Monday, May 3, 2021

Status Epilepticus Case File

Posted By: Medical Group - 5/03/2021 Post Author : Medical Group Post Date : Monday, May 3, 2021 Post Time : 5/03/2021
Status Epilepticus Case File
Eugene C. Toy, MD, Manuel Suarez, MD, FACCP, Terrence H. Liu, MD, MPH

Case 31
A 68-year-old white woman is hospitalized in the coronary care unit and has suffered  3 continuous tonic-clonic seizures within the past 45 minutes, each lasting about 5 minutes. She is 2 days postoperative from a  repaired ascending aortic aneurysm. She never recovered wakefulness in the postoperative  period. There are multiple hypodense embolic strokes revealed on a CT scan of the brain performed  the day after her surgery.  Her electroencephalogram (EEG) shows bursts of active seizure activity. Her respiratory rate is 18 breaths/minute, blood pressure is 160/90 mm Hg, heart rate is 150 beats/minute, and temperature is 99.9°F. She weighs 60 kg.

What is the most likely diagnosis?
What is the most likely mechanism responsible for the patient's condition?
What is the best immediate treatment?

ANSWER TO CASE 31:

Status Epilepticus

Summary: This 68-year-old patient has undergone multiple embolic strokes following aortic bypass surgery for the repair of an ascending aortic aneurysm. She has had 3 seizures within 45 minutes and had decreased sensorium since surgery. 
  • Most likely siagnosis: Status epilepticus. 
  • Mechanism: Multiple embolic strokes after aortic bypass surgery, leading to a decreased seizure threshold. 
  • Best immediate treatment: Intravenous benzodiazepines followed by an antiepileptic such as phenytoin. If needed, general anesthesia with midazolam or propofol can be used to assist in seizure control.
ANALYSIS

Objectives
  1. To understand the most common causes for seizures.
  2. To discuss the diagnosis and treatment of status epilepticus.
  3. To understand the role of medications and toxins in causing seizures.
Considerations
This 68-year-old patient has undergone an aortic bypass surgery for the repair of an ascending aortic aneurysm. She has been in coma since surgery, and the brain imaging reveals multiple embolic strokes. She has had 3 seizures within 45 minutes each lasting 5 minutes, which is consistent with status epilepticus. The most likely mechanism for the multiple seizures are the multiple embolic strokes after aortic bypass surgery leading to decreased seizure threshold in the region of the cerebrovascular accidents (CVAs). The most management important steps are to maintain oxygenation, suction oral secretions to prevent aspiration, and control the seizures. The best immediate treatment includes intravenous benzodiazepines, followed by an antiepileptic such as phenytoin. As a last resort, general anesthesia with IV midazolam or propofol can be used to assist in seizure control. Associated complications include aspiration of gastric secretions (airway control, elevation of head of bed to 45 degrees) , trauma from seizure activity (bed padding), and elevated creatine phosphokinase (CPK) levels with rhabdomyolisis and renal toxicity (hydration).

Approach To:
Status Epilepticus

Status epilepticus (SE) is defined as a condition in which continuous or rapidly repeated seizures occur without regaining consciousness between seizures. The pathophysiology of status epilepticus is incompletely understood. Up to 30% of adult 

seizure disorders

patients with a new diagnosis of epilepsy present as SE. The frequency of cases in the United States is approximately 150,000 per year, with 55,000 deaths annually. The mortality rate of status epilepticus is high, especially if treatment is not initiated quickly.

SE is a life-threatening condition requiring prompt management. SE with seizures lasting longer than 30 minutes or failure to regain consciousness between seizures carries a poor prognosis. SE is considered a medical emergency. An ambulance should be called for seizures lasting longer than 5 minutes. Approximately 2 million persons in the United States have epilepsy, making the prevalence of this disorder similar to that of type 1 diabetes mellitus. Annually, 100,000 new cases of epilepsy are diagnosed in the United States. Among the elderly epilepsy is dramatically higher (see Table 31-1).


MANAGEMENT
Control of the airway and effective ventilation are imperative. Hyperventilation and hypocapnia help offset the SE associated metabolic acidosis which results from the increased muscle metabolism and lactic acidosis. Once the seizures cease, this acidosis rapidly reverses if adequate perfusion returns the skeletal muscle. The use of intravenous bicarbonate should be avoided except in the most severe cases of acidosis. The patient must remain in a controlled environment to avoid bodily trauma. Periods of hypoventilation, cyanosis, and high mechanical ventilator (MV) pressures during active seizures should be anticipated. This may require paralysis of the patient if mechanical ventilation cannot be undertaken because of the high MV pressures. The patient should not be overly restrained while in an active state of seizure to avoid fractures and dislocations.

