Preoperative Preparation

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CHAPTER 9 Preoperative Preparation

Elliot J. Krane, Peter J. Davis and Zeev N. Kain

In addition to having a sound understanding of a child’s medical disease and anticipated surgical procedure, the anesthesiologist must also appreciate the emotional stresses that affect both the child and parent. The preoperative meeting with the patient and his or her parents is not only a responsibility of the anesthesiologist but also an important opportunity to learn facts that could otherwise be missed. It is a chance to win the confidence of the patient and the parents, if they are present (Fig. 9-1).

FIGURE 9-1 An instructive approach to the anesthesia induction can be taken during the preoperative visit, enabling the anesthesiologist to gain the child’s trust and confidence.

A careful preoperative examination of the child and the child’s medical record enables the anesthesiologist to assess the child’s general state of health and to identify the presence of chronic, acute, or intercurrent diseases, as well as to recognize previous anesthetic problems (Black, 1999). From this knowledge, appropriate subspecialty consultation can be sought, the operative medical condition can be optimized for the surgery, and the anesthetic plans can be made. In addition to monitoring practices and anesthetic techniques, anesthetic plans should include provisions for the patient’s postoperative care, particularly an analgesic plan. It is the general goal of the preanesthetic visit to anticipate potential complications before they occur, to avert them when possible, and, in so doing, to minimize the risks to the health of the child. The risk of anesthesia is assessed during the preoperative visit, and the child’s parents should be informed of the plans for anesthesia and monitoring, and they should be apprised of the anticipated risk.

Preanesthetic Visit

The preanesthetic visit should begin with a careful review of the medical record; particular attention should be paid to previous anesthetic agents and problems encountered, the successful and unsuccessful techniques used in the past for airway management, and any history of cardiorespiratory diseases or airway anomalies. A history of medical or environmental allergies should be elicited, and it should include questions specifically directed toward evaluating the presence of allergy to latex in children at risk, notably those with meningomyelocele or urogenital anomalies, those who undergo bladder self-catheterization, or those whose medical histories indicate a significant amount of latex exposure in the past (Holzman 1997; Porri et al., 1997; Hollnberger et al., 2002; Pires et al., 2002; Eustachio et al., 2003; Dehlink et al., 2009; Rendeli et al., 2006; Bostancy et al., 2007; Dieguez et al., 2007; Garcia 2007; Baker and Hourihane, 2008; De Queiroz et al., 2009). Results of laboratory tests should be reviewed, focusing on hematologic evaluations, renal function, and electrolyte profiles, as well as blood gas analysis and pulmonary function tests when appropriate.

The anesthesiologist must be aware of the child’s current drug therapy and how it may interact with the anesthetic. The perioperative administration of bronchodilators, cancer chemotherapeutic agents, or anticholinesterases has significant implications for anesthesia (Schein and Winoker, 1975; Selvin, 1981; Drummond, 1984). Corticosteroid administration is traditionally recommended for patients who receive chronic corticosteroid therapy and for patients who have received steroids in the past, although evidence for the necessity of doing so is lacking (see Chapter 36, Systemic Disorders). Current drug therapy must also include questions regarding the use of herbal medications. Potential complications in the perioperative period have been attributed to the use of complementary medicines. Table 9-1 summarizes the most commonly used herbal remedies (Ang-lee et al., 2001).

TABLE 9-1 Pharmacologic Effects and Potential Perioperative Complications of Eight Commonly Used Herbal Remedies

Name of Herb	Common Uses	Potential Perioperative Complications
Echinacea, purple cone flower root	Prophylaxis and treatment of viral, bacterial, and fungal infections	Reduced effectiveness of immunosuppressants; potential for wound infection; may cause hepatotoxicity when used with other hepatotoxic drugs
Ephedra, ma-huang	Diet aid	Dose-dependent increase in heart rate and blood pressure; arrhythmias with halothane; tachyphylaxis with intraoperative ephedrine
Garlic, ajo	Antihypertensive, lipid-lowering agent, anti-thrombus forming	May potentiate other platelet inhibitors; perioperative bleeding
Ginkgo, maidenhair; fossil tree	Circulatory stimulant; Alzheimer’s disease, peripheral vascular disease, and erectile dysfunction	May potentiate other platelet inhibitors; perioperative bleeding
Ginseng	To protect the body against stress and restore homeostasis	Perioperative bleeding; potential for hypoglycemia
Kavakava, pepper	Anxiolytic	Potentiates sedative effects of anesthetic agents; possible withdrawal syndrome after sudden abstinence; kavakava-induced hepatotoxicity
St. John’s wort, goatweek, amber, hardhay	Treatment for depression and anxiety	Decreased effectiveness of cyclosporine, alfentanil, midazolam, lidocaine, calcium channel blockers, and digoxin
Valerian, vandal root, all heal	Anxiolytic and sleep aid	Potentiates sedative effects of anesthetic agents; withdrawal-type syndrome with sudden abstinence

From Skinner CM, Rangasami J: Preoperative use of herbal medicines: a patient survey, Br J Anaesth 89:792-795, 2002.

Many unusual syndromes occur in childhood, and they often have multisystem involvement; consequently, they have an important impact on anesthetic management. An important caveat in pediatric medicine is that when one congenital anomaly exists, there is a significant likelihood of anomalies involving other organs. For example, infants with tracheoesophageal fistulas have an increased incidence of congenital heart disease, and some forms of radial dysplasia are associated with thrombocytopenia or atrial septal defects. The topic of congenital anomalies was extensively discussed in a review by Lynn (1985). The remainder of this section is a review of pediatric diseases that may be important to the anesthesiologist. Information regarding these problems may be forthcoming from the child’s medical history, the physical examination, or both.

Physical Examination

The extent of the physical examination that the anesthesiologist performs depends on the circumstances. If a small infant scheduled for a minor operation has been crying and has finally dropped off to sleep, one can observe from the bedside the child’s general nutritional state, skin color, character of respiration, and presence or absence of nasal discharge. Although the surgeon’s or pediatrician’s notes are helpful, they should not be a substitute for the anesthesiologist’s independent examination.

Certain general principles are applied to the preoperative evaluation. When examining a child, the anesthesiologist should look for somewhat different signs than when examining an adult. Between the ages of 4 and 8 years, children must be examined for loose primary teeth. Finding an empty dental socket after an operation is not disturbing if one knows that the child lost the tooth before admission. There is always the danger of the recent onset of an upper respiratory tract infection with cough, rhinitis, and pharyngitis. If an infant or child has rhinitis, it may be challenging to determine whether it is because of an infection, seasonal allergies, or simply the result of crying. Enlarged cervical nodes and otitis media occur in association with respiratory tract infections; clear, colorless rhinitis suggests crying or an allergic etiology.

Partial airway obstruction may result from infection, anatomic anomalies, or tumors. When possible, a diagnosis should be made before anesthesia is begun. Unilateral nasal discharge is unusual and suggests a foreign body (or, less often, choanal atresia) (Fig. 9-2).

FIGURE 9-2 Unilateral nasal discharge can be from a foreign body like a bead (A), or a unilateral choanal atresia (B).

(From Yellon RF, McBride TP, Davis HW: Otolaryngology. In Zitelli J and Davis HW, editors: Atlas of pediatric physical diagnosis, ed 5, St Louis, 2007, Mosby.)

Whenever possible the anesthesiologist should personally observe or palpate the location and size of the lesion, such as a laceration, tumor, or nevus, that may be the reason for surgery. A tumor may be the size of a pea or a melon, and a nevus may be a spot on a child’s elbow or cover half a limb. The anesthesia cannot be planned intelligently without knowledge of these points.

Review of Body Systems (Table 9-2)

Central Nervous System

Disorders of the neuromuscular system only rarely escape notice during the history and review of systems; the purpose of the central nervous system (CNS) examination is primarily to assess the severity of the abnormality and the implications for anesthetic care.

