CHAPTER 182 Anesthesia in Pediatric Otolaryngology
Because of the inherent complexity of the structure-function relationship in otolaryngology, pediatric otolaryngologists and anesthesiologists must work together closely in the operating room to provide optimal care to the patient. This chapter focuses on anesthesia topics that are relevant for the pediatric otolaryngologist, beginning with the safety of anesthesia for children, followed by preoperative assessment of pediatric patients. Perioperative management, including choice of drug and technique to match the situational demands, is described next. Finally, the anesthetic implications of specific diseases and the anesthetic considerations in commonly performed pediatric otolaryngology procedures are reviewed.
Anesthesia carries increased risk in children as compared with adults, as reported more than 50 years ago.1 Work from the 1960s correlated this increased risk with age less than 1 year.2 Nowadays children younger than 1 month of age are recognized as being at the highest risk,3 which suggests that the risk of adverse events with anesthesia induction in infants is inversely proportional to age. In view of the physiologic changes that occur during the first year of life, this is not surprising. Respiratory control is immature in infants; carbon dioxide (CO2) response curve is lower than it is in older children and adults, and hypoxia may induce apnea rather than hyperventilation. Cardiovascular responses also are immature: The myocardium is poorly compliant, so cardiac output is rate dependent. Similarly, responses to anesthetic agents differ in accordance with patient age. Preterm and full-term newborns require lower concentrations of inhaled anesthetics than those needed in older children or adults. Inhalational agents may cause more depression of cardiac output in infants and may have a more profound effect on baroreflexes. Pharmacokinetic parameters of volume of distribution, hepatic clearance, and renal clearance differ profoundly from those in older children, affecting the dose of nearly every drug.
These differences in physiology and pharmacology are reflected in the types of anesthetic mishaps that tend to occur in newborns and infants. Inadequate ventilation and anesthetic overdose have been the most frequent sources of anesthetic morbidity and mortality in the 1980s.4 Changes in anesthetic practice, such as improvement in monitoring (e.g., pulse oximeters and CO2 monitors) and use of different drugs (e.g., sevoflurane instead of halothane) have decreased respiratory events and shifted the number of anesthesia-related cardiac arrests in infants toward cardiovascular causes of cardiac arrest.5,6
Adherence to the American Society of Anesthesiologists (ASA) monitoring standards7 is basic to all anesthesia care performed by an anesthetist and has reduced the incidence of intraoperative complications.8 The components of these standards are presented in Box 182-1. Most anesthesiologists consider pulse oximetry to be an indispensable part of the intraoperative monitoring armamentarium, although it has been difficult to document improvement in outcome as a result of this technique, even in a very large series.9,10 The use of pulse oximetry alone or in combination with capnography has reduced the relative frequency of adverse respiratory events as compared with adverse cardiovascular events, perhaps because pulse oximetry and capnography are more effective for preventing respiratory events than cardiovascular events.11
Box 182-1 Intraoperative Monitoring Standards
Elective procedures should be deferred until the infant is at least 6 months to 1 year old, when anesthetic risk is likely to be lower. This is particularly true in infants who were born prematurely, because they have an increased risk of postoperative apnea until approximately 55 weeks of postconceptual age (see following). The use of trained subspecialty pediatric anesthesiologists for the care of infants and children has been suggested to be associated with improved outcomes,12 although this contentious claim is difficult to prove.13 More recent concern has been raised about the potential for neuronal damage in the developing brain caused by anesthetic agents. The available data are still preliminary, and no definitive human studies proving this concept have been performed. The United States Food and Drug Administration (FDA) recently launched the first phase of SAFEKIDS (Safety of Key Inhaled and Intravenous Drugs in Pediatrics), an initiative to provide seed funding for several clinical projects.13a Pediatric practitioners should be aware that more information probably will be presented in the coming years and may influence decisions about what age is safe to perform elective procedures.14
Current estimates of anesthetic mortality vary widely, depending on the definition of anesthetic death. However, mortality in healthy pediatric outpatients as the result of an anesthetic-related cause is very rare, with rates perhaps as low as 0.36 in 10,000 cases.6,15 Accordingly, parents of otherwise healthy children can be reassured that outcomes in modern-day pediatric anesthesia are excellent.
