Physiologic and Pathophysiologic Responses to Intubation

Published on 27/02/2015 by admin

Filed under Anesthesiology

Last modified 27/02/2015

Print this page

rate 1 star rate 2 star rate 3 star rate 4 star rate 5 star
Your rating: none, Average: 4.5 (4 votes)

This article have been viewed 14842 times

Chapter 7 Physiologic and Pathophysiologic Responses to Intubation

II Cardiovascular Responses during Airway Manipulation

A Cardiovascular Reflexes

The cardiovascular responses to noxious airway manipulation are initiated by proprioceptors responding to tissue irritation in the supraglottic region and in the trachea.7 Located in close proximity to the airway mucosa, these proprioceptors consist of mechanoreceptors with small-diameter myelinated fibers, slowly-adapting stretch receptors with large-diameter myelinated fibers, and polymodal endings of nonmyelinated nerve fibers.8 (The superficial location of these proprioceptors and their nerves explains why topical local anesthesia of the airway is such an effective means of blunting cardiovascular responses to airway interventions.) The glossopharyngeal and vagal afferent nerves transmit these impulses to the brainstem, which, in turn, causes widespread autonomic activation through the sympathetic and parasympathetic nervous systems. Bradycardia, often elicited in infants and small children during laryngoscopy or intubation, is the autonomic equivalent of the laryngospasm response. Although seen only rarely in adults, this reflex results from an increase in vagal tone at the sinoatrial node and is virtually a monosynaptic response to a noxious stimulus in the airway.

In adults and adolescents, the more common response to airway manipulation is hypertension (HTN) and tachycardia mediated by the cardioaccelerator nerves and sympathetic chain ganglia. This response includes widespread release of norepinephrine from adrenergic nerve terminals and secretion of epinephrine from the adrenal medulla.9 Some of the hypertensive response to endotracheal intubation also results from activation of the renin-angiotensin system, including release of renin from the renal juxtaglomerular apparatus, which is innervated by β-adrenergic nerve terminals.

In addition to activation of the autonomic nervous system, laryngoscopy and endotracheal intubation result in stimulation of the central nervous system, as evidenced by increases in electroencephalographic (EEG) activity, cerebral metabolic rate, and cerebral blood flow (CBF).10 In patients with compromised intracranial compliance, the increase in CBF may result in elevated intracranial pressure (ICP), which, in turn, may result in herniation of brain contents and severe neurologic compromise.

The effects of endotracheal intubation on the pulmonary vasculature are probably less well understood than the responses elicited in the systemic circulation. They are often coupled with changes in airway reactivity associated with intubation. Acute bronchospasm or a main stem bronchial intubation results in a marked maldistribution of perfusion to poorly ventilated lung units, causing desaturation of pulmonary venous blood and subsequent reduction in systemic arterial oxygen (O2) tension. In addition, institution of positive end-expiratory pressure (PEEP) after endotracheal intubation causes a reduction in cardiac output related to impaired venous return to the left side of the heart from the pulmonary circulation. The impact of these changes can be profound in patients with severely compromised myocardial function or intravascular volume depletion.

B Intubation in the Presence of Cardiovascular Disease

Myocardial ischemia results when there is an imbalance between myocardial O2 supply and demand. In the presence of a stable O2 content of whole blood (the product of hemoglobin concentration and saturation, with a minor contribution from dissolved O2), the myocardial O2 supply is almost entirely determined by coronary blood flow and distribution, because O2 extraction at the cellular level is at or near maximum even under resting conditions.

The chief components on the demand side of the myocardial O2 balance equation are beat frequency or heart rate (HR) and myocardial wall tension. Of the two, increases in HR are of greatest concern, because cardiac inotropism (contractility) subserves cardiac chronotropism (rate). Not only does tachycardia increase myocardial O2 consumption per minute at constant wall tension, but elevations in rate effectively reduce the diastolic period. Because full diastolic relaxation may be impaired, a subsequent increase in resting wall tension will impair subendocardial blood flow, thereby reducing myocardial O2 supply. Concomitantly, the rate of intraventricular pressure development in systole (dP/dT), a measure of myocardial contractility and another determinant of myocardial O2 demand, will also increase.

