Pretreatment refers to the administration of drugs 3 minutes before the paralysis step of rapid sequence intubation (RSI) in an attempt to attenuate the adverse effects of laryngoscopy and intubation, mainly intracranial pressure (ICP) rise, blood pressure changes, and increases in airways resistance. The timing of pretreatment agents and a brief overview of their use are provided in Chapter 19.

The acts of intubation, laryngoscopy, and tracheal intubation are exceedingly stimulating, leading to as much as a doubling of heart rate and systolic blood pressure. Increases in left ventricular (LV) ejection velocity leads to an increase in arterial wall shear forces. Bradycardia, particularly in children younger than 1 year, may also occur. Laryngoscopy and endotracheal intubation may cause a rise in ICP, and the stimulation of the upper airway reflexes may incite coughing, laryngospasm, or bronchospasm.

The mechanisms behind these responses are believed to include the 9th and 10th cranial nerves. Sympathetic activation releases norepinephrine from adrenergic nerve terminals and epinephrine from the adrenal glands. The subsequent elevation in blood pressure may be exacerbated by the activation of the renin-angiotensin system. Parasympathetic activation can result in bronchoconstriction and coughing. The clinical relevance of these responses is not clear, but there is some evidence that these responses to laryngoscopy and intubation can contribute to adverse outcomes.

A wide variety of pharmacologic agents have been studied in an attempt to identify agents that can blunt these reflexes in both elective and emergency airway management. Practically, lidocaine ultra-short-acting opioids, such as fentanyl (Sublimaze) and its derivatives, and atropine are the most appropriate for emergency intubations. Of these, lidocaine and the ultra-short-acting opioids have undergone the most evaluation. Although these drugs may be helpful when given before intubation in both elective and emergency airway management situations, few formal studies have examined the ability of the drugs to mitigate responses and improve outcome in the context of emergency RSI.

Table 20-1 lists the recommendations for the use of lidocaine and fentanyl in emergency RSI. Lidocaine blunts reflexive rises in ICP during intubation, and mitigates reactive increases in small- and medium-size airways resistance in patients with reactive airways disease who are undergoing intubation. Fentanyl and other ultra-short-acting opioids have been reported to blunt the reflex sympathetic response to laryngoscopy (RSRL) in a dose-related fashion. Control of this sympathetic response attenuates the magnitude of the rise in ICP by mitigating blood pressure increases during laryngoscopy and intubation. Similarly, patients at risk from the adverse effects of a sudden rise in blood pressure, myocardial oxygen demand, or LV ejection velocity may benefit from attenuating sympathetic activation. For example, patients with coronary artery disease, neurovascular events such as intracranial hemorrhage, or major vascular disorders such as aortic dissection should ideally not be exposed to the effects of a sudden and significant release of catecholamines.

Atropine is used to treat bradycardia when it occurs (after excluding hypoxia as a possible cause). The empiric administration of atropine to children younger than 1 year who will be receiving succinylcholine is considered a reasonable (optional) practice (see Chapter 4).

Lidocaine functions by blocking fast sodium channels in neurons. It is an amide local anesthetic agent that is metabolized in the liver and excreted in the urine. A single intravenous (IV) dose need not be adjusted in renal failure patients. IV lidocaine is absolutely contraindicated in patients allergic to amide local anesthetic agents (exceedingly rare) and in patients with high-grade heart
block or bradycardia unless a pacemaker has been placed. Lidocaine can aggravate hypovolemic and cardiogenic shock, and is relatively contraindicated in Wolff-Parkinson-White syndrome. Box 20-1 shows the drugs for which severe drug interactions have been reported with lidocaine.

Adverse effects are rare, but include central nervous system (CNS) toxicity (seizures and coma) and cardiac conduction abnormalities (severe bradycardia and dysrhythmias), and cardiogenic shock when used at high doses. The available evidence supports the use of lidocaine at a dose of 1.5 mg per kg to suppress the cough reflex and to mitigate the ICP response to upper airway manipulation, laryngoscopy, and intubation. The recommendation regarding ICP is based predominantly on the results of older studies of patients with elevated ICP undergoing various airway procedures, including tracheal suctioning and laryngoscopy, although there is some conflict in the literature. No studies have directly addressed its use in emergency RSI, and none has used patient outcome as a primary end point. However, we recommend the use of lidocaine for patients with elevated ICP. This is based on the cough suppression effect, the potential to reduce the ICP response during laryngoscopy and intubation, and the fact that the drug at the recommended dose is safe and commonly used, and therefore unlikely to cause patient harm or lead to medication error. Lidocaine also appears to diminish the reflex bronchospasm that may occur with the intubation of patients with reactive airways disease. We believe that the evidence is sufficient recommend the use of lidocaine as a pretreatment agent in patients with reactive airways disease who are undergoing intubation. The recommendations for the use of lidocaine as a pretreatment agent for emergency RSI are shown in Box 20-2.

Given in sufficiently high doses, most sedative/hypnotic agents will attenuate the RSRL. However, the drug dose required to produce this degree of CNS depression will usually produce significant hypotension.

Fentanyl (Sublimaze) is an opioid receptor agonist that selectively activates the µ-receptor. It is metabolized in the liver and has first-phase redistribution within 5 minutes, and an elimination half-life of 7 hours. Fentanyl has a time to onset of 2 to 3 minutes and duration of action of approximately 30 to 60 minutes. It is a class C drug in pregnancy. Major side effects include dose-related respiratory depression and hypotension in patients who are dependent on sympathetic tone.