Today’s emphasis on cost containment has forced many changes in the practice of pediatric anesthesia. More and more patients with complex medical problems are having procedures as outpatients, which forces the preoperative contact between the anesthesiologist and the patients and family into a very few minutes. In addition, efficiency pressures have forced institutions to search for ways to maximize patient flow in surgery areas and to minimize unexpected delays or cancellations. Preoperative anesthesia clinics have developed in response to these changes.
A visit to the preanesthesia clinic before the day of surgery affords the opportunity for taking an anesthetic history; performing a physical examination; obtaining necessary laboratory tests; and informing the family about the anticipated procedures, including times for restriction of oral intake to nothing by mouth (i.e., NPO [nil per os]) status), premedication, anesthetic induction and maintenance, and postoperative pain management techniques. It also allows confirmation that all necessary paperwork, such as consent and surgical history and physical, is present in the medical record. An attending anesthesiologist is available for consultation for more complicated cases or to address specific clinical questions. Anesthetic risk can be discussed with patients and their families, with ample time allowed for them to ask questions. In addition, the clinic nurse can take this opportunity to educate the patient and family about the impending surgical visit and to identify fears and concerns of the parents and child.
A preoperative medical assessment includes a review of body systems and the patient’s response to previous anesthetics, current medications, allergies, recent illnesses (including upper respiratory infections), and family history of problems with anesthesia. The physical examination concentrates on airway anatomy, including the mouth, jaw, teeth, and neck, and includes chest and heart auscultation to confirm the absence of significant cardiorespiratory disease. Laboratory tests are obtained as indicated by the child’s condition and type of surgery planned, rather than as a routine component of the assessment.16 Identification of clinical problems at a preanesthesia visit also allows appropriate evaluation or referral before surgery, thereby avoiding delay or cancellation on the day of surgery.
The days and hours leading up to surgery can be an anxious time for both children and parents. Fears about hospitalization are common among children, including fear of separation, pain, loss of control, and even death. Many of these fears are dependent on the child’s age17 (Table 182-1). Awareness of these developmental stages allows the anesthesiologist to better anticipate the needs of most children. In addition, understanding the impact of parental anxiety on a child’s anxiety can help in the selection of interventions that will be helpful to both the child and the parents.
|Infant (6-18 months)
|Toddler (1-2 years)
|Fear of strangers, loss of mastery of the environment
|Preschool (2-5 years)
|Separation anxiety; difficulty distinguishing reality from fantasy; fear of pain, mutilation
|School age (6-12 years)
|Fear of the unknown, pain, mutilation, loss of control, autonomy
|Adolescent (13-18 years)
|Precarious sense of self; fear of pain, mutilation, loss of control, autonomy
From Orr RJ, Lynn AM. Curr Rev Clin Anesth. 1991;12:29.
