Most children can be well managed in this friendly environment. An anesthesia mask may be given to the child to play with in the waiting area before induction (Fig. 13-1). Allowing children to choose a flavor (e.g., bubble gum, cherry, or grape) can provide them with a sense of control. The additional support of pacifiers, toys, and music boxes is often helpful. Children should keep the objects brought from home, particularly security blankets or other transitional objects, during the induction of anesthesia. Clowns have also been used for the prevention of preoperative anxiety in children (Vagnoli et al., 2005; Golan et al., 2009).

FIGURE 13-1 An anesthesia mask may be given to the child to play with in the waiting area before induction.

Family responses, questions, and interactions with the child are important to note. It is essential for the pediatric anesthesiologist to include patients and families in decisions regarding anesthetic induction and care. Together they should agree on the needs for premedication, parental presence, and the type of induction technique (inhalation vs. intravenous) to ensure the smoothest and safest induction possible. Unfortunately, even the best of plans can fail, and back-up measures such as another premedicant, induction room, or means of induction, must be readily at hand. For older, combative children scheduled for elective procedure, postponing the procedure until the child is properly prepared should be considered. Inhalation induction by force should be a measure of last resort.

Premedication

As stated above, the use of premedication is the most reliably effective intervention for reducing preinduction anxiety and stress for young patients and their parents. Preoperative medications are described in detail in Chapter 9, Preoperative Preparation, and are discussed only briefly here. Historically, premedication referred to long-acting sedatives and anticholinergic agents that were often given intramuscularly (IM) or rectally (PR) to prepare children in inpatients’ units for their trip to the operating room. Contemporary administration of sedatives, typically by mouth, is administered just before induction to facilitate child-parent separation, anesthetic mask acceptance, and/or patient cooperation. IM administration is almost now solely reserved for extremely agitated, uncontrollable children.

Benzodiazepines

Midazolam, a water-soluble benzodiazepine, is the most commonly used preinduction medication (Kain et al., 1997). Given orally at 0.5 mg/kg mixed with fruit-flavored syrup, midazolam will create a calm, euphoric, or drowsy state in most children within 15 to 30 minutes. To potentiate its effect, children should be kept in a nonstimulating environment, and ambulatory children who may become unsteady should be held carefully on the parent’s lap or placed in bed. Coté et al. (2002) showed that a wider range of doses can be effective, adjusting for time of onset, and that respiratory compromise does not occur in otherwise healthy, unmedicated children. Paradoxical reactions, including restlessness, agitation, and disinhibition, occur in approximately 1% to 3% of patients (McMillan et al., 1992; Golparvar et al., 2004). The bitter taste of midazolam, which is difficult to conceal, may reduce acceptance. Midazolam can also be administered via nasal mucosal delivery at 0.2 mg/kg with a more rapid onset but has the disadvantage of an unpleasant burning sensation (Zedie et al., 1996). Prolonged recovery times are not seen with the use of midazolam premedication (Davis et al., 1995b; Bevan et al., 1997). Acetaminophen (20 mg/kg), in fruit-flavored syrup, can also be mixed with midazolam as part of premedication for postoperative analgesia, especially for short ear cases, such as myringotomies (Watcha et al., 1992).

Opioids

The use of opioids for premedication is uncommon in healthy children who are undergoing elective procedures. Even with noninvasive delivery systems such as oral transmucosal fentanyl citrate (OTFC), the advantage of relatively rapid onset is offset by the disadvantages of dysphoria, pruritus, nausea, and vomiting (Goldstein-Dressner, 1991; Ashburn et al., 1993; Epstein et al., 1996). Opioid premedication is best reserved for children experiencing pain, in which analgesia and sedation can be synergistic. The risk of respiratory depression, especially in infants younger than 6 months of age, should always be taken into account.

Ketamine

Ketamine can be given via the oral, nasal, rectal, or IM route (Stewart et al., 1990; Gutstein et al., 1992; Weksler et al., 1993; Tanaka et al., 2000). Ketamine is an effective sedative, but it can also cause increased secretions, nausea, vomiting, psychological disturbances, and prolonged recovery. IM injection of ketamine, 2 to 3 mg/kg (undiluted) may be useful in uncooperative, combative children as the last resort to avoid inhalation induction by force, which increases the risk of physical and psychological trauma to patients (Hannallah and Patel, 1989).

