Manual of Emergency Airway Management, 3rd Edition

33.Prolonged Seizure Activity

Robert J. Vissers

The Clinical Challenge

A general discussion of the diagnosis and treatment of seizure disorder is beyond the scope of this book. This chapter focuses on the considerations of airway management in the seizure patient. In the simple, self-limited, grand mal seizure, airway management is directed at termination of the seizure and prevention of hypoxia from airway obstruction. Paralysis and intubation should be considered when S_pO₂ falls below 90% or when typical first-line measures fail to terminate the seizure in a reasonable time. For the simple seizure, basic airway maneuvers, expectant observation (most seizures end spontaneously), supplemental high-flow oxygen, and vigilance are usually all that is necessary. Airway protection from aspiration is rarely required in the simple, self-limited seizure because the uncoordinated motor activity precludes coordinated expulsion of gastric contents.

Determining when to proceed from supportive measures to intubation is the main clinical challenge in the airway management of the seizing patient. Status epilepticus has been defined as continuous seizure activity for 30 minutes or multiple seizures without recovery of consciousness in between. The rationale for 30 minutes was that this is the minimum seizure duration that has been believed to produce neuronal injury. Recent neurology literature questions the practical value of this and suggests that clinicians wait no longer than 10 minutes before initiating aggressive therapy. Some have suggested any seizure lasting longer than 5 minutes is concerning because most single seizures are much shorter in duration than this. The mortality rate for status epilepticus is more than 20% in most series. Therefore, the discussion focuses on when intubation may be indicated in the patient with prolonged seizure activity. The absolute and relative indications for intubation in the seizing patient are listed in Box 33-1.

Approach to the Airway

Self-limited Seizure

Most seizures terminate rapidly, either spontaneously or in response to medication, and require only supportive measures. Positioning the patient on his or her side, providing oxygen by face mask, suctioning secretions and blood carefully, and occasionally using the jaw thrust to relieve obstruction from the tongue are usually all that is necessary to prevent hypoxia and aspiration. Bite-blocks should not be placed in the mouths of seizing patients. They are not indicated and will only serve to increase the likelihood of injury. Attempts to ventilate during a seizure are usually ineffective and rarely necessary.

BOX 33-1 Indications for Endotracheal Intubation for the Seizing Patient

Absolute indications

1. Hypoxemia (S_pO₂ <90%) secondary to hypoventilation or airway obstruction

2. Treatment of underlying etiology (e.g., intracranial bleed with elevated intracranial pressure)

3. Prolonged seizure refractory to anticonvulsants (to prevent accumulating metabolic debt [acidosis, rhabdomyolysis])

4. Generalized status epilepticus

Relative indications

1. Prophylaxis for the respiratory depressant effect of large doses of anticonvulsants (e.g., benzodiazepines, barbiturates)

2. Termination of seizure activity to facilitate diagnostic workup (e.g., CT scanning)

3. Airway protection in prolonged seizures

Prolonged Seizure Activity

Although most self-limited seizures do not require intubation, there are several indications for intubation in the prolonged seizure. Extensive generalized motor activity will eventually cause hypoxia, significant acidosis, rhabdomyolysis, and hyperthermia. Respiratory depression may result from high doses or combinations of anticonvulsants. Oxygen saturation of <90%, despite supplemental high-flow oxygen, is an indication for immediate intubation.

There is no clear guideline that specifically defines the duration of seizure activity requiring intubation. A good rule of thumb is that seizures lasting more than 10 minutes despite appropriate anticonvulsant therapy should be considered for intubation. Generally, when first-line (benzodiazepine) anticonvulsants fail to terminate grand mal seizure activity, rapid sequence intubation (RSI) is indicated. Phosphenytoin, which has a relatively short loading time, may be initiated as a second-line agent before intubation, if time allows. Other second-line anticonvulsants (phenytoin, phenobarbital) require at least 20 minutes for a loading dose; therefore, at the time of initiation of such a load, intubation is advisable. The initiation of a propofol or phenobarbital infusion is also an indication for intubation because of its respiratory depressant effects. Both agents also act synergistically with benzodiazepines, which increases the likelihood of apnea and the need for airway management.