Details of the anesthetic and surgical experience should be presented in age-specific language for children of appropriate age.18 Children who are given specific information before surgery have been shown to be less anxious than children who are given only general information.19 Movies or videotapes can help children and parents cope with the mysteries of hospital routines.20 Comprehensive preoperative preparation programs have been shown to be helpful for reducing preoperative anxiety and enhancing coping behavior in children.21 This may be especially important for children who will require repeated procedures, allowing them to learn coping strategies and to develop a better understanding of the environment in which they will receive their care. Parents also should be involved in these programs, because decreasing their anxiety is likely to provide the added benefit of decreasing the child’s anxiety further.22 These efforts are important even if pharmacologic agents will be used to decrease anxiety, because the combination of psychological and pharmacologic interventions can produce synergistic effects.23
The choice of premedication is based on the age and specific needs of the patient. The usual goals of premedication are to reduce anxiety and to ease separation from parents. Because most children fear needles, the oral administration of sedatives has become the standard of care at many institutions. Children who are younger than 8 months of age generally do not need premedication and separate easily from their parents. Children between 8 months and 8 years of age often experience enough preoperative anxiety that preoperative medication may be helpful. Midazolam (0.5 to 1.0 mg/kg up to a maximum of 20 mg), mixed in flavored syrup and administered orally 10 to 20 minutes beforehand, usually smoothes the separation from the parents and induction of anesthesia, and has become the most popular agent for preoperative sedation for children.24 Midazolam usually is well tolerated, although a rare decrease in oxygen saturation or blood pressure may be observed. In addition, intravenous flumazenil (10 µg/kg, administered over 1 minute, repeated as needed for a total of 5 doses; maximum 0.2 mg/dose, and 1 mg total dose) can be administered to reverse adverse effects such as oversedation, paradoxical effect, or emergence delirium.
Older children may be willing to have an intravenous line started preoperatively, especially if a topical anesthetic cream such as EMLA (eutectic mixture of local anesthetics) or ELA-Max (Ferndale Laboratories, Ferndale, Michigan) is used. EMLA cream is a mixture of lidocaine and prilocaine that penetrates intact skin and, when applied for 60 minutes or more, significantly decreases the pain associated with an intravenous insertion.25,26 EMLA should be used with caution in children younger than 3 months of age or in children who are receiving other medications that may induce methemoglobin because of the risk of methemoglobinemia.27 Plasma concentrations of lidocaine and prilocaine achieved with topical application are well below the toxic level,27 but they may be higher in children with traumatized or inflamed skin. Another effect of EMLA that may be problematic is vasoconstrictive blanching, which makes the identification of potential intravenous insertion sites difficult for some practitioners. ELA-Max is an alternative to EMLA, and it contains only lidocaine in a liposomal matrix that allows for effective absorption across intact skin.28 ELA-Max has been shown to provide equal topical anesthesia to EMLA, and it has a quicker onset of 30 minutes.8,29 ELA-Max also produces less blanching than that seen with EMLA. If an intravenous line is placed, midazolam or another sedative can be titrated intravenously until the desired effect is achieved. Although the topical anesthetic creams are the most frequently used, alternative methods for providing topical anesthesia may be standard in some institutions.
Younger children may not accept oral premedication well, making this method of administration as anxiety-provoking as separating the child from his or her parents without any premedication. Alternative methods do exist. Intranasal administration of midazolam (0.2 to 0.3 mg/kg) using either an atomizer or simply a needle-less tuberculin syringe is easy in a patient small enough to be held or restrained.30 This agent begins acting immediately after dosing and reaches peak concentrations by 14 minutes, having the advantage of increased bioavailability with minimal first-pass metabolism in the liver.31 Intramuscular administration of premedication becomes necessary in larger children with behavioral issues that limit patient cooperation—autism, for instance. Because intramuscular injection is technically easier than intravenous line placement, this technique can be achieved quickly, and the child then be allowed some time with the parent, to minimize the trauma from the encounter. Intramuscular ketamine at a dose of 2 to 5 mg/kg or a combination of intramuscular ketamine and midazolam causes sedation and dissociation from the environment, making the patient more approachable for procedures, anesthesia induction, and so on. Larger doses of ketamine administered intramuscularly (up to 10 mg/kg) can induce general anesthesia (see following discussion). Anticholinergic agents may be desirable when copious airway secretions (commonly seen with ketamine) are a concern, or when vagal tone from airway manipulation produces decreases in heart rate and cardiac output. Halothane, an inhalation agent used only in a few countries outside of the United States, is more likely to cause bradycardia and a significant reduction in cardiac output in children younger than 6 months of age, than in in older children. The routine use of anticholinergic agents with halothane in these younger patients can prevent these changes.32 Atropine (0.02 mg/kg) or glycopyrrolate (0.01 mg/kg) given intravenously at the time of induction can obviate the pain of an intramuscular injection.
