Physiologic and Pathophysiologic Responses to Intubation

Cardiovascular Reflexes

The cardiovascular responses to airway manipulation are initiated by sensory receptors responding to tissue irritation in the supraglottic region and in the trachea. Located in close proximity to the airway mucosa, these sensory receptors consist of mechanoreceptors with small-diameter myelinated fibers, slowly adapting stretch receptors with large-diameter myelinated fibers, and polymodal endings of nonmyelinated nerve fibers. ^, The superficial location of these receptors and their nerves makes topical local anesthesia of the airway an effective means of blunting cardiovascular responses to airway interventions. The glossopharyngeal and vagal afferent nerves transmit these impulses to the brainstem, leading to 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 essentially a monosynaptic response to a noxious stimulus in the airway.

In adults and adolescents, the more common response to airway manipulation is 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. Notably, patients with pheochromocytoma or other catecholamine-secreting tumors may have a markedly exaggerated sympathetic response with airway manipulation. A component of the hypertensive response to tracheal intubation also results from activation of the renin-angiotensin system, including release of renin from the renal juxtaglomerular apparatus via direct stimulation by β-adrenergic nerves.

In addition to activation of the autonomic nervous system, laryngoscopy and tracheal intubation result in stimulation of the central nervous system, as evidenced by increases in electroencephalographic (EEG) activity, cerebral metabolic rate of oxygen consumption (CMR o ₂ ), and cerebral blood flow (CBF). In patients with compromised intracranial compliance due to head injury, increases in CBF may result in elevated intracranial pressure (ICP), which, if prolonged, may result in herniation of brain contents and severe neurologic compromise. Tachycardia and HTN associated with tracheal intubation have not been shown to be the cause of severe complications of head injury in isolation.

The effects of tracheal intubation on the pulmonary vasculature are poorly understood as they are often coupled with changes in airway reactivity associated with intubation. Acute bronchospasm or mainstem bronchial intubation results in a marked maldistribution of perfusion to poorly ventilated lung units, increasing transpulmonary shunting, which subsequently reduces systemic arterial oxygen tension and leads to an increase in pulmonary vascular resistance triggered by hypoxic pulmonary vasoconstriction. In addition, impaired venous return to the left side of the heart from the pulmonary circulation as a result of positive end-expiratory pressure (PEEP) after tracheal intubation causes a reduction in cardiac output (CO). The impact of these changes can be profound in patients who have compromised myocardial function or depleted intravascular volume. ,

Intubation in the Presence of Cardiovascular Disease

Perioperative myocardial ischemia often occurs in patients with preexisting cardiac risk factors, such as advanced age, smoking history, HTN, obesity, hypercholesterolemia, diabetes mellitus, or a family history of coronary artery disease. However, it has also been reported in young, healthy patients without notable risk factors during emergence from general anesthesia.

Myocardial ischemia results from an imbalance between myocardial oxygen supply and demand. In the presence of stable oxygen content in the blood, myocardial oxygen supply is determined almost entirely by coronary blood flow and distribution, because oxygen extraction at the cellular level is near maximum even under resting conditions.

The chief components of myocardial oxygen demand are heart rate (HR) and myocardial wall tension. Of the two, increases in HR are of greatest concern, because cardiac inotropy (contractility) subserves cardiac chronotropy (rate). Not only does tachycardia increase myocardial oxygen consumption per minute at a constant wall tension, but elevations in rate effectively reduce the diastolic period. This reduces the time for full diastolic relaxation and leads to an increase in resting wall tension, impairing subendocardial blood flow and thereby reducing myocardial oxygen supply. It follows, then, that neuroendocrine responses to airway manipulation resulting in tachycardia and HTN may result in a variety of complications in patients with underlying cardiac disease, particularly myocardial ischemia. This explains the ischemic electrocardiographic ST-segment depression and increased pulmonary artery diastolic blood pressure (BP) sometimes observed when intubation is performed in patients with arteriosclerosis; patients who experience greater increases in BP and HR during intubation exhibit a higher rate of ischemic electrocardiography (ECG) changes. Occasionally, these episodes foreshadow the occurrence of a perioperative myocardial infarction. Short, transient ischemic episodes (<10 minutes) evidenced by electrocardiographic ST-segment depression, such as those associated with brief 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 or cumulative durations lasting longer than 1 hour do seem to be an important factor associated with adverse perioperative cardiac outcomes. ^,