Alpha 2-Adrenergic Receptor Agonists

Oral (4 mcg/kg) and rectal (5 mcg/kg) clonidine can produce excellent perioperative sedation and anxiolysis while reducing the anesthetic requirement, emergence agitation, and postoperative pain, shivering, nausea, and vomiting (Bergendahl et al., 2004; Schmidt et al., 2007; Tazeroualti et al., 2007). The prolonged postoperative sedation seen with clonidine premedication may be advantageous after major surgical procedures but can delay discharge for same-day surgery patients. Similar findings have been described with transmucosal dexmedetomidine 0.5 to 1 mcg/kg (Schmidt et al., 2007; Yuen et al., 2008).

Topical Anesthesia

For children who require or prefer an intravenous (IV) induction, there are multiple approaches to achieving topical anesthesia. Local anesthetics can be delivered without needles through the skin’s protective stratum corneum into the innervated dermal layers via eutectic (EMLA) and liposomal (EL-MAX) creams or driven by mechanisms such as heat, iontophoresis, laser-assistance, or pressurized helium (Hung et al., 1997; Baron et al., 2003; Zempsky et al., 2004; 2008; Sawyer et al., 2009). These techniques, each with limitations, are capable of providing analgesia within 1 to 60 minutes of application. Reported satisfactory anesthesia varies with technique and patient age. Children younger than 6 or 7 years of age tend to report pain, secondary to fear and anticipation of needlesticks, even with apparent anesthesia (Arts et al., 1994; Kleiber et al., 2002).

Parental Presence During Induction

Parental presence during induction of anesthesia (PPIA), in the operating room or a separate area such as an induction room, has increased significantly in the United States over the last decade (Kain et al., 2004). Although the practice avoids separating children from their parents, it has not been shown to decrease patient anxiety or increase cooperation during induction (Kain et al., 1998; Arai et al., 2007). One benefit, which is important in terms of family-centered care, is an increase in parental satisfaction scores. Kain and colleagues, in 2006, confirmed the previous findings of Bevan et al. from 1990 that PPIA had a measurable benefit when a calm parent accompanied an anxious child, and a worsening effect when an anxious parent accompanied a calm child. There was no measurable benefit when both parent and child were calm. Subsequently, they have determined that parental preparation to reduce anxiety (e.g., learning distraction techniques, and avoiding reassuring behavior) can significantly improve the outcome of PPIA (Kain et al., 2007).

The logistical disadvantages of PPIA in the operating room include limited space, noise, unfamiliar equipment, and the need for parents to wear gowns and masks. Induction rooms can help anesthesiologists avoid some of these problems, but in both settings the parents must be prepared for the changes that can occur during induction, especially rapid loss of consciousness, uncoordinated movements, increased respiratory rate, and signs of upper airway obstruction. The anesthesiologist should be prepared to reassure the parent and respond quickly, especially if something goes wrong during induction. Parents need to be escorted to the waiting room as soon as their child loses consciousness.

Preparation for Induction

In the operating room or an induction room, anesthetic and monitoring equipment and supplies must be complete, confirmed, and readily available. The preinduction checklist for equipment should include a checked anesthesia machine, the gas pressures of accessory oxygen and nitrous oxide cylinders, an air-tight breathing circuit, the availability of a self-inflating bag, working suction, size-appropriate airway supplies (larger, smaller, and predicted, and including face masks, oral and nasal airways, laryngoscope blades and endotracheal tubes), and medications for induction and maintenance of anesthesia, as well as emergency medications. With the exception of patients suffering from malignant hyperthermia, emergency drugs for all pediatric inductions are atropine and succinylcholine, which should always be drawn into syringes of an appropriate size for the patient’s age and weight and clearly labeled in case of severe laryngospasm. Supplies for starting and securing IV access should be prepared. Additional ancillary equipment such as tongue depressors, adhesive tape, and soft suction catheters should also be at hand. If laryngeal mask airway (LMA) use is planned, appropriate size LMAs should be included in the set up. Monitoring devices, such as an in-flow oxygen analyzer, a pulse oximeter, a capnograph, an electrocardiograph (ECG), and an automated blood pressure cuff, should all be checked and ready. The temperature of the operating room should be properly adjusted and warming devices (e.g., Bair Hugger and other warming blanket or a radiant heat lamp) should be used.

