Recently gained confusion, severe apathy, stupor or coma implies dysfunction of the cerebral hemispheres, the diencephalon and/or the upper brainstem.³ Focal lesions in supratentorial structures may damage both hemispheres, or may produce swelling that compresses the diencephalic activating system and midbrain, causing transtentorial herniation and brainstem damage. Primary subtentorial (brainstem or cerebellar) lesions may compress or directly damage the reticular formation anywhere between the level of the midpons and, (by upward pressure), the diencephalon. Metabolic or infectious diseases may depress brain functions by a change in blood composition or the presence of a direct toxin. Impaired consciousness may also be due to reduced blood flow (as in syncope or severe heart failure) or a change in the brain’s electrical activity (as in epilepsy). Concussion, anxiolytic drugs and anaesthetics impair consciousness without producing detectable structural changes in the brain.

Many of the enzymatic reactions of neurons, glial cells, and specialised cerebral capillary endothelium in the brain must be catalysed by the energy-yielding hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate. Without a constant and generous supply of ATP, cellular synthesis slows or stops, neuronal functions decline or cease, and cell structures quickly fall apart.⁴ The brain depends entirely on the process of glycolysis and respiration within its own cells to provide its energy needs. Even a short interruption of blood flow or oxygen supply threatens tissue vitality.

Seizures

A seizure is an uninhibited, abrupt discharge of ions from a group of neurons resulting in epileptic activity.⁵ The majority of patients experiencing seizures in the ICU do not have preexisting epilepsy, and their chances of developing epilepsy in the future are usually more dependent on the cause than on the number or intensity of seizures that they experience. However, because of other deleterious neuronal and systemic effects of seizures, their rapid diagnosis and suppression during a period of critical illness is necessary.

Seizures are classified depending on how they start as (a) partial or focal seizures, (b) generalised or full body seizures involving both cerebral hemispheres, or (c) partial seizures with secondary generalisation. A patient may still be conscious during a partial seizure whereas in generalised seizures they are not. As partial seizures may not always progress to tonic-clonic movement or alteration in consciousness, partial seizure represents one of the most elusive diagnoses in neurology and is often misdiagnosed. One of the most helpful points in the history of a partial seizure patient is the preepileptic event, the aura. The patient will describe the aura as a virtually identical sensation every time.

Aetiology of seizures

Seizures may either prompt the patient’s admission to ICU (because of status epilepticus) or develop as a complication of another illness.⁶ Seizures can be due to vascular, infectious, neoplastic, traumatic, degenerative, metabolic, toxic or idiopathic causes. Factors influencing the development of posttraumatic epilepsy include an early posttraumatic seizure, depressed skull fracture, intracranial haematoma, dural penetration, focal neurological deficit and posttraumatic amnesia (PTA) over 24 hours with the presence of a skull fracture or haematoma. Seizures in critically ill patients are most commonly due to drug effects; metabolic, infectious or toxic disorders; and intracranial mass lesions although they may be due to trauma or neoplasm.⁷ Conditions producing seizures tend either to increase neuronal excitation or to impair neuronal inhibition. A few generalised disorders (e.g. non-ketotic hyperglycaemia) may produce partial or focal seizures.

Alterations in Motor and Sensory Function

Alterations of motor and sensory function include skeletal muscle weakness and paralysis. They result from lesions in the voluntary motor and sensory pathways, including the upper motor and sensory neurons of the corticospinal and corticobulbar tracts, or the lower motor and sensory neurons that leave the CNS and travel by way of the peripheral nerve to the muscle and sensory receptors.

Muscle tone, which is a necessary component of muscle movement, is a function of the muscle spindle (myotatic) system and the extrapyramidal system, which monitors and buffers input to the lower motor neurons by way of the multisynaptic pathways.⁸ Upper motor neuron lesions produce spastic paralysis, and lower motor neuron lesions produce flaccid paralysis. Damage to the upper motor and sensory neurons of the corticospinal, corticobulbar and spinothalamic tracts is a common component of stroke.⁹ Polyneuropathies involve multiple peripheral nerves and produce symmetrical sensory, motor, and mixed sensorimotor deficits:

• Lesions of the corticospinal and corticobulbar tracts: result in weakness or total paralysis of predominantly distal voluntary movement, Babinski’s sign (i.e. dorsiflexion of the big toe and fanning of the other toes in response to stroking the outer border of the foot from heel to toe), and often spasticity (increased muscle tone and exaggerated deep tendon reflexes).

• Disorders of the basal ganglia: (extrapyramidal disorders) do not cause weakness or reflex changes. Their hallmark is involuntary movement (dyskinesia), causing increased movement (hyperkinesias) or decreased movement (hypokinesia) and changes in muscle tone and posture.

• Cerebellar disorders: cause abnormalities in the range, rate and force of movement. Strength is minimally affected.

Autonomic Nerve Dysfunction

Dysfunctions of the autonomic nervous system (ANS) or autonomic dysreflexia are recognised by the symptoms that result from failure or imbalance of the sympathetic or parasympathetic components of the ANS such as (i) increased (>120/min) or decreased (<50/min) heart rate, (ii) increased respiratory rate (>24/min), (iii) raised temperature (>38.5°C), (iv) increased (>160 mmHg) or decreased (<85 mmHg) systolic blood pressure, (v) increased muscle tone, (vi) decerebrate (extensor) or decorticate (flexor) posturing, and (vii) profuse sweating. For example, in spinal injury the presence of a noxious stimulus can be transmitted from the periphery to the spinal cord and activates dysfunctional sympathetic response.

There is strong evidence for numerous interactions among the central nervous system (CNS), peripheral nervous system (both sympathetic and parasympathetic branches), the endocrine system, and the immune system, hence ANS dysfunction is related to that complex triad.¹⁰ Autonomic nerve (AN) dysfunction ranges from alterations in the sympathetic–parasympathetic balance to almost complete cessation as occurs in spinal cord injury. As the ANS controls organ function AN dysfunction is related to all-organ alteration and failure. The immune system is connected to the nervous system through the ANS with many of the patients with infections, systemic inflammatory response and multi-organ failure exhibiting AN dysfunction. AN dysfunction is closely related to systemic inflammation hence those with conditions with increased levels of inflammatory markers such as chronic disease and obesity have predisposing AN dysfunction. AN dysfunction is assessed by time and spectral domain heart rate variability and is currently being researched as a neurological assessment technique.¹¹

Alterations in Cerebral Metabolism and Perfusion

For decades, impairment of cerebral metabolism has been attributed to impaired oxygen delivery, mediated by reduced cerebral perfusion in the swollen cerebral parenchyma. Accordingly, reduction of ICP is usually argued for restoration of previously compromised cerebral perfusion for improvement of cerebral metabolism. Although uncontrolled ICP elevation has been shown to be responsible for reduced oxygen delivery, non-ischaemic impairment of oxidative metabolism and mitochondrial damage has only recently been recognised as a prominent source of energy crisis triggered by brain injury in the presence of adequate cerebral blood flow.¹² Accumulating evidence has shown that the mitochondrion has a pivotal role in post traumatic neuronal death by integrating numerous noxious signals responsible for both structural and functional damage on one hand and by amplifying these signals through activation of several cellular signalling events leading to cell death. In addition, more complex processes with the alteration of cerebral perfusion, such as cerebral hypoperfusion, ischaemia, reperfusion injury, inflammation and oedema result in increased intracranial pressure (ICP).

Cerebral Ischaemia

Ischaemia is the inadequate delivery of oxygen, the inadequate removal of carbon dioxide from the cell, and an increase in the production of intracellular lactic acid. Ischaemia can be caused by an increase in nutrient utilisation by the brain in a hyperactive state, a decrease in delivery related to either cerebral or systemic complications, and/or a mismatch between delivery and demand.¹³ The ischaemic cascade is described in Figure 17.1. Inflammation, together with oxidative stress, excitotoxicity, disrupted calcium homeostasis and energy failure, is one of the key pathological changes in ischaemic brain damage.¹⁴ There is a significant inflammatory response in ischaemic brains, including leucocyte and monocyte infiltration into the brain, activation of microglia and astrocytes, elevated production of inflammatory cytokines and chemokines and increased expression and activity of adhesion molecules, complement and metalloproteinases. Of importance, brain ischaemia can lead to significant inflammatory responses in the central nervous system and can also cause significant changes in the peripheral immune system. There are two phases. In the relatively early phase, activated spleen cells and lymph nodes and blood mononuclear cells secrete significantly enhanced levels of TNF-α, IL-6 and IL-2. This then results in global immunosuppression affecting the spleen, lymph nodes, thymus and a significant decrease in the number of immune cells in the circulation.¹⁵ When cerebral blood flow (CBF) falls to about 40% of normal, EEG slowing occurs. When CBF falls below 10 mL/100 g/min (20%), the function of ionic pumps fails, which leads to membrane depolarisation. Cerebral ischaemia and reperfusion injury contribute to the cascade of physiological events, termed secondary brain injury. Recent studies have shown that low-dose paracetamol reduces inflammatory protein release from brain endothelial cells exposed to oxidant stress¹⁶ and that propofol protects against neuronal apotosis.¹⁷

FIGURE 17.1 Ischaemic cascade. In cerebral ischaemia, energy failure causes depolarisation of the neuronal membrane, and excitatory neurotransmitters such as glutamate are released together. A marked influx of Ca²⁺ into neurons then occurs, which provokes the enzymatic process leading to irreversible neuronal injury. Inflammation is also a contributing factor in the development of ischaemic damage.

Cerebral Oedema

Cerebral oedema is defined as increased brain water content. The brain is particularly susceptible to injury from oedema, because it is located within a confined space and cannot expand, and because there are no lymphatic pathways within the CNS to carry away the fluid that accumulates. The white matter is usually much more involved, as myelinated fibres have a loose extracellular space, while the grey matter has a much higher cell density with many connections and much less loose extracellular space.¹⁸ The two main subdivisions of cerebral oedema are extracellular and intracellular.

Intracellular (cytotoxic) oedema

Cellular swelling, usually of astrocytes in the grey matter, is generally seen after cerebral ischaemia caused by cardiac arrest or minor head injury.¹⁹ The blood–brain barrier (BBB) is intact and capillary permeability is not impaired. The cause of intracellular oedema is anoxia and ischaemia; it is usually not clinically significant, and is reversible in its early phases.

Extracellular (vasogenic) oedema

Extracellular oedema involves increased capillary permeability, and had been termed ‘BBB breakdown’.²⁰ Rises in brain water content with extracellular oedema are often quite dramatic, because the fluid that results from increased capillary permeability is usually rich in proteins, resulting in the spread of oedema and brain ischaemia. This can lead to cytotoxic oedema, and to the progressive breakdown of both astrocytes and neurons.¹⁹ While the classification of oedema is useful to define specific treatments, it is somewhat arbitrary, as cytotoxic and vasogenic oedema often occur concurrently. In fact, each of these processes may cause the other. Ultimately, these changes can lead to raised intracranial pressure and herniation.

Hydrocephalus

Hydrocephalus is the result of an imbalance between the formation and drainage of cerebrospinal fluid (CSF). Reduced absorption most often occurs when one or more passages connecting the ventricles become blocked, preventing movement of CSF to its drainage sites in the subarachnoid space just inside the skull.²¹ This type of hydrocephalus is called ‘non-communicating’. Reduction in absorption rate, called ‘communicating hydrocephalus’ can be caused by damage to the absorptive tissue. Both types lead to an elevation of the CSF pressure within the brain. A third type of hydrocephalus, ‘normal pressure hydrocephalus’, is marked by ventricle enlargement without an apparent rise in CSF pressure, which mainly affects the elderly.

Hydrocephalus may be caused by: congenital brain defects; haemorrhage, in either the ventricles or the subarachnoid space; CNS infection (syphilis, herpes, meningitis, encephalitis or mumps); and tumours. Irritability is the commonest sign of hydrocephalus in infants and, if untreated, may lead to lethargy. Bulging of the fontanelle, the soft spot between the skull bones, may also be an early sign. Hydrocephalus in infants prevents fusion of the skull bones, and causes expansion of the skull. Symptoms of normal pressure hydrocephalus include dementia, gait abnormalities and incontinence.²² Treatment includes ventriculostomy drainage of CSF in the short term, or a surgical shunt for those with chronic conditions. Either is predisposed to blockage and infection.

