Status epilepticus

Status epilepticus is defined as epileptic activity that continues for longer than 5–30 minutes, either as a single seizure or as recurrent seizures without inter-ictal return of consciousness. The seizure activity is usually classified as partial or generalized. Most episodes of status develop without a prior history of epilepsy. This fact is of major clinical relevance as the emergency management of all patients with status epilepticus must include a search for underlying causes. Although status epilepticus is an uncommon admission diagnosis among patients admitted to a general intensive care unit, a sound knowledge of the causes and treatment of this medical emergency is essential for prompt and effective management. Convulsive seizure activity causes marked systemic disturbances and neuronal injury proportional to the duration of seizure activity. Non-convulsive status epilepticus should be suspected in patients with impaired consciousness without obvious cause and can be definitely diagnosed only with electroencephalography monitoring. An intravenous bolus dose of a benzodiazepine (diazepam or lorazepam) should be used initially to terminate seizures. After this, an appropriate antiepileptic agent (phenytoin) should be started and any systemic disturbances treated. Patients with status epilepticus refractory to the above treatment measures should have general anaesthesia induced and maintained with infusions of an agent with γ-aminobutyric acid (GABA)-ergic activity (thiopentone, propofol or midazolam), aiming for electro-encephalographic burst suppression for 24 hours in the first instance, but longer if necessary.     

Treatment of Pediatric Status Epilepticus

Status epilepticus is characterized by a prolonged, self-sustaining seizure or repeated seizures without return to baseline. The clinical manifestations of status epilepticus in children and adults range from overt generalized convulsions to more subtle behavioral manifestations, including unresponsiveness in the setting of the intensive care unit. Status epilepticus is the most common neurologic emergency of childhood. A large proportion of these episodes are the result of a prolonged febrile seizure or an acute symptomatic etiology. Fortunately, status epilepticus occurs without consequence for many children, but for others, it is correlated with long-term neurologic dysfunction or death. Treatment of status epilepticus should commence promptly upon its recognition, using predefined treatment protocols. The goal of treatment is the rapid termination of the seizure, to minimize the acute and chronic effects of this emergency and to allow for the prompt assessment and management of the underlying precipitant. Currently, the drug class of first choice in the in-hospital and out-of-hospital treatment of status epilepticus is the benzodiazepines, which may need to be quickly followed by a next-line agent, as the efficacy of the benzodiazepines is negatively correlated with seizure duration. Traditionally, these next-line agents have included phenobarbital and phenytoin, but emerging evidence supports the use of intravenous formulations of other antiepileptic drugs. If the first two agents fail, high-dose intravenous midazolam or anesthetic therapy should be rapidly initiated. This paper reviews the current treatment options and strategies for pediatric patients with status epilepticus.     

Anaesthesia and epilepsy

Epilepsy is the most common serious neurological disorder, with a prevalence of 0.5-1% of the population. While the traditional antiepileptic drugs (AEDs) still play a significant role in treatment of seizures, there has been an influx of newer agents over the last 20 yr, which are now in common usage. Anaesthetists are frequently faced with patients with epilepsy undergoing emergency or elective surgery and patients suffering seizures and status epilepticus in the intensive care unit (ICU). This review examines perioperative epilepsy management, the mode of action of AEDs and their interaction with anaesthetic agents, potential adverse effects of anaesthetic agents, and the acute management of seizures and refractory status epilepticus on the ICU. Relevant literature was identified by a Pubmed search of epilepsy and status epilepticus in conjunction with individual anaesthetic agents.     

Status epilepticus: pharmacokinetic basis of anticonvulsant treatment in adults

In status epilepticus, the optimal efficacy of the antiepileptic drugs depends notably on effective, quickly reached and sufficiently lasting cerebral concentrations and the optimal tolerability notably on the lack of excessive storage in the brain and other tissues. So, the best efficacy-tolerability ratio of these drugs is largely determined by their pharmacokinetic properties. A linear kinetics, a not too short distribution half-life, a neither too brief nor too long elimination half-life, a fast and easy crossing of the blood-brain barrier and the lack of long-lasting accumulation in fat tissues are among the main ideal pharmacokinetic properties. Any of the antiepileptic drugs currently used in status epilepticus has all these properties together. An accurate knowledge of the pharmacokinetics is absolutely crucial to rationally decide the route of administration, the loading dose and the maintenance doses. However, pharmacokinetics must only complete, but cannot replace, the clinical experience and judgement, especially because some limitations: kinetic equations are mathematically exact but theoretical; individual kinetics in a given patient is exceptionally known in clinical practice; finally the pharmacokinetics may be significantly modified during a status epilepticus, especially of the generalized convulsive type, due to systemic consequences and complications of the seizures. In the emergency situation of status epilepticus, the correlation between the clinical efficacy and the so-called "therapeutic" plasma levels remains ill defined. The reported values are often very high and their range appears very large. Nevertheless plasma levels are useful, especially for the monitoring of the evolution; they are mandatory for nonlinear-kinetics drugs.     