SE most commonly manifests itself as a series of tonic-clonic seizures. Tonic-clonic SE is managed by a regimen of intravenous diazepam or lorazepam plus intravenous phenytoin or fosphenytoin. If this fails to control the seizures, the patient is at risk for prolonged seizures and brain damage. Some patients with SE are unresponsive and may have myoclonus or focal motor activity. A characteristic series of electroencephalographic changes accompanies status epilepticus, and an electroencephalogram (EEG) must be obtained to confirm the diagnosis. SE is still a dangerous condition that is difficult to treat.

Benzodiazepines are the drugs of choice for the acute control of SE. Subsequent medications should include phenytoin or fosphenytoin in a continuous fashion to maintain therapeutic blood levels. If SE persists after the use of benzodiazepines and phenytoin compounds, drugs such as phenobarbital to induce coma should be

status epilepticus

Figure 31-1
. Algorithm for the treatment of status epilepticus.

considered. Failure to stop the convulsions with the regimen above requires anesthesia with midazolam or propofol as the next step in management. SE or seizures that have continued for more than 60 to 90 minutes while in the ICU tend to have severe systemic disturbances (eg, extreme hyperthermia, acidosis). Figure 31-1 indicates the approach to a stepwise treatment and the preferred dosages of antiepileptic medications, respectively.

Neurological Consultation
Neurological consultation should be undertaken in the evaluation of SE, especially if the diagnosis is uncertain, 2 or more antiepileptic drugs have failed to control the seizures, the patient is considering becoming pregnant, or the patient has a form of epilepsy that is particularly difficult to treat.

CAUSES OF SEIZURES
Drug-Induced seizures
The most common reason for seizures is noncompliance with antiepileptic drug therapy, most commonly phenytoin. Many medications are known to decrease the seizure threshold and cause seizures in otherwise healthy patients. Table 31-2 summarizes these drugs by class. Special attention must be paid to patients in renal 

seizure threshold

insufficiency or with CNS comorbidity when determining the preferred dosage of any of these antiepileptic drugs. Phenytoin itself can induce a positive antinuclear antibody (ANA) test, a lupus-like syndrome, drug fever, and even Stevens-Johnson syndrome. The ANA in drug- induced cases is of RNA origin; ANA of DNA origin is seen in SLE.

Infectious Causes
Infections are an important cause of seizures. Infections of the CNS and other sites produce acute seizures and can lead to chronic epilepsy. Direct infection of CNS tissues as in bacterial meningitis, viral encephalitis, neurosyphilis, cerebral malaria, and disseminated Lyme disease can all cause seizures. Systemic infections, such as bacterial endocarditis, include vegetations that embolize to the brain which can lead to a seizure. HIV/AIDS are also associated with several pathogens that can lead to convulsive states, including Toxoplasma and Polyomavirus , the agent of progressive multifocal encephalopathy (PME). Cryptococcal meningitis may also induce epilepsy. Among the childhood exanthems, measles can give rise to subacute sclerosing panencephalitis (SSPE) years after the infection, leading to a state of chronic recurrent seizures. Neurocysticercosis, caused by infection with Taenia solium (the pork tapeworm), is the most common parasitic pathogen of the CNS, which can lead to SE and is the most common cause of acquired epilepsy in developing countries.

Ethanol
Ethanol, through its effects on the GABA neurotransmitter, produces seizures both in instances of acute intoxication and in withdrawal situations (delirium tremens, DT). Complications of alcohol abuse such as head trauma, subdural hematomas, and stroke may lead to seizures. Alcohol withdrawal seizures carry a 5% risk of progressing to DT, a severe state of alcohol withdrawal associated with a hypermetabolic state and a high mortality. The treatment of seizures related to alcohol involves long-acting benzodiazepines (lorazepam, diazepam, or chlordiazepoxide). Chronic phenytoin therapy is not effective and should not be used.