Intracranial Hypertension

Intracranial pressure is the pressure exerted by the contents of the brain within the confines of the skull and the BBB. The Munro–Kelly hypothesis states that the contents of the cranium (60% water, 40% solid) are not compressible and thus an increase in volume causes a rapid rise in pressure and changes to the compensatory reserve and pulse amplitude, as illustrated in Figure 17.2.²³ Normal ICP is 0–10 mmHg, and a sustained pressure of >15 mmHg is termed intracranial hypertension, with implications for CBF.²⁴ Areas of focal ischaemia appear when ICP is >20 mmHg and global ischaemia occurs at >50 mmHg. ICP waveform contains valuable information about the nature of cerebrospinal pathophysiology. ICP increased to the level of systemic arterial pressure extinguishes cerebral circulation, which will restart only if arterial pressure rises sufficiently beyond the ICP to restore cerebral blood flow. Autoregulation of cerebral blood flow and compliance of the cerebrospinal system are both expressed in ICP. Methods of waveform analysis are useful, both to derive this information and to guide the management of patients.²⁵

FIGURE 17.2 The volume–ICP curve relationship.²¹

Initially, intracranial compliance allows compensation for rises in intracranial volume due to autoregulation. During a slow rise in volume in a continuous mode, the ICP rises to a plateau level at which the increased level of CSF absorption keeps pace with the rise in volume with ample compensatory reserve. This is expressed as an index, as shown in Figure 17.3.²⁶ Intermittent expansion causes only a transient rise in ICP at first. When sufficient CSF has been absorbed to accommodate the volume, the ICP returns to normal. The ICP finally rises to the level of arterial pressure which itself begins to rise, accompanied by bradycardia or other disturbances of heart rhythm (termed the Cushing’s response). This is accompanied by dilation of the small pial arteries and some slowing of venous flow, which is followed by pulsatile venous flow.

FIGURE 17.3 In a simple model, pulse amplitude of intracranial pressure (ICP) (expressed along the y-axis on the right side of the panel) results from pulsatile changes in cerebral blood volume (expressed along the x-axis) transformed by the pressure–volume curve. This curve has three zones: a flat zone, expressing good compensatory reserve, an exponential zone, depicting poor compensatory reserve, and a flat zone again, seen at very high ICP (above the ‘critical’ ICP) depicting derangement of normal cerebrovascular responses. The pulse amplitude of ICP is low and does not depend on mean ICP in the first zone. The pulse amplitude increases linearly with mean ICP in the zone of poor compensatory reserve. In the third zone, the pulse amplitude starts to decrease with rising ICP. RAP, index of compensatory reserve.²⁶

The respiratory changes depend on the level of brainstem involved. A midbrain involvement results in Cheyne-Stokes respiration. When the midbrain and pons are involved, there is sustained hyperventilation. There are rapid and shallow respirations with upper medulla involvement, with ataxic breathing in the final stages (see Figure 17.4).²⁷

FIGURE 17.4 Injury to the brainstem can result in various abnormal respiratory patterns.²⁷

Often, neurogenic pulmonary oedema may occur due to increased sympathetic activity as a result of the effects of elevated ICP on the hypothalamus, medulla or cervical spinal cord. The causes of intracranial hypertension are classified as acute or chronic. Acute causes include brain trauma, ischaemic injury and intracerebral haemorrhage. Infections such as encephalitis or meningitis may also lead to intracranial hypertension. Chronic causes include many intracranial tumours, such as ependymomas, or subdural bleeding that may gradually impinge on CSF pathways and interfere with CSF outflow and circulation. As the ICP continues to increase, the brain tissue becomes distorted, leading to herniation and additional vascular injury.²⁸

Neurological Therapeutic Management

This section explores cerebral perfusion, oxygenation and assessment. The objective of assessment is to identify and then initiate strategies in an attempt to prevent secondary insults and ischaemia. ICP monitoring is discussed in terms of therapeutic management.

Optimising Cerebral Perfusion and Oxygenation

Intracranial hypertension and cerebral ischaemia are the two most important secondary injury processes that can be anticipated, monitored and treated in the ICU. This applies to all aetiologies of brain injury including trauma. This section discusses the modalities of neuroprotection, including the management of intracranial hypertension, vasospasm and cerebral ischaemia. Nursing interventions for the prevention of secondary insults and promotion of cerebral perfusion are described in Table 17.1. Importantly, the aims of nursing management are based on published guidelines and are directed at optimising cerebral perfusion and metabolism by various initiatives.

TABLE 17.1 Nursing interventions for the promotion of cerebral perfusion in acute brain injury

Aim	Goal	Interventions
Maintain oxygenation	SaO₂ 98%, PaO₂ 100 mmHg, PbtO₂ >20	• Maintain airway. • Use 100% O₂ during initial resuscitation phase. • Intubate as soon as possible for Glasgow Coma Scale less than 8 or diaphragmatic respiratory insufficiency (C – spine number). • Obtain arterial blood gas and manipulate set FiO₂ to meet parameter goal. • Suction patient as needed. • Consider need for kinetic therapy, e.g. rotation/percussion therapy bed within spinal precautions. Use frequent subglottal suctioning, and maintain head of bed elevation at 30° or more to prevent VAP. • In recovery: assess for upper airway weakness and reflex (prevent aspiration), sputum retention and atelectasis.

Maintain PaCO₂ PaCO₂ 35–40 mmHg

• ABG assessment.

• Adjust ventilator settings to obtain PaCO₂ of 35–40 mmHg.

• Ensure optimal PaCO₂ for your patient: observe PbtO₂ and ICP during manipulation of PaCO₂.

• Monitor end-tidal CO₂ continuously.

• Observe for hypoventilation.

Maintain mean arterial pressure (MAP) MAP 90 mmHg

• Maintain euvolaemia.

• Give IV volume as prescribed to maintain CVP and PCWP within parameters.

• Use noradrenaline once euvolaemic in order to optimise MAP.

• Observe PbtO₂ for sedation-induced hypotension.

• Transfuse to haematocrit of 33% or haemoglobin content 80–100 g/L.

• Stroke: thrombolytic, embolic and ICH, MAP 90–120 mmHg

Maintain cerebral perfusion pressure 50–70 mmHg CPP 50–70 mmHg

• Effectively reduce ICP while preserving or improving CPP

• Position body with neck straight and no knee elevation in order to maintain venous outflow.

• Make sure cervical collar and endotracheal tube ties are not too tight, especially behind the neck.

• If patient has a ventriculostomy, drain per doctor’s orders.

Maintain intracranial pressure (CP) <20 mmHg ICP <20 mmHg

• Elevate head of bed above the level of the heart to obtain optimal level of ICP and CPP. Monitor ICP, CPP and PbtO₂ to ensure optimal level for your patient (15–30°).

• Sedate using propofol, morphine, fentanyl and/or lorazepam/midazolam

• Mannitol prescription at 0.25–1.0 g/kg IV for ICP sustained at less than 20 mmHg (watch serum osmolality and consider holding for values >320 mOsmol/kg) OR Hypertonic Saline 7.5% prescription

• Consider paralytics if positioning, cooling, sedation and mannitol does not resolve increased ICP.

• Maintain the brain temperatures at 36–37°C, using cooling measures; prevent shivering (increases cerebral metabolic demands)

• Prepare for surgical craniotomy if indicated.

Maintain environment/reduce stimulation SjO₂ 50–75% PbtO₂ >20

• Group necessary interventions in a timely manner to allow for rest periods.

• Screen visitors.

• Minimise noise and lighting.

• Avoid stimulation and prioritise interventions if ICP precarious.

• Sedation as prescribed.

Maintain cerebral blood flow PbtO₂ <20

• Optimise CPP to prescribed levels (60–70 mm Hg).

• Optimise PaCO₂ as indicated to increase CBF.

• Optimise sedation and consider paralytics.

• Consider barbiturate prescription if above measures are not successful.

• PaO₂ 100 mmHg and SaO₂ 98%.

• Maintain CVP of 5–10 mmHg, and a PCWP of 10–15 mmHg.

• Administer normal saline and/or colloids as prescribed to maintain parameters.

• Transfuse to haematocrit of 33% or haemoglobin content 80–100 g/L. (Prescription to correct coagulopathies).

• Monitor closely for signs and symptoms of neurogenic pulmonary oedema, especially in patients with cardiac history.

• Maintenance of brain temperature at 36–37°C, with active cooling if necessary.

• Transcranial Doppler image to check for vasospasm.

• Non-traumatic SAH, administer IV nimodipine or magnesium infusion to prevent vasospasm as prescribed; consider components of HHH therapy.

• Ischaemic stroke, administer tPA within 3 hours of event.

• ICH, prevent rebleeding; administer prescribed recombinant factor VII, reduce hypertension.

Maintain nutrition

• Ensure early enteric feeding.

• Oral enteric feeding tube (nasogastric contradicted in TBI).

• Dietitian referral for metabolic requirements.

• Stress ulcer prophylaxis.

Management of Cerebral Oxygenation and Perfusion

Cerebral monitoring in brain-injured patients has focused on the prevention of secondary injury to the brain owing to impaired perfusion. However, ICP monitoring and ICP manipulation does not equal cerebral oxygenation.²⁹ There are currently four techniques that can be used to assess cerebral oxygenation: jugular venous oxygen saturation, positron emission tomography, near-infrared spectroscopy, and brain tissue oxygenation monitoring (PbtO₂). Their strengths and weaknesses are the subject of several recent reviews.^30,³¹ The selection among these forms of oxygenation monitoring is focused on the appropriateness of focal or global monitoring, the location of the monitor in relation to the injury, and the intermittent or continuous nature of the monitoring. The use of PbtO₂, as assessed by the intraparenchymal polarographic oxygen probe, has the advantage of directly monitoring the zone of injury and thus earlier detection of perfusion abnormalities that may impact global cerebral oxygenation later. This may also allow the rescue of watershed areas of perfusion. However, there is controversy regarding the appropriate placement of such monitors. Insertion of the probe into non injured areas yields data equivalent to global assessments of cerebral oxygenation. Consequently, close attention should be paid to the location of the catheter in relation to the injury in interpretation and use of PbtO₂ results. Jugular venous oxygen saturation (SjO₂) is representative of global cerebral oxygen metabolism, but technically it is difficult to obtain reproducible results. Cerebral tissue oxygenation values of <20 mmHg are targeted for intervention based on Brain Trauma Foundation (BTF) guidelines but only at level III evidence.³² PbtO₂ can be increased by increasing the FiO₂/PaO₂ ratio and by reducing cerebral metabolic requirements for oxygen (CMRO₂) using brain temperature control with active cooling and metabolic rate control with sedation and adequate feeding. Additional interventions such as volume infusion, transfusion, and inotropic support directed at improving cardiac output can also be used to increase oxygen delivery.³³

Brain inflammation after injury contributes to impaired oxygenation and perfusion, but currently its management has not translated to successful clinical management. However, the use of cerebral microdialysis (MD) and the measurement of biochemical markers (lactate, glutamate, pyruvate, glycerol and glucose) of cerebral inflammation and metabolism do contribute towards early warnings of impending hypoxia/ischaemia and neurological deterioration, and this may allow timely implementation of neuroprotective strategies. Elevation of the lactate/pyruvate ratio is typically seen in cerebral ischaemia and mitochondrial dysfunction, and has been used to tailor therapy.³⁴ However, MD reflects only local tissue biochemistry and the accurate placement of the catheter is crucial. Furthermore, because there are wide variations in measured variables, trend data are more important than absolute values. Although MD is used routinely in a few centres it has not yet been introduced into widespread clinical practice and, at present, should be considered a research tool for use in specialist centres. MD has the potential to become established as a key component of multi-modality monitoring during management of acute brain injury during neurointensive care.

Management of Intracranial Hypertension

Raised ICP is treated by removing mass lesions and/or increasing the volume available for expansion of injured tissue. This may be achieved by reducing one of the other available intracranial fluid volumes:

1. CSF by ventricular drainage (as discussed previously)

2. cerebral blood volume by hyperventilation, osmotic diuretic therapy or hypothermia

3. brain tissue water content by osmotic diuretic therapy

4. removing swollen and irreversibly injured brain

5. increasing cranial volume by craniotomy decompression.

Each modality will be discussed in terms of its physiological effect, efficacy and potential use for prevention of secondary brain injury.