It follows, then, that neuroendocrine responses to airway manipulation resulting in tachycardia and HTN may result in a variety of complications in patients with cardiac disease, myocardial ischemia chief among them. This set of circumstances is responsible for episodes of ischemic electrocardiographic ST-segment depression and increased pulmonary artery diastolic blood pressure (BP) that may be seen when intubation is performed in patients with arteriosclerosis; occasionally, these episodes presage the occurrence of a perioperative myocardial infarction.2 However, short ischemic episodes (<10 minutes) evidenced by electrocardiographic ST-segment depression, such as those that may be experienced only during airway manipulation, have not been shown to correlate with postoperative myocardial infarction. In contrast, ST-segment changes of a single duration lasting longer than 20 minutes (mean SD 20 ± 30 minutes) or cumulative durations of longer than 1 hour (mean SD 1 ± 2 hours) do seem to be an important factor associated with adverse perioperative cardiac outcomes.11,12

Patients with aneurysmal disease of the cerebral and aortic circulation may also be at particular risk of complications related to a sudden increase in BP during airway instrumentation. Laplace’s law defines the transmural wall tension of a blood vessel (the determinant of its likelihood of rupture) as the product of the pressure inside the vessel and its radius divided by the wall thickness. The presence of a thin-walled vascular aneurysm (higher transmural wall tension at baseline) combined with a sudden increase in intraluminal pressure can lead to rupture of the affected vessel and abrupt deterioration in the patient’s status. Leaking aortic aneurysms are partially tamponaded by intra-abdominal pressure but can suddenly expand into the retroperitoneal space during arterial HTN. The results are significant blood loss and additional technical problems for the surgeon trying to resect the lesion and insert a vascular prosthesis.

D Intubation in Patients with Neuropathologic Disorders

Reflex responses to endotracheal intubation are also a potential hazard to patients with compromised intracranial compliance resulting from neuropathologic processes such as intracranial mass lesions, brain edema, or acute hydrocephalus. Uncontrolled coughing can result in a marked increase in intrathoracic and intra-abdominal pressure that, in turn, increases cerebrospinal fluid pressure and may result in impairment of cerebral perfusion. In patients with impaired cerebral autoregulation (e.g., brain trauma, cerebrovascular accidents, neoplasms), the normal tendency for CBF to remain constant over the mean BP range of 50 to 150 mm Hg is impaired. When endotracheal intubation causes an increase in arterial BP, there is a marked increase in CBF and cerebral blood volume, which in turn can cause dangerous increases in ICP.6 This effect is magnified by the fact that noxious stimuli, such as airway manipulation, result in increased CBF, which summates with the hypertensive BP response, occasionally causing profound increases in ICP (Fig. 7-1).

E Neuromuscular Blocking Drugs and Cardiovascular Responses

Neuromuscular blocking drugs (NMB) are often administered to optimize conditions for intubation. Accordingly, it is appropriate to consider the cardiovascular and cerebrovascular responses to the administration of these agents. Indeed, the hypertensive-tachycardic response to endotracheal intubation was not identified until NMB agents were introduced into clinical practice, because before that time intubation was performed only with the patient under such deep levels of anesthesia that relatively little cardiovascular response was generated.13

The depressor effects of benzylisoquinolinium relaxants (atracurium and mivacurium) are mediated by histamine release.14 This effect could be viewed as a potential antagonist to the pressor response to laryngoscopy and endotracheal intubation. In the case of patients at risk for intracranial HTN, however, histamine-induced cerebral vasodilation may produce increases in ICP even as the BP falls.15 By contrast, pancuronium, rocuronium, and, to a lesser extent, vecuronium may initiate a hyperdynamic cardiovascular state that can potentiate the cardiovascular responses seen after endotracheal intubation in lightly anesthetized patients. The faster onset of rocuronium (doses of up to 2 mg/kg have a 90% chance of providing perfect intubating conditions) are the reason for its current widespread use as an alternative to succinylcholine for rapid-sequence intubation (RSI) and in operations expected to last longer than 1 hour.16