To minimize the risk of the aspiration of gastric contents during the induction of anesthesia, an adequate period of fasting must be maintained. Traditionally, both food and fluids have been withheld after the midnight before surgery. However, a prolonged period of fasting is uncomfortable for children, is unpleasant for the family, and risks hypovolemia. It has recently been recognized that the administration of clear liquids to children up to 2 to 3 hours before induction does not increase gastric residual volume or acidity as compared with a more prolonged fast.33,34 In addition, morbidity and mortality rates for aspiration of gastric contents in children are exceedingly low.35 Thus, fasting guidelines have been liberalized in recent years, and they are shown in Table 182-2. There is some debate about whether breast milk should be considered a solid or clear liquid, with many institutions allowing breastfeeding within the same guidelines as clear liquids. Nevertheless, in giving these instructions to parents, it is important to emphasize the safety issues involved to maximize compliance and avoid unnecessary delays in the start of the procedure.
|Minimum Fasting Period (hours)
Adapted from Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures: a report by the American Society of Anesthesiologists Task Force on Preoperative Fasting. Anesthesiology. 1999;90:896-905.
Anesthesia can be induced by mask inhalation of a potent anesthetic agent in oxygen with or without nitrous oxide (inhalation induction), by injection of a sedative-hypnotic agent through an intravenous catheter (intravenous induction), or by intramuscular injection. As much as possible, the choice of technique is given to children; younger children tend to fear needles and prefer an inhalation induction, whereas older children and teenagers usually accept an intravenous induction.Inhalation induction will take longer in teen aged and older patients than in younger patients because of age-related physiologic differences. This prolonged time to effect must be taken into consideration if an inhalation induction is selected in this age group but does not preclude such an induction. Certain clinical factors (e.g., obesity, severe gastroesophageal reflux, full stomach) also may influence the choice of induction technique toward intravenous.
With increasing frequency, parents are expressing a desire to be present at the time of their child’s anesthetic induction.36 Although parents’ motives vary, most hope that the child’s anxiety will be lessened by the emotional comfort of their presence. Some hospitals have induction areas outside of the sterile envelope of the operating room. If not, parents can be dressed in cover gowns and escorted into and out of the operating room for the induction.
Studies examining the impact of parental presence have had variable results, with some showing no significant impact,37 some showing a decrease in patient anxiety,38,39 and others showing an increase in patient anxiety.40 Parents with a high anxiety level seem to have a negative impact on their child, whereas calm parents seem to have a positive impact on their anxious child during induction.41 One survey reported that a majority of anesthesiologists are in favor of the practice of having parents present during induction,42 and many hospitals tend to support this request as a mechanism to improve patient and parent satisfaction. Thus, it is likely that the trend will continue. Parents should be thoroughly educated about what to expect and how they can best help their child. They must agree to leave the induction area immediately when instructed to do so, and one member of the care team must be identified to help them during the induction. Highly anxious parents should be encouraged not to participate.
For many years, halothane was the agent of choice for inhalation induction because of its lack of pungency relative to other agents. A more recently developed alternative, sevoflurane, is even less pungent than halothane and has fewer cardiovascular side effects, making it the current pediatric inhalational induction agent of choice. A small amount of favorably scented liquid (e.g., bubble gum flavor, for instance) applied to the inside of the mask disguises the odor of the anesthetic agent and improves the patient’s acceptance of the technique.
Many anesthesiologists will begin the induction with the patient breathing 50% to 70% nitrous oxide (which is odorless) before introducing sevoflurane, thus making the addition of the sevoflurane less distressing. Noise in the room should be kept to a minimum during anesthesia induction, and the anesthesiologist often tells the child an entertaining story to direct the child’s thoughts away from the reality of the situation. As the concentration of the anesthetic agent is increased, most children lose consciousness in less than 1 minute. The parents, if present, can be ushered out at this point, and an intravenous catheter can then be placed.
