The Acutely Unwell Or Periprocedural Patient

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People with epilepsy are often considered to be at higher risk when undergoing procedures. This is mainly due to the possibility of seizures occurring periprocedurally or due to the potential for interactions between drugs used during the procedure and the patient's AEDs.

Factors which may exacerbate seizures, such as sleep deprivation and alcohol, should be avoided prior to a procedure, and patients undergoing surgery should be advised to take their usual AEDs on the morning of surgery, even if fasting, and should continue their usual doses as soon as it is safe to do so.

Seizures are common after neurosurgical procedures, and are also common following cardiac operations [59], possibly due to complex alterations in metabolism, haemodynamic changes, alteration in blood/clotting factors and cerebral perfusion which may occur during cardiopulmonary bypass.

Although most of the local and general anaesthetic agents may have pro- as well as anti-convulsant effects [60], the actual risk of inducing a seizure is small. Enflurane appears to be associated with the highest risk of seizure [61].

Benzodiazepines are often used perioperatively and may prevent acute seizures, but care must be taken when weaning off these agents to avoid withdrawal seizures. Some analgesics such as the opiates - pethidine (meperidine) in particular - are associated with seizures, and should be avoided, where possible, post-operatively.

AED levels may be altered significantly post-operatively due to changes in hydration, volume of distribution, pharmacokinetics, pharmacodynamics, altered protein binding and blood loss. It is useful to have a baseline AED level at which the patient is seizure free to allow comparison and dose alterations post-operatively.

Patients with epilepsy in the intensive care unit (ICU) are at high risk of seizures. Seizures are often precipitated by this environment, even in patients without any history of epilepsy [62]. Organ failure, metabolic changes, electrolyte and fluid imbalance, cerebral oedema, hypoxia, hypotension and hypoglycaemia are all common occurrences, as is the presence of many drugs which may lower the seizure threshold. Most patients in the ICU are also sleep deprived [63]. Pre-existing AED regimens are often disturbed due to altered absorption, metabolism, dosing schedules and because the patient is unable to take drugs orally. In addition, because of the frequent use of sedation and neuromuscular blocking drugs, it may be difficult to know if a patient is actually seizing.

Oral dosing may be limited in patients who are fasting, post-ictal, have a reduced level of consciousness or who are intubated. Most AEDs can be given via an alternative route if the patient cannot swallow tablets:

• Phenytoin may be given intravenously, in suspension form via enteric tubes, or rectally. If given enterally, it should be given separately from feeds as these may reduce absorption.

• Fosphenytoin, a pro-drug of phenytoin, may be substituted. It can be given intramuscularly, which is useful when access is difficult, or intravenously.

• Phenobarbital may be given intravenously, intramuscularly or rectally. It is also available in liquid form which may be given via enteric tubes.

• Valproate may be given intravenously, as a syrup which may be given via enteric tubes, or by rectal suppositories which give good bioavailability.

• Carbamazepine can be given by suppository using the same dose as orally, and is also available in suspension form which can be given via enteric tubes.

• Benzodiazepines are usually used for acute seizure management rather than for chronic epilepsy treatment, but are available in many different forms which may be useful for patients who are acutely unwell. Lorazepam may be given intravenously or sublingually. Rectal diazepam is well absorbed, and is also available intravenously. Midazolam can be given into the buccal cavity or intranasally.

Most of the newer AEDs are still not available in intravenous form. However, most can be given via enteric tubes in the following preparations:

• Oxcarbazepine suspension

• Lamotrigine (tablets may be crushed)

• Topiramate (sprinkles may be injected using water)

• Levetiracetam liquid (intravenous levetiracetam is at an advanced phase of development and is expected to be commercially available in the near future)

• Gabapentin liquid.

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