Hyperventilation

Hyperventilation reduces PaCO₂ and will reduce ICP by vasoconstriction induced by alkalosis but it also decreases cerebral blood flow.³⁵ The fall in ICP parallels the fall in CBV. Hyperventilation decreases regional blood flow to hypoperfused areas of the brain. Thus, generally PaCO₂ should be maintained in the low normal range of about 35 mmHg. Hyperventilation should be utilised only when ICP elevations are refractory to other methods and when brain tissue oxygenation is in the normal range.³⁶ The BTF Guidelines recommend hyperventilation therapy only for brief periods when there is no neurological deterioration or for longer periods when ICP is refractory to other therapies.³²

Osmotherapy

Acute administration of an osmotic such as mannitol or hypertonic saline produces a potent antioedema action, primarily on undamaged brain regions with an intact BBB. This treatment causes the movement of water from the interstitial and extracellular space into the intravascular compartment, thereby improving intracranial compliance or elastance. In addition to causing ‘dehydration’ of the brain, osmotic agents have been shown to exert beneficial non-osmotic cerebral effects, such as augmentation of cerebral blood flow (by reducing blood viscosity, resulting in enhanced oxygen delivery), free radical scavenging, and diminishing CSF formation and enhancing CSF reabsorption.³⁷

The BTF recommends mannitol in intracranial hypertension in bolus administration, keeping the serum osmolarities greater than 320 mOsm/L, plasma Na+ <160 mmol/L and avoiding hypovolaemia. Urine output after mannitol administration needs to be replaced, generally with normal saline. Brain free water is increased with 5% dextrose and hyperglycaemia; hence these need to be avoided. The use of frusemide in conjunction with mannitol promotes a synergistic action, particularly in patients refractory to mannitol alone. Recent studies now suggest that mannitol and frusemide have antiepileptic properties ³⁸ and that mannitol has a role in ischaemic stroke.

Intravenous hypertonic saline (HTS) increases cerebral perfusion and decreases brain swelling and inflammation more effectively than conventional resuscitation fluids. HTS behaves like 20% mannitol in acute cerebral oedema but maintains haemodynamic status. However, unlike HTS, mannitol induces a diuresis, which is relatively contraindicated in patients with both TBI and hypovolaemia as it may worsen intravascular volume depletion and decrease cerebral perfusion. Therefore, despite theoretical advantages of HTS resuscitation in patients with TBI, an Australian randomised controlled trial ³⁹ found no difference in outcome between HTS and other resuscitation fluids in prehospital resuscitation. However, in many Australian and New Zealand intensive care units, HTS is used as a preferred alternative to mannitol in patients with raised ICP.

Normothermia

Hyperthermia occurs in up to 40% of patients with ischaemic stroke and intracerebral haemorrhage and in 40–70% of patients with severe TBI or aneurysmal subarachnoid haemorrhage. Hyperthermia is independently associated with increased morbidity and mortality after ischaemic and haemorrhagic stroke, and in subarachnoid haemorrhage and TBI patients temperature elevation has been linked to raised intracranial pressure. Temperature elevations as small as 1–2°C above normal can aggravate ischaemic neuronal injury and exacerbate brain oedema.⁴⁰ Mild hypothermia protects numerous tissues from damage during ischaemic insult.⁴¹ The use of paracetamol, cooling blankets, ice packs, evaporative cooling and new cooling technologies may be useful in maintaining normothermia. Hyperaemia (increased blood flow) may occur during rewarming, resulting in acute brain swelling and rebound intracranial hypertension.⁴² In an original study, Marion and colleagues.⁴³ demonstrated a higher mortality rate than in more recent trials,⁴⁴ possibly due to rapid rewarming and rebound hyperaemia and cerebral oedema.

Maintenance of body temperature at 35°C may be optimal.⁴⁵ Intracranial pressure falls significantly at brain temperatures below 37°C but no difference was observed at temperatures below 35°C. Cerebral perfusion pressure peaks at 35–36°C and decreases with further falls in temperature.⁴⁵ At a temperature below 35°C, both oxygen delivery and oxygen consumption decrease. Cardiac output decreases progressively with hypothermia. Therefore, cooling to 35°C may reduce intracranial hypertension and maintain sufficient CPP without associated cardiac dysfunction or oxygen debt.⁴⁶ As the temperature is lowered from 34°C to 31°C, the volume of IV fluid infusion and inotrope requirements increase substantially and, despite such interventions, mean arterial pressure decreases. At 31°C serum potassium, white blood cell count and platelet counts are diminished.⁴⁷ Thus, it seems that hypothermia to 35°C may be optimal.

Corticosteroids

Excessive inflammation has been implicated in the progressive neurodegeneration that occurs in multiple neurological diseases, including cerebral ischaemia. The efficacy of glucocorticoids is well established in ameliorating oedema associated with brain tumours and in improving the outcome in subsets of patients with bacterial meningitis. Despite encouraging experimental results, clinical trials of glucocorticoids in ischaemic stroke, intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage and traumatic brain injury have not shown a definite therapeutic effect. Furthermore, the CRASH (corticosteroid randomisation after significant head injury) trial demonstrated an increased risk of death from use of steroids from all causes within two weeks of injury, and was stopped early.⁴⁸ Consequently, the BTF Guidelines state that the use of steroids is not recommended for TBI.³²

The evidence supporting glucocorticoid therapy for spinal cord injury is controversial; however, methylprednisolone continues to be widely employed in this setting (this is discussed further below under Spinal injury management).

Barbiturates and sedatives

The BTF Guidelines state that high-dose barbiturate therapy may be considered in haemodynamically-salvageable severe TBI patients with intracranial hypertension refractory to maximal medical and surgical interventions.⁴⁹ The utilisation of barbiturates for the prophylactic treatment of ICP has not been indicated. Barbiturates exert cerebral protective and ICP-lowering effects through alteration in vascular tone, suppression of metabolism and inhibition of free radical-mediated lipid peroxidation. Barbiturates may effectively lower cerebral blood flow and regional metabolic demands. The lower metabolic requirements decrease cerebral blood flow and cerebral volume. This results in beneficial effects on ICP and global cerebral perfusion. Barbiturates within the BTF guidelines are now included under the heading of Anaesthetics, Analgesics and Sedatives and these also recommend (Level II) that it is beneficial to minimise painful or noxious stimuli as well as agitation as they may potentially contribute to elevations in ICP. Therefore propofol is recommended for the control of ICP, but does not improve mortality or six-month outcome. High dose propofol should be avoided as it can produce significant morbidity.⁴⁹

Surgical interventions

The European TBI Guidelines suggest that operative management be considered for large intracerebral lesions within the first four hours of injury. The use of unilateral craniectomy after the evacuation of a mass lesion, such as an acute subdural haematoma or traumatic intracerebral haematoma, is accepted practice. Surgery is also recommended for open compound depressed skull fractures that cause a mass effect.⁵⁰

Decompressive craniectomy, for refractory intracranial hypertension, has been performed since 1977, with a significant reduction in ICP for both TBI ⁵⁰ and ischaemic stroke.⁵¹ In 2011 a multi-centre prospective randomised trial of early decompressive craniectomy in patients with severe traumatic brain injury reported that in adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but surprisingly was associated with more unfavorable outcomes at both 6 and 12 months using the Extended Glasgow Outcome Scale.⁵²

Prevention of Cerebral Vasospasm

Cerebral vasospasm is a self-limited vasculopathy that develops 4–14 days after subarachnoid haemorrhage (SAH) and/or TBI (see Figure 17.5). Oxyhaemoglobin, a product of haemoglobin breakdown, probably initiates vasoconstriction, leading to smooth-muscle proliferation, collagen remodelling and cellular infiltration of the vessel wall. The resulting vessel narrowing can lead to ischaemia. SAH patients develop cerebral vasospasm, and about one-third develop symptomatic vasospasm, which is associated with neurological signs and symptoms of ischaemia. Posttraumatic brain injury cerebral vasospasm occurs in approximately 10–15% of patients.

FIGURE 17.5 Pathophysiology of traumatic brain injury.

Calcium antagonists, such as nimodipine, have not been effective in TBI subarachnoid haemorrhage with vasospasm, and recent studies have suggested that calcium antagonists even prevent neurogenesis after TBI. Nimodipine has demonstrated effectiveness in the treatment of vasospasm in aneurysmal SAH and is now an option for recommended practice. An initial study of nimodipine in patients with TBI demonstrated no difference in outcome, and a Cochrane Systematic Review supports this conclusion.⁵³

Magnesium may prevent cerebral vasospasm through several mechanisms. Increased ATP entry into cells could decrease ischaemic depolarisation and limit infarction size. Magnesium also both inhibits the presynaptic release of excitatory amino acids and is a non-competitive antagonist to postsynaptic NMDA receptors. The drug can also cause vasodilation by inhibiting calcium channel-mediated smooth muscle contraction. Finally, magnesium increases cardiac contractility, which may improve cerebral perfusion in dysautoregulated brain tissue. TBI animal studies have demonstrated promising neuroprotection, but this is still to be confirmed in clinical trials.⁵⁴ Magnesium, however, does not cross the intact BBB easily, limiting its effect to injury and disease with leaky BBB. A randomised clinical trial of aneurysmal SAH patients receiving magnesium found that IV magnesium infusion reduced the frequency of delayed cerebral ischaemia in patients with aneurysmal SAH and subsequent poor outcome.⁵⁵

In SAH, more aggressive intravascular volume expansion and induced hypertension are used in conjunction with haemodynamic monitoring. By maintaining haematocrit at 30–33%, a shift in the oxygen dissociation curve is avoided.⁵⁶ Haemodilutional therapy increases collateral circulation at the site of haemorrhage, while reducing aggregation of erythrocytes where small vessel spasm has occurred. However, there is some emerging physiological data suggesting that normovolaemic hypertension may be the component most likely to increase cerebral blood flow after subarachnoid haemorrhage. In contrast, hypervolaemic haemodilution is associated with increased complications and might also lower the haemoglobin to excessively low levels.⁵⁶ Also in aneurysmal SAH, endovascular therapies, such as intra-arterial papaverine infusion, are employed. Papaverine acts immediately and increases arterial calibre and cerebral blood flow, but its effects are short-lived. Balloon angioplasty is particularly effective as a durable means of alleviating arterial narrowing and preventing stroke in patients with symptomatic vasospasm after aneurysmal SAH. The timing of endovascular intubation and use of inotropes in patients with cardiac dysfunction are unresolved issues.⁵⁷

Other Neuroprotective Measures

Many promising animal studies have not transferred to successful human clinical trials and there have been a plethora of different mechanisms that block single molecular processes but do not address the complex molecular processes involved in brain injury. Currently there is interest in antioxidants (Tirilazad mesylate), leukocyte adhesion inhibition (Enlimomab), and continued interest in erythropoietin, progesterone and their metabolites and receptors as neuroprotective targets and treatments.

Central Nervous System Disorders

CNS disorders include brain and/or spinal injury from trauma, infection or immune conditions. The pathophysiology and aetiology of these disorders are discussed here, including management of these conditions.

Traumatic Brain Injury

Head injury is a broad classification that includes injury to the scalp, skull or brain. Traumatic brain injury (TBI) is the most serious form of head injury. The range of severity of TBI is broad, from concussion through to post coma unresponsiveness. The Australian age-standardised incidence rate of TBI in 2004/5 was about 150 per 100,000 population. Approximately 90,211 Australians ^58,⁵⁹ and 16,000–22,500 New Zealanders⁶⁰ are hospitalised for TBI every year. Males aged 15–19 years have the highest incidence rates and suffer TBI at a rate almost three times that of women. The very young (0–4 years) and the very old (over 85 years) are also at increased risk.⁶¹ Indigenous Australians suffer TBI at almost three times the rate (410 per 100,000) of non-Indigenous Australians.⁶² It is estimated that 40,000 Australians are living with a disability as a result of TBI.⁶³ Despite definition issues relating to TBI epidemiology, there was an average annual decline of 5% in the TBI rate to 1997/98 but the incidence has increased since then. An Australian and new Zealand epidemiological study⁶⁴ of TBI (see Research vignette) found that the mean age was 41.6 years; 74.2% were men; 61.4% were due to vehicular trauma, 24.9% were falls in elderly patients, and 57.2% had severe TBI (Glasgow Coma Scale score ≤8). Twelve-month mortality was 26.9% in all patients and 35.1% in patients with severe TBI.