Technique

RSI is the method of choice in the seizing patient. In addition to its technical superiority, RSI ends all motor activity, allowing the body to begin to correct the metabolic debt. However, cessation of motor activity while the patient is paralyzed does not represent termination of the seizure, and effective loading doses of appropriate anticonvulsants (e.g., phenytoin) are required immediately after intubation. The recommended technique for the seizure patient is described in Box 33-2.

BOX 33-2 Rapid Sequence Intubation for Patients with Prolonged Seizure Activity

Standard RSI technique is appropriate in the seizing patient with the following modifications:

1. Preoxygenation may be suboptimal because of uncoordinated respiratory effort; therefore, pulse oximetry is critical. After giving succinylcholine, the patient may desaturate below 90% before complete relaxation and thus may require oxygenation using a bag and mask before attempts at intubation.

2. Sodium thiopental shares anticonvulsant activity with other barbiturates and may be the best choice for induction in the absence of hypotension. Midazolam is an equally efficacious alternative and preferred in the hemodynamically compromised patient. The induction dose of midazolam for an actively seizing patient is 0.3 mg/kg, but it can be reduced to 0.1 to 0.2 mg/kg if the patient is hemodynamically compromised. Etomidate has an unclear effect on seizure activity and therefore should be considered only if associated hypotension precludes the use of sodium thiopentothal or midazolam. Although etomidate may raise the seizure threshold (and therefore inhibit seizure activity) in generalized seizures, it lowers the threshold in focal seizures. Propofol has also been used as an induction agent in this setting at doses of 1 mg/kg. Little data exist on propofol as an induction agent in patients with seizures, however.

3. Prolonged, deep sedation with an agent that suppresses seizures is desirable for the first hour after intubation to facilitate investigations (e.g., CT scan) and to allow acidosis to correct with controlled ventilation. Long-term neuromuscular blockade should be avoided, if at all possible; however, if it is used, it should be accompanied by EEG monitoring, if available (see item 4).

4. Continuous bedside EEG monitoring is necessary in the paralyzed patient to assess for ongoing seizure activity. If this is not immediately available, motor paralysis frequently should be allowed to wear off to evaluate the effectiveness of anticonvulsant therapy.

5. If elevated intracranial pressure (ICP), head injury, known central nervous system pathology, or suspected meningitis is present, ICP intubation technique should be used (see Chapter 28).

Drugs and Dosages

1. Preintubation seizure management

· Lorazepam 0.02 mg/kg intravenously (IV)

or

· Diazepam 0.1 mg/kg IV or 0.5 mg/kg per rectum

with

· Phosphenytoin 18 mg/kg (as milligrams of phenytoin equivalent)

2. Induction agents

· Sodium thiopental 3 mg/kg

or

· Midazolam 0.3 mg/kg

3. Postintubation sedation and therapy

· Midazolam 0.05 to 0.1 mg/kg/hour IV infusion, or

· Propofol 1–5 mg/kg/hour IV infusion

Tips and Pearls

1. Always ensure that hypoglycemia is not the cause of the seizure. Check glucose or administer IV dextrose solution in all cases. Similarly, check for hyponatremia.

2. Even in the difficult airway, RSI is generally preferred for airway management in the actively seizing patient. If the airway is assessed to be difficult, a double setup may be desirable.

3. The paralyzed patient may continue to seize, possibly causing neurological injury despite the lack of motor activity. Administer effective doses of long-acting anticonvulsants, and use benzodiazepines for long-term sedation. Avoid long-term paralysis, if possible. If a long-acting neuromuscular blocking agent is used, arrange continuous EEG monitoring, if possible, or allow motor recovery frequently (at least every hour) to assess response to therapy.

4. Prolonged seizure activity almost always represents a significant change in seizure pattern for the patient. A careful search for an underlying cause, including head CT scan, is indicated.

