Cerebral blood flow is normally maintained at a constant level over a wide range of cerebral perfusion pressures, a phenomenon known as autoregulation (Fig. 11.1). In normotensive patients, autoregulation occurs at cerebral perfusion pressures between 50 and 150 mmHg. In previously hypertensive patients, the curve is shifted to the right and autoregulation occurs at a higher blood pressure.

Fig. 11.1 Autoregulation curves.

Following significant brain injury, autoregulation is often deranged and cerebral blood flow becomes directly related to cerebral perfusion pressure (CPP).

Cerebral perfusion pressure is effectively the driving pressure across the cerebral circulation. It is calculated as shown:

Central venous pressure is sometimes included in this equation. This is because the cranium behaves as a Starling resistor – so where the CVP exceeds the ICP, the CVP becomes the effective downstream pressure and should be used to calculate CPP.

Inadequate CPP results in inadequate cerebral blood flow and the maintenance of an adequate CPP is therefore crucial. However, there is debate about what constitutes an adequate CPP and what the target values for therapy should be. Typical target values are shown in Table 11.2.

TABLE 11.2 Typical target values for cerebral perfusion (mmHg)*

* There is debate about the ideal target values. Some accept lower target values.

The skull can be conceptually considered as a rigid box containing the brain, CSF and blood. If the volume of one of these components is increased, e.g. by cerebral oedema, then the volume of the others must be reduced. Initially, CSF is displaced into the spinal canal, followed by a reduction in blood volume. Eventually, when no further compensation is possible, the ICP will rise rapidly, impairing cerebral perfusion. If the pressure is not relieved, the brain itself may become displaced, leading to so-called herniation or coning. (See Control of intracranial pressure, p. 288.)

In the presence of reduced intracranial compliance, the cerebral blood volume is an important determinant of ICP. If the cerebral circulation becomes vasodilated, cerebral blood volume increases and ICP may increase. Hypercapnia and hypoxia both cause cerebral vasodilatation and should be avoided. Brain-injured patients are normally ventilated to a PaCO₂ of 4–4.5 kPa. Hyperventilation to a lower PaCO₂ than this should be avoided, as there is a risk of significant cerebral vasoconstriction and ischaemia.

The initial assessment includes:

A Airway (with cervical spine control)

B Breathing

C Circulation

D Disability (neurological assessment).

The maintenance of a clear airway and the prevention of hypoxia and hypercapnia are paramount. Indications for intubation and ventilation are shown in Box 11.1.

(See Practical procedures: Intubation of the trachea, p. 398.)

Laryngoscopy and tracheal intubation are a major stimulus and may produce a significant elevation in blood pressure and ICP. Adequate anaesthesia and muscle relaxation must be provided in order to blunt this response and avoid potential worsening of the brain injury.

Establish intravenous access. Give volume loading, particularly if there is haemorrhage and other injuries. Blood, colloid or crystalloid is used as appropriate. If possible, establish direct arterial pressure monitoring.

Check all intubation equipment, breathing circuits, ventilators and suction, etc. Monitoring should be available for BP, ECG, SaO₂ and ETCO₂.

Note the baseline GCS score and pupil size for reference. The pupils are the principal clinical monitor of the brain following anaesthesia and paralysis.

Assume there is cervical spine injury until proved otherwise. A second person should provide in-line immobilization of the neck. (It may be useful to use a bougie / airway exchange catheter / video laryngoscope to facilitate intubation without extending the neck.)

Assume the stomach is full and perform a rapid sequence induction. Preoxygenate with 100% oxygen. Ask a trained assistant to apply cricoid pressure. Use etomidate if the BP is low, otherwise thiopentone or propofol are suitable induction agents. Suxamethonium is used to provide muscle relaxation (unless absolutely contraindicated, see p. 43).

Opioid, e.g. fentanyl 100 μg increments or remifentanil by infusion, 0.1 μg kg⁻¹ min⁻¹ can be used to help block the hypertensive response to intubation.

Intubate the patient and pass an orogastric tube to drain stomach contents.

Ventilate to normocapnia or moderate hypocapnia (PaCO₂ 4–4.5 kPa). Significant hypocapnia is associated with cerebral vasoconstriction and reduced cerebral perfusion. This may potentially cause cerebral ischaemia and worsen brain injury.

