Status epilepticus

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Chapter 43 Status epilepticus

Status epilepticus (SE) is a medical emergency requiring prompt intervention to prevent the development of irreversible brain damage.

The duration of seizure activity required to define SE has not been universally agreed upon. Most authors have defined SE as more than 30 minutes’ duration of either a single seizure, or intermittent seizures with no regaining of consciousness between seizures.¹^–⁴ This definition is most useful for epidemiological research and is based on experimental studies that show that irreversible neuronal damage occurs after 30 minutes of seizure activity.^5,⁶

More recently an operational definition of SE as 5 minutes of continuous seizure activity, or two or more discrete seizures with no intervening recovery of consciousness, has been used.⁷ This definition promotes earlier diagnosis and treatment of SE. It has arisen from the generally accepted need to initiate treatment for SE rapidly and the observation that seizures persisting beyond this duration are unlikely to remit spontaneously.⁸

Refractory SE is defined as failure of initial therapy, such as benzodiazepines and phenytoin, with seizures persisting beyond 1–2 hours and usually requiring agents that induce general anaesthesia to control them.^9,¹⁰ Refractory SE is associated with a worse prognosis.^9,¹¹

SE is commonly separated into two categories:

1 Generalised convulsive SE (GCSE). Seizures are primary or secondarily generalised and the patient has generalised tonic and/or clonic convulsive movements with loss of consciousness.

2 Non-convulsive SE (NCSE). There is altered consciousness without convulsive movements but electroencephalography (EEG) evidence of seizures. NCSE may evolve from GCSE when electrical seizure activity continues with loss of motor manifestations. NCSE includes absence SE and complex partial SE.

The incidence of SE is U-shaped, being greatest under 1 year and over 60 years of age.²

PATHOPHYSIOLOGY

Ongoing or recurrent seizures result from failure of normal seizure-terminating mechanisms or excessive excitation causing seizure activity to persist. The major inhibitory mechanism in the brain is γ-aminobutyric acid A (GABA_A) receptor-mediated inhibition. Glutamatergic excitatory synaptic transmission is important in sustaining SE.¹²

The pathophysiological effects of seizures on the brain are thought to result from both direct excitotoxic neuronal injury and secondary injury due to systemic complications such as hypotension, hypoxia and hyperthermia. Ongoing excitation results in excessive intracellular calcium flux through the opening of NMDA (N-methyl-D-aspartate) receptor-mediated calcium channels, inducing a cascade of intracellular neurochemical events that damage or kill the cell.

AETIOLOGY

SE may occur de novo (approximately 60% of presentations) or, less commonly, in a previously diagnosed epileptic.² The aetiologies of SE, in decreasing order of frequency as they occur in adults, are given in Table 43.1.²

Table 43.1 Causes of status epilepticus in adults

Low antiepileptic drug levels (poor compliance, recent dose reduction or discontinuation)

Temporally remote causes (previous central nervous system injury e.g. stroke, trauma, tumour, meningitis)

Stroke – vascular occlusion or haemorrhage

Cerebral hypoxia/anoxia

Metabolic disturbances (electrolyte abnormalities, uraemia, hyperglycaemia, hypoglycaemia)

Alcohol – withdrawal or intoxication

Central nervous system tumours – primary or secondary

Systemic infection

Idiopathic

Central nervous system infection – meningitis, encephalitis

Head trauma

Drug toxicity (tricyclic antidepressants, phenothiazines, theophylline, isoniazid, cocaine, amphetamine)

For SE that has its onset in the intensive care unit (ICU), the following should be considered as possible causes:

• drug withdrawal (narcotics, benzodiazepines, omission of anticonvulsant medications)

• metabolic disturbance (hyponatraemia, hypocalcaemia, hyperglycaemia, hypoglycaemia, uraemia, hepatic encephalopathy)

• drug toxicity (pethidine, theophylline, ciclosporin, tacrolimus, antibiotics, e.g. penicillins, cephalosporins, ciprofloxacin, imipenem in renal failure)

• stroke – vascular occlusion or haemorrhage

GENERALISED CONVULSIVE STATUS EPILEPTICUS

GCSE is the most common and dangerous type of SE and accounts for approximately 75% of cases.² It encompasses a broad spectrum of clinical presentations, from overt generalised tonic-clonic seizures to subtle convulsive movements in a profoundly comatose patient.¹³

CLINICAL

Typically, early in the evolution of seizures, patients are unresponsive with obvious tonic (sustained contractions) and/or clonic (rhythmic jerking) movements (overt GCSE). Motor manifestations may be symmetrical or asymmetrical.