Evidence

1. Which benzodiazepine is best? The answer depends on the setting in which it is being used. In one multicenter study, 570 patients with status epilepticus were randomized to lorazepam (0.1 mg/kg), phenytoin (18 mg/kg), diazepam (0.15 mg/kg), and phenytoin or phenobarbital (15 mg/kg) (1). Lorazepam alone was most effective in terminating seizures within 20 minutes and maintaining a seizurefree state in the first 60 minutes after treatment. There was no difference in 30-day outcome or adverse events (1). Lorazepam also performed better than diazepam or placebo in a double-blind prehospital study of 205 patients with status epilepticus, where termination of seizures occurred in 59% of patients versus 43% and 21%, respectively (2). Diazepam remains a popular agent in the emergency setting because of its rapid onset (<20 seconds, compared to 1 minute for midazolam and 2 minutes for lorazepam) (3). Diazepam is stable at room temperature in a premixed form and is readily absorbed rectally; therefore, it is often the benzodiazepine of choice stocked on a resuscitation cart.

There are no data on the ideal benzodiazepine as an induction agent in status epilepticus; however, the relatively rapid onset, familiarity, and effectiveness of midazolam argue that it is the best choice.

2. Midazolam, propofol, or pentobarbital for postintubation therapy? For postintubation care, the patient should be sedated using a drug that not only provides amnesia and anxiolysis, but also optimizes antiepileptic therapy. Benzodiazepines have all these properties and are readily available in the acute care setting. Midazolam is preferred over diazepam and lorazepam as a continuous IV infusion because of its shorter half-life, water solubility, hemodynamic stability, and greater clinical experience in refractory status epilepticus (3,4).

Recent reports suggest midazolam or propofol being preferred as a first-line agent, then pentobarbital as a second-line drug; however, no prospective randomized trial exists comparing these therapies directly (5,6). A systematic review to evaluate the efficacy and outcomes of these three agents in refractory status epilepticus found 28 studies that described a total of 193 patients (5). Pentobarbital was more effective at preventing breakthrough seizures; however, it was also associated with more episodes of hypotension, and there was no difference in outcomes between any of the agents. Pentobarbital is less desirable because it is rarely used in the emergency setting, making it less familiar or available.

Despite the popularity of propofol for refractory seizure management in the intensive care unit setting, there is little experience in the emergency setting, and the ICU studies are too small to draw any conclusions (7,8,9,10). The recommended dosing for propofol is 1 to 2 mg/kg IV bolus (or induction) followed by a 1 to 5 mg/kg/hour infusion (11). Higher sustained doses have been associated with a propofol infusion syndrome.

References

1. Abou Khaled KJ, Hirsch LJ. Advances in the management of seizures and status epilepticus in critically ill patients. Crit Care Clin 2006;22(4):637–659.

2. Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. N Engl J Med 1998;339(12):792–798.

3. Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001;345(9):631–637.

4. Treiman DM. Pharmacokinetics and clinical use of benzodiazepines in the management of status epilepticus. Epilepsia 1989;30:4–15.

5. Kumar A, Bleck TP. Intravenous midazolam for the treatment of refractory status epilepticus. Crit Care Med 1992;20:483.

6. Claassen J, Hirsch LJ, Emerson RG, et al. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002;43(2):146–153.

7. Claassen J, Hirsch LJ, Emerson RG, et al. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Neurology 2001;57:1036–1042.

8. Prassad A, Worrall BB, Bertam EH, et al. Propofol and midazolam in the treatment of refractory status epilepticus. Epilepsia 2001;42:380–386.

9. Stecker MM, Kramer TH, Raps EC, et al. Treatment of refractory status epilepticus with propofol: clinical and pharmacokinetic findings. Epilepsia 1998;39(1):18–26.

10. Bradford JC, Kyriakedes CG. Evaluation of the patient with seizures: an evidence-based approach. Emerg Med Clin North Am 1999;17:203–220.

11. Rossetti AO, Reichhart MD, Schaller MD, et al. Propofol treatment of refractory status epilepticus: a study of 31 episodes. Epilepsia 2004;45:757–763.