Aetiology

In Australia, motor vehicle-related trauma accounts for about two-thirds of moderate and severe TBI, with falls and assaults being the next most common causes. New Zealand has a higher proportion of recreational injuries compared to vehicle-related trauma. Sporting accidents and falls account for a far greater percentage of mild injuries. Alcohol is associated with up to half of all cases of TBI. In Australia and New Zealand, blunt trauma (falls and vehicle-related), rather than penetrating (stabbing and firearms) or blast, is the predominant mechanism of injury.⁶³ The transfer of energy to the brain tissue actually causes the damage and is a significant determinant in the severity of injury (and routinely noted in ED on admission). In the past 10 years, the introduction of safer car designs, airbags and other road traffic initiatives (e.g. redesigning hazardous intersections, driver education campaigns, random breath testing and reducing speed limits) have decreased the overall number of road fatalities; improvements in retrieval, neurosurgery and intensive care in the past few decades have enabled many people to survive injuries that would previously have been fatal. Research into and prevention of falls and shaken-baby syndromes has had a small impact on incidence reduction.^65,⁶⁶

Pathophysiology of TBI

TBI is a heterogeneous pathophysiological process (see Figure 17.5). The mechanisms of injury forces inflicted on the head in TBI produce a complex mixture of diffuse and focal lesions within the brain.⁶⁷ Damage resulting from an injury can be immediate (primary) or secondary in nature. Secondary injury results from disordered autoregulation and other pathophysiological changes within the brain in the days immediately after injury. Urgent neurosurgical intervention for intracerebral, subdural or extradural haemorrhages can mitigate the extent of secondary injury. Scalp lesions can bleed profusely and quickly lead to hypovolaemic shock and brain ischaemia. Cerebral oedema, haemorrhage and biochemical response to injury, infection and increased ICP are among the commonest physiological responses that can cause secondary injury. Tissue hypoxia is also of major concern and airway obstruction immediately after injury contributes significantly to secondary injury. Poor cerebral blood flow, as a result of direct (primary) vascular changes or damage, can lead to ischaemic brain tissue, and eventually neuronal cell death.⁶⁸ Systemic changes in temperature, haemodynamics and pulmonary status can also lead to secondary brain injury (Figure 17.6). In moderate to severe and, occasionally in mild, injury, cerebral blood flow is altered in the initial 2–3 days, followed by a rebound hyperaemic stage (days 4–7) leading to a precarious state (days 8–14) of cerebral vessel unpredictability and vasospasm.⁶⁴ More than 30% of TBI patient have AN dysfunction characterised by episodes of increased heart rate, respiratory rate, temperature, blood pressure, muscle tone, decorticate or decerebrate posturing, and profuse sweating.⁷⁰ Lack of insight into these processes and implementing early weaning of supportive therapies can lead to significant secondary insults.

FIGURE 17.6 Conceptual changes in cerebral blood flow and intracranial pressure (ICP) over time following traumatic brain injury: (A) cytotoxic oedema; (B) vasogenic oedema; (C) cerebral blood flow CPP = cerebral perfusion pressure; MAP = mean arterial pressure.

Focal injury

Because of the shape of the inner surface of the skull, focal injuries are most commonly seen in the frontal and temporal lobes, but they can occur anywhere. Contact phenomena are commonly superficial and can generate superficial or contusional haemorrhages through coup and contrecoup mechanisms.⁷¹ Cerebral contusions are readily identifiable on CT scans, but may not be evident on day 1 scans, becoming visible only on days 2 or 3. Deep intracerebral haemorrhages can result from either focal or diffuse damage to the arteries.

Diffuse injury

Diffuse (axonal) injury (DAI) refers to the shearing of axons and supporting neuroglia; it may also traumatise blood vessels and can cause petechial haemorrhages, deep intracerebral haematomas and brain swelling.⁷¹ DAI results from the shaking, shearing and inertial effects of a traumatic impact. Mechanical damage to small venules as part of the BBB can also trigger the formation of haemorrhagic contusions. This vascular damage may increase neuronal vulnerability, causing post-traumatising perfusion deficits and the extravasation of potentially neurotoxic blood-borne substances. The most consistent effect of diffuse brain damage, even when mild, is the presence of altered consciousness. The depth and duration of coma provide the best guide to the severity of the diffuse damage. The majority of patients with DAI will not have any CT evidence to support the diagnosis. Other clinical markers of DAI include the high speed or force strength of injury, absence of a lucid interval, and prolonged retrograde and anterograde amnesia. Figure 17.7 contrasts CT scans with haematoma formation and DAI.

FIGURE 17.7 Extradural haematoma and a subtle subdural haematoma (left), subdural haematoma (middle left), diffuse axonal injury (middle right), and combination injuries (right).

Mild TBI

Mild TBI often presents as a component of multitrauma or sports injury and can be overlooked at the expense of other peripheral injuries. Risk factors such as vomiting, dizziness, facial and skull fractures; including the loss of CSF from the nose or the ear, will categorise those needing further surveillance. Routine head CT and assessment of PTA are recommended to exclude mass lesions and DAI. Diagnosis and management in the acute phase of mild TBI is as crucial to functional outcome and rehabilitation as in moderate-to-severe TBI.⁷²

Skull fractures

Skull fractures are present on CT scans in about two-thirds of patients after TBI. Skull fractures can be linear, depressed or diastatic, and may involve the cranial vault or skull base. In depressed skull fractures the bone fragment may cause a laceration of the dura mater, resulting in a cerebrospinal fluid leak.⁷³ Basal skull fractures include fractures of the cribriform plate, frontal bones, sphenoid bones, temporal bone and occipital bones. The clinical signs of a basal skull fracture may include: CSF otorrhoea or rhinorrhoea, haemotympanum, postauricular ecchymoses, periorbital ecchymoses, and injury to the cranial nerves: VII (weakness of the face), VIII (loss of hearing), olfactory (loss of smell), optic (vision loss) and VI (double vision).

Nursing Practice

The surveillance and prevention of secondary injury is the key to improving morbidity and mortality outcomes ⁶⁹ (see Table 17.1). It should be noted that in a post hoc in analysis of saline critically ill patients with TBI, fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline.⁷⁴ Interventions are targeted at maintaining adequate cerebral blood flow and minimising oxygen consumption by the brain in order to prevent ischaemia. The anticipation and prevention of systemic complications are also of vital importance. Assessment is vital to establish priorities in care and is discussed in Chapter 16.

Nursing management of the neurologically impaired, immobilised, mechanically ventilated patient is described in Table 17.2 and is an adaptation of the current guidelines³² (see Table 17.3) to clinical practice (see Online resources for TBI-related protocols). In all TBI multitrauma patients, disability and exposure/environmental control assessment includes the routine trauma series of X-rays, namely chest, pelvis and cervical spine (lateral, anteroposterior and odontoid peg views). These should be reviewed by a radiologist and areas of concern, particularly in the upper and lower regions of the cervical spine, should be clarified with further investigations such as CT scans. Isolated TBI requires CT scanning of the head and upper spine. The management of TBI should include spinal precautions until spinal injury is definitively excluded.

TABLE 17.2 Nursing management of the neurologically impaired, immobilised, mechanically-ventilated patient

Nursing domain	Nursing outcome	Nursing interventions
Ventilation and oxygenation	• Airway patent. • Arterial pH, PaO₂, PbtO₂, SaO₂ within normal range. • PaCO₂ & ETCO₂ within normal range. • Lungs clear to auscultation. • No evidence of atelectasis or aspiration. • Chest X-ray clear of pathology.

• Assess ventilation parameters: ensure ET patency and position.

• Assess bilateral chest movement: listen for airway obstruction or ET cuff leak; auscultate for air entry.

• Assess chest X-ray.

• Adequate sedation and ventilation to maintain PbtO₂, ICP, CPP.

• Suction only as necessary: preoxygenate, avoid prolonged coughing; effective technique.

• Avoid ICP complications of PEEP.

• Position to avoid aspiration.

• Provide meticulous oral hygiene.

Mobility/safety

• Cerebral blood flow uncompromised.

• Minimal and transient changes in PbtO₂–ICP–CPP and return to desired parameters within 5 min of nursing intervention.

• Patient integument maintained and infection free: skin, mucous membranes, cornea, wounds, invasive lines

• Complications of immobility prevented: DVT, pneumonia, muscle strength.

• Patient safety enabled, preventing nosocomial infection, secondary brain injury, self-harm.

• Nutrition prescribed according to patient need.

• Healing defined and uneventful.

• Haemodynamic stability maintained. Brain ischaemia and intracranial hypertension controlled.

• Nursing interventions planned for minimal disturbance; efficient intervention.

• Pressure-relieving mattress: allows minimal position changes for integument protection, with minimal CMRO₂ requirement, sequential compression device for venous return.

• Hygiene maintained: assess integument, assess cornea, assess mucous membranes.

• Maintain infection control interventions with invasive devices and wounds.

• Administer preventive plan of treatment with vigilance and prediction.

• Enable communication with other health professionals.

• Chemical and physical restraint applied per assessment and prescription, within institutional policy.

Psychological/family

• Family and significant others informed and supported.

• Psychological wellbeing of patient in recovery

• The patient will feel safe.

• Refer and coordinate information and service provision from other health professionals.

• The provision of quality, informed and inclusive care to the patient provides family and significant others with the confidence that the nurse advocates for the patient in their place.

• Ensure psychological assessment and administer prescribed therapy for delirium and post traumatic stress.

• Nursing interventions planned to allow for rest and recovery.

• Administer coordinated rehabilitation strategies.

TABLE 17.3 Summary of guidelines of the management of severe traumatic brain injury from the Brain Trauma Foundation ³²

Spinal Cord Trauma

In Australia, nearly 11,000 people live with a disability from spinal cord injury (SCI), with an age-adjusted incidence rate of 13.6 per million of the population.⁷⁵ In 2007–08 there were 362 new spinal cord injuries, the majority of which (79%) were due to traumatic causes. SCI were most frequent in the 15–24 year age group (30%), although trends show a significant increase in the average age at injury from 38 years in 1995–96 to 42 years in 2007–08. Males accounted for 84% of traumatic SCI. Transport-related injuries (46%) and falls (28%) were the main contributors to traumatic SCI.

In 2001–02 New Zealand had an unadjusted rate of 27 per million and has one of the highest SCI incidences in the Western world, related mostly to snowboarding and rugby.⁶⁰ SCI occurs three times more often in men, and the incidence among those aged 15–34 years is roughly double the rate in those 35 years and over. More than half of the SCIs are due to vehicular trauma and a quarter due to motorcycle crashes. Falls account for nearly a third of the injuries, with nearly half occurring in older people. Recreational and sporting injuries account for 15% of SCI, and 19% are work-related. Of all SCI cases, 51% resulted in complete tetraplegia (loss of function in the arms, legs, trunk and pelvic organs). The predominant risk factors for SCI include age, gender, and alcohol and drug use. The vertebrae most often involved in SCI are the 5th, 6th and 7th cervical (neck), the 12th thoracic, and the 1st lumbar. These vertebrae are the most susceptible because there is a greater range of mobility in the vertebral column in these areas.⁷⁶ Damage to the spinal cord ranges from transient concussion or stunning (from which the patient fully recovers) to contusion, laceration and compression of the cord substance (either alone or in combination), to complete transection of the cord (which renders the patient paralysed below the level of the injury).

Mechanisms of Injury

Cervical injury can occur from both blunt and penetrating trauma but in reality is a combination of different mechanisms of acceleration and deceleration with and without rotational forces and axial loading.⁷⁷ An illustrative example is a diving injury, caused by a direct load through the head and cervical spine. In reality, cervical trauma is produced by a combination of these mechanisms as listed below.

• Hyperflexion: These injuries usually result from forceful decelerations and are often seen in patients who have sustained trauma from a head-on motor vehicle collision (MVC) or diving accident. The cervical region is most often involved, especially at the C5–C6 level.

• Vertical compression or axial loading: This typically occurs when a person lands on the feet or buttocks after falling or jumping from a height. The vertebral column is compressed, causing a fracture that result in damage to the spinal cord.

• Hyperextension: This is the most common type of injury. Hyperextension injuries can be caused by a fall, a rear-end MVC, or hit on the head (e.g. during a boxing match). Hyperextension of the head and neck may cause contusion and ischaemia of the spinal cord without vertebral column damage. Whiplash injuries are the result of hyperextension. Violent hyperextension with fracture of the pedicles of C2 and forward movement of C2 on C3 produces the ‘Hangman’s fracture’.

• Extension–rotation: Rotational injuries result from forces that cause extreme twisting or lateral flexion of the head and neck. Fracture or dislocation of vertebrae may also occur. The spinal canal is narrower in the thoracic segment relative to the width of the cord, so when vertebral displacement occurs it is more likely to damage the cord. Until the age of 10, the spine has increased physiological mobility due to lax ligaments, which affords some protection against acute SCI. Elderly patients are at a higher risk due to osteophytes and narrowing of the spinal canal.

