Introduction
Head and neck surgery requires a cooperative relationship between surgeon and anesthesiologist. This is especially true in surgical procedures involving the airway. In fact, in most situations a common bond exists between otolaryngologist and anesthesiologist. In critical situations, where airway compromise is anticipated, it is the anesthesiologist and the otolaryngologist who have the best appreciation for the severity of the situation. In this chapter we will discuss briefly the pharmacology of some of more commonly used drugs in anesthesia. While a majority of these drugs are used by anesthetists in monitored conditions, these drugs may also be used in procedures requiring conscious sedation. It is hence of great importance for the physician or nurse involved on conscious sedation to be knowledgeable about the use and limitations of drugs used in conscious sedation.
This is followed by an overview of anesthesia equipment as pertains to the needs of the otolaryngologist. Quite often, surgery of the head and neck will involve the use of special equipment for endotracheal intubation. The otolaryngologist must have some knowledge of the available equipment for optimum operating conditions. This section is followed by a review of the difficult airway and suggested methods for control of the difficult airway. In the final section, an outline of the presurgical evaluation for patients with coexisting cardiovascular and pulmonary disease is presented, and anesthetic considerations for some common head and neck surgical procedures are presented. These procedures are discussed in greater detail in other parts of the text.
Pharmacology of Some Commonly Used Anesthetic Drugs
Opioids mediate analgesia through a complex interaction of opioid receptors in the supraspinal central nervous system (CNS). They produce reliable analgesia as well as provide some sedation and euphoria. There is no significant impairment of myocardial contractility, but sympathetically mediated vascular tone is reduced. Ventilation is depressed due to elevation of the carbon dioxide threshold for respiration. Opioids given at recommended doses do not reliably produce unconsciousness. They may, however, cause decreased bowel motility, biliary spasm, nausea, and pruritus. A brief review of some of the pharmacology of some of the more common opioids is presented below.
Morphine is relatively hydrophilic and thus has a slower onset with a longer clinical effect. Only a small amount of administered morphine gains access to the CNS, but it accumulates rapidly in the kidneys, liver, and skeletal muscles. Profound vein vasodilatation may be induced due to the effects of histamine release and reduction of sympathetic nervous system tone.
A synthetic opioid, fentanyl has similar effects, but is more lipid soluble and has more rapid onset and shorter duration of action. This reflects faster entrance into the CNS and prompt redistribution. Elevated doses may lead to progressive saturation in adipose tissues. When this occurs, plasma concentrations do not decline promptly. Thus, pharmacodynamic effects, including ventilatory depression, may be prolonged.
Remifentanyl was recently introduced and has a much more rapid onset and offset than fentanyl. With an initial dose, anesthesia may be achieved in 30–60 seconds, and offset of the drug can occur within 5–10 minutes after the discontinuation of an infusion. Because remifentanil is metabolized in blood and skeletal muscle, it can be administered as a single dose or in infusion. Due to the potency of this opioid and since chest wall rigidity may occur, this drug should be administered by an anesthesiologist or an anesthetist.
Commonly known as Demerol, meperidine has one-tenth the potency of morphine and a shorter duration of action. In low doses it has been shown to decrease the shivering associated with rewarming after surgery and after amphotericin administration. Several metabolites are excreted by the kidney and may accumulate in the presence of renal disease. The major metabolite, normeperidine is a proconvulsant and may cause seizures in renal compromised patients.
Opioids may be given by intermittent intravenous (IV) or intramuscular (IM) routes. Plasma level peaks and valleys may lead to variations in desired analgesia or excessive side effects. Continuous infusions or patient-controlled analgesia with smaller, more frequent doses has been shown to lead to better analgesia, with fewer side effects and less total drug use. Fentanyl and morphine may also be administered by an intrathecal or epidural route. This allows placement of opioids in the vicinity of receptors in the spinal cord. A growing body of information supports the use of these routes in high-risk patients to provide superior analgesia, less sedation, and less decrement in pulmonary function.
