Disorders of consciousness

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Chapter 42 Disorders of consciousness

Balasubramanian Venkatesh

NEUROANATOMY AND PHYSIOLOGY OF WAKEFULNESS

A normal level of consciousness depends on the interaction between the cerebral hemispheres and the rostral reticular activating system (RAS) located in the upper brainstem. Although the RAS is a diffuse projection, the areas of RAS of particular importance to the maintenance of consciousness are those located between the rostral pons and the diencephalon. In contrast, consciousness is not focally represented in any of the cerebral hemispheres and is in many ways related to the mass of functioning cortex. Thus anatomical bilateral hemispheric lesions or brainstem lesions may result in an altered conscious state.¹ Large unilateral hemispheric lesions may produce impairment of consciousness by compression of the upper brainstem. In addition metabolic processes may result in coma from interruption of energy substrate delivery or alteration of neuronal excitability. Disorders of consciousness are characterised by an alteration in either the level or content of consciousness (Table 42.1). The last few conditions described in Table 42.1 are a frequent source of confusion and require further discussion (Table 42.2). These neurological states are seen more frequently in modern-day clinical practice partly because of the advances in therapy of severe brain injury and intensive care which have led to the survival of many patients who would otherwise have died.

Table 42.1 Disorders of consciousness

Consciousness	An awake individual demonstrates full awareness of self and environment
Confusion	Inability to think with customary speed and clarity, associated with inattentiveness, reduced awareness and disorientation
Delirium	Confusion with agitation and hallucination
Stupor	Unresponsiveness with arousal only by deep and repeated stimuli
Coma	Unarousable unresponsiveness
Locked-in syndrome	Total paralysis below third cranial nerve nuclei; normal or impaired mental function
Persistent vegetative state	Prolonged coma > 1 month, some preservation of brainstem and motor reflexes
Akinetic mutism	Prolonged coma with apparent alertness and flaccid motor tone
Minimally conscious state	Preserved wakefulness, awareness and brainstem reflexes, but poorly responsive

Table 42.2 Coma-like syndromes and related states

DIFFERENTIAL DIAGNOSIS OF COMA

Although the aetiology of coma is invariably multifactorial, the differential diagnosis of coma can be broadly grouped into three classes:

1 diseases that produce focal or lateralising signs

2 coma without focal or lateralising signs, but with signs of meningeal irritation

3 coma without focal or lateralising signs or signs of meningeal irritation

These are considered in greater detail in Table 42.3.

Table 42.3 Differential diagnosis of coma

CLINICAL EXAMINATION OF THE COMATOSE PATIENT

The neurological examination of the comatose patient is of crucial importance to assess the depth of coma and to locate the site of lesion. Although the detailed neurological examination which can be carried out in a conscious patient is not possible in a comatose individual, useful information can be obtained by performing a thorough general examination and a neurological examination, particularly evaluating the level of consciousness, brainstem signs and motor responses in coma.

GENERAL EXAMINATION

General examination of the patient may point to the aetiology of coma. Skin changes may be seen in carbon monoxide poisoning (cherry-red discoloration of skin), alcoholic liver disease (telangiectasia, clubbing), hypothyroidism (puffy facies) and hypopituitarism (sallow complexion). The presence of cutaneous petechiae or ecchymoses may point to meningococcaemia, rickettsial infection or endocarditis as possible causes of coma. Needle puncture marks may suggest substance abuse. Bullous skin lesions are a feature of barbiturate overdose. An excessively dry skin may indicate diabetic ketoacidosis or anticholinergic overdose.

Periorbital haematomas (raccoon eyes) indicate an anterior basal skull fracture, particularly if there is associated cerebrospinal fluid rhinorrhoea. The other signs of a basal skull fracture include Battle’s sign and cerebrospinal fluid otorrhoea. Nuchal rigidity may be seen in meningoencephalitis and subarachnoid haemorrhage, although this sign may not be present in the elderly and in patients in deep coma.