TABLE 9-2 Medical History and Review of Systems: Anesthetic Implications

System	History	Potential Anesthetic Implication
Central nervous and neuromuscular systems	Seizure Head trauma Hydrocephalus Central nervous system tumor Developmental delay Neuromuscular disease Muscle disease	Medications: drug interactions, inadequate anticonvulsant therapy, drug-induced hepatopathology Elevated intracranial pressure Anemia Elevated intracranial pressure Elevated intracranial pressure Chemotherapeutic drug interactions History of steroid useBulbar dysfunction Risk of aspiration Altered response to relaxants Risk of malignant hyperthermia Risk of rhabdomyolysis and hyperkalemia
Cardiovascular system	Heart murmur Cyanotic heart defect History of squatting Diaphoresis with feeding or crying Hypertension	Risk of right-to-left air embolism of intravenous air bubbles Need for SBE prophylaxis Right-to-left cardiac shunt Risk of right-to-left air embolism of intravenous air bubbles Hemoconcentration Need for SBE prophylaxis Teratology of Fallot Congestive heart failure Coarctation of the aorta, renal disease, or pheochromacytoma
Respiratory system	Prematurity Bronchopulmonary dysplasia Respiratory infection, cough Croup Snoring Asthma Cystic fibrosis	Increased risk of postoperative apneaLower airway obstruction Reactive airways disease Subglottic stenosis Pulmonary hypertension Reactive airways and bronchospasm Medication history Subglottic stenosis or anomaly Obstructive sleep apnea Perioperative airway obstructionβ-Agonist or theophylline therapy History of steroid useDrug interactions Pulmonary toilet Pulmonary dysfunction and VQ mismatch Reactive airways disease
Gastrointestinal/hepatic systems	Vomiting, diarrhea Growth failure Gastroesophageal reflux JaundiceLiver transplant recipient	Electrolyte abnormality, especially hypokalemia Dehydration Risk of aspiration Low glycogen reserves/risk of hypoglycemia AnemiaRisk of aspiration Reactive airways disease Anemia Altered drug metabolism Risk of hypoglycemia Coagulopathy Altered drug metabolism Immunosuppression Coagulopathy
Renal system	Frequency, nocturia Renal failure/dialysis Kidney transplant recipient	Occult diabetes mellitus Electrolyte disturbance Urinary sepsis Electrolyte disturbance Hypervolemia or hypovolemia Anemia Medication history Immunosuppression Poor toleration of hypotension Hypertension
Endocrine system	Diabetes Steroid therapy	Insulin requirement Intraoperative hyperglycemia or hypoglycemia Adrenocorticoid suppression
Genitourinary system	Pregnancy	Teratogenic effects Risk of spontaneous abortion
Hematologic system	Anemia Bruising, history of bleeding Sickle cell disease Human immunodeficiency virus infection	Transfusion requirement Occult hemoglobinopathy Coagulopathy Anemia Need for hydration Limb tourniquet use Susceptibility to infection Infectious risk to medical personnel
Dental system	Loose primary teeth	Risk of aspiration if tooth avulsed

SBE, Subacute bacterial endocarditis; VQ, ventilation perfusion.

Modified from Coté CJ, Todres ID, Ryan JF: Preoperative evaluation of pediatric patients. In Ryan JF, Todres ID, Coté CJ, et al., editors: A practice of anesthesia for infants and children, New York, 1986, Grune & Stratton. (With permission from Elsevier.)

Trauma is the most common cause of death in children, and most fatal trauma involves injury to the CNS. Head injuries often result in an altered level of consciousness, cerebral edema, and elevated intracranial pressure. Tumors of the brain are the most common solid tumors of childhood and usually occur in the posterior fossa. They generally increase intracranial pressure as a mass effect but also often obstruct cerebrospinal fluid pathways, resulting in hydrocephalus. The anesthetic care of children with elevated intracranial pressure is discussed in Chapter 22, Anesthesia for Neurosurgery.

To ensure both therapeutic levels and the absence of toxic levels, serum levels of certain anticonvulsant drugs should be measured or should have been measured before elective surgery in children with chronic seizure disorders. Most anticonvulsants have a long plasma half-life; therefore, missing one dose in the perioperative period does not significantly diminish the serum level and efficacy. Of the commonly used anticonvulsants, only phenobarbital, phenytoin, or valproate may be given intravenously in the perioperative period. Other commonly administered anticonvulsants, however, such as gabapentin, pregabalin, levatiracetam, or lamotrigene, are available only as oral medications. If a prolonged period without oral intake is anticipated (such as after abdominal surgery), a neurologist should be consulted about possible alternative parenteral drug therapy.

Conditions such as developmental delay and spastic cerebral palsy have important implications for anesthesia. In such children, the response to opioids and anesthetic agents is less predictable than that with healthy children. Many patients with cerebral palsy or intellectual impairment have difficulty managing oral secretions, and gastroesophageal reflux is particularly common in these children. They are at a greater risk of aspirating oral or gastric contents during induction. Cerebral palsy in older children often produces restrictive lung disease as a result of deformities of the spine and thoracic cage and from uncoordinated respiratory muscle function.

Neuromuscular diseases, such as congenital myotonia, muscular dystrophy, and the various forms of myositis, contraindicate the use of succinylcholine even in emergency airway management, although it is rarely used in current pediatric anesthetic practice (see Chapter 36, Systemic Disorders). In myotonia, succinylcholine produces a sustained contracture of skeletal muscle that may impede the ability to maintain a patent airway and ventilate the lungs. In other myopathies, such as clinically active dermatomyositis, succinylcholine produces life-threatening hyperkalemia. Some forms of muscular dystrophy (central core disease) are statistically associated with malignant hyperthermia, whereas others may result in a malignant hyperthermia-like syndrome that is equally life threatening (Guis et al., 2004; Rosenberg et al., 2007; Driessen and Snoeck, 2008; Hayes et al., 2008; Puel et al., 2008; Takagi and Nakase, 2008; Schwartz and Raghunathan, 2009). Although not all children with Duchenne’s or other muscular dystrophies are genetically susceptible, Rosenberg and Heiman-Patterson (1983), as well as Takagi and Nakase (2008), recommend that precautions against malignant hyperthermia be taken in patients with this disorder because of rhabdomyolysis and hypermetabolism that may occur in myopathic children after exposure to triggering agents. For further discussion please refer to Chapter 37, Malignant Hyperthermia.

Cardiovascular System

Evaluation of the cardiovascular system is critical to the delivery of safe anesthesia. The physical examination seldom reveals an unexpected CNS lesion, but a careful history and auscultation of the child’s chest often reveal a congenital cardiac lesion that may be unknown to the parents or the child’s surgeon.

The history-and-systems review yields information regarding known cardiac anomalies of an acquired disease, cyanotic defects, or the presence of congestive heart failure. Symptoms of congestive heart failure may be insidious. In an infant, whose level of activity is not high, the symptoms of congestive heart failure or cyanosis are most likely limited to a few times of physical exertion, such as feeding and crying, and the only symptoms of congestive heart failure may be pallor and diaphoresis, which are subtle findings. Parents should be asked about diaphoresis during nursing or sucking. Resting tachypnea and failure to thrive are also consequences of more advanced degrees of congestive heart failure, which may be the result of ventricular volume overload (most commonly, a ventricular septal defect, patent ductus arteriosus, or anomalous pulmonary venous return), either right- or left-sided outflow obstruction, or pulmonary hypertension.

Preoperative evaluation of a patient with a known or suspected heart defect that is physiologically significant should include a thorough history and physical examination; an electrocardiogram (ECG) and echocardiogram; determination of hematocrit value, a baseline oxygen saturation value (SpO₂); a chest radiograph; and a definitive understanding of the type of cardiac lesion, its degree of severity, and its physiologic effect on cardiac efficiency and oxygen delivery. Such patients should be examined meticulously and should not be accepted for anesthesia until they are in the best possible physical condition. For children with compromising lesions or those requiring cardiac medication, it is advisable to consult the cardiologist shortly before surgery.