Intravenous induction requires the presence of an intravenous catheter and thus is reserved for older children or teenagers, children with a preexisting intravenous catheter, children who need a rapid-sequence induction because of a full stomach, or children who object to an inhalation induction. Owing to slower uptake of inhaled anesthetic agents, inhalational induction takes much longer in older, heavier children, with consequently higher risk for laryngospasm and bronchospasm. An intavenous induction is therefore also the preferable method in this patient group.
The most common agent for intravenous induction is propofol, an alkylphenol that is formulated as a 1% solution in a white soybean oil, egg lecithin, and glycerol emulsion. Propofol is highly lipophilic and rapidly redistributes throughout body compartments, with a distribution half-life of approximately 2 minutes and an elimination half-life of approximately 30 minutes. The dose for the induction of anesthesia varies with age43: Infants 1 to 6 months of age require approximately 3 mg/kg, whereas older children require approximately 2.5 mg/kg. The major advantages of propofol are a rapid, clear-headed recovery with minimal associated nausea and vomiting. This has made it the intravenous induction agent of choice for outpatient procedures. The major disadvantage is pain on injection, particularly into small veins.44 Lidocaine (0.5 to 1.0 mg/kg) administered intravenously before or during propofol injection may decrease the incidence of pain. Propofol may cause hypotension, apnea, and desaturation. Propofol also can be used for anesthesia maintenance as an intravenous infusion of 100 to 200 µg/kg per minute. This technique can be very useful for patients who have a history of severe postoperative nausea or who are undergoing procedures in which postoperative nausea is especially common (e.g., tympanoplasty). Many pediatric anesthesiologists use a propofol infusion to provide anesthesia during bronchoscopy, because it provides a reliable, stable method of administering anesthesia with spontaneous ventilation while sharing the airway and decreases the exposure of the surgeon to unscavenged anesthetic gases.
An alternative intravenous agent for induction is thiopental, an ultrashort-acting barbiturate that produces sleep in healthy, unpremedicated children; a dose of 4 to 6 mg/kg induces sedation within 1 minute of administration.45 This drug can produce hypotension through both vasodilating effects and direct myocardial depression and must be used with caution in hypovolemic patients or patients with poor myocardial contractility. It also can produce prolonged sedation as a consequence of accumulation in fat stores if higher doses or repeated doses are given.
Patients with a full stomach are at increased risk for the aspiration of stomach contents during the induction of anesthesia. Patients who require full stomach precautions include those who have not fasted for an adequate period, those with gastrointestinal obstruction, trauma patients whose gastric motility is depressed, or those who are at a mechanical predisposition for aspiration (e.g., patients with ascites). It is mandatory that these patients have an intravenous induction. Patients are preoxygenated with 100% oxygen by mask and then given an induction dose of a hypnotic and a rapid-acting muscle relaxant—either succinylcholine (2 mg/kg) or rocuronium (1.2 mg/kg). Application of manual pressure over the cricoid (known as the Sellick maneuver) can be performed in an attempt to seal the esophagus and to prevent passive regurgitation.46 Pressure is not released until the endotracheal tube is in place, proper position is confirmed, and the cuff, if necessary, is inflated. At the end of the procedure, these patients should be allowed to emerge completely before extubation, to ensure adequate airway protection.
Ketamine is a derivative of phencyclidine with potent analgesic and amnestic properties. Anesthetic induction can be achieved with the recommended dose of 1 to 3 mg/kg intravenously or 5 to 10 mg/kg intramuscularly. As noted previously, ketamine is very useful as an intramuscular induction agent in children who are combative or unable to cooperate with a standard inhalation or intravenous induction, often because of intellectual disabilities and behavioral disorders. Ketamine is an excellent choice for anesthetic induction in hypovolemic patients because of its sympathomimetic properties; it rarely causes hypotension in these patients. Ketamine may be the intravenous induction agent of choice in patients with reactive airways47 because it increases circulating catecholamines and causes the relaxation of tracheal, bronchial, and alveolar smooth muscle.
