Preoperative Preparation for Infants and Children - Smith's Anesthesia for Infants and Children

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

PART TWO – General Approach to Pediatric Anesthesia

Chapter 8 – Preoperative Preparation for Infants and Children

Elliot J. Krane,Peter J. Davis

Preanesthetic Visit, 255

Physical Examination, 256

Review of Body Systems, 258

		Central Nervous System,258
		Cardiovascular System, 258
		Respiratory System, 259
		Gastrointestinal System, 260
		Renal System, 261
		Hematologic System, 261

Child With Physical or Mental Handicaps, 261

		Brain Damage, 261
		Cerebral Palsy, 261
		Mental Retardation and Psychological Disorders,262
		Hyperactivity and Lack of Cooperation, 262

Drug-Abusing Child and Adolescent, 262

		Cocaine, 262
		Amphetamine-Related Designer Drugs, 264
		Marijuana Abuse, 264
		Phencyclidine and Lysergic Acid Diethylamide Abuse,264

Preoperative Pregnancy Testing, 265

Preoperative Orders, 265

Preanesthetic Medications, 266

		Anticholinergic Agents, 266
		Opioids, 266
		Hypnotics, 267
		Ketamine, 267
		α₂-Adrenoreceptor Agonists,268

Summary, 268

In addition to appreciating the emotional stresses that affect both the child and parent, the anesthesiologist must have a sound understanding of the child's medical disease and anticipated surgical procedure. 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 gratitude of the parents, if they are present. The anesthesiologist should conduct the preoperative visit wearing the operating room scrub attire and hat (Fig. 8-1 ), so that when the child comes to the operating room and is met by the anesthesiologist, the face and garb are familiar.

A careful preoperative examination of the child and the child's medical record enables the anesthesiologist to assess the 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 apprised of the anticipated risk.



FIGURE 8-1 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.

▪ PREANESTHETIC VISIT

The preanesthetic visit should begin with a careful review of the medical record; particular attention is 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, including 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 frequent latex exposure in the past ( Beal, 1992 ; Levy, 1992 ; Sussman, 1992 ; Yassin et al., 1992 ; Meeropol et al., 1993 ). 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 for patients who are receiving chronic corticosteroid therapy and for patients who have received steroids in the past must be addressed (see Chapter 32 , 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 8-1 summarizes the most commonly used herbal remedies ( Ang-lee et al., 2001 ).

TABLE 8-1 -- 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; used to treat 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 cyclosporin, 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 frequency of congenital heart disease, and some forms of radial dysplasia may be associated with thrombocytopenia or atrial septal defects. The topic of congenital anomalies was extensively discussed in a review byLynn (1985) . Table 8-2 describes the anesthetic implications of positive findings derived from the medical history and review of systems. 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.

TABLE 8-2 -- Medical history and review of systems: Anesthetic implications

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

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

SBE, subacute bacterial endocarditis; VQ, ventilation perfusion.

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

▪ 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 all afternoon 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. In examining a child, one should look for somewhat different signs than in 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 has a runny nose, it may be hard to determine whether it is due to an infection or simply the result of crying. Enlarged cervical nodes and otitis media occur frequently with respiratory tract infections.

Partial airway obstruction may result from infection, anatomic anomalies, or tumors. The exact diagnosis should be made before anesthesia is started. Unilateral nasal discharge is unusual and suggests a foreign body (or, rarely, choanal atresia).

When a child is scheduled for procedures such as repair of lacerations, removal of a tumor, or excision of a nevus, the anesthesiologist should personally observe the location and size of the lesion. 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.

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

▪ REVIEW OF BODY SYSTEMS

▪ 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.

Trauma is the most frequent cause of death in children, and most fatal trauma involves injury to the CNS. Head injuries frequently 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 and often obstruct cerebrospinal fluid pathways, resulting in hydrocephalus. The anesthetic care of children with elevated intracranial pressure is discussed in Chapter 18 , Anesthesia for Neurosurgery.

Serum levels of certain anticonvulsant drugs should be measured or should have been measured before elective surgery in children with chronic seizure disorders to ensure therapeutic levels. Most anticonvulsants have a long plasma half-life; missing one dose in the perioperative period does not significantly diminish the serum level. Of the commonly used anticonvulsants, only phenobarbital and phenytoin may be given intravenously in the perioperative period. Other frequently administered anticonvulsants, however, such as sodium valproate and carbamazepine, 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 concerning possible alternative drug therapy.

Conditions such as a development 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 mental retardation 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 later years frequently produces restrictive lung disease resulting from 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 (see Chapter 32 , Systemic Disorders). In myotonia, succinylcholine produces a sustained contracture of skeletal muscle, which may impede the ability to maintain a patent airway and ventilate the lungs. In other myopathies, such as clinically active dermatomyositis, succinylcholine may produce life-threatening hyperkalemia.

Several case reports noted cardiac arrest and rhabdomyolysis after the administration of halothane and succinylcholine or succinylcholine alone to children with Duchenne's muscular dystrophy ( Genever, 1971 ; Miller et al., 1978 ; Seay et al., 1978 ; Brownell et al., 1983 ; Kelfer et al., 1983 ). As a result, the suggestion has been made that the incidence of malignant hyperthermia (MH) may be elevated in Duchenne's muscular dystrophy ( Miller et al., 1978 ; Brownell et al., 1983 ). In these cases, the diagnosis of malignant hyperthermia was based on muscle biopsy and caffeine or halothane contracture test results ( Brownell et al., 1983 ; Kelfer et al., 1983 ; Rosenberg and Heiman-Patterson, 1983 ). Although not all children with Duchenne's muscular dystrophy are susceptible, Rosenberg and Heiman-Patterson (1983) recommend that precautions against malignant hyperthermia be taken in all patients with this disorder.

▪ CARDIOVASCULAR SYSTEM

Evaluation of the cardiovascular system is critical to the delivery of safe anesthesia. The physical examination infrequently reveals an unexpected CNS lesion, but a careful history and auscultation of the child's chest more frequently demonstrate a congenital cardiac lesion unknown to the parents or the child's surgeon.

The history and systems review yield 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 of course not high, the symptoms of congestive heart failure or cyanosis are most likely limited to those few periods 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 also are 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 physiologically significant heart defect should include thorough history and physical examination, an electrocardiogram (ECG) and echocardiogram, determination of hematocrit, a baseline oxygen saturation value (Spo₂), a chest radiograph, and definitive knowledge of the type of cardiac lesion, its degree of severity, and its physiologic effect on cardiac efficiency and oxygen delivery. These 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 should be ascertained in children with cyanotic heart disease; a hematocrit 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 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 appearance 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, bacterial endocarditis prophylaxis is indicated for procedures that may result in bacteremia, such as dental surgery, gastrointestinal or urogenital endoscopy, and nasotracheal intubation (see inside cover). Atrial septal defects contraindicate the use of the sitting position for suboccipital craniotomies, to minimize the risk of paradoxical air embolism (Fischler, 1992), and may make intraoperative transesophageal echocardiography desirable in certain cases that have been associated with venous air embolism (e.g., posterior spine fusions, liver transplantation), to detect the movement of air from the pulmonary to the systemic circulation. 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. Many congenital anomalies and syndromes are associated with cardiac defects or other cardiovascular problems; Box 8-1 provides an outline of these conditions.

BOX 8-1

Pediatric Syndromes Associated With Cardiac Conditions

Syndromes Associated With Congenital Heart Disease

Apert's syndrome

Aspenia syndrome (Ivemark's syndrome)

Conradi's syndrome

DiGeorge syndrome

Down syndrome (trisomy 21)

Edwards' syndrome (trisomy 18)

Ellis-van Creveld syndrome

Goldenhar's syndrome

Holt-Oram syndrome

I-cell disease

Laurence-Moon-Biedl syndrome

LEOPARD syndrome (multiple lentigines syndrome)

Marfan syndrome

Meckel's syndrome

Noonan's syndrome

Patau's syndrome (trisomy 13)

Polysplenia

Rubinstein's syndrome

Sebaceous nevi syndrome

TAR syndrome (thrombocytopenia-absent radius syndrome)

VACTERL (vertebral, anal, cardiac, tracheal, esophageal, renal, and limb) association

VATER (vertebral defects, imperforate anus, tracheoesophageal fistula, radial and renal dysplasia) association

Williams syndrome

Syndromes Associated With Cardiomyopathy

Cretinism

Duchenne's muscular dystrophy

Farber's disease

Friedreich's ataxia

Hunter's syndrome

Hurler's syndrome

Maroteaux-Lamy syndrome

Myotonic dystrophy

McArdle's disease

Pompe's disease

Stevens-Johnson syndrome

Syndromes Associated With Autonomic Dysfunction or Arrhythmias

Albright's osteodystrophy

Guillain-Barré syndrome

Jervell and Lange-Nielsen syndrome

Riley-Day syndrome

Shy-Drager syndrome

Short QT syndrome

Sipple's syndrome

Wolff-Parkinson-White syndrome

Syndromes Associated With Thromboses or Ischemic Heart Disease

Ehlers-Danlos syndrome

Fabry's disease

Grönblad-Strandberg syndrome

Homocystinuria

Progeria

Tangier disease

Werner's syndrome

▪ RESPIRATORY SYSTEM

Chapter 2 , Respiratory Physiology, 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 Down syndrome (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.