Tolerance developed by induction of hepatic microsomal enzymes may occur over the course of days to weeks. The effects of narcotics may be reversed with a variety of antagonists (ie, naloxone). Acute reversal may be accompanied by agitation, pulmonary and systemic hypertension, and pulmonary edema.
Benzodiapines produce anxiolysis and sedation by facilitation of the inhibitory actions of GABA on nerve conduction in the cerebral cortex. They may be used to produce sedation and amnesia, facilitate cooperation with care, attenuate alcohol withdrawal syndrome, treat seizures, and relieve muscle spasm.
Benzodiapines have no analgesic properties. They may cause transient decreases in blood pressure, due to decreased catecholamine levels and systemic vascular resistance, but with little effect on contractility. Respiratory depression is usually well tolerated in clinical doses, but may be accentuated in the elderly and those with COPD. Titration to a cooperative, oriented, and tranquil state (level 2 on Ramsey Scale) is the desired effect. Patients with a history of heavy alcohol or sedative use may require considerably more drug to achieve this response. Diazepam, midazolam, and lorazepam are three of the more commonly used benzodiapines.
Diazepam has a long clinical duration due to the long half life of several active metabolites. It is not water soluble and the parenteral suspension of propylene glycol is irritating when given intravenously or intramuscularly. Because diazepam requires microsomal nonconjugative pathways for degradation and elimination, it should not be used for patients with acute hepatitis.
Midazolam is the most commonly used benzodiazepine in the intensive care unit (ICU). It is water soluble, with short clinical duration, and few active metabolites. Midazolam offers a more rapid onset and a greater degree of amnesia, which makes it a good choice for brief procedures such as EGD and bronchoscopy.
Lorazepam is another frequently used long-acting benzodiazepine. There is no pain on injection and no active metabolites. This agent has become a popular choice for patients with liver disease because its metabolism is not dependent on microsomal enzymes.
Tolerance to benzodiapines develops as with prolonged alcohol and opiate use. Withdrawal may result in profound sympathetic autonomic response. Replacement of benzodiazepine plasma levels and transient autonomic control would be indicated for control of withdrawal symptoms.
Reversal of benzodiazepine-induced sedation has been reported with physostigmine and aminophylline. Flumazenil, a specific benzodiazepine receptor antagonist, provides consistent reversal of sedation within 2 minutes of IV administration. The duration of reversal is short; thus resedation is a possibility in cases of benzodiazepine overdose. Flumazenil has also been reported to transiently reverse the somnolence of hepatic encephalopathy. Therapy with this agent should be gradual, to avoid excitatory symptoms. Convulsions have been reported in seizure-prone and benzodiazepine-dependent patients.
The α2-agonist Dexmedetomidine is a class of sedative drug that has been approved by the FDA for use as a sedative and analgesic in the operating room and in the ICU. Dexmedetomidine has similar pharmacologic actions as clonidine except that its affinity for the α2-receptor is 8 times greater, making Dexmedetomidine 5–10 times more potent than clonidine. In the past few years, the use of Dexmedetomidine for the management of sedation and analgesia in the perioperative setting has increased significantly. Dexmedetomidine also possesses several properties that may additionally benefit to postoperative patients who have an opioid tolerance or who are sensitive to opioid-induced respiratory depression. In spontaneously breathing volunteers, IV Dexmedetomidine caused marked sedation with only mild reductions in resting ventilation at higher doses. Head and neck surgeons will find this drug useful for conscious sedation cases, for augmented sleep studies, and for fiberoptic intubations and tracheostomy placement.
The drug does cause some cardiovascular instability, although this can be avoided when the drug is titrated carefully. Nevertheless, it should be appreciated that Dexmedetomidine does cause some moderate reductions in blood pressure and heart rate.