With time, the clinical manifestations may become subtle, and patients have only small-amplitude twitching movements of the face, hands or feet or nystagmoid jerking of the eyes (late or subtle GCSE).¹³

Later still some patients will have no observable repetitive motor activity and the detection of ongoing seizures requires EEG (electrical GCSE). Most authors classify this as a form of NCSE.¹⁴^–¹⁶ Such patients are still at risk of central nervous system (CNS) injury and require prompt treatment.

EEG CHANGES

Just as there is a progression from overt to increasingly subtle motor manifestations, there is also a predictable sequence of EEG changes during untreated GCSE. Initially, discrete electrographic seizures merge to a waxing and waning pattern of seizure activity, followed by continuous monomorphic discharges, which become interspersed with increasing periods of electrographic silence and, eventually, periodic epileptiform discharges on a relatively flat background.^13,¹⁷ The presence of any of these EEG patterns should suggest the diagnosis of GSCE.

ENDOCRINE AND METABOLIC EFFECTS

Early in GCSE there is a marked increase in plasma catecholamines, producing systemic physiologic changes that resolve if SE is stopped early (Table 43.2). However, if seizures continue, many of these early physiologic changes reverse and the resultant hypotension and hypoglycaemia may exacerbate neurological injury.¹⁸

Table 43.2 Physiological changes in generalised convulsive status epilepticus ^18,⁵⁶

Hypoxia

Respiratory acidosis

Lactic acidosis

Hyperpyrexia

Hypertension (early)/hypotension (late)

Hyperglycaemia (early)/hypoglycaemia (late)

Tachycardia

Cardiac arrhythmias

Blood leukocytosis

Cerebrospinal fluid pleocytosis, increased cerebrospinal fluid protein

Intracranial hypertension

Neurogenic pulmonary oedema

Aspiration pneumonitis

Rhabdomyolysis

Hyperthermia is due to both muscle activity and central sympathetic drive, and thus may still occur when paralysing agents prevent motor activity. In early SE, both cerebral metabolic activity and cerebral blood flow (CBF) are increased. In late SE, although cerebral metabolic activity remains high, CBF may fall due to hypotension and loss of cerebral autoregulation, leading to cerebral ischaemia.

An important differential diagnosis of generalised convulsive epilepsy is pseudoseizures. These can occur in patients with or without a history of epilepsy.¹⁹ Clinical features suggestive of pseudoseizures are listed in Table 43.3. Distinction between the two may be extremely difficult, and can only be made with complete certainty using EEG monitoring.¹⁹ Pseudo-status, misdiagnosed as true SE, is often refractory to initial therapy and can lead to patients receiving general anaesthesia and mechanical ventilation.

Table 43.3 Features suggestive of pseudoseizures

Lack of stereotyped seizures, with behavioural manifestations varying from event to event

Lack of sustained convulsive activity – ‘on–off’ appearance

Increase in movement if restraint is applied

Abolition of motor movements with reassurance or suggestion

Resistance to eye opening and gaze aversion

Poor response to treatment, refractory status epilepticus

Absence of pupillary dilatation

Normal tendon reflexes and plantar responses immediately after convulsion

Lack of metabolic consequences despite some hours of apparent fitting

NON-CONVULSIVE STATUS EPILEPTICUS

This may account for approximately 25% of SE, though its incidence is probably underestimated because of failure to recognise and diagnose the condition.