Monitor the SaO₂ and ETCO₂. Measure direct arterial blood pressure and blood gases as soon as possible. Maintain adequate cerebral perfusion pressure with fluids and vasoactive drugs (see below).

Maintain sedation with benzodiazepines, propofol and opioids. During the early resuscitation and stabilization phase continue paralysis with a cardiovascularly stable non-depolarizing muscle relaxant.

It is vital to maintain adequate cerebral perfusion pressure in brain-injured patients:

Give colloid or normal saline to restore circulating volume. Avoid hyponatraemic fluids as these worsen outcome.

Give blood if Hb low and correct any coagulopathy.

Consider inotropes / vasopressors early to maintain blood pressure.

Boluses of hypertonic saline (3–7.5%) may be valuable to maintain perfusion / circulating volume and limit cerebral oedema formation. Follow local protocols or seek advice.

Exclude other sites of bleeding.

(See Intensive care management below.)

Neurological assessment requires serial documentation of conscious level, pupillary signs, lateralizing limb signs (suggesting space-occupying lesion), tone and posture. Fundal haemorrhages, papilloedema, CSF rhinorrhea / otorrhoea and bleeding from the ear should be documented.

The simplest assessment of conscious level utilizes a four-point scale:

A Alert

V Responds to Vocal stimuli

P Responds to Painful stimuli

U Unresponsive.

This score is insufficiently sensitive for neurological assessment of the brain-injured patient and is only used during A&E resuscitation to give a broad indication of conscious level. Response to pain only represents a significant decrease in conscious level equivalent to a GCS score of 8 or less.

The Glasgow Coma Scale (GCS), shown in Table 11.3, is a more comprehensive neurological assessment, which is universally used to describe conscious level and has prognostic value. It should be performed as soon as the patient is stabilized. It is repeated throughout the resuscitation process to identify any deterioration in the patient’s condition, which may suggest expanding intracerebral haematoma or brain swelling.

TABLE 11.3 Glasgow Coma Scale (GCS)

Maximum score 15. Minimum score 3. (A modified GCS is used for children under 5 years)

Pupillary size and response to light (direct and consensual) should be documented regularly. Any asymmetry greater than 1 mm or a change in response to light must be assumed to be due to the effects of an intracranial space-occupying lesion causing compression of the ipsilateral third nerve. Urgent CT scan of the brain is required. Bilateral, dilated and unresponsive pupils in the context of a brain injury and in the absence of mydriatic agents is a grave sign.

Having completed a primary survey and stabilized the patient, the patient should be reassessed before moving on to secondary survey. Traumatic brain injury may be an isolated injury, but this should never be assumed. The care of the brain injury must proceed alongside the continuing re-evaluation and resuscitation of the other injuries according to ATLS protocols. In particular, remember:

cervical spine injury (immobilize, X-ray lateral cervical spine, CT spine)

cardiothoracic trauma (CXR, CT ± drains)

abdominal injuries (diagnostic peritoneal lavage, US, CT, laparotomy)

pelvic fractures (X-ray, early external fixation)

splint limb injuries (assess neurovascular integrity).

In the multiply-injured patient with a brain injury priorities must be decided. The following are important considerations:

Many brain injuries do not require neurosurgical intervention.

Any brain injury will be worsened by significant hypoxia or hypotension.

Any injury that compromises the airway, breathing or circulation takes priority. In particular, life-threatening bleeding from the chest or abdomen requires immediate surgical intervention and should not be delayed by CT head scan or neurosurgery. In exceptional cases, blind burr holes or craniotomy can be performed simultaneously with other surgery, and a CT scan performed before transfer to ICU.

Maintain the CPP above 60 mmHg in adult patients. It may need to be even higher in elderly hypertensive patients (normal autoregulation curve shifted to the right). Similarly CPP may need to be higher if there is evidence of cerebral vasospasm (e.g. in subarachnoid haemorrhage) or inadequate perfusion (e.g. low SjO₂). (See Jugular venous bulb oxygen saturation, p. 259.)

Titrate fluid therapy according to CVP. If there is no improvement or if the patient is haemodynamically unstable, consider the use of advanced haemodynamic monitoring devices (optimize cardiac output, stroke volume, vascular resistance etc.).

After adequate fluid resuscitation, if CPP remains low, use vasopressors, e.g. noradrenaline (norepinephrine) or phenylephrine to increase mean arterial pressure and improve CPP.