Classification of Spinal Cord Injuries

SCIs can be broadly classified as complete or incomplete.⁷⁸ The diagnosis of complete SCI cannot be made until spinal cord shock resolves. If the bulbocavernosus reflex (BCR) is present (involuntary contraction of the rectal sphincter after squeezing the glans penis or clitoris or tugging on an indwelling urinary catheter) it indicates a complete injury. If, after the return of the BCR, the patient has some sensation below the level of injury, he/she is considered to be sensory-incomplete. If the BCR has returned and the patient has some motor function and sensation below the level of injury, he/she is considered to be sensory- and motor-incomplete. There are four incomplete SCI syndromes as follows:

• Anterior cord syndrome: Injury to the motor and sensory pathways in the anterior parts of the spine; thus patients are able to feel crude sensation, but movement and detailed sensation are lost in the posterior part of the spinal cord. Clinically, the patient usually has complete motor paralysis below the level of injury (corticospinal tracts) and loss of pain, temperature, and touch sensation (spinothalamic tracts), with preservation of light touch, proprioception and position sense. The prognosis for anterior cord syndrome is the worst of all the incomplete syndrome prognoses.

• Posterior cord syndrome: This is usually the result of a hyperextension injury at the cervical level and is not commonly seen. Position sense, light touch and vibratory sense are lost below the level of the injury.

• Central cord syndrome: Injury to the centre of the cervical spinal cord, producing weakness, paralysis and sensory deficits in the arms but not the legs. Hyperextension of the cervical spine is often the mechanism of injury, and the damage is greatest to the cervical tracts supplying the arms. Clinically, the patient may present with paralysed arms but with no deficit in the legs or bladder.

• Brown-Séquard syndrome: This involves injury to the left or right side of the spinal cord. Movements are lost below the level of injury on the injured side, but pain and temperature sensation are lost on the opposite side of injury. The clinical presentation is one in which the patient has either increased or decreased cutaneous sensation of pain, temperature and touch on the same side of the spinal cord at the level of the lesion. Below the level of the lesion on the same side, there is complete motor paralysis. On the patient’s opposite side, below the level of the lesion, there is loss of pain, temperature and touch, because the spinothalamic tracts cross soon after entering the cord.

Pathophysiology

SCIs can be separated into two categories: primary injuries and secondary injuries. Primary injuries are the result of the initial insult or trauma, and are usually permanent. The force of the primary insult produces its initial damage in the central grey matter of the cord. Secondary injuries are usually the result of a contusion or tear injury, in which the nerve fibres begin to swell and disintegrate. Secondary neural injury mechanisms include ischaemia, hypoxia and oedema. Ischaemia, the most prominent post-SCI event, may occur up to 2 hours post-injury and is intensified by the loss of autoregulation of the spinal cord microcirculation.⁷⁸ This will decrease blood flow, which is then dependent on the systemic arterial pressure in the presence of hypotension or vasogenic spinal shock. Oedema develops at the injured site and spreads into adjacent areas. Hypoxia may occur as a result of inadequate airway maintenance and ventilation. Immune cells, which normally do not enter the spinal cord, engulf the area after a spinal cord injury and release regulatory chemicals, some of which are harmful to the spinal cord. Highly reactive oxidising agents (free radicals) are produced, which damage the cell membrane and disrupt the sodium–potassium pump.

Free-radical production and lipid peroxidation lead to vasoconstriction, increased endothelial permeability and increased platelet activation. A secondary chain of events produces ischaemia, hypoxia, oedema and haemorrhagic lesions, which in turn result in the destruction of myelin and axons. Autoregulation of spinal cord blood flow may be impaired in patients with severe lesions or substantial oedema formation. These secondary reactions, believed to be the principal causes of spinal cord degeneration at the level of injury, are now thought to be reversible 4–6 hours after injury. Therefore, if the cord has not suffered irreparable damage, early intervention is needed to prevent partial damage from developing into total and permanent damage.⁸⁰

Spinal shock occurs with physiological or anatomical transection or near-transection of the spinal cord; it occurs immediately or within several hours of a spinal cord injury and is caused by the sudden cessation of impulses from the higher brain centres.⁷⁹ It is characterised by the loss of motor, sensory, reflex and autonomic function below the level of the injury, with resultant flaccid paralysis. Loss of bowel and bladder function also occurs. In addition, the body’s ability to control temperature (poikilothermia) is lost and the patient’s temperature tends to equilibrate with that of the external environment.

Neurogenic spinal shock occurs as a result of mid- to upper-level cervical injuries and is the result of sympathetic vascular denervation and peripheral vasodilation. The loss of spinal cord vasculature autoregulation occurs, causing the blood flow to the spinal cord to be dependent on the systemic blood pressure. Signs and symptoms include hypotension, severe bradycardia, and loss of the ability to sweat below the level of injury. The same clinical findings pertaining to disruption of the sympathetic transmissions in spinal shock occur in neurogenic shock.⁷⁸

Investigations and alignment

Following the initial assessment of the patient, detailed diagnostic radiography defines the bone damage and compression of the spinal cord. First, lateral, anteroposterior, odontoid and possibly oblique cervical spine radiographs are obtained. If there is no evidence of injury, flexion and/or extension views may be considered. If any of these radiographs suggest cervical spine abnormalities, specific radiological procedures such as cervical myelography, high-resolution CT scan or magnetic resonance imaging will identify fractures, dislocation of bony fragments, and spinal cord contusion.⁸² In patients with a dislocated cervical fracture, decompression and anatomical bony realignment may be achieved with traction forces applied manually, or with halo or Gardner–Wells systems under radiological control. If the anatomical bony alignment procedures and traction forces fail to decompress the cord, surgical intervention to remove the lesion is required. The timing of surgical intervention remains controversial. While urgent surgical decompression or internal stabilisation should be performed in all patients with deteriorating neurological status, some centres tend to defer surgical treatment in patients with spinal cord injury but stable neurological deficit.

Concepts of Neuroprotection and Regeneration

There have been many negative SCI clinical trials in regard to neuroprotection with the exception of methylprednisolone within 8 hours after SCI, which has shown some beneficial effect.⁷⁷ The failure of these neuroprotective agents has been attributed to the attempt of blocking only one molecular pathway of a complex range of SCI molecular mechanisms. However, there has been renewed interest in regeneration which involves stem cell transplantation or similar restorative approaches designed to optimise spontaneous axonal growth and myelination but is still in its infancy in Australia and NZ due to limiting legislation in regard to stem cell research.

Collaborative Management

Patients with acute cervical spinal cord injury require ICU monitoring, observation and support of ventilation, a nasogastric tube to reduce abdominal distension and risk of aspiration, a urinary catheter and thermal maintenance.

• Tracheostomy is indicated in high cervical spine injury and ischaemia, sometimes only while the early oedema is resolving.

• Spinal alignment and immobilisation requires careful positioning with dedicated neck support by experienced clinicians.

• Shoulder and lumbar support pillows are often prescribed. Pressure-relief mattresses must be suitably designed for spine immobilisation and when prescribed can be tilted to facilitate ventilation.

• Meticulous integument and bowel care are indicated with daily protocols for regular stool softeners and peristaltic stimulants essential for the prevention of autonomic dysreflexia and autonomic nerve dysfunction.

• Early nutritious feeding is essential, whether oral or enteric; however, aspiration must be prevented. The supplementation of feeding with high-energy protein fluids to match the catabolic state assists with recovery (see Chapter 19).

• Hyperglycaemia is associated with increased inflammation and must be controlled to less than 10 mmol/Hg, avoiding hypoglycaemia.⁸⁴

• The concept of pain relief and sedation in patients with spinal cord injury is based on the maintenance of coupling between metabolism and spinal cord blood flow while achieving hypnosis, analgesia and a ‘relaxed cord’. This concept includes maintenance of normal to high systemic perfusion pressures, normoxia and normocapnia.

• Psychological and empathetic support is essential and appropriate referral for grieving and stress is paramount. Rehabilitation counselling and planning starts at the acute stage in order to give the family unit some future focus and hope.

See the Online resources for specific protocols related to spinal injury.

Cerebrovascular Disorders

Cerebral vascular disorders include cerebrovascular disease and cerebral vascular accidents (stroke). A stroke (acute brain injury of vascular origin) may be either ischaemic or haemorrhagic and is defined as an interruption of the blood supply to any part of the brain, resulting in damaged brain tissue.

Stroke

Stroke is the primary cerebrovascular disorder in Australia and New Zealand and is still the third-leading cause of death. Every year approximately 40,000 people in Australia are admitted to hospital with a diagnosis of stroke; approximately 6000 New Zealanders suffer from a stroke every year and approximately 2000 deaths each year are attributable to stroke.^85,⁸⁶ The prevalence of stroke is higher among men than women (1.4% versus 1.0%). Almost 60% of people who have had a stroke are aged 65 years and over, while 18% are under the age of 55 years. Indigenous Australians have higher rates of death and illness from heart, stroke and vascular diseases than other Australians. In 2007–08, death rates were 2.6 times as high and hospitalisation rates 1.4 times as high as for other Australians.⁸⁵ Stroke is currently the biggest single cause of adult disability in Australasia. Strokes can be divided into two major categories: ischaemic (85%), in which vascular occlusion and significant hypoperfusion occur; and haemorrhagic (15%), in which there is extravasation of blood into the brain. Although there are some similarities between the two broad types of stroke, the aetiology, pathophysiology, medical management, surgical management and nursing care differ.

Aetiology

Hypertension is the leading risk factor for stroke. Other risk factors include diabetes, cardiac disease, previous cerebrovascular disease (transient ischaemic attack or stroke or myocardial infarction), age, sex, lipid disorders, excessive ethanol ingestion, elevated hematocrit, elevated fibrinogen and cigarette smoking. Cerebral arteriosclerosis predisposes indiuiduals to both ischaemic and haemorrhagic stroke. Smoking is the strongest risk factor for aneurysmal SAH. Atrial fibrillation, endocarditis and medications containing supplemental oestrogen are risk factors for embolic stroke. Seizures develop in approximately 10% of cases, usually appearing in the first 24 hours and more likely to be focal than generalised. Most patients with aphasia will have a cerebral infarction in the distribution of the left middle cerebral artery.⁸⁷

Ischaemic Stroke

Ischemic stroke compromises blood flow and energy supply to the brain, which triggers mechanisms that lead to cell death. Infarction occurs rapidly in the region of most severe ischaemia (termed ischaemic penumbra) and expands at the expense of the surrounding hypoxic tissue, from the centre to the periphery. Therapeutic strategies in acute ischaemic stroke are based on the concept of arresting the transition of the penumbral region into infarction, thereby limiting ultimate infarct size and improving neurological and functional outcome. Ischaemic stroke can be further categorised as middle cerebral artery occlusion, acute basilar occlusion, and cerebellar infarcts.⁸⁸

The management of an ischaemic stroke comprises four primary goals: restoration of cerebral blood flow (reperfusion), prevention of recurrent thrombosis, neuroprotection, and supportive care. The timing of each element of clinical management needs to be implemented in a decisive manner. Refer to Table 17.4 for classification and treatment strategies and to Online resources for specific ischaemic stroke protocols.

TABLE 17.4 Classification and type of ischaemic stroke and treatment options

Classification	Treatment options
Middle cerebral artery occlusion	Intravenous or intra-arterial tissue plasminogen activator (tPA). Exclusion criteria: >3 hours elapsed from stroke onset and widespread early infarct changes on CT scan. Tolerate autoprotective hypertension for perfusion of the ischaemic penumbra.

Acute basilar occlusion

Anticoagulation with intravenous heparin.

Thrombolysis up to 12 hours after onset.

Cerebellar infarcts

May be difficult to recognise because of the slow evolution of brainstem and cerebellar signs.

Aspirin, antihypertensives and conventional cerebral oedema strategies.

