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

PART FOUR – Associated Problems in Pediatric Anesthesia

Chapter 35 – History of Pediatric Anesthesia

Robert M. Smith,Mark A. Rockoff



Phase I: Pediatric Anesthesia Before 1940, 1173



Primitive Period, 1173



Early Control of Pain: Ether and Chloroform,1173



Phase II: Emergence of Pediatric Anesthesia (1940-1960), 1175



Factors in the Rapid Development of Interest,1175



Foundations of Clinical Control and Support,1176



Teaching and Research, 1180



Phase III: Era of Nonflammable Anesthetics (1960-1980), 1180



Increasing Clinical Precision, 1181



Surgical Progress, 1181



Postoperative Patient Management: Ventilation, Resuscitation, and Intensive Care,1182



Organized Teaching, 1182



Phase IV: Progress and Sophistication (1980-Present), 1183



Recognition of Risk, 1183



Growth in Pediatric Facilities, 1183



Changing Patterns of Care, 1183



New Developments in Anesthesia,1184



Progress in Monitoring, 1185



Advances in Surgery, 1185



Research Efforts, 1185



Development of the Subspecialty, 1186



Summary, 1186

The goal of the individual pediatric anesthesiologist is generally neither to diagnose nor to cure but rather to guide and support each young patient through the operative experience with the least possible mental and physical stress. The history of pediatric anesthesia is best told by tracing the steps toward increasing precision in the regulation (maintaining within normal limits) or controlling (carrying beyond normal limits) of neurologic, respiratory, cardiovascular, and other body systems to serve both surgeon and child ( Smith, 1991 ).

The goals of pediatric anesthesiology as a specialty include the reduction of perioperative morbidity and mortality and the promotion of ancillary resuscitative and supportive fields through teaching, research, and organizational activity throughout the world.



Before the introduction of ether in 1846, not only circumcisions but amputations, excisions of tumors, and correction of gross deformities were performed on infants and children without any relief of pain. Struggling could be controlled by use of force, but pain was accepted as an unavoidable part of life. Crude attempts occasionally made with alcoholic “spirits,” nerve compression, or even brief strangling, coupled with headlong surgical speed, resulted in predictably poor outcome for both operation and patient. Harelip repair had been attempted without pain relief measures in many parts of the world for hundreds of years. In Japan, general anesthesia with the herb mixture tsu san sen was used successfully for breast cancer operations in 1804 by Seishu Hanaoka. In 1837, Gancho Homma reported a series of general anesthesia with the use of the same herb mixture for children over 5 years of age for harelip repair but withheld it from use in younger patients because of its toxicity ( Iwai and Satoyoshi, 1992 ). The conviction that small infants did not need anesthesia was not effectively suppressed until recently ( Anand and Hickey, 1987 ). For many years, the “whiskey nipple” had been used widely as a sedative supplement to local anesthesia in infants undergoing abdominal procedures; wine has been given for ritual circumcisions for millennia.


The introduction of ether was the first giant step in the history of anesthesia. Although Crawford Long used ether in his rural practice in Georgia beginning in 1842 and his third ether anesthetic procedure was for a toe amputation in a 7-year-old boy ( Long, 1849 ), it was not until the famous public demonstration of ether anesthesia at the Massachusetts General Hospital in Boston in 1846 that ether was widely accepted for use during surgery ( Morton, 1847 ). The discovery that sensation, or pain, could be abolished temporarily by ether, and along with it consciousness and motion, was widely acclaimed, but little was known about its actions, how to use it, or what its dangers might be. Ether was accepted only gradually over several years, with many surgeons retaining the belief that ordinary men (the wealthy excluded) should be able to tolerate surgery without anesthesia! However, for children and ladies, who were considered to be “more sensitive,” anesthesia was considered appropriate ( Warren, 1847; Pernick, 1975 ), although Morton himself was reluctant to administer it to very young subjects because of the high incidence of nausea and vomiting in this population ( Bigelow, 1846 ).

It was soon found that pouring ether onto a handkerchief or small cloth was a practical method of administration with small children. One simply pressed the cloth to the patient's face until the child was quiet and limp. Then it was withdrawn, and the surgeon was granted 3 or 4 minutes to operate as the child regained consciousness. The use of continuous administration of ether caught on slowly with gradual familiarization with the new agent. The early impression that ether was easy to administer, effective, and safe led to the belief that it was a trivial service that any inexperienced person, often an orderly or a parent, could perform. The unfortunate result of this in the United States was that throughout the rest of the century, the administration of anesthesia continued to be held in poor repute as a medical activity, rarely attracting physicians with special interest or ability in the field. Nurses eventually began to assume increasing responsibilities for providing anesthesia care. As late as 1940, a physician, in the lead article published in the first edition of the new journal Anesthesiology, noted, “During my internship I was trained by a nurse. I was given a cone, a can of ether and a few empirical tricks” ( Haggard, 1940 ).

In England, chloroform was accepted more readily because of its smoother and more rapid action. Soon, however, the incidence of deaths became so alarming that the British established a dictum that only physicians should be allowed to administer anesthesia ( Eckenhoff, 1966 ). The fortunate result was that throughout the British Empire anesthesia flourished as a medical specialty, its workers gaining equal status with other physicians, and establishing early leadership in this field for several decades, particularly in the development of pediatric anesthesia.

Another great advantage for the British in the early development of anesthesia was the presence of the astounding John Snow (1813-1858), whose contributions included epidemiologic advances of national importance and an active medical practice while keeping notes on hundreds of anesthetic experiences and research experiments, mostly between 1846 and his death a decade later ( Griffith, 1934 ). Snow formulated the first description of signs by which one could monitor and control the depth of anesthesia in patients of all ages ( Snow, 1847 ). His five stages of anesthesia, based on excitement, loss of consciousness, relaxation, eye movement, and depth of respiration, served as guidelines throughout the remainder of the century and formed the basis of Guedel's important guide Inhalation Anesthesia,published in 1937. Snow explored both ether and chloroform, preferring the latter, which he found well suited to infants and children. However, he warned of its danger with excessive depth ( Snow, 1858 ). His record of successfully anesthetizing 147 infants for harelip repair is hardly conceivable in view of the mortality that this operation continued to bear well into the next century!

Following the remarkable beginning made by Snow, anesthesia in England progressed at a slower pace. For nearly 20 years, chloroform and ether remained the only anesthetic agents available, and progress consisted chiefly of developing methods of their administration, comparing their advantages and dangers, and simply trying to find out how to keep children asleep and still for longer periods of time. Despite its recognized danger, chloroform remained the principal agent in England and throughout Europe. Efforts to reduce the complications associated with chloroform included many warnings as well as more effective steps, such as diluting it with ether (CE) and with alcohol and ether (ACE). The introductions of nitrous oxide into general use by 1870 and ethyl chloride shortly after 1900 were important advances, reducing or replacing the use of chloroform in many operations not requiring relaxation. The fact that both of these agents were nonirritating and relatively acceptable made them particularly adaptable for induction and initiated early interest in special methods of handling this troublesome stage of anesthesia.

British physician anesthetists began to publish articles and texts in increasing numbers. Buxton alone producing five editions of his Anaesthetics: Their Uses and Administration between 1888 and 1912. Many adult texts contained advice on pediatric problems, among which that of harelip continued to attract the most attention. Numerous references to pediatric anesthesia could be found in The Lancet,Britain's premier medical journal, and in 1923 C. Langton Hewer wrote Anaesthesia for Children, the first text on pediatric anesthesia to be written in English.

In the United States, the special needs of children were given slight consideration for many years. The child was treated as “a little man,” surgeons operated with large instruments, and all equipment was adult sized. Ether remained the principal agent. Although criticism of chloroform became more vehement ( Kopetsky, 1903 ), its use was advocated in the United States as recently as 1957 ( Schwartz, 1957). Progress was made by trial and error, with little communication among those using anesthesia. Most literature in the United States concerning anesthesia for children was written by surgeons before 1900.

Interest grew slowly in widely separated areas where adept nurses and occasionally unsuccessful surgeons developed skills sufficient to carry children through longer and more difficult procedures. Tonsillectomy, practiced since 1887, was being performed by the thousands in 1900, and appendectomy became an accepted, although often dangerous, procedure. Orthopedic surgery was definitely the most active type of pediatric surgery at the turn of the century, and most procedures were easily managed by simple ether techniques. One of the first signs of concern for the child's anxiety when undergoing anesthesia was voiced by James Gwathmey in 1907, when he recommended that one should “add a few drops of the mother's cologne to the ether mask and induce the child in the mother's arms.” Another step toward easing induction came in 1928 with the entry of tribromoethanol, the German Avertin, which was used widely as a rectal agent. It provided almost certain sleep in 7 to 8 minutes and was of special value prior to ether induction because, unlike the barbiturates used later, it had a bronchodilating effect and facilitated rather than retarded induction. Unfortunately, the drug required preparation immediately before use and that, plus the frequent occurrence of fecal incontinence, led to its abandonment.

Between 1925 and 1940, activity in both pediatric surgery and anesthesia began to accelerate. William Ladd, whose interest stemmed from his experience in caring for children injured in a massive explosion in Halifax, Nova Scotia in 1917, led the development of pediatric surgery in North America ( Goldbloom, 1917 ; Steward, 1983 ). His work at Children's Hospital Boston was particularly devoted to the correction of neonatal defects including, of course, harelip. He performed harelip repair seated, with the infant held facing him in the lap of a nurse, while the anesthetist stood behind the nurse, directing ether from a vaporizing bottle into the infant's mouth via a metal mouth hook.[*]

The introduction of cyclopropane in 1930 proved particularly helpful for pediatric anesthetists in the management of infants, although it required assembly of a closed-system apparatus. Lamont and Harmel developed a miniaturization of the to-and-fro canisters Waters described in Wisconsin and used this technique for Blalock's “blue baby” (tetralogy of Fallot) operations at Johns Hopkins Hospital. In Boston, Betty Lank ( Fig. 35-1 ),[*] an enterprising nurse anesthetist, further redesigned the miniature to-and-fro apparatus with less dead space and shrank adult celluloid masks to infant size, enabling her to provide anesthesia, relaxation, and controlled respiration for Ladd's infants as well as for Robert Gross' widely heralded division of a patent ductus arteriosus in 1938' without endotracheal intubation.


FIGURE 35-1  Ms. Betty Lank served as chief nurse anesthetist at Children's Hospital Boston from 1935 to 1969 (see text).



By 1940, considerable progress had been made in the ability of minimally trained anesthetists to provide quite satisfactory operating conditions for the surgeons of that time. Ladd strenuously corrected the previous concept by establishing the dictum “the child is not a little man.” Supportive warming, preoperative correction of electrolyte balance, and intraoperative charting became standardized. Clinical signs of anesthetic depth, described by Guedel in 1937, served well. This might be termed the height of the art of pediatric anesthesia in the United States, where simple expedients still prevailed.

In England, there had been more progress in airway control. Following World War I, Magill and Rowbotham popularized tracheal intubation for adult procedures, and in 1937, Philip Ayre of Newcastle-Upon-Tyne reported his classic method of endotracheal intubation with a T-tube device for harelip repair in neonates ( Ayre, 1937 ). Although Robson of Toronto had described intubation of children using digital guidance rather than a laryngoscope ( Robson, 1936 ), it had received little attention.

*  An accurate description of the first anesthetic agents given by one of the writers (R.M.S.) for Dr. Ladd at Children's Hospital Boston in 1946.

*  Ms. Lank, who served as chief nurse anesthetist at Children's Hospital Boston from 1935 to 1969, was one of several remarkable nurses who provided much of the anesthesia care for children at major pediatric centers in the United States until physician anesthesiologists trained and experienced during World War II returned home and began developing interest and expertise in pediatric care.

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

Copyright © 2005 Mosby, An Imprint of Elsevier



Before and during this period, activity accelerated in related fields and much information became available defining normal and abnormal infants in such texts as Clement Smith's The Physiology of the Newborn Infant (1945) , Taussig's Congenital Malformations of the Heart (1947) , and Nelson's Textbook of Pediatrics ( Nelson, 1950 ). The practice of adult anesthesia had become established, providing fresh information on new agents and techniques easily adaptable to children. As yet, the only established pediatric anesthesiologist in North America was Charles Robson, in Toronto, and in England, Robert Cope, at London's Hospital for Sick Children. Among those who became interested in pediatric anesthesia, M. Digby Leigh made himself well known ( Fig. 35-2 ). Trained by Waters in Wisconsin, he was appointed head of anaesthesia at Montreal Children's Hospital, where he taught and innovated and, with his invaluable associate Kathleen Belton, authored Paediatric Anaesthesia (1948), the first North American text on this subject. Here, they described the use of spinal anesthesia for intrathoracic procedures, an original pediatric circle absorption apparatus, and a nonrebreathing valve. Leigh moved to Vancouver, British Columbia in 1947 and to Los Angeles in 1954, where he started the first annual pediatric anesthesia teaching conference in America. He was a brilliant technician and a stern teacher, and he delighted his audiences with his stinging repartee. His foresighted attempts to monitor exhaled carbon dioxide in 1952, however, were rebuffed by incredulous scoffers ( Conn, 1992 ).


FIGURE 35-2  Dr. M. Digby Leigh.



