The reflex sympathetic response to laryngoscopy (RSRL) is stimulated by the rich sensory innervation of the supraglottic larynx. Use of the laryngoscope, and particularly the attempted placement of an endotracheal tube, results in a significant afferent discharge that increases sympathetic activity to the cardiovascular system mediated through direct neuronal activity and release of catecholamines. More prolonged or aggressive attempts at laryngoscopy and intubation result in greater sympathetic nervous system stimulation. This catecholamine surge leads to increased heart rate and blood pressure, which significantly enhances cerebral blood flow (CBF) at the apparent expense of the systemic circulation through redistribution. These hemodynamic changes may contribute to increased ICP, particularly if autoregulation is impaired; therefore, it is desirable to mitigate this RSRL. Gentle intubation techniques that minimize airway stimulation and pharmacologic adjuncts (e.g., β-blockade, lidocaine, and synthetic opioids) have been studied to accomplish this mitigation.

Evidence is mixed regarding the use of lidocaine to blunt the hemodynamic response to laryngoscopy. Studies in patients without cardiovascular disease have failed to show effect. Other studies have shown variable results with respect to hemodynamic protection, with some appearing to demonstrate benefit and others showing none. As a result, lidocaine cannot be recommended at the present time for mitigation of the RSRL associated with emergency intubation. However, it is useful as a premedication agent, as discussed in the evidence section of this chapter and in chapters 19 and 20.

The short-acting β-blocker esmolol, in contrast, has consistently demonstrated the ability to control both heart rate and blood pressure responses to intubation. A dose of 2 mg per kg given 3 minutes before intubation has been shown to be effective. Unfortunately, administration of β-blocking agents in emergency situations may be problematic for several reasons. Even a shortacting agent, such as esmolol, may exacerbate hypotension in a trauma patient, or confound
interpretation of a decrease in the blood pressure immediately following intubation. For these reasons, although esmolol is consistent and reliable for mitigation of RSRL in elective anesthesia, it is generally not used for this purpose for emergency intubation.

Fentanyl at doses of 3 to 5 µg per kg has also been shown to attenuate the RSRL associated with intubation. Although a full sympathetic blocking dose of fentanyl is 9 to 13 µg per kg, the recommended pretreatment dose of fentanyl for emergency RSI is 3 µg per kg and should be administered as a single pretreatment dose over 60 seconds. This technique permits effective mitigation of the RSRL, with greatly reduced chances of apnea or hypoventilation before sedation and paralysis (see Chapter 20).

Several studies have investigated the potential advantages of flexible endoscopic intubation over direct laryngoscopy, working on the premise that these techniques minimize tracheal stimulation and thus the RSRL. Results of these studies are mixed and do not permit any conclusions recommending one technique over the other. In a controlled operating room setting, the insertion of the endotracheal tube into the trachea is more stimulating than a routine laryngoscopy.

At present, based on the best available evidence, it seems advisable to administer 3 µg per kg of fentanyl intravenously (IV) as a pretreatment agent 3 minutes before administration of the induction and neuromuscular blocking agents to mitigate the RSRL. Fentanyl should not be administered to patients with incipient or actual hypotension or to those who are dependent on sympathetic drive to maintain an adequate blood pressure for cerebral perfusion. In such cases, the ensuing hypotension may cause further central nervous system injury. In addition to pharmacologic maneuvers to reduce RSRL, intubation should be performed in the gentlest manner possible, limiting both the time and intensity of laryngoscopy.

Laryngoscopy may also increase the ICP by a direct reflex mechanism not mediated by sympathetic stimulation of the blood pressure or heart rate. The details of this reflex are poorly elucidated. Insertion of the laryngoscope or endotracheal tube may, therefore, further elevate ICP, even if the RSRL is blunted. It would seem desirable to blunt this ICP response to laryngoscopy in patients at risk for having elevated ICP. The literature related to the use of lidocaine to blunt ICP response to laryngoscopy and intubation is discussed in Chapter 20. In patients with elevated ICP, lidocaine should be administered as a pretreatment drug in the dose of 1.5 mg per kg IV 3 minutes before the induction agent and succinylcholine (SCh) to mitigate the ICP response to laryngoscopy and intubation.

SCh itself may be capable of causing a mild and transient increase in ICP. Studies have shown that this increase is temporally related to the presence of fasciculations in the patient, but is not the result of synchronized muscular activity leading to increased venous pressure. Rather, there appears to be a complex reflex mechanism originating in the muscle spindle and ultimately resulting in an elevation of ICP. One recent study challenged the claim that SCh causes an elevation of ICP, and SCh remains the drug of choice for management of patients with elevated ICP because of its rapid onset and short duration. Although we recommended in early editions of this manual the routine use of a defasciculating agent when SCh is administered to a patient with elevated ICP, we no longer advocate this practice. There is insufficient evidence to support the use of a defasciculating agent, and it adds unnecessary complexity.

When managing the patient with potential brain injury, it is important to choose an induction agent that will not adversely affect CPP. Ideally, one would like to choose an induction agent that is capable of improving or maintaining CPP and providing some cerebral protective effect. Sodium thiopental is an ultra-short-acting barbiturate induction agent. Historically, sodium thiopental
often was the drug of choice for patients with elevated ICP. Thiopental confers some cerebroprotective effect because it decreases the basal metabolic rate of oxygen utilization of the brain (CMRO₂). This effect can be likened to decreasing myocardial oxygen demand in the ischemic heart. In addition, sodium thiopental decreases CBF, thus decreasing ICP. This combination of characteristics, the decrease in ICP and the decrease in CMRO₂, make thiopental a desirable agent for use in patients with elevated ICP and a normal or high blood pressure. However, thiopental is a potent venodilator and negative inotrope. Therefore, it has a tendency to cause significant hypotension and thus reduce CPP, even in relatively hemodynamically stable patients. In the hemodynamically unstable patient, this hypotensive effect can be profound. A single episode of hypotension significantly increases mortality in acute, severe head injury. Therefore, although thiopental has some desirable attributes for management of patients with elevated ICP, its hemodynamic instability relegates it to an alternative role, with etomidate being the agent of choice. Thiopental generally is difficult to obtain in North America and likely will fall out of use altogether.

Etomidate is a short-acting imidazole derivative that has a similar profile of activity to thiopental, but without the tendency to cause hemodynamic compromise. In fact, etomidate is the most hemodynamically stable of all commonly used induction agents except ketamine (see Chapter 21). Its ability to decrease CMRO₂ and ICP in a manner analogous to that of sodium thiopental and its remarkable hemodynamic stability make it the drug of choice for patients with elevated ICP. The use of etomidate in patients with elevated ICP has been challenged on the basis of evidence from a few animal studies. This preliminary evidence, which is addressed in Chapter 21, does not justify avoidance of etomidate, with its excellent hemodynamic profile, in patients with elevated ICP.

Ketamine, in general, has been avoided in patients with known elevations in ICP because of the belief that it may elevate the ICP further. The evidence regarding this phenomenon is mixed, however, and is discussed in Chapter 21