The presence of hepatomegaly or stigmata of chronic liver disease may suggest hepatic encephalopathy. Bilateral enlarged kidneys may indicate polycystic kidney disease and should prompt one to consider subarachnoid haemorrhage as a possible aetiology of coma. The breath may smell of alcohol or other poisons (organophosphates). The smell of ketones on the breath is an unreliable sign and hepatic and uraemic foetor are rare.

This is assessed by the Glasgow Coma Scale (GCS),² which takes into account a patient’s response to command and physical stimuli. The GCS (Table 42.4) which was originally developed to grade the severity of head injury and prognosticate outcome, has now been extended for all causes of impaired consciousness and coma. Although it is a simple clinical score, easily performed by both medical and nursing staff by the bedside, there are a number of caveats:

1 The GCS should always be determined prior to administration of sedative drugs or endotracheal intubation.

2 It should also be defined with regard to a patient’s vital signs, namely blood pressure, heart rate and temperature.

3 The GCS must be interpreted in the light of previous or concomitant drug therapy.

4 The presence of alcohol in the breath or in the serum should always be documented.

5 Because of the considerable interobserver variation in scoring, it is important to define the responses in descriptive terms rather than emphasising the numerical score associated with each response.

6 Measurement of awareness by the GCS is limited. Subtle changes in brainstem reflexes are not adequately assessed by the GCS.

Table 42.4 Glasgow Coma Scale

Eye opening	Points
Spontaneous	4
To speech	3
To pain	2
Nil	1
Best verbal response
Oriented	5
Confused	4
Inappropriate	3
Incomprehensible	2
Nil	1
Intubated	T
Best motor response
Obeys commands	6
Localises to pain	5
Withdraws to pain	4
Abnormal flexion	3
Extensor response	2
Nil	1

PUPILLARY RESPONSES IN COMA ³

The presence of normal pupils (2–5 mm and equal in size and demonstrating both direct and consensual light reflexes) confirms the integrity of the pupillary pathway (retina, optic nerve, optic chiasma and tracts, midbrain and third cranial nerve nuclei and nerves). The size of the pupil is a balance between the opposing influences of both sympathetic (causing dilatation) and parasympathetic (causing constriction) systems. Pupillary abnormalities have localising and diagnostic value in clinical neurology (Table 42.5). When the pupils are miosed, the light reaction is difficult to appreciate and may require a magnifying glass.

Table 42.5 Pupillary abnormalities in coma

Abnormality	Cause	Neuroanatomical basis
Miosis (< 2 mm in size)
Unilateral	Horner’s syndrome	Sympathetic paralysis
	Local pathology	Trauma to sympathetics
Bilateral	Pontine lesions
	Thalamic haemorrhage	Sympathetic paralysis
	Metabolic encephalopathy
	Drug ingestion
	Organophosphate	Cholinesterase inhibition
	Barbiturate
	Narcotics	Central effect
Mydriasis (> 5 mm in size)
Unilateral fixed pupil	Midbrain lesion	Third-nerve damage
	Uncal herniation	Stretch of third nerve against the petroclinoid ligament
Bilateral fixed pupils	Massive midbrain haemorrhage	Bilateral third-nerve damage
	Hypoxic cerebral injury Drugs	Mesencephalic damage
	Atropine	Paralysis of parasympathetics
	Tricyclics	Prevent local reuptake of catecholamines by nerve endings
	Sympathomimetics	Stimulation of sympathetics

OPHTHALMOSCOPY IN COMA

The pupils should never be dilated pharmacologically without prior documentation of the pupillary size and the light reflex. The presence of papilloedema suggests the presence of intracranial hypertension, but is frequently absent when the lesion is acute. Subhyaloid and vitreous haemorrhages are seen in patients with subarachnoid haemorrhage.⁴

EYE MOVEMENTS IN COMA ⁵

Horizontal eye movements to the contralateral side are initiated in the ipsilateral frontal lobe and closely coordinated with the corresponding centre in the contralateral pons. To facilitate conjugate eye movements, yoking of the third-, fourth- and sixth-nerve nuclei is achieved by the medial longitudinal fasciculus.

