Local anesthetics cause reversible block of the conduction of nerve impulses with subsequent sensory, motor, and autonomic blockade. Cocaine was the first topical anesthetic discovered, but it was soon found to cause topical irritation and psychological dependence. Subsequently, synthetic local anesthetics lacking such side effects were discovered. Procaine, the first synthetic local anesthetic, was introduced by Einhorn in 1905 and was followed by lidocaine, which was synthesized in 1943 by Löfgren. Synthetic local anesthetics have a lipophilic benzine ring linked via an amide or an ester bond to a hydrocarbon chain that is attached to a hydrophilic tertiary amine structure. Local anesthetics are classified according to the type of their linking bond to ester or amide local anesthetics. The nature of the linking bond affects the metabolism of the local anesthetic as well as its potential to produce an allergic reaction. Amide local anesthetics, which are commonly used in bronchoscopy, are metabolized by the liver microsomal enzymes and are also extracted through the lungs. The addition of epinephrine at 1:200,0000 (5 μg/mL) concentration or 0.25% phenylephrine causes local vasoconstriction, which slows down the absorption of the local anesthetic, prolongs its duration of action, and decreases its systemic toxicity.

Absorption of large amounts of local anesthetics from the application site or direct accidental intravascular injection of large dose can result in systemic toxicity, e.g., lidocaine plasma level of 5 μg/mL or greater than 8.2 mg/kg of lidocaine instilled in the airway can result in systemic toxicity [13]. The toxic dose of benzocaine is 100 mg, and the toxic dose of tetracaine is 100 mg (but toxicity has been reported at 40 mg).

Central nervous system (CNS) toxicity initially presents with symptoms of CNS excitation such as restlessness, vertigo, tinnitus, and slurred speech. The symptoms may progress to tonic–clonic seizure followed by CNS depression in the form of coma and possibly death. Seizures should be immediately treated with small doses of intravenous benzodiazepine (diazepam or midazolam), intravenous thiopental, or propofol. Hypoxemia should be treated with supplemental oxygen. Additionally hyperventilation with subsequent respiratory alkalosis causes hyperpolarization of the nerve membrane, increases the threshold for seizure, and increases the amount of local anesthetic bound to protein thus decreases the delivery of free drug to the brain. If seizures continue despite treatment, intubation is warranted to protect the airway.

Cardiovascular toxicity due to blockade of the cardiac sodium channels can result in hypotension, long PR interval, and widening of the QRS complex. More severe cardiotoxicity can present with severe hypotension, cardiac arrhythmias, and atrioventricular heart block.

Methemoglobinemia occurs when local anesthetic oxidize the iron molecule in the hemoglobin from the ferrous to ferric state. Hemoglobin with iron molecule in the ferric state is called methemoglobin and is characterized by its inability to release bound oxygen to tissue. Patients with methemoglobinemia present with cyanosis, chocolate-colored blood, stupor, coma, and death. Methemoglobinemia is easily treated by the administration of 1–2 mg/kg of methylene blue intravenously.

Allergic reactions to local anesthetics are rare but are more common with ester local anesthetic metabolite para-aminobenzoic acid (PAPA). In addition, the preservatives used with either ester or amide local anesthetics (e.g., methylparaben) can be a source of allergic reaction. It is noteworthy that cross sensitivity does not exist between ester and amide local anesthetics.

Sensation to the nasal mucosa is provided by the middle division (V2) of the trigeminal nerve (CN V), the sphenopalatine ganglion, and the ethmoid nerve. The nasal mucosa and the nasopharynx can be topicalized using a cotton-tipped applicators or pledgets soaked in the 1, 2, or 4% lidocaine solution with or without a vasoconstricting agent. The applicators are placed sequentially along the inferior turbinate, the middle turbinate, and the superior turbinate. Each applicator should be left in place for 5 min.

Sensation of the mouth and oropharynx is supplied by branches of the glossopharyngeal, vagus, and facial nerves. The lingual branch of the glossopharyngeal nerve provides sensation to the posterior third of the tongue, the vallecula, and the anterior surface of the epiglottis. The pharyngeal branch provides sensation to the posterior and lateral walls of the pharynx, and the tonsillar branch supplies the tonsillar pillars. The tongue can be anesthetized by placing a tongue blade coated with lidocaine gel on the tongue for several minutes. Oral and pharyngeal mucosa are anesthetized by inhalation of nebulized 4% lidocaine or 0.5% tetracaine or by using an Cetacaine atomizer spray (tetracaine and benzocaine combination). Gargle with 2–4 mL of viscous lidocaine for 30 s can provide additional anesthesia to the posterior pharyngeal wall.

The superior laryngeal nerve (SLN) is a branch of the vagus nerve that divides lateral to the cornu of the hyoid bone into internal and external branches. The internal branch passes under the greater cornu of the hyoid bone before piercing the thyrohyoid membrane and entering the pyriform recess where it provides sensory innervation to the base of the tongue, the superior epiglottis, the aryepiglottic folds, the arytenoids, and the laryngeal mucosa above the vocal cords. The external branch supplies motor innervation to the cricothyroid muscle.