Succinylcholine, or diacetylcholine, is associated with bradycardia in children, particularly when doses are repeated, but is a cardiovascular stimulant in adults. This phenomenon is often associated with activation of the EEG, and patients with brain tumors may sustain marked increases in ICP after succinylcholine administration if intracranial compliance is compromised and cerebrovascular autoregulation is impaired.17 This has been shown in dogs to be a result of increased CBF related primarily to succinylcholine-induced increases in afferent muscle spindle activity at the time of fasciculation and secondarily to an elevated arterial carbon dioxide tension from fasciculation-induced carbon dioxide production.18 The evidence to substantiate the clinical relevance of these findings is lacking, however. Whereas it has been reported that succinylcholine administered to patients with brain tumors may elevate ICP by a mean of 5 to 12 torr, cerebral perfusion pressure does not change significantly, and a negative effect on neurologic outcome has not been documented.19,20 Additionally, this phenomenon can be prevented by pretreatment with defasciculating doses of nondepolarizing NMB drugs.19 Further, when adequate ventilation is maintained, succinylcholine administered to intubated patients being treated for intracranial HTN of various causes or to those who have suffered severe head injuries caused by blunt trauma had no effect on ICP, cerebral perfusion pressure, or CBF.21,22 As a result, succinylcholine is still considered a first-line agent for RSI in patients with acute head injury but is ideally used after pretreatment with a nondepolarizing agent and in the presence of slight hypocapnia.

F Cardiopulmonary Consequences of Positive-Pressure Ventilation

Venous return is defined by the pressure gradient between the mean systemic pressure in the peripheral venous system and the mean right atrial pressure. An increase in mean intrathoracic pressure due to positive-pressure ventilation (PPV) may be transmitted to the thin-walled, compressible superior and inferior venae cavae, effectively elevating the downstream pressure for venous return and thereby reducing venous blood return to the right atrium. Because the left side of the heart can only pump what the right side delivers, cardiac output and subsequently arterial BP may fall with PPV. Patients with decreased intravascular volume may have an exaggerated hypotensive response as a result of this phenomenon.

Those with impaired myocardial reserve may also be sensitive to the effects of PPV. However, a failing heart may also benefit from the combined effects of decreased preload and decreased afterload. In other words, PPV, particularly PEEP or continuous positive airway pressure (CPAP), diminishes the transmural wall tension of the left heart by raising juxtacardiac pressures. One common clinical scenario is a patient who responds to intubation with a brisk increase in BP and then suddenly develops acute hypotension as PPV is instituted. In such a situation, volume expansion, positional changes, and judicious use of α-adrenergic agents such as phenylephrine may be needed.

It should also be noted that both hypoxemia and hypercapnia lead to a stress-induced catecholamine response, which may mask other potential causes of hypotension. This becomes readily apparent only after intubation in critically ill patients. Prophylactic volume expansion and the immediate availability of vasoactive infusions decrease severe hemodynamic collapse in this situation.23

III Prevention of Cardiovascular Responses

A Technical Considerations: Minimizing Stimulation of Airway Proprioceptors

As a general rule, cardiovascular responses to airway maneuvers can be minimized by limiting airway proprioceptor stimulation, starting with manipulation of the larynx itself. For instance, cricoid cartilage pressure with a posterior force of 4.5 kg is widely used to prevent regurgitation of gastric contents or to facilitate laryngeal visualization. In a double-blind study, cricoid pressure resulted in a significantly greater HR and BP response to endotracheal intubation than occurred in patients whose cricoid area was gently palpated.24 This is a little-recognized effect of cricoid pressure that should be considered when estimating the risk-benefit ratio of this procedure in individual patients.

Laryngoscopy itself is a moderately stimulating procedure, and use of a straight blade (Miller blade) with elevation of the vagally innervated posterior aspect of the epiglottis results in significantly higher arterial BP than does use of a curved blade (Macintosh or Corazzelli–London–McCoy [CLM]).25 Newer video and optical laryngoscopes, which do not require alignment of the laryngeal axes for adequate visualization of the vocal cord inlet and subsequent intubation, have the potential to minimize the pressor response to airway manipulation by reducing the amount of force needed to displace oropharyngeal tissues and limiting cervical spine motion compared to traditional laryngoscopy with a Macintosh laryngoscope blade.26 Nonetheless, reports documenting this advantage are few.