Haemorrhagic Stroke

Haemorrhagic strokes are caused by bleeding into the brain tissue, the ventricles or the subarachnoid space.⁸⁹ Primary intracerebral haemorrhage from a spontaneous rupture of small vessels accounts for approximately 80% of haemorrhagic strokes and is primarily caused by uncontrolled hypertension. Secondary intracerebral haemorrhage is associated with arteriovenous malformations (AVMs), intracranial aneurysms, or certain medications (e.g. anticoagulants and amphetamines). Symptoms are produced when an aneurysm or arteriovenous malformation (AVM) enlarges and presses on nearby cranial nerves or brain tissue or, more dramatically, when a blood vessel, aneurysm or AVM ruptures, causing intracerebral or subarachnoid haemorrhage. When an aneurysm ruptures, arterial pressure forces blood into the subarachnoid space between the arachnoid mater and the surface of the brain. Free blood then travels through the fissures into the basal cisterns and across the surface of the brain. When clotted, this blood can interfere with the circulation and reabsorption of cerebrospinal fluid (CSF), potentially causing obstructive hydrocephalus and raised intracranial pressure. The commonest cause is a leaking aneurysm in the area of the circle of Willis or a congenital AVM of the brain. Blood in the subarachnoid space is a powerful meningeal irritant, and it is this irritation that causes most of the initial signs and symptoms of SAH.

In intracerebral haemorrhage the bleeding is usually arterial and occurs most commonly in the cerebral lobes, basal ganglia, thalamus, brainstem (mostly the pons) and cerebellum. Occasionally, the bleeding ruptures the wall of the lateral ventricle and causes intraventricular haemorrhage, which is often fatal.⁸⁹

Normal brain metabolism is disrupted by the brain being exposed to blood. The sudden entry of blood into the subarachnoid space or brain parenchyma results in a rise in ICP, which then leads to compression and ischaemia resulting from the reduced perfusion pressure and vasospasm that often accompany intracerebral and subarachnoid haemorrhage. Depending on the severity, clinical findings include severe headache, nuchal rigidity, photophobia, nausea and vomiting, hypertension, ECG changes, pyrexia, cranial nerve deficits, visual changes, sensory or motor deficits, fixed and dilated pupils, seizures, herniation and sudden death.

The Factor Seven for Acute Hemorrhagic Stroke (FAST) multicentre international clinical trial recently reported that haemostatic therapy with recombinant activated factor VII (rFVIIa) reduced growth of the haematoma but did not improve survival or functional outcome after intracerebral haemorrhage.⁹⁰

Subarachnoid Haemorrhage

Admission to ICU is indicated for subarachnoid haemorrhage Hunt-Hess SAH severity Scale III (see Table 17.5) and greater to manage systemic complications, recognise and treat clinical deterioration, investigate the cause of the haemorrhage and to treat any underlying aneurysm or arteriovenous malformation. Resuscitation is directed towards maintaining cerebral perfusion pressure by ensuring adequate arterial blood pressure (often with the use of inotropes to produce relative hypertension although reactive hypertension is often present), ensuring a relatively high circulating blood volume (hypervolaemia), and producing relative haemodilution (’triple H therapy’).⁹¹

TABLE 17.5 Hunt-Hess scale for SAH

Score	Description
0	Unruptured; asymptomatic discovery
I	Asymptomatic or minimal headache with slight nuchal rigidity
II	Moderate to severe headache, nuchal rigidity; no neurological deficit other than cranial nerve deficit
III	Drowsiness, confusion, or mild focal deficit (e.g. hemiparesis), or a combination of these findings
IV	Stupor, moderate to severe deficit, possibly early decerebrate rigidity and vegetative disturbances
V	Deep coma, decerebrate rigidity, moribund appearance

Hypovolaemia occurs in 30–50% of patients, as does excessive hyponatraemia in 30% of patients. In the first six days, plasma volume decreases of greater than 10% can occur following SAH, thus increasing the risk of vasospasm and ischaemia. Women have been found to have more significant drops in blood volume than men following SAH.⁹² ‘Third space’ loss, insensible losses and blood loss account for this drop in fluid volume, as well as electrolyte disturbances.

Other aspects of management in the acute stages include suitable analgesia, seizure control, and treatment with nimodipine to prevent secondary ischaemia caused by vasospasm. Vasospasm often occurs 4–14 days after initial haemorrhage when the clot undergoes lysis (dissolution), increasing the chances of rebleeding. It is believed that early surgery to clip the aneurysm prevents rebleeding and that removal of blood from the basal cisterns around the major cerebral arteries may prevent vasospasm.^93,⁹⁴ (See previous section on Management of vasospasm.)

ICP monitoring and drainage of CSF via ventriculostomy is indicated in SAH but not in cerebral haemorrhage.⁸⁹ SAH causes increased sympathetic activation from the presence of haemoglobin in the subarachnoid space. This results in elevated catecholamine levels, which may result in focal myocardial necrosis, explaining the presence of inverted T waves, ST depression, prominent U waves, and Q-T intervals in more than 50% of patients. As cardiac function is one of the determinants for adequate cerebral blood flow, it is essential to identify such occurrences early and treat them accordingly.⁹⁵ Hyponatraemia occurs from alterations in atrial natriuretic factor (ANF) in response to sympathetic nervous system activation. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is primarily responsible for hyponatraemia in those with SAH, as is cerebral salt-wasting syndrome; however, both mechanisms are still relatively misunderstood.⁹⁰

Cerebral Venous Thrombosis

Cerebral venous thrombosis is particularly important to recognise because there is general consensus that early anticoagulation can result in good clinical outcomes.⁹⁶ MR and CT vascular imaging has made it easier to establish the diagnosis, but close monitoring of the patient is essential, as late deterioration can occur.

Collaborative Management of Stroke

Expected outcomes for patients with acute ischaemic and haemorrhagic stroke include prevention of secondary injury, of airway and respiratory complications, and the maintenance of haemodynamic stability. Timely assessment and intervention is paramount in the management of ischaemic stroke, especially regarding interventional pharmacology and prevention of cerebral haemorrhage. See Online resources for specific protocols related to stroke.

Atrial fibrillation and deep vein thrombosis (DVT) prevention (in ischaemic stroke) requires anticoagulation control. In haemorrhagic stroke, sequential compression device and stockings are indicated for DVT prophylaxis as anticoagulants are a risk factor for rebleeding. Maintenance of bowel and bladder function and prevention of integument complications, malnutrition, seizures and increasing neurological deficits are important goals. Environmental precautions are implemented to provide a non-stimulating environment, preventing rises in ICP and further bleeding.

Sensory perceptual and motor alterations need to be assessed in regard to effective communication and pain management. Rehabilitation and psychological support for the patient and significant others are integrated into the acute care phase for a smooth transition.

Infection and Inflammation

The CNS infections of major interest in the ICU are divided into those which affect the meninges (meningitis) and those which affect the brain parenchyma (encephalitis). They may be viral or bacterial in aetiology. There are also numerous medical conditions that may produce an encephalopathic illness which may mimic viral encephalitis. In patients recently returning from abroad, particular vigilance must be paid to the possibility of such non-viral infections as cerebral malaria, which may be rapidly fatal if not treated early. A number of metabolic conditions, including liver and renal failure and diabetic complications, may also cause confusion due to the manifestation of cerebral oedema. The possible role of alcohol and drug ingestion must always be considered.

Meningitis

The incidence of disease caused by Neisseria meningitidis remains an issue of public health concern in Australia and New Zealand. The introduction of a publicly funded program of selective vaccination with conjugate serogroup C meningococcal vaccine in 2004 has resulted in a significant reduction in the number of cases of meningococcal disease.⁹⁷ Nationally in 2008 only 15 serogroup C infections were identified and serogroup B accounted for 88% of all infections. New Zealand has one of the highest rates of meningococcal B disease in the developed world but the incidence has declined. There were 132 cases of meningococcal disease notified in 2009, which equates to a rate of 3.8 per 100,000 population. The number of confirmed cases was 117, giving a confirmation rate of 88.6% which is the third-equal-highest confirmation rate since 1991. Five deaths occurred in 2009, giving a case-fatality rate of 3.8%. Since 1991 a total of 265 deaths have been recorded, an overall case-fatality rate of 4.2%. The policy of giving antibiotics prior to hospital admission, implemented in 1995, reduced the case-fatality rate for those receiving antibiotics. In addition this rate has reduced from 470 cases in 2001, prior to the immunisation for meningococcal B commencing in 2004.⁹⁸ The incidence of meningococcal disease varies seasonally, rising in June and peaking in October each year. The highest incidence of meningococcal disease was for children aged 4 years and under. A secondary peak in the incidence of meningococcal disease is seen in adolescents and young adults.⁹⁹ However, during the H1N1 influenza epidemic there were several cases of H1N1 influenza-related meningitis. See Table 17.6 for CSF profiles for acute meningitis and encephalitis and Table 17.7 for the classification, treatment and clinical presentation of meningitis.

TABLE 17.6 Typical profiles of cerebrospinal fluid in acute meningitis and encephalitis

TABLE 17.7 Classification of acute meningitis

Acute meningitis	Bacterial – notifiable disease	Viral
Aetiology	Neisseria meningitis • Serogroups A,B,C – 90% invasive isolates • Serogroup B – most disease • Serogroup A – epidemic disease and indigenous haemophilus influenzae type B streptococcus pneumoniae listeria monocytogenes

Enteroviruses: 85–95% of cases

HIV infection can also present as aseptic meningitis

Postinfectious encephalomyelitis: may occur following a variety of viral infections, usually of the respiratory tract.

Cryptococcus neoformans

Fungal isolates

Pathophysiology

Rapid recognition and diagnosis of meningitis is imperative.

Quick and insidious progress of disease

Colonisation of mucosal surfaces (nasopharynx)

Haematogenous or contiguous spread

Specific antibodies important defence

Bacterial invasion of meninges: inflammatory response, breakdown of the BBB, cerebral oedema, intracranial hypertension

Vasculitis, spasm and thrombosis in cerebral blood vessels

The physical signs are not so marked and the illness is not as severe and prolonged as bacterial meningitis.

Viral infection of mucosal surfaces of respiratory or gastrointestinal tract

Virus replication in tonsillar or gut lymphatics

Viraemia with haematogenous dissemination to the CNS

Meningeal inflammation, BBB breakdown, cerebral oedema, vasculitis and spasm

Clinical presentation and progression

Presents with non-specific symptoms, viral respiratory illness, diarrhoea, fever, headache, photophobia, vomiting, anorexia, rash, cough and myalgia.

Occurs in summer or late autumn.

Enteroviral, pleurodynia, chest pain, hand-foot-mouth disease

HSV-2: acute genital herpes

Treatment

If meningococcal infection is suspected, the best way to reduce mortality is to administer

Empirical IV therapy immediately

Ceftriaxone 2g IV 12hrly or

Cefatoxime 2g IV 6hrly or immediately

Consequent dose, times and type of antibiotic need to be modified after full investigation and a detailed examination have taken place.

Dexamethasone may be prescribed: Needs to be at same time of antibiotic as outcome neurologically is reduced if given after antibiotic. Reduces BBB permeability.

Supportive treatment and resuscitation

Management of intracranial hypertension/ischaemia

Administer intravenous aciclovir.

Dexamethasone may be prescribed: reduces BBB permeability.

Supportive treatment and resuscitation

Management of intracranial hypertension/ischaemia

Complications

Complications of meningitis vary according to the aetiological organism, the duration of symptoms prior to initiation of appropriate therapy, and the age and immune status of the patient.¹⁰⁰ Temporary problems include development of haemodynamic instability and disseminated intravascular coagulopathy, particularly in meningococcal infection, SIADH or other dysregulation of the hypothalamic–pituitary axis (e.g. diabetes insipidus) and an acute rise in ICP.

Focal neurological signs may develop in the early stages of meningitis, but are more common later. The development of subdural empyema, brain abscess and acute hydrocephalus may require surgical intervention. Bacterial meningitis with accompanying bacteraemia can lead to a marked systemic inflammatory response with septic shock, respiratory distress syndrome and disseminated intravascular coagulation.

Collaborative care

Neurological derangement often coexists with circulatory insufficiency, impaired respiration, metabolic derangement and seizures. Protecting the patient from injury secondary to raised ICP and seizure activity is essential. Prevention in relation to complications associated with immobility, such as decubitus and pneumonia, is required. It is important to institute droplet infection control precautions in those attending the patient until 24 hours after the initiation of antibiotic therapy (oral and nasal discharge is considered infectious). See Online resources for infection control protocols relating specifically to meningitis.

Encephalitis

Encephalitis implies inflammation of the brain substance (parenchyma), which may coexist with inflammation of the meninges (meningoencephalitis) or spinal cord (encephalomyelitis). Encephalitis may be mild and self-limited, or may produce devastating illness.