Monitoring During Induction

At a minimum, monitoring during induction should include pulse oximetry and capnography. The precordial stethoscope, once the sine qua non of pediatric anesthesia, has apparently been displaced by more accurate and adaptable monitors (Watson and Visram, 2001). However, the precordial stethoscope is still an essential and more sensitive and continuous monitor for changes in breath sounds and the quality of heart beat, especially in infants and young children. Vital signs can vary markedly during the induction of anesthesia and should be observed continuously with a precordial stethoscope and in accordance with the ASA standards for patient safety (1986). If the child is anxious, it is probably best to place additional monitors like ECG pads and a blood pressure cuff after induction instead of losing the opportunity for a calm induction. However, medical condition and early infancy may necessitate full monitoring before and during induction. If this is the case, the baseline measurements should be obtained before the patient is exposed to any anesthetic agent.

Methods of Induction

There are many approaches for safely inducing general anesthesia in children. The particular technique chosen depends on the patient’s age; surgical procedure; underlying illness; discharge disposition; and in part, the preference of the anesthesiologist, the patient, and their family. The induction methods include: inhalational, IV, IM, and various combinations of these techniques.

Inhalation Induction

Whether sedated or awake, accompanied or alone, lying down or sitting up, a child breathing sevoflurane with or without nitrous oxide through a mask and circuit will become anesthetized. It is this simple fact that has made inhalation induction the most commonly used technique in pediatric anesthesia in the United States. In this manner, the induction of anesthesia is achieved with relative ease, speed, and safety, while avoiding the fear and pain of intravenous catheter insertion. Successfully selecting the approach, guiding the child and family through the process, and smoothly adapting to their needs is the challenge and reward of pediatric anesthesia induction.

When transitioning a child from the preoperative area to the site of induction, it is paramount that the well-sedated or asleep child is minimally stimulated or disturbed and that the awake or lightly sedated child is kept occupied and distracted by an anesthesiologist or family member. One person, either the anesthesiologist or a family member, should do all the talking, which should be reassuring and continuous. Giving patients and families the choice to have the child carried, walked, or wheeled to the induction location is another way to encourage participation and give them a sense of control. Perioperative staff need to remain quiet immediately before and during the induction, or they should be asked to step away. Regardless of location, age of the patient, or intended procedure, induction of anesthesia should be completely focused on the child and uninterrupted by other activities or last-minute preparations.

Once in the operating or induction room, the child may be given the choice to lie down or sit up. If sitting is elected and parents are present, the child can be offered the option to sit in a parent’s lap or next to them (Fig. 13-2). The anesthetic mask, either one introduced in the waiting area or one detached from the anesthesia circuit, should be shown (again) to the child. Putting artificial fruit or candy flavors in the mask may help disguise the odor of the anesthetic. One should never place the mask on the child’s face without warning. Even with preparation, some children, especially those with previous experience with inhalation inductions, may strongly reject the anesthesia mask (Przybylo et al., 2005). The mask may become more acceptable if a family or staff member initially tries it on, or if the anesthesiologist applies it to one of the child’s toys or random body parts before placing it near his or her face. Other methods to introduce the mask include having the child watch the insufflation of the anesthetic bag or hold the mask him or herself as he or she begins to breathe into the circuit. Making a game out of this activity is far better than getting into battle of wills. Distraction techniques such as storytelling, singing, counting, or just talking nonsense are strongly encouraged. If the child still emphatically objects to the mask, other approaches such as supplemental sedation or an IV induction should be considered.

FIGURE 13-2 Sitting up during induction of anesthesia is an option. If parents are present, the child can sit in a parent’s lap or next to a parent.

One way to initiate inhalation induction and avoid a negative reaction to the smell of the inhalation agent is to begin with a high flow of nitrous oxide and oxygen at a 2:1 ratio. The mask should be loosely applied to the child’s face until sedation is evident. The full sedative effect of nitrous oxide will occur within 2 minutes and be observable as the respiratory rate slows. Sevoflurane can then be added and increased rapidly to 6% to 8%. Except in young infants, short exposure to high concentrations of sevoflurane does not cause significant hemodynamic changes. Timing of the introduction of sevoflurane, the rapidity of increase, and the distraction techniques employed should vary with the child and family’s mood, level of anxiety, and degree of cooperation. Hyperventilation should be discouraged to avoid apnea during the induction. If the child objects to the smell of the inhaled anesthetic, breathing through the mouth to reduce the smell can be suggested.