To look to the left, the movement originates in the right frontal lobe and is coordinated by the left pontine region and vice versa. In contrast to horizontal gaze, vertical eye movements are under bilateral control of the cortex and upper midbrain.

The position and movements of the eyes are observed at rest. The presence of spontaneous roving eye movements excludes brainstem pathology as a cause of coma. In a paralytic frontal-lobe pathology, the eyes will deviate towards the side of the lesion, whilst in pontine pathologies, the eyes will deviate away from the side of the lesion. Ocular bobbing, an intermittent downward jerking eye movement, is seen in pontine lesions due to loss of horizontal gaze and unopposed midbrain controlled vertical gaze activity.⁶ Skew deviation (vertical separation of the ocular axes) occurs with pontine and cerebellar disorders.⁷

The presence of full and conjugate eye movements in response to oculocephalic and oculovestibular stimuli demonstrates the functional integrity of a large segment of the brainstem. Corneal reflexes are preserved until late in coma. Upward rolling of the eyes after corneal stimulation (Bell’s phenomenon) implies intact midbrain and pontine function.

LIMB MOVEMENTS AND POSTURAL CHANGES IN COMA

Restlessness, crossing of legs and spontaneous coughing, yawning, swallowing and localising movements suggest only a mild depression of the conscious state. Choreoathetotic or ballistic movements suggest a basal ganglion lesion. Myoclonic movements indicate a metabolic disorder, usually of postanoxic origin. Asterixis is seen with metabolic encephalopathies. Hiccup is a non-specific sign and does not have any localising value.

Decerebrate rigidity is characterised by stiff extension of the limbs, internal rotation of the arms and plantar flexion of the ankles. With severe rigidity, opisthotonos and jaw clenching may be observed. These movements may be unilateral or bilateral, and spontaneous or in response to a noxious stimulus. Whereas animal studies suggest that the lesion is usually in the midbrain or caudal diencephalon (leading to exaggeration of antigravity reflexes), in humans such posturing may be seen in a variety of disease states: midbrain lesion, certain metabolic disorders such as hypoglycaemia, anoxia, hepatic coma and in drug intoxication.Decorticate posturing is characterised by flexion of elbows and wrists and extension of the lower limbs. The lesion is usually above the midbrain in the cerebral white matter.

RESPIRATORY SYSTEM ⁸

Abnormal respiratory rate and patterns have been described in coma, but their precise localising value is uncertain. As a general rule, at lighter levels of impaired consciousness tachypnoea predominates, whereas respiratory depression increases with the depth of coma. Some of the commonly observed respiratory abnormalities are summarised in Table 42.6. Respiratory failure in comatose patients may result from hypoventilation, aspiration pneumonia and neurogenic pulmonary oedema, a sympathetic nervous system-mediated syndrome seen in acute brain injury.

Table 42.6 Disorders of respiratory rate and pattern in coma

Abnormality	Significance
Bradypnoea	Drug-induced coma, hypothyroid coma
Tachypnoea	Central neurogenic hyperventilation (midbrain lesion),
	metabolic encephalopathy
Cheyne–Stokes respiration	Deep cerebral lesions, metabolic encephalopathy (hyperpnoea alternating regularly with apnoea)
Apneustic breathing (an inspiratory pause)	Pontine lesions
Ataxic breathing	Medullary lesions
(Ataxic breathing normally progresses to agonal gasps and terminal apnoea)

BODY TEMPERATURE IN COMA

The presence of altered core body temperature is a useful aid in the diagnosis of coma. Hypothermia (< 35°C) is frequently observed with alcohol or barbiturate intoxication, sepsis with shock, drowning, hypoglycaemia, myxoedema, coma and exposure to cold. Severe hyperthermia may be seen in pontine haemorrhage, intracranial infections, heat stroke and anticholinergic drug toxicity.