Patients with aneurysmal disease of the cerebral and aortic circulation may also be at increased 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 or ruptured aortic aneurysms are partially tamponaded by intraabdominal pressure but can suddenly expand into the retroperitoneal space during abrupt or sustained arterial HTN. This results in significant blood loss and additional technical challenges during surgical resection of the lesion and/or placement of a vascular prosthesis. Similarly, sudden increases in BP and contractility can result in propagation of false lumens in patients with aortic dissection.

Implications for Patients With Neurovascular Disease

Intracranial aneurysms and arteriovenous malformations (AVMs) may present with a “sentinel” hemorrhage that could serve as a warning for further neurologic risk. During subsequent periods of elevated arterial BP, these lesions can rebleed, which may result in sudden and permanent neurologic injury. Many neurosurgeons and interventional neuroradiologists attempt to stabilize cerebral aneurysms and AVMs soon after hospitalization in an effort to minimize the risk of rebleeding, necessitating anesthesia and airway manipulation at a time when the clot tamponading the aneurysm or AVM is particularly delicate. A small increase in arterial transmural pressure during tracheal intubation can increase the shearing forces on the vessel and could cause rerupture. It is important, therefore, to pay meticulous attention to attenuating these responses during the course of anesthetic induction and tracheal intubation.

Intubation in Patients With Neuropathologic Disorders

Reflex responses to tracheal intubation causing intracranial HTN are also potential hazards 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 intraabdominal pressure that, in turn, increases cerebrospinal fluid pressure and may compromise cerebral perfusion. In patients with impaired cerebral autoregulation (e.g., brain trauma, cerebrovascular accidents, or neoplasms), the normal tendency for CBF to remain constant over the mean BP range of 70 to 150 mm Hg is impaired. When tracheal intubation causes an increase in arterial BP in these patients, there is a marked increase in CBF and cerebral blood volume, which in turn can cause dangerous increases in ICP. This effect is magnified by the fact that noxious stimuli, such as airway manipulation, also result in increased CBF, which summates with the cardiovascular response, occasionally causing profound increases in ICP ( Fig. 7.1 ).

The presence of a spinal cord injury may attenuate or enhance the hemodynamic response to intubation, depending on the spinal cord level and the chronicity of the injury. Patients with a high-level injury leading to quadriplegia (injury above C7) tend not to have the typical increase in BP but do exhibit an increase in HR in response to tracheal intubation. In contrast, patients with acute paraplegia (injury below T5) often have an exaggerated hypertensive response that tends to normalize over time. Furthermore, patients with traumatic brain injury can show a severe hypertensive response to laryngoscopy and intubation that can worsen cerebral edema and place them at risk for secondary injury.

Neuromuscular Blocking Drugs and Cardiovascular Responses

Neuromuscular blocking drugs (NMBDs) 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 tracheal intubation was not identified until NMBDs were introduced into clinical practice. Before that time, intubation was performed only with the patient under such deep levels of anesthesia that relatively little cardiovascular response was generated.

The depressor effects of benzylisoquinolinium relaxants (atracurium and mivacurium) are mediated by histamine release. This effect could be viewed as a potential antagonist to the pressor response to laryngoscopy and tracheal 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. By contrast, pancuronium, rocuronium, and, to a lesser extent, vecuronium may initiate a hyperdynamic cardiovascular state that can potentiate the cardiovascular responses seen after tracheal intubation in anesthetized patients.

Succinylcholine is associated with bradycardia as a result of muscarinic stimulation, particularly when doses are repeated and, more commonly, in children. Studies of this phenomenon demonstrate that treatment with atropine had no effect on patient outcomes so routine administration for “reflex” treatment is not advised.