The diagnosis of NCSE should be considered in any patient with an unexplained altered conscious state, particularly those with CNS injury, metabolic disturbance, hepatic encephalopathy and sepsis. Series where EEG has been performed in critically ill patients with an unexplained depressed conscious state have found a high incidence of NCSE (8–18%).²⁰^–²² EEG monitoring is required in patients with GCSE who do not recover consciousness after resolution of overt convulsive activity; in one study more than 14% of such patients had NCSE.¹⁴

Considerable debate exists regarding the precise criteria for diagnosing NCSE and published reports often describe diverse cohorts of patients. The diagnosis of NCSE generally requires a change in behaviour and/or mentation from baseline for at least 30 minutes, no overt seizure activity and an EEG with epileptiform discharges. A response to intravenous antiepileptic drugs (e.g. benzodiazepines), with clinical improvement and resolution or improvement in EEG epileptic activity, is helpful in confirming the diagnosis.²³

Various classifications for NCSE have been suggested.^4,²³^–²⁵ Traditionally NCSE is divided into absence SE (ASE) and complex partial SE (CPSE), though it may not always be possible to differentiate between the two types.^23,²⁴

ASE is characterised by bilateral diffuse synchronous seizures.²³ Typical ASE has generalised 3-Hz spike-wave discharge EEG activity occurring with altered behaviour or loss of responsiveness and is seen in children with idiopathic generalised epilepsy who are otherwise normal. This form of SE is relatively benign. Atypical ASE is a heterogeneous syndrome occurring in patients with mental retardation and epilepsy with multiple seizure types, or with other forms of diffuse cerebral dysfunction. The prognosis is usually poor and is related to the underlying condition.

CPSE, also referred to as ‘epileptic twilight state’ and ‘temporal-lobe SE’, is accompanied by lateralised seizure activity on EEG.²³ A wide variety of clinical features and degree of impairment of consciousness is possible and includes confusion, agitation, bizarre or aggressive behaviour and coma. Behavioural accompaniments such as lip smacking, automatisms and gaze deviation may occur, depending on the seizure origin within the brain. Debate exists over whether the seizure activity causes brain injury and much of the morbidity appears attributable to the underlying illness.

NCSE is often mistaken for other conditions, resulting in a delay in diagnosis and treatment. A high index of suspicion must therefore be present to trigger investigation with an EEG.

The differential diagnosis of NCSE is:

• metabolic encephalopathy

• drug intoxication

• cerebrovascular disease

• psychiatric syndromes (dissociative reactions, acute psychosis)

• postictal confusion

EPILEPTIFORM ENCEPHALOPATHIES

Some variants of SE deserve mention, such as comatose patients with epileptiform patterns on EEG who do not fit into the traditional classification of NCSE. Some of these cases may be late GCSE but many occur without prior clinical convulsions. In such situations it is unclear whether the abnormal discharges seen on the EEG are responsible for, or contribute to, the altered consciousness and abnormal movements, or are merely a reflection of a severe cerebral insult.²⁴

Myoclonic SE that follows a hypoxic insult falls into this category. Patients have incessant, at times asynchronous, rhythmic jerks that may involve the entire body. This clinical appearance after an anoxic insult is associated with an extremely poor outcome.²⁶

INVESTIGATIONS

Not all of the investigations listed in Table 43.4 need to be performed in every patient. The selection of tests depends on both the patient’s history and presentation.

Table 43.4 Investigations in status epilepticus

Initial studies

Blood glucose, electrolytes (sodium, potassium, calcium, magnesium), urea

Oximetry Spo₂ or arterial blood gases

Anticonvulsant drug levels

Full blood count

Urinalysis

Further investigations after stabilisation

Liver function tests, lactate, creatine kinase

Toxicology screen

Lumbar puncture

Electroencephalogram

Brain imaging with computed tomography or magnetic resonance imaging

NEUROIMAGING

Most patients with SE should have a computed tomography (CT) scan of the brain performed at some point. Many patients with established epilepsy who have already been thoroughly evaluated do not require another brain-imaging procedure after an episode of SE.¹ However, if there is reason to suspect a new problem, and when the need for imaging is not urgent, magnetic resonanceimaging (MRI) may be preferable because it occasionally reveals abnormalities not visualised on CT scans. In children, emergent imaging is required if there is a persisting neurological deficit or abnormal mental state, and electively for focal seizures. Imaging should only be performed after control of SE and patient stabilisation.²⁷