Ketamine tends to produce copious secretions and should be accompanied by the administration of atropine or glycopyrrolate. Nystagmus and diplopia are common side effects and will resolve as the drug is cleared from the patient’s circulation. Intraoperative and postoperative dreams and hallucinations have been reported,48 more often in older than in younger children, and less often when other sedative-hypnotic agents are used in conjunction with ketamine. If this agent is given preoperatively with the parents still present, they should be informed to expect these side effects.
Nitrous oxide is a widely used inhalational induction agent in children. Its popularity is a result of its low solubility, which results in rapid uptake and distribution. Nitrous oxide also is odorless and does not cause cardiovascular depression. Although nitrous oxide allows the delivery of lower concentrations of other anesthetic agents, nitrous oxide itself is not a very potent anesthetic agent. Consequently, it must be delivered in high concentration to have an analgesic and hypnotic effect, thereby limiting the concentration of oxygen that can be delivered; it is not useful for patients who require high concentrations of oxygen and should be avoided in patients with pulmonary hypertension as it may aggravate it. Because of the lack of potency and the controversial increased incidence of postoperative nausea and vomiting (PONV), it has been used less and less for anesthesia maintenance. A 34-fold difference has been noted in the blood-gas coefficients of nitrogen (0.013) and nitrous oxide (0.46); thus, nitrous oxide will enter air-filled cavities faster than nitrogen can leave. In a fixed cavity such as the middle ear, the result is an increase in pressure. During tympanoplasty, the middle ear pressure generated by nitrous oxide can lift off the tympanic membrane graft. Therefore, nitrous oxide usually is avoided entirely during those procedures.49 Nitrous oxide use also may present a hazard for patients with previous reconstructive middle ear surgery.50
Sevoflurane has completely taken the place of halothane in pediatric institutions in the United States. It is a valuable addition to the anesthesiologist’s armamentarium for several reasons. First, it is less pungent than halothane, and it is even better tolerated during inhalation induction. Second, it has a blood-gas partition coefficient similar to that of nitrous oxide, so induction and emergence times are shorter than with halothane. Third, it has fewer cardiovascular effects than halothane.
Sevoflurane has several disadvantages: Its offset is so rapid that without adjunctive administration of narcotics, the perception of and response to pain may be accentuated.51 There are reports in the literature of a significant incidence of emergence excitement associated with cases in which sevoflurane was used.52 For these reasons, sevoflurane has assumed a role as an induction agent and a maintenance agent for very short procedures, but it often is replaced by isoflurane or desflurane after induction, depending on case type and anesthesiologist preference. Like all halogenated inhalational agents, it is a potential trigger agent for malignant hyperthermia and should be avoided in susceptible patients.
Isoflurane has been used for many years as a standard maintenance inhalational agent for children and adults. In practice, it offers no clear advantage for the pediatric otolaryngology patient. It is more pungent and not nearly as well accepted by children during inhalation induction as sevoflurane. Isoflurane does increase rather than decrease heart rate. It also causes decreases in blood pressure, but unlike with halothane, the mechanism is peripheral vasodilation rather than direct myocardial depression.53
Desflurane is the newest inhalational agent to be introduced into clinical practice. Its principal advantage is its quicker time to recovery as compared with sevoflurane.51 It appears to be well tolerated as a maintenance anesthetic, because it provides stable hemodynamics and respiratory parameters during its use. Similar to sevoflurane, desflurane has been associated with increased agitation and emergence delirium.44 However, this effect does not seem to occur frequently enough to avoid its use in children.