RECOGNITION OF BRAIN HERNIATION ^9,¹⁰

When patients with impaired level of consciousness deteriorate, it is important to consider brain herniation as a possible cause of worsening. Brain herniation results from the downward displacement of the upper brainstem (central herniation) with or without involvement of the uncus (lateral herniation). The clinical signs of a central herniation are progressive obtundation, Cheyne–Stokes respiration, small pupils followed by extensor posturing and medium-sized fixed dilated pupils. Uncal herniation differs from central herniation in that pupillary dilatation occurs early in the process because of third-nerve compression. The traditional Cushing’s response of hypertension and bradycardia is not always a feature of herniation and any heart rhythm may be present.

DIFFERENTIATING TRUE COMA FROM PSEUDOCOMA

Patients feigning coma resist passive eye opening and may even hold their eyes tightly closed. They may blink in response to a threat and do not demonstrate spontaneous roving eye movements. In contrast, they move the eyes concomitantly with head rotation and, with cold caloric testing, they may wake up or demonstrate preservation of the fast component of nystagmus. They also demonstrate avoidance of ‘self-injury’. In addition, the pattern of clinical ‘abnormalities’ does not fit any specific neurological syndromes.

MANAGEMENT OF THE COMATOSE PATIENT

EMERGENT THERAPEUTIC MEASURES

Irrespective of the aetiology of coma, certain emergent therapeutic measures apply to the care of all patients. These take precedence over any diagnostic investigation.

1 Ensure adequate airway and oxygenation.

2 Secure intravenous access and maintain circulation.

3 Administer 50% dextrose after drawing a sample of blood for serum glucose levels. Although there are theoretical concerns about augmentation of brain lactic acid production ^11,¹² in anoxic coma, the relatively good prognosis for hypoglycaemic coma when treated expeditiously far outweighs any potential risks of glucose administration.

4 Thiamine must always be administered in conjunction with dextrose to prevent precipitation of Wernicke’s encephalopathy.

5 Consideration should be given to administering naloxone when there is a suspicion of narcotic overdose with impending respiratory arrest.

6 If hypertension, bradycardia and fixed dilated pupils are present at the time of the initial presentation, suggestive of marked intracranial hypertension and tentorial herniation, 20% mannitol at a dose 0.5–1 g/kg body weight should be administered. Consideration should be given to the emergency placement of an external ventricular drain.

7 Treat suspected meningitis with antibiotics even if cerebrospinal fluid results are not available. A combination of penicillin and ceftriaxone is usually recommended for community-acquired bacterial meningitis.

8 Control of seizures must be achieved as outlined in Chapter 43.

9 Treat extreme body temperatures.

INVESTIGATIONS

The order of investigation depends on the clinical circumstances. In the majority of cases, history and examination will provide enough information to be able to perform specific cause-related investigation. In general, the investigations can be grouped as follows.

ROUTINE INVESTIGATIONS

Measurements of serum glucose, electrolytes, arterial blood gases, liver and renal function tests, osmolality, blood count and blood film are part of the routine investigations. When drug overdose is suspected, a toxicology screen for alcohol, paracetamol, salicylates, benzodiazepines and tricyclic antidepressants should be performed. A sample of serum should be stored for later analysis for uncommon drug ingestions.

NEUROIMAGING

COMPUTED TOMOGRAPHY (CT) SCAN

The most commonly used radiological investigation for evaluation of the comatose patient is CT scan of the brain. This is useful for diagnosing central nervous system trauma, subarachnoid and intracerebral haemorrhage, haemorrhagic and non-haemorrhagic strokes, cerebral oedema, hydrocephalus and the presence of a space-occupying lesion (SOL) (Figures 42.1–42.10). Frequently a CT is performed prior to a lumbar puncture (LP) to exclude rather than confirm the presence of severe cerebral oedema or an SOL. Its other advantages include lower cost, easy availability, short examination time and safety in the presence of pacemakers, surgical clips and other ferromagnetic substances. The advent of helical CT whereby multiple images are possible has reduced scanning times and is suitable for the uncooperative patient. Limitations of a CT scan include:

