Status Epilepticus - Management, Prognosis, and EEG utilization

Introduction

• Status epilepticus (SE)
• ≥5 minutes of continuous clinical and/or electrographic seizure activity
• Recurrent seizure activity without recovery (returning to baseline) between seizures

Emergency Management

• Non-invasive airway protection and gas exchange with head positioning Timing: Immediate (0-2 minutes) Goals: maintaining airway patency; to avoid snoring; administering O2

• Intubation
• Indications
• Airway/gas exchange compromised
• Elevated ICP suspected
• Glasgow coma scale <8
• If patient fails first- and second-line therapies
• Timing: Immediate (0-10 minutes)
• Goals: Establish secure oxygenation and ventilation

• Initial monitoring: O2, BP, HR, and ECG
• Timing: Immediate (0-2 minutes)
• Goals: Establish and support baseline vital signs

• Vasopressor support
• Indication - MAP <70 mmHg
• Timing: Immediate (5-15 minutes)
• Goals: Support cerebral perfusion pressure

• Finger stick blood glucose
• Timing: Immediate (0-2 minutes)
• Goals: Diagnose hypoglycemia

• Peripheral IV access
• Timing: Immediate (0-5 minutes)
• Goals
• Emergent initial AED therapy [First AED]
• Fluid resuscitation
• Nutrient resuscitation (thiamine + glucose)

• Urgent SE control therapy with AED [Second AED]
• Timing: Immediate after initial AED given (5-10 minutes)

• Neurologic exam
• Timing: Urgent (5-10 minutes)
• Goals: Evaluate for mass lesion; acute intracranial process

• Triage lab test panel
• Timing: Immediate (5 minutes)
• Goals: Diagnose life threatening metabolic condition

• RSE treatment
• Timing: Urgent (20-60 minutes after 2nd AED)
• Treatment strategies based on individual patient response and AED concentrations

• Urinary catheter
• Timing: Urgent (0-60 minutes)

• Continuous EEG
• Timing: Urgent (15-60 minutes)
• Evaluate for NCSE if not waking up after clinically obvious seizures cease

• Diagnostic testing: CT, LP, and MRI
• Selection depends on clinical presentation
• Timing: Urgent (0-60 minutes)
• Goals: Evaluate for mass lesions, meningitis, encephalitis

• Intracranial pressure monitoring
• Timing: Urgent (0-60 minutes of imaging diagnosis)
• Goals: Measure and control ICP
 

Table 1: Drug categorization on the basis of level of evidence available

American Epilepsy Society (AES) Proposed Algorithm for Convulsive SE

Initial Therapy Phase or Emergent Initial Therapy

• Benzodiazepines are considered as agent of choice

• I/V lorazepam through either dose method (Level A)
• Weight Based: 0.1 mg/kg at maximum rate of 2 mg/minute
• Wait for one minute
• Reassess
• If seizures continue
• Second IV catheter placement
• Additional doses of lorazepam can be infused
• Fixed dose based: Initial loading dose of lorazepam 4mg fixed dose; repeated if still seizing
• Adverse effects
• Hypotension
• Respiratory depression
• Considerations
• Dilute 1:1 with saline
• IV contains propylene glycol
• Treiman et al.
• Subgroup of 384 patients with overt generalized convulsive SE (GCSE)
• Lorazepam was successful in 64.9%
• Terminated seizures within 20 minutes
• Maintained seizure-free for first 60 minutes after administration
• Advantage: Effective duration against seizures is 4-12 hours

• If lorazepam is not available
• I/V diazepam: 0.15 mg/kg, up to 10 mg per dose (Level A)
• Adverse effects
• Hypotension
• Respiratory depression
• Considerations
• Rapid redistribution (short duration)
• Active metabolite
• IV contains propylene glycol
• Chamberlain et al.
• 140 patients on diazepam vs 133 patients on lorazepam (all randomized; pediatric patient groups)
• Absolute efficacy difference was only 0.8%
• No significant difference between both for convulsive SE treatment in pediatric population
• Advantage: Stability in liquid form for longer periods at room temperature, hence easy accessibility and availability

• If no I/V access available
• I/M midazolam: 10 mg for >40 kg, 5 mg for 13-40 kg; single dose (Level A)
• Adverse effects
• Hypotension
• Respiratory depression
• Considerations
• Active metabolite
• Renal elimination
• Rapid redistribution (short duration)
• If neither of the above options are available, either of the following
• I/V phenobarbital: 15 mg/kg/dose; single dose (Level A)
• Adverse effects
• Hypotension
• Respiratory depression
• Considerations
• IV contains propylene glycol
• Rectal diazepam: 0.2-0.5 mg/kg, max: 20 mg/dose; single dose (Level B)
• I/N midazolam (Level B)
• Buccal midazolam (Level B)

• If seizure control has reached clinically and electrophysiologically (as seen on EEG)
• Nonbenzodiazepine antiseizure drug loading dose should follow
• Symptomatic medical care should continue

Second Therapy Phase or Urgent Control Therapy

• Goals
• For patients who respond to emergent initial therapy and have complete resolution
• the goal is rapid attainment of therapeutic levels of an AEDContinued dosing for maintenance therapy
• For patients who fail emergent initial therapy, the goal is to stop SE

• If seizure continues, AED’s should be given in combination with benzodiazepines