In the meantime, in Liverpool, G. Jackson Rees ( Fig. 35-3 ) had been named anaesthetist at the Alder Hey Children's Hospital by his mentor and teacher Cecil Grey. Together, they conceived the idea that practically all surgery could be performed under the simple and nonexplosive combination of nitrous oxide and curare. Rees, adapting the Ayre T-tube system by adding an expiratory limb and breathing bag (the well-known Jackson Rees system), proceeded to carry out this concept with astounding success. With minor alterations this technique was to survive through years of short-lived, complicated types of apparatus. Rees' conviction that respiration be controlled in infants with reduced tidal volumes and rates of 60 to 80 times per minute also met criticism but proved to be rational when increased tidal volumes were found to cause surfactant washout and barotrauma.


FIGURE 35-3  Dr. G. Jackson Rees.



The new field of pediatric surgery, spearheaded by Gross, was calling for more skilled anesthetists, and at the end of World War II, large numbers of young physicians were released from military service, many of whom chose the uncharted field of pediatric anesthesia. McQuiston and Smith found posts at children's hospitals in Chicago and Boston, respectively, and Rackow worked at Columbia Presbyterian Hospital in New York, each to participate in early advances. In 1946, C. Everett Koop recruited Margo Deming to head the Department of Anesthesia at the Children's Hospital of Philadelphia as a teacher and investigator. Dr. Koop is currently Professor of Surgery at Dartmouth Medical School.

Little had happened in anesthesia on the home front during World War II. After the war, numerous problems, many not even envisioned at the outset, were resolved by the exceptionally harmonious cooperation between pediatric surgeons and anesthesiologists. While the success of individual operations is the natural goal of the surgeon, and improved supportive measures are the steps noted by anesthesiologists, all are interdependent and are considered together.


Neonatal Surgery and Anesthesia

Chief among the surgical challenges at the beginning of this period were three congenital defects: tracheoesophageal fistula (TEF), omphalocele, and congenital diaphragmatic hernia (CDH). Both Leven and Ladd performed secondary multiprocedure repair of TEF in 1939. Primary repair, first accomplished by Haight in 1941, then became the most important challenge in pediatric surgery, each case demanding all-out day and night efforts of all participants. In Boston, the operation was carried out under cyclopropane by mask with a to-and-fro apparatus, endotracheal intubation then being reserved for emergency use during operation. Control of the exposed pleura during esophageal anastomosis required complete immobility, and the operation, in the words of Ladd, was “like stitching the wing of a butterfly.” Supportive management played a large part in the survival of these infants, both during and after the operation. Warmth was maintained by heating and humidifying the operating room, wrapping limbs in sheet-wadding, and using a semiclosed to-and-fro absorption technique. Blood pressure was measured by a locally introduced cuff with a latex bladder encircling the arm ( Fig. 35-4 ). Fluids and blood were administered via a open-top burette with rubber tubing and “cut down” metal cannula in the saphenous vein. Postoperative survival depended largely on the remarkably able service of one or two very special nurses.


FIGURE 35-4  Smith's latex blood pressure cuffs: newborn and infant sizes.



Repair of omphalocele posed different problems. Here the forceful closure of the abdomen over the extruded viscera often caused severe compression of the lungs and abdominal blood vessels. The challenge to the anesthetist was that of providing adequate relaxation while preserving ventilation and circulation. Skin closure was possible only rarely, leaving the alternative of delayed closure, which frequently failed. The use of muscle relaxants facilitated closure but increased the risk of postoperative hypoventilation. Mortality was appreciable.

Of the three defects, CDH at first appeared to be the easiest to correct, and anesthesia frequently was managed with open-drop ether without mortality. By 1950, however, postoperative deaths became an obvious but unsolved problem until it became evident that they were caused by earlier recognition of the defect in sicker infants who previously would have died before repair could be attempted. The management of CDH subsequently became, and still is, one of the most engrossing problems of neonatal surgery.

Herniorrhaphy and Pyloromyotomy

Herniorrhaphy and pyloromyotomy could be performed under local anesthesia by the average surgeon, but open-drop divinyl ether (Vinethene)-ether was definitely preferable. The problem most often encountered in infants with inguinal hernia was whether to cancel the operation when the infant's hemoglobin was 9.8 g/dL instead of the “required” 10 g/dL or to transfuse. Transfusion frequently was chosen. Before 1912, attempts to correct pyloric stenosis by gastroenterostomy had resulted in a 50% mortality rate. The Ramstedt pyloromyotomy effected one of the great achievements of pediatric surgery in creating a simple procedure for this commonly occurring lesion, thereby saving the life of an otherwise normal child. Anesthetic management after early diagnosis centered on the prevention of aspiration of the accumulated stomach contents, best accomplished by drainage via a large-bore urethral catheter immediately before operation. In Boston, trachea intubation was not considered necessary unless contrast medium had been used for diagnosis, whereas intubation was routinely used in other centers. In cases of delayed diagnosis, operation was postponed for rehydration and correction of electrolyte disorders or anemia.

Early Attempts to Control Fear

It soon became evident that for the small child, the fear of needles and the horrors of anesthetic induction were deeply upsetting and of long duration. Concern about this most unfortunate anesthetic byproduct was voiced by psychologists ( Levy, 1945 ), pediatricians ( Jackson, 1951 ), anesthesiologists ( Eckenhoff, 1953 ), and others, as well as numerous mothers reporting prolonged night terrors, bed-wetting, and dependence.

Some attention had been paid to premedication shortly before this time. French Armand-Delille (1932) recommended morphine and Waters (1938) promoted the combination of morphine and scopolamine, but the response to the outburst of concern came in a flood of reports on a variety of ineffective agents. The basic error in most studies was, and still is, the use of age and/or weight for estimation of drug dosage, when neither reflects the child's state of mind. General use of intramuscular barbiturates plus morphine mixed with either atropine or scopolamine resulted in severe horror of needles, an uncomfortably dry mouth, and an unpredictable degree of sedation, seldom better than 65% successful. Attempts to improve this record continued to play a large part in the activities and literature of pediatric anesthesiologists with only slight improvement with regard to the effectiveness of sedative drugs. However, the concentration of attention of numerous investigators on this problem did result in the development of close personal interest in each child studied, quite possibly responsible for much of the benefit credited to the drug being promoted.

Methods of induction showed somewhat more success than those of sedation. Thiopental replaced rectal Avertin, providing greater ease of administration via either the intravenous or the rectal route (Weinstein, 1939 ), whereas induction with nitrous oxide, cyclopropane, or divinyl ether eliminated much use of the dreaded ether. With the repeated failure of sedative agents, greater skills were developed by caring anesthetists to gain the confidence of children in preoperative visits and then to divert their attention at induction by telling them stories or by simply lulling them to sleep. Hypnosis was used for induction by Betcher (1958) , Marmer (1959) , and a few others for the total operation in short procedures. It was particularly valuable for the repair of facial lacerations in small children who had recently eaten. Unfortunately, this potentially useful and harmless method gained only limited acceptance.

Control of the Airway

The importance of airway management became evident with the first anesthetics, and after years of progress it still presents formidable difficulties. For patients of all ages, hypoxia resulting from laryngospasm, oral secretions or blood, abscesses or tumors, aspiration of vomitus, or simply blockage by the tongue has been an ever-present danger. Many deaths from early harelip procedures resulted primarily from hemorrhage, as were later deaths from tonsillectomy.

By 1940, two simple but extremely fundamental aids had been introduced. To prevent obstruction by the tongue, metal and rubber oral airways, often fitted with a metal nipple for insufflation of vaporized ether, had been used successfully for a decade. Suction apparatus was first available in the form of bulb syringes used alone or fitted with rubber catheters and then later as portable motorized pumps situated at the head of the operating table (ether and cyclopropane notwithstanding) or by means of a centrally operated pipeline.

Endotracheal Intubation

The outstanding advance in pediatric anesthesia between 1940 and 1960 was in control of the airway by tracheal intubation. Early use in England and Canada met with little resistance. In the United States, however, opposition by surgeons raised the first major obstacle to progress in the new specialty. (One must admit that reasonable concern had been aroused in those who had witnessed the traumatic attempts of inexperienced individuals to perform unnecessary intubations.) It was the efforts of Rees in England, Leigh, then in Canada, the British-American Gillespie (1939) , and Americans Deming (1952) , Pender (1954) , and others, and their supportive younger surgeons, that brought forth grudging acceptance of tracheal intubation of infants and children in the United States in the 1940s and 1950s.

The ongoing development of this technique led to (1) an increased understanding of laryngeal anatomy ( Eckenhoff, 1951 ); (2) replacement of the “classic” hyperextension of the head by use of the “sniffing” position for intubation; (3) a succession of different types of tracheal tubes, including the tapered tube of Cole (1945) that enjoyed more than a decade of popularity; (4) a variety of tube materials progressing from coarse rubber to nonreactive plastic; and (5) laryngoscopes of several types and sizes.

As with ether and other major advances, the advent of tracheal intubation brought a host of disadvantages and a few real dangers that, in turn, led to a glut of literature concerning complications ( Flagg, 1951 ), including subglottic stenosis ( Colgan and Keats, 1957 ), laryngeal irritation from large tubes ( Baron and Kohlmoos, 1951 ), and tracheitis caused by contamination ( Smith, 1953a ). This proved to be just the beginning.

“Total Control” of Respiration: The Muscle Relaxants

Following the first clinical use of d-tubocurarine by Griffith and Mitchell in Canada in 1942, Canadians and British accepted it readily and began extensive use in both children and adults ( Anderson, 1951 ;Stead, 1955 ; Leigh et al., 1957 ; Rees, 1958 ), to be followed by much investigation in later years. Again, in the United States there was much opposition, this time by anesthesiologists ( Beecher and Todd, 1954 ) as well as surgeons ( Gross, 1953 ), to whom the concept of total “takeover” of an essential body function, termed controlled respiration, appeared to be a dangerous and unacceptable “physiologic trespass.” Beecher threatened one of these writers (R.M.S.) that “heads would roll” if he and others persisted in support of its use. In the meantime, Cullen (1943) had found it quite safe for adults and children, using it as a sole agent for infant surgery. This practice was abandoned after Scott Smith of Utah ( Smith, 1947 ; Smith et al., 1947 ) was tested under total curarization and suffered acutely on painful stimulation. As with tracheal intubation, the total acceptance of neuromuscular blocking agents in the United States required many years. By 1960, however, the terms “controlled” and “assisted” respiration had gained widespread use.

Pediatric Breathing Systems: Assisted and Controlled Respiration

With the stimulating effect of ether on respiration in light surgical planes, assisted respiration was seldom needed. Open chest surgery, cyclopropane, and particularly muscle relaxants definitely changed this picture and led to a succession of considerably diverse devices ( Dorsch and Dorsch, 1975 ). The to-and-fro absorption method, using soda lime canisters of graduated sizes, was particularly adaptable to infants but caused heat retention and the aspiration of lime dust. For larger children, the canisters were bulky and heat retention was even more troublesome.

Special interest was taken in infant circle absorption systems. The Leigh ( Leigh and Belton, 1948 ), Ohio, and Bloomquist models were not only difficult to handle but also introduced the problems of valve resistance and dead space.

To eliminate problems of carbon dioxide accumulation, several nonrebreathing valves were designed by Leigh (1948) , Stephen and Slater (1948) , and others. Although compact in design, they were not easy to manage and were definitely ill suited for use with explosive agents.

The saga of apparatus variously called rebreathing (British), nonrebreathing (United States), and partial rebreathing (general) is complicated and involved numerous studies and modifications of the basic Ayre T-system ( Ayre, 1937 ) ( Fig. 35-5 ) over a period of 30 years. Following the Rees elongation of the expiratory limb with an attached breathing bag, the addition of exhaust valves placed either proximal (Mapleson A) or distal (Mapleson D) to the face brought intensive examination, as did the estimation of proper flow rates of incoming gases. Evaluation by Mapleson (1954) and Inkster (1956) did much to clarify these issues at the time, but more problems lay ahead.


FIGURE 35-5  Original Ayre T-tube nonrebreathing system.



Cardiovascular and Thermal Control

Between 1940 and 1960, revolutionary advances were made in several areas involving the combined efforts of anesthesiologists and surgeons. The intentional reduction of arterial blood pressure, extensively explored by Enderby (1950) and others in England, was cautiously extended to pediatric use by Sheila Anderson (1955) with trimethaphan camphorsulfonate (Arfonad). This served as a reasonably safe agent. It was the initial step in induced hypotension to reduce surgical blood loss in major pediatric surgery and to prevent excessive blood pressure elevation during correction of coarctation of the aorta. However, the agent was unpredictable and soon was replaced by more controllable agents and techniques.

Controlled Reduction of Body Temperature and Cardiopulmonary Arrest

Following Gross' ligation of a patent ductus arteriosus in 1938, correction of coarctation of the aorta, repair of vascular rings, and shunt procedures for tetralogy of Fallot were successfully performed under closed or semiclosed inhalation anesthesia, usually with cyclopropane ( Harmel and Lamont, 1948 ; Harris, 1950 ; Smith, 1952 ). McQuiston, endeavoring to reduce the oxygen requirement of Dr. Potts' cyanotic infants, cooled them 3° to 4°C on a simple ice-water mattress, thereby introducing the practice of hypothermic control of body metabolism into pediatric anesthesia ( McQuiston, 1949 ). Efforts to reduce oxygen demand by further lowering temperatures to 30°C with immersion in ice water provided surgeons time for simple intracardiac aortic or pulmonary valvotomy ( Lewis and Taufic, 1953 ;Virtue, 1955 ).