1 the need to transfer the patient to a site where resuscitation and monitoring facilities are limited

2 the need to sedate and possibly endotracheally intubate patients who are agitated

3 its low sensitivity to demonstrate an abnormality in the acute phase of a stroke

4 its low sensitivity for detecting brainstem lesions

5 the need to administer intravenous contrast agents. The two major side-effects of intravenous contrast include anaphylaxis (with an approximate death rate of 1 in 40 000) and renal failure. The use of N-acetylcysteine, sodium bicarbonate and haemodialysis has been reported to reduce the incidence of contrast-induced nephropathy, although data in critically ill patients are minimal.¹³

Figure 42.1 Right middle cerebral artery infarct. There is anterior and posterior sparing. Loss of right lateral ventricle. Moderate mass effect with midline shift.

Figure 42.2 Blood. Right thalamic intraparenchymal bleed with subarachnoid blood. (a) Fourth ventricle; (b) both lateral ventricles; (c) ventricles and intraparenchymal blood.

Figure 42.3 Subarachnoid haemorrhage. Blood in the Sylvian fissure and in basal cisterns.

Figure 42.4 Acute left subdural haematoma. Crescenteric pattern within the skull with high attenuation. Loss of ventricle.

Figure 42.5 Chronic left subdural haematoma. Isodense fluid filling space. The small white area may suggest a recent acute bleed.

Figure 42.6 Right extradural haematoma. Note soft-tissue swelling.

Figure 42.7 Right frontoparietal bleed. Note oedema, loss of lateral ventricle and minor midline shift.

Figure 42.8 Multiple enhanced lesions – metastases. (a) Left frontal lesion; (b) right thalamic lesion.

Figure 42.9 Frontal meningioma. (a) Precontrast; (b) postcontrast.

Figure 42.10 Abscess. (a) Precontrast; (b) postcontrast.

MAGNETIC RESONANCE IMAGING (MRI)

MRI scans provide superior contrast and resolution of the grey and white matter as compared to CT scans, thus facilitating easy identification of the deep nuclear structures within the brain. MRI is more sensitive than CT for the detection of acute ischaemia, diffuse axonal injury and cerebral oedema, tumour and abscess. Brainstem and posterior fossa structures are better visualised (Figures 42.11–42.13). It can also show vasculature (see Figure 42.13b and c). The other advantage of MRI is the use of non-ionising energy. The use of gadolinium, a paramagnetic agent, as a contrast agent permits sharp definition of lesions. MR coupled with angiography (MRA) may enable diagnosis of vascular lesions. MRI is however limited by:

1 the need for special equipment

2 long imaging times

3 the need to transfer the patient to a site where resuscitation and monitoring facilities are limited

4 the need to sedate and possibly endotracheally intubate patients who are agitated

5 the risk of dislodgement of metal clips on blood vessels and resetting of pacemakers

Figure 42.11 Cerebellar infarct.

Figure 42.12 Posterior cerebral bleed.

Figure 42.13 (a) Pontine ischaemia seen on magnetic resonance imaging (MRI). MRI can also be used to show vasculature. (b) Ocluded left vertebral artery; (c) critical stenosis of left internal carotid artery.

PET AND SPECT SCANS

Newer nuclear medicine scans such as single-photon emission with computed tomography (SPECT) and positron emission tomography (PET) are useful for the assessment of cerebral blood flow and oxygenation and in the prognostication of neurotrauma, but have little role to play in the management of acute disorders of consciousness. In PET scans, positron-emitting isotopes such as ¹¹C, ¹⁸F and ¹⁵O are incorporated into biologically active compounds such as deoxyglucxose or fluorodeoxyglucose which are metabolised in the body. By determining the concentration of the various tracers in the brain and constructing tomographic images, cerebral blood flow and metabolism can be measured by PET scanning.