Use of the Pentax-AWS video laryngoscope (Pentax, Tokyo, Japan) has been reported to attenuate the hemodynamic response to endotracheal intubation after fentanyl/propofol induction when compared to either the GlideScope (Verathon, Bothell, WA) or the Macintosh laryngoscope (Fig. 7-2).27 This finding is not universal. An earlier study comparing the Pentax-AWS to Macintosh laryngoscopy reported no significant differences in systolic BP, diastolic BP, or HR after intubation, and a separate study comparing the GlideScope and Macintosh laryngoscopy also failed to find significant differences in hemodynamic values at any point in the study.28 None of these studies included patients with known cardiac disease or chronic HTN, who often have exaggerated pressor responses to stimulation; the newer airway devices may have greater value among this group compared with traditional laryngoscopy.

The act of passing an endotracheal tube (ETT) is far more hemodynamically stimulating than just laryngoscopy. Surprisingly, the use of a lighted intubation stylet fails to prevent hemodynamic stimulation when the ETT is advanced past the vocal cords.29 Insertion of a conventional laryngeal mask airway (LMA) after induction of general anesthesia with thiopental or propofol and fentanyl has been shown to cause less cardiovascular and endocrine response than laryngoscopy or endotracheal intubation.3033 The LMA has the advantage of avoiding the vagally mediated infraglottic stimulation entailed by the use of a laryngoscope, thus enabling lighter levels of general anesthesia. Furthermore, because muscle relaxation is not required for airway control, spontaneously initiated ventilation is possible, with avoidance of the adverse hemodynamic consequences of PPV. In contrast, endotracheal intubation using the intubating LMA (iLMA) resulted in a hemodynamic and endocrine response similar to that resulting from direct laryngoscopy and intubation after propofol induction.34 Therefore, if endotracheal intubation is necessary, there does not appear to be a hemodynamic advantage to instrumenting the airway with the iLMA.

Whatever the technique employed to manage the airway, it must be emphasized that the hypertensive-tachycardic response to intubation is a manifestation of insufficient anesthesia. Insofar as the pressor response can also be influenced by prolonged intubation time, rapid first-attempt success is also of particular importance.7

B Topical and Regional Anesthesia

Topical anesthesia applied to the upper airway is effective in blunting hemodynamic responses to endotracheal intubation,35,36 but it has almost invariably proved to be less effective than systemic administration of lidocaine. During general anesthesia, rigid laryngoscopy and instillation of lidocaine solution initiate the same adverse reflexes caused by placement of an ETT (Fig. 7-3).37 Furthermore, a laryngotracheal spray of lidocaine solution may, in itself, produce profound cardiovascular stimulation in adults, and in children it may produce the same sort of bradycardic response associated with endotracheal intubation.38 If topical lidocaine is administered to the upper airway, there should be an intervening period of at least 2 minutes to allow initiation of anesthetic effect before airway instrumentation begins.39


Figure 7-3 Mean arterial pressure (MAP) response to endotracheal intubation after either intravenous (IV) or intratracheal (LTA) lidocaine instillation.

(From Hamill JF, Bedford RF, Weaver DC, Colohan AR: Lidocaine before endotracheal intubation: IV or laryngotracheal? Anesthesiology 55:578, 1981.)

Excellent topical anesthesia of the airway obtained before awake flexible fiberoptic intubation was responsible for reports suggesting that there was less cardiovascular stimulation after this procedure than after intubation with a rigid laryngoscope.40 Later studies performed with patients under general anesthesia demonstrated no difference between the two modes of intubation with regard to hemodynamic impact, probably because the more profound stimulus results from placement of the ETT below the level of the glottis.4144

Increasing the concentration of lidocaine used, and thus the total dose, also does not appear to mitigate this effect, although it may improve intubating conditions during awake flexible fiberoptic intubation.45,46 Although both 2% and 4% lidocaine administered through an epidural catheter in the working channel of the flexible fiberoptic bronchoscope by a “spray-as-you-go” technique provided similar intubating conditions and hemodynamic profiles, the former resulted in a smaller overall dose, lower plasma levels, and therefore less chance for toxicity reactions.46 Lower concentrations of lidocaine (1%) provided lower plasma levels and similar hemodynamics but appeared to provide less optimal intubating conditions than atomized 2% lidocaine when used for topical anesthesia before airway manipulation.45