Management of status epilepticus: a narrative review

Status epilepticus causes prolonged or repetitive seizures that, if left untreated, can lead to neuronal injury, severe disability, coma and death in paediatric and adult populations. While convulsive status epilepticus can be diagnosed using clinical features alone, non-convulsive status epilepticus requires confirmation by electroencephalogram. Early seizure control remains key in preventing the complications of status epilepticus. This is especially true for convulsive status epilepticus, which has stronger evidence supporting the benefit of treatment on outcomes. When status epilepticus becomes refractory, often due to gamma-aminobutyric acid and N-methyl-D-aspartate receptor modulation, anaesthetic drugs are needed to suppress seizure activity, of which there is limited evidence regarding the selection, dose or duration of their use. Seizure monitoring with electroencephalogram is often needed when patients do not return to baseline or during anaesthetic wean; however, it is resource-intensive, costly, only available in highly specialised centres and has not been shown to improve functional outcomes. Thus, the treatment goals and aggressiveness of therapy remain under debate, especially for non-convulsive status epilepticus, where prolonged therapeutic coma can lead to severe complications. This review presents an evidence-based, clinically-oriented and comprehensive review of status epilepticus and its definitions, aetiologies, treatments, outcomes and prognosis at different stages of the patient’s journey.     

Antiepileptic treatment in cerebral lesions: what are the indications and the main practical use?

The aim of this report is to review the indication and the practical use of the antiepileptic drugs in patients with cerebral lesions. The use of antiepileptic drugs to treat seizure or status epilepticus in an emergency is well catalogued and reported in this paper. Practical use of antiepileptic drugs, after a first seizure or to prevent a seizure, in patients with a cerebral lesion, is controversial. The question of antiepileptic drugs in seizures and in prophylaxis is discussed in different types of cerebral lesions: head injury, stroke, cerebral arteriovenous malformation and cerebral tumour.     

Epilepsy in anaesthesia and intensive care

Epilepsy is defined as recurrent (two or more) epileptic seizuresunprovoked by any immediately identifiable cause. A seizurecan be defined as the clinical manifestation of an abnormaland excessive discharge of neurones, which is seen as alterationof consciousness, motor, sensory or autonomic events. Epilepsyis relevant to the anaesthetist for several reasons, for examplemedication and drug interactions, postoperative seizures, andintensive care management of status epilepticus.     

Status epilepticus

Status epilepticus is a medical emergency that requires rapid and vigorous treatment to prevent neuronal damage and systemic complications. Failure to diagnose and treat status epilepticus accurately and effectively results in significant morbidity and mortality. Cerebral metabolic decompensation occurs after approximately 30 min of uncontrolled convulsive activity, and the window for treatment is therefore limited. Therapy should proceed simultaneously on four fronts: termination of seizures; prevention of seizure recurrence once status is controlled; management of precipitating causes of status epilepticus; management of the complications. This article reviews current opinions about the classification, aetiology and pathophysiology of adult generalised convulsive status epilepticus and details practical management strategies for treatment of this life-threatening condition.     

Rapidly lethal progression of a therapy-resistant status epilepticus

We present a case of death after first manifestation of generalised convulsive status epilepticus in a young man. A previously healthy 23-year-old man was admitted to our emergency department by ambulance service with approximately 20 min of generalised convulsive seizures. First line treatment in the emergency ward with benzodiazepines failed. The patient was cardiopulmonary stable until, after more than 30 min of status epilepticus, he developed tachycardia and became bradypnoeic. Intubation and ventilation was performed and anticonvulsive treatment was escalated with thiopental. Fifteen minutes later he developed ventricular fibrillation. CPR was started. The patient became asystolic after 90 min CPR following the ILCOR (International Liaison Committee on Resuscitation) Instructions. CPR was continued for another 30 min without success. The patient died after 120 min of maximal efforts. Autopsy and toxicology were performed, neuropathologic examination showed general brain edema and neuronal cell loss in purkinje cell layers of the cerebellum and olive knots which may be the consequence of generalised convulsive status epilepticus. We conclude: status epilepticus becomes refractory in approximately 30 % of cases. Until now, there are no randomised trials on the optimal treatment of refractory status epilepticus. Better treatment algorithms are urgently needed.     