SPECT scans use iodine-containing isotopes incorporated into biologically active compounds and, like PET scans, their cranial distribution is determined after a dose of tracer. Information on cerebral blood flow and metabolism can be obtained from SPECT scans. The advantage of a PET scan is that it does not require a cyclotron for the generation of isotopes. Despite their many advantages, both these technologies continue to be research tools and are not routinely available in many medical centres.

LUMBAR PUNCTURE ¹⁴

Cerebrospinal fluid is most commonly obtained by means of an LP. This should be performed after ensuring that raised intracranial pressure has been excluded clinically or radiologically. The major use of an LP is to diagnose an intracranial infection and to detect abnormal cytology in cases of suspected malignant meningeal infiltration. The advent of CT scans has diminished the role of LP in the diagnosis of subarachnoid haemorrhage. Some of the commonly reported complications post-LP include postpuncture headache (12–39%) and traumatic tap (15–20%). Brain herniation is a rare potential complication seen with conditions associated with raised intracranial pressure due to an SOL.

ELECTROENCEPHALOGRAM (EEG) IN COMA ^15,¹⁶

The usefulness of EEG in coma is summarised in Table 42.7. Continuous EEG monitoring in the intensive care unit (ICU) has been reported to be useful in the identification of acute cerebral ischaemia and non-convulsive seizures.

Table 42.7 Usefulness of electroencephalogram in coma

Identification of non-convulsive status epilepticus

Diagnosis of hepatic encephalopathy

Presence of paroxysmal triphasic waves

Assessing severity of hypoxic encephalopathy

Presence of theta activity

Diffuse slowing

Burst suppression (seen with more severe forms)

Alpha coma (seen with more severe forms)

Herpes encephalitis

Periodic sharp spikes

EVOKED POTENTIALS

Visual, brainstem and somatosensory evoked potentials test the integrity of neuroanatomical pathways within the brain and the spinal cord. They may be used in the diagnosis of blindness in comatose patients and in the assessment of locked-in states. There are data to suggest that they have better prognostic value than clinical judgement in patients with anoxic coma.¹⁷

BIOCHEMICAL ABNORMALITIES ¹⁸

A number of biomarkers of brain injury have been evaluated as predictors of severity of brain injury and to assess progression of injury severity from traumatic and non-traumatic aetiologies. These include neurone-specific enolase (cytoplasm of neurons), S-100 B protein (astroglial cells), CK-BB fraction (astrocytes), glial fibrillary acidic protein (glial origin), calpain and caspase. Whilst early studies showed S-100B to be a reliable marker of traumatic brain injury, concerns remain about their sensitivity and specificity for assessment of severity and prediction of outcome.

CARE OF THE COMATOSE PATIENT

AIRWAY

As mentioned before, assessment of airway adequacy should take precedence over any diagnostic investigation in comatose patients. This is best done by assessing the patient’s response to command and physical stimulation, and whether a gag reflex is present. Securing the airway will depend on the level of consciousness. This may entail simple manoeuvres such as jaw thrust, chin lift, use of oropharyngeal airways or in the comatose patient mandate endotracheal intubation. All of these patients are at risk of pulmonary aspiration and there must be a low threshold for establishing a definitive airway.

As a general rule, patients presenting with medical causes of coma may be nursed on their side (in the coma position) if the airway is adequate. However, all traumatised patients should be assumed to have a potential cervical spine injury and must be nursed with the cervical spine in the neutral position and/or with a rigid collar until an injury is excluded by definitive radiological views. All patients with disordered consciousness must receive supplemental oxygen.

VENTILATION

It is important to ensure optimal gas exchange and avoid hypoxia and hypercapnia. Generally a PaO₂ of > 80 torr and PCO₂ of 35–40 torr is desirable. If spontaneous ventilatory efforts are not adequate to achieve these levels of arterial blood gases, mechanical ventilatory support may be necessary.