Adrenaline (epinephrine) may be used if invasive monitoring indicates that the primary reason for a low MAP is low CO.

The use of progressively higher doses of vasopressors in order to maintain a target CPP may produce subendocardial myocardial ischaemia and other end-organ damage. If increasingly higher doses are required, seek advice.

The measurement of ICP is now routine practice in the management of head injury. It may also be used in other conditions where there is likely to be raised ICP, e.g. the management of metabolic conditions such as liver failure. It is used to give an indication of increasing cerebral oedema, the re-accumulation of haematoma, and to calculate CPP.

Normal ICP is less than 10 mmHg and a sustained pressure higher than 20 mmHg is associated with poorer outcomes. If ICP is greater than 20–30 mmHg then intervention may be necessary, particularly in the first 24–48 h following injury. Table 11.5 provides a checklist of causes of a raised ICP. Exclude measurement errors and avoidable rises before starting treatment.

TABLE 11.5 Checklist for management of raised ICP

If all factors are optimized, exclude the development or re-accumulation of haematoma. Consider repeat CT scan to exclude evolving intracranial pathology (e.g. expanding haematoma) and seek neurosurgical opinion. Correct any coagulation defects. Other measures to control ICP include the following.

1st line

Mannitol 0.5 g / kg over 20 min, and / or furosemide (frusemide) 0.5 mg / kg. Any benefit tends to be temporary.

Hypertonic saline infusion / boluses (3–7.5% saline). Follow local protocols or seek advice.

Moderate hyperventilation. Do not reduce PaCO₂ to less than 4 kPa. Lower levels may result in excessive cerebral vasoconstriction and may produce areas of ischaemia. Any benefits will tend to disappear over a few hours.

CSF drainage via external ventricular drain.

Ensure that adequate CPP is maintained at all times. If there is no response to simple measures, consider further increasing CPP. The benefit of this may not be immediate and may take a few hours.

2nd line

Thiopental (thiopentone) infusion. 15 mg / kg 1st hour, 8 mg / kg 2nd hour, 5 mg / kg / h thereafter. The aim is to achieve burst suppression on CFM monitoring. The disadvantage of this approach is that the time taken for thiopental to wear off once the infusion is stopped delays the ability to clinically assess the patient. Monitor levels over time.

Decompressive craniotomy. Removal of bone flap and lobectomy.

Induced hypothermia.

Aggressive hyperventilation to PaCO₂ < 3 kPa. See note above.

Haemodynamic instability is common and may be seen in association with neurogenic pulmonary oedema (see below). The importance of an adequate cerebral perfusion pressure has already been stressed. Hypotension may be due to a combination of factors. You should exclude causes such as hypovolaemia, pneumothorax and sepsis. All patients should have direct arterial pressure and CVP monitoring. In complex cases, consider other monitoring devices to guide fluids, inotropes and vasopressor therapy, as for any shock state.

Sudden increases in pupil size, particularly if unilateral and non-reactive to light, may be due to stretching of the 3rd cranial nerve and may herald brainstem herniation. This is an indication for an urgent repeat CT scan. Dilated pupils may reflect underlying seizure activity. Bilateral persistent fixed dilated pupils are an ominous sign, suggesting impending brain death, but should not be considered in isolation.

Generalized or focal seizures are common with brain injury from any cause. In the complicated ICU patient the distinction between focal and generalized seizures is indistinct and usually of little relevance. Continued seizure activity increases the oxygen requirement of the brain and worsens brain injury, therefore seizures should be treated promptly

Acutely brain injured patients at risk of repeated seizures will usually be ventilated. The use of muscle relaxants blocks the peripheral manifestations of seizure activity making clinical detection more difficult. Seizure activity may be accompanied by changes in blood pressure / heart rate and pupils but these signs are unreliable.

Cerebral function monitors (CFM) or cerebral function analysing monitors (CFAM) are frequently used to detect abnormal seizure activity in paralysed patients. The simplest of these displays two channels, base line activity (to detect artifacts) and global cerebral electrical activity. Seizures are indicated by an abrupt elevation of the cerebral activity level. A saw tooth pattern is typical of recurrent short seizures.

More advanced CFAMs display the electrical activity of each cerebral hemisphere separately and have multiple channels able to display separately the various frequencies that make up global cerebral activity (alpha, beta, theta delta activity). You should seek advice on the interpretation of the output of these monitors.