Aetiology

Herpes simplex virus (HSV) is the commonest cause of non-seasonal encephalitis in Australia. Without treatment, HSV encephalitis is fatal in up to 80% of cases, and leaves up to 50% of survivors with long-term sequelae.¹⁰¹

• In the absence of particular risk factors, other common causes are enteroviruses, influenza virus and Mycoplasma pneumoniae. However, the likely pathogens in encephalitis are dramatically influenced by geographic location, history of travel and animal exposure, and vaccination.

• Murray Valley encephalitis (MVE) virus causes seasonal epidemics of encephalitis at times of high regional rainfall. This arthropod-borne virus is the commonest flavivirus to cause encephalitis in Australia.

• Since 2005, the distribution of Japanese B encephalitis virus has expanded into Australia via the Torres Strait Islands.¹⁰² It causes disease clinically similar to MVE. In addition, two novel encephalitis viruses were recently identified in Australia, the Hendra virus and Australian bat lyssavirus. These should be considered if there is a history of animal exposure, or if no other pathogen can be implicated.

• Mycobacterium tuberculosis, the yeast Cryptococcus neoformans and Treponema pallidum (syphilis) may also affect the brain parenchyma but usually produce chronic or subacute meningitis in such circumstances.

Pathophysiology

In the majority of encephalitis cases, the offending organism finds access to the brain via the nasopharyngeal epithelium and the olfactory nerve system. Arboviruses are transmitted from infected animals to human through bite of infected animals.¹⁰³ The cytokine storm results in neural cell damage, as well as the apoptosis of astrocytes. The disruption of the blood–brain barrier progresses to the systemic cytokine storm, resulting in septic shock, disseminated intravascular coagulopathy (DIC) and multiorgan failure (MOF).

Clinical features and diagnosis

Encephalitis may present with progressive headache, fever and alterations in cognitive state (confusion, behavioural change, dysphasia) or consciousness. Focal neurological signs (paresis) or seizures (focal or generalised) may also occur. Upper motor signs (hyperreflexia and extensor–plantar responses) are often present, but flaccid paralysis and bladder symptoms may occur if the spinal cord is involved. Associated movement disorders or the SIADH secretion may be seen. In northern Australia, it may be desirable to distinguish MVE from Japanese encephalitis clinically. Both conditions often affect the brainstem and basal ganglia, but MVE often involves the spinal cord, while Japanese encephalitis may produce striking meningeal signs, with or without thalamic involvement. Both have high mortality (25–33%) and high rates of chronic sequelae in survivors (~50%).¹⁰¹

The most sensitive type of imaging for diagnosis of encephalitis is MRI; in HSV encephalitis, CT scans may initially appear normal, but MRI usually shows involvement of the temporal lobes and thalamus.^103,¹⁰⁴ Examination of CSF can assist in differential diagnosis. Electroencephalography is less sensitive but may be helpful if it shows characteristic features (e.g. lateralising periodic sharp and slow-wave patterns). Refer to Table 17.6 for CSF profiles.

Collaborative management

Support in an ICU is often required in encephalitis to maintain ventilation, protect the airway and manage complications, such as cerebral oedema. The management of acute viral encephalitis includes aggressive airway, ventilation, sedation, seizure, haemodynamic, and fluid and nutritional support. Clinical deterioration in encephalitis is usually the result of severe cerebral oedema with diencephalic herniation or systemic complications, including generalised sepsis and multiple organ failure. The use of ICP monitoring in acute encephalitis remains controversial but should be considered if there is a rapid deterioration in the level of consciousness, and if imaging suggests raised ICP. Prolonged sedation may be necessary. Decompressive craniotomy may be successful in cases where there is rapid swelling of a non-dominant temporal lobe, as poor outcome is otherwise likely.¹⁰⁵

Neuromuscular Alterations

Generalised muscle weakness can manifest in several disorders that require ICU admission or complicate the course of patients. These may involve motor neuron disease, disorders of the neuromuscular junction, peripheral nerve conduction and muscular contraction. These disorders manifest as Guillain–Barré syndrome, myasthenia gravis, and critical illness polyneuropathy and myopathy.

Guillain–Barré Syndrome

Guillain–Barré syndrome (GBS) is an immune-mediated disorder resulting from generation of autoimmune antibodies and/or inflammatory cells which cross-react with epitopes on peripheral nerves and roots, leading to demyelination or axonal damage or both, and autoimmune insult to the peripheral nerve myelin. In Australia, Guillain–Barré has an average incidence of about 1.5 per 100,000, in men slightly higher than in women.¹⁰⁶ Of all patients, 85% recover with minimal residual symptoms; severe residual deficits occur in up to 10%. Residual deficits are most likely in patients with rapid disease progression, those who require mechanical ventilation, or those 60 years of age or over. Death occurs in 3–8% of cases, resulting from respiratory failure, autonomic dysfunction, sepsis or pulmonary emboli.¹⁰⁷

Aetiology

The diagnosis of GBS is confirmed by the findings of cytoalbuminological dissociation (elevation of the CSF protein without concomitant CSF pleocytosis), and by neurophysiological findings suggestive of an acute (usually demyelinating) neuropathy. These abnormalities may not be present in the early stages of the illness.¹⁰⁶ There are two forms of GBS. The demyelinating form, the more common one, is characterised by demyelination and inflammatory infiltrates of the peripheral nerves and roots. In the axonal form the nerves show Wallerian degeneration with an absence of inflammation. Discrimination between the axonal and demyelinating forms relies mainly on electrophysiological methods. There is a close association between GBS and a preceding infection, suggesting an immune basis for the syndrome. The commonest infections are due to Cambylobacter jejuni, cytomegalovirus and Epstein–Barr virus.

Pathophysiology

GBS is the result of a cell-mediated immune attack on peripheral nerve myelin proteins. The Schwann cell is spared, allowing for remyelination in the recovery phase of the disease. With the autoimmune attack there is an influx of macrophages and other immune-mediated agents that attack myelin, cause inflammation and destruction and leave the axon unable to support nerve conduction. This demyelination may be discrete or diffuse, and may affect the peripheral nerves and their roots at any point from their origin in the spinal cord to the neuromuscular junction. The weakness of GBS results from conduction block and concomitant or primary axonal injury in the affected motor nerves. Pain and paraesthesias are the clinical correlates of sensory nerve involvement.

Clinical manifestations

Onset is rapid, and approximately 20% of cases lead to total paralysis, requiring prolonged intensive therapy with mechanical ventilation. The therapeutic window for GBS is short, and the current optimal treatment with whole plasma exchange or IV immunoglobulin (IVIg) therapy lacks immunological specificity and only halves the severity of the disease.¹⁰⁸ GBS has three phases – acute, plateau, and recovery – each stage lasting from days to weeks and in recovery to months and years. The patient presents with:

• symmetrical weakness, diminished reflexes, and upward progression of motor weakness. A history of a viral illness in the previous few weeks suggests the diagnosis

• changes in vital capacity and negative inspiratory force, which are assessed to identify impending neuromuscular respiratory failure.

Indications for ICU admission include the following: ventilatory insufficiency, severe bulbar weakness threatening pulmonary aspiration, autonomic instability, or coexisting general medical factors,¹⁰⁹ and often a combination of factors, are present. The incidence of respiratory failure requiring mechanical ventilation in GBS is approximately 30%.

Ventilatory failure is primarily caused by inspiratory muscle weakness, although weakness of the abdominal and accessory muscles of respiration, retained airway secretions leading to pulmonary aspiration and atelectasis are all contributory factors. The associated bulbar weakness and autonomic instability reinforce the need for control of the airway and ventilation.

Acute motor and sensory axonal neuropathy, the acute axonal form of GBS, usually presents with a rapidly developing paralysis developing over hours, and a rapid development of respiratory failure requiring tracheal intubation and ventilation. PaCO₂ may remain constant until just before intubation, emphasising the importance of not relying purely on arterial blood gas analysis to make decisions regarding intubation.

Recently sensory involvement in relation to pain has been studied asserting the clinical observation of pain ranging from mild to severe in the acute and rehabilitant phases. Chronic pain is often present in survivors of GBS.¹¹⁰

There may be total paralysis of all voluntary muscles of the body, including the cranial musculature, the ocular muscles and the pupils. Prolonged paralysis and incomplete recovery are more likely, and prolonged ventilatory support may be necessary. Walgaard and colleagues found that GBS patients who experience rapid disease progression, bulbar dysfunction, bilateral facial weakness or autonomic nerve dysfunction were more likely to require mechanical ventilation.¹¹¹ Tracheostomy is usually performed within 2 weeks, and mechanical ventilation is delivered in a supportive mode with minimal yet adequate sedation and pain management.

Nursing practice

Assessment and understanding of neuromuscular weakness through motor and sensory neurological assessment is vital in the acute care and rehabilitation of GBS patients:

• Comprehensive respiratory assessment (level of overall patient comfort, frequency and depth of breathing, forced vital capacity, use of accessory muscles, presence of paradoxical respiration and integrity of upper airway reflexes), ABG data and chest radiography determine levels of fatigue in both the acute stage (for intubation and ventilation) and rehabilitation (weaning) stage. Long-term ventilation increases the risk of ventilator-acquired pneumonia (VAP), and routine surveillance for VAP is vital.

• Cardiovascular assessment is important, as serious tachyarrhythmias and bradyarrhythmias and destabilising fluctuations in blood pressure caused by autonomic impairment are prevalent. This feature is common during fatigue, sleep and states of dehydration. Often, autonomic dysfunction is worst in the early stages of a nosocomial infection.¹¹²

• Cranial nerve assessment and dermatome (for sensory) and muscle strength assessment assist in mapping the progression, severity and rehabilitation of the disease and determining the risk of aspiration. Pain (especially neuropathic) is particularly common in GBS during changes in myelination, and can be difficult to treat.¹¹³ Assessment will include all aspects as indicated for the long-term immobile, intubated, ventilated and neuromuscular-impaired patient.

Independent practice

When caring for a neuromuscular-impaired patient, a structured care plan is essential for continuity of care and should involve the patient and family. This is of particular importance in the long-term recovery phase, where the provision of sleep, good nutrition and prevention of the complications of immobility (nosocomial infections, DVT, integument and muscular weakening, adequate nutrition and constipation) is important:

• Endotracheal and pharyngeal suction can be demanding (weakened upper airway reflexes), and sputum plugging and retention requires frequent repositioning and physiotherapy.

• Routine daily gentle exercise as part of a flexible program improves wellbeing and strength.

• Fatigue must be avoided, as autonomic nerve dysfunction, deafferent pain syndromes, muscle pain and depression can be exacerbated.

• Suctioning, coughing, bladder distension, constipation and the Valsalva manoeuvre can also aggravate autonomic nerve dysfunction instability.

• Therapeutic massage, warm and cold packs and careful positioning contribute to comfort and pain management.

• The patient’s surroundings should be pleasant and presentable, especially during long recovery.

• Communication techniques need to be refined to prevent fatigue and frustration.

• Patience, tolerance, empathy, humour and family involvement assist the patient in psychological resilience and recovery.

Collaborative management

In the acute phase, accurate diagnosis and timely ventilatory support are provided by effective communication between primary and in-hospital care providers. Patients who require mechanical ventilation typically present with rapidly progressive weakness. Of interest, PaCO₂ may remain constant until just before intubation, emphasising the importance of not relying on arterial blood gas analysis to make decisions regarding intubation.

The side effects of IVIg administration include low-grade fever, chills, myalgia, diaphoresis, fluid imbalance, neutropenia, nausea and headaches, and at times acute tubular necrosis. Administration and assessment require adherence to transfusion protocols. Plasmapheresis is performed by transfusion nurse specialists in collaboration with the patient care nurse. Multidisciplinary case management is utilised after stabilisation in the acute phase, especially when the level of severity is determined. Recovery and rehabilitation process information is provided to the patient and family so that consultation and communication is effective in recovery.

Myasthenia gravis

Myasthenia gravis is an autoimmune disorder caused by autoantibodies against the nicotinic acetylcholine receptor on the postsynaptic membrane at the neuromuscular junction. It is characterised by weakness and fatiguability of the voluntary muscles. It peaks in the third and sixth decades of life. Its prevalence in Western countries is 14.2/100,000.¹¹⁴ Prevalence rates have been rising steadily over the past decades, probably due to decreased mortality, longer survival, and higher rates of diagnosis. The development of respiratory failure, progressive bulbar weakness leading to failure of airway protection and severe limb and truncal weakness causing extensive paralysis, as in a myasthenic crisis, all may result in admission to ICU.