• Preferred second therapy of choices (given as single dose)
• I/V fosphenytoin: 20 mg phenytoin equivalents (PE)/kg, max: 1500 mg PE/dose; single dose (Level U)
• Adverse effects
• Hypotension
• Arrhythmias
• Considerations
• Compatible in saline, dextrose, and LR solutions
• Infusion of fosphenytoin should be done with cardiac monitoring, due to increased risk for QT prolongation and arrhythmias
• Advantage: Can be infused rapidly as compared to phenytoin due to reduced risk of local irritation at the site of injection

• I/V levetiracetam: 60 mg/kg, max: 4500 mg/dose; single dose (Level U by AES 2016 and Level C by Brophy et al. 2012)

• I/V valproic acid: 40 mg/kg, max: 3000 mg/dose; single dose (Level B)
• Adverse effects
• Hyperammonemia
• Pancreatitis
• Thrombocytopenia
• Hepatotoxicity
• Considerations
• Use with caution in patients with traumatic head injury
• May be a preferred agent in patients with glioblastoma multiforme
• Contraindicate in Europe in pregnancy

• If none of the above are available

• I/V phenobarbital: 15 mg/kg; single dose (Level B)Adverse effectsHypotensionRespiratory depressionCardiac depressionParalytic ileusAt high doses, complete loss of neurological functionConsiderationsRequires mechanical ventilationIV contains propylene glyco

Table 2: Evidence for choice of AED in second therapy phase

EEG Utilization

• No data to support a standardized regimen for the intensity and duration of treatment of RSE

• It is usually dictated by continuous EEG (cEEG) findings

• Common practice is to achieve electrographic burst suppression
• 1-2 sec bursts of cerebral activity interspersed by 10 sec intervals of background suppression
• Pattern should be continued for 24-48 hours before sedation is lightened
• During burst suppression, continuation of other AED is controversial
• Stopping other AED to allow for down-regulation of receptors while patient is on pentobarbital may be useful

Table 3: Frequency and mortality associated with acute and chronic causes of SE in adults

Complications and Prognosis

• Generalized convulsive SE (GCSE)
• Complications include cardiac arrhythmias, hypoventilation, hypoxia, fever, and leukocytosis in patients with
• Risk factors leading to increase in complications include aspiration pneumonitis, pulmonary edema, and respiratory failure
• Important predictors of outcome
• Etiology
• Older age
• Medical comorbidity
• High APACHE-II scores
• Increased duration of SE in the setting of acute neurological insult are risk factors for long-term neurologic disability
• SE recurs in about one-third of patients with a first episode of SE
• 40% of patients with first episode of SE develop subsequent epilepsy

• Focal motor SE
• Prognosis depends on prognosis of underlying lesion
• Long-term morbidity in terms of weakness, sensory, and visual loss, and language dysfunction can be substantial, and many patients have severe cognitive problems
• Cortical laminar necrosis (CLN) can be a sequela; based on case reports derived from Donaire et al.
• Radiologically defined as high intensity cortical lesions on T1 weighted MRI images following a gyral distribution
• Histopathologically characterized by pan-necrosis of the cortex involving neurons, glial cells, and blood vessels
• Two patients with SE discussed in the case reports
• Both patients displayed permanent brain imaging abnormalities consistent with CLN after prolonged focal SE
• No metabolic or significant decreases in blood pressure during the episodes of focal SE
• The authors hypothesized that necrosis in these patients is primarily a consequence of repeated seizures
• The hypothesis is supported by the fact that CLN is seen in the same areas as those displaying acute cortical edema and hyperperfusion during the acute phase of SE

• Myoclonic SE (MSE)
• Prognosis depends on form of MSE
• Benign primary epilepsy syndromes leading to MSE have best prognosis
• Secondary myoclonic epilepsy syndromes leading to MSE are more refractory to AED’s
• Poorest prognosis in patients with MSE due to an acute new illness
• Presence of myoclonic seizures early after anoxia has been identified as a poor prognostic factor
• 89% of patients died in a review study of 134 cases of post-anoxic MSE

• According to Vignatelli et al., 30-day case fatality was 39% (33% excluding postanoxic patients) in Italians

• From a systemic review on 61 studies by Neligan et al.
• The main outcome measure was in-hospital mortality or 30-day case fatality expressed as proportional mortality
• SE in adults
• Estimated pooled proportional mortality of 15.9%
• Studies before year 2000 had higher pooled mortality of 24%
• All-age population pooled mortality ratio of 13%
• Pediatrics: Pooled mortality of 3.6%
• RSE: Pooled mortality was at 17.3%

• Mortality was 15.6% among 96 patients with a first SE episode in study by Rossetti et al.

• Seizures lasting more than 30 minutes are less likely to terminate spontaneously and are associated with a higher mortality than seizures lasting less than 30 minutes

• Case mortality rate in patients with RSE was recorded as 38% by Sutter et al.

• Chronic epilepsy and low AED levels are the most common causes of SE among chronic or acute causes and are associated with a relatively low mortality

• Rosetti et al. developed “Status Epilepticus Severity Score” (STESS) to predict in-hospital mortality
• Outcome predictors are determined before treatment institution, which are
• Age
• History of seizures
• Seizure type
• Extent of consciousness impairment
• Maximum score of 6; optimal cut-off value at ≥3 with sensitivity of 0.94, specificity of 0.60, NPV of 0.97, and PPV of 0.39
• Predictive value of STESS was assessed by Aukland et al.
• STESS correlated significantly with overall mortality though with lower odds ratios
• STESS was reliable for in-hospital mortality
• STESS did not allow correct estimation of mortality after discharge

Refractory Status Epilepticus (RSE)

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Further Reading

Bibliography

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