To perform SLN block, the patient should be placed in a supine position with the head slightly extended, and the greater horn of the hyoid bone is palpated above the thyroid cartilage. The needle (size 22 or 23 gauge) is inserted toward the greater horn of the hyoid bone and then moved caudally until a pop is felt when the thyroid ligament is pierced at a depth of about 1–2 cm. Negative aspiration is then followed by injecting 2–3 mL of 2% lidocaine with epinephrine. Bilateral blocks should be performed (Fig. 5.2).

The recurrent laryngeal provides motor innervation to the vocal cords and sensory innervation to both the trachea and vocal cords. In a supine patient with hyperextended neck, the skin over the cricothyroid membrane is anesthetized with lidocaine 1–2% with a 22-gauge needle. A 22-gauge IV catheter is then inserted through the cricothyroid membrane into the tracheal lumen at an angle of 45° caudally. Air should be aspirated to confirm intratracheal position. The needle should then be removed leaving the plastic catheter in the tracheal lumen. The patient is asked to take a deep breath followed by forced exhalation while 3–4 cc of 1–2 or 4% lidocaine is injected through the catheter. This maneuver commonly result in cough that aids in spreading the local anesthetic over the vocal cords and the trachea.

The American College of Chest Physicians has suggested in its consensus statement in 2011 that all physicians performing bronchoscopy should consider using topical anesthesia, analgesic, and sedative agents, when feasible [14]. The advantages of conscious sedation are the reduction of patient anxiety, pain, airway reflexes such as cough and gag, and the dyspnea associated with the insertion of the bronchoscope. Amnesia from the procedure also increases patient satisfaction and willingness to undergo another bronchoscopic procedure. In addition, the ability of the bronchoscopist to adequately perform advanced diagnostic and therapeutic procedures in shorter duration improves with sedation.

Different drug regimens have been used, and they vary depending on the bronchoscopist’s preference and experience. The most commonly used classes of drugs are benzodiazepines for anxiolysis and amnesia in combination with opioids for suppression of cough and pain. The combination of narcotics and benzodiazepines has an additive effect on the suppression of the respiratory drive and cardiovascular hemodynamics thus increasing the likelihood of apnea, desaturation, and hypotension. Therefore, these drugs should be titrated gradually to achieve the desired effect and avoid undesired side effects.

Benzodiazepines act primarily by enhancing the action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) causing increased resistance of neuronal excitation. This translates clinically to anxiolysis, sedation, anterograde amnesia, centrally mediated muscle relaxation, and minimal depression of ventilation or of the cardiovascular system. When compared with no sedation for bronchoscopy, benzodiazepine, as a single sedating agent, was associated with increased patient satisfaction and willingness to undergo another bronchoscopy. However, the post-procedure recovery time was longer in the benzodiazepine-treated patients without an increase in complication rates [15].

The three commonly used benzodiazepines for procedural sedation are midazolam, diazepam, and lorazepam. Midazolam is the most preferred benzodiazepine because of its water solubility, absence of pain with injection, rapid onset, short duration of action, and rapid clearance. The average dose of midazolam is 0.06–0.07 mg/kg with special consideration to use lower doses in elderly patients. Diazepam is a water-insoluble drug that is dissolved in the organic solvent propylene glycol that causes pain on intravenous or intramuscular injection. Diazepam is metabolized into two active metabolites desmethyldiazepam and oxazepam by the liver. The activity of these metabolites may cause prolonged sedation for 2–4 days in elderly patients and in those with impaired liver function. Lorazepam is an intermediate-acting benzodiazepine with a stronger amnestic effect and a delayed peak effect, making it the least favored benzodiazepine for procedural sedation (Table 5.2).

Flumazenil is the only known benzodiazepine antagonist. A dose of 0.2 mg IV every 1 min to a total dose of 1–3 mg per 1 h is commonly used. The onset of action is at 1–3 min, the peak is at 10 min, and the duration of action is 20 min. Additional doses may be required to maintain antagonism and prevent the recurrence of sedation by longer-acting benzodiazepines. Side effects of flumazenil include nausea, vomiting, tachycardia, hypertension, headache, and rarely seizures.

Opioids are natural and synthetic substances that bind opioid receptors in the central nervous system and peripheral tissue, causing presynaptic inhibition of release of neurotransmitters (e.g., acetylcholine, dopamine, norepinephrine, and substance P). Activation of the opioid receptors mu, kappa, and delta results in varying degrees of analgesia and side effects such as depression of ventilation, urinary retention, constipation, miosis, and physical dependence. The naturally occurring opioid morphine and the synthetic opioids meperidine, fentanyl, sufentanil, alfentanil, and remifentanil have been used for bronchoscopic procedural sedation. Fentanyl is the most commonly used opioid for bronchoscopy sedation due to its rapid onset of action and short half-life. Although therapeutic bronchoscopy is not associated with significant somatic pain, opioids were found to cause suppression of airway reflexes in particular cough, tachycardia, and hypertension associated with bronchoscopy [16]. See Table 5.3 for a comparison between the pharmacodynamics of different opioids. Noteworthy is that the combination of an opioids and a benzodiazepine is associated with better patient’s tolerance of bronchoscopy when compared to each agent alone [17] (Table 5.3).