If in doubt about the presence or absence of seizure activity in the paralysed patient request a formal EEG. Alternatively, there is usually little harm in temporarily reducing / stopping muscle relaxants to assess seizure activity; ensure adequate doses of sedative / analgesic drugs first!

Exclude any treatable precipitating cause such as hypoxia, hypercapnia, hyperthermia or electrolyte disturbance.

1st line treatment

Intravenous benzodiazepines, e.g. diazepam 5–10 mg or clonazepam as necessary. Large cumulative doses may be needed. Midazolam is also effective.

Intravenous phenytoin. Loading dose 15 mg / kg. Give 300 mg loading dose over 1 h and then 1200 mg over next 24 h. Daily dose 300 mg thereafter. Measure levels over time. Phenytoin may cause disturbances of cardiac rhythm in some patients.

Intravenous propofol, bolus followed by infusion 200–400 mg / h may also be effective.

2nd line treatment

If seizure activity is not controlled, then additional anticonvulsant agents such as clonazepam, sodium valproate, phenobarbital, clormethiazole, paraldehyde or magnesium may be required. Seek expert advice and check dose regimens in BNF.

Consider thiopental (thiopentone) bolus 500 mg over 5 min, followed by infusion 2.5–5 g daily. Check levels over time.

Prophylactic anticonvulsants may be given to at-risk patients; for example, patients with significant contusions on CT or documented seizures after injury. Phenytoin is the usual drug as it does not produce significant sedation (see doses above).

Neurogenic DI results from failure of the posterior pituitary to produce antidiuretic hormone (ADH). It may result from either localized damage to the pituitary / hypothalamic area or from diffuse brain injury / brain death. It is manifest as excessive urine output due to inability to concentrate the urine. Untreated, this results in progressive dehydration and hypernatraemia.

DI should be considered if urine outputs persist at greater than 300–400 mL / h in the absence of diuretics. Other causes of excessive urine output include excretion of resuscitation fluids and use of mannitol or other diuretics.

To confirm the diagnosis, check urine / plasma osmolality. Normal plasma osmolality is 286 mosmol / L. If increased > 310 mosmol / L then urine should be highly concentrated. In this context urine osmolality <500 mosmol / L implies DI.

Give DDAVP 1–2 μg i.v. as required.

Replace urinary losses with 5% dextrose with added K⁺.

Respiratory problems are very common in the presence of brain injury and are often a reason for initial ICU admission or delayed discharge. The precise mechanisms are multifactorial, but may include inadequate cough and gag reflexes, pulmonary aspiration, chest infection (particularly staphylococcal), pulmonary capillary leak and depressed immune function. (See Hospital acquired pneumonia, p. 143.)

Many patients with severe brain injury require a tracheostomy to facilitate airway management for short-to-medium term care. Neurological function is typically assessed 48–72 h post-injury if the patient is stable enough to awake and assess. If the patient is thought to have a survivable injury but is obtunded consider early tracheostomy to avoid the scenario of repeated extubation and reintubation and then subsequent tracheostomy. Tracheostomy protects the airway, is more comfortable for the patient, allows early reduction in sedative and analgesic drugs, aids nutrition and mobilization, and allows easier weaning of ventilatory support. If survival from the brain injury is uncertain or the patient remains unstable (e.g. raised ICP, critical oxygenation), then it may be prudent to delay tracheostomy until the situation is clearer.

Pulmonary oedema is a well-recognized complication of brain injury. In its severest form, it is characterized by extreme cardiovascular instability with profuse pink frothy pulmonary oedema. Simplistically, it is thought to result from a catecholamine surge caused by a rapid rise in ICP. This results in an acute increase in left ventricular afterload and left ventricular dysfunction, increased pulmonary vascular volume (blood returned from peripheries) pulmonary hypertension and increased permeability of pulmonary vascular endothelium, all of which may contribute to the development of oedema.

The management of acute neurogenic pulmonary oedema is supportive with IPPV, high FiO₂ and PEEP. Diuretics are not usually effective and the volume of fluid leaking into the alveoli and out of the lung may lead to marked hypovolaemia. Cardiac instability will often require advanced haemodynamic monitoring, inotropes / vasopressor therapy. The pulmonary oedema usually settles over time but may produce an acute lung injury leading to ARDS. (See Acute lung injury, p. 154.)