Acute upper respiratory tract infections provide a frequent dilemma for the anesthesiologist ( Tait and Malviya, 2005 ). In the best of all worlds, no child would be anesthetized electively during an acute respiratory illness. Although not all have identified acute respiratory illness as a cause of perioperative complications in children ( Elwood et al., 2003 ), there is compelling evidence that the occurrence of both intraoperative and postoperative hypoxemia and other airway complications is increased in children with upper respiratory tract infection ( 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 ) and that the incidence of bronchospasm is increased in the presence of upper respiratory infections in children who are intubated ( Rolf and Coté, 1992 ). In a prospective study, Tait and others (2001) noted that endotracheal intubation, a history of prematurity, reactive airway disease, parental smoking, airway surgery, and nasal congestion were risk factors associated with respiratory complications in infants and children with an upper respiratory infection who were 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 in the decision to postpone surgery. For example, the small additional 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 many 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 myringotomy is therapeutic in these children and is not associated with an incidence of increased postoperative pulmonary complications ( Tait and Knight, 1987 ).

The presence of acute disease of the lower airways, however, should 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 viral lower respiratory tract infection, such as influenza, develop airway hyperreactivity that is indistinguishable from bronchial asthma and can last as long as 6 to 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 frequently medicated with β₂-adrenergic agents and inhaled corticosteroids. Other first-line drugs include cromolyn sodium and leukotriene receptor antagonists; sometimes theophylline preparations are administered. The serum concentration of theophylline should be measured preoperatively to ensure a therapeutic level (10 to 20 mcg/mL), and the anesthesiologist should be aware of potential interactions among theophylline, β₂-adrenergic drugs, and halothane (although infrequently used). Asthmatic children who receive corticosteroids should also receive perioperative therapy with stress doses of corticosteroids if steroid therapy has been recent; 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 32 , Systemic Disorders).

Severe kyphoscoliosis frequently leads to significant restrictive lung disease. The cause of the kyphoscoliosis should be assessed because it frequently results from neuromuscular disease such as cerebral palsy or muscular dystrophy. Preoperative pulmonary function testing also predicts which children will need admission to the intensive care unit with or without mechanical ventilation postoperatively (seeChapter 21 , Anesthesia for Orthopedic Surgery).

A growing population, now frequently seen in the operating room, consists of infants who have graduated from neonatal intensive care. The formerly premature infant is often left with residual chronic obstructive pulmonary disease, called bronchopulmonary dysplasia, the consequence of both oxygen toxicity and ventilator-induced lung injury to immature lungs. Children with bronchopulmonary dysplasia exhibit a combination of fibrotic changes in the lung parenchyma and reactive small airways disease with or without wheezing and air trapping. The latter may respond to steroids and bronchodilators to 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; abnormal serum electrolyte levels are common preoperatively. Adequate arterial saturation must be ensured at all times, which reduces pulmonary hypertension, and perioperative bronchodilator therapy should be given. Alterations in anesthetic care include judicious, if any, use of nitrous oxide, to avoid aggravation of pulmonary gas trapping; very careful fluid therapy and restriction of sodium load; 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 formerly premature infant who is still less than 45 or as old as 60 weeks of postconceptional age (the sum of gestational age and the 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 formerly premature infants include a history of mechanical ventilation, a 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 and others (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.

Congenital diseases of the lungs are usually recognized and surgically corrected in the newborn period. These conditions and their anesthetic management are discussed in Chapter 32 , Systemic Disorders.

▪ GASTROINTESTINAL SYSTEM

The primary concern of the anesthesiologist is to assess the integrity of the gastroesophageal sphincter, the emptiness of the stomach, and, hence, the risk of aspiration on induction of or emergence from anesthesia. Gastroesophageal reflux occurs as an isolated entity in some otherwise normal infants. Parents describe frequent spitting up after meals, and there may be a history of frequent lower respiratory tract infections, small airways disease, wheezing, or esophagitis, which point to the diagnosis. Gastroesophageal reflux is very common in the developmentally delayed child. After repair of tracheoesophageal fistulas, abnormalities of esophageal motility and decreased competence of the gastroesophageal sphincter are often present, increasing the risk of vomiting and aspiration on induction of anesthesia. Children who fall into these categories should be considered to have a “full stomach.”

▪ RENAL SYSTEM

Renal failure is infrequent in childhood. Chronic renal failure is typically managed with either peritoneal dialysis or, in the older child, hemodialysis. The evaluation of the child with preoperative renal disease includes serial measurements of blood pressure to assess the adequacy of antihypertensive therapy, careful determination of vascular volume, and measurement of serum levels of electrolytes, urea nitrogen, creatinine, phosphate, calcium, and magnesium, as well as hematocrit. Electrolyte levels should be within a reasonably normal range; if significant derangement exists, additional electrolyte therapy or dialysis should be performed before elective surgery. The acceptable lower limit of hematocrit is generally considered to be about 20% with chronic renal failure. Such an assumption of adaptation, however, is controversial because the blood levels of 2,3-diphosphoglycerate in these children are not necessarily increased, depending on the chronicity of anemia or recent history of dialysis.

Milder degrees of renal dysfunction may also affect anesthetic care. In small children with mild or moderate underlying renal disease, clinically significant hypervolemia may occur without compensation by augmented urine output, and an excessive sodium or free water load further deranges the serum electrolyte level. Particular caution is important in the management of fluids in children, and central venous pressure monitoring is required during major surgery in which significant blood loss or fluid shifts are anticipated (see Chapter 4 , Regulation of Body Fluids and Electrolytes).

▪ HEMATOLOGIC SYSTEM

Underlying disorders of the hematologic system are infrequent. The systems review should include an inquiry into unusual bleeding in the family's or child's medical history to explore possible genetic coagulopathies. A report of excessive bleeding from a circumcision or tonsillectomy should raise the possibility of thrombocytopenia, von Willebrand's disease, or one of the inherited factor deficiencies and is a reason to measure platelet count, bleeding time, and coagulation times (see Chapter 32 , Systemic Disorders).

Sickle cell anemia typically produces no symptoms in early childhood, so a systems review is unlikely to detect its presence. For this reason, children of African heritage should be screened for sickle cell disease before surgery. A positive result should be followed by a hemoglobin electrophoresis to confirm the diagnosis or to define other hemoglobinopathies. The anesthetic plan may then be altered to ensure preoperative and postoperative hydration and to provide a high concentration of inspired oxygen. The use of a tourniquet during orthopedic surgery is contraindicated when sickle cell disease or trait is present, to prevent ischemia and subsequent sickling in the operated limb. This has become controversial, however.

In a report by the Preoperative Transfusion in Sickle Cell Disease Study Group, aggressive treatment (transfusion to a hemoglobin S level of less than 30%) was compared with a more conservative management regimen (hemoglobin maintained at 10 g/dL). The conservative approach was equally as effective as the aggressive approach in preventing serious complications but associated with half the number of transfusion-associated complications ( Vichinsky et al., 1995 ). A hematologic consultation should be sought when diagnosis is made (see Chapter 32 , Systemic Disorders).

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

▪ CHILD WITH PHYSICAL OR MENTAL HANDICAPS

The most important principle in dealing with all types of physically and/or mentally handicapped children is to be considerate. In any situation involving the care of handicapped patients, it is appropriate to show appreciation of the position of the families and the dedication and deprivation they endure with remarkably little complaint. It is frequently inspiring to learn about their ability to cope with misfortune.

▪ BRAIN DAMAGE

Children surviving severe hypoxic or traumatic brain damage and those with postinfectious encephalopathy may undergo various surgical procedures. Preoperative evaluation should include determination of the type and degree of 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 tracheostomy, which, if still present, may simplify induction of anesthesia, but if the patient was decannulated in the past, the upper airway may have been rendered stenotic.