DuBois et al. (1999) compared three induction techniques of conventional tidal-volume breathing of sevoflurane: incremental increasing concentrations (2% to 6% to 8%) in 100% oxygen, 8% in 100% oxygen, and 8% in a 1:1 mixture of nitrous oxide and oxygen. There were minimal differences among the three approaches. Lejus and colleagues (2006) compared the two different breathing techniques of conventional tidal volume and single-breath vital capacity of 7% sevoflurane in children older than 5 years of age. Eyelash-reflex loss was more rapid in the vital-capacity group compared with the tidal-volume group, but the time to deep anesthesia, bispectral index values 60 and 40, and the incidences of side effects were similar in both groups. Of note, the vital-capacity technique was preferred over the tidal-volume technique by the children. The authors propose that the decreased exposure to the smell of sevoflurane and decreased awareness of losing consciousness explained the higher preference scores in the vital-capacity group.

If a child has fallen asleep or is well sedated in a parent’s arms or on a stretcher, anesthesia can be induced by the “steal technique,” as originally described by Guedel in 1921 (Calverley, 1986). While avoiding moving or awakening the child, 70% nitrous oxide at high flows via an anesthesia mask is held closely over the child’s face. At first the mask should not touch the skin, but as sedation deepens it is placed gently on the face while incrementally increasing the concentration of sevoflurane. Monitoring devices should be attached as soon as possible. Once adequately anesthetized, the child can be transferred to a stretcher or operating-room bed if needed.

Once the patient has accepted the mask and is breathing the inhalation agent, it is extremely important to closely follow the progress of induction. The first sign is usually nystagmus, especially if nitrous oxide is being used. The eyes then usually close; the limbs and head may relax; and respiration becomes slower, regular, and deeper—then shallower and more rapid. Often children will have uncoordinated movements during the hyperreflexic phase of anesthesia and develop “snoring” or noisy breathing as the anesthetic depth deepens and as the patient develops partial upper airway obstruction. Although prepared for this preoperatively, parents should be reminded and reassured that this is normal during the induction of anesthesia. Until the eyelash reflex is gone, nothing should be done to move or stimulate the patient, unless airway obstruction or a similar need arises. Nurses and surgeons should not touch the patient without getting permission from the anesthesiologist. As soon as anesthesia is induced and the patient can tolerate moderately painful stimuli, an IV catheter can be started.

Unless excessive fluid or blood loss is anticipated, a 20-gauge catheter for children and a 22- or 24-gauge catheter for infants and small children fulfill the need for routine elective procedures. It is an error to use small-gauge catheters in infants and children merely because of their size. If adequate percutaneous sites are not available, use of a central venous catheter or surgical cut-downs may be indicated. Conversely, in children undergoing relatively minor procedures where major fluid shifts or blood loss are not anticipated, it is much better to have a working 22-gauge IV rather than a nonfunctioning 20-gauge catheter or multiple infiltrated IVs in an attempt to get larger venous access. If a scalp vein is used, caution is advised. Inadvertent subcutaneous injection of certain drugs, such as calcium, can cause tissue destruction and sloughing of the scalp.

Maintenance of the Upper-Airway Patency

Upper airway obstruction can arise during induction of anesthesia (even in healthy infants and children) for several reasons, including tongue displacement, excess soft tissue, velopharyngeal collapse, and laryngospasm. Applying pressure to the soft tissue between the rami of the mandible when holding a mask on a patient’s face can push the tongue against the hard and soft palate or displace it posteriorly, leading to occlusion of the oral pharynx or its outlet, respectively. Even minimal relaxation of the pharyngeal and laryngeal muscles during induction can significantly reduce oral and nasal passages already compromised by enlarged or increased amounts of lymphoid tissue. Relaxation of the pharyngeal and laryngeal muscles, accompanied by a marked increase in respiratory effort and excessive generation of negative pressure, which can occur in response to pain and other stimulation, may result in collapse of the velopharynx. To prevent upper airway obstruction from these causes, the pediatric anesthesiologist must learn to hold the anesthesia mask snugly to the patient’s face and perform the triple airway maneuver—neck extension, jaw thrust, and mouth opening—without applying pressure to the soft tissue or causing pain (Fig. 13-3). In addition, a moderate amount of continuous positive airway pressure (CPAP; 10 to 15 cm H₂O) can counteract the collapsing force on the relaxed upper airway (Motoyama, 1997; Hammer et al., 2001). Careful and continuous monitoring of breath sounds via a precordical stethoscope is essential to guide and maximize the effectiveness of upper-airway maintenance by hand.