Intracerebral hemorrhage immediately following the operation of chronic subdural hematoma

Complications following the operations for chronic subdural hematoma include recurrence of the hematoma, infection, seizure, and failure of the brain to expand due to cerebro-cranial disproportion. This report presents cases with intracerebral hemorrhage which is relatively rare complication. In case 1, a 35-year-old man developed status epilepticus immediately after the operation for chronic subdural hematoma. An emergency CT scan revealed acute brain swelling, and still, after the external decompressive craniotomy, CT scan showed severe brain swelling with subcortical diapedetic hemorrhage. In case 2, a 78-year-old woman whose CT scan had shown bilateral CSH and brain herniation, demonstrated intracerebral hemorrhage in the medial occipital lobe when examined post-operatively by CT scan. It is possible that the mechanisms of intracerebral bleeding following the operation for CSH are 1) diapedesis through increased permeability of parenchymal blood vessels due to the sudden increase in cerebral blood flow following the existence of longstanding extracerebral mass, and 2) hemorrhagic infarction due to recanalization of posterior cerebral artery compressed by the herniating medial temporal lobe. We should therefore avoid sudden decompression in the management of the cases which showed pre-operative consciousness disturbance or abnormal low or high density on CT scan, because these findings may be preoperative indications of brain fragility.     

Cerebral hyperperfusion syndrome associated with non-convulsive status epilepticus following superficial temporal artery-middle cerebral artery anastomosis. Case report

A 77-year-old man developed cerebral hyperperfusion syndrome with temporal deterioration of consciousness and worsening of left hemiparesis on the 6(th) postoperative day following superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for right M(1) occlusion. Electroencephalography (EEG) revealed frequent ictal discharges in the right hemisphere, although convulsive seizures were not apparent. Administration of anticonvulsants was performed based on the diagnosis of non-convulsive status epilepticus (NCSE). Complete recovery from hyperperfusion syndrome was achieved with rapid improvement of EEG findings. The present case demonstrates the pathophysiological mechanism of hyperperfusion syndrome associated with NCSE after STA-MCA anastomosis.     

Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring.

OBJECT: The early pathophysiological features of traumatic brain injury observed in the intensive care unit (ICU) have been described in terms of altered cerebral blood flow, altered brain metabolism, and neurochemical excitotoxicity. Seizures occur in animal models of brain injury and in human brain injury. Previous studies of posttraumatic seizures in humans have been based principally on clinical observations without a systematic approach to electroencephalographic (EEG) recording of seizures. The purpose of this study was to determine prospectively the incidence of convulsive and nonconvulsive seizures by using continuous EEG monitoring in patients in the ICU during the initial 14 days post-injury. METHODS: Ninety-four patients with moderate-to-severe brain injuries underwent continuous EEG monitoring begin-ning at admission to the ICU (mean delay 9.6+/-5.4 hours) and extending up to 14 days postinjury. Convulsive and nonconvulsive seizures occurred in 21 (22%) of the 94 patients, with six of them displaying status epilepticus. In more than half of the patients (52%) the seizures were nonconvulsive and were diagnosed on the basis of EEG studies alone. All six patients with status epilepticus died, compared with a mortality rate of 24% (18 of 73) in the nonseizure group (p<0.001). The patients with status epilepticus had a shorter mean length of stay (9.14+/-5.9 days compared with 14+/-9 days [t-test, p<0.031). Seizures occurred despite initiation of prophylactic phenytoin on admission to the emergency room, with maintenance at mean levels of 16.6+/-2.8 mg/dl. No differences in key prognostic factors (such as the Glasgow Coma Scale score, early hypoxemia, early hypotension, or 1-month Glasgow Outcome Scale score) were found between the patients with seizures and those without. CONCLUSIONS: Seizures occur in more than one in five patients during the 1st week after moderate-to-severe brain injury and may play a role in the pathobiological conditions associated with brain injury.     

A clinical approach to coma: neurological assessment of the comatose patient

Coma is a state marked by the absence of arousal (wakefulness, vigilance) and awareness of one's self and environment. Patients in coma do not respond to internal or external stimuli and cannot be roused. Coma results from diffuse dysfunction of neuronal systems that govern awareness and arousal, and is a neurological emergency. The three main mechanisms of coma are structural brain lesions, diffuse neuronal dysfunction, and rarely psychiatric causes. Firstly, the patient should be stabilized by treating life-threatening conditions. Diagnostic and therapeutic steps should occur simultaneously. The history, physical examination and investigation results should be used to identify structural causes and diagnose treatable conditions. In many instances, the diagnosis is clear. Adoption of a systematic approach, based on the underlying principles of coma pathophysiology, combined with knowledge of the reversible causes increases the probability of establishing an early diagnosis. Patients not undergoing brain imaging should be regularly re-assessed. If CT imaging is unrevealing, then consideration should be given to advanced imaging and looking for evidence of treatable infection or poisoning, seizures including non-convulsive status epilepticus, endocrine disorders or thiamine deficiency.     