Because of difficulty in 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 frequently have gastrostomy tubes for feeding, which should be identified, drained before the induction of anesthesia, and left open throughout the operative period to prevent gastric distension.

Old injuries, strictures, flexions, deformities, and scars should be noted, with careful description of the 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 or spastic diplegia or quadriplegia ( Nolan et al., 2000 ). Inexperienced personnel frequently make the serious mistake of assuming that patients with spastic diplegia or quadriplegia are mentally retarded, which may not be true. Cerebral palsy is a general term applied to several different forms of neuromuscular disability ( Stiles, 1981 ), arising from various anatomic lesions of the brain, and not always involving mental retardation. 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.

▪ MENTAL RETARDATION AND PSYCHOLOGICAL DISORDERS

The term mental retardation is one of the broadest in medicine, encompassing about 30 different forms ( Thorn et al., 1977 ). Simple familial retardation, Down syndrome, autism, and phenylketonuria are well-known forms; information on more obscure forms may be found in special texts, such as that of Katz and Steward (1987) . Familial mental retardation bears no specific outward stigmata, and anesthesia is adapted to the child's level of consciousness and cooperation. Down syndrome is frequently associated with congenital heart defects as well as other congenital defects. It is also frequently 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 ) (see Chapter 32 , Systemic Disorders).

Autistic children are difficult to deal with and frequently are wildly resistant to any intervention. These patients may appear to be remarkably alert, in contrast to most mentally retarded patients, 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 et al., 2001 ). As for other mentally retarded children, the presence of a parent at induction often has a soothing effect. Premedication with oral midazolam is often effective to sedate these children and to improve cooperation.

▪ HYPERACTIVITY AND LACK OF COOPERATION

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

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 benzodiazepines may be helpful. Intramuscular ketamine (2 to 4 mg/kg) may be used as a last resort.

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

▪ DRUG-ABUSING CHILD AND ADOLESCENT

Drugs such as cocaine, marijuana, and lysergic acid diethylamide (LSD) have been of increasing social and medical concern. Abuse of illicit drugs is unfortunately not limited to adults. In 1993, about one of three (35.5%) high school seniors in the United States had used marijuana in their lifetime ( Fig. 8-2 ) ( 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 frequently 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 8-2 Percentage of high school seniors in the United States who had used marijuana in their lifetime.

▪ COCAINE

Cocaine is an alkaloid derived from the leaves of the South American shrub Erythroxylon coca; it is prepared by dissolving the alkaloid base to form a water-soluble salt (cocaine hydrochloride), which can be marketed as crystals or granules ( Fleming et al., 1990 ). 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 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 8-2 ) ( 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 increase 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/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 ).

BOX 8-2

Medical Complications of Cocaine Abuse

Cardiac

Myocardial ischemia/infarction

Arrhythmias

Cardiomyopathy

Myocardial depression

Neurologic

Seizures

Cerebral infarctions

Subarachnoid hemorrhage

Intracerebral bleed

Obstetric

Preterm labor

Premature rupture of membranes

Abruptio placentae

Precipitate delivery

Sudden infant death syndrome

Pediatric

Prematurity

Congenital anomalies

Neurobehavioral abnormalities

Partial ankyloglossia

Necrotizing enterocolitis

Pulmonary

Cocaine-induced asthma

Hypersensitivity pneumonitis

Chronic cough

Pulmonary edema

Pneumothorax

Pulmonary hemorrhage

Cocaine-related pulmonary effects occur primarily in patients who smoke crack; these include cocaine-induced asthma, hypersensitivity pneumonitis, chronic cough, pulmonary edema, and pneumopericardium ( Albrecht et al., 2000 ). The prevalence of cocaine abuse in the obstetric population reportedly ranges from 7.5% to 45% ( Kain et al., 1993 ). Acute cocaine use during the third trimester may result in abruptio placenta and premature labor. In the newborn, meconium staining, multiple congenital anomalies, and increased incidence of sudden infant death syndrome have been reported ( Kain et al., 1993 ). Short- and long-term neurobehavioral problems have also been described.

Anesthetic Management

Identification of the cocaine user during the preoperative assessment presents a special challenge to the anesthesiologist, as self-reporting of drug abuse is notoriously unreliable. The nasal mucosa should be carefully observed for ulceration signs. All extremities should be examined for sclerosis of peripheral veins and needle marks from intravenous injections. Recent cocaine injection sites may also have a characteristic look of multiple ecchymoses. 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 ).

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 present with pseudo-obstruction.

Cocaine-induced thrombocytopenia has been reported among parturients, and until the incidence of cocaine-induced thrombocytopenia is defined through prospective studies, a platelet count should be obtained before instituting a regional anesthetic. Ester local anesthetics, which undergo metabolism by plasma cholinesterase, may compete with cocaine, resulting in decreased metabolism of both drugs.

Induction and Maintenance of Anesthesia

Of concern is that (1) ketamine should be used with extreme caution in these patients because it can markedly potentiate the cardiovascular toxicity of cocaine; (2) because both cocaine and succinylcholine undergo metabolism by plasma cholinesterase, the use of succinylcholine may result in prolonged paralysis; (3) an increased anesthetic requirement for volatile anesthetics may be present in the acutely intoxicated patient; and (4) the temperature rise and sympathomimetic effects associated with cocaine can mimic malignant hyperthermia (MH), and it may be difficult to differentiate between the two.

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 presents with chest pain. Labetalol, hydralazine, and esmolol have been documented to adequately control cocaine-induced hypertension ( Hollander, 1995 ). Intravenous nitroglycerin, which was shown to reverse both cocaine-induced hypertension and coronary vasoconstriction, may be the preferable drug. Further,Brogan and others (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.

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 present with cocaine-associated chest pain and cardiac ischemic changes and for patients who present with convulsions. Also, although there are no clinical data to support the use of acetylsalicylic acid (aspirin) in patients with cocaine-associated ischemia, there is experimental evidence to support the use of this drug ( 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 [“Ecstasy”]), which resembles chemically 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 generally lasts up to 6 hours ( Milroy, 1999 ). Ecstasy is metabolized by the liver and excreted by the kidney. Ecstasy was first produced in 1914 by Merck as an appetite suppressant, but it never became commercially successful ( Shulgin, 1986 ). It resurfaced in the 1950s as a method of lowering inhibitions in patients undergoing psychoanalysis ( Shulgin, 1986 ). Recreational use of MDMA began to surface in the early to mid-1980s in Great Britain and later in the United States. Most MDMA use occurs during “raves” (dance parties attended by thousands in abandoned warehouses) ( Boot et al., 2000 ).

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 MDMA 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. Severe reported complications from MDMA ingestion 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 ( Henry, 2000 ) and seems to be a function of hyperthermia and resulting shock and disseminated intravascular coagulopathy.

The usual presentation of cases of acute toxicity includes hyperthermia, muscle rigidity, and 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 suggest that serum MDMA concentrations be measured in the admission blood sample of young adults who develop hyperthermia during general anesthesia ( Rittoo and Rittoo, 1992 ). 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 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). In addition, the use of bicarbonate for rhabdomyolysis and correction of electrolyte abnormalities may be needed in the management of these patients.

▪ MARIJUANA ABUSE

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 well as an increase 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 present to the operating room is small. Severe tachycardia should be controlled preoperatively with labetalol or esmolol. Animal studies demonstrated decreased dose requirements for volatile anesthetics, barbiturates, and ketamine after 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 phenomenon ( 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 examines 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 that of cocaine, Ecstasy, or amphetamines ( Ghuran and Nolan, 2000 ). These patients may also present with 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 continue to fall, reaching record lows for the United States in 2002, 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 19th birthday, and a significant percentage of girls who present for elective or emergent surgery in their teen years have unsuspected or unrecognized pregnancies. General anesthesia and surgery in this population place them at risk for spontaneous abortions and the fetus at risk to exposure to known teratogenic substances during both the anesthetic and the perioperative period, after which the patient is no longer under the control of the anesthesiologist. It is this knowledge that leads many departments of anesthesiology 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 as follows:

	•	If an unsuspected (and, chances are, unwanted) pregnancy is discovered, the disclosure of this upsetting information to the patient and her family is a challenging task best done by a physician 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 obstetrical care, must be prospectively determined before embarking on a testing program.
	•	Complicating test result disclosure further is the fact that in the United States, it is illegal to share confidential medical information with a third party without the consent of the patient. If a preoperative screening pregnancy test is positive, it is necessary to share the result with the patient, who may well be a child, but it remains illegal to share the test result with a parent without the consent of the patient. This creates a challenging logistical problem for the anesthesiologist.
	•	The fact that there is a teenage pregnancy may imply the prior commitment of a criminal offense against the child, such as statutory 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, antineoplastic agents, etc. 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 (“NPO orders,” Box 8-3 ), the anesthesiologist must consider the patient's age, size, and general medical condition as well as the scheduled time of surgery, if that is known. The younger the child, the smaller are the glycogen stores, and the more likely is the occurrence of hypoglycemia with prolonged intervals of fasting. 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 ; Ferrari et al., 1999 ). When surgery is to be delayed beyond the anticipated time, it is important that small infants, generally younger than 12 to 18 months, are offered clear fluids or given intravenous fluids to prevent significant dehydration or hypovolemia.