The drive to bypass both heart and lungs initiated by Gibbon in 1937 became exciting in the early 1950s, with competing surgeons Lillihei, Kirklin, and Kay and their respective anesthesiologists Matthews, Buckley, and Van Bergen (1957) , Patrick, Theye, and Moffit (1957) , and Mendelsohn, Mackrell, Machlan, and others (1957) all contributing toward the first practical use of the pump oxygenator in 1955, 2 years before publication of the articles cited.

The supplementation to bypass perfusion by moderate hypothermia (30°C) and different methods of induced cardiac arrest produced the greatest “takeover” of body function to date and the means of performing intracardiac surgery on all but small infants.

Mild and moderate hypothermia techniques were also used in this period for neurosurgery, orthopedic surgery, and harelip repair ( Kilduff et al., 1956 ).

Control During Maintenance of Anesthesia

As more extensive procedures were developed and surgeons began to prefer accuracy to speed, 4-hour operations became more frequent and the methods of maintenance and support more demanding. Experience, skill, and constant observation were still primary factors, assisted by a few simple devices ( Fig. 35-6 ). During this time the precordial stethoscope became essential for use with every infant or child throughout anesthesia ( Smith, 1953b ). A precordial or esophageal stethoscope ( Smith, 1991 ) served, first, to keep the anesthetist in direct contact with the child at all times, providing unaltered information as to the clarity and strength of breath sounds and the rate, rhythm, and strength of heart sounds. Strength of heart sounds was an important guide to the degree of blood loss at that time. Arterial blood pressure could be obtainable with standard apparatus for larger children and with a specially constructed latex cuff with an inflatable bladder for infants (Smith cuff). During this phase, the electrocardiograph was occasionally brought into operating rooms, encased in antiexplosive shielding (shaped like a torpedo), and served relatively little purpose. Body temperature was measured intermittently at oral, nasal, or rectal sites, the standard glass thermometer giving way to the safer but less accurate thermostat devices. The anesthesia chart was considered a necessary item, gaining in importance as procedures grew increasingly complex and legal suits more frequent.


FIGURE 35-6  Smith's teaching precordial stethoscope with a single chest piece and two headpieces.



Control of Blood Loss

Methods of estimating blood loss at the time consisted of assessing blanching of conjunctivae, evaluating the strength of heart sounds, measuring arterial blood pressure, and weighing bloodied sponges, purposely used without moistening. While speed was still considered essential in pediatric surgery during the excision of Wilms' and other large tumors, massive hemorrhage might exsanguinate small infants before replacement was possible. Attempts to restore the loss with cold, acidified blood brought failing hearts to irreversible arrest. A major advance to control these situations occurred when surgeons were persuaded to time their work by the advice of the anesthesiologist rather than by the clock. Although the cautery soon reduced blood loss drastically when used, it was not adopted immediately by all.

Progress in Local Anesthesia

Ladd had used local infiltration for abdominal procedures in premature infants in the late 1930s, and Leigh wrote of spinal anesthesia for open chest work in the 1940s, but improved inhalation methods outmoded both. Except for brachial plexus block ( Small, 1951 ; Eather, 1958 ), little attention was paid to these methods in the United States. In many other countries, however, where inhalation anesthesia was less advanced, there was considerable dependence on regional and spinal anesthesia for both infants and children.

Halothane Opens a New Era

Although anesthesia with relaxants and nitrous oxide permitted the use of electrical instruments in the operating room, explosive gases were still popular until the introduction of halothane. Following its first use in England by Johnstone in 1956 (in 10% concentration), this nonflammable, nonirritating, and potent agent was promptly introduced in Canada by Junkin, Smith, and Conn (1957) and in the United States by Stephen, Lawrence, Fabian, and others (1958) . Subsequently flammable anesthetic agents were totally abolished in the United States, thus opening the way to revolutionary changes, first in the control of blood loss by cautery and then in the development of electronic devices for monitoring and physiologic control.

Supportive Care and Oxygen Therapy

Related fields brought important aid to pediatric anesthesiologists during this period. The time-honored rule developed by Holliday and Segar (1957) for pediatric fluid administration based on metabolic requirements serves to this day. Also of great importance, particularly in reducing the morbidity and mortality of small surgical infants, was the control of infection by the use of antibiotic agents.

The interest of pediatricians caring for neonates led to the development of enclosed incubators with regulated oxygen, warmth, and humidification for infants with respiratory distress syndrome. Improved oxygen tents were developed for older children including those with cystic fibrosis. The poliomyelitis epidemics of the 1950s in Europe and North America initiated a succession of ventilating devices to replace the enclosed “iron lung” in use since 1929. Pediatric anesthesiologists and pediatricians shared responsibility for this work, which opened a new field for anesthesiologists.

In related areas, Virginia Apgar introduced her scoring system for neonatal assessment ( Apgar, 1953 ), Peter Safar launched his crusade for mouth-to-mouth ventilation and further work in cardiopulmonary resuscitation, and the first multidisciplinary adult intensive care unit in North America was developed ( Safar, 1958 ).

The first pediatric intensive care unit was established in Goteburg, Sweden, in 1955. Similar units were established in Stockholm (Hans Feychtung), Liverpool (Rees), and Melbourne (MacDonald and Stocks) between 1960 and 1964. In North America, the first pediatric intensive care unit was established by John J. Downes at the Children's Hospital of Philadelphia in 1967, followed by Children's Hospital of Pittsburgh (Kampschulte), Yale-New Haven Hospital (Gilman), Massachusetts General Hospital (Todres and Shannon), and the Hospital for Sick Children in Toronto (Conn) within the following 4 years ( Downes, 1992 ).


Throughout Europe and North America, communication among anesthesiologists began to accelerate. The Great Ormand Street Hospital for Sick Children in London and the Alder Hey Hospital in Liverpool became teaching centers in England; the Hospital for Sick Children in Toronto in Canada and the Children's Hospitals of Boston and Los Angeles in the United States became centers to which various novice and experienced anesthetists came from all parts of the world for clinical training. Residents on affiliation from teaching hospitals were rotated through brief training periods for instruction in basic, safe, and practical methods of anesthetic control of children undergoing standard operations and in special methods for those at higher risk.

On the heels of Leigh and Belton's Pediatric Anesthesia (1948) , Stephen's Elements of Pediatric Anesthesia (1954) and Smith's Anesthesia for Infants and Children (1959) were published, with details of advances to date. Articles on new agents and techniques steadily increased in the anesthetic literature. While some reported personal early experiences based on limited numbers, many were of lasting value, including those involving tracheal abnormalities by Eckenhoff (1951) and Colgan and Keats (1957) , tracheoesophageal repair by Zindler and Deming (1953) , and the important warning of Leigh, McCoy, Belton, and others (1957) concerning bradycardia after the intravenous administration of succinylcholine.

Research, on the other hand, was still in its infancy, there being little space, time, or funds for sophisticated investigation. As previously mentioned, many clinical studies offered practical current value concerning new agents and techniques. While those concerning preoperative sedation outnumbered others, many reports covered airway resistance, valves, and dead space ( Macon and Bruner, 1950 ;Mapleson, 1954 ; Orkin et al., 1954 ; Hunt, 1955 ; Inkster, 1956 ). The introduction of muscle relaxants initiated other studies, including those of Stead (1955) , Hodges (1955) , Telford and Keats (1957) , and Bush and Stead (1962) . The addition of halothane late in this period led to a more critical analysis of this agent than had been done for previous anesthetics.

This period established such fundamental techniques and basic concepts that Rees subsequently (1991) stated, “Paediatric anaesthesia in Great Britain and Ireland shows that by 1950 it had reached a point at which current practice is recognizable…. Future pediatric anesthetists are therefore unlikely to experience the great excitement their predecessors enjoyed between 1930 and 1950, but will derive satisfaction from changes less dramatic as the curve of improvement approaches perfection.”

Copyright © 2008 Elsevier Inc. All rights reserved. -

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

Copyright © 2005 Mosby, An Imprint of Elsevier


With sound fundamental approaches defined and restrictions resulting from flammable agents eliminated, the way was cleared for rapid and extensive advances in all areas of pediatric anesthesia. Clinical control would drive ahead and research would become more productive, but this period saw the greatest progress in the development of organized teaching and communication.

Unfortunately, progress was not marked in the control of fear. Despite continued efforts to address this problem by many skilled workers ( Poe and Karp, 1946 ; Rackow and Salanitre, 1962 ; Root, 1962 ), sedatives were still unpredictable and intramuscular needles were still in general use. The introduction of ketamine (Ketalar) by Domino, Chodoff, and Corsson (1965) created mixed feelings based on its early postoperative psychologic reactions, but the agent found a place in pediatric use for uncontrollable patients and to accomplish minor but painful procedures.

A major change in the methods for controlling fear was in giving permission to parents, first, for free admission to the child's bedside at all times, including “sleep-in” privileges, and later, to preinduction and induction areas. While many parents were assuaged by these moves, statistics failed to show great help for the children ( Schulman et al., 1967 ).


Modification of the partial rebreathing systems by Bain and Spoerel (1972) , by which the exhalation tube passes inside the inhalation arm, provided a means of scavenging expired gases, thereby greatly enhancing the use of this popular pediatric method. This marked a major evolution of airway systems for pediatric anesthesia.

Steps toward greater precision in monitoring were taken in the measurement of infant blood pressure by Doppler sonography and by oscillotonometry (Dinamap) ( Marcy and Cook, 1988 ). In the determination of arterial oxygen saturation, the transcutaneous electrode (ear oximetry) was used with limited success ( Saunders et al., 1976 ). It was during this period that “control by the numbers” gained predominance over the unreliable art of anesthesia. Led by Downes of Philadelphia and others, arterial blood gas determinations, blood sugar, hemoglobin, electrolytes, and other measurements were serially evaluated intraoperatively in adjacent laboratories. Insertion of arterial and central venous catheters became commonplace, and urinary catheterization became an important guide to fluid and electrolyte replacement.

Progress in controlling fluid balance included the recognition of the importance of electrolytes in all intravenous solutions ( Bennett et al., 1970 ; Herbert et al., 1971 ). New concepts concerning blood replacement included Davenport's practical recommendation to give blood when loss reached 10% of blood volume ( Davenport and Barr, 1963 ), followed later by Furman's more precise suggestion to maintain the hematocrit level above 28% to 30% in children and 40% in the newborn ( Furman et al., 1975 ). At this time, the concept of replacement of preoperative fluid deficit was widely adopted.

Airway problems presented ongoing challenges, and their management continued to register improved methods of control. Great emphasis was placed on the prevention of food aspiration and the damaging effects of hypoxia. The Sellick maneuver (1961) and Salem's many warnings about “the full stomach” (1970) were forever fixed in the mind of each new resident.

The treatment of acute epiglottitis by nasotracheal intubation instead of the former mandatory use of tracheostomy was a major change and clear advance, speeding recovery and significantly reducing serious complications (Oh and Motoyama, 1977 ).

Management of “the difficult airway” began to assume a larger role in both adult and pediatric anesthesia as more complicated procedures were undertaken on more deformed patients. By this time, some 120 different types of laryngoscope blades had been invented, each with some minor modifications to suit the designer, usually with no major advantage. It was the introduction of the fiberoptic laryngoscope ( Taylor and Towley, 1972 ; Stiles, 1974 ) that enabled anesthesiologists to intubate infants and children for whom this had been virtually impossible.

The startling appearance of what became known as malignant hyperthermia caused great concern, but widespread warnings about “triggering agents” and the discovery of a specific counteragent, dantrolene, usually brought it under reasonable control at least when recognized early ( Denborough et al., 1960 ; Britt, 1979 ; Gronert, 1980 ).


Interesting progress occurred in the evolution of infant surgery. Tracheoesophageal fistula repair became a standardized procedure, and mortality was generally limited to infants with serious cardiac defects. Problems related to omphalocele repair were largely overcome by the introduction of Schuster's staged mesh sac closure (1967). Congenital diaphragmatic hernia, however, brought increasing difficulties as smaller and more premature infants were encountered. Acidosis, shunting ( Raphaely and Downes, 1973 ), and pulmonary hypertension ( Dibbins, 1976 ) posed problems yet to be solved. Attempts to use extracorporeal membrane oxygenation (ECMO) predicted later value ( Bartlett et al., 1979 ).

Following the breakthrough in cardiac surgery accomplished by the establishment of extracorporeal circulation in larger children, the next step was to find a means of operating within the hearts of neonates, without obstruction by intracardiac catheters. In 1965 the use of hyperbaric oxygenation served as a temporary answer, providing surgeons 3 to 5 minutes of inflow occlusion for the performance of aortic valvotomy and other brief procedures ( Bernhard et al., 1966 ). The use of oxygen at 3 to 4 atmospheres of pressure substantially increased plasma oxygen-carrying capacity, while presenting increased potency of nitrous oxide and increased flammability ( Smith et al., 1964 ).