The presence of polycythemia is uncommon in modern clinical practice but still should be ruled out in children with cyanotic heart disease; a hematocrit value of greater than 65% may be reduced by red blood cell pheresis or isovolemic hemodilution. Dehydration must be avoided, preferably through the use of controlled intravenous hydration beginning the night before surgery or by following the nil per os (NPO) guidelines and ensuring adequate oral intake of clear liquids up until 2 hours before surgery.

Particular care must be taken to rule out the existence of any infection, especially in the throat, ears, skin, or genitourinary tract. Bacteremia and infections of the teeth or gums should be controlled with appropriate antibiotics. The preoperative occurrence of fever or rhinitis or a significant preoperative exposure to a source of infection should be considered a possible indication for postponement of the operation.

Asymptomatic cardiac murmurs occasionally have implications for anesthesia. If they represent small ventricular septal defects or mild valvular disease, prophylaxis against bacterial endocarditis is indicated for procedures that may result in bacteremia, such as dental surgery, gastrointestinal or urogenital endoscopy, and nasotracheal intubation (Wilson et al., 2007). Atrial septal defects contraindicate the use of the sitting position for suboccipital craniotomies in order to minimize the risk of paradoxical air embolism (Fischler, 1992). The defects may also make intraoperative transesophageal echocardiography desirable in certain cases that have been associated with venous air embolism (e.g., posterior spine fusions or liver transplantation), so the movement of air from the pulmonary to the systemic circulation may be detected. If the anesthesiologist detects a previously undescribed murmur in these circumstances, a consultation with the cardiologist is indicated to further delineate the nature of the lesion (Fig. 9-3). Many congenital anomalies and syndromes are associated with cardiac defects or other cardiovascular problems; Box 9-1 provides an outline of these conditions.

FIGURE 9-3 Sites for auscultation where murmurs are heard best.

(From Beerman LB, Kreutzer J, Park SC: Cardiology. In Zitelli J, Davis HW, editors: Atlas of pediatric physical diagnosis, ed 5, St Louis, 2007, Mosby.)

Box 9-1 Pediatric Syndromes Associated with Cardiac Conditions

Syndromes Associated With Thromboses Or Ischemic Heart Disease

Ehlers-Danlos syndrome

Fabry’s disease

Grönblad-Strandberg syndrome

Respiratory System

Chapter 3, Respiratory Physiology in Infants and Children, describes the anatomic and physiologic differences between the pediatric and adult respiratory systems. The differences in dimension and function predispose the child to perioperative airway obstruction, which mandates a critical preoperative evaluation of the airway. The upper airway of the child may be further compromised by many entities, including: tonsillar or adenoidal hypertrophy or both; craniofacial anomalies such as Crouzon’s disease, Apert’s syndrome, hemifacial microsomia, Goldenhar’s syndrome, Treacher Collins syndrome (or Pierre Robin syndrome); lingular hypertrophy (common in trisomy 21); Beckwith’s syndrome and the various forms of mucopolysaccharidosis (Hurler’s syndrome and Hunter’s syndrome being the most common); isolated airway anomalies, such as cleft palate, laryngeal web or cleft, laryngomalacia, or subglottic stenosis; or tumors, such as hemangiomas and lymphangiomas, which may occur anywhere along the airway. Cutaneous cervicofacial hemangiomas along a beard distribution are suggestive of an association with upper airway or subglottic hemangiomas (Orlo et al., 1997).

Acute upper respiratory tract infections provide a common dilemma for the anesthesiologist. The mere volume of publications that evaluate the risk of adverse events of anesthesia in children with upper airway infections speaks to the ongoing controversy (Tait and Malviya, 2005). In the best of all worlds, no child would be anesthetized electively during an acute respiratory illness. Although not all studies have identified acute respiratory illness as a cause of perioperative complications in children, there is compelling evidence that the occurrence of both intraoperative and postoperative hypoxemia and other airway complications are increased in children with upper respiratory tract infections (DeSoto et al., 1988; Cohen and Cameron, 1991; Kinouchi et al., 1992; Levy et al., 1992; Rolf and Coté, 1992; Parnis et al., 2001; Bordet et al., 2002; Elwood et al., 2003; Tait, 2005). There is also evidence that the incidence of bronchospasm is increased in the presence of upper respiratory infections in children who are intubated (Rolf and Coté, 1992; Rachel Homer et al., 2007; von Ungern-Sternberg et al., 2007). In a prospective study, Tait and colleagues (2001) noted that endotracheal intubation, a history of prematurity, reactive airways disease, parental smoking, airway surgery, and nasal congestion are all risk factors associated with respiratory complications in infants and children who have upper respiratory infections and who are undergoing anesthesia. Furthermore, the child with an acute respiratory disease exposes other patients and health care workers to their contagion, which may not be a trivial concern when these individuals are immunocompromised.

Other considerations, however, must be taken into account before making the decision to postpone surgery. For example, the relatively small risk to the child must be weighed against the expense and effort the family has made to come to the hospital, often from a distant locale and at the cost of lost income. Some children, particularly those seen for otolaryngologic surgery, appear to never be free from respiratory infections during much of the year. Postponement of surgery may not be practical in these circumstances. Indeed, one study indicates that myringotomy is therapeutic in these children and is not associated with an increased incidence of postoperative pulmonary complications (Tait and Knight, 1987).

The presence of acute disease of the lower airways, however, should generally delay elective surgery. The presence of fever, cough, and an abnormal auscultatory examination is reason for radiographic evaluation and possibly cancellation of scheduled surgery. Patients with a viral lower respiratory tract infection such as influenza may develop airway hyperreactivity that is indistinguishable from bronchial asthma and can last as long as 6 or 7 weeks from onset.

Chronic diseases of the lower respiratory tract occur in both children and adults. Asthma and cystic fibrosis are the most common chronic pulmonary diseases of childhood. A careful history and physical examination usually suffice in the preoperative evaluation of these diseases. If preoperative impairment is severe, however, or if the planned surgery is extensive, formal pulmonology consultation and pulmonary function testing may provide the anesthesiologist with information that can be used to provide optimal postoperative care. Children with asthma are commonly medicated with β₂-adrenergic agents and inhaled corticosteroids. Other first-line drugs include cromolyn sodium and leukotriene receptor antagonists; rarely are theophylline preparations administered at this time. However, when theophylline is a part of the patient’s treatment, serum concentration of theophylline should be measured preoperatively to ensure blood levels in a therapeutic range (10-20 mcg/mL), and the anesthesiologist should be aware of potential interactions among theophylline, β₂-adrenergic drugs, and halothane (although it is not often used). Asthmatic children who receive corticosteroids should also be considered for perioperative therapy with stress doses of corticosteroids if steroid therapy has been recent, although as previously stated, the evidence to support this convention is lacking. For those children who have required systemic steroids in the past, a short course of steroids beginning 1 to 2 days before the day of surgery may be beneficial (see Chapter 36, Systemic Disorders).

Severe kyphoscoliosis typically leads to significant restrictive lung disease. This is particularly true in cases of kyphoscoliosis that occur before the teenage years. Particularly in this age group, the cause of the kyphoscoliosis should be assessed, because it typically results from neuromuscular diseases such as cerebral palsy or muscular dystrophy or from anatomic anomalies such as hemivertebrae, which may be part of a syndrome that is associated with other congenital anomalies of importance to the anesthesiologist (e.g., VATER association). Preoperative testing of pulmonary function may be useful in predicting which children will require admission to an intensive care unit with or without mechanical ventilation postoperatively, but usually the decision to mechanically ventilate patients after spinal surgery is based on general preoperative condition, duration and difficulty of surgery, blood loss, and other surgical factors, rather than on the test of pulmonary function itself (see Chapter 26, Anesthesia for Orthopedic Surgery).