CIRCULATION

Adequacy of circulation should be assessed by conventional clinical endpoints. The goals of circulatory therapy in coma include prompt restoration of appropriate mean arterial blood pressure, correction of dehydration and hypovolaemia and urgent attention to life-threatening causes of shock.

SPECIFIC TREATMENT

This will depend on the underlying aetiology of the coma and is discussed in the relevant chapters. Avoidance of secondary insults is of paramount importance in the management of these patients.¹⁹

NURSING CARE

Meticulous eye and mouth care, regular changes in limb position, limb physiotherapy, bronchial toilet and psychological support are mandatory. Nosocomial infections and iatrogenic complications are associated with an increased mortality and morbidity in these patients and must be promptly diagnosed and treated. The rational use of daily investigations, invasive procedures and antibiotic prescription is essential.

OTHER THERAPY

Stress ulcer and deep-vein thrombosis prophylaxis should be instituted. Early establishment of enteral feeding via a nasoenteric tube is preferable. It is important to exclude a basal skull fracture before insertion of a nasoenteric tube.

ANOXIC COMA/ENCEPHALOPATHY

Cardiac arrest is the third leading cause of coma resulting in ICU admission after trauma and drug overdose. The symptomatology and clinical outcome of patients with anoxic brain damage depend on the severity and duration of oxygen deprivation to the brain. A number of criteria have been developed to prognosticate outcome in anoxic coma. Although a number of laboratory and imaging criteria contribute to the prognostic assessment, clinical signs still have major prognostic impact. The important clinical predictors of outcome are listed in Table 42.8. However there are data to suggest that electrophysiological studies using evoked potential have far greater prognostic accuracy compared to clinical assessment.²⁰

Table 42.8 Clinical and laboratory predictors of unfavourable prognosis in anoxic coma ^17,³⁶^–³⁸

Clinical predictor	Unfavourable prognosis
Duration of anoxia	8–10 min
(time interval between collapse and initiation of CPR)
Duration of CPR	> 30 min
(time interval between initiation of CPR and ROSC)
Duration of postanoxic coma	> 72 hours
Pupillary reaction	Absent on day 3
Motor response to pain (absent = a motor response worse than withdrawal)	Absent on day 3
Roving spontaneous eye movements	Absent on day 1
Elevated neuron specific enolase	> 33 μg/l
SSEP recording	Absent N20

CPR, cardiopulmonary resuscitation; ROSC, restoration of spontaneous circulation; SSEP, somatosensory evoked potential.

THE CONFUSED/ENCEPHALOPATHIC PATIENT IN THE ICU

‘Encephalopathy’ is a term used to describe the alteration in the level or content of consciousness due to a process extrinsic to the brain. Metabolic encephalopathy, particularly of septic aetiology, is the most common cause of altered mental status in the ICU setting.²¹ A number of processes can lead to metabolic encephalopathy (Table 42.9). A number of features in the history and examination help to differentiate metabolic from structural causes of altered conscious states (Table 42.10).

Table 42.9 Aetiology of metabolic/toxic encephalopathy ³⁹^–⁴¹

Hepatic failure

Renal failure

Respiratory failure

Sepsis

Electrolyte abnormalities: hyponatraemia, hypernatraemia, hypercalcaemia

Hypoglycaemia and hyperglycaemia

Acute pancreatitis

Endocrine – addisonian crisis, myxoedema coma, thyroid storm

Drug withdrawal – benzodiazepine, opiates

Hyperthermia

Toxins: alcohols, glycols, tricyclic antidepressants

Intensive care unit syndrome

D-lactic acidosis

Table 42.10 Distinguishing features of structural and metabolic encephalopathy ⁴¹

Feature	Structural	Metabolic
State of consciousness	Usually fixed level of depressed conscious state, may deteriorate progressively	Milder alteration of conscious state, waxing and waning of altered sensorium
Fundoscospy	May be abnormal	Usually normal
Pupils	May be abnormal, either in size or response to light	Usually preserved light response (although pupil shape and reactivity affected in certain overdoses: see above)
Eye movements	May be affected	Usually preserved
Motor findings	Asymmetrical involvement	Abnormalities usually symmetrical
Involuntary movements	Not common	Asterixis, tremor, myoclonus frequently seen

Owing to their increased frequency in and exclusiveness to the critical care setting, two types of encephalopathy will be considered in detail: septic encephalopathy and ICU syndrome.