In contrast to topical anesthesia of the airway, which appears to provide inconsistent benefit, regional nerve blocks involving the sensory pathways from the airway prevent hemodynamic responses to intubation. The superior laryngeal nerve (SLN) innervates the superior surface of the larynx, and the glossopharyngeal nerve innervates the oropharynx. Depositing local anesthetic on each cornu of the hyoid bone can block the SLN. Blockade of the glossopharyngeal nerve at the tonsillar pillars (sensory distribution above the level of the epiglottis) potentiates this effect by decreasing the stimulus of laryngoscopy.47 The inferior surfaces of the larynx and trachea require topical anesthesia, however, because they are innervated by the recurrent laryngeal nerve and the vagus, which cannot be directly blocked. With the preceding combination, awake patients exhibit little response as the ETT is inserted.

Instillation of lidocaine via an ETT to prevent alterations in cerebrovascular hemodynamics in patients with severe head injury may be of some benefit. A dose of 1.7 mg/kg lidocaine instilled at body temperature given slowly (1 mL/sec) through a fine tube advanced to the end of the ETT but not in contact with the tracheal mucosa was reported to be efficacious in half of the patients treated.48

C Inhalational Anesthetics

Defining the anesthetic dose requirement for effectively blocking (or even blunting) hemodynamic and ICP responses to endotracheal intubation has remained an elusive goal. Airway maneuvers are typically brief interventions that produce short-lived responses during a dynamic perioperative period, with drug concentrations rapidly fluctuating both in blood and at effect sites. Agents that are capable of preventing responses may also produce profound cardiovascular depression before and after the stimulation of endotracheal intubation. Accordingly, there are relatively few well-controlled dose-response studies, and those that are available often give information that is not useful for the clinical anesthesiologist.

For inhalational anesthetics, endotracheal intubation using doses in the range of the minimum alveolar concentration (1 MAC) resulted in marked cardiovascular stimulation during anesthesia with nitrous oxide (N2O) supplemented with either halothane or morphine.49 It should not be surprising that 1 MAC is insufficient, because it is known that approximately 1.5 to 1.6 MAC is needed to block the adrenergic and cardiovascular responses to a simple surgical skin incision (MAC-BAR).50 The dose of anesthetic required to prevent coughing during endotracheal intubation with sevoflurane may exceed MAC by a factor of 2.86 in adults,51 although this factor appears to be close to 1.3 in children.52

Accordingly, it appears that the dose of volatile anesthetic required to block the cardiovascular response to endotracheal intubation must be inordinately high, resulting in profound cardiovascular depression before endotracheal intubation.53 From a cerebrovascular viewpoint, this approach is totally impractical, because high doses of volatile anesthetics cause cerebral vasodilation and marked increases in ICP in patients with compromised intracranial compliance. Furthermore, from a cardiovascular point of view, the arterial hypotension and reduced cerebral perfusion pressure before intubation would be entirely unacceptable for patients with cerebrovascular disease or brain injury.

D Intravenous Agents

Propofol, barbiturates, and benzodiazepines are all associated with profound hypotension at doses that suppress the hemodynamic and ICP responses to intubation.5456 In the case of etomidate, the effective dose for blocking the cardiovascular response to intubation can be identified by a burst-suppression pattern on the cortical surface EEG, indicating fairly deep cerebral depression.57 Because etomidate supports BP at such deep levels of anesthesia, it is probably the only contemporary agent that, by itself, can achieve suppression of cardiovascular responses without first producing undue arterial hypotension and compromise of coronary and cerebral perfusion.

Because it is clinically impractical to achieve sufficient anesthetic depth for preventing a hyperdynamic response to intubation solely with an intravenous (IV) or inhalational agent (etomidate excepted), a wide variety of anesthetic drug combinations, adjuvants, or both have been used in attempts to potentiate anesthetic effects while minimizing hemodynamic depression.