The final hurdle in the approach to infant cardiac surgery was passed by the successful combination of deep hypothermia ( Horiuchi et al., 1963 ) and extracorporeal circulation ( Hikasa et al., 1967 ), providing time for the most complicated reconstruction of neonatal cardiac defects. Rendering an infant virtually dead by complete cessation of respiration and circulation, at a body temperature of 15°C, appeared to be the ultimate in physiologic control. Agents and techniques have undergone several changes in subsequent years but remain fundamentally similar.

Somewhat less dramatic, but also of great importance, was the initiation of renal transplantation in 1950, which saved the lives of thousands of children and adults with end-stage renal disease.

Among many well-known tenets established, two of particular interest to anesthesiologists were the danger of succinylcholine in patients with elevated serum potassium levels ( Powell and Miller, 1975 ) and the evident tolerance to anesthesia in patients with hemoglobin levels as low as 6 g/dL.

The craniofacial repair devised by Tessier and others (1967) for correction of the disfiguring deformities of Apert's and Crouzon's diseases was a bold undertaking. It was equally challenging for the anesthesiologists involved, with difficult airway management, prolonged maintenance, marked fluid and blood loss, and a particularly precarious period of recovery while the child's head was so completely swathed in tight bandaging that only the endotracheal tube was visible.

Anesthetic management to separate conjoined twins at birth was of such unique interest that any report of a single case was welcomed for publication. A separate team of surgeons and anesthesiologists was assigned to each twin, and multiple problems of shared organ systems, hemorrhage, and airway obstruction were noted ( Furman et al., 1971 ; Winston et al., 1987 ).


For many years, much attention had been directed toward controlling the responses of children during the introductory phases of anesthesia. Postoperative care, however, often consisted of little more than a prompt return to the child's room with orders for checks every 4 hours and nothing by mouth. The advent of various new and extensive operations made it evident that the survival of patients depended to a large extent on their supportive control during recovery'a third dimension of anesthesia.

One of the first needs to be met was the ability to provide prolonged tracheal intubation, fostered by Brandstater (1962) , MacDonald and Stocks (1965) , and Hatch (1968) . The continuation of earlier efforts to devise ventilation machines for infants and children with cardiopulmonary pathology brought a succession of models, some as adaptations of those made for adults and others designed specifically for younger patients.

So-called recovery rooms or postanesthesia care units (PACUs) for routine postoperative care had been established in many hospitals over previous decades, but areas staffed by highly trained personnel and fully equipped for high-risk patient care became mandatory. The earliest units of this type, termed critical care or intensive care units, appeared in Goteburg, Sweden, in 1955[*]; others were established in France in 1962, England in 1964, Australia in 1963, and America by those in Philadelphia in 1967, Pittsburgh and Boston in 1969, and Toronto in 1971, where Conn established a prototype of the modern multidisciplinary unit for infants and children, including near-drowning survivors ( Downes and Raphaely, 1975 ; Conn et al., 1980 ).

Important new approaches to resuscitation replaced such outmoded maneuvers as anal dilatation, drugs promoted as respiratory stimulants, and the prone pressure method. During the trial-and-error development of pediatric cardiac surgery and the poliomyelitis epidemics, apparent death became an indication for immediate slashing into the chest and manual cardiac compression. When it became evident that the patients occasionally survived both the original insult and the therapeutic assault, the term “cardiac arrest” was coined ( Singer, 1977 ). Because the exact cause of these mishaps frequently was uncertain, each was considered “an act of God” and successful resuscitation was considered a feather in the cap of any anesthesiologist who had been associated with one. Intelligent procedures of ventilation and closed-chest cardiac compression, combined with electric and pharmacologic stimulation, brought far greater reason, order, and success.

*  The excellent first-hand report of Downes (1992) on the development of pediatric critical care is recommended.

This period marked the definite establishment of teaching facilities for the specialized training of pediatric anesthesiologists. With markedly enlarged departmental staffs, didactic and clinical instruction became available in numerous institutions. Residents became capable of managing most types of cases and also received instruction in ancillary services. Accreditation for residency training in pediatric centers was established in Boston in 1970, to be followed by several others by 1980.

Teaching clinics were established for residents and others throughout the United States, Canada, and England. Edward Eger stood out as teacher par excellence over three decades. Annual symposia on pediatric anesthesia initiated by Leigh in 1962 were followed by those organized by Conn in Toronto, Downes in Philadelphia, Salem in Chicago, Ryan in Boston, and others. Literature became increasingly available in periodicals, including both new editions of previously published texts and added texts such as those by Davenport (1967) of Canada and an excellent Australian text by Brown and Fisk (1979) . Early exponents of the specialty became popular at local and national meetings, and an international exchange of speakers grew rapidly, stimulating interest and exchanging information on the rapidly developing scene.

International Progress

At this time, it became evident that considerable progress was being made in many parts of the world. In France, M. Delegue pioneered the modern stage, her text Memento a l'Uusage de l'Anesthesiologiste-Reanimateur Pediatrique passing through several editions. Rapid advances have taken place in France in many aspects of pediatric anesthesia. A marked difference in their approach appeared with their use of combinations of intravenous phenothiazines, antihistamines, and barbiturates in place of inhalation agents, with remarkable success (G. Durand-Gurry, personal communication, 1993). Their work in regional anesthesia and pharmacology has also been outstanding ( Saint Maurice et al., 1986 ; Murat et al., 1988 ).

Other early leaders in Europe include Suuterinen of Finland, Swensson, Feyting, and Ekstrom-Jodal of Sweden, and Rondio and Wezyk of Poland. South African and Australian workers, adopting British methods, also kept abreast or ahead of other areas. Douglas Wilson has been called the real pioneer of pediatric anesthesia in Western Australia, and Margaret McLellan, John Stocks, Ian McDonald, M. A. Denborough, and others have contributed on local and international levels. Japanese interest in pediatric anesthesia began later but proceeded vigorously beginning in 1958 ( Iwai and Satoyoshi, 1992 ); the publication of Pediatric Anesthesia in 1958 by Onchi and Fujita served as a valuable guide. Throughout Latin America, Brazilian physicians ( Fortuna, 1967 ) and others followed North American methods to some extent, but in these countries, and especially in Mexico, local and regional anesthetic techniques were depended on and consequently more highly developed than inhalation anesthesia ( Melman et al., 1975 ). The great number of students who studied in North America and Europe from India, the Philippine Islands, and other Asiatic areas resulted in growth of this organized activity and clinical excellence in their respective nations.

Research Stimulated by Clinical Advances

The introduction of various breathing devices, new muscle relaxants, and the halogenated agents alone provided material for extensive investigation, and other problems still lay unanswered. The demonstration of the more rapid uptake of anesthetic gases by infants than by adults ( Salanitre and Rackow, 1969 ) became a classic study, as did Motoyama's measurements of pulmonary mechanics (Motoyama, 1977 ; Motoyama and Cook, 1980 ), with some of his many contributions elaborating the pulmonary physiology of infants and children. Bush and Stead (1962) , Cook (1974) , Goudsouzian and others (1975) , and other researchers did much to establish the comparable actions of successive neuromuscular blocking agents in the search for safer, shorter-acting, and reversible types'hence, greater control. The advent of new halogenated agents aroused the pharmacologic investigation of metabolism, toxicity, cardiovascular depression, and seizures, and the increased potency demanded vaporizers of greater accuracy ( Brennan, 1957 ; Fabian et al., 1958 ; Lomaz, 1965 ). Other notable achievements included the establishment of minimum effective doses (ED50) of halothane by Nicodemus, Nassiri-Rahimi, Bachman, and others (1969) and the minimum alveolar concentration (MAC) as a standard measure of potency ( Eger et al., 1965 ), followed by the application of MAC to demonstrate the higher halothane requirement for infants than for adults ( Gregory et al., 1969 ).


This latest phase consists of many events now in progress that are described in this book. The entire scenario in the operating room has evolved enormously with anesthesiologists setting their multicomputerized monitors and infusion pumps, with numerous syringes loaded and coded, and a large cabinet within reach, holding drugs and other equipment for all possible occasions. The patient is brought in, and anesthesia is induced with minimal resistance. The next variable time is consumed while surgeons await the fixation of monitors, endotracheal tubes, and numerous catheters. Multiple medications are delivered by the intravenous route, frequently measured now by micrograms or “mics” per kilogram. The ventilator is set at a prescribed rate and tidal volume, and surgeons are allowed to approach and drape the patient, erecting a high sterile shield between themselves and the anesthesiologist. Charting is frequently automated. Chatting occurs with other anesthesiologists and the surgeons and nurses. Boredom in long simple cases can be a major hazard, as is a tendency to watch the monitors rather than the patient.

Fortunately, this is only one part of the picture. In the next room, a premature infant may be receiving spinal anesthesia for herniorrhaphy, and in a third, a liver transplantation may have been in progress for the past 8 hours. In the remaining 20 operating rooms, various procedures go on, more than half of which are outpatient cases.


During this period, there has been a widespread appreciation that infants and very small children are at increased risk of complications from anesthesia and surgery. Previous reports ( Salem, 1975) had shown that these were frequently related to cardiovascular factors (including hypovolemia, anemia), respiratory difficulties (airway obstruction, hypoxia, inadequate ventilation), or electrolyte imbalance (hyperkalemia, hyponatremia, hypoglycemia). Additional reports from the United States ( Morray et al., 1993 ; Keenan et al., 1994 ; Holzman, 1994 ) described some of the problems in greater detail, as did others from France ( Tiret et al., 1988 ), Scandinavia ( Olsson and Hallen, 1988 ), Canada ( Cohen et al., 1990 ), and England ( Lunn, 1992 ). In particular, postoperative apnea, especially in very premature infants, was noted by several investigators ( Steward, 1982 ; Gregory and Steward, 1983 ; Liu et al., 1983 ), and overnight hospitalization in these situations was widely adopted. Furthermore, there were indications that risk in small children could be decreased if individuals specially trained and experienced in pediatric anesthesia provided the anesthesia care ( Keenan et al., 1991 ; Morray, 1994 ; Berry, 1995 ; Downes, 1995 ). Although this concept remains controversial, surgeons, pediatricians, and parents increasingly began to appreciate the important role of pediatric anesthesiologists.


In part because the post-World War II “baby boomers” were now having their own children, pediatric facilities exhibited enormous growth. Freestanding children's hospitals, which had existed for more than a century, expanded and new pediatric hospitals were established. Some of these evolved as pediatric “hospitals within a hospital,” whereby large general hospitals developed specific buildings, wings, or floors to provide specialized care for children. Currently, several large children's hospitals in the United States are performing more than 20,000 surgical procedures per year. Some children's hospitals perform more operations and have more operating rooms and staff than major hospitals caring for adult patients. Reports are being published indicating that the outcome, at least for some conditions in small children, is better if surgery is performed by pediatric specialists in large pediatric centers ( Bratton et al., 2001 ; Kososka et al., 2001 ). The American Academy of Pediatrics (2002, 2003) has disseminated several policy statements emphasizing the need to have proper personnel and facilities available whenever children require surgery and/or anesthesia.


There has also been a great impetus to perform surgical procedures in younger and younger patients. While this was not possible or was fraught with danger in earlier eras, better equipment and surgeons well trained in pediatric subspecialties have made this not only feasible, but also ultimately desirable for children. Outcome studies in several areas have shown that corrective procedures performed in infancy, rather than palliative procedures done initially followed by full repair later in life, lead to improved long-term results. For example, the American Academy of Pediatrics in 1975 advocated surgical repair of elective urologic defects in children after the age of 4 years, but by 1996 was recommending these repairs occur in infancy. Likewise, repair of congenital cardiac anomalies shifted from early palliative procedures (largely shunts) to corrective repairs in the neonatal period ( Jenkins et al., 1995 ). This tendency to perform more complex surgical procedures in younger patients undoubtedly contributed to the growth of major pediatric centers.

At the opposite end of the age spectrum, pediatric institutions were also seeing an increasing population of older patients who had survived diseases generally considered pediatric in nature. For example, patients treated for cystic fibrosis, meningomyelocele and hydrocephalus, congenital heart disease, leukemias, and many “syndromes” were now routinely surviving into adulthood and presenting well past childhood for surgical procedures. Hospitals and/or their physicians catering to adults often exhibited a reluctance to manage these patients. This has led to the interesting paradox of pediatric subspecialists and pediatric hospitals being involved in the ongoing management of patients who clearly are no longer children. Compounding this has been the growth of surgical specialties where the care of children and adults is frequently undertaken simultaneously, such as fetal surgery or transplantation from living related donors. Thus, pediatric hospitals are now caring for patients well into their 20s, 30s, and beyond.

It is not simply the age of patients requiring surgery that has been changing but also the setting of much of the surgery itself. The vast majority of pediatric surgical procedures currently occurs in ambulatory patients who never remain overnight in the hospital. Patients frequently arrive for their procedure in the morning and go home later the same day. This creates additional challenges to anesthesiologists who must rely on surgeons to screen patients for significant coexisting medical problems, because patients are usually not seen in advance of the procedure by their anesthesiologist. Even when hospitalization following surgery is required, elective patients are rarely admitted prior to the day of the procedure. This is the case even when the surgical procedure will be quite complex, such as scoliosis repair, craniofacial reconstruction, repair of congenital cardiac lesions, etc. For these situations, anesthesiologists developed preoperative clinics where patients can be evaluated by an anesthesiologist along with any necessary consultants and have laboratory and radiologic studies obtained and blood cross-matched when necessary. This also provides an opportunity to answer questions about anesthesia and/or the perioperative experience and attempt to manage patient and parental anxiety.