An infant who was born prematurely is often left with a residual chronic obstructive pulmonary disease called bronchopulmonary dysplasia, the consequence of both oxygen toxicity and ventilator-induced lung injury to immature lungs. The incidence and severity of this disabling condition have been dramatically reduced by the use of surfactant in neonatal intensive care units. Children with bronchopulmonary dysplasia exhibit a combination of fibrotic and cystic changes in the lung parenchyma with reactive small airways disease, with or without wheezing and air trapping. These children may respond to steroids and bronchodilators in varying degrees. More advanced bronchopulmonary dysplasia is associated with chronic hypoxia, carbon dioxide retention, pulmonary hypertension, and ultimately cor pulmonale (Berman et al., 1982).

As in the adult with chronic pulmonary disease, elective surgery is best delayed until preoperative cardiopulmonary function has been optimized. Children with severe bronchopulmonary dysplasia are usually treated with diuretics to reduce extravascular lung water; consequently, abnormal serum electrolyte levels are common preoperatively (e.g., hypokalemia, hypochloremia, or metabolic alkylosis). Arterial saturation should be maximized at all times to reduce pulmonary hypertension, and perioperative bronchodilator therapy should be considered. Alterations in anesthetic care include: judicious, if any, use of nitrous oxide to avoid exacerbation of pulmonary gas trapping and pulmonary vascular resistance; very conservative fluid therapy and restriction of sodium; and continuation of bronchodilator therapy. Postoperative mechanical ventilation may be required in this population.

Life-threatening apnea and bradycardia may occur after general anesthesia, most commonly in the preterm infant who is still younger than 45 weeks’ or as old as 60 weeks’ postconceptional age (the sum of gestational age and postnatal age) (Liu et al., 1980; Kurth et al., 1986; Wellborn et al., 1986). Hospital admission and respiratory monitoring are necessary for infants at risk, even after brief general anesthesia. Risk factors for postoperative apnea in preterm infants include: a history of mechanical ventilation, history of apnea and bradycardia, and anemia at the time of surgery (Kurth and LeBard, 1991; Wellborn et al., 1991; Spear, 1992; Malviya et al., 1993; Coté et al., 1995). In a meta-analysis of eight studies, Coté et al. (1995) reported that the postconceptual age required to reduce the risk of postoperative apnea to 1% was 54 weeks for infants born at 35 weeks’ gestation and 56 weeks for infants born before 32 weeks’ gestation. For further information, see Chapter 17, Neonatology for Anesthesiologists, Figure 17-10.

Congenital diseases of the lungs are usually recognized and surgically corrected in the newborn period. These conditions and their anesthetic management are discussed in Chapters 18 and 23, Anesthesia for General Surgery in the Neonate, and Anesthesia for General Abdominal, Thoracic, Urologic, and Bariatric Surgery.

The Child With Physical Or Mental Disabilities

One of the most important principles in dealing with all types of physically and/or mentally disabled children is to be considerate. In any situation involving the care of patients with disabilities, it is appropriate to show appreciation for the position of the families and the dedication they show and deprivation they endure, usually with remarkably little complaint. It is often inspiring to learn about their abilities to cope with misfortune.

Brain Damage

Children who survive severe hypoxic or traumatic brain damage and children with postinfectious encephalopathy may need to undergo various surgical procedures. Preoperative evaluation should include determination of the type and degree of the original neurologic lesion and the patient’s present neurologic status. Patients with severe neurologic lesions may depend on implanted ventriculoperitoneal shunts, and shunt patency should be ensured before the administration of anesthesia. Signs and symptoms of a blocked shunt include an abnormally low or high heart rate or blood pressure, headache, vomiting, irritability, and drowsiness. At some point in the child’s past, pulmonary management may have required a tracheostomy, which, if still present, may simplify the induction of anesthesia. However, if the patient was decannulated in the past, the upper airway may have been rendered stenotic.

Because they may have difficulty swallowing, these patients often aspirate secretions, and atelectasis or pneumonia may develop. Consequently, a chest radiograph may be indicated to determine the presence and degree of ventilatory compromise. The same patients commonly have gastrostomy tubes for feeding, which should be identified, drained before the induction of anesthesia, and then left open throughout the operative period to prevent gastric distension.

Old injuries, strictures, flexions, deformities, and scars should be noted, with careful descriptions made of signs of recent injuries, pressure sores, or self-inflicted scratches and marks that might otherwise be attributed to anesthetic care. During anesthesia, added care is taken to protect all parts of the body from abnormal pressure and positioning.

Cerebral Palsy

Special consideration is needed when caring for patients with the diagnosis of cerebral palsy, spastic diplegia, or quadriplegia (Nolan et al., 2000). Inexperienced personnel commonly make the serious mistake of assuming that patients with spastic diplegia or quadriplegia also suffer from cognitive impairment, which may not be true. Cerebral palsy is a general term applied to several different forms of neuromuscular disability, arising from various anatomic lesions of the brain and not always involving intellectual impairment (Stiles, 1981). The treatment of patients with cerebral palsy should include careful assessment of their level of intelligence. When in doubt, as with all patients who have difficulty communicating, one should assume that they can both hear and understand what is said.

Developmental Delay, Cognitive Dysfunction, and Psychological Disorders

The term mental retardation is one of the broadest in medicine, encompassing many different forms, and it is pejorative in its tone. The anesthesiologist is encouraged to use more sensitive terminology, such as cognitive dysfunction, developmental delay, or intellectual impairment, to name a few more acceptable terms. Trisomy 21 (or other trisomies), autism, and phenylketonuria are well-known forms of this affliction; information on more obscure forms may be found in special texts, such as that of Katz and Steward (1993). Developmental delays that are genetic bear no specific outward stigmata or congenital anomalies, and anesthesia is adapted to the child’s level of consciousness and cooperation. Trisomy 21 and other chromosomal forms of intellectual impairment are often associated with congenital heart defects, as well as other congenital organ defects. Trisomy 21 is also commonly associated with blunting of the styloid process of the second cervical vertebra, which combined with the ligamental laxity of the syndrome allows atlanto-occipital subluxation, or dislocation on marked flexion of the head and neck, resulting in spinal cord injury (Moore et al., 1987; Williams et al., 1987) For more on this subject, see Chapter 36, Systemic Disorders.

Children with autism are difficult to deal with and are sometimes wildly resistant to any intervention. These patients may appear to be remarkably alert, but they also appear to be locked within themselves. The management of the autistic child must be individualized to the dynamics particular to each child’s circumstances (Rainey et al., 1998; van der Walt and Moran, 2001). As for other intellectually impaired children, the presence of a parent at induction often has a soothing effect. Premedication with oral midazolam or clonidine is often effective for sedating these children and improving cooperation.

Hyperactivity and Lack of Cooperation

Hyperactive, aggressive, resistant, and uncooperative children offer challenging situations to the anesthesiologist. Such attitudes are seen in pure behavioral syndromes without developmental handicaps, as well as in various forms of neurologic disease or posthypoxic encephalopathy.

The history is carefully reviewed to determine the extent of the hyperactivity and factors that affect the behavior. Parents or attendants are questioned as to which approaches have succeeded in the past and which have not. Trial-and-error methods are not advisable. Oral premedication with midazolam, clonidine, or ketamine may be helpful. Intramuscular ketamine (2 to 4 mg/kg) may be used as a last resort (Hannallah and Patel 1989).

Drug Abuse In The Child And Adolescent

Abuse of illicit drugs is unfortunately not limited to adults. Drugs such as cocaine, marijuana, and lysergic acid diethylamide (LSD) are of social and medical concerns. In 1993, about 1 in 3 high school seniors in the United States (35.5%) had used marijuana in their lifetime (Fig. 9-4) (Johnston et al., 1994). A survey of schoolchildren in Great Britain showed that 15.8% of boys have been offered the drug Ecstasy and that 5.7% have taken it (Milroy, 1999). A survey among college students in Great Britain indicated that the most commonly used drugs are marijuana (59%), amphetamines (19%), cocaine (18%), and LSD (18%) (Christophersen, 2000). Because drug abuse may result in increased morbidity and mortality, a thorough understanding of the consequences of drug abuse is essential for the practicing anesthesiologist.

FIGURE 9-4 Percentage of high school seniors in the United States who have used marijuana and other illegal substances in their lifetime.