BOX 8-3

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 the amount of time for which 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 pathology associated with ileus, vomiting, and electrolyte disorders. In addition, children with medical disorders associated with fluid and electrolyte abnormalities (such as diabetic ketoacidosis) are at risk for regurgitation and aspiration secondary to delayed gastric emptying.

In these children at risk for aspiration, appropriate medical evaluation is important and preanesthetic medication with a nonparticulate antacid (e.g., Bicitra [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.

▪ PREANESTHETIC MEDICATIONS

Preoperative anxiety not only is an unpleasant experience for the patient but also makes the induction and recovery from anesthesia more complicated (Aono et al., 1999). In addition to allaying the anxieties of surgery, separation, pain, and body disfigurement, premedication should allow a smoother and safer induction of anesthesia. The issue of which child should be premedicated and what agent should be used must be considered according to the specific needs of each child ( Coté, 1999 ; McCann and Kain, 2001 ).

Which is the best agent to use for premedication? The sheer volume of articles on the subject in the literature 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 (1959) remarked more than 40 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.”

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, any form other than intramuscular is preferred.
	2.	Children who undergo frequent hospitalizations need as much or more preoperative medication during preparation than do patients undergoing surgery 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. Some children may be sedated, others may be excited and restless. In addition, to obtain a given level of sedation, some children may need half the recommended dose, others may need twice the recommended dose. The dosages in Table 8-3 are intended to serve only as useful guidelines.

TABLE 8-3 -- Guidelines for commonly used preanesthesia medications in children

	ROUTE OF ADMINISTRATION
Medication	*Oral*	*Intravenous*	*Transmucosal*	*Rectal*
Midazolam (mg/kg)	0.25 to 1	0.1	0.2 to 0.3 (nasal)
Morphine (mg/kg)		0.05 to 0.1
Fentanyl (mcg/kg)		0.5 to 1	10 to 15 (oral)
Methohexital (mg/kg)				20 to 30
Ketamine (mg/kg)	5 to 10	1		5 to 10

Anticholinergic Agents

Anticholinergic agents are at present uncommonly used, although in years past they were often administered to prevent unwanted autonomic vagal reflexes or bradycardia associated with airway instrumentation, nasopharyngeal stimulation, and anesthetic drugs, particularly halothane. In addition, these compounds were administered to block the excessive secretions formerly encountered on induction of anesthesia when diethyl ether was commonly administered. There are few indications for routine premedication with an anticholinergic agent, and fewer still that cannot wait until the patient has had anesthesia induced and intravenous access established, allowing intravenous administration of the agent. Like all anesthetic agents, use of anticholinergic agents, whether as premedication or as a vagolytic agent during surgery, should be governed by the same considerations as any anesthetic agent. Side effects (temperature elevation, flushing, dry mouth, and CNS irritability) 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 still must 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

Most pediatric anesthesiologists prefer not to use opioid premedication in infants younger than 6 months ( Kupferberg and Way, 1963 ; Way et al., 1965 ). Opioid premedication can result in unpleasant dysphoria and an increased incidence of preoperative and postoperative vomiting. Opioids can be administered via oral, rectal, intravenous, intramuscular, and transmucosal routes. Interest in the use of opioids as preanesthetic medications has focused on the intranasal ( Henderson et al., 1988 ) and oral transmucosal ( Leiman et al., 1987 ; Nelson et al., 1989 ) forms of administration. 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 ( Stanley et al., 1989 ) and delays the time that children require to tolerate postoperative fluids ( Ashburn et al., 1990 ).

Pharmacokinetic studies have demonstrated that OTFC is absorbed 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%). In blinded studies in children in which OTFC (15 to 20 mcg/kg) was compared with placebo, OTFC was superior to placebo in allowing children to separate from parents and undergo inhalation induction of anesthesia ( Moore et al., 2000 ) but was associated with considerable untoward side effects, including nausea and vomiting, oversedation, and oxygen desaturation ( Nelson et al., 1989 ; Streisand et al., 1989; 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). The optimum dose as a preanesthetic medication appears to be 10 to 15 mcg/kg, whereas the dose for breakthrough cancer pain and postoperative analgesia may be higher (Ashburn et al., 1989, 1993 [8] [9]). Because of the high incidence of reported side effects, as well as the need for continuous pulse oximetry while this drug is administered, OTFC as a preoperative sedative in children has not gained widespread use or popularity.

Hypnotics

Midazolam (Versed) is a water-soluble benzodiazepine with a more rapid onset time and a shorter duration of action than diazepam (Valium). 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 5 to 60 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. 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 ). The experience with midazolam is extensive and demonstrates the drug to be highly effective in alleviating anxiety, increasing cooperation ( Payne et al., 1991a ; Parnis et al., 1992 ; Gillerman et al., 1996 ), and diminishing antegrade recall without affecting retrograde memory ( Twersky et al., 1993 ; McCann and Kain, 2001 ). Premedication with midazolam is safe and free of side effects and 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 ). Furthermore, Davis and others (1995)demonstrated that nasal midazolam (0.2 to 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 on administration because it irritates the nasal passages. Midazolam can also be administered sublingually (0.2 to 0.3 mg/kg), but it may be difficult to prevent small children from either swallowing the midazolam or spitting it out immediately ( Karl et al., 1993 ). 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 1.0 mg/kg was reported to effectively reduce the anxiety of children before induction of anesthesia, although about 20% of the children who receive rectal midazolam develop hiccups ( Marhofer et al., 1999 ).

Flunitrazepam is a benzodiazepine 10 times more potent than diazepam. Its hypnotic and amnesic effects predominate over its sedative, anxiolytic, muscle-relaxing, and anticonvulsant effects. Flunitrazepam is relatively insoluble and has slow times of onset and recovery. Studies of this drug 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 (Halcion) is another benzodiazepine used as a preanesthetic medication. It has a short half-life, reaches peak serum concentrations in 1 to 2 hours, and has no active metabolites ( Pakes et al., 1981 ). Baughman and others (1989) noted that in healthy adult surgical patients, 0.5 mg of triazolam provided better anxiolysis, sedation, and amnesia than placebo but similar anxiolysis and sedation as oral diazepam (15 mg). Its use in pediatric anesthesia is not well established. In children requiring dental procedures, 0.02 mg/kg of triazolam was noted to be as effective as 40 mg/kg of chloral hydrate compared with 25 mg of hydroxyzine ( Meyer et al., 1990 ).

Ketamine

In high doses (4 to 12 mg/kg), intramuscular ketamine has been frequently 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 reported. Rectal administration of ketamine has been reported in children undergoing a wide variety of surgical procedures. Van der Bijl and others (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 and others (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 has also been shown to be an effective means of premedicating children. Weksler and others (1993) demonstrated that 6.0 mg/kg of nasal ketamine 20 to 40 minutes before surgery achieved satisfactory sedation in 78% of the patients.

Oral ketamine has been used as a preoperative anesthetic medication in healthy children undergoing routine surgical procedures and in children undergoing corrective surgery for congenital heart defects (Stewart et al., 1990 ). Gutstein and others (1992) , in a double-blind, prospective study, evaluated placebo and oral ketamine at both 3.0 and 6.0 mg/kg doses as a preanesthetic medication in children. At some time during the study, 100% of the children administered 6.0 mg/kg were sedated as opposed to 73% of the children administered 3.0 mg/kg. In both groups of children who received ketamine, the onset of sedation occurred in 12 minutes, and in the 6.0 mg/kg group, 67% of patients were sufficiently sedated to have an intravenous cannula inserted. Similarly, Funk and others (2000) reported that the combination of oral midazolam and oral ketamine had a 90% success rate of satisfactory anxiolysis compared with less than 75% with either drug alone. 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 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 ).