Finally, pediatric anesthesiologists have become increasingly involved in caring for children outside the operating rooms when immobility and/or analgesia is required for nonsurgical procedures. This has largely occurred in the radiology departments, where increasingly sophisticated equipment and techniques have led to major advances in diagnosis (computed tomography, magnetic resonance imaging, positron emission tomography, etc.) and new, less-invasive treatment options (in the catheterization laboratory, radiation therapy suite, etc.). Anesthesiologists are being requested to provide care for patients in several other areas of the hospital as well, including the gastrointestinal suite for endoscopy, oncology unit for lumbar punctures and bone marrow aspirations, and so on. While children clearly benefit from relief of pain and anxiety in these situations, this has greatly increased demands for anesthesia services.

When anesthesiologists are unable or unwilling to assist in these areas, physicians from other specialties (including pediatricians, intensivists, hospitalists) or nurses have stepped in ( Malviya et al., 1997 ;Lowrie et al., 1998 ). Whether this affords a comparable degree of safety to administration of anesthesia by anesthesiologists in these situations remains to be seen. In any case, the large number of children requiring sedation/immobilization for nonoperative procedures has led to the development of “sedation guidelines” by several organizations representing anesthesiologists, pediatricians, emergency physicians, dentists, and others, with some variability among them ( American Academy of Pediatrics, 1992 ; American Society of Anesthesiologists, 1996 ; American College of Emergency Physicians, 1997 ; American Academy of Pediatric Dentistry, 1997 ). A group of pediatric anesthesiologists at Dartmouth Hitchcock Medical Center convened a conference in 2000 to try to develop consensus among physicians from varied disciplines in this regard, and they continue to disseminate a bulletin via email to individuals interested in this ongoing issue (Dartmouth, 2000).


Although the scope of new developments in anesthesia is the subject of much of the remainder of this book, there are several major changes worth noting. The age-old, frequently used restriction of preoperative intake ultimately underwent scrutiny with resulting changes in concept and reduction of fasting time ( Coté, 1990 ; Ferrari et al., 1999 ).

New, potent, inhalational anesthetic agents have been developed, virtually replacing halothane as the “standard” for the previous generation. To induce anesthesia via mask, sevoflurane is used almost exclusively because it acts faster and results in less bradycardia and hypotension ( Sarner et al., 1995 ; Holzman et al., 1996 ). This has been especially important in infants. Isoflurane is frequently used for maintenance of anesthesia, in part because it is currently less expensive; desflurane may be used when particularly rapid awaking is desired, although the need for special, temperature-regulated vaporizers has limited its popularity. None of these newer agents, however, have the smooth induction properties of sevoflurane. Concerns have been raised about breakdown products that may develop when sevoflurane interacts with some carbon dioxide absorbents, especially when dessicated, leading to overheating of the absorbent system, carbon monoxide production, or both ( Holak et al., 2003 ). The clinical significance of this remains to be determined.

A new, major feature in airway management has been the promotion of the laryngeal mask airway to eliminate tracheal intubation for many simple procedures, as well as provide airway access in emergency situations when intubation is difficult ( Brain, 1983 ; Mason and Bingham, 1990 ; Pennant and White, 1993 ). Endoscopes have also been developed that permit fiberoptic intubation even in small children.

Several “descendents” of fentanyl have been developed, with remifentanil capable of providing very potent and transient analgesia when administered via constant intravenous infusion ( Davis et al., 2001 ;Galinkin et al., 2001 ; Ross et al., 2001 ). Fentanyl transcutaneous “patches” have also been developed, largely to provide analgesia for chronic pain, and fentanyl is sometimes administered transnasally or transorally (Friesen et al., 1995; Viscusi et al., 2004 ). Potent opioids have been particularly useful for cardiac procedures when inhaled anesthetic agents are not well tolerated ( Hickey and Hansen, 1984 ). Perhaps more significant, the prolonged debate over the need for anesthesia at all during surgery on small infants was finally terminated when Anand and Hickey (1987) produced evidence of physiologic stress in infants under light anesthesia. This brought general agreement that all infants should receive anesthesia during surgery, although the best method for doing this, especially when the patient is a fetus, remains to be fully elucidated.

Propofol has become the most common intravenous induction agent for adults but has not completely replaced thiopental in children because propofol causes some discomfort when injected into small peripheral veins. Midazolam has replaced diazepam as the intravenous benzodiazepine of choice for sedation in children; midazolam is also the most popular oral sedative in the preoperative setting ( Kain et al., 2000 ). Midazolam can also be administered via several other routes (including intranasal) and is sometimes used rectally because production of methohexital, often used for this purpose, has ceased for economic reasons. The use of lidocaine-prilocaine (EMLA) or other creams ( Freeman et al., 1993 ) for skin desensitization eases the discomfort of venipuncture for intravenous induction but requires adequate time to become effective. Intramuscular injections are rarely necessary now in pediatric anesthesia practice.

Several new, nondepolarizing muscle relaxants have replaced curare. Although pancuronium is commonly used for lengthy procedures, several shorter-acting agents (especially cisatracurium and vecuronium) are frequently administered for brief procedures and have fewer side effects. Rocuronium is often used to facilitate emergency endotracheal intubation, and succinylcholine is no longer administered without good cause, because masseter spasm, malignant hyperthermia, or both occasionally develop after its administration, especially in the presence of potent inhaled anesthetic agents (Schwartz et al., 1984 ). In addition, the Food and Drug Administration (1997) issued a “black box” warning due to serious complications (including cardiac arrest resulting from acute hyperkalemia) associated with its use, particularly in young boys with unrecognized muscular dystrophy.

Although there had been some use of local and regional anesthesia for children before 1940, the development of improved inhalation methods soon largely displaced other forms of anesthesia. Regional anesthesia has become more commonplace in children, beginning in Europe, with “single-shot” techniques (spinal, caudal, peripheral nerve block) reducing the requirements for general anesthesia and providing postoperative analgesia ( Abajian et al., 1984 ; Yaster and Maxwell, 1989 ). In addition, continuous infusions of local anesthetics with or without fentanyl are often delivered intraoperatively and postoperatively via catheters placed during surgery, especially via the epidural route. This is a reflection of the much greater emphasis being devoted to the needs of the pediatric patient in the postoperative period. Pain control following surgery has been a major focus of pediatric anesthesiologists with patient-, parent-, or nurse-controlled analgesia available via computer-controlled infusion pumps for delivery of medications by the intravenous or epidural route. Pain treatment services have become more important aspects of the mission of most departments of pediatric anesthesia; they provide care for children with medical, as well as surgical, pain ( Zeltzer et al., 1989 ; Schecter et al., 2002).

In addition, outpatient pain treatment clinics evaluate and treat many chronic pain conditions in childhood; although largely directed by anesthesiologists, these are best multidisciplinary in nature and use many different techniques (including nerve blocks, oral medications, acupuncture, hypnosis, behavioral modification) and involve the participation of neurologists, neurosurgeons, physiatrists, physical therapists, psychologists, and many other ancillary medical and nursing personnel. Greater attention has also been directed toward assessing and allaying preoperative fears and anxiety of patients and their families. Preoperative clinics are used to evaluate many patients in advance of their procedures, and significant attention has been devoted to methods of easing induction of anesthesia, especially the use of oral premedicants and parental presence during mask induction ( Kain et al., 1998 , 2003). In all instances, kindness remains the essential feature in preoperative management.


Technical advances have also greatly enhanced patient monitoring. Smaller equipment is now readily available so that very young patients can be monitored as carefully as critically ill adults. Percutaneous catheters can be inserted directly into virtually any peripheral vein or artery; the Seldinger technique (if necessary with ultrasound guidance) can be used to insert central catheters. Echocardiography can be performed transthoracically or transesophageally in small children as well as in adults. Its use has greatly facilitated the ability of cardiac surgeons to assess the repair of congenital heart lesions intraoperatively ( Ungerleider et al., 1990 ). “Standard” monitoring is now quite extensive and sophisticated as promulgated by the American Society of Anesthesiologists in 1986 and includes continuous pulse oximetry and capnography. It appears that the average anesthesiologist is frequently able to manage a procedure with little or no direct observation of the patient, although a precordial or an esophageal stethoscope is still considered valuable by many pediatric anesthesiologists.

Advances in the intensive care unit also have been significant during this time and extended into the operating rooms. Patients with severe lung injury are now managed with several new forms of respiratory support, including advanced mechanical ventilators, inhaled nitric oxide, and ECMO ( Neonatal Inhaled Nitric Oxide Study Group, 1997 ; Bartlett et al., 2000 ; Aharon et al., 2001 ; Campbell et al., 2003 ). This latter technique can be used for weeks at a time and as an emergency method of resuscitation from cardiac arrest when a reversible condition is suspected (Laussen, 2002).


Numerous developments have occurred in surgical techniques that have greatly influenced anesthesia practice and are discussed elsewhere in this text. However, it is worthwhile noting that laparoscopic techniques, robotics, and intraoperative imaging have progressed so extensively and so rapidly into pediatric practice that anesthesiologists have had to accommodate the special problems and challenges presented by these situations. Perhaps nowhere is this more apparent than the field of fetal surgery, where surgeons, obstetricians, anesthesiologists, and neonatologists must collaborate to care for two patients simultaneously as techniques for surgical repair of prenatal anomalies are developed and assessed (Harrison et al., 1982, 1993 [105] [103]; Rosen, 1992 ).

Organ transplantation has extended beyond kidneys, and transplantation of the liver ( Starzl et al., 1963 ) became a major challenge for pediatric surgeons and anesthesiologists. To support a young patient who has hepatic failure through a repeat liver transplant requiring replacement of multiple blood volumes while monitoring and maintaining cardiac function, temperature, and many components of blood chemistry during an 8- to 12-hour operation is one of the most demanding anesthetic tasks known. The record of 1000 liver transplantations performed at the Children's Hospital of Pittsburgh between 1980 and 1990 with a nearly 70% survival rate stands as a remarkable accomplishment of both surgeons and anesthesiologists ( Robertson and Borland, 1990 ). Transplantation of the heart, lungs, or both appears similarly impressive, although it is not associated with the same degree of blood loss ( Jamieson et al., 1984 ). In any case, a shortage of available organs, especially those of a small size, greatly limits pediatric transplantation, and attempts to grow organs in cell culture has evolved into the new and fascinating field of tissue engineering ( Lanza et al., 2000 ).


Activity in research is reaching a new level of excellence and productivity, while demands for clinical service and limitations of funding make this an ongoing challenge and old problems persist. As noted by Berry (1993) , failure in the endless search for better preoperative sedation lies in controversies regarding basic ground rules for investigation, especially in children. In many fields, understanding of the problems has been gradually extended, with resultant improvement in the practical management of patients. Physiologic studies of cerebral circulation in the neonate by Rogers, Nugent, and Trystman (1980) , gas exchange in cardiac patients ( Lindahl, 1989 ; Fletcher, 1993 ), pharmacologic biotransformation of sedatives ( Saint-Maurice et al., 1986 ), the infant and the myoneural junction ( Goudsouzian and Standaert, 1986 ), and hypoxia in children following anesthesia ( Motoyama and Glazener, 1986 ) are but a few of the important initial studies. The report by Lerman and others (1986) concerning postanesthetic vomiting after strabismus surgery is another illustration of one of the problems of the conscious child that remains particularly difficult to control. Advances in molecular biology, mapping the human genome, and genomic pharmacology offer great hope that it will be possible to “customize” care for individual patients in a continuing attempt to drive the curve of improvement mentioned by Rees (1991) “closer to perfection.”


Pediatric anesthesia organizations have advanced greatly over the recent generation. Although a small group of anesthesiologists from the United States and Canada have had a section within the American Academy of Pediatrics since 1966 (now called the Section on Anesthesiology and Pain Medicine), it was not until 1973 that pediatric activities formally became a part of the American Society of Anesthesiologists. At this same time, a separate organization devoted to pediatric anesthesiology was established in the United Kingdom, but it was not until 1986 that the Society for Pediatric Anesthesia (SPA) was created in the United States. This is now the largest organization in the world devoted to pediatric anesthesiology, with more than 4000 members largely from the United States. The SPA has held annual meetings since 1987 in association with the annual meeting of the American Society of Anesthesiologists; for several years, it has also organized an additional winter educational meeting. The goals of the SPA are listed in Box 35-1 ; the society's presidents are listed in Table 35-1 .

BOX 35-1 

Goals of the Society for Pediatric Anesthesia



To advance the practice of pediatric anesthesia through new knowledge



To provide educational programs on clinical, scientific, and political issues that are important to pediatric anesthesia practice



To promote scientific research in pediatric anesthesia and related disciplines



To provide a forum for exchange of ideas and knowledge among practitioners of pediatric anesthesia



To support the goals of the American Society of Anesthesiologists and the American Academy of Pediatrics

TABLE 35-1   -- Presidents of the Society for Pediatric Anesthesia




1986 to 1988

Myron Yaster, M.D.