Once a mainstay in sedation management, barbiturates now seem to have fallen out of favor, mainly due to availability of more titratable alternatives. They have numerous sites of action, but most likely promote the inhibitory effects of GABA on neuronal function. They have no analgesic effect and cause dose-related CNS, cardiac, and respiratory depression. Short-acting agents such as methohexital and thiopental are useful to produce unconsciousness for very short procedures such as cardioversions and intubations. Both agents can also be used for short-term procedures such as examination of the oropharynx in a noncooperative patient. As with most anesthetic induction drugs, patients should be adequately monitored (heart rate, blood pressure, electrocardiogram [ECG], and pulse oximetry), and supplemental oxygen should be given. Emergency endotracheal intubation equipment should be readily available together with emergency medications. Doses must be judicious due to the increased likelihood of respiratory and hemodynamic depression, especially in elderly patients.
Medium-acting (pentobarbital IV/PO) and long-acting (phenobarbital PO) agents have been used for violent agitation refractory to other agents, status epilepticus, andthe induction of barbiturate coma to treat increased intracranial pressure.
Propofol is an ultra-short-acting IV anesthetic agent. Unconsciousness may be induced in less than 30 seconds followed by awakening in 4–8 minutes. It has potent sedative hypnotic activity, but unlike other agents, awakening is markedly rapid from even deep sedation with minimal residual sedative effects, and good antiemetic qualities. Hepatic metabolism is rapid, but rapid redistribution also plays a role in early awakening. It has no pharmacologic active metabolites. Propofol has been shown to decrease systemic blood pressure as a result of myocardial depression and vasodilatation. When used in low doses (10–50 mcg/kg/min) as a continuous infusion for sedation, these effects are minimal. It has no analgesic effects but has been shown to decrease narcotic requirements.
One of the disadvantages is that propofol is only slightly water soluble. It must be formulated in an oil/water emulsion of soybean oil, egg lecithin, and glycerol. This is similar to 10% Intralipid. Thus, this agent is contraindicated in patients with potential for allergic responses to the emulsion components. Pain is frequent on injection. This is often attenuated by pretreatment of the vein with a 20- to 40-mg lidocaine bolus prior to infusion. Blood chemistries should be assessed because prolonged use may result in hypertriglyceridemia.
Propofol should be treated with the same degree of caution as parenteral nutrition solutions. Multiple reports of bacterial contamination due to manipulations of the emulsion medium demonstrate that it supports rapid bacterial growth. Recent formulations of propofol have included bacteriostatic agents, such as EDTA or sulfites, which have made this issue less of a clinical concern. Nonetheless, clinical guidelines still limit handling opened vials to less than 24 hours and, when used as an infusion, advocate line changes at regular (usually 12-hour) intervals.
A soluble cousin of propofol marketed as Aquavan (fospropofol disodium) is currently awaiting FDA approval.The drug is described to have similar properties as propofol without the pain experienced during injection. The drug has been used for conscious sedation for colonoscopies with success in several phase III studies. Aquavan does have the respiratory depression function of propofol.
Ketamine is a phencyclidine derivative (similar to LSD) that produces a dossal, dissociative state that may be exploited as a sedative. Agitated patients may be given IM injection (3–5 mg/kg) or titration of 10-mg IV boluses in order to produce a cataleptic state in which the eyes remain open with a slow nystagmic gaze. Amnesia is present and analgesia is intense. Additional advantages include maintenance of airway reflexes, cardiovascular stimulation, and bronchial relaxation. Disadvantages include increased airway secretions, transient increases in intracranial pressure, and an association with unpleasant visual or auditory illusions. Addition of benzodiazepines may attenuate these untoward sensory effects. Examples of clinical utility include conscious sedation for burn wound dressing changes and facilitation of endotracheal intubation in the hypotensive patient.