LUMBAR PUNCTURE

In any patient, especially in young children with fever and SE, CNS infection and lumbar puncture along with blood cultures should be considered. Meningitis is an uncommon cause of SE in adults and, unless the suspicion of CNS infection is high, brain imaging should be performed before a lumbar puncture. Contraindications to lumbar puncture include intracranial hypertension, mass lesion and hydrocephalus. If meningitis is suspected but a lumbar puncture cannot be performed expediently, antibiotics should be administered immediately rather than delayed. Approximately 20% of patients have a modest CSF white cell count pleocytosis after SE and such patients should be treated for suspected meningitis until the diagnosis is excluded by culture or other means.¹

MANAGEMENT

GENERALISED CONVULSIVE STATUS EPILEPTICUS

An accurate history should be obtained, with particular emphasis on eye-witness accounts of the onset and nature of the seizures, and a full physical examination performed. However, neither should delay initial emergency management. There is evidence that the longer SE goes untreated, the harder it is to control with drugs.^28,²⁹

Management of SE involves termination and prevention of recurrence of seizures, treating precipitating causes and underlying conditions, and avoidance of complications.

Few controlled data are available to support the use of any particular agents. The most useful evidence comes from a randomised, double-blind clinical trial for treatment of GCSE which found that lorazepam, phenobarbital or diazepam followed by phenytoin are all acceptable as initial treatment, but that phenytoin alone was not as effective as lorazepam.²⁹ Another randomised controlled trial in the pre-hospital setting found intravenous lorazepam and diazepam to be equally effective and superior to placebo in terminating GCSE.⁷

The EEG goal of treatment for refractory SE remains controversial, with some advocating EEG background suppression (isoelectric) and others suppression of seizures regardless of the EEG background activity.^10,^16,³⁰

Various protocols for SE management have been suggested.^1,^16,³⁰ One approach is outlined in Box 43.1.

Box 43.1 Protocol for management of status epilepticus

1 Assess A, B, C, GCS

2 Give O₂ and consider need for intubation/ventilation

3 Monitor blood pressure, ECG, pulse oximetry

4 Obtain IV access and draw blood for investigations

5 If patient is hypoglycaemic, or if blood glucose estimation is not available, give glucose:

Adults: give thiamine 100 mg IV and 50 ml of 50% glucose IV

Children: give 2 ml/kg of 25% glucose IV

6 Seizure control:

A Give benzodiazepine,* for example:

Diazepam 0.2 mg/kg IV at 5 mg/min up to total dose of 20 mg

Lorazepam 0.1 mg/kg IV at 2 mg/min up to total dose of 10 mg

Clonazepam 0.01–0.02 mg/kg IV at 0.5 mg/min up to total dose of 4 mg

If diazepam stops the seizures, phenytoin should be given next to prevent recurrence

Repeat dose every 2–5 min if required. Note: risk of respiratory depression with cumulative doses

B If seizures persist, give phenytoin:

Phenytoin 15–20 mg/kg (adults ≤ 50 mg/min; children ≤ 1 mg/kg per min) or fosphenytoin 15–20 phenytoin equivalents (PE) mg/kg IV (adults ≤ 150 mg/min; children ≤ 3 mg/kg per min)

Additional doses of 5 mg/kg IV, to a maximum dose of 30 mg/kg, can be given for persistent seizures

Monitor blood pressure and ECG during infusion. If hypotension or arrhythmias develop, stop or slow the rate of the infusion

C If seizures persist (refractory status epilepticus), intubate and ventilate patient. Give either:

Thiopental: slow bolus 3–5 mg/kg IV, followed by infusion 1–5 mg/kg per h or

Propofol: slow bolus 1–2 mg/kg IV, followed by infusion 2–5 mg/kg per h ^† or

Midazolam: slow bolus 0.1–0.2 mg/kg, followed by infusion 0.1–1.0 mg/kg per h

Titrate doses based on clinical and electrographic evidence of seizures, targeting electrographic suppression of seizures or EEG background suppression (isoelectric)