Baltimore, MD

1988 to 1990

Robert Crone, M.D.

Seattle, WA

1990 to 1992

Aubrey Maze, M.D.

Phoenix, AZ

1992 to 1994

Charles Lockhart, M.D.

Denver, CO

1994 to 1996

William Greeley, M.D.

Durham, NC

1996 to 1998

Mark Rockoff, M.D.

Boston, MA

1998 to 2000

Steven Hall, M.D.

Chicago, IL

2000 to 2002

Peter Davis, M.D.

Pittsburgh, PA

2002 to 2004

Anne Lynn, M.D.

Seattle, WA

2004 to 2006

Francis McGowan, M.D.

Boston, MA



The SPA collaborated with other groups interested in pediatric anesthesiology in developing a proposal to have fellowship training formally accredited by the Accreditation Council for Graduate Medical Education ( Rockoff and Hall, 1997 ). This was successful in 1997; there are 43 programs in the United States that offer 1 year of training in pediatric anesthesiology to individuals who have completed a basic residency in anesthesiology ( American Medical Association, 2003 ). Furthermore, subspecialization within pediatric anesthesiology continues to advance informally with individuals developing additional experience in areas such as pediatric pain medicine, pediatric intensive care, pediatric cardiac anesthesiology, and others.

Finally, many additional textbooks directed to pediatric anesthesia have been published and several have been updated into multiple editions; these include texts by Gregory (2002) ; Coté, Todres, Goudsouzian, and Ryan (2001); Smith (now edited by Motoyama and Davis, 2005 ); Berry (1990) ; Brown and Fisk (1992) ; Sumner and Hatch (1999) ; Steward and Lerman (2001) ; Bisonnette and Dalens (2002) ; and others. The further development of pediatric anesthesiology into subspecialties became evident in texts on topics such as uncommon diseases ( Katz and Steward, 1993 ), neonatal anesthesia (Hatch, Sumner, and Hellmann, 1995 ), pediatric pain ( Bush and Harkins, 1991 ; Tobias, 1996; Schechter, Berde and Yaster, 2002 ), regional anesthesia ( Saint-Maurice and Steinberg, 1990 ), cardiac anesthesia ( Lake, 1998 ), and intensive care ( Rogers, 1996 ; Todres, 1996 ; and others). The journal Paediatric Anaesthesia, originally edited by Bush in Liverpool and Saint-Maurice in Paris, became the first independent monthly publication devoted to this field; with its international editorial board members, it has led to enhanced worldwide relationships among pediatric anesthesiologists. Anesthesia & Analgesia, one of the largest anesthesia journals in the world, has also developed a separate section devoted to pediatric anesthesia. Furthermore, pediatric anesthesiologists are members of the editorial boards of Anesthesiology and several other well-respected international anesthesia journals.

Copyright © 2008 Elsevier Inc. All rights reserved. -

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

Copyright © 2005 Mosby, An Imprint of Elsevier


Pediatric anesthesia has advanced enormously from the days when anesthesiologists and surgeons adapted adult techniques and equipment to small children. It is clear that pediatric anesthesiology is a well-established and well-recognized subspecialty in its own right. It is one of the most popular fields to pursue by individuals who desire further training after completing basic anesthesia residency, and its practitioners are desired by surgeons, pediatricians, and parents alike.

Challenges are ongoing as more complex surgical and diagnostic techniques are performed on younger and younger patients. In addition, society will always have limited resources, and ensuring adequate allocation of funding, personnel, and research priorities is an increasing problem for those who care for children as the “baby-boomer” population ages, adults live longer with ever more complicated medical conditions, and geriatric problems demand society's greater attention.

Nevertheless, history has shown that talented and dedicated individuals can and will meet the challenges ahead, and there are few who doubt that things are better now for pediatric anesthesiologists'and most important, for their patients'than ever before.

Copyright © 2008 Elsevier Inc. All rights reserved. -

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

Copyright © 2005 Mosby, An Imprint of Elsevier


Abajian et al., 1984. Abajian JC, Mellish RW, Browne AF, et al: Spinal anesthesia for the high-risk infant.  Anesth Analg  1984; 63:359.

Aharon et al., 2001. Aharon AS, Drinkwater DC, Churchwell KB, et al: Extracorporeal membrane oxygenation after repair of congenital cardiac lesions.  Ann Thorac Surg  2001; 72:2095.

American Academy of Pediatric Dentistry, 1997. American Academy of Pediatric Dentistry : Guidelines for the elective use of pharmacologic conscious sedation and deep sedation in pediatric dental patients.  Pediatr Dent  1997; 19:48.

American Academy of Pediatrics, Clinical Report, 2003. American Academy of Pediatrics, Clinical Report : Facilities and equipment for the care of pediatric patients in a community hospital.  Pediatrics  2003; 111:1120.

American Academy of Pediatrics, Committee on Drugs, Section on Anesthesiology, 1992. American Academy of Pediatrics, Committee on Drugs, Section on Anesthesiology : Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures.  Pediatrics  1992; 89:1110.

American Academy of Pediatrics, Section on Urology, 1996. American Academy of Pediatrics, Section on Urology : Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychologic effects of surgery and anesthesia.  Pediatrics  1996; 97:590.

American Academy of Pediatrics, Surgical Advisory Panel, 2002. American Academy of Pediatrics, Surgical Advisory Panel : Guidelines for referral to pediatric surgical specialists.  Pediatrics  2002; 110:187.

American College of Emergency Physicians, 1997. American College of Emergency Physicians : The use of pediatric sedation and analgesia.  Ann Emerg Med  1997; 29:834.

American Medical Association, 2003. American Medical Association : Graduate Medical Education Directory,  Chicago, AMA, 2003.

American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists, 1996. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non-Anesthesiologists : Practice guidelines for sedation and analgesia by non-anesthesiologists.  Anesthesiology  1996; 84:459.

Anand and Hickey, 1987. Anand KJS, Hickey PR: Pain and its effects in the human neonate and fetus.  N Engl J Med  1987; 317:1321.

Anderson, 1955. Anderson SM: Controlled hypotension with Arfonad in pediatric surgery.  Br Med  1955; 72:103.

Anderson, 1951. Anderson SM: Use of depressant and relaxant drugs in infants and children.  Lancet  1951; 2:965.

Apgar, 1953. Apgar V: Proposal for new method of evaluation of newborn infants.  Anesth Analg  1953; 32:260.

Armand-Delille, 1932. Armand-Delille PF: Morphine injection before induction of general anesthesia in children.  Bull Acad Natl Med  1932; 107:890.

Ayre, 1937. Ayre P: Endotracheal anesthesia for babies with special reference to harelip and cleft lip operations.  Anesth Analg  1937; 16:330.

Bain and Spoerel, 1972. Bain JA, Spoerel WE: A streamlined anaesthetic system.  Can Anaesth Soc J  1972; 19:426.

Baron and Kohlmoos, 1951. Baron SH, Kohlmoos HW: Laryngeal sequelae of endotracheal anesthesia.  Ann Otol Rhinol Laryngol  1951; 60:67.

Bartlett et al., 1979. Bartlett RH, Gazzaniga AB, Huxtable RH: Extracorporeal membrane oxygenation (ECMO) in newborn respiratory failure: Technical consideration.  Trans Am Soc Artif Organs  1979; 25:473.

Bartlett et al., 2000. Bartlett RH, Roloff DW, Custer JR, et al: Extracorporeal life support: The University of Michigan experience.  JAMA  2000; 283:904.

Beecher and Todd, 1954. Beecher HK, Todd DP: A study of the deaths associated with anesthesia and surgery.  Ann Surg  1954; 140:2.

Bennett and Bowyer, 1982. Bennett EJ, Bowyer DE: Principles of pediatric anesthesia,  Springfield, IL, Charles C Thomas, 1982.

Bennett et al., 1970. Bennett EJ, Dougherty MJ, Jenkins MT: Fluid requirements for neonatal anesthesia and operation.  Anesthesiology  1970; 32:343.

Bernhard et al., 1966. Bernhard WF, Navarro RV, Yagi H, et al: Cardiovascular surgery in infants performed under hyperbaric conditions.  Vasc Dis  1966; 3:33.

Berry, 1986. Berry FA: Anesthesia for the child with a difficult airway.   In: Berry FA, ed. Anesthetic management of difficult and routine pediatric patients,  New York: Churchill Livingstone; 1986.

Berry, 1990. Berry FA: Anesthetic management of difficult and routine pediatric patients,  2nd ed.. New York, Churchill Livingstone, 1990.

Berry, 1993. Berry FA: Editorial: When is a control group not a control?.  Paediatr Anaesth  1993; 3:63.

Berry, 1995. Berry FA: The winds of change.  Paediatr Anaesth  1995; 5:279.

Betcher, 1958. Betcher AM: Hypno-induction techniques in pediatric anesthesia.  Anesthesiology  1958; 19:279.

Bigelow, 1846. Bigelow HJ: Insensibility during surgical operations produced by inhalation.  Boston Med Surg J  1846; 35:16.

Bissonnette and Dalens, 2002. Bissonnette B, Dalens BJ: Pediatric anesthesia: Principles and practice,  New York, McGraw-Hill, Medical Pub. Division, 2002.

Black and Fisk, 1979. Black TCK, Fisk GC: Anaesthesia for children including aspects of intensive care,  London, Blackwell Scientific Publications, 1979.

Brain, 1983. Brain AIJ: The laryngeal mask: A new concept in airway management.  Br J Anaesth  1983; 55:801.

Dartmouth Pediatric Sedation Project Site.   Brandstater BM: Prolonged intubation: An alternative to tracheostomy in infants. In Proceedings of the European Congress of Anaesthesia, 1962.

Bratton et al., 2001. Bratton SL, Haberkern CM, Waldhausen JHT, et al: Intussusception: Hospital size and risk of surgery.  Pediatrics  2001; 107:299.

Brennan, 1957. Brennan HJ: Vaporizer for fluothane.  Br J Anaesth  1957; 29:332.

Britt, 1979. Britt BA: Etiology and patho-physiology of malignant hypothermia.  Fed Proc  1979; 38:44.

Brown and Fisk, 1979. Brown TCK, Fisk GC: Anaesthesia for children,  Oxford, Blackwell Publishing, 1979.

Brown and Fisk, 1992. Brown TCK, Fisk GC: Anaesthesia for children,  2nd ed.. Oxford, Blackwell, 1992.

Bush and Stead, 1962. Bush GH, Stead AL: The use of d-tubocurarine in neonatal anaesthesia.  Br J Anaesth  1962; 34:721.

Bush and Harkins, 1991. Bush JP, Harkins SW: Children in pain: Clinical and research issues from a developmental perspective,  New York, Springer-Verlag, 1991.

Buxton, 1888. Buxton DW: Anaesthetics: Their use and administration,  London, HK Lewis Co Ltd., 1888.

Campbell et al., 2003. Campbell BT, Braun T, Schumacher R, et al: Impact of ECMO on neonatal mortality in Michigan (1980–1999).  J Pediatr Surg  2003; 38:290.

Cohen et al., 1990. Cohen MM, Cameron CB, Duncan PG: Pediatric anesthesia morbidity and mortality in the perioperative period.  Anesth Analg  1990; 70:160.

Cole, 1945. Cole F: A new endotracheal tube for infants.  Anesthesiology  1945; 6:87.

Colgan and Keats, 1957. Colgan FC, Keats AS: Subglottic stenosis, a cause of difficult intubation.  Anesthesiology  1957; 18:265.

Conn et al., 1980. Conn AW, Montes JE, Barker GA, et al: Cerebral salvage in near-drowning following neurological classification by triage.  Can Anaesth Soc J  1980; 27:201.

Conn, 1992. Conn AW: Origins of paediatric anaesthesia in Canada.  Paediatr Anaesth  1992; 2:179.

Cook, 1974. Cook DR: Neonatal anesthetic pharmacology: A review.  Anesth Analg  1974; 53:544.

Cook and Marcy, 1988. Cook DR, Marcy JH: Neonatal anesthesia,  Pasadena, CA, Appleton Davies, 1988.

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

Coté et al., 2001. Coté CJ, Todres ID, Goudsouzian N, Ryan JF: A practice of anesthesia for infants and children,  3rd ed.. Philadelphia, WB Saunders, 2001.

Crasilneck and Hally, 1985. Crasilneck HB, Hally JA: Clinical hypnosis: Principles and application,  2nd ed.. New York: Grune & Stratton; 1985:262.

Cullen, 1943. Cullen SC: The use of curare for the improvement of abdominal muscle relaxation during inhalation anesthesia.  Surgery  1943; 14:261.

Food and Drug Administration.   Dartmouth Pediatric Sedation Project Site: Available at

Davenport, 1967. Davenport HT: Paediatric anaesthesia,  Philadelphia, Lea & Febiger, 1967.

Davenport and Barr, 1963. Davenport HT, Barr MN: Blood loss during pediatric operations.  Can Med Assoc  1963; 789:1309.

Davis et al., 2001. Davis PJ, Galinkin J, McGowan FX, et al: A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy.  Anesth Analg  2001; 93:1380-1387.