FIGURE 13-3 To maintain upper airway patency, the pediatric anesthesiologist holds the anesthesia mask snugly to the patient’s face and performs the triple airway maneuver—neck extension, jaw thrust, and mouth opening—without applying pressure to the soft tissue or causing pain.

When the patient is sufficiently anesthetized, an oropharyngeal airway may be inserted to further aid in maintaining a patent airway. Insertion of an oral airway in an inadequately anesthetized patient risks triggering laryngospasm. The proper length of an oral airway, with the tip behind the base of the tongue, can be estimated by holding the airway over the side of the child’s face extending from the ear to the angle of the mandible. A preferred method for inserting an oral airway is to slide it gently forward and downward over the tongue while the tongue is pulled outward by a tongue depressor. The technique of inserting the airway upside down and then correcting the orientation in the posterior pharynx should be avoided in children. It tends to push the tongue posteriorly and obstruct the oral pharynx, particularly in infants (Smith, 1980). A nasopharyngeal airway is better tolerated when the anesthesia is too light for insertion of an oropharyngeal airway. This type of airway should be well lubricated and inserted very gently to prevent mucosal injury and bleeding.

If the obstruction is not relieved by airway maneuvers, the patient may have laryngospasm, which can result from laryngeal mucosal irritation and is often initiated by the aspiration of saliva. Vigorous positive pressure ventilation may push the secretions down into the larynx, which intensifies the spasm and further inflates the stomach, compromising pulmonary gas exchange. The risk of regurgitation and aspiration of gastric contents also increases. A healthy child can tolerate a few moments of laryngospasm. A more successful approach is to maintain moderate continuous positive pressure and synchronous ventilation with the “expiratory” phase of laryngospasm, which is when the vocal cords momentarily relax. By using 100% oxygen and intermittent positive pressure, one can ventilate enough gas through the glottis to avoid serious hypoxemia. If rapid oxygen desaturation and bradycardia ensue, IV succinylcholine (2 mg/kg) and atropine (0.02 mg/kg) or 5 mg/kg of IM succinylcholine should be administered without delay (Liu et al., 1981; Hannallah et al., 1986). Airway patency needs to be reestablished with or without tracheal intubation.

Intravenous Induction

In children and adults, induction via the IV route has the advantage of speed and avoids the unpleasant odors and sensations of an inhalation induction. The major disadvantage involves the difficulty and fear associated with venipuncture in young children. Topical anesthetic, as discussed previously, can significantly reduce pain associated with catheter insertion if it is used appropriately and enough time is allowed. Children younger than 6 or 7 years of age have shown less overall benefit from the use of topical anesthetics than older children, probably because the fact that young children, although numb, continue to associate needles with pain. Children who are 8 to 10 years of age and older may prefer an IV induction to a mask, often because they have unpleasant memories from a previous experience. Dorsal hand, radial, and if needed, antecubital veins are typically most visible, accessible, and acceptable sites for IV catheter insertion. Wrist, foot, and saphenous veins are other possibilities, but they are difficult to access unless the extremity is immobilized and the skin is anesthetized.

The anesthesiologist should always be honest with children, explaining each step of the procedure without frightening them. Using distraction techniques during the placement of the catheter is superior for reducing pain and agitation, compared with using encouragement and complements on good behavior or courage. Before the delivery of any medications, the anesthesiologist should ensure that the IV catheter is easily flushed to avoid inadvertent subcutaneous infusions. Securing the IV insertion site is particularly important in children, because they often emerge in an uncooperative and agitated state. The extremity in which the catheter is inserted should be taped to a cushioned board with a loop of IV tubing to prevent accidental pull and removal of the catheter.