Clear or bloodstained fluid from nose or ear may represent a CSF leak, which is a feature of injuries to the frontal sinus and base of skull. CSF tests positive for glucose on test strips. In the past, antibiotic prophylaxis was thought to be necessary, but most centres have stopped this practice. It is usual to wait about 10 days to see if the leak will cease spontaneously, if not then craniotomy and placement of a dural patch may be required.

Irritability and restlessness are common in patients with minor brain injury or in the recovery phase of more severe injuries. In the latter, there will often be severe movement disorders in the form of extensor spasms. Despite the theoretical risks of masking neurological signs it is often necessary to give sedatives (benzodiazepines) and major tranquillizers (chlorpromazine / haloperidol) to such patients to allow nursing care and prevent further injury. Large doses of drugs may be required. The patient with extensor spasms will generally benefit from a tracheostomy to prevent biting on the endotracheal tube and airway obstruction.

Consider nursing such patients on a mattress on the floor to avoid them falling out of bed (cot sides do not always prevent this and increase the height of the fall!). NG tubes tend to be repeatedly pulled out by such patients. Feeding gastrostomy / jejunostomy may be required in the longer term.

Routine in most centres. Intracranial pressure can be monitored using an intraventricular catheter (measures CSF pressure and allows drainage of CSF) or via transducers placed in the subdural space or in brain parenchyma. Various devices are available, typically consisting of a micro-pressure transducer on the end of a flexible wire. These can be inserted on the intensive care unit via a small burr hole and are usually placed on the side most affected, as indicated by surgery / CT scan. (See Management of traumatic brain injury above.)

Measuring the saturation in venous blood from the brain gives an indication of the adequacy of oxygen delivery and utilization by the brain. The normal range is 55–75%. Changes are more valuable than isolated values and reflect global / regional perfusion and oxygenation.

A low SjO₂ implies inadequate oxygen delivery. Consider measures to improve cerebral blood flow, in particular raising CPP. If the saturation is high then the brain is either hyperaemic or failing to extract oxygen. Barbiturates may be helpful to control ICP in the presence of hyperaemia. In brain death, the saturation may approach 100% as the brain ceases to extract oxygen.

This technique uses light absorption to measure brain tissue oxygenation. Light of a particular wavelength is passed through the skull and the absorption by brain cytochrome aa3 (representing the terminal step of the mitochondrial electron transport chain) is detected. The technique is limited by the depth to which the incident light is able to penetrate effectively. Changes probably reflect perfusion / oxygen delivery in superficial areas of the brain only.

Brain tissue PO₂ can be measured directly using a miniaturized electrode placed within or on the surface of the brain through a cranial burr hole. It is usually combined with an ICP device.

A microdialysis catheter is placed into brain parenchyma through a small cranial burr hole. Fluid is passed through the catheter and allowed to equilibrate with brain tissue interstitial fluid. This is then aspirated and analysis of the chemical content of the fluid retrieved provides an indication of local tissue perfusion and oxygenation. Except in a few specialized neurosurgical units, this technique remains largely a research tool.

The traditional approach to monitoring of cerebral activity in brain-injured patients who are sedated and paralysed has been based on the use of cerebral function monitors (CFM) and cerebral function analysing monitors (CFAM) and intermittent EEG. These are limited either by the amount of clinically useful information they provide, difficulty in interpretation or their intermittent nature. Newer approaches to monitoring cerebral activity aim to provide real time, clinically relevant assessment of cerebral activity.

Compressed spectral array provides a way of continuously monitoring and displaying the EEG signal in a simple, easily interpretable, bedside monitor. It is likely to replace traditional CFAM as the standard monitor of cerebral activity in brain injury.

Bispectral index (BIS®) uses a proprietary algorithm to produce a single numerical value indicative of conscious level. Its primary role is as a guide to depth of anaesthesia during surgical procedures. It is not formally validated for use in a head injury, and gives only a general guide as to the conscious level.

A number of advanced neurophysiological imaging techniques are available in specialist centres, including functional magnetic resonance imaging, SPECT scanning, PET scanning and xenon CT. At present, these are primarily diagnostic and research tools, although they are likely to become more routine in future clinical practice.

For patients with lower grades of bleed, there is established benefit in early angiography and embolization or clipping of aneurysm to reduce the risk of rebleeding and further neurological insult.

Patients with significant subarachnoid bleeds and large intracerebral haematomas may require emergency, surgical evacuation of the haematoma. Intraventricular drainage may be used to decompress the brain and treat hydrocephalus. These patients will require intensive care support.