Deming, 1952. Deming MV: Agents and techniques for induction of infants and young children.  Anesth Analg  1952; 31:113.

Denborough et al., 1960. Denborough MA, Forster FA, Lovell RRH, et al: Anaesthetic deaths in a family.  Lancet  1960; 2:45.

Dibbins, 1976. Dibbins AW: Neonatal diaphragmatic hernia: A physiologic challenge.  Am J Surg  1976; 131:408.

Domino et al., 1965. Domino EF, Chodoff P, Corssen G: Pharmacologic effects of CI-581, a new dissociative anesthetic in man.  Clin Pharm Ther  1965; 6:279.

Dorsch and Dorsch, 1975. Dorsch JA, Dorsch SE: Understanding anesthetic equipment,  Baltimore, Williams & Wilkins, 1975.

Downes and Raphaely, 1975. Downes JJ, Raphaely RC: Pediatric intensive care.  Anesthesiology  1975; 43:238.

Downes, 1992. Downes JJ: The historical evolution, current status, and prospective development of pediatric critical care.  Crit Care Clin  1992; 8:1.

Downes, 1995. Downes JJ: What is a paediatric anaesthesiologist? The American perspective.  Paediatr Anaesth  1995; 5:277.

Eather, 1958. Eather KE: Axillary brachial plexus block.  Anesthesiology  1958; 19:683.

Eckenhoff, 1966. Eckenhoff JE: Anesthesia from Colonial times,  Philadelphia: JB Lippincott; 1966:27.

Eckenhoff, 1953. Eckenhoff JE: Relationship of anesthesia to postoperative personality changes in children.  Am J Dis Child  1953; 86:587.

Eckenhoff, 1951. Eckenhoff JE: Some anatomic considerations of the infant larynx influencing endotracheal intubation.  Anesthesiology  1951; 12:401.

Eger et al., 1965. Eger EI, Saidman LJ, Branstater B: Minimum alveolar concentration: A standard of anesthetic potency.  Anesthesiology  1965; 26:756.

Enderby, 1950. Enderby GEH: Controlled circulation with hypotensive drugs and posture to reduce bleeding in surgery.  Lancet  1950; 1:1145.

Fabian et al., 1958. Fabian LW, Newton GW, Stephen CR: Simple and accurate Fluothane vaporizer.  Anesthesiology  1958; 19:284.

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

Finch and Jamleson, 1987. Finch E, Jamleson S: Anesthesia for combined heart and lung transplantation.   In: Brown Jr BR, ed. Anesthesia and transplantation surgery: Contemporary anesthesia practice,  Philadelphia: FA Davis; 1987.

Flagg, 1951. Flagg PJ: Endotracheal inhalation anesthesia: Special reference to postoperative reaction and suggestions for their elimination.  Laryngoscope  1951; 61:1.

Fletcher, 1993. Fletcher R: Gas exchange during anaesthesia and controlled ventilation in children with congenital heart disease.  Paediatr Anaesth  1993; 3:5.

Hodges, 1955.   Food and Drug Administration: Cardiac arrest in children and adolescent patients receiving succinylcholine: Succinylcholine-induced hyperkalemia. Available at

Fortuna, 1967. Fortuna A: Caudal analgesia: A simple and safe technique in paediatric surgery.  Br J Anaesth  1967; 39:165.

Freeman et al., 1993. Freeman JA, Doyle E, Im NG, et al: Topical anaesthesia of the skin.  Paediatr Anaesth  1993; 3:129.

Friesen, 1995. Friesen RH, et al: Oral transmucosal fentanyl citrate for preanaesthetic medication for pediatric cardiac surgery patients.  Paediatr Anaesth  1995; 5:29.

Furman et al., 1971. Furman EB, Roman DG, Hairabet J, et al: Management for surgical separation of newborn conjoined twins.  Anesthesiology  1971; 34:95.

Furman et al., 1975. Furman EB, Roman DG, Hemmer E, et al: Specific therapy in water, electrolyte and blood volume replacement during pediatric surgery.  Anesthesiology  1975; 42:187.

Galinkin et al., 2001. Galinkin JL, Davis PJ, McGowan FX, et al: A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy.  Anesth Analg  2001; 93:1387.

Gibbon, 1937. Gibbon JH: Artificial maintenance of circulation during experimental occlusion of pulmonary artery.  Arch Surg  1937; 34:1105.

Gillespie, 1939. Gillespie NA: Endotracheal anaesthesia in infants.  Br J Anaesth  1939; 17:2.

Goldbloom, 1917. Goldbloom RB: Halifax and the precipitate birth of pediatric surgery.  Pediatrics  1917; 11:164.

Goudsouzian et al., 1975. Goudsouzian NG, Donlon JN, Savarese JJ: Re-evaluation of dosage and duration of action of d-tubocurarine in the pediatric age group.  Anesthesiology  1975; 43:416.

Goudsouzian and Standaert, 1986. Goudsouzian NG, Standaert FG: The infant and the myoneural junction.  Anesth Analg  1986; 65:1208.

Graff et al., 1964. Graff TD, Benson DW, Holzman RS, et al: Acid-base balance in infants during halothane anesthesia with the use of an adult circle absorption system.  Anesth Analg  1964; 43:583.

Gregory, 2002. Gregory GA: Pediatric anesthesia,  4th ed.. Philadelphia, Churchill Livingstone, 2002.

Gregory et al., 1969. Gregory GA, Eger EI, Munson ES: The relationship between age and halothane requirement.  Anesthesiology  1969; 31:344.

Gregory and Steward, 1983. Gregory GA, Steward DJ: Life-threatening perioperative apnea in the ex-premie.  Anesthesiology  1983; 59:495.

Griffith, 1934. Griffith HR: John Snow, pioneer specialist in anesthesia.  Anesth Analg  1934; 13:45.

Gronert, 1980. Gronert GA: Malignant hyperthermia.  Anesthesiology  1980; 53:395.

Gross, 1953. Gross RE: The surgery of infancy and childhood,  Philadelphia, WB Saunders, 1953.

Guedel, 1937. Guedel A: Inhalation anesthesia,  New York, The Macmillan Co, 1937.

Gwathmey, 1907. Gwathmey JT: Anesthesiology in infants and children.  Pediatrics  1907; 19:734.

Haggard, 1940. Haggard HW: The place of the anesthetist in American medicine.  Anesthesiology  1940; 1:1.

Harmel and Lamont, 1948. Harmel HH, Lamont A: Anesthesia in the surgical treatment of congenital pulmonary stenosis.  Anesthesiology  1948; 7:477.

Harris, 1950. Harris AJ: Management of anesthesia for congenital heart operation in children.  Anesthesiology  1950; 11:328.

Harris, 1957. Harris JS: Special pediatric problems in fluid and electrolyte therapy in surgery.  Ann N Y Acad Sci  1957; 66:966.

Harrison et al., 1993. Harrison MR, Adzick NS, Flake AW, et al: Correction of congenital diaphragmatic hernia in utero: VI. Hard lessons learned.  J Pediatr Surg  1993; 28:1411.

Harrison et al., 1990. Harrison MR, Adzick NS, Longaker MT, et al: Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax.  N Engl J Med  1990; 322:1582.

Harrison et al., 1982. Harrison MR, Golbus MS, Filly RA, et al: Open fetal surgery was performed at UCSF.  N Engl J Med  1982; 308:591.

Hatch et al., 1995. Hatch D, Sumner E, Hellmann J: Surgical neonate: Anaesthesia and intensive care,  3rd ed.. New York, Oxford University Press, 1995.

Hatch, 1984. Hatch DJ: Neonatal anaesthesia,  London, Churchill Davidson, 1984.

Hatch, 1968. Hatch DJ: Prolonged nasotracheal intubation in infants and children.  Lancet  1968; 1:1272.

Herbert et al., 1971. Herbert WI, Scott EB, Lewis GB: Fluid management of pediatric patients.  Anesth Analg  1971; 50:376.

Hewer, 1923. Hewer CL: Anaesthesia in children,  London, HK Lewis Co. Ltd., 1923.

Hickey and Hansen, 1984. Hickey PR, Hansen DD: Fentanyl- and sufentanil-oxygen-pancuronium anesthesia for cardiac surgery in infants.  Anesth Analg  1984; 63:117.

Hikasa et al., 1967. Hikasa Y, Shirocani H, Satomura K, et al: Open-heart surgery in infants with an aid of hypothermic anesthesia.  Arch Jpn Chir  1967; 36:495.

Laussen, 2005.   Hodges RJH: Suxamethonium tolerance and pseudocholinesterase levels in children. Proceedings of World Conference of Anaesthetists, Sheveningen, the Netherlands, September 5–10, 1955, pp. 247–251.

Holak et al., 2003. Holak EJ, Mei DA, Dunning MB, et al: Carbon monoxide production from sevoflurane breakdown: Modeling of exposures under clinical conditions.  Anesth Analg  2003; 96:757.

Holliday and Segar, 1957. Holliday MA, Segar WE: The maintenance need for water in parenteral fluid therapy.  Pediatrics  1957; 19:823.

Holzman, 1994. Holzman RS: Morbidity and mortality in pediatric anesthesia.  Pediatr Clin North Am  1994; 41:239.

Holzman et al., 1996. Holzman RS, van der Velde ME, Kaus SJ, et al: Sevoflurane depresses myocardial contractility less than halothane during induction of anesthesia in children.  Anesthesiology  1996; 85:1260.

Horiuchi et al., 1963. Horiuchi T, Koyamada K, Matano I, et al: Radical operation for ventricular septal defect in infancy.  J Thorac Cardiovasc Surg  1963; 46:180.

Hunt, 1955. Hunt KH: Resistance in respiratory valves and canisters.  Anesthesiology  1955; 16:190.

Inkster, 1956. Inkster JS: The T-piece technique in anaesthesia.  Br J Anaesth  1956; 28:512.

Iwai and Satoyoshi, 1992. Iwai S, Satoyoshi M: History of paediatric anaesthesia in Japan.  Paediatr Anaesth  1992; 2:275.

Jackson, 1951. Jackson K: Psychological preparation as a method of reducing the emotional trauma of anesthesia in children.  Anesthesiology  1951; 12:293.

Jamieson et al., 1984. Jamieson SW, Stinson EB, Baldwin JC, Shumway NE: Operative technique for heart-lung transplantation.  J Thorac Cardiovasc Surg  1984; 87:930.

Jenkins et al., 1995. Jenkins KJ, Newburger JW, Lock JE, et al: In-hospital mortality for surgical repair of congenital heart defects: Preliminary observations of variation in caseload.  Pediatrics  1995; 95:323.

Johnstone, 1956. Johnstone M: The human cardiovascular response to Fluothane anesthesia.  Br J Anaesth  1956; 28:392.

Junkin et al., 1957. Junkin CL, Smith C, Conn AW: Fluothane for pediatric anesthesia.  Can Anaesth Soc J  1957; 4:259.

Kain et al., 2003. Kain ZN, Caldwell-Andrews AA, Wang SM, et al: Parental intervention choices for children undergoing repeated surgeries.  Anesth Analg  2003; 96:970.

Kain et al., 2000. Kain ZN, Hofstadter MB, Mayes LC, et al: Midazolam: effects on amnesia and anxiety in children.  Anesthesiology  2000; 93:676.

Kain et al., 1998. Kain ZN, Mayes LC, Wang SM, et al: Parental presence during induction of anesthesia versus sedative medication: Which intervention is more effective?.  Anesthesiology  1998; 89:1147.

Kass, 1996. Kass E: Timing of elective surgery on the genitalia of male children with particular reference to the risks, benefits, and psychological effects of surgery and anesthesia.  Pediatrics  1996; 97:590.

Katz and Steward, 1993. Katz J, Steward DJ: Anesthesia and uncommon pediatric diseases,  2nd ed.. Philadelphia, WB Saunders, 1993.

Keenan and Boyan, 1985. Keenan RL, Boyan CP: Cardiac arrest due to anesthesia.  JAMA  1985; 253:2373.

Keenan et al., 1991. Keenan RL, Shapiro JH, Dawson K: Frequency of anesthetic cardiac arrests in infants: Effect of pediatric anesthesiologists.  J Clin Anesth  1991; 3:433.

Keenan et al., 1994. Keenan RL, Shapiro JH, Kane FR, Simpson PM: Bradycardia during anesthesia in infants: an epidemiologic study.  Anesthesiology  1994; 80:976.

Kilduff et al., 1956. Kilduff CJ, Wyant GM, Dale RH: Anaesthesia for repair of cleft lip and palate in infants using moderate hypothermia.  Can Anaesth Soc J  1956; 3:102.

Kopetsky, 1903. Kopetsky SJ: The selection of anesthesia in children.  Med Rec  1903; 14:534.

Kososka et al., 2001. Kososka ER, Minkes RK, Silen ML, et al: Effect of pediatric surgical practice on the treatment of children with appendicitis.  Pediatrics  2001; 107:1298.

Lake, 1998. Lake CL: Pediatric cardiac anesthesia,  3rd ed.. Stamford, CT, Appleton & Lange, 1998.

Lanza et al., 2000. Lanza RP, Langer R, Vacanti JP: Principles of tissue engineering,  2nd ed.. New York, Academic Press, 2000.