Cocaine

Cocaine is an alkaloid derived from the leaves of the South American shrub, Erythroxylum coca. Cocaine can be abused via every possible route, including oral, nasal, intravenous, and rectal. The hydrochloride form can be chemically altered to the base form, which is then concentrated by extraction in ether or baking soda (Perez-Reyes et al., 1982; Fleming et al., 1990). The residue from this method is a form of cocaine base commonly called crack (based on the cracking sounds it makes when heated) (Fleming et al., 1990; Julien, 1994). High levels of cocaine may persist in a person for 6 hours after nasal administration (Inaba et al., 1978). The metabolism of cocaine occurs primarily through plasma and hepatic cholinesterase, and patients with pseudocholinesterase deficiency are at increased risk for cocaine toxicity. Less than 5% of ingested cocaine is excreted unchanged in the urine (Inaba et al., 1978). Ecgonine methyl ester and benzoylecgonine constitute over 80% of cocaine metabolites and are detected in the urine for 14 to 60 hours after cocaine use.

Medical Complications

Myocardial ischemia and infarction have been described among young cocaine users with no other known cardiac risk factors (Box 9-2) (Mittleman et al., 1999; Feldman et al., 2000). The pathophysiologic basis for cocaine-related cardiac effects is not clear, and multiple mechanisms have been postulated, including increases in myocardial oxygen demand, accelerated atherosclerosis, thrombus formation, coronary vasospasm and vasoconstriction, and abnormally enhanced platelet aggregation (Pitts et al., 1997). Endothelin-1, a potent vasoconstrictor, is released by cocaine and may play a significant role in vasospastic angina, acute myocardial infarction, and sudden cardiac death (Wilbert-Lampen et al., 1998). Cocaine abuse has also been associated with ventricular hypertrophy, myocardial depression, and cardiomyopathy (Ghuran and Nolan, 2000). Dysrhythmias associated with cocaine use include sinus tachycardia, ventricular premature contractions, ventricular tachycardia or fibrillation, and asystole (Mouhaffel et al., 1995). Dilated cardiomyopathy, myocarditis, and congestive heart failure have also been reported secondary to cocaine use (Kloner et al., 1992; Mouhaffel et al., 1995). In addition, there is an increased incidence of hemorrhagic cerebrovascular accidents in patients who abuse cocaine (Brust, 1993). The smoking of crack cocaine produces alteration in pulmonary function, as would be expected.

Anesthetic Management

Identification of the cocaine user during the preoperative assessment presents a special challenge to the anesthesiologist, because self-reporting of drug abuse is notoriously unreliable. The nasal mucosa may show signs of ulceration. Extremities should be examined for sclerosis of peripheral veins and needle marks from intravenous injections. Auscultation over the lungs is important to exclude cocaine-induced asthma, and a careful cardiovascular and neurologic examination is necessary (Fleming et al., 1990; Kain and Rosenbaum, 1994).

When cocaine use is suspected or confirmed, preoperative laboratory tests include: complete blood cell count with a platelet count to rule out thrombocytopenia; ECG to identify signs of rhythm disturbance or myocardial ischemia; chest radiography to rule out any pulmonary or cardiac involvement; and abdominal radiography—cocaine and heroin addicts may experience pseudo-obstruction.

Induction and Maintenance of Anesthesia

Of concern is that ketamine should be used with extreme caution in these patients because it can markedly potentiate the cardiovascular toxicity of cocaine. Because both cocaine and succinylcholine undergo metabolism by plasma cholinesterase, the use of succinylcholine may result in prolonged paralysis, an increased anesthetic requirement for volatile anesthetics may be present in the acutely intoxicated patient, and the temperature rise and sympathomimetic effects associated with cocaine can mimic malignant hyperthermia (MH), so it may be difficult to differentiate between the MH and the influence of cocaine.

Acutely Intoxicated Patient

General stabilization and hemodynamic control should precede induction of anesthesia. Propranolol was used successfully in the past to treat the β-adrenergic cardiac effects of cocaine (Fleming et al., 1990). Propranolol may worsen coronary vasoconstriction and should not be used if the patient is experiencing chest pain. Intravenous nitroglycerin, which has been shown to reverse both cocaine-induced hypertension and coronary vasoconstriction, may be the preferable drug. Furthermore, Brogan et al. (1991) reported that sublingual nitroglycerin, in a dose sufficient to reduce the mean arterial pressure by 10% to 15%, reverses cocaine-induced coronary artery vasoconstriction. Labetalol, hydralazine, and esmolol have been documented to adequately control cocaine-induced hypertension (Hollander, 1995).

Clinical experience and experimental evidence support the use of benzodiazepines as a first-line treatment for cocaine-intoxicated patients (Hollander, 1995). In addition to anxiolytic effects, benzodiazepines may lower blood pressure and heart rate, thereby decreasing myocardial oxygen consumption. Benzodiazepines are recommended for patients who are experiencing cocaine-associated chest pain and cardiac ischemic changes, as well as for patients who are having convulsions. In addition, although no clinical data exist to support the use of acetylsalicylic acid (aspirin) in patients with cocaine-associated ischemia, some experimental evidence supports the use of aspirin (Rezkalla et al., 1993).

Amphetamine-Related Designer Drugs

The term designer drugs includes compounds that have been chemically altered from federally controlled substances to produce special effects and to bypass legal regulation. The largest group consists of the methylenedioxy derivatives of amphetamine and methamphetamine. Amphetamine designer drugs produce indirect sympathetic activation by releasing norepinephrine, dopamine, and serotonin from terminals in the central and autonomic central nervous system (Albertson et al., 1999; Christophersen, 2000). The best known and most widely used designer drug is 3,4-methylenedioxymethamphetamine (MDMA, or Ecstasy), which chemically resembles a combination of amphetamine and mescaline (Milroy, 1999). The drug can be ingested orally, injected, smoked, or snorted. The onset of action is directly related to the route of administration, and for an oral dose, onset usually occurs in 20 to 45 minutes and lasts up to 6 hours (Milroy, 1999). Ecstasy is metabolized by the liver and excreted by the kidneys.

Most people who use Ecstasy experience no complications, but a number of deaths have occurred as a result of hyperthermia or idiosyncratic reactions to the drug. The most commonly seen reaction to severe or toxic ingestion of Ecstasy is a syndrome of altered mental status, tachycardia, tachypnea, profuse sweating, and hyperthermia (Henry, 2000). This constellation of symptoms closely resembles that caused by acute amphetamine overdose, which is not surprising given the chemical similarity of MDMA. Reported severe complications from ingestion of Ecstasy include hyperthermia, rhabdomyolysis, renal failure, cardiovascular collapse, disseminated intravascular coagulation, hepatic failure, hyponatremia, urinary retention, cerebral infarct, and cerebral hemorrhage (Hall, 1997a; Milroy, 1999; Ghuran and Nolan, 2000; Henry, 2000; Reneman et al., 2000). Liver damage was recognized among the first deaths in the United Kingdom and seems to be a function of hyperthermia and the resulting shock and disseminated intravascular coagulopathy (Henry, 2000).

The usual presentation in cases of acute toxicity includes hyperthermia, muscle rigidity, and a rise in creatinine kinase (CK) (Hall, 1997b). These patients may deteriorate toward multiple-organ failure, requiring intensive cardiovascular and respiratory support. These patients should be treated with active cooling and dantrolene given over 72 hours (Dar and McBrien, 1996). MDMA-induced hyperthermia results from augmentation of central serotonin function by stimulation of neuronal serotonin release (Dar and McBrien, 1996). Interestingly, Rittoo and Rittoo (1992) suggest that serum MDMA concentrations be measured in the admission blood sample of young adults who develop hyperthermia during general anesthesia. They also raise the question of whether patients who develop hyperthermia after Ecstasy use are at higher risk for the development of severe hyperthermia after general anesthesia.