Aetiology

Myasthenic crisis occurs when weakness from acquired myasthenia gravis becomes severe enough to necessitate intubation for ventilatory support or airway protection. At some point in their illness, usually within 2–3 years after diagnosis, 12–16% of myasthenic patients experience crisis. This occurrence is most likely in patients whose history includes previous crisis, oropharyngeal weakness or thymoma. Possible triggers include infections, aspiration, physical and emotional stress and changes in medications. Most antibiotics have a trigger effect and should be carefully prescribed by an informed physician.

Pathophysiology

In myasthenia gravis both structural changes in the architecture of the neuromuscular junction and dynamic alterations in the turnover of acetylcholine receptors erode the safety margin and efficiency of neuromuscular transmission. Of all patients with myasthenia gravis, 80–85% have an identifiable and quantifiable antibody found in the IgG fraction of plasma, which is responsible for blocking receptors to the action of acetylcholine at the neuromuscular junction.¹¹³ Therefore, successful neuromuscular transmission is markedly affected by small and subtle changes in acetylcholine release and other triggers (as above), and this gives rise to the decrement in transmission with repetitive stimulation and the characteristic fatiguable muscle weakness. Pharmacological management for myasthenia gravis includes the use of anticholinesterases (pyridostigmine), steroids, azathioprine and cyclophosphamide. Thymectomy reduces the antibodies responsible for acetylcholine blockade and is often performed early in the disease.¹¹⁵ Plasmapheresis and IVIg are used in the short term for myasthenic crisis and are especially useful for preventing respiratory collapse or assisting with weaning.

Clinical manifestations

In a myasthenic crisis, vital capacity falls, cough and sigh mechanisms deteriorate, atelectasis develops and hypoxaemia results.¹¹⁵ Ultimately, fatigue, hypercarbia and ventilatory collapse occur. Commonly superimposed pulmonary infections lead to increased morbidity and mortality. Assessment for triggers begins with a careful review of systems, with attention to recent fevers, chills, cough, chest pain, dysphagia, nasal regurgitation of liquids and dysuria. Detailed history-taking should note any trauma, surgical procedures and medication use. General assessment includes vital signs; ear, nose and throat inspection; chest auscultation; and abdominal check. In addition to supportive care and the removal of triggers, management of myasthenic crisis includes treatment of the underlying myasthenia gravis. An experienced neurologist, who will ultimately provide the patient’s care outside the ICU, should be part of the care team. Options for treatment during crisis include: use of AChE inhibitors, plasma exchange, IV immunoglobulins, and immunosuppressive drugs, including corticosteroids. Median duration of hospitalisation for crisis is 1 month. The patient usually spends half of this time intubated in the ICU. About 25% of patients are extubated on hospital day 7, 50% by hospital day 13, and 75% by hospital day 31. The mortality rate during hospitalisation for crisis has fallen from nearly 50% in the early 1960s to between 3% and 10% today. With the incidence of crisis remaining stable over the past 30 years, this fall in mortality rates probably reflects improvements in the intensive care assessment and management of these patients.¹¹⁴

Nursing practice

Careful and accurate assessment by the nurse in the presenting myasthenic crisis patient determines the triggers of the event and incorporates a history, including infections and prescribed medications. These medications can exacerbate the acetylcholine receptor blockade, and respiratory demand proves too much for the myasthenic patient. Awareness by the nurse of trigger medications ensures advocacy for the patient when the prescription is uncertain.¹¹⁴

• Respiratory and cardiovascular assessment incorporates upper and lower airway muscle weakness. ABGs are a poor marker for intubation and ventilation because these values change late in the decompensation cycle. Being able to recognise fatigue (inability to speak, poor lung expansion, VC below 1 L, shoulder and arm weakness) in patients with neuromuscular weakness and air hunger is important.¹¹⁷

• Non-invasive ventilation can be difficult to administer safely, with the potential for aspiration due to insidious upper airway weakness, however the option should be considered with careful assessment of gag, swallow and cough reflexes in order to prevent intubation.¹¹⁶

• Neuromuscular blockade should be avoided (residual long-term paralysis), with the use of glottal local anaesthetic spray for emergency intubation and ventilation.

• Placement of small-bore duodenal tubes decreases the risk of aspiration and may be more comfortable than regular nasogastric tubes for the patient.

• Tracheostomy is generally not needed, as the duration of intubation is often less than 2 weeks.

• Cardiac assessment needs to include assessment for arrhythmias of both atrial and ventricular origin due to autonomic nerve dysfunction.¹¹² These can be insidious and can be provoked by subtle changes in electrolytes.

• Nursing care will relate to the needs of long-term immobilised, intubated, ventilated patients with neuromuscular alterations.

Myasthenia gravis patients have similar care needs to those of patients with GBS (refer to Independent practice for GBS). Fatigue and the structure and timing of care are very important. Flexibility of care is important, as energy fluctuates on an hourly basis.¹¹⁷ Despite having a shorter recovery time than GBS, weaning and recovery in myasthenia gravis is a still a slow process and impulsive extubation is discouraged.¹¹⁸ Therapy should be tailored on an individual basis using best clinical judgment.

Selected Neurological Cases

Status Epilepticus

Status epilepticus (SE) has been generally defined as enduring seizure activity that is not likely to stop spontaneously. The traditional SE definition is 30 minutes of continuous seizure activity (which has recently been updated due to neurological alteration to 5 minutes only)or 2 or more seizures without full recovery of consciousness between the seizures.¹¹⁹ There are as many types of SE as there are types of seizures. The distinction between convulsive and nonconvulsive SE depends on clinical observation and on a clear understanding of several SE types. Estimates of the overall incidence of SE have varied from 10 to 60 per 100,000 person-years, depending on the population studied and the definitions used.¹²⁰ Over half the cases of SE are acute symptomatic, emphasising the importance in management of identifying an acute precipitant. Infections with fever are the major cause of SE, accounting for 52% of cases, while in adults low antiepileptic drug levels, cerebrovascular accident, hypoxia, metabolic causes and alcohol represent the main acute causes. The mortality in status epilepticus is about 20%; most patients die of the underlying condition rather than the status epilepticus itself. SE can result in permanent neurological and mental deterioration, particularly in young children; the risks of morbidity greatly increase with longer duration of the status epilepticus episode. SE in the intensive care setting falls into two main groups: those transferred to the ICU because of uncontrolled SE (refractory SE), and those who are admitted to the ICU for another reason and have SE as an additional finding.¹²¹

Pathophysiology

At a cellular level, status epilepticus results from a failure of normal inhibitory pathways, primarily mediated by gamma-aminobutyric acid (GABA) acting via GABA (A) receptors. This loss of inhibitory drive allows the activation of excitatory feedback loops, leading to repetitive, synchronous firing of large groups of neurons. As seizure activity continues, there is further decline in GABAergic function. Continued excitatory input mediated primarily by glutamate leads to neuronal cell death.¹¹⁹

Clinical Manifestations

Convulsive SE is a medical emergency. The initial consequence of a prolonged convulsion is a massive release of plasma catecholamines, which results in a rise in heart rate, blood pressure and plasma glucose. During this stage cardiac arrhythmias are often seen, and may be fatal. Cerebral blood flow is greatly increased, and thus glucose delivery to active cerebral tissue is maintained. As the seizure continues, hyperthermia above 40°C with lactic and respiratory acidosis continues to intensify especially without adequate resuscitation and control of the seizure.¹²²

The SE may then enter a second, late phase in which cerebral and systemic protective measures progressively fail. The main characteristics of this phase are: a fall in blood pressure; a loss of cerebral autoregulation, resulting in the dependence of cerebral blood flow on systemic blood pressure; and hypoglycaemia due to the exhaustion of glycogen stores and increased neurogenic insulin secretion. Intracranial pressure can rise precipitously in SE. The combined effects of systemic hypotension and intracranial hypertension may result in a compromised cerebral circulation and cerebral oedema. Intracranial pressure monitoring is advisable in prolonged severe SE when raised intracranial pressure is suspected. Further complications that can occur include rhabdomyolysis leading to acute tubular necrosis, hyperkalaemia and hyponatraemia.¹²²

Nursing Practice

The following nursing practice should be undertaken.

Resuscitation

SE requires control of the seizure and then investigation regarding the cause. Airway protection is often difficult in the seizing patient, so the first line of treatment includes basic life-support measures followed by the administration of IV propofol, midazolam or, in refractory cases, phenytoin. Neuromuscular blockade will be required to facilitate intubation in patients who continue to have tonic–clonic seizure activity despite these pharmacological interventions. Rocuronium (1 mg/kg), a short-acting, non-depolarising muscle relaxant that is devoid of significant haemodynamic effects and does not raise intracranial pressure, is the preferred agent. Succinylcholine should be avoided if possible, as the patient may be hyperkalaemic as a consequence of possible rhabdomyolysis. Prolonged neuromuscular blockade should be avoided as it only stops the motor response hence masking the altered neuronal activity.¹²³ Once the seizures are controlled, intubation and ventilation can protect the airway and potentially reverse the acidosis. In the patient who already has an airway secured, urgent IV administration of propofol, midazolam or phenytoin is indicated.¹²⁴

Specific post-SE patient assessment

Post-SE, the patient remains intubated, ventilated and sedated. Neurological assessment is limited in the sedated patient. Pupillary response is usually sluggish and reflects the medication prescribed. Routine monitoring in an ICU is essential, with CT and MRI to exclude mass lesions. The blood glucose level should be checked immediately by bedside testing. Blood should be tested for electrolytes, magnesium, phosphate, calcium, liver and renal function, haematocrit, WBC count, platelet count, antiepileptic drug levels, toxic drugs (particularly salicylates) and alcohol.

EEG monitoring in the ICU for refractory SE is essential, as a patient may enter a drug-induced coma with little outward sign of convulsions yet have ongoing electrographic epileptic activity. Furthermore, continuous recording will give an indication of worsening of generalised convulsive status epilepticus regardless of the presence or absence of sedating drugs or paralysing agents. This can be monitored only by EEG and manifests as bilateral EEG ictal discharges. Deeper sedation and anaesthesia is then indicated and can be titrated to EEG results.¹²⁴

Collaborative practice

Because only a small fraction of seizures go on to become SE, the probability that a given seizure will proceed to SE is small at the start of the seizure and increases with seizure duration. The goal of pharmacological therapy is to achieve the rapid and safe termination of the seizure, and to prevent its recurrence without adverse effects on the cardiovascular and respiratory systems or without altering the level of consciousness. Diazepam, lorazepam, midazolam, phenytoin and phenobarbitone have all been used as first-line therapy for the termination of SE.¹²⁵ The antiseizure activity of phenytoin is complex; however, its major action appears to block the voltage-sensitive, use-dependent sodium channels. Once SE is controlled, attention turns to preventing its recurrence. The best regimen for an individual patient will depend on the cause of the seizure and any history of antiepileptic drug therapy. A patient who develops SE in the course of alcohol withdrawal may not need antiepileptic drug therapy once the withdrawal has run its course. In contrast, patients with new, ongoing epileptogenic stimuli (e.g. encephalitis or trauma) may require high doses of antiepileptic medication to control their seizures.

Intracerebral Haemorrhage

Intracerebral haemorrhage (ICH) is an acute and spontaneous extravasation of blood into the brain parenchyma and is one of the most serious subtypes of stroke, affecting over a million people worldwide each year, most of whom live in Asia. About one-third of people with ICH die early after onset. The majority of survivors are left with major long-term disability. ICH accounts for 10–30% of all stroke admissions to hospital, and leads to catastrophic disability, morbidity, and a 6-month mortality of 30–50%.¹²⁶ Long-term outcomes are poor: only 20% of patients regain functional independence at 6 months. ICH is most common in men, in elderly people, and in Asians and African–Americans. The annual crude incidence of stroke in Australia has been estimated at 17.8 per 100,000 126 and in 2006 there were 8484 deaths attributable to stroke.¹²⁷

There are several modifiable risk factors for spontaneous ICH. Hypertension is by far the most important and prevalent risk factor, directly accounting for about 60–70% of cases.¹²⁸ Chronic hypertension causes degeneration, fragmentation, and fibrinoid necrosis of small penetrating arteries in the brain, which can eventually result in spontaneous rupture. Hypertensive ICH typically occurs in the basal ganglia (putamen, thalamus or caudate nucleus), pons, cerebellum, or deep hemispheric white matter.