In adults, succinylcholine is typically a cardiovascular stimulant. 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. This has been demonstrated 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. The evidence to substantiate the clinical relevance of these findings is lacking, however. While it has been reported that succinylcholine administered to patients with brain tumors may elevate ICP by a mean of 5 to 12 mm Hg, cerebral perfusion pressure does not change significantly, and a negative effect on neurologic outcome has not been established. Classical teaching that this phenomenon can be prevented by pretreatment with defasciculating doses of nondepolarizing NMBDs has not been demonstrated in the literature. Furthermore, when adequate ventilation is maintained, succinylcholine administered to intubated patients being treated for intracranial HTN of various causes had no effect on ICP, cerebral perfusion pressure, or CBF. As a result, succinylcholine is still considered a first-line agent for rapid sequence induction and intubation (RSI) in patients with acute head injury.

Cardiopulmonary Consequences of Positive-Pressure Ventilation

The transition from spontaneous, negative-pressure ventilation to positive-pressure ventilation (PPV) at the time of intubation and subsequent mechanical ventilation significantly alters hemodynamics via compression of mediastinal structures by the lungs as positive inspiratory pressures cause an increase in mean intrathoracic pressure. Elevated intrathoracic pressure diminishes the gradient driving venous blood from the periphery to the right atrium, reducing the flow of blood through the right heart and pulmonary circulation, ultimately impairing left ventricular preload. This can lead to decreased CO, especially in preload-dependent states such as hypovolemia, atrial arrythmias, tachycardias, ventricular diastolic failure, and decreased ventricular afterload. As CO drops, mean arterial blood pressure (MAP) falls with especially exaggerated hypotension observed in patients unable to compensate due to intravascular volume depletion or a significant vasodilatory response from anesthetic induction agents. 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.

Whereas preexisting impaired cardiac function may worsen in the setting of PPV, some patients see improvement in cardiac function, depending on the variable impacts of decreased preload and decreased afterload. PPV, particularly PEEP or continuous positive airway pressure (CPAP), diminishes the transmural wall tension of the left heart by raising juxtacardiac pressures, leading to decreased left ventricular afterload and potentially improved left ventricular performance.

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

Minimizing Stimulation of Airway Sensory Receptors

As a general rule, cardiovascular responses to airway maneuvers can be minimized by limiting airway sensory receptor stimulation, including manipulation of the larynx itself. Application of cricoid pressure results in a significantly greater HR and BP response to tracheal intubation than does gentle palpation of the cricoid area. This underrecognized effect of cricoid pressure should be considered when estimating the risk-benefit ratio of this procedure in individual patients.

Laryngoscopy is a moderately stimulating procedure, and the use of a straight blade (e.g., a Miller blade) with elevation of the vagally innervated posterior aspect of the epiglottis results in significantly higher arterial BP than does the use of a curved blade (e.g., a Macintosh blade). Video-assisted laryngoscopy (VAL), which does not require approximation of the anatomical axes for adequate visualization of the glottis and subsequent intubation, has the potential to minimize the pressor response to airway manipulation, but this has be countered with the fact that VAL may take longer than direct laryngoscopy (DL). Manikin studies have demonstrated that VAL requires less force to displace oropharyngeal tissues than DL with a Macintosh blade. ^, Channel-based videolaryngoscopes also have been shown to attenuate the hemodynamic responses of tracheal intubation compared to a Macintosh laryngoscope.