Management is aimed at controlling symptoms. Benzodiazepines are suggested for agitation or seizures, and dopamine or norepinephrine is recommended for hypotension unresponsive to fluid challenges. Also suggested are phentolamine or nitroprusside for hypertension, lidocaine for ventricular dysrhythmias, and aggressive cooling and possibly the use of dantrolene (Milroy, 1999; Ghuran and Nolan, 2000; Henry, 2000). Additionally, the use of bicarbonate for rhabdomyolysis and correction of electrolyte abnormalities may be needed in the management of these patients.

Marijuana

Marijuana is the most commonly used illegal drug. The hemp plant Cannabis sativa, from which marijuana grows throughout the world, flourishes in most temperate and tropical regions. Marijuana is commonly ingested by smoking, which increases the bioavailability of the primary psychoactive constituent, tetrahydrocannabinol (THC) (Musty et al., 1995; Hall and Solowij, 1998). Inhalation of marijuana smoke produces euphoria, signs of increased sympathetic nervous system activity, and decreased parasympathetic nervous system activity (Schwartz, 1987). At high doses, however, sympathetic activity is inhibited and parasympathetic activity is increased, leading to bradycardia and hypotension. Reversible ECG abnormalities have been reported, as have increases in supraventricular and ventricular ectopic activity (Ghuran and Nolan, 2000). The clinical relevance of this finding is unclear.

Pharmacologic effects of inhaled marijuana occur within minutes but rarely persist longer than 2 to 3 hours. The likelihood that an acutely intoxicated patient would come to the operating room is small. Severe tachycardia should be controlled preoperatively with labetalol or esmolol. Animal studies have demonstrated decreased dose requirements for volatile anesthetics, barbiturates, and ketamine after the intravenous injection of THC. Possible intraoperative complications include bronchospasm secondary to airway irritability by the marijuana smoke, although marijuana is a bronchodilator.

Phencyclidine and Lysergic Acid Diethylamide Abuse

Phencyclidine (PCP) was developed in 1956, and it was briefly used as an anesthetic in humans before being abandoned because of the high incidence of bizarre and serious psychiatric reactions, including agitation, excitement, delirium, disorientation, and hallucinatory phenomena (Abraham et al., 1996). If taken orally, the effects of PCP develop in 1 to 2 hours and last from 8 to 12 hours. The mechanisms of action of both PCP and LSD are quite complex and include agonist, partial agonist, and antagonist effects at various serotonin, dopaminergic, and adrenergic receptors (Abraham et al., 1996). No data exist that examine PCP and its effect on patients undergoing general anesthesia, but anesthesiologists should be familiar with the management of issues related to PCP, because this product is a structural analogue of ketamine (Jansen, 1993).

The CNS effects of LSD begin approximately 15 to 30 minutes after intake and last about 6 to 12 hours (Abraham et al., 1996). The psychological effects related to LSD are intense and include alterations in mood and emotion, euphoria, dysphoria, and visual hallucinations (Abraham and Aldridge, 1993). LSD abuse is associated with only a mild sympathetic discharge that does not resemble those of cocaine, Ecstasy, or amphetamines (Ghuran and Nolan, 2000). These patients may also experience severe attacks of anxiety and panic. Anesthesia and surgery may precipitate these uncontrollable panic responses; diazepam or midazolam may be useful for the management of such responses. Postoperative hallucinations in patients undergoing general anesthesia have been reported as well (Morris and Magee, 1995).

Preoperative Pregnancy Testing

Although the pregnancy rates for teenagers fell to record lows for the United States in 2002, teen pregnancy rates have since risen, and teen pregnancy remains a significant public health concern and poses a dilemma for pediatric anesthesiologists. The birth rate for the youngest teenagers is about 0.7 birth per 1000 females aged 10 to 14 years and about 44 per 1000 for girls aged 15 to 19 years (Martin et al., 2003). At least 5% of girls are or have been pregnant by the time they reach their nineteenth birthday, and a substantial percentage of girls who are screened for elective or emergency surgery in their teen years have unsuspected or unrecognized pregnancies. General anesthesia and surgery in this population place the patient at risk for spontaneous abortion and the fetus at risk of exposure to known teratogenic substances during both anesthesia and the perioperative period, when the patient is no longer under the control of the anesthesiologist. It is this knowledge that leads many anesthesiology departments to have a policy of routinely screening postmenarchal girls for pregnancy.

On the other hand, routine pregnancy screening opens a Pandora’s box of legal, ethical, and practical concerns. Some of the issues are discussed in the following paragraphs.

If an unsuspected (and, chances are, unwanted) pregnancy is discovered, the disclosure of this information to the patient and her family is a challenging task best done by a physician who is well acquainted with the family. The likelihood is that the anesthesiologist, and often the surgeon, have little personal knowledge of the patient and the family. How to best disclose test results and then ensure appropriate high-risk obstetric care must be prospectively determined before embarking on a testing program.

Complicating test result disclosure further is the fact that in the United States, the Health Insurance Portability and Accountability Act (HIPAA) restricts the disclosure of confidential medical information to a third party (parent) without the consent of the patient (pregnant child). This creates a challenging logistical problem for the anesthesiologist.

The fact that there is a teenage pregnancy may imply a previous criminal offense against the child, such as rape or incest. Because of mandatory reporting requirements when child abuse is suspected, there may be criminal legal overtones to a positive pregnancy test that the anesthesiologist must address.

Finally, although the recognition of an unsuspected teen pregnancy may be a theoretically advantageous accomplishment before elective anesthesia, the fact is that within a hospital there are many more potentially injurious events that can occur to a fetus, including exposure to ionizing radiation, teratogenic antibiotics, and antineoplastic agents. A pregnancy screening program makes more sense if instituted on a hospital-wide basis rather than strictly within a preoperative screening program. Hospital-wide institution of such a program relieves the anesthesiologist of the burden of test-result disclosure and institution of appropriate social services.

Preoperative Orders

After the medical history and physical examination have been completed, preoperative orders are written.

For preoperative fasting, the anesthesiologist must consider the patient’s age, size, and general medical condition, as well as the scheduled time of surgery if it is known (Table 9-3). The younger the child, the smaller the glycogen stores; therefore, the occurrence of hypoglycemia with prolonged intervals of fasting is more likely. For this reason, fasting time is reduced in the infant and young child. In general, solid food and milk products are prohibited within 8 and 6 hours, respectively, before surgery (generally after midnight); breast milk is prohibited within 4 hours of surgery; and clear liquids are prohibited within 2 hours of surgery. Liquids such as apple or grape juice, flat cola, and sugar water may be encouraged up to 2 hours before the induction of anesthesia. Ample experience has shown that shortened fasting times are safe, diminish preoperative anxiety and agitation, and may reduce the volume of gastric contents (Coté, 1990; Miller et al., 1990; Schreiner et al., 1990; Emerson et al., 1998; American Society of Anesthesiologist Task Force on Preoperative Fasting, 1999; Ferrari et al., 1999). When surgery is to be delayed beyond the anticipated time, it is important that small infants, generally those younger than 12 to 18 months old, are offered clear fluids or given intravenous fluids to prevent dehydration or hypovolemia.

TABLE 9-3 Fasting (NPO) Guidelines for Elective Surgery in Infants and Children

Substance	Minimum Hours of Fasting
Solid food	8
Commercial formula	6
Milk or milk products	6
Citrus juices	6
Breast milk	4
Clear liquids	2

Regardless of how long the patient fasts, there remains a defined population of children who are at an increased risk for regurgitation and aspiration of stomach contents. This group of children includes patients who have not fasted the requisite length of time and have sustained a severe injury during this period and children with esophageal dysmotility, incompetent gastroesophageal sphincters (gastroesophageal reflux diseases), delayed gastric emptying times, and abdominal conditions that are associated with ileus, vomiting, and electrolyte disorders. In addition, children with medical disorders that are associated with fluid and electrolyte abnormalities (such as diabetic ketoacidosis) are at risk for regurgitation and aspiration secondary to delayed gastric emptying.