Pseudoseizures
Psychogenic nonepileptic seizures (PNES), or pseudoseizures, must be distinguished from SE or any other true epileptic condition. Iatrogenic complications may ensue from improper treatment with anticonvulsants. Features that should raise suspicion of pseudoseizures are psychiatric comorbidities, gradual onset of the seizures, motor activity characterized by pelvic thrusting or head rolling, and vocalization such as crying and shouting in the middle of the seizure. Physical examination often reveals geotropic eye movements or eyes moving away from the examiner, and briskly reactive
pupils. The absence of cyanosis and seizure activity that intensifies when the patient is restrained are also consistent with pseudoseizures. The gold standard for diagnosis of PNES is video electroencephalography, in which no encephalographic changes would be expected while the patient was observed to have a seizure. Management of PNES must also concentrate on treating any underlying psychiatric comorbidity.

Electroencephalographic Studies
Approximately 50% of epileptic patients will have no abnormality on a single EEG. The EEG provides confirmation of abnormal electrical activity, the type of seizure, and its location. EEG results shortly after a seizure may be misleading; therefore, EEG studies should be performed 48 hours or more after a suspected seizure. The EEG should include recordings with provocation such as with sleep deprivation, photic stimulation, and hyperventilation.

Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (NMS) is a life-threatening neurological disorder caused by an adverse reaction to neuroleptic or antipsychotic drugs (haloperidol). NMS presents with muscle rigidity, fever, autonomic instability, and delirium. NMS elevates CPK and causes renal failure. Antipsychotics users should be monitored for this side effect. Treatment includes removal of the drug, aggressive hydration, and dantrolene therapy.


CLINICAL CASE CORRELATION
  • See also Case 27 (Traumatic Brain Injury), Case 30 (Altered Mental Status), and Case 32 (Stroke).

COMPREHENSION QUESTIONS

31.1 A 25 -year-old insulin-dependent diabetic was found unconscious in bed. His mother stated that he had taken his morning insulin but had not eaten breakfast. She heard noises and saw the patient having a tonic-clonic seizure in his bedroom. He is now arousable but in a postictal state. What is the most likely cause of the seizure in this case?
A. Head trauma with cerebral bleeding
B. Neutropenia
C. New onset of seizure disorder
D. Nutritional deficiency
E. Occult alcohol use

31.2  A patient with SE refractory to benzodiazepines and phenytoin treatment is intubated for control of the airway. The patient has been seizing for the past 2 hours while in the ICU. What is the next best step in this patient's management?
A. Call neurosurgery for operative intervention.
B. Get an MRI.
C. Consider general anesthesia and or propofol.
D. Administer magnesium intravenous bolus followed by continuous drip.
E. Consider phenobarbital orally or IM.


ANSWERS TO QUESTIONS

31.1  D. The most likely cause for the seizure on this diabetic patient is hypoglycemia, especially with the omission of breakfast. Rapid reversal of hypoglycemia is the key to recovery. The use of intramuscular glucagon is indicated and avoids the risk of aspiration when oral glucose is given. If oral glucose must be used, powdered sugar is preferred over liquid forms to prevent aspiration. The longer the CNS is depleted of glucose and oxygen the greater the likelihood of a neurological insult, and of the affected brain tissue being predisposed to seizure activity.

31.2  C. Once the main resources to stop seizures have been exhausted, general anesthesia with midazolam or propofol must be considered. In the treatment cascade, phenobarbital may follow benzodiazepines and phenytoin. This patient has been in SE for more than 90 minutes. Management of intractable SE includes general anesthesia as a final resort to reduce mortality from SE.


CLINICAL PEARLS

 Early control of seizures reduces the risk of chronic neurological damage.
 The first drugs of choice for the control of tonic-clonic seizures are the benzodiazepines. 
 Consider neuroleptic malignant syndrome as a cause of SE in cases where fever is present and there is a known use of haloperidol and/or succinylcholine. 
 Patients with SE may have rhabdomyolysis and acidosis, which is treated with hydration and urinary alkalinization. 
 Consider general anesthesia for cases of intractable SE. 
 Endotracheal intubation may be needed for airway control. 
 There is a 30% chance of seizures in a patient with a subdural hematoma. 
 Commonly used drugs can decrease the seizure  threshold, causing seizures in normal individuals. 
 SE patients should be adequately hydrated, and CPK,  electrolytes, BUN, and creatinine levels should be followed. 
 Infections in the CNS and external to the CNS can cause acute as well as chronic seizure states. 

References

Browne T, Holmes G. Review article. Primary care, epilepsy. N Engl} Med. 2001;344: 1145- 1151. 

Clifford S, Deutschman MS. Evidence Based Practice of Critical Care. Philadelphia: Saunders; 2010. 

Loscalzo J. Harrison's Pulmonary and Critical Care Medicine. McGraw-Hill; 2010.

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