Definitive management is either by embolization of the aneurysm under radiological control or surgical clipping depending on the nature of the lesion. Timing depends upon the patient’s age (increasing risk of cerebrovascular disease and cerebral infarction) preoperative status and the perceived risk of rebleeding. Early intervention reduces the risk of rebleeding and of intercurrent medical problems, but where surgical intervention is required is technically more difficult and is associated with an increased risk of cerebral vascular spasm. Delayed intervention (10–14 days post-bleed) is technically easier and carries less risk of vasospasm, but increases the risk of bleeding in the intervening period.

Patients with spontaneous subarachnoid haemorrhage (SAH) frequently require intensive care, either early at presentation, after surgery or some time later due to respiratory or other complications.

The ICU management of SAH is essentially no different from other causes of brain injury. Cerebral vasospasm may occur. The exact mechanism by which this occurs is unclear but it can result in areas of ischaemic infarction. It is diagnosed by angiography or transcranial Doppler. Management is centred on prevention.

Maintenance of cerebral perfusion pressure using fluids and vasopressors is crucial. Aim for mean systemic pressure of 90–100 mmHg. It is not usual to monitor ICP. Vasopressor therapy is usually used and may be required for up to 3 weeks.

The Ca²⁺ channel blocker nimodipine has been shown to improve neurological outcome. Its effect is thought to be independent of any anti-vasospasm action. Its systemic vasodilator effects may worsen CPP and require vasopressor therapy. It is available in oral and i.v. preparations.

Cardiac dysrhythmias are common in SAH. These do not usually require treatment.

Typically many patients are managed in an HDU / ward area. More severe cases may need a period of ventilation in ICU, followed by a period of weaning and tracheostomy.

The prediction of long-term outcome after hypoxic brain injury is difficult. If the patient does not awaken, longer-term management will depend upon the patient’s background health, age, previous wishes (advance directives, etc.). The patient’s relatives and family need to be kept aware of the situation and their wishes must also be considered. Unless a consensus is reached regarding withdrawal of active management, the patient should be stabilized, weaned from IPPV, usually via a tracheostomy, established on enteral feeding and transferred for ward-based care awaiting neurological change over time. If the patient does not improve over time and all parties agree that further treatment is futile, then it is reasonable to wean from assisted ventilation, extubate the trachea, and await events. (See Treatment limitation decisions, p. 430.)

Following cardiac arrest, a proportion of patients enter a vegetative or near vegetative state. The duration of such a state is often difficult to predict. In some cases it is permanent, whereas in a very small minority of cases, meaningful recovery has been described after months or years. Such patients need assessment by a neurologist with an interest in rehabilitation.

It is unusual for adults to require intensive care when meningitis is the primary presenting diagnosis. In the case serious enough to warrant intensive care it is advisable to perform CT scan prior to lumbar puncture to exclude cerebral oedema and the potential risk of coning after lumbar puncture. If lumbar puncture is contraindicated, empirical antibiotic therapy is then started. Steroids have been shown to reduce longer-term neurological sequelae in both adults and children presenting with Haemophilus, pneumococcal and recently meningococcal meningitis and should be given on presentation.

Occasionally more severe cases develop secondary hydrocephalus and may benefit from intraventricular CSF drainage; therefore, perform a CT scan in patients who deteriorate or who fail to improve over time.

As for meningitis, it is unusual for adults to require intensive care. Occasionally encephalitis needs to be considered as a diagnosis of exclusion in cases of coma. There are characteristic EEG changes with herpes encephalitis. A brain biopsy may be indicated to confirm the diagnosis. Start aciclovir and broad-spectrum antibiotics (cefotaxime and clarithromycin) until diagnosis is proved / disproved.

(See Empirical antibiotic therapy, p. 336.)

This is an occasional cause of ICU admission. Look for embolic sources of infection, e.g. endocarditis, and local sources, e.g. middle ear infection. Check tuberculosis status. Immune-suppressed patients (e.g. HIV) may present with unusual CNS abscesses / meningitis, e.g. toxoplasmosis and cryptosporidiosis. Large abscesses require surgical drainage. Seek neurosurgical advice.