In children at risk for aspiration, appropriate medical evaluation is important and preanesthetic medication with a nonparticulate antacid such as sodium citrate/citric acid (0.5 mL/kg), metoclopramide (0.1 mg/kg), and/or H₂-blocking agents (e.g., ranitidine 2.5 mg/kg) may be considered.

Two issues related to the NPO guidelines that commonly arise involve the safety of clear-liquid fasting in overweight and/or obese children for the recommended 2 hours before surgery and gastric fluid volume in children who have been chewing gum before the induction of anesthesia. Cook-Sather and colleagues (2009) noted in a study of ambulatory surgical patients, in which 27% of the patients were overweight or obese, that weight and obesity did not change the ratio of the patients’ gastric fluid volume to their ideal body weights. Thus, the 2-hour fasting interval is appropriate in overweight and obese patients.

Chewing gum has the potential to increase gastric fluid volume and acidity. In adults who chewed sugared or sugarless gum before surgery, gastric fluid volume and pH did not change (Dubin et al., 1994). However, Schoenfelder et al. (2006) noted that children who chewed gum had larger gastric volumes than those children who did not. The significance of these findings remains unclear in that the incidence of aspiration is still exceedingly low.

Preanesthetic Medications

Preoperative anxiety not only is an unpleasant experience for the patient but also makes the induction and recovery from anesthesia more complicated (Holm-Knudsen et al., 1998; Aono et al., 1999; Kain et al., 1999; Zuwala and Barber, 2001; Wollin et al., 2003). Indeed, inadequate preoperative premedication not only results in stormier anesthetic inductions, but also greater postoperative pain and behavioral abnormalities in children that persist long after surgical recovery occurs (Kain et al., 2006). In addition to allaying the anxieties of surgery, separation, pain, and body disfigurement, premedication should therefore allow a smoother and safer induction of anesthesia. The issue of which child should be premedicated and what agent should be used, and whether a parent may be present during induction of anesthesia must be considered according to the specific needs of each child and within the context of the anesthetic practice and clinical setting (Coté, 1999; McCann and Kain, 2001; Leelanukrom et al., 2002; Caldwell-Andrews et al., 2005; Kain et al., 2007a; 2007b).

Which is the best agent to use for premedication? The sheer volume of articles on the subject attests to the lack of an ideal agent or combination of agents as premedication for children. Most preoperative medication is dictated by tradition. As Beecher remarked more than 50 years ago, “Empirical procedures firmly entrenched in habits of good doctors seem to have a vigor and life, not to say an immortality of their own” (1959).

The remainder of this chapter offers a discussion on the various premedications according to their drug classification. In selecting premedication, three important factors must be remembered:

1. A child’s major fear concerning hospitalization is pain from needles and injections. Often hospitalization is synonymous with needles. Many children remember the premedication injection more than they do the pain associated with the operative procedure. Thus in selecting a premedication agent, most any route of administration is preferable to intramuscular injection.

2. Children who undergo regular hospitalizations need as much, or more, preoperative medication than patients undergoing anesthesia for the first time. Previous hospital experiences have formed the basis of their fears, so questions directed at determining their past experiences are invaluable. The previous anesthetic record should be reviewed, with careful attention given to the premedication agent and its effect.

3. The effects of premedications in children vary significantly. Some children may be sedated, others may be excited and restless after drug administration. In addition, to obtain a given level of sedation, some children may need half a recommended dose, and others may need twice the recommended dose. Therefore the dosages in Table 9-4 are intended to serve only as useful guidelines.

TABLE 9-4 Guidelines for Commonly Used Preanesthesia Medications in Children

Anticholinergic Agents

Anticholinergic agents are mentioned in this chapter only for historical reference; in years past they were routinely administered to prevent unwanted autonomic vagal reflexes or bradycardia associated with airway instrumentation, nasopharyngeal stimulation, and anesthetic drugs (particularly halothane and morphine). Before that use, these compounds were administered to block the excessive secretions that were caused by the administration of diethyl ether at induction of anesthesia. At present they are uncommonly used and have few indications; fewer still are the indications that cannot wait until the patient has had anesthesia induced and intravenous access established, allowing intravenous administration of an anticholinergic. As with all pharmacologic agents, the use of anticholinergic agents—whether as an antisialagogue premedication or as a vagolytic agent during surgery—should be governed by specific considerations of the potential side effects (temperature elevation, flushing, dry mouth, tachycardia, and CNS irritability) that can be significant.

Although atropine is the most commonly used agent, scopolamine and glycopyrrolate may also be used to premedicate children. Atropine, in doses of 0.02 mg/kg (0.03 mg/kg in infants), is an extremely effective vagolytic agent.

Oral atropine has been shown to be effective in preventing the adverse cardiovascular changes during induction of anesthesia (Miller and Friesen, 1987). Although injection is avoided with the use of oral atropine, the timing of its use relative to the operative procedure must still be anticipated.

Glycopyrrolate is a quaternary ammonium complex that does not cross the blood-brain barrier. As a result, it has a minimal CNS effect. It causes less tachycardia than atropine, but it is as effective as atropine at half the dose (0.01 mg/kg) as a vagolytic and antisialagogue. Studies in children have shown that glycopyrrolate reduced gastric fluid volume and altered its pH (Brock-Utne et al., 1978; Stoelting, 1978).

Opioids

Opioid premedication, once routinely administered as an intramuscular morphine injection in children, is nearly as uncommon and unnecessary as anticholinergic premedication. Opioid premedication can result in unpleasant dysphoria and an increased incidence of preoperative and postoperative vomiting. When given, opioids can be administered via the oral, rectal, intravenous, intramuscular, or transmucosal route. Interest in the use of opioids as preanesthetic medications has focused on the intranasal and oral transmucosal forms of administration (Leiman et al., 1987; Henderson et al., 1988; Nelson et al., 1989). The advantage of the latter technique is that the dose of premedication can be titrated to effect. Oral transmucosal fentanyl (OTFC) appears to have a relatively short onset time without adversely increasing gastric pH, but it does slightly increase gastric volume and delays the time that children need to tolerate postoperative fluids (Stanley et al., 1989; Ashburn et al., 1990).

Pharmacokinetic studies have demonstrated that OTFC is absorbed well through the buccal mucosa (Streisand et al., 1991). In volunteers administered an oral drink of both fentanyl and OTFC, OTFC produced higher and earlier peak plasma concentrations, as well as increased bioavailability (50% versus 30%), compared with swallowed fentanyl. In blinded studies of children in which OTFC (15 to 20 mcg/kg) was compared with placebo, OTFC is superior to placebo in allowing children to separate from parents and undergo inhalation induction of anesthesia (Moore et al., 2000; Tamura, et al., 2003). However, it was associated with considerable untoward side effects, including nausea and vomiting, oversedation, and oxygen desaturation (Nelson et al., 1989; Streisand et al., 1989, 1991; Ashburn et al., 1990; Goldstein-Dresner et al., 1991; Moore et al., 2000). The postoperative nausea and vomiting are not attenuated by intraoperative intravenous droperidol (50 mcg/kg) (Freisen and Lockhart, 1992). Because of the high incidence of reported side effects, as well as the need for continuous pulse oximetry while and after this drug is administered, OTFC as a preoperative sedative in children has not gained widespread use or popularity.

Hypnotics

Midazolam is a water-soluble benzodiazepine with a more rapid onset time and a shorter duration of action than diazepam. Its water solubility allows better absorption after intramuscular injection and eliminates the venous irritant properties associated with diazepam (Ghoneim and Korttila, 1977). Midazolam’s peak plasma concentration occurs 45 minutes after intramuscular injection, but its anxiolytic effects occur in as little as 5 minutes. Its duration of action is usually 2 hours, with a range of 1 to 6 hours (Reves et al., 1985).