Monitor BP and maintain normotension by reducing infusion rate and/or giving fluids/pressor agents

D Insert nasogastric tube and administer usual anticonvulsant medications if patient is receiving treatment for pre-existing epilepsy

E Beware of ongoing unrecognised seizures

Use EEG monitoring until seizures are controlled and then for 1–2 h after seizures stop. Continue to monitor the EEG continuously, or for periods of more than 30 min every 2 h, during the maintenance phase

Avoid muscle relaxants (use continuous EEG if giving repeated doses of muscle relaxants)

F Discontinue midazolam or thiopental, or start reducing propofol, approximately 12 h after resolution of seizures. Use continuous EEG monitoring and observe for further clinical and/or EEG seizure activity. If seizures recur, reinstate the infusion and repeat this step at 12–24-h intervals or longer if the patient’s seizures remain refractory

In addition:

Look for and treat cause and precipitant ^‡

Look for and treat complications: hypotension, hyperthermia, rhabdomyolysis

^* If IV access is not obtainable, consider rectal diazepam, buccal/sublingual or intranasal or intramuscular midazolam, intramuscular fosphenytoin.

^† High infusion rates for prolonged periods require caution.

^‡ In refractory status epilepticus, consider giving pyridoxine for children < 18 months or if isoniazid toxicity is suspected in adults.GCS, Glasgow Coma Score; ECG, electrocardiogram; IV, intravenous; EEG, electroencephalogram; BP, blood pressure.

NON-CONVULSIVE STATUS EPILEPTICUS

Patients with NCSE are a heterogeneous group who are likely to vary in their response to treatment depending on the underlying aetiology.²³

There is considerable debate as to whether NCSE presents the same degree of risk of neurological injury as GCSE.²⁵ Prompt treatment is generally recommended and the use of additional non-anaesthetising anticonvulsants, such as phenobarbital and valproate, prior to embarking on general anaesthesia has been suggested.^16,²³ Others recommend that, for comatose patients with NCSE, a similar treatment approach to GCSE be taken.³⁰

The potential side-effects of aggressive treatment (hypotension, immunosuppression) need to be balanced against the potential neurologic morbidity of NCSE.^24,³¹ Particularly in elderly patients, aggressive treatment and anaesthesia may be associated with more risk than benefit and result in a worse outcome.^31,³²

Prognosis is most closely related to the underlying aetiology.³³

DRUGS FOR STATUS EPILEPTICUS

BENZODIAZEPINES

Benzodiazepines are fast-acting antiseizure drugs and are therefore preferred as initial therapy. They act mainly by enhancing the neuroinhibitory effects of GABA_A. The efficacy of benzodiazepines may diminish with prolonged use in SE due to reduced receptor affinity for benzodiazepines.¹²

Diazepam is a highly lipid-soluble drug with rapid CNS penetration, but with a short duration of action. It can be administered intravenously or by the rectal route. Rectal administration can be achieved using a specially formulated rectal gel or the intravenous preparation can be diluted with an equal amount of saline and flushed into the rectum. Rectal administration should be considered when vascular access is delayed and may be particularly useful in the pre-hospital setting.

Lorazepam is less lipid-soluble than diazepam and after intravenous injection, brain and CSF levels rise at a slower rate than those of diazepam. However, a double-blind, randomised comparison of intravenous diazepam and lorazepam in SE in the pre-hospital setting found both drugs to be equally safe and effective.⁷ Despite their equivalence as initial therapies, lorazepam has a longer duration of antiseizure effect than diazepam, and has a lower incidence of seizure recurrence when used alone.¹

Midazolam has a short duration of action that may allow earlier assessment of the patient’s postictal neurologic condition than longer-acting benzodiazepines. Midazolam has the advantage of being able to be administered via buccal, intranasal and intramuscular routes. Intranasal midazolam is as effective as intravenous diazepam in children ³⁴ and buccal midazolam is as effective as rectal diazepam in prolonged seizures.³⁵ Whereas intramuscular administration of diazepam and lorazepam is not recommended owing to their slow absorption, intramuscular midazolam is rapidly absorbed and in one study it was equally efficacious as intravenous diazepam in treating motor seizures in children.³⁶ These alternative routes of administration may be more convenient and acceptable than intravenous and rectal administration, particularly in the pre-hospital setting and when intravenous access is difficult.