However, some studies show no difference between VAL and DL with respect to increases in HR and BP. ^, One possible explanation for the lack of hemodynamic advantage to less stimulating intubation devices is that the act of tracheal intubation is far more hemodynamically stimulating than laryngoscopy itself. For example, the use of a lighted intubation stylet fails to prevent hemodynamic stimulation once an ETT is advanced past the vocal cords. This has also been demonstrated with VAL. ^,

Insertion of a laryngeal mask airway (LMA) after induction of general anesthesia with thiopental or propofol and fentanyl has been shown to cause a lower cardiovascular and endocrine response than laryngoscopy or tracheal intubation. ^, The LMA has the advantage of avoiding the vagally mediated infraglottic stimulation entailed by the use of a laryngoscope, thus requiring lighter levels of general anesthesia. Furthermore, because neuromuscular blockade is not required for airway control, spontaneous ventilation and avoidance of the adverse hemodynamic consequences of PPV are possible. In contrast, tracheal intubation via an intubating LMA results in a hemodynamic and endocrine response similar to that of DL and intubation after propofol induction. Therefore, if tracheal intubation is necessary, there may not be a hemodynamic advantage to instrumenting the airway with the intubating LMA or other less stimulating devices. Notably, placement of a Combitube (Kendall-Sheridan Catheter Corp., Argyle, NY) was found to cause significantly greater elevations in BP and catecholamine release when compared with tracheal intubation or LMA placement as there is gross stimulation of multiple airway structures as well as the esophagus.

Whichever technique is used to manage the airway, it must be emphasized that the hypertensive-tachycardic response to intubation may be a manifestation of insufficient anesthesia, which is often caused by a failure to maintain an appropriate level of anesthetic during intubation. Insofar as the pressor response can also be influenced by prolonged intubation time, rapid first-attempt success is also of particular importance, with multiple attempts being associated with increased risk of hemodynamic complications including bradycardia and cardiac arrest.

Topical and Regional Anesthesia

Topical anesthesia applied to the upper airway is effective in blunting hemodynamic responses to tracheal intubation, but it has almost invariably proven to be less effective than systemic administration of lidocaine. During general anesthesia, DL and instillation of lidocaine solution initiate the same adverse reflexes caused by placement of an ETT ( Fig. 7.2 ). 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 tracheal intubation. 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.

Excellent topical anesthesia of the airway obtained before awake flexible scope intubation (FSI) results in less cardiovascular stimulation after this procedure than after intubation with DL. 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 resulting from placement of the ETT below the level of the glottis had been suppressed by local anesthetic topicalization in the patients undergoing awake intubation. ^, This further supports the concept that intubation of the trachea with the ETT predominates over laryngoscopy as the major noxious driver of the hemodynamic response to intubation.

Increasing the concentration of lidocaine used, and thus the total dose, also does not appear to provide any increased benefit, although it may improve intubating conditions during awake FSI. ^, Although both 2% and 4% lidocaine administered through a flexible intubation scope (FIS) 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 a reduced risk of toxicity. Lower concentrations of lidocaine (1%) provided even 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. Lidocaine has been compared in both spray and viscous form for procedural topical airway anesthesia and the spray form has been demonstrated to result in a higher procedural completion rate, greater ease of intubation, and greater patient and proceduralist satisfaction and is currently recommended.

In contrast to topical anesthesia of the airway, which appears to provide inconsistent benefit, regional blocks of airway sensory nerves have been shown to prevent hemodynamic responses to intubation. The superior laryngeal nerve (SLN) innervates the superior surface of the larynx, and the glossopharyngeal nerve innervates the oropharynx. Injecting local anesthetic at each cornu of the hyoid bone can block the SLN. Blockade of the glossopharyngeal nerve is performed at the tonsillar pillars or palatoglossal fold. ^, The inferior surfaces of the larynx and trachea are innervated by the recurrent laryngeal nerve and the vagus, which cannot be directly blocked, and require topical anesthesia (see Chapter 13 ).

Instillation of lidocaine via an ETT can be effective in preventing alterations in cerebrovascular hemodynamics after tracheal intubation in patients with severe head injury. A dose of 1.7 mg/kg of lidocaine at body temperature instilled slowly (1 mL/s) through a fine tube advanced to the end of the ETT, but not in contact with the tracheal mucosa, was reported to effectively prevent tracheal suctioning-induced ICP increase and cerebral perfusion pressure reduction.