Propofol

An induction dose of propofol is 2.5 to 3.0 mg/kg in healthy unpremedicated children between the ages of 3 and 12 years (Manschot et al., 1992). In induction studies, children younger than 2 years of age required a significantly larger dose (2.6 to 3.4 mg/kg), whereas older children needed less (Aun et al., 1992; Manschot et al., 1992). Induction with propofol in children can cause significant decreases in blood pressure and inotropy, similar to those observed after thiopental (Mirakhur, 1988; Hannallah et al., 1991; Manschot et al., 1992).

A major drawback to propofol is the pain it causes on injection. In a quantitative systematic review, Picard and Tramèr (2000) determined that the only approach that had a reliably low number of needed-to-be-treated (NNT) patients was the lidocaine-tourniquet technique (similar to a Bier block; see Chapter 16, Regional Anesthesia) and that preinjection of local lidocaine and analgesics, temperature of medication, speed of infusion, and vein size had no significant effect. Yew et al. (2005) and Rochette et al. (2008) have shown that the addition of medium-chain triglyceride to propofol preparation also decreases pain on injection. Propofol offers the advantage of having antiemetic properties (Borgeat et al., 1990).

Thiopental

The induction dose of thiopental in healthy children is 5 to 6 mg/kg (Coté et al., 1981). In infants between 1 and 6 months of age, the median effective dose (ED50) is reported to be 6.8 mg/kg; in infants younger than 2 weeks of age, it is 3.4 mg/kg (Jonmarker et al., 1987). The dose for induction in infants younger than 5 months was almost twice that for older children (see Chapter 7, Pharmacology of Pediatric Anesthesia, Fig. 7-18). Like propofol, thiopental is a cardiac depressant and vasodilator, and it should be used with care in patients suspected to have hypovolemia or decreased cardiac function.

Etomidate

The induction dose of etomidate in healthy children is 0.3 mg/kg, and it is often recommended in patients who have limited hemodynamic reserve. Sarkar and colleagues (2005) confirmed that in children there are no significant changes in right atrial, aortic, or pulmonary artery pressure, or systemic or pulmonary vascular resistance after bolus dosing. Side effects include pain on injection and myoclonic movements.

Ketamine

Ketamine is a dissociative anesthetic, and a dose of 2 mg/kg produces a catatonic-like state in children within 1 to 2 minutes. Its ability to stimulate the release of endogenous catecholamine and subsequently elevate heart rate and blood pressure and dilate bronchial airways supports its use in patients who may benefit from these properties. Ketamine increases oral and airway secretions and is associated with psychological and behavioral sequelae in children. To minimize these side effects, antisialagogues (glycopyrrolate, 0.1 mg/kg) and benzodiazepines (0.5 mg/kg) are recommended, respectively.

Maintenance of anesthesia

After induction, the anesthesiologist is responsible for maintaining patient analgesia, amnesia, and immobility, as well as maintaining autonomic and hemodynamic stability to allow for optimum working conditions for surgical procedures. Today, a balanced anesthetic technique that is tailored toward each patient and accounts for his or her medical conditions, as well as the surgical procedure and planned postoperative management, is preferred. To do this, the anesthesiologist has several options with respect to anesthetic drugs, including inhalational versus intravenous agents. Adjuvant drugs for pain control, muscle relaxation, and prevention of postoperative nausea and vomiting are also used. Furthermore, in certain patients, regional anesthesia allows for improved pain control with a reduction in the use of opioids that can have significant side effects.

During the maintenance phase, the anesthesiologist must always be vigilant, with careful and continual monitoring of anesthetic depth, oxygenation, ventilation, cardiovascular function, fluid balance, body temperature, and glucose and electrolyte levels. In more critically ill patients, the anesthesiologist may need to place more invasive monitors for more accurate observation of the patient’s status. Ultimately, the anesthesiologist is the patient’s advocate in the operating room, communicating with the surgeons and allowing for a safe, comfortable, and successful outcome in the perioperative period.