Sepsis-associated encephalopathy (SAE) has been reported to occur in 8–80% of patients with sepsis.²² The criteria to diagnose SAE include presence of impaired mental function, evidence of an extracranial infection and absence of other obvious aetiologies for the altered conscious state. Although the precise mechanism of damage to the brain has not been delineated, the pathogenesis of the encephalopathy is thought to be multifactorial: alteration in cerebral blood flow induced by mediators of inflammation, generation of free radicals by activated leukocytes resulting in erythrocyte sludging in the microcirculation, breakdown of the blood–brain barrier resulting in cerebral oedema, reduced brain oxygen consumption induced by endotoxin and cytokines, neuronal degeneration and increased neuronal apoptosis, increases in aromatic amino acids resulting in altered neurotransmitter function and increased gamma-aminobutyric acid (GABA)-mediated neurotransmission leading to general inhibition of the central nervous system. Hypotension may contribute to the encephalopathy. The asterixis, tremor and myoclonus – features of other metabolic encephalopathies – are uncommon in sepsis. The presence of lateralising signs are extremely rare in SAE and warrant exclusion of other causes, such as stroke. The mortality of patients with SAE is higher than in those with sepsis without encephalopathy.²³ Therapy is largely directed at the underlying septic process.

ICU ENCEPHALOPATHY OR ICU SYNDROME ^24,²⁵

This is a term used to describe behavioural disorders which develop in patients 5–7 days after admission to intensive care. Clinically this may present as agitation, restlessness and frank delirium. The causes are multifactorial: prolonged ventilation, sleep deprivation,^26,²⁷ distortion of perception with loss of day–night cycles, immobilisation, noisy environment and monotony. Coupled with administration of multiple sedatives and neurological consequences of the underlying disease, these factors can precipitate psychotic behaviour in the ICU. It is important to bear in mind that this is a diagnosis of exclusion and that all other reversible causes are looked for (seeTable 42.7) before this diagnostic label is applied.

Abnormal behaviour can increase patient morbidity (self-extubation, ripping of catheters, soft-tissue damage). It is important to identify the underlying cause of the abnormal behaviour to institute appropriate therapy. Management of this condition may require the use of restraints, sedation and major tranquillisers. Improvement of sleep quality (minimising interruption of nocturnal sleep, adjusting lighting in the ICU), reducing patient boredom by the use of television and music and better communication with the patient may reduce the incidence and severity of this syndrome.

PROGNOSIS IN COMA

Drug-induced comas usually have a good prognosis unless hypoxia and hypotension have resulted in severe secondary insults. Coma following head injury has a statistically better outcome compared to non-traumatic coma (coma occurring during the course of a medical illness). In non-traumatic coma lasting for 6 hours or greater, only 15% of the patients make a meaningful recovery to be able to return to their premorbid state of health.²⁸ The prognosis following anoxic coma has been described in a separate section. Within the non-traumatic coma category, coma resulting from infection, metabolic causes and multiple-organ dysfunction syndrome has a better outcome compared to anoxic coma.²⁹ A number of outcome scales have been developed to assess neurological recovery following brain injury.³⁰ These include the Barthel index, Rankin scale and the Glasgow Outcome Scale (GOS). The GOS is widely used to assess recovery after traumatic brain injury. It has five broad categories: 1 = good recovery; 2 = moderate disability; 3 = severe disability; 4 = persistent vegetative state; and 5 = death. It is simple, easy to administer and has been reported to have good interrater agreement.

REFERENCES

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