Opioids are the adjuvants most commonly administered in addition to other IV or inhaled agents to facilitate induction of anesthesia and subsequent airway manipulation. Their use in this capacity relates to their historical use as part of a N2O-narcotic anesthetic often used in patients with marginal cardiac reserve. For example, Bennet and Stanley compared the cardiovascular responses after administration of N2O-morphine 0.4 mg/kg versus N2O-fentanyl 4 µg/kg 10 minutes before intubation. The HR, cardiac output, and systolic and mean BP were reduced compared to baseline and remained unaffected by intubation in the N2O-fentanyl group, but these parameters were all significantly elevated compared with preanesthetic controls in the N2O–morphine group.58 Whereas the assumed potency of fentanyl in this study was 100 times that of morphine, the lack of effect of morphine suggests that, with respect to suppression of pressor responses to laryngotracheal manipulation, fentanyl is more than 100 times as potent.

As reported by Bennett and Stanley58 and later by other investigators,59 fentanyl may not achieve its peak central nervous system effect until 10 minutes after bolus IV injection. Fentanyl appears to provide blunting of hemodynamic responses in a graded manner: 2 µg/kg IV given several minutes before induction only partially prevented HTN and tachycardia during an RSI with thiopental and succinylcholine. In this situation, 6 µg/kg was considerably more effective.60 Chen and coworkers reported almost complete suppression of hemodynamic response to intubation with both 11 and 15 µg/kg of IV fentanyl, whereas higher IV doses (30 to 75 µg/kg) allowed only a very occasional response to intubation.61

In doses that prevent hemodynamic response to intubation, however, fentanyl is not a short-acting agent, and the risk of prolonged postoperative respiratory depression must be weighed against the advantages of perioperative cardiovascular stability. With this risk in mind, it has been observed that pretreatment with 2 µg/kg IV fentanyl given 10 minutes before intubation during an infusion of propofol sufficient to reduce the Bispectral Index Score to 45 prevented a significant increase in HR or BP compared with awake preanesthetic values.10 Similar results were observed when intubation was performed after administration of fentanyl, 2 µg/kg, and propofol bolus doses of 2.0 to 3.5 mg/kg.10

Fentanyl and propofol require 6.4 and 2.9 minutes, respectively, to achieve effect-site equilibrium after IV bolus administration.10 Therefore, the common practice of administering 1 to 2 mL (50 to 100 µg) just before or almost simultaneously with other induction medications would not be expected to have any effect based on inadequate dose and inappropriate timing of administration. Rather, this may provide a more plausible explanation for hypotension during the minutes-long quiescent period between endotracheal intubation and actual surgical incision. It is strongly recommended that laryngoscopy and intubation be timed to coincide with the peak effect of these agents.

Opioids with shorter onset and offset times have some advantages over fentanyl for modulating circulatory responses to intubation. Alfentanil has a smaller steady-state distribution volume and shorter terminal elimination half-life than fentanyl.62 Ausems and colleagues demonstrated that an alfentanil plasma concentration of 600 ng/mL effectively prevented hemodynamic responses to intubation during induction of N2O anesthesia.63 This was achieved by a 30-second infusion of alfentanil at 150 µg/kg. During this induction period, N2O and succinylcholine were also administered. Only 5 of the 35 patients studied sustained an increase in HR or BP greater than 15% above preinduction values.

Remifentanil has been found to be highly effective in preventing hemodynamic responses to intubation, albeit always with the cost of impressive bradycardia or hypotension, or both, before and after airway manipulation.64 Many studies have used vagolytic agents to avoid bradycardia, at the risk of an elevated HR response after intubation. Remifentanil’s half-time for equilibration between blood and effect site is 1.3 minutes,65 and it has a brief half-life of 3 to 5 minutes due to hydrolysis by tissue and blood esterases.66 Typical remifentanil infusion rates used for blunting hemodynamic responses are 0.25 to 1.0 µg/kg/min in association with cautious propofol administration and nondepolarizing neuromuscular blockade.67 For RSI with thiopental and succinylcholine, the optimal dose of remifentanil appears to be 1.0 µg/kg administered over 30 seconds, with laryngoscopy performed 1 minute after induction. A bolus dose of 1.25 µg/kg was associated with unsatisfactory bradycardia, whereas 0.5 µg/kg resulted in excessive cardiovascular stimulation.68 This dosing recommendation is supported by another report that found remifentanil 1 µg/kg given over 30 seconds, followed by thiopental 5 mg/kg and rocuronium 1 mg/kg 100 seconds later, was more effective than lidocaine and esmolol in attenuating the hemodynamic response to RSI.69