Now approved as a premedication for children and marketed as an oral preparation, midazolam has become the most commonly administered premedication before routine surgery in virtually every pediatric center; it is now the gold standard with which other premedications are compared. A national survey of over 5000 anesthesiologists has indicated that midazolam is the preoperative sedative of choice in more than 90% of all routine cases in children (Kain et al., 1997; Brosius and Bannister, 2002). The experience with midazolam is extensive and demonstrates the drug to be highly effective in alleviating anxiety, increasing cooperation, and diminishing antegrade recall without affecting retrograde memory (Payne et al., 1991a; Parnis et al., 1992; Twersky et al., 1993; Gillerman et al., 1996; McCann and Kain, 2001; Millar et al., 2007). Premedication with midazolam is safe and free of side effects, and it does not prolong recovery times (Payne et al., 1991b; Sievers et al., 1991; McMillan et al., 1992; Weldon et al., 1992; Davis et al., 1995; Viitanen et al., 1999; Brosius and Bannister, 2002). Finally, midazolam premedication smoothes the postoperative recovery of children and diminishes the incidence of delirium (Ko et al., 2001).

Nasal midazolam has also been reported to be highly effective in reducing anxiety in children within 10 to 12 minutes of administration (Griffith et al., 1998; Gautam et al., 2007). Furthermore, Davis et al. (1995) demonstrated that nasal midazolam (0.2-0.3 mg/kg) administered to patients undergoing myringotomies led to reduced preoperative anxiety and did not prolong recovery time and hospital discharge time. A drawback of nasal midazolam, however, is that more than 50% of children cry at administration because it irritates the nasal passages. The only rationale for administration of nasal midazolam is if a child without intravenous access cannot or will not swallow the oral preparation. Occasionally, younger children who refuse to take oral or nasal midazolam are more inclined to accept the midazolam rectally (McCann and Kain, 2001). Midazolam administered rectally in doses of 0.5 to 1 mg/kg effectively reduces the anxiety of children before induction of anesthesia.

Other benzodiazepines have not gained the popularity of midazolam nor have shown any advantage over the use of midazolam. Studies of flunitrazepam in children are limited, but it appears to be an effective pediatric premedication (Richardson and Manford, 1979). As with other benzodiazepines, flunitrazepam can be administered as a rectal premedication. In a double-blind, placebo-controlled study, 0.04 mg/kg of rectal flunitrazepam provided better sedation and mask-acceptance scores without prolonging recovery from anesthesia (Esteve and Saint-Maurice, 1990). Triazolam has been used as a preanesthetic medication in adults (Yamakage et al., 2002) but its use in children has not been evaluated, nor has it been compared with conventional agents.

Ketamine

In high doses (4 to 12 mg/kg), intramuscular ketamine has often been used to induce and maintain anesthesia in children (Wyant, 1971). Hannallah and Patel (1989) demonstrated that at low doses (2 mg/kg), intramuscular ketamine can facilitate inhalation induction of anesthesia. In this study of uncooperative children undergoing tympanostomy tube insertion, low-dose intramuscular ketamine was very effective in completing a mask induction with halothane in a shorter time than in cooperative children who did not need premedication. Although the induction time was shorter in the group receiving ketamine, ketamine did prolong the hospital discharge times.

As an alternative to intramuscular administration, rectal, nasal transmucosal, and oral routes of ketamine administration have been described. Rectal administration of ketamine has been reported in children undergoing a wide variety of surgical procedures. Van der Bijl and colleagues (1991) compared rectal administration of midazolam (0.3 mg/kg) with rectal administration of ketamine (5 mg/kg). Thirty minutes after the administration of either drug, good anxiolysis, cooperation, and sedation were achieved. In doses of 8 to 10 mg/kg, Saint-Maurice et al. (1979) noted that the interval from rectal administration to loss of verbal contact and acceptance of the facemask was 7 and 9 minutes, respectively.

Nasal transmucosal ketamine is an effective means of premedicating children. Weksler and colleagues demonstrated that 6 mg/kg of nasal ketamine administered 20 to 40 minutes before surgery achieved satisfactory sedation in 78% of the patients, whereas smaller doses of 5 mg/kg produced comparable sedation and ease of separation from parents as nasal midazolam (Weksler et al., 1993; Gautam et al., 2007).

Oral ketamine, of course the most acceptable route in most situations, has been used for nearly 20 years as a preoperative anesthetic medication in healthy children who are undergoing routine surgical procedures and in children undergoing corrective surgery for congenital heart defects (Stewart et al., 1990). Gutstein et al. (1992), in a double-blind, prospective study, evaluated placebo and oral ketamine at both 3 and 6 mg/kg doses as a preanesthetic medication in children. At some time during the study, 100% of the children administered 6 mg/kg were sedated as opposed to 73% of the children administered 3 mg/kg. In both groups of children who received ketamine, the onset of sedation occurred in 12 minutes, and in the 6 mg/kg group, 67% of patients were sufficiently sedated to have an intravenous cannula inserted. Similarly, the combination of oral midazolam and oral ketamine has a very high success rate of satisfactory anxiolysis compared with a somewhat lower success rate for either drug alone (Funk et al., 2000; Ghai et al., 2005). Postanesthesia care-unit discharge time of children who received orally administered ketamine is reported not to be prolonged compared with orally administered midazolam, provided that the duration of surgery is longer than 30 minutes (Funk et al., 2000). Oral ketamine has also been found to be an effective premedication in alleviating the distress of invasive procedures in pediatric oncology patients (Tobias et al., 1992). An oral transmucosal lozenge containing ketamine was under development for some time as a surgical premedication, and was found to be equally effective as oral midazolam; the present status of this drug development project is unknown at the time of this writing (Horiuchi et al., 2005).

Alpha-2-Adrenoreceptor Agonists

The role of α₂-adrenoreceptor agonists for both premedication of children before surgery and as analgesics during and after surgery is continuing to evolve. In adults, α₂-adrenoreceptor agonists have been shown to provide perioperative sedation, postoperative analgesia, improved perioperative hemodynamic stability, and reduced anesthetic requirements (Ghignone et al., 1987; Wright et al., 1990; Carabine et al., 1991). The MAC-sparing effect of premedication with 1 to 10 mcg/kg of oral clonidine has been demonstrated (Nishina et al., 1996; 1997; Inomata et al., 2002).

Clonidine

In a double-blind, randomized study, Mikawa and colleagues demonstrated that in children, oral clonidine produces sedation in a dose-dependent manner, and that at a dose of 4 mcg/kg, clonidine provides satisfactory sedation, a better quality of child/parent separation, and better mask acceptance than does standard oral diazepam premedication (0.4 mg/kg) (1993). Fazi and colleagues (2001) showed that oral clonidine was generally inferior to oral midazolam; however, clonidine 4 mcg/kg was associated with faster awakening than midazolam 0.5 mg/kg. These authors found that after clonidine premedication, children were more distressed and agitated during inhalation induction and had higher pain scores and greater analgesic requirements in the postoperative period. Yet few other citations in the literature have found similar results. Virtually all other authors have shown that oral clonidine in doses of 4 to 5 mcg/kg is comparable in efficacy with oral midazolam 0.5 mg/kg; whereas the onset of sedation tends to be less after the use of clonidine, the degree of sedation tends to be greater (Inomata et al., 2002; Bergendahl et al., 2004; Almenrader et al., 2007a; 2007b). Clonidine may be a useful premedication in children who have previously experienced delirium, agitation, or paradoxical reactions to midazolam or other benzodiazepines in the past (Stella and Bailey, 2008).

Importantly, clonidine premedication has beneficial effects that go beyond the preoperative period. It has become clear both from clinical experience and from clinical research that the analgesic effect of clonidine persists well into the postoperative period, reducing measures of surgical pain in children (Schmidt et al., 2007). This may be closely related to why the incidence of emergence delirium is reduced following clonidine premedication (Ko et al., 2001; Bock et al., 2002; Malviya et al., 2006) and is not after midazolam premedication (Breschan et al., 2007), and why the neuroendocrine stress response to surgery is attenuated in those children who were premedicated with clonidine (Kain et al., 2000).

Clonidine, therefore, is emerging as a premedication that is equal in sedative efficacy to midazolam, but that possesses salutory effects over and above midazolam. Its role in pediatric anesthesia will continue to evolve and be better defined in the future.