▪ α₂-ADRENORECEPTOR AGONISTS

The role of α₂-adrenoreceptor agonists is continuing to be developed. 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 ). In children, less is known about the role of α₂-adrenoreceptor agonists. The MAC-sparing effect of premedication with 1 to 10 mcg/kg of oral clonidine has been demonstrated (Nishina et al., 1996, 1997 [116] [117]; Inomata et al., 2002 ). In a double-blind, randomized study, Mikawa and others (1993) demonstrated that in children, oral clonidine could produce sedation in a dose-dependent manner, and that at a dose of 4 mcg/kg, clonidine provided satisfactory sedation and better quality of child/parent separation and facemask acceptance than did standard (0.4 mg/kg) oral diazepam premedication. Fazi and others (2001) showed that oral clonidine was generally inferior to oral midazolam; although clonidine 4 mcg/kg was associated with faster awakening than midazolam 0.5 mg/kg. After clonidine premedication, children were more distressed and agitated during inhalation induction and had higher pain scores and greater analgesic requirement in the postoperative period.

Oral clonidine produces several desirable aspects of a premedication agent, notably sedation and analgesia, but the necessity to administer it 60 minutes before induction renders it an impractical drug to use for this purpose in most practices. In children, peak plasma concentration is at 60 to 90 minutes for orally administered clonidine and 50 minutes for rectally administered clonidine ( Nishina et al., 1999 ).

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

▪ SUMMARY

The pediatric anesthesiologist not only must recognize developmental differences in anatomy and physiology but also must understand and deal effectively with the emotional reactions and needs of children at various ages. Although premedication agents often alleviate the anxieties of anesthesia and surgery, these pharmacologic adjuncts cannot substitute for a thorough and thoughtful preoperative visit and discussion with the patient and family.

Motoyama & Davis: Smith's Anesthesia for Infants and Children, 7th ed.

REFERENCES

Abraham and Aldridge, 1993. Abraham H, Aldridge A: Adverse consequences of lysergic acid diethylamide. Addiction 1993; 88:1327-1334.

Abraham et al., 1996. Abraham H, Aldridge A, Gogia P: The psychopharmacology of hallucinogens. Neuropsycopharma 1996; 14:285-298.

Albertson et al., 1999. Albertson TE, Derlet RW, Van Hoozen BE: Methamphetamine and the expanding complications of amphetamines. West J Med 1999; 170:214-219.

Albrecht et al., 2000. Albrecht CA, Jafri A, Linville L, et al: Cocaine-induced pneumopericardium. Circulation 2000; 102:2792-2794.

American Academy of Pediatrics Committee on Hospital Care, 1993. American Academy of Pediatrics Committee on Hospital Care : Child life programs. Pediatrics 1993; 91:671-673.

Ang-lee et al., 2001. Ang-lee MK, Moss J, Yuan CS: Herbal medicines and perioperative care. JAMA 2001; 286:208.

Arthur and McNichol, 1986. Arthur DS, McNichol LR: Local anaesthetic techniques in paediatric surgery. Br J Anaesth 1986; 58:760.

Ashburn et al., 1989. Ashburn MA, Fine PG, Stanley TH: Oral transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: A case report. Anesthesiology 1989; 71:615.

Ashburn et al., 1993. Ashburn MA, Lind GH, Gillie MN, et al: Oral transmucosal fentanyl citrate (OTFC) for the treatment of postoperative pain. Anesth Analg 1993; 76:377.

Ashburn et al., 1990. Ashburn MA, Streisand JB, Tarver SD, et al: Oral transmucosal fentanyl citrate for premedication in paediatric outpatients. Can J Anaesth 1990; 37:857.

Baughman et al., 1989. Baughman VL, Becker GL, Ryan CM, et al: Effectiveness of triazolam, diazepam, and placebo as preanesthetic medications. Anesthesiology 1989; 71:196.

Beal, 1992. Beal JA: Latex allergy risk management considerations. Implant Soc 1992; 3:5.

Beecher, 1959. Beecher H: Measurement of subjective responses—a quantitative effect of drugs, New York, Oxford University Press, 1959.

Bellew et al., 2002. Bellew M, Atkinson KR, Dixon G, et al: The introduction of a paediatric anaesthesia information leaflet: An audit of its impact on parental anxiety and satisfaction. Paediatr Anaesth 2002; 12:124-130.

Berman et al., 1982. Berman W, Yabek SM, Dillon T: Evaluation of infants with bronchopulmonary dysplasia using cardiac catheterization. Pediatrics 1982; 55:783.

Bhatt-Mehta and Rosen, 1991. Bhatt-Mehta V, Rosen DA: Management of acute pain in children. Clin Pharm 1991; 10:667.

Black, 1999. Black AE: Medical assessment of the paediatric patient. Br J Anaesth 1999; 83:3-15.

Boot et al., 2000. Boot BP, McGregor IS, Hall W: MDMA (Ecstasy) neurotoxicity: Assessing and communicating the risks. Lancet 2000; 355:1818-1821.

Bordet et al., 2002. Bordet F, Allaouchiche B, Lansiaux S, et al: Risk factors for airway complications during general anaesthesia in paediatric patients. Paediatr Anaesth 2002; 12:762-769.

Brock-Utne et al., 1978. Brock-Utne JG, Rubin J, Wilman S, et al: The effect of glycopyrrolate (Robinul) on the lower esophageal sphincter. Can Anaesth Soc J 1978; 25:14.

Brogan et al., 1991. Brogan 3rd WC, Lange RA, Kim AS, et al: Alleviation of cocaine-induced coronary vasoconstriction by nitroglycerin. J Am Coll Cardiol 1991; 18:581-586.

Brosius and Bannister, 2002. Brosius KK, Bannister CF: Oral midazolam premedication in preadolescents and adolescents. Anesth Analg 2002; 94:31-36.

Brownell et al., 1983. Brownell AKW, Paasuke RT, Elash A, et al: Malignant hyperthermia in Duchenne muscular dystrophy. Anesthesiology 1983; 58:180.

Brust, 1993. Brust JC: Clinical, radiological, and pathological aspects of cerebrovascular disease associated with drug abuse. Stroke 1993; 24(Suppl I):I-129-I-133.discussion I-134–I-135

Carabine et al., 1991. Carabine UA, Wright PMC, Moore J: Preanesthetic medication with clonidine: A dose-response study. Br J Anaesth 1991; 67:79.

Christophersen, 2000. Christophersen AS: Amphetamine designer drugs—an overview and epidemiology. Toxicol Lett 2000; 112/113:127-131.

Cohen and Cameron, 1991. Cohen MM, Cameron CB: Should you cancel the operation when a child has an upper respiratory tract infection?. Anesth Analg 1991; 72:282.

Coté, 1990. Coté CJ: NPO after midnight for children—a reappraisal. Anesthesiology 1990; 72:589.

Coté et al., 1986. Coté CJ, Todres ID, Ryan JF: Preoperative evaluation of pediatric patients. In: Ryan JF, Todres ID, Coté CJ, Goudsouzian N, ed. A practice of anesthesia for infants and children, New York: Grune & Stratton; 1986:27.

Coté et al., 1995. Coté CJ, Zaslavsky A, Downes JJ, et al: Postoperative apnea in former preterm infants after inguinal herniorrhaphy: A combined analysis. Anesthesiology 1995; 82:809-822.

Coté, 1999. Coté CJ: Preoperative preparation and premedication. Br J Anaesth 1999; 83:16-28.

Dalens et al., 1986. Dalens B, Tanguy A, Haberer JP: Lumbar epidural anesthesia for operative and postoperative pain relief in infants and young children. Anesth Analg 1986; 65:1069.

Dar and McBrien, 1996. Dar KJ, McBrien ME: MDMA induced hyperthermia: Report of a fatality and review of current therapy. Intensive Care Med 1996; 22:995-996.

Davis et al., 1995. Davis P, Tome J, McGowan F, et al: Preanesthetic medication with intranasal midazolam for brief surgical procedures. Anesthesiology 1995; 82:2-5.

Davis, 1995. Davis PJ, et al: Preanesthetic medication with intranasal midazolam for brief pediatric surgical procedures: Effect on recovery and hospital discharge times. Anesthesiology 1995; 82:2-5.

DeSoto et al., 1988. DeSoto H, Patel RI, Soliman IE, et al: Changes in oxygen saturation following general anesthesia in children with upper respiratory infection and symptoms undergoing otolaryngological procedures. Anesthesiology 1988; 68:276.

Drummond, 1984. Drummond JC: Of venous air embolism, aminophylline, and volatile agents. Anesthesiology 1984; 60:389.

Elwood et al., 2003. Elwood T, Morris W, Martin LD, et al: Bronchodilator premedication does not decrease respiratory adverse events in pediatric general anesthesia. Can J Anaesth 2003; 50:277-284.