Midazolam administered by bolus and infusion may terminate seizures when other agents have failed. It may also have fewer side-effects than alternative agents available for the treatment of refractory SE.³⁷ A limiting factor in its use is tachyphylaxis, which may necessitate a several-fold increase in the dose to maintain seizure control.³⁰ There is a wide variation in recommended infusion rates, from 0.1–0.4 mg/kg per hour¹⁶ to 0.2–2.9 mg/kg per hour.¹⁰

Clonazepam has a longer duration of action than diazepam and is given by intravenous bolus. Early reports suggested that it has better efficacy and fewer side-effects than diazepam, though there are no published comparisons.

PHENYTOIN

Phenytoin is useful for maintaining a prolonged antiseizure effect after rapid termination of seizures with a benzodiazepine, or when benzodiazepines fail. When used alone as initial therapy phenytoin is not as efficacious as benzodiazepines for terminating seizures.²⁹

When phenytoin is infused at the maximal adult recommended rate of 50 mg/min, hypotension occurs in up to 50% of patients and cardiac rhythm disturbance occurs in 2%. These adverse effects are more common in older patients and those with cardiac disease and are due to the phenytoin itself as well as the propylene glycol diluent. Blood pressure and the ECG should be monitored during infusion of phenytoin and the infusion slowed or stopped if cardiovascular complications occur.

Intramuscular administration of phenytoin is not recommended as absorption is erratic and it can cause local tissue reactions.

Fosphenytoin, a new water-soluble prodrug of phenytoin, is converted to phenytoin by endogenous phosphatases.³⁸ Doses of fosphenytoin are expressed as phenytoin equivalents (PE). Fosphenytoin can be administered at rates of up to 150 PE mg/min, since it is not formulated with propylene glycol, allowing therapeutic serum concentrations of fosphenytoin to be attained within 10 minutes. However, this may not necessarily result in more rapid CNS penetration and onset of action.³⁹

Systemic side-effects are similar for phenytoin and fosphenytoin, although reactions at the infusion site are less common with fosphenytoin.³⁸

Fosphenytoin can also be administered intramuscularly, though absorption is slower than intravenous administration, and this route should only be used when intravenous access is not possible.

SODIUM VALPROATE

There are reports of intravenous valproate being used to treat both GCSE and NCSE in adults and children. It is non-sedating and it appears to be well tolerated with few reports of hypotension or respiratory depression.⁴⁰ An initial dose of 25–45 mg/kg administered at a maximum rate of up to 6 mg/kg per min has been recommended.¹⁶ The exact role of valproate in the management of SE remains to be established and there are insufficient data to recommend its use before phenytoin.

BARBITURATES

Phenobarbital is a potent anticonvulsant with a long duration of action. The usual dose is 15–20 mg/kg intravenously. It has equal efficacy to benzodiazepines and phenytoin when used first-line, but may cause greater depression of respiration, blood pressure and consciousness and therefore is often only used if these agents fail. However, many would advocate alternative and more aggressive measures for treatment of refractory SE at this point as the likelihood of phenobarbital controlling seizures when these other agents have failed is small.^10,¹⁵

Thiopental is an intravenous anaesthetic agent used for refractory SE. A dose of 3–5 mg/kg is usually given for intubation, followed by repeated doses of 0.5–1 mg/kg until seizures are controlled. Following bolus intravenous administration, the drug is rapidly redistributed into peripheral fat stores and an infusion of 1–5 mg/kg per hour is required for ongoing suppression of seizures. Once lipid stores are saturated the duration of action is prolonged and recovery may take hours to days. Prolonged therapy requires the use of EEG monitoring to ensure that the seizures remain suppressed and to allow titration to the lowest dose that achieves the EEG target of seizure and/or EEG background suppression. Side-effects include hypotension, myocardial depression and immunosuppression with increased risk of infection.