Status epilepticus can be defined as seizures lasting longer than 30 min, or so frequently that no recovery occurs between attacks. Patients are at risk of brain injury, cerebral oedema, hypoxia and aspiration. Typically, intensive care referral occurs when first-line drug treatment has failed and the patient becomes increasingly obtunded due to the effects of ongoing seizures and sedative drug accumulation. If untreated, patients may suffer further complications from immobility, hypothermia, hyperthermia and rhabdomyolysis.

Occasionally patients will present with convincing pseudo-seizures as part of a Münchausen-type syndrome. If there is doubt as to whether jerky movements or loss of consciousness represent a true seizure, request an EEG.

Most cases severe enough to require admission to ICU will need a period of tracheal intubation and assisted ventilation. Consider CT scanning and / or lumbar puncture to exclude treatable disorders. Correct any metabolic abnormality or derangement of body temperature. For first line anticonvulsant therapy, consider the following, then seek specialist advice:

Intravenous benzodiazepines, e.g. diazepam 5–10 mg or clonazepam as necessary. Large cumulative doses may be needed. Midazolam and propofol are also effective.

Intravenous phenytoin. Loading dose 15 mg / kg. Give 300 mg loading dose over 1 h and then 1200 mg over next 24 h. Daily dose 300 mg thereafter. Measure levels over time. Phenytoin may cause disturbances of cardiac rhythm in some patients.

Before brainstem tests are performed, there are a number of preconditions that must be satisfied in order to exclude potentially reversible causes of brainstem dysfunction. These are shown in Box 11.4.

Active measures to maintain blood pressure, temperature and normal electrolytes may be required if the patient is to fulfil preconditions, and to be potentially suitable for organ donation. This may require fluids, inotropes, vasopressors and DDAVP in the hours prior to tests (often overnight). Replacement of the large urine volumes seen with diabetes insipidus with isotonic saline or synthetic colloid solutions will lead to progressive hypernatraemia. Use DDAVP and fluid replacement with dextrose solutions (with added K⁺) to avoid this. (See Diabetes insipidus, p. 286, Practicalities of donor management, p. 438.)

Before performing tests ensure that all preconditions are satisfied. Always confirm the integrity of the neuromuscular junction and exclude the effects of muscle relaxants by use of a nerve stimulator (see p. 43). Scrutinize the drug chart and intensive care chart to ensure that sufficient time has elapsed for any centrally acting drugs to have been metabolized and eliminated. Beware of active metabolites, which may have long half-lives. If in doubt, drug levels can be measured. Check the patient’s core temperature and recent biochemistry results.

In the UK, the tests are carried out by two doctors who are 5 years post-registration. At least one these must be a consultant who should have been responsible for the patient during the admission and neither should be associated with the transplant services. The tests should be performed together and each doctor should satisfy themselves of the results. The tests should be repeated at a suitable interval to confirm the findings. Following the completion of the second set of tests, brainstem death is confirmed.

Occasionally families will ask to observe the tests being done. This is acceptable providing that staff have taken the time to explain the process and they understand the nature of the tests including spinal reflexes. The whole process of testing, counselling the family and explaining the concept of brain death and organ donation is, of necessity, time consuming.

Most hospitals will have pre-printed documentation for brainstem death tests and organ donation. The tests required are listed in Table 11.9.

TABLE 11.9 Brainstem death tests

Deep pain is produced peripherally by pressure on sensitive points such as the nail beds and centrally by pressure over the supraorbital nerves, while observing for a response within the cranial nerve distribution. Peripheral non-purposeful movements in response to peripheral pain represent spinal reflexes, and are not indicative of brainstem function. Simplistically these reflect the loss of descending control over the spinal cord from higher centres and may become exaggerated over time. Relatives and attending staff should be warned of these and their significance explained.

The patient is preoxygenated with 100% O₂, and then disconnected from the ventilator and connected to a breathing circuit with high flow 100% O₂. If the lungs are healthy, oxygenation is maintained and the PaCO₂ rises gradually. The PaCO₂ must be allowed to rise to a level at which the patient could be expected to breathe (PaCO₂ of 6.6 kPa for a previously healthy patient, higher in patients with chronic lung disease and CO₂ retention). The rise in CO₂ usually takes about 10 min. If pulmonary function is poor, there is a risk of profound hypoxia and cardiac arrest during apnoea testing. In such cases ventilate slowly with 100% oxygen and added CO₂, or add a dead space into the circuit, then briefly disconnect the ventilator to look for respiratory movement.

