Page 1146 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 85: Seizures in the Intensive Care Unit 785

more definitive treatment strategy for patients who have entered refrac- leukocytes. The intensivist must be vigilant in monitoring for infection
tory SE (RSE). since barbiturate-induced poikilothermia may mask fever. Despite these
■ REFRACTORY STATUS EPILEPTICUS side effects, barbiturate anesthesia should not be rapidly discontinued
if it is successful in terminating refractory SE. Continuing therapy for
Refractory status epilepticus evolves in 31% to 44% of patients in at least 48 hours, gradual tapering of the infusion dose, and the admin-
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SE. Failure of a first-line anticonvulsant drug to terminate SE usually istration of phenobarbital during the drug taper are recommended.
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requires the use of a definitive therapy in anesthetic doses that are highly Pentobarbital is loaded at 5 to 12 mg/kg followed by an infusion of 1 to
likely to cause significant respiratory suppression and hypotension. 10 mg/kg per hour. As an alternative, thiopental sodium may be given in
Therefore, mechanical ventilation is necessary, and invasive hemody- 75- to 125-mg IV boluses followed by infusion rates of 1 to 5 mg/kg per
namic monitoring is frequently required. Concomitant continuous EEG hour. Both medications rapidly redistribute into adipose tissue; recovery
monitoring is also mandatory to confirm treatment success and monitor of consciousness usually takes much longer after thiopental infusions
depth of sedation. The traditional goal of therapy is burst-suppression than after pentobarbital. Elimination times can be greatly increased in
pattern on EEG for 12 to 24 hours prior to any attempts to wean medi- obese patients after prolonged infusions. 90-100
cation. Since the available data suggest that successful treatment and The efficacy of alternative regimens needs further evaluation to define
improved outcome probably required seizure suppression regardless of their role in the treatment of seizure emergencies. While there are many
background EEG activity, we recommend cessation of electrographic case reports, no convincing evidence or randomized trials are available
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seizures as the goal instead. to support early initiation of these interventions. 6
The agents used most frequently include propofol, midazolam, and In brain tumor patients with RSE, the use of phenytoin, levetiracetam,
barbiturates. Propofol is an intravenous anesthetic agent that acts and pregabalin to abort RSE has been found safe and highly effective. 102
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primarily on the GABA receptor. Smaller series and case reports Lacosamide, a modulator of voltage-gated sodium channels, has
A
documenting its efficacy in RSE are abundant, but studies examining also gained attention for the use in refractory SE. It has been reported
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direct comparisons with other agents have had mixed results. 90-92 An effective as an adjunct in refractory NCSE, especially focal SE ; how-
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initial bolus of 1 to 2 mg/kg should be followed with a maintenance ever, other series have not been able to confirm its efficacy in RSE.
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infusion at 1 to 15 mg/kg per hour. Propofol is fast acting, highly lipid It is available intravenously, and is easy to administer. Common
soluble, and has little propensity to accumulate even with prolonged dosing is a loading dose of 200 to 300 mg IV, followed by 100 to 200 mg
infusions. Because of its rapid clearance, propofol should not be maintenance every 12 hours. Success in the termination of RSE has
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abruptly discontinued, but instead tapered gradually. Respiratory also been reported for isoflurane, intravenous valproate, ketamine, and
depression and hypotension are extremely common, especially after topiramate. Ketamine in particular is often described, probably at least
the initial bolus. Nutritional support must be adjusted in the setting of partly due to its lack of cardiosuppressive side effects, and its potential
propofol infusion due to the high lipid and calorie content of the solu- neuroprotective capacity given its structure as NMDA antagonist. 106
tion. Acidosis and rhabdomyolysis have been reported in both adults Emerging insight into antibody-induced seizures and SE, mainly
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and children. Careful monitoring of creatine kinase and blood pH NMDA-receptor antibodies, has also triggered exploration of emergency
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are prudent. treatment of SE with immunosuppressants in selected cases, with high
Midazolam is a water-soluble benzodiazepine that has demonstrated dose methylprednisolone and/or intravenous immunoglobulin. 106
high efficacy in refractory SE in adults and children. 96-98 Midazolam is The application of therapeutic hypothermia, the use of which in RSE
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loaded at 0.2 mg/kg followed by continuous infusion of 0.05 to 2.0 mg/kg has anecdotally been reported successful, lacks data on a larger scale.
per hour. Respiratory depression may be encountered less frequently Once SE is addressed, one must manage the major systemic complica-
than with other hypnosedatives, but should be anticipated. Since most tions of SE. Patients with GCSE should be screened for rhabdomyolysis
patients with RSE are already intubated, concern for respiratory effects with urine myoglobin and serum creatin kinase (CK) determination.
should not limit use. Clinically significant hypotension is rare even at If myoglobinuria is present or if the CK concentration is more than
the very high doses that are often required to address tachyphylaxis. 10 times the upper limit of normal, rehydration and urinary alkaliniza-
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Sedation is quickly reversed after short-term infusions are discontinued. tion should be instituted. Prolonged or severe hyperthermia should be
However, terminal half-lives of three to eight times normal have aggressively treated with cooling blankets, ice packs, or other cooling
been reported with extended administration. In addition, prolonged modalities.
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elimination times have been associated with critical illness and hepa- ■
torenal dysfunction. High-dose barbiturates, most commonly pentobar- SPECIAL CONSIDERATIONS FOR CHILDREN
bital, are extremely useful in RSE when used as third-line therapeutic Treatment of seizures or SE in critically ill children generally parallels
choice, but side effects can be severe and may limit use (Table 85-3). that for adults. Intravenous access is often more difficult to achieve in
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Hypotension can be refractory to initial resuscitative efforts, and the children. Lorazepam and diazepam can both be administered by the rec-
patient may benefit from pulmonary artery catheterization to plan fluid tal route (usually 0.5 mg/kg per rectum for both agents) and midazolam
and vasopressor management. Pulmonary infection is common due to (0.2 mg/kg) via the IM, nasal, or buccal routes. Lorazepam is probably
prolonged intubation and impaired function of both respiratory cilia and the first-line drug of choice for terminating SE in children as for adults.
TABLE 85-3 Drugs for the Treatment of Refractory Status Epilepticus
Drug IV loading Dose Maintenance Dose Advantages Disadvantages
Ketamine 4-5 mg/kg over 1-5 mg/kg per hour Unlikely to cause Not well studied for status epilepticus
2-4 minutes hemodynamic instability
Midazolam 0.2 mg/kg IV bolus 0.05-2 mg/kg per hour Fast onset of action Tachyphylaxis
Pentobarbital 5-12 mg/kg at 50 mg/min 1-10 mg/kg per hour Readily available Hypotension; immune suppression
Propofol 1-2 mg/kg IV bolus 1-15 mg/kg per hour Easy to adjust High lipid and calorie content; “propofol infusion syndrome” (metabolic acidosis, and
on occasion rhabdomyolysis, with doses greater than 5 mg/kg per hour)
Thiopental sodium 75-125 mg IV bolus 1-5 mg/kg per hour Fast onset of action Can have prolonged effects after extended infusions due to absorption into adipose tissue

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