Emerson et al., 1998. Emerson BM, Wrigley SR, Newton M: Pre-operative fasting for paediatric anaesthesia. A survey of current practice. Anaesthesia 1998; 53:326-330.

Esteve and Saint-Maurice, 1990. Esteve C, Saint-Maurice C: Rectal flunitrazepam as premedication in preschool children. A double-blind, randomized study. Acta Anaesthesiol Scand 1990; 34:662.

Fazi et al., 2001. Fazi L, Jantzen EC, Rose JB, et al: A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient. Anesth Analg 2001; 92:56-61.

Feldman et al., 2000. Feldman JA, Fish SS, Beshansky JR, et al: Acute cardiac ischemia in patients with cocaine-associated complaints: Results of a multicenter trial. Ann Emerg Med 2000; 36:469-476.

Ferrari et al., 1999. Ferrari LR, Rooney FM, Rockoff MA: Preoperative fasting practices in pediatrics. Anesthesiology 1999; 90:978-980.

Fishchler, 1992. Fishchler M: Patent foramen ovale and sitting position. Anesthesiology 1992; 76:46.

Fleming et al., 1990. Fleming JA, Byck R, Barash PG: Pharmacology and therapeutic applications of cocaine. Anesthesiology 1990; 73:518-531.

Funk et al., 2000. Funk W, Jakob W, Reidl T, et al: Oral preanaesthetic medication for children: Double-blind randomized study of a combination of midazolam and ketamine vs midazolam or ketamine alone. Br J Anaesth 2000; 84:335-340.

Gauderer et al., 1989. Gauderer MW, Lorig JL, Eastwood DW: Is there a place for parents in the operating room?. J Pediatr Surg 1989; 24:705-706.

Genever, 1971. Genever EE: Suxamethonium-induced cardiac arrest in unsuspected pseudohypertrophic muscular dystrophy: Case report. Br J Anesth 1971; 43:984.

Ghignone et al., 1987. Ghignone M, Calvillo O, Quintin L: Anesthesia and hypertension: The effects of clonidine on perioperative hemodynamics and isoflurane requirements. Anesthesiology 1987; 67:3.

Ghoneim and Korttila, 1977. Ghoneim MM, Korttila K: Pharmacokinetics of intravenous anaesthetics: Implications for clinical use. Clin Pharmacokinet 1977; 2:344.

Ghuran and Nolan, 2000. Ghuran A, Nolan J: Recreational drug misuse: Issues for the cardiologist. Heart 2000; 83:627-633.

Gillerman et al., 1996. Gillerman RG, Hinkle AJ, Green HM, et al: Parental presence plus oral midazolam decreases frequency of 5% halothane inductions in children. J Clin Anesth 1996; 8:480-485.

Griffith et al., 1998. Griffith N, Howell S, Mason D: Intranasal midazolam for premedication of children undergoing day-case anaesthesia: Comparison of two delivery systems with assessment of intra-observer variability. Br J Anaesth 1998; 81:65-69.

Gutstein et al., 1992. Gutstein HB, Johnson KL, Heard MB, et al: Oral ketamine preanesthetic medication in children. Anesthesiology 1992; 76:28.

Hall, 1997a. Hall AP: “Ecstasy” and the anaesthetist. Br J Anaesth 1997; 79:697-698.

Hall, 1997b. Hall AP: Ecstasy: Creatinine kinase. Anaesth Intens Care 1997; 25:586-587.

Hall and Solowij, 1998. Hall W, Solowij N: Adverse effects of cannabis. Lancet 1998; 352:1611-1616.

Hannallah and Patel, 1989. Hannallah R, Patel RI: Low-dose intramuscular ketamine for anesthesia pre-induction in young children undergoing brief outpatient procedures. Anesthesiology 1989; 70:598.

Henderson et al., 1988. Henderson JM, Brodsky DA, Fisher DM, et al: Pre-induction of anesthesia in pediatric patients with nasally administered sufentanil. Anesthesiology 1988; 68:671.

Henry, 2000. Henry J: Metabolic consequences of drug misuse. Br J Anaesth 2000; 85:136-142.

Hollander, 1995. Hollander JE: The management of cocaine-associated myocardial ischemia. N Engl J Med 1995; 333:1267-1272.

Inaba et al., 1978. Inaba T, Stewart DJ, Kalow W: Metabolism of cocaine in man. Clin Pharmacol Ther 1978; 23:547-552.

Inomata et al., 2002. Inomata S, Kihara S, Miyabe M, et al: The hypnotic and analgesic effects of oral clonidine during sevoflurane anesthesia in children: A dose-response study. Anesth Analg 2002; 94:1479-1483.table of contents

Jansen, 1993. Jansen K: Non-medical use of ketamine. BMJ 1993; 306:601-602.

Johnston et al., 1994. Johnston L, O'Malley P, Bachman J: National survey results on drug use from the monitoring the future study, 1975–1993. Volume I: Secondary school students, DHHS Publication No. [NIH] 94–0000, . Rockville, MD, National Institute on Drug Abuse, 1994.

Julien, 1994. Julien R: Psychostimulants: Cocaine and amphetamines, ed 7. New York, W.H. Freeman, 1994.

Kain, 2001. Kain Z: Parental presence and premedication revisited. Curr Opin Anesth 2001; 14:331-337.

Kain et al., 1997. Kain Z, Mayes LC, Bell C, et al: Premedication in the United States: A status report. Anesth Analg 1997; 84:427-432.

Kain and Rosenbaum, 1994. Kain Z, Rosenbaum H: Physiology and management of cocaine exposure preceding emergency anesthesia and surgery. Curr Opin Anesthesiol 1994; 7:293-298.

Kain et al., 1996. Kain ZN, Mayes LC, Caramico LA, et al: Parental presence during induction of anesthesia. A randomized controlled trial. Anesthesiology 1996; 84:1060-1067.

Kain et al., 1993. Kain ZN, Rimar S, Barash PG: Cocaine abuse in the parturient and effects on the fetus and neonate. Anesth Analg 1993; 77:835-845.

Kam et al., 1998. Kam PC, Voss TJ, Gold PD, et al: Behaviour of children associated with parental participation during induction of general anaesthesia. J Paediatr Child Health 1998; 34:29-31.

Karl et al., 1993. Karl HW, Rosenberger JL, Larach MG, et al: Transmucosal administration of midazolam for premedication of pediatric patients. Comparison of the nasal and sublingual routes. Anesthesiology 1993; 78:885-891.

Katz and Steward, 1987. In: Katz J, Steward DJ, ed. Anesthesia and uncommon pediatric diseases, Philadelphia, PA: WB Saunders; 1987.

Kelfer et al., 1983. Kelfer HM, Singer WD, Reynolds RN: Malignant hyperthermia in a child with Duchenne muscular dystrophy. Pediatrics 1983; 71:118.

Kinouchi et al., 1992. Kinouchi K, Tanigami H, Tashiro C, et al: Duration of apnea in anesthetized infants and children required for desaturation of hemoglobin to 95%. The influence of upper respiratory infection. Anesthesiology 1992; 77:1105.

Kloner et al., 1992. Kloner RA, Hale S, Alker K, et al: The effects of acute and chronic cocaine use on the heart. Circulation 1992; 85:407-419.

Ko et al., 2001. Ko YP, Huang CJ, Hung YC, et al: Premedication with low-dose oral midazolam reduces the incidence and severity of emergence agitation in pediatric patients following sevoflurane anesthesia. Acta Anaesthesiol Sin 2001; 39:169-177.

Koinig, 2002. Koinig H: Preparing parents for their child's surgery: Preoperative parental information and education. Paediatr Anaesth 2002; 12:107-109.

Korsch, 1975. Korsch BM: The child and the operating room. Anesthesiology 1975; 43:251.

Kotiniemi et al., 1996. Kotiniemi LH, Ryhanen PT, Moilanen IK: Behavioural changes following routine ENT operations in two-to-ten-year-old children. Paediatr Anaesth 1996; 6:45-49.

Krane et al., 1987. Krane EJ, Jacobson LE, Lynn AM, et al: Caudal morphine for postoperative analgesia in children. Anesth Analg 1987; 66:647.

Kupferberg and Way, 1963. Kupferberg HJ, Way EL: Pharmacologic basis for the increased sensitivity of the newborn rat to morphine. J Pharmacol Exp Ther 1963; 141:105.

Kurth and LeBard, 1991. Kurth CD, LeBard SE: Association of postoperative apnea, airway obstruction and hypoxemia in former premature infants. Anesthesiology 1991; 75:22.