Desflurane does have an irritant effect on the airway, making it contraindicated for inhalational induction or for use during airway procedures such as bronchoscopy. However, many centers have adopted a practice of inducing anesthesia with sevoflurane and then switching to desflurane to take advantage of its quick recovery time while avoiding its airway effects during induction. It also has been suggested that this agent may be particularly useful in neonates and formerly premature babies, in whom residual anesthesia effects may increase the risk of apnea postoperatively.54
Fentanyl is the most commonly used supplement to anesthesia in children. Although the usual intravenous dose is 1 to 2 µg/kg, doses in excess of 100 µg/kg have been given to cardiac surgery patients with minimal cardiovascular depression.55 An initial peripheral vasodilation occurs, but tachyphylaxis to this side effect occurs with additional dosing. Preterm and full-term newborns have variable and prolonged clearance, probably related to reduced hepatic blood flow.56 In addition, they are extremely sensitive to the effects of fentanyl on chest wall rigidity. In neonatal patients who are not intubated, fentanyl should be given only in small increments.
The effect of low-dose fentanyl is terminated largely by redistribution, thereby resulting in a rapid reduction in clinical effect. Because fentanyl is highly lipophilic, however, higher or repeated doses result in drug accumulation. Clearance then becomes dependent on metabolism,57 and the clinical effect, including respiratory depression, may last for hours. Chest wall rigidity has been reported after rapid fentanyl administration, although the etiology of this problem is unclear. Bradycardia may occur as a result of increased vagal tone, especially when given with other agents that may have a similar effect.
Overall, morphine is the most frequently used opioid in children. It can be used in the operating room to supplement inhalational agents and to provide postoperative analgesia. The usual intravenous dose is 0.05 to 0.1 mg/kg as part of a balanced anesthetic technique, although higher doses may be used for a narcotic-based technique. The dose may need to be reduced in critically ill children or young infants. The half-life after intravenous administration is approximately 3 hours in older children but is significantly longer in infants as a result of diminished clearance.58 The major side effect is respiratory depression, which results in diminished minute ventilation, with a greater effect on respiratory rate than tidal volume. Many believe that newborns are at higher risk than older children for respiratory depression, although it is unclear whether this reflects a difference in pharmacokinetics or pharmacodynamics. Infusions of morphine at rates of 10 to 30 µg/kg per hour have been described in small infants without significant respiratory depression.59 Appropriate monitoring for apnea should occur in premature infants and those neonates with a history of apnea and bradycardia. Histamine release is also common with the administration of morphine, and it most commonly results in a localized or generalized rash. Bronchospasm and hypotension have been reported, but they are much less common.
Hydromorphone has become a commonly used alternative to morphine. It is approximately five to seven times more potent than morphine, with the usual intravenous dose ranging from 0.015 to 0.02 mg/kg. Its half-life is similar to that of morphine, and it has a similar duration of action. Hydromorphone may be useful in patients with renal failure, because its metabolic by-products are less active than morphine’s are. In addition, hydromorphone may be a good alternative for those patients who suffer side effects (e.g., itching, nausea, hallucinations) with morphine. As with other opioids, respiratory depression is the most concerning side effect, but it is rare with appropriate dosing.
The use of meperidine has dramatically decreased due to its unique side effect profile and the availability of equianalgesic alternatives. The principal metabolite of meperidine is normeperidine, a compound that can cause neurologic excitation manifested as tremors, irritability, or seizures. This side effect is especially pronounced with prolonged use or in patients with hepatic or renal dysfunction. Meperidine’s superiority over other opioid agonists in the treatment of postoperative shivering probably is related to its kappa receptor activity and the one reason that it has not become entirely obsolete.
As a short-acting analog of fentanyl, alfentanil commonly is used for short outpatient procedures. It is approximately one-fourth as potent as fentanyl and has one-third the duration of action. It has a very fast onset of action (1 minute) and a short elimination half-time (1.5 hours). It is less lipophilic than fentanyl, and the dose range is 10 to 20 µg/kg, given intravenously. Renal failure does not alter the clearance of alfentanil. Besides the opioid-related side effects, thorax rigidity and bradycardia may be seen.