Pharmacologic Agents

Sevoflurane affects respiratory function, with some studies suggesting it does so to a greater extent than other agents (Doi et al., 1994; Yamakage et al., 1994). Brown and colleagues (1998) found that compared with halothane, minute ventilation and respiratory frequency were lower in infants on 1 MAC of sevoflurane, but that there were only moderately increased end-tidal carbon dioxide (CO₂) levels. Sevoflurane is, however, an effective bronchodilator (May et al., 1996). Neurologically, sevoflurane has been associated with cortical epileptiform electroencephalograms, although no lasting clinical sequelae (such as seizures) have been attributed to sevoflurane alone. Further studies are necessary to determine which patients are at risk and what can be done to decrease the incidence of these EEG changes (Constant et al., 2005).

As much as 5% of sevoflurane is metabolized, with defluorination producing an inorganic fluoride that is then excreted in the urine. Peak fluoride concentrations, although higher in sevoflurane than in isoflurane, are still well below the accepted nephrotoxic level of 50 mmol/L. There is rapid elimination, and these levels remain below toxic levels even with prolonged anesthetics (Levine et al., 1996; Hatch, 1999). In addition, the metabolism of sevoflurane by the P₄₅₀E₁ system is mostly in the liver and not the kidneys. Thus, the concern of nephrogenic diabetes insipidus (DI) by elevated fluoride levels does not appear to be an issue.

Sevoflurane reacts with soda lime in the anesthesia circuit, resulting in the production of compound A. Compound A increases more when Baralyme brand (Allied Healthcare Products Inc., St. Louis, Mo) is used, when dry rather than wet absorbents are used, and when lower fresh gas flows (0.5 to 1 L) are used, resulting in increased canister temperatures (Frink et al., 1992a). Ebert and colleagues did not find evidence of renal injury after sevoflurane was administered in high concentrations (3% end-tidal) for 8 hours (1998). Kharasch and colleagues (1997) also found no significant renal dysfunction in patients with low-flow sevoflurane (1 L/min) when compound A was detected. Other studies have also documented no worsening of renal function after sevoflurane, even in patients with preexisting renal impairment (Conzen et al., 1995). New generation CO₂ absorbers, including DragerSorb Free and Amsorb Plus, have been shown to provide adequate CO₂ absorption while reducing the production of compound A, even at fresh gas flows as low as 500 mL/min (Marini et al., 2007).

Spontaneous ignition, fire, and explosion resulting from an exothermic reaction of sevoflurane with desiccated CO₂ absorbers have also been reported (Castro et al., 2004; Wu et al., 2004). With high fresh gas flow, the increasing dryness of the absorbent increases degradation of sevoflurane. Dunning et al. (2007) demonstrated that up to 3 mol of hydrogen were produced in the reaction of sevoflurane with heated, desiccated absorbent. The authors postulate that this hydrogen is the most likely fuel in anesthesia machine fires. Special attention should be paid to situations in which absorbent desiccation may be greater, such as in seldom-used anesthesia machines and in operating rooms where high fresh-gas flows relative to body size are used (Wu et al., 2004). The use of newer absorbents or Mapleson D circuits can also help avoid this problem (Woehlck, 2004).

While the question of sevoflurane-related hepatitis has been raised in case reports, metabolism of sevoflurane does not result in the trifluoroacetylated liver proteins that trigger the immune-mediated hepatitis seen with halothane, and immune-based hepatitis after sevoflurane has not been reported (Kharasch, 1995; 2008). Malignant hyperthermia has been reported with sevoflurane use (Otsuka et al., 1991).

Both postanesthetic emergence time and the time when discharge criteria are met are significantly lower in patients given sevoflurane compared with those receiving halothane; however, patients receiving sevoflurane had significantly higher pain scores that required analgesics to be administered earlier (Naito et al., 1991; Sarner et al., 1995). In a meta-analysis of randomized controlled trials, Kuratani and Oi (2008) demonstrated that sevoflurane had a higher probability of emergence agitation compared with halothane (Fig. 13-4). Treatment or pretreatment with either dexmedetomidine, fentanyl, or propofol can mitigate emergence agitation after sevoflurane anesthesia.

FIGURE 13-4 Meta-analysis of emergence agitation caused by sevoflurane (Sevo) versus halothane (Halo). The center of each purple diamond is the odds ratio (OR) for individual trials, and the corresponding horizontal line is the 95% confidence interval (CI). The open diamond is the pooled result.

(From Kuratani N, Oi Y: Greater incidence of emergence agitation in children after sevoflurane anesthesia as compared with halothane: a meta-analysis of randomized controlled trials, Anesthesiology 109:229, 2008.)