Prehospital management of patients with severe head injuries

Advanced prehospital emergency medical care of patients with a severe head injury must essentially focus on the impact of secondary cerebral insults of systemic origin on the outcome. The first objective of prehospital care is to prevent hypoxaemia and hypercapnia. Therefore, all patients with a Glasgow Coma Scale score equal to or lower than 8 must be treated with endotracheal intubation and controlled ventilation under continuous monitoring of SpO2 and PETCO2. Treatment is similar in head-injured patients with significant deterioration of consciousness level, seizures, respiratory distress, or severe facial and thoracoabdominal injuries. The endotracheal tube is inserted by the orotracheal route under direct laryngoscopy, after a rapid induction sequence of anaesthesia and immobilization of the cervical spine in neutral position. For the induction of anaesthesia in these high-risk patients (full stomach, unknown medical history, deteriorated haemodynamic status), etomidate and suxamethonium are the preferred agents. Sedation is maintained with an hypnoticopioid association (fentanyl). Simultaneously, the main goal is the maintenance of an optimal cerebral perfusion pressure, as arterial hypotension severely worsens cerebral ischaemia. Volume loading is accomplished with 0.9% saline and hydroxyethyl starch.     

Isoflurane in the management of status epilepticus after surgery for lesion around the motor area

Summary When conventional treatment for status epilepticus fails, general anaesthesia is recommended. We present our experience with isoflurane, an inhalational anaesthetic, in the management of four patients with status epilepticus which occurred soon after surgery for motor area lesion. The seizures were controlled with relatively small concentrations of isoflurane. Hypotension, the only adverse effect of isoflurane, was managed easily with the use of dopamine in physiological saline. Although status epilepticus occurring soon after surgery is transient, it carries a risk of persistent brain damage if active treatment is not instituted promptly. Isoflurane general anaesthesia may be recommended to control it in the intensive neurosurgical care.     

Das neurogene Lungenödem Pathogenese, Klinik und Therapie

Neurogenic pulmonary edema (NPE) is a rare but always life-threatening complication in patients with central nervous system lesions. NPE is evident if patients shortly after cerebral lesions suddenly develop pulmonary edema and other causes of the symptoms, such as aspiration of gastric content, congestive heart failiure and direct toxic exposure, are ruled out. Methods: The current body of literature, partially obtained by computer-guided search (Winspirs) regarding epidemiology, pathophysiology and therapy of NPE was reviewed. Additionally, the case of a patient who developed a sudden pulmonary edema after an episode of tonic-clonic seizures is analyzed. We first provide information about history, definition, incidence and mortality of NPE. Second, a case report of a postictal NPE is presented to illustrate the clinical picture of NPE, and the applied therapeutic strategies are discussed. Third, recent pathophysiologic concepts about symptoms and possible therapeutic principles are reviewed. Fourth, a rational therapeutic plan for the prehospital emergency therapy of NPE is outlined. Results: The different ethiologies all have one characteristic feature: an acute emergency which causes increased intracerebral pressure (ICP). NPE is known in patients after cerebral trauma, intracranial hemorrhage, stroke, intracranial tumor or seizures. The incidence is estimated at around 1% after cerebral trauma, at 71% after cerebral hemorrhage and at 2% after seizures. Mortality is appraised to lie between 60 and 100%, independent of etiology. There is a definite pathophysiologic sequence leading to NPE: a central nervous system lesion causes a sudden increase in ICP which triggers an upregulation of sympathetic signal transduction to assure brain perfusion. Increased tonus of venous and arterial vessels and of myocardial function are the immediate consequences. However, if systemic vascular resistance (SVR) increases excessively, left ventricular failure and finally pulmonary edema (NPE) may result. Additionally, the protein-rich edema fluid points to an increased endothelial permeability within the pulmonary circuit. This is thought to be caused by the acute pressure increase and by neurohumoral mechanisms, possibly similar to those described for the systemic inflammatory response syndrome (SIRS). The most important central nervous system structures involved in NPE are the medulla oblongata and the hypothalamus. Conclusion: NPE is always a life-threatening symptom after increased ICP, where immediate therapeutic interventions are imperative. A rational therapeutic approach needs to be focused on decreasing ICP as primary goal. Additionally, attempts should be made to optimize body oxygenation, decrease pre- and afterload and increase myocardial contractility. Postictal patients suspicious for incipient ventilation problems must be admitted to hospital for further evaluation.     