Remifentanil has the same analgesic potency as that of fentanyl. The key feature of remifentanil is the ester side chain hydrolysis by blood and tissue esterases, resulting in rapid metabolism (elimination half-time is 10 to 20 minutes). This results in zero order kinetics, meaning that its offset of action is 10 to 20 minutes after discontinuation of the infusion, regardless of the duration of the infusion. Said differently, it does not accumulate. It does have a rapid onset, and because of its short duration of action, it usually needs to be administered as an continuous intravenous infusion at the rate of 0.05 to 1 µg/kg/min for neonates and up to 2 µg/kg/min for older children. Pharmacokinetic parameters of remifentanil are unchanged by hepatic or renal disease. Disadvantages are the high cost and the lack of postoperative analgesia, which can be overcome with application of longer-acting opioids at the end of surgery.
Succinylcholine is the only depolarizing muscle relaxant. With the advent of intermediate-acting nondepolarizing relaxants, the use of succinylcholine for routine surgical procedures is declining, primarily as a result of side effects that relate to its depolarizing mode of action (see later). However, it remains the most rapid-acting of all muscle relaxants, and it is still indicated for use in rapid-sequence inductions and in the treatment of laryngospasm. Intravenous administration of 1.5 to 2.0 mg/kg achieves 95% twitch depression in 40 seconds,60 resulting in excellent intubating conditions. Succinylcholine also can be given intramuscularly (4 to 5 mg/kg) if the intravenous route is unavailable, although the clinical effect is delayed in onset, depending on perfusion to the area of deposition.
The side effects of succinylcholine are numerous. Some degree of increase in masseter muscle tone is common and, in some cases, is extreme enough to mimic true trismus.61 This is an important distinction to make, because as many as 50% of patients with trismus after succinylcholine are biopsy positive for susceptibility to malignant hyperthermia.62 Succinylcholine can also cause bradycardia as a result of an increase in vagal tone; this effect is especially prominent in younger children and infants. The decline in heart rate usually is transient and, if not, is responsive to intravenous atropine; occasionally, asystole is seen. Hyperkalemia can be seen as a result of depolarization of the myoneural junction; increases of serum potassium of 0.5 mEq/L occur even in normal children.63 Life-threatening hyperkalemia after succinylcholine administration can occur in children with burns, tetanus, paraplegia, encephalitis, crush injuries, and neuromuscular disease.63 Myoglobinemia occurs in approximately 40% of children anesthetized with halothane who are given succinylcholine; this effect can be partially attenuated with a previous dose of a nondepolarizing agent to prevent fasciculations. A series of cardiac arrests were reported in boys who were given succinylcholine, with subsequent development of massive muscle breakdown and potassium release. The presumed etiology was previously undiagnosed muscular dystrophies.64 In 1994, in response to these reports, the manufacturer placed a warning on the package insert cautioning the practitioner about the routine use of succinylcholine. As a result, many pediatric anesthesiologists have abandoned the routine use of succinylcholine except for rapid-sequence inductions and to treat laryngospasm. Succinylcholine may soon be replaced in that role by rocuronium, which has an onset of action of less than a minute, making it suitable for a rapid sequence induction. The disadvantage of rocuronium has been the long time to reversal after an intubating dose has been given. This makes it suboptimal and perhaps contraindicated for patients with a difficult airway. Sugammadex, a selective relaxant-binding agent, is in phase 3 trials. If approved, it would make rocuronium rapidly reversible and thereby make the risks of succinylcholine unnecessary. Sugammadex is not yet available for use in the United States.
Of note, 90% of an intravenous dose of succinylcholine is rapidly hydrolyzed in the plasma by pseudocholinesterase. Patients with deficient or reduced levels of pseudocholinesterase exhibit a prolonged effect from succinylcholine.
A variety of nondepolarizing muscle relaxants are available. These agents vary in dose, speed of onset, and duration of action. As shown in Table 182-3, the pharmacologic properties of these drugs may be different in infants from those in older children. The choice generally is based on the duration of the surgical procedure. As noted, rocuronium has been shown to produce good intubating conditions, but with a slightly longer onset of action (less than 1 minute) than with succinylcholine (less than 30 seconds).