Kurth et al., 1986. Kurth CD, Spitzer AR, Broennie AM, et al: Postoperative apnea in preterm infants. Anesthesiology 1986; 66:483.

Leigh et al., 1977. Leigh JM, Walker J, Janaganathan P: Effect of preoperative anaesthetic visit on anxiety. Br J Med 1977; 2:987.

Leiman et al., 1987. Leiman BC, Walford A, Rawal N, et al: The effects of oral transmucosal fentanyl citrate premedication on gastric volume and acidity in children. Anesthesiology 1987; 87:A489.

Levy et al., 1992. Levy DA, Charpin D, Pecquet C, et al: Allergy to latex. Allergy 1992; 47:579.

Levy et al., 1992. Levy L, Pandit UA, Randel GI, et al: Upper respiratory tract infections and general anaesthesia in children. Perioperative complications and oxygen saturation. Anaesthesia 1992; 47:678.

Liu et al., 1980. Liu LMP, Coté CJ, Goudsouzian NG, et al: Life-threatening apnea in infants recovering from anesthesia. Anesthesiology 1980; 59:283.

Lockhart, 1984. Lockhart CH: Preoperative preparation of the child for hospitalization, anesthesia, and surgery. Annual Refresher Course Lectures, American Society of Anesthesiologists, Philadelphia, No. 125, 1984, Lippincott.

Lynn, 1985. Lynn AM: Unusual conditions in paediatric anaesthesia. Clin Anaesth 1985; 3:379.

Malviya et al., 1993. Malviya S, Swartz J, Lerman J: Are all preterm infants younger than 60 weeks post conceptual age at risk for postanesthetic apnea?. Anesthesiology 1993; 78:1076.

Marhofer et al., 1999. Marhofer P, Glaser C, Krenn CG, et al: Incidence of therapy of midazolam induced hiccups in paediatric anaesthesia. Paediatr Anaesth 1999; 9:295-298.

Martin et al., 2003. Martin JA, Hamilton BE, Sutton PD, et al: Births: Final data for 2002. National vital statistics reports, Hyattsville, MD, National Center for Health Statistics, 2003. publication 52(10).

Mather and Mackie, 1983. Mather L, Mackie J: The incidence of postoperative pain in children. Pain 1983; 15:271.

McCann and Kain, 2001. McCann M, Kain ZN: Management of preoperative anxiety in children: An update. Anesth Analg 2001; 93:98-105.

McMillan et al., 1992. McMillan CO, Spahr Schopfer IA, Sikich N, et al: Premedication of children with oral midazolam. Can J Anaesth 1992; 39:545.

Meeropol et al., 1993. Meeropol E, Frost J, Pugh L, et al: Latex allergy in children with myelodysplasia: A survey of Shriners hospitals. J Pediatr Orthop 1993; 13:1.

Meyer et al., 1990. Meyer ML, Mourino AP, Farringtron FH: Comparison of triazolam to a chloral hydrate/hydroxyzine combination in the sedation of pediatric dental patients. Pediatr Dent 1990; 12:283.

Mikawa et al., 1993. Mikawa K, Mackawa N, Nishina K, et al: Efficacy of oral clonidine premedications in children. Anesthesiology 1993; 79:926.

Miller and Friesen, 1987. Miller BR, Friesen RH: Oral atropine premedication in infants. Anesthesiology 1987; 67:A491.

Miller et al., 1990. Miller BR, Tharp JA, Isaacs WB: Gastric residual volume in infants and children following a 3-hour fast. J Clin Anesth 1990; 2:301.

Miller et al., 1978. Miller Jr ED, Sanders DB, Rowlington JC, et al: Anesthesia-induced rhabdomyolysis in a patient with Duchenne's muscular dystrophy. Anesthesiology 1978; 48:146.

Milroy, 1999. Milroy CM: Ten years of “ecstasy.”. J R Soc Med 1999; 92:68-71.

Miluk-Kolasa et al., 1994. Miluk-Kolasa B, Obminski Z, Stupnicki R, et al: Effects of music treatment on salivary cortisol in patients exposed to pre-surgical stress. Exp Clin Endocrinol 1994; 102:118-120.

Mittleman et al., 1999. Mittleman MA, Mintzer D, Maclure M, et al: Triggering of myocardial infarction by cocaine. Circulation 1999; 99:2737-2741.

Moore et al., 2000. Moore PA, Cuddy MA, Magera JA, et al: Oral transmucosal fentanyl pretreatment for outpatient general anesthesia. Anesth Prog 2000; 47:29-34.

Moore et al., 1987. Moore RA, McNicholas KW, Warren SP: Atlantoaxial subluxation with symptomatic spinal cord compression in a child with Down's syndrome. Anesth Analg 1987; 66:89.

Morris and Magee, 1995. Morris G, Magee P: Anaesthesia and past use of LSD. Can J Anaesth 1995; 42:177.

Mouhaffel et al., 1995. Mouhaffel AH, Madu EC, Satmary WA, et al: Cardiovascular complications of cocaine. Chest 1995; 107:1426-1434.

Musty et al., 1995. Musty R, Reggio P, Consroe P: A review of recent advances in cannabinoid research and the 1994 International Symposium on Cannabis and the Cannabinoids. Life Sci 1995; 56:1933-1940.

Nelson et al., 1989. Nelson PS, Streisand JB, Mulder SM, et al: Comparison of oral transmucosal fentanyl citrate and an oral solution of meperidine, diazepam, and atropine for premedication in children. Anesthesiology 1989; 70:616.

NIH Consensus Development Panel on Acupuncture, 1998. NIH Consensus Development Panel on Acupuncture : Acupuncture. JAMA 1998; 280:1518-1524.

Nishina et al., 1999. Nishina K, Mikawa K, Shiga M, et al: Clonidine in paediatric anaesthesia. Paediatr Anaesth 1999; 9:187-202.

Nishina et al., 1996. Nishina K, Mikawa K, Maekawa N, et al: The efficacy of clonidine for reducing perioperative haemodynamic changes and volatile anaesthetic requirements in children. Acta Anaesthesiol Scand 1996; 40:746-751.

Nishina et al., 1997. Nishina K, Mikawa K, Shiga M, et al: Oral clonidine premedication reduces minimum alveolar concentration of sevoflurane for tracheal intubation in children. Anesthesiology 1997; 87:1324-1327.

Nolan et al., 2000. Nolan J, Chalkiadis GA, Low J, et al: Anaesthesia and pain management in cerebral palsy. Anaesthesia 2000; 55:32-41.

Pakes et al., 1981. Pakes GE, Brogden RN, Heel RC, et al: Triazolam: A review of its pharmacological properties and therapeutic efficacy in patients with insomnia. Drugs 1981; 22:81.

Parnis et al., 2001. Parnis SJ, Barker DS, van der Walt JH: Clinical predictors of anaesthetic complications in children with respiratory tract infections. Paediatr Anaesth 2001; 11:29-40.

Parnis et al., 1992. Parnis SJ, Foate JA, van der Walt JH, et al: Oral midazolam is an effective premedication for children having day-stay anaesthesia. Anaesth Intensive Care 1992; 20:9-14.

Payne et al., 1991a. Payne KA, Coetzee AR, Mattheyse FJ: Midazolam and amnesia in pediatric premedication. Acta Anaesthesiol Belg 1991; 42:101.

Payne et al., 1991b. Payne KA, Coetzee AR, Mattheyse FJ, et al: Oral midazolam in paediatric premedication. S Afr Med J 1991; 79:372.

Perez-Reyes et al., 1982. Perez-Reyes M, Di Guiseppi S, Ondrusek G, et al: Free-base cocaine smoking. Clin Pharmacol Ther 1982; 32:459-465.

Pitts et al., 1997. Pitts W, Lange R, Cigarroa J, et al: Cocaine-induced myocardial ischemia and infarction: Physiology, pathology, recognition, and management. Prog Cardiovasc Dis 1997; 40:65-76.

Rainey and van der Walt, 1998. Rainey L, van der Walt JH: The anaesthetic management of autistic children. Anaesth Intensive Care 1998; 26:682-686.

Reneman et al., 2000. Reneman L, Habraken JB, Majoie CB, et al: MDMA (“Ecstasy”) and its association with cerebrovascular accidents: Preliminary findings. AJNR Am J Neuroradiol 2000; 21:1001-1007.

Reves et al., 1985. Reves JG, Fragen RJ, Vinik HR, et al: Midazolam: Pharmacology and uses. Anesthesiology 1985; 62:310.

Rezkalla et al., 1993. Rezkalla SH, Mazza JJ, Kloner RA, et al: Effects of cocaine on human platelets in healthy subjects. Am J Cardiol 1993; 72:243-246.