Following completion of the second set of brainstem tests, brainstem death is confirmed and the patient can be declared legally dead. Although two sets of tests are performed, the time of death is taken to be the time of the completion of the first set of tests. (In this respect, the second set of tests are confirming the original findings of brainstem death.) The death should be reported to the coroner if this is required (see Reporting deaths to the coroner, p. 436).

Following confirmation of brainstem death, arrangements may be made to retrieve organs for transplantation if consent has been obtained. (See Organ donation, p. 437.) Alternatively ventilation may be withdrawn. The family should be offered the opportunity to sit with the patient and allowed time for distant relatives to visit. At the time of ventilator disconnection they may choose to stay with the patient. Alternatively, some prefer to say their farewells before the event and leave or visit later.

If, during brainstem testing, residual brainstem function is demonstrated (usually residual cough or respiratory effort), ventilatory support should be continued and the situation reassessed. Assuming catastrophic brain injury has occurred, residual brainstem activity will usually disappear over 24–48 h and then repeat brainstem tests can be performed to confirm brainstem death. Alternatively, further discussions may be held with the family to consider withdrawal of active treatment in anticipation of death according to conventionally accepted criteria. (See Withdrawal of treatment, p. 431.)

Some patients, despite suffering an apparently catastrophic and presumed fatal brain injury, retain some residual brainstem function. They cannot be declared brainstem dead, yet appear to have no prospect of meaningful survival. Honest discussions with the family regarding the benefits versus burdens of continuation or withdrawal of treatment should take place, so that decisions can be reached over a period of time that are in the best interests of the patient. If a consensus is reached that further active management is inappropriate, then treatment should be withdrawn. Such patients may be suitable for consideration as asystolic or non-beating heart organ donors. (See Non-heart beating organ donation, p. 439.)

Increasing numbers of patients with inherited neuromuscular disease are surviving into young adulthood. Many of these will require nocturnal CPAP or non-invasive ventilatory support. They frequently require intensive care admission for intercurrent chest infection. In many cases, however, there is a gradual decline in respiratory function, cough reflex and general condition over time. There may come a point, therefore, at which further intensive care admission is no longer appropriate. This may lead to difficult discussions with the patient and their relatives / carers. Always seek senior advice.

This autoimmune disease results from antibodies to the cholinergic receptors in the neuromuscular junction. The mainstay of treatment is with anticholinesterase drugs, which increase the level of acetylcholine available at the cholinergic receptors.

Deterioration, increasing muscle weakness and subsequent respiratory failure may result from intercurrent disease, surgery or overdosage of anticholinesterase drugs (cholinergic crisis). The short-acting anticholinesterase edrophonium may be given to test whether muscle function can be improved (‘Tensilon test’). In practice, by the time myasthenic patients require intensive care it is often difficult to distinguish a cholinergic crisis from other causes of muscle fatigue.

Acute exacerbations are treated by increases in anticholinergic drugs, steroids and plasma exchange. Azathioprine, cyclophosphamide and thymectomy are useful treatments in the longer term.

This condition of ascending muscle paralysis usually follows an intercurrent illness. The early use of intravenous immunoglobulin and plasmapheresis may reduce the need for assisted ventilation. Patients who require assisted ventilation may take weeks or months to recover, and recovery is not always complete. Autonomic disturbances and neuropathic pain are common. A variant of this condition, known as Miller Fisher syndrome, predominantly affects the cranial nerves. Treatment options include plasmapheresis, immunoglobulins and steroids. Plasmapheresis is generally arranged through the regional transfusion service.

This is rare in the UK, due to successful immunization programmes. It is, however, a major problem abroad. The toxins produced by the bacteria Clostridium tetani disrupt normal neuromuscular control and produce severe spasms and autonomic disturbances. The management is supportive, with wound debridement, antibiotics, immunoglobulins, control of autonomic dysfunction and muscle spasms. Baclofen (systemically and intrathecally) has been used for muscle relaxation with variable effectiveness. Severe cases may require protracted sedation and assisted ventilation. Seek specialist advice.

This is rare in the UK but occasional outbreaks have been associated with contaminated packaged food. Toxin produced by Clostridium botulinum blocks cholinergic receptors. Nausea and vomiting are followed by blurred vision, laryngeal and pharyngeal paralysis and generalized paralysis. Tachycardia, urinary retention and constipation occur. Treatment is largely supportive. Seek specialist advice.