Should we monitor with bispectral index in all patients at high risk for seizures in the operating room?

We report the case of a patient with a cerebral aneurysm, located in the left middle cerebral artery. During the clipping of this aneurysm, the bispectral index (BIS) increased for no apparent reason. This was then interpreted as intraoperative non-convulsive status epilepticus. This clinical condition may have negative impact in the prognosis of the patient, so it is very important to be able to detect this conditions as early as possible. Measuring the BIS while the patient is anaesthetised could be useful in this situation, considering that an increase in values greater than 60, associated with acidosis and without any other peri-anaesthetic explanation, may provide evidence of a convulsive equivalent state, allowing appropriate action to be taken.     

Treatment of convulsive and nonconvulsive status epilepticus

Opinion statement Status epilepticus (SE) should be treated as quickly as possible with full doses of medications as detailed in a written hospital protocol. Lorazepam is the drug of choice for initial treatment. If intravenous access is not immediately available, then rectal diazepam or nasal or buccal midazolam should be given. Prehospital treatment of seizures by emergency personnel is effective and safe, and may prevent cases of refractory SE. Home treat-ment of prolonged seizures or clusters with buccal, nasal, or rectal benzodiazepines should be considered for all at-risk patients. Nonconvulsive SE is underdiagnosed. An electroencephalogram should be obtained immediately in anyone with unexplained alter-ation of behavior or mental status and after convulsive SE if the patient does not rapidly awaken. Delay in diagnosis of SE is associated with a worse outcome and a higher likeli-hood of poor response to treatment. For refractory SE, continuous intravenous midazolam and propofol (alone or in combination) are rapidly effective. Randomized trials are needed to determine the best treatment for SE after lorazepam.     

Diagnosis and treatment of nonconvulsive status epilepticus in an intensive care unit setting

Opinion statement Nonconvulsive status epilepticus (NCSE) in adults is a heterogeneous epileptic emergency and includes absence status (AS), complex-partial status epilepticus (CPSE), and the status epilepticus of epileptic encephalopathy (SEEE). The latter seems to be strikingly frequent among patients in intensive care units (ICU). Diagnosis of NCSE is difficult, but has to be made quickly. It relies on clinical signs and a confirmation electroencephalography (EEG). According to the different etiologies and outcomes of AS, CPSE, and SEEE, treatment has to be individually adapted, but needs to follow some basic principles-treatment should take place in the ICU and be monitored by continuous EEG. With a few exceptions, the first drug is an intravenous benzodiazepine, mainly lorazepam. Intravenous fosphenytoin or phenytoin or valproate may follow next. If some forms of NCSE are resistant to first- and second-line treatments, single or combinations of anesthetics and enteral antiepileptic drugs (AEDs) may be added. This opinion is not evidence-based, and randomized controlled prospective trials to evaluate optimal treatment of NCSE are of first priority.     

Sustained Low-Efficiency Daily Diafiltration with Hemoperfusion as a Therapy for Severe Star Fruit Intoxication: A Report of Two Cases

Abstract

Over the past decade, star fruit (Averrhoa carambola) intoxication decreased in the Taiwanese society due to improved public education on chronic kidney disease (CKD). Various complications including hiccups, altered levels of consciousness, coma, and seizures have been reported in individuals with renal failure who ingested fresh star fruit or star fruit juice. A high mortality rate (from 33 to 80%) was observed in patients with altered levels of consciousness, despite prompt dialysis and supportive care. According to previous case reports, the proposed treatment of choice for severe star fruit intoxication may be continuous renal replacement therapy with or without hemoperfusion. We report two cases of star fruit intoxication with stage V CKD (one case is predialysis) presenting with coma and generalized tonic-clonic seizures. The two patients were treated with sustained low-efficiency daily diafiltration (SLEDD-f) and charcoal hemoperfusion. Status epilepticus was controlled fairly quickly after treatment with SLEDD-f and hemoperfusion. However, the outcomes in this report are still poor (both remained comatose; one of two patients died). Currently, there are no data for the use of SLEDD-f with hemoperfusion for severe star fruit intoxication. SLEDD-f with charcoal hemoperfusion may play a role in managing refractory status epilepticus in patients with severe star fruit poisoning.