Pentobarbital (the first metabolite of thiopental) is available in the USA as the alternative to thiopental.

Compared with other agents used in refractory SE (midazolam and propofol), barbiturates may result in a lower frequency of short-term treatment failure and breakthrough seizures but more hypotension and slower recovery from anaesthesia.⁴¹

PROPOFOL

Propofol (2,6-diisopropylphenol) is an anaesthetic agent that has become increasingly popular for the treatment of refractory SE. It is administered as an intravenous bolus followed by infusion and intubation and ventilation are required.

Compared with high-dose barbiturates (pentobarbital) in adult patients with refractory SE, propofol has been found to control seizures more quickly and, because of its shorter duration of action, allows earlier re-emergence from anaesthesia.⁴² However, seizures tend to recur with sudden discontinuation of propofol, necessitating recommencement of the infusion and a more gradual tapering of the dose, such that both drugs may ultimately result in similar duration of ventilation and ICU stay.⁴²

There is concern that prolonged high-dose propofol use (e.g. > 5 mg/kg per hour) may result in myocardial failure, hypoxia, metabolic acidosis, lipaemia, rhabdomyolysis and death (propofol infusion syndrome).⁴³ Initial reports were in children but later also adults and, as such, its use requires caution. There are series, however, of prolonged high-dose propofol use in adults with SE without major adverse effects.⁴⁴

NEUROMUSCULAR-BLOCKING AGENTS

Paralysis is indicated if uncontrolled fitting causes difficulty with providing adequate ventilation or severe lactic acidosis. Neuromuscular blockade should only be used if continuous EEG monitoring is available, as the clinical expression of seizure activity is abolished.

OTHER AGENTS OF POTENTIAL USE IN REFRACTORY STATUS EPILEPTICUS

Ketamine may be a useful adjuvant in the treatment of refractory SE.⁴⁵ The newer antiepileptic drugs such as topiramate may also have a role in refractory SE treatment.⁴⁶ Inhalational anaesthetic agents such as isoflurane may also be useful.⁴⁷

SURGERY

Surgery has occasionally been used in refractory SE with procedures based on standard epilepsy surgery techniques. Some success has been reported with focal resections, subpial transection, corpus callosotomy, hemispherectomy and vagus nerve stimulation.⁴⁸^–⁵⁰

INTENSIVE CARE MONITORING

Monitoring using ECG, intra-arterial and central venous catheters, capnography and pulse oximetry should be considered in patients with, or at risk of, cardiorespiratory compromise. Indications for EEG monitoring are listed in Table 43.5. Cerebral function monitors are useful in titrating doses of anaesthetic agents to EEG background suppression, but may not have sufficient sensitivity to detect seizure activity at other times. Intracranial pressure monitoring should be considered if elevated intracranial pressure is suspected.

Table 43.5 Indications for electroencephalogram (EEG) monitoring ¹⁴

Refractory status epilepticus, to aid the titration of anticonvulsant anaesthetic drugs (minimising dose and toxicity) and ensure suppression of seizure activity*

Patients receiving neuromuscular blockade*

Patients who continue to have a poor conscious state after apparent cessation of seizures

Suspected non-convulsive status epilepticus in a patient with an altered conscious state

Suspected pseudoseizures

* Continuous or regular intermittent EEG monitoring is recommended.

OUTCOME

The prognosis of patients with SE is most strongly related to age and aetiology.^3,³³ Overall 30-day mortality is 15–20%.^3,⁴ Children have a much lower mortality of 3%⁵¹ whereas those aged over 65 years have a mortality rate of 30%.^3,⁴ SE that is precipitated by low antiepileptic drug levels or systemic infection has a very low mortality.³ Patients who develop SE secondary to an acute CNS or systemic metabolic insult have a higher mortality than those who develop SE without a clear precipitant.³ SE precipitated by hypoxia is usually fatal.²⁶ NCSE detected in comatose critically ill patients, despite recognition and treatment, has a poor outcome.^22,³² Refractory SE carries a worse prognosis that is mainly determined by the underlying cause.^9,¹¹