Richardson and Manford, 1979. Richardson F, Manford M: Comparison of flunitrazepam and diazepam for oral premedication in older children. Br J Anaesth 1979; 51:313.

Rittoo and Rittoo, 1992. Rittoo DB, Rittoo D: Complications of “ecstasy” misuse. Lancet 1992; 340:725-726.

Rolf and Coté, 1992. Rolf N, Coté CJ: Frequency and severity of desaturation events during general anesthesia in children with and without upper respiratory infections. J Clin Anesth 1992; 4:200.

Rosenberg and Heiman-Patterson, 1983. Rosenberg H, Heiman-Patterson T: Duchenne's muscular dystrophy and malignant hyperthermia: another warning [letter]. Anesthesiology 1983; 59:362.

Saint-Maurice et al., 1979. Saint-Maurice C, Laguenie G, Couturier C, et al: Rectal ketamine in paediatric anaesthesia. Br J Anaesth 1979; 51:573.

Saint-Maurice et al., 1986. Saint-Maurice C, Meistelman C, Rey E, et al: The pharmacokinetics of rectal midazolam for premedication in children. Anesthesiology 1986; 65:536.

Schechter, 1986. Schechter NL: Status of pediatric pain control. Pediatrics 1986; 77:11.

Schein and Winoker, 1975. Schein PS, Winoker SH: Immunosuppressive and cytotoxic chemotherapy: Long-term complications. Ann Intern Med 1975; 82:84.

Schreiner et al., 1990. Schreiner MS, Triebwasser A, Keon TP: Ingestion of liquids compared with perioperative fasting in pediatric outpatients. Anesthesiology 1990; 72:593.

Schwartz, 1987. Schwartz R: Marijuana: An overview. Pediatr Clin North Am 1987; 34:305-317.

Seay et al., 1978. Seay AR, Ziter FA, Thompson JA: Cardiac arrest during induction of anesthesia in Duchenne muscular dystrophy. J Pediatr 1978; 93:88.

Selvin, 1981. Selvin BL: Cancer chemotherapy: Implications for the anesthesiologist. Anesth Analg 1981; 60:425.

Shulgin, 1986. Shulgin A: The background and chemistry of MDMA. J Psychoactive Drugs 1986; 18:291-304.

Sievers et al., 1991. Sievers TD, Yee JD, Foley ME, et al: Midazolam for conscious sedation during pediatric oncology procedures: Safety and recovery parameters. Pediatrics 1991; 88:172.

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

Spear, 1992. Spear RM: Anesthesia for premature and term infants: Perioperative implications. J Pediatr 1992; 120:165.

Stanley et al., 1989. Stanley TH, Leiman BC, Rawal N, et al: The effects of oral transmucosal and gastric volume and acidity in children. Anesth Analg 1989; 69:328.

Steward, 1983. Steward DJ: Psychological preparation and premedication. In: Gregory GA, ed. Pediatric anesthesia, New York: Churchill Livingstone; 1983.

Stewart et al., 1990. Stewart KG, Rowbottom SJ, Aiken AW, et al: Oral ketamine premedication for paediatric cardiac surgery—a comparison with intramuscular morphine (both after oral trimeprazine). Anaesth Intensive Care 1990; 18:11.

Stiles, 1981. Stiles CM: Anesthesia for the mentally retarded patient. Orthop Clin North Am 1981; 12:45.

Stoelting, 1978. Stoelting RK: Responses to atropine, glycopyrrolate, and Riopan on gastric fluid pH and volume in adult patients. Anesthesiology 1978; 18:367.

Streisand et al., 1991. Streisand JB, Varvel JR, Stanski DR, et al: Absorption and bioavailability of oral transmucosal fentanyl citrate. Anesthesiology 1991; 75:223.

Sussman, 1992. Sussman GL: Latex allergy: Its importance in clinical practice. Allergy Proc 1992; 13:67.

Tait and Knight, 1987. Tait AR, Knight PR: The effects of general anesthesia on upper respiratory tract infections in children. Anesthesiology 1987; 67:930.

Tait et al., 2001. Tait AR, Malviya S, Voepel-Lewis T, et al: Risk factors for perioperative adverse respiratory events in children with upper respiratory tract infections. Anesthesiology 2001; 95:299-306.

Tait and Malviya, 2005. Tait AR, Malviya S: Anesthesia for the child with an upper respiratory tract infection: Still a dilemma?. Anesthesiol Analg 2005; 100:59-65.

Thorn et al., 1977. Thorn GW, Adams RD, Braunwaid E, et al: Harrison's principles of internal medicine, ed 8. New York, McGraw-Hill Book Co., 1977.

Tobias et al., 1992. Tobias JD, Phipps S, Smith B, et al: Oral ketamine premedication to alleviate the distress of invasive procedures in pediatric oncology patients. Pediatrics 1992; 90:537.

Twersky et al., 1993. Twersky RS, Hartung J, Berger BJ, et al: Midazolam enhances antegrade but not retrograde amnesia in pediatric patients. Anesthesiology 1993; 78:51.

Van der Bijl et al., 1991. Van der Bijl P, Roelofse JA, Stander IA: Rectal ketamine and midazolam for premedication in pediatric dentistry. J Oral Maxillofac Surg 1991; 49:1050.

van der Walt and Moran, 2001. van der Walt JH, Moran C: An audit of perioperative management of autistic children. Paediatr Anaesth 2001; 11:401-408.

Vernon and Bailey, 1974. Vernon DTA, Bailey WC: The use of motion pictures in the psychological preparation of children for induction of anesthesia. Anesthesiology 1974; 40:68.

Vichinsky et al., 1995. Vichinsky EP, Haberkern CM, Neumayr L, et al: The Preoperative Transfusion in Sickle Cell Disease Study Group: A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. N Engl J Med 1995; 333:206-213.

Viitanen et al., 1999. Viitanen H, Annila P, Viitanen M, et al: Midazolam premedication delays recovery from propofol-induced sevoflurane anesthesia in children 1–3 yr. Can J Anaesth 1999; 46:766-771.

Visintainer and Wolfer, 1975. Visintainer MA, Wolfer JA: Psychological preparation for surgical pediatric patients: The effect on children's and parent's stress responses and adjustment. Pediatrics 1975; 56:187.

Way et al., 1965. Way WL, Costley EC, Way EL: Respiratory sensitivity of the newborn infant to meperidine and morphine. Clin Pharmacol Ther 1965; 6:454.

Weksler et al., 1993. Weksler N, Ovadia L, Muati G, et al: Nasal ketamine for paediatric premedication. Can J Anaesth 1993; 40:119.

Weldon et al., 1992. Weldon BC, Watcha MF, White PF: Oral midazolam in children: Effect of time and adjunctive therapy. Anesth Analg 1992; 75:51.

Wellborn et al., 1991. Wellborn LG, Hannallah RS, Luban NL, et al: Anemia and postoperative apnea in former preterm infants. Anesthesiology 1991; 74:1003.

Wellborn et al., 1986. Wellborn LG, Ramirez N, Oh TH, et al: Postanesthetic apnea and periodic breathing in infants. Anesthesiology 1986; 65:658.

Wilbert-Lampen et al., 1998. Wilbert-Lampen U, Seliger C, Zilker T, et al: Cocaine increases the endothelial release of immunoreactive endothelin and its concentrations in human plasma and urine: Reversal by coincubation with sigma-receptor antagonists. Circulation 1998; 98:385-390.

Williams et al., 1987. Williams JO, Somerville GM, Miner ME, et al: Atlanto-axial subluxation and trisomy-21: Another perioperative complication. Anesthesiology 1987; 67:253.

Wright et al., 1990. Wright PMC, Carabine UA, McClune S, et al: Preanesthetic medication with clonidine. Br J Anaesth 1990; 65:628.

Wyant, 1971. Wyant GM: Intramuscular ketalar (CI-581) in paediatric anaesthesia. Can Anaesth Soc J 1971; 18:72.

Yassin et al., 1992. Yassin MS, Sanyurah S, Lierl MB, et al: Evaluation of latex allergy in patients with meningomyelocele. Ann Allergy 1992; 69:207.

Yaster et al., 1989. Yaster M, Deshpande JK, Maxwell LG: The pharmacologic management of pain in children. Compre Ther 1989; 15:14.

Zuwala and Barber, 2001. Zuwala R, Barber KR: Reducing anxiety in parents before and during pediatric anesthesia induction. AANA J 2001; 69:21-25.

Page

Contents

If you find an error or have any questions, please email us at admin@doctorlib.org. Thank you!