In the operating room, general anesthesia is commonly maintained with inhaled anesthetics. These agents also provide some analgesia, amnesia, and muscle relaxation. In pediatric cases where there is no IV access, anesthesia may be induced by inhalation. All of the inhaled anesthetics with the exception of nitrous oxide are bronchodilators and may be useful in patients with reactive airways. Most inhaled agents will reduced blood pressure due to direct cardiac depression (eg, halothane), or by vasodilation (eg, isoflurane, sevoflurane, or desflurane). The rapidity of induction of anesthesia as well as emergence from anesthesia is based on the lipid solubility characteristics of the inhaled anesthetic. Hence, the more insoluble the anesthetic agent, the faster the induction of anesthesia. Also, the agents with high lipid solubility prolong the emergence from anesthesia.
Nitrous oxide produces general anesthesia through interaction with the cellular membranes of the CNS. It is the only nonorganic inhaled anesthetic in clinical use. Although it is nonvolatile, it does support combustion, and caution should be taken in the event of airway fires. Uptake and elimination of nitrous oxide are relatively rapid compared with other inhaled anesthetics, primarily as a result of its low blood-gas partition coefficient. Elimination of nitrous oxide is via exhalation. It produces analgesia, amnesia (with a concentration greater than 60%), mild myocardial depression, and mild sympathetic nervous system stimulation. It does not significantly affect heart rate or blood pressure. Nitrous oxide is a mild respiratory depressant, although less than the volatile anesthetics.
Until recently isoflurane was the most commonly used inhaled anesthetic in the United States of America. Isoflurane is noted for its minimal cardiac depression. Like other volatile, isoflurane causes respiratory depression with a fall in minute ventilation. The ventilatory response to hypoxia and hypercapnia are diminished. Another characteristic in common with other volatile anesthetics is the ability of isoflurane to cause bronchodilation. This effect occurs despite its ability to cause airway irritation.
Isoflurane increases skeletal muscle blood flow, decreases systemic vascular resistance, and lowers arterial blood pressure. High concentrations of isoflurane may increase cerebral blood flow (CBF) and intracranial pressure. These effects are effectively reduced by hyperventilation. At even higher concentrations isoflurane reduces cerebral metabolic oxygen requirements and provides cerebral protection. Isoflurane decreases renal blood flow, glomerular filtration rate, and urinary output.
The structure of desflurane is very similar to isoflurane except for substitution of a fluorine atom for a chlorine atom. This makes desflurane highly insoluble. Its low solubility in blood and body tissues causes a very rapid wash-in and washout of anesthetics. Wake-up times are approximately half as long as those observed following isoflurane administration. Desflurane has cardiovascular and cerebral effects similar to those of isoflurane.
Sevoflurane has begun to replace halothane as a primary inhaled anesthetic agent used in the induction of anesthesia where an IV induction cannot be performed. It is used primarily in pediatrics where IV access is not available and induction has to be achieved by other means. Nonpungency and rapid increase in alveolar anesthetic concentration make it an excellent choice for smooth and rapid inhalation induction of anesthesia. Sevoflurane’s solubility in blood is slightly greater than that of desflurane. Sevoflurane mildly depresses myocardial contractility. Systemic vascular resistance and arterial blood pressure decline slightly less than with isoflurane or desflurane. As with isoflurane and desflurane, sevoflurane causes slight increases in CBF and intracranial pressure at normocarbia. Sevoflurane is reported to have potential for nephrotoxicity and hence should be used with a gas flow of greater than 2 L.
Halothane is a halogenated alkane that is used primarily for induction of anesthesia in patients where an IV induction is not possible. Halothane’s nonpungent and sweet-smelling odor makes it especially suitable for this purpose. Halothane causes a dose-depression reduction in arterial pressure by myocardial depression. It also causes respiratory depression. Halothane has been associated with a drug-induced hepatitis known as halothane hepatitis. This condition is extremely rare (1 in 35,000) and has an increased incidence in patients exposed to multiple halothane anesthetics within short intervals, in middle-aged obese women, and in patients with a genetic predisposition to halothane hepatitis.