IV lidocaine may also blunt hemodynamic and cerebrovascular responses to intubation. When given in a bolus of 1.5 mg/kg IV, it adds approximately 0.3 MAC of anesthetic potency.70 Significant reductions in hemodynamic response to endotracheal intubation have been noted when lidocaine (3 mg/kg) was used as an adjunct to high-dose fentanyl anesthesia,71 as well as during other light anesthetic techniques, such as thiopental-N2O-O2.72 However, smaller doses of lidocaine (1.5 mg/kg) have not been consistently reported to be effective in reducing the hemodynamic response to laryngoscopy and endotracheal intubation.73,74

The general anesthetic properties of lidocaine tend to reduce cerebral metabolic rate for O2 and CBF, thus lowering ICP in patients with compromised intracranial compliance.75 Theoretically, these properties of lidocaine might be exploited to mitigate rises in ICP during airway manipulation in those patients with acute intracranial pathology or compromised intracranial compliance. However, only a single human study has been reported specifically evaluating the ability of IV lidocaine to blunt intubation-related elevations in ICP. Bedford and colleagues compared 1.5 mg/kg IV lidocaine with placebo in 20 patients diagnosed with brain tumor. When administered 2 minutes before intubation, lidocaine failed to prevent a rise in ICP from the preanesthesia baseline, although the increase was more modest than that observed with the placebo (−12.1 mm Hg; 95% confidence interval, −22.8 to −1.4 mm Hg; P = 0.03).76 This dearth of direct benefit was underscored by a systematic review that also failed to identify any evidence that pretreatment with IV lidocaine before RSI consistently reduced ICP or positively affected neurologic outcome.77 This review is now more than a decade old, but because no new direct evidence has been published in the interim, its conclusion remains valid.

With regard to the patient at risk for intracranial HTN, it is important that agents used to control cardiovascular responses to intubation also have a minimal adverse impact on ICP. Agents that act as cerebral vasodilators, such as volatile anesthetics, nitroglycerin, nitroprusside, or hydralazine, are generally avoided if there is a serious risk of intracranial HTN.

E Nonanesthetic Adjuvant Agents

A final means for modifying the cardiovascular responses to endotracheal intubation is prophylactic administration of vasoactive substances that directly affect the cardiovascular system. This approach was introduced in 1960 by DeVault and associates, who found that pretreatment with phentolamine, 5 mg IV, prevented the hypertensive-tachycardic response to endotracheal intubation during a light barbiturate-succinylcholine anesthetic technique.78 Since then, a large number of articles have appeared advocating the use of various vasodilators and adrenergic blocking agents as pretreatment before endotracheal intubation, including diltiazem, verapamil, and nicardipine7982; hydralazine83; nitroprusside84; nitroglycerin85; labetalol86; esmolol80,8789; and clonidine.90,91 Virtually all of these agents appear to be somewhat effective when compared to placebo, particularly when used in high doses.

Esmolol is the best studied of the group. In a large, multicenter, placebo-controlled trial, esmolol at doses of 100 or 200 mg suppressed the hemodynamic response to endotracheal intubation, particularly when combined with a moderate-dose opiate.87 However, esmolol doses of 200 mg were associated with a doubling of the incidence of hypotension compared to placebo. In another study, smaller doses of esmolol (1 mg/kg) had no effect on the hemodynamic response to laryngoscopy and intubation compared to placebo.80 Most recently, the combination of lidocaine (1.5 mg/kg) and esmolol at a dose of 1 mg/kg effectively attenuated the pressor response to intubation but was not as effective as 1 µg/kg remifentanil.69 Currently, the optimal use of any of these agents is undefined, although their use as adjuncts to RSI is reasonable taking into account evidence-based dosing recommendations for the situation.