recovery will not
occur and prolongation of treatment will be inappropriate. Such is the setting
in which DCD donation often takes place.
Neuroendocrine changes associated with brain death Following
brainstem death a number of neuroendocrine changes occur, most notably the
cessation of ADH secretion, resulting in diabetes insipidus and consequent
hypernatraemia. This is treated by the administration of exogenous ADH and 5%
dextrose. Other components of the hypothalamic-pituitary axis may also merit
treatment to optimise the organs, including the administration of glucocorticoids and triiodothyronine (T3).