Droperidol has greater antiemetic and sedative effects, but may also produce respiratory depression. If administered alone, dysphoria can happen; at clinical doses it is used in combination with a narcotic or benzodiazepine for sedation. More recently, the FDA has discouraged the use of droperidol in an unmonitored setting.
Ondansetron and dolasetron are selective antagonists of serotonin 5-HT3 receptors with little or no effect on dopamine receptors. Unlike droperidol they do not cause sedation, extrapyramidal signs, or alteration of the GI motility and lower esophageal sphincter tone. 5-HT3 receptors are found in the chemoreceptor trigger zone of the area postrema, in the nucleus tractus solitarius, and also along the gastrointestinal tract. The most common reported side effect is headache. Dolasetron can prolong the QT interval.
In the last few years, two new medications have been approved for the treatment of nausea and vomiting. Palonosetron, a 5-HT3 antagonist, has been shown to be effective in delayed emesis and has been shown to be superior to other the 5-HT3 antagonists ondansetron and dolasetron. In most studies, however, the efficacy has been best when the 5-HT3 antagonist was given with 20 mg of Dexamethasone. Another new antiemetic is aprepitant, an NK1 receptor antagonist. The scientific basis of aprepitant is based on its antagonism of substance P, a pro-emetic, which exerts its biological effect (emesis), by binding to the tachykinin neurokinin NK1 receptor. Aprepitant antagonizes this binding. The antiemetic effects of Aprepitant had added efficacy when given with Dexamethasone.
Neuromuscular blocking agents are used in most cases for endotracheal intubation and in the operating room when patient movement is detrimental to the surgical procedure. The most prominent side effect of giving neuromuscular blockers is that they cause paralysis of the muscles of respiration. Hence, ventilation of the patient is in the hands of the anesthesiologist and can be achieved with a mask or with a secured endotracheal tube.
Most muscle relaxants induce paralysis by blocking acetylcholine receptors at the neuromuscular junction of skeletal muscle. They have no intrinsic sedative or analgesic properties and must be used in concert with other medications. At a minimum, these agents should be used in conjunction with an anxiolysis agent. Inadequate sedation and hypnosis during use of neuromuscular blockers can produce unpleasant recall by patients with long-term side effects. Neuromuscular blockers can be classified as depolarizing neuromuscular blockers, such as succinylcholine, which bind to the acetylcholine receptor and produces a “persistent” depolarization of the neuromuscular junction. Muscle relaxation is achieved because propagation of action potentials is prevented by the area of inexcitability that occurs around the acetylcholine receptors. The second type of neuromuscular blockers is termed nondepolarizing neuromuscular blockers, which directly bind the acetylcholine receptor and prevent the binding of acetylcholine. All drugs described belong to the nondepolarizing neuromuscular blocker group (Table 5–1).
| Clinical Pharmacology of Neuromuscular Blocking Agents | ||||
|---|---|---|---|---|
| Agent | Intubation Dose (mg/kg) | Time to Onset (minutes.) | Time to Recovery (minutes.) | Infusion Rate (mcg/kg/min) |
| Vecuronium | 0.1 | 2–3 | 25–30 | 1–2 |
| Cisatracurium | 0.2 | 1–2 | 50–60 | NA |
| Pancuronium | 0.1 | 5 | 80–100 | NA |
| Rocuronuim | 1.2 | 1–2 | 40–150 | NA |
Vecuronium is a popular relaxant due to its short clinical duration (30–60 minutes) and lack of hemodynamic side effects. It may be given as a bolus or continuous infusion. It is metabolized by the liver and excreted by the kidney.
Cisatracurium undergoes degradation in plasma at physiologic pH and temperature by organ-independent Hofmann elimination. Metabolism and elimination appear to be independent of renal or liver failure. It does not affect heart rate or blood pressure, nor does it produce autonomic effects.
Pancuronium has a longer duration of action (60–90 minutes) and is eliminated primarily by renal mechanisms. The major limiting factor to its use is tachycardia, especially after bolus administration, resulting from a vagolytic effect.