Laussen, 2005.   Laussen PC: Mechanical support of the circulation: The ABC&E of pediatric resuscitation. Available at Accessed March 24, 2005.

Leigh and Belton, 1948. Leigh MD, Belton MK: Pediatric anesthesia,  New York, The Macmillan Co., 1948.

Leigh et al., 1957. Leigh MD, McCoy DD, Belton MK, et al: Bradycardia following intravenous administration of succinylcholine chloride to infants and children.  Anesthesiology  1957; 18:698.

Lerman et al., 1986. Lerman J, Eustis S, Smith DR: Effect of droperidol pretreatment on postanesthetic vomiting in children undergoing strabismus surgery.  Anesthesiology  1986; 65:322.

Levy, 1945. Levy DM: Psychic trauma of operation in children.  Am J Dis Child  1945; 69:75.

Lewis and Taufic, 1953. Lewis FJ, Taufic M: Closure of atrial septal defect with the aid of hypothermia: Experimental accomplishments and report of one successful case.  Surgery  1953; 33:52.

Lindahl, 1989. Lindahl SGE: Oxygen consumption and carbon dioxide elimination in infants and children during anaesthesia and surgery.  Br J Anaesth  1989; 62:70.

Liu et al., 1983. Liu LMP, Coté CJ, Goudsouzian NG, et al: Life-threatening apnea in infants recovering from anesthesia.  Anesthesiology  1983; 59:506.

Lomaz, 1965. Lomaz JG: Halothane and jaundice in paediatric anesthesia.  Anaesthesia  1965; 20:70.

Long, 1849. Long CW: An account of the first use of sulphuric ether by inhalation as an anaesthetic in surgical operations.  S Med Surg J  1849; 5:45.

Lowrie et al., 1998. Lowrie L, Weiss AH, Lacombe C: The pediatric sedation unit: A mechanism for pediatric sedation.  Pediatrics  1998; 102:E30.

Lunn, 1992. Lunn JN: Implications of the national confidential enquiry into perioperative deaths for paediatric anaesthesia.  Paediatr Anaesth  1992; 2:69.

MacDonald and Stocks, 1965. MacDonald IH, Stocks JG: Prolonged nasotracheal intubation: A review of its development in a paediatric hospital.  Br J Anaesth  1965; 37:161.

Macon and Bruner, 1950. Macon EB, Bruner HD: The scientific aspect of endotracheal tubes.  Anesthesiology  1950; 11:313.

Malviya et al., 1997. Malviya S, Voepel-Lewis T, Tait AR: Adverse events and risk factors associated with the sedation of children by non-anesthesiologists.  Anesth Analg  1997; 85:1207.

Mapleson, 1954. Mapleson WW: The elimination of rebreathing in various semi-closed anesthetic systems.  Br J Anaesth  1954; 26:323.

Marcy and Cook, 1988. Marcy JH, Cook DR: Basic neonatal anesthesia and monitoring.   In: March JH, Cook DR, ed. Neonatal anesthesia,  Pasadena, CA: Appleton Davies; 1988.

Marmer, 1959. Marmer MJ: Hypnosis as an adjunct to anesthesia in children.  Am J Dis Child  1959; 97:314.

Mason and Bingham, 1990. Mason DG, Bingham RM: The laryngeal mask airway in children.  Anaesthesia  1990; 45:760.

Matthews et al., 1957. Matthews JH, Buckley JJ, Van Bergen FH: Acute effect of low-flow extracorporeal circulation on cerebral circulation.  Anesthesiology  1957; 18:169.

McQuiston, 1949. McQuiston WO: Anesthetic problems in cardiac surgery in children.  Anesthesiology  1949; 10:590.

Melman et al., 1975. Melman E, Pennelas J, Maruffo J: Regional anesthesia in children.  Anaesth Analg  1975; 54:387.

Mendelsohn et al., 1957. Mendelsohn Jr D, Mackrell TN, Machlan MA, et al: Experiences using the pump-oxygenator for open heart surgery in man.  Anesthesiology  1957; 18:223.

Morray, 1994. Morray JP: Implications for subspecialty care of anesthetized children.  Anesthesiology  1994; 80:969.

Morray, 1993. Morray JP, et al: A comparison of pediatric and adult anesthesia closed malpractice claims.  Anesthesiology  1993; 78:461.

Morray et al., 2000. Morray JP, Geiduschek JM, Ramamoorthy C, et al: Anesthesia-related cardiac arrest in children: Initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry.  Anesthesiology  2000; 93:6.

Morton, 1847. Morton WTG: Remarks on the proper mode of administering the sulphuric ether by inhalation,  Boston, Dutton & Wentworth, Printers, 1847.

Motoyama, 1977. Motoyama EK: Pulmonary mechanics during early postnatal years.  Pediatr Res  1977; 11:220.

Motoyama and Cook, 1980. Motoyama EK, Cook CD: Respiratory physiology.   In: Smith RM, ed. Anesthesia for infants and children,  4th ed.. St. Louis: CV Mosby; 1980:38-87.

Motoyama and Davis, 2005. Motoyama EK, Davis PJ: Smith's anesthesia for infants and children,  7th ed.. Philadelphia, Elsevier, 2005.

Motoyama and Glazener, 1986. Motoyama EK, Glazener CH: Hypoxemia after general anesthesia in children.  Anesth Analg  1986; 65:267.

Murat et al., 1988. Murat I, Montay G, Delleur MM, et al: Bupivacaine pharmacokinetics during epidural anaesthesia in children.  Eur J Anaesthesiol  1988; 5:113.

Nelson, 1950. Nelson WE: Nelson's textbook of pediatrics,  Philadelphia, WB Saunders, 1950.

Neonatal Inhaled Nitric Oxide Study Group, 1997. Neonatal Inhaled Nitric Oxide Study Group : Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia.  Pediatrics  1997; 99:838.

Nicodemus et al., 1969. Nicodemus HF, Nassiri-Rahimi C, Bachman L, et al: Median effective doses (ED50) of halothane in adults and children.  Anesthesiology  1969; 31:344.

Oh and Motoyama, 1977. Oh TH, Motoyama EK: Comparison of nasotracheal intubation and tracheostomy in management of epiglottitis.  Anesthesiology  1977; 46:214.

Olsson and Hallen, 1988. Olsson GL, Hallen B: Cardiac arrest during anesthesia: A computerized study.  Acta Anaesthesiol Scand  1988; 32:653.

Onchi and Fujita, 1958. Onchi O, Fujita M: Pediatric anesthesia,  Tokyo, Nankodo & Co Ltd., 1958.

Onchi et al., 1947. Onchi Y, Hayashi T, Veyama H: Studies on the Ayre T piece technique.  Far East J Anaesth  1947; 1:30.

Orkin et al., 1954. Orkin LK, Siegel M, Rovenstine EA: I. Resistance to breathing by apparatus used in anesthesia.  Anesth Analg  1954; 33:217.

Patrick et al., 1957. Patrick RT, Theye RA, Moffitt EA: Studies in extracorporeal circulation. V. Anesthesia and supportive care during intracardiac surgery with the Gibbon-type pump-oxygenator.  Anesthesiology  1957; 18:673.

Pender, 1954. Pender JW: Endotracheal anesthesia in children.  Anesthesiology  1954; 15:495.

Pennant and White, 1993. Pennant JH, White PF: Review article: The laryngeal mask airway. Its uses in anesthesiology.  Anesthesiology  1993; 79:144.

Pernick, 1975. Pernick MS: A calculus of suffering,  New York, Columbia University Press, 1975.

Poe and Karp, 1946. Poe MF, Karp M: Seconal as a basal anesthetic in children: A preliminary report.  Anesth Analg  1946; 25:88.

Powell and Miller, 1975. Powell DR, Miller RD: The effect of repeated doses of succinylcholine on serum potassium in patients with renal failure.  Anesth Analg  1975; 54:746.

Rackow and Salanitre, 1962. Rackow H, Salanitre E: A dose effect study of preoperative medication in children.  Anesthesiology  1962; 23:747.

Raphaely and Downes, 1973. Raphaely RC, Downes Jr JJ: Congenital diaphragmatic hernia: Prediction of survival.  J Pediatr Surg  1973; 8:815.

Rees, 1991. Rees GJ: An early history of paediatric anaesthesia.  Paediatr Anaesth  1991; 1:3.

Rees, 1960. Rees GJ: Paediatric anaesthesia.  Br J Anaesth  1960; 32:132.

Rees, 1958. Rees GJ: The child as a subject for anaesthesia.   In: Evans FT, Gray TC, ed. Modern trends in anaesthesia,  New York: Harper & Row Publishers; 1958.

Rice and Baker, 1993. Rice LJ, Baker SB: Review article: Congenital diaphragmatic hernia. Does extracorporeal membrane oxygenation (ECMO) improve survival?.  Paediatr Anaesth  1993; 3:205.

Robertson and Borland, 1990. Robertson K, Borland LM: Anesthesia for organ transplantation.   In: Motoyama EK, Davis PJ, ed. Smith's anesthesia for infants and children,  St. Louis: CV Mosby; 1990.

Robson, 1936. Robson CH: Anesthesia in children.  Am J Surg  1936; 34:468.

Rockoff and Hall, 1997. Rockoff MA, Hall SC: Subspecialty training in pediatric anesthesiology: What does it mean?.  Anesth Analg  1997; 85:1185.

Rogers, 1996. Rogers MC: Textbook of pediatric intensive care,  3rd ed.. Baltimore, Williams & Wilkins, 1996.

Rogers et al., 1980. Rogers MC, Nugent S, Traystman RJ: Control of cerebral circulation in the neonate and infant.  Crit Care Med  1980; 8:570.

Root, 1962. Root B: Problems in evaluating effects of premedication in children.  Anesth Analg  1962; 41:180.

Rosen, 1992. Rosen MA: Anesthesia for fetal procedures and surgery.   In: Snider SM, Levinson G, ed. Anesthesia for obstetrics,  3rd ed.. Baltimore: Williams & Wilkins; 1992:281-285.

Ross et al., 2001. Ross AK, Davis PJ, Dear G, et al: Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures.  Anesth Analg  2001; 93:1393.

Rowe and Oribe, 1971. Rowe MI, Oribe FL: Hypoxia and the newborn infant: Blood gas and pH considerations.  Surgery  1971; 70:758.

Safar, 1958. Safar P: Ventilatory efficiency of mouth-to-mouth artificial respiration.  JAMA  1958; 167:335.

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.

Saint-Maurice and Steinberg, 1990. Saint-Maurice C, Steinberg OS: Regional anaesthesia in children,  Fribourg, Switzerland, Mediglobe, 1990.

Salanitre and Rackow, 1969. Salanitre E, Rackow H: The pulmonary exchange of nitrous oxide and halothane in infants and children.  Anesthesiology  1969; 30:388.

Salem, 1970. Salem MR: Anesthetic management of patients with a “full stomach.” A critical review.  Anesth Analg  1970; 49:47.

Salem et al., 1975. Salem MR, Bennett EJ, Schweiss JF, et al: Cardiac arrest related to anesthesia. Contributing factors in infants and children.  JAMA  1975; 233:238-241.

Sarner et al., 1995. Sarner JB, Levine M, Davis PJ, et al: Clinical characteristics of sevoflurane in children: A comparison with halothane.  Anesthesiology  1995; 82:38.

Saunders et al., 1976. Saunders NA, Powles ACP, Rebuck AS: Ear oximetry accuracy practicability in the assessment of arterial oxygenation.  Am Rev Respir Dis  1976; 113:745.

Schechter et al., 2002. Schechter NL, Berde CB, Yaster M: Pain in infants, children, and adolescents,  2nd ed.. Baltimore, Williams & Wilkins, 2002.

Schulman et al., 1967. Schulman JL, Foley JM, Vemon DTA, et al: A study of the effect of the mother's presence during anesthesia induction.  Pediatrics  1967; 39:111.

Schuster, 1967. Schuster SR: A new method for the staged repair of large omphaloceles.  Surg Gynecol Obstet  1967; 125:837.

Schwartz, 1957. Schwartz H: Chloroform anesthesia for ophthalmic examination.  Am J Ophthalmol  1957; 43:27.

Schwartz et al., 1984. Schwartz L, Rockoff MA, Koka BV: Masseter spasm with anesthesia: incidence and implications.  Anesthesiology  1984; 61:772.

Sellick, 1961. Sellick BA: Cricoid pressure to control the regurgitation of stomach contents during induction of anaesthesia.  Lancet  1961; 2:204.

Singer, 1977. Singer JJ: Cardiac arrest in children.  J Am Coll Emerg Physicians  1977; 6:198.

Small, 1951. Small GA: Brachial plexus block anesthesia in children.  JAMA  1951; 147:1648.

Smith, 1954. Smith AOC: An endo-oesophageal stethoscope.  Anesthesiology  1954; 15:566.

Smith, 1945. Smith CA: The physiology of the newborn infant,  Springfield, IL, Charles C Thomas, 1945.

Smith, 1959. Smith RM: Anesthesia for infants and children,  St. Louis, CV Mosby, 1959.

Smith, 1953b. Smith RM: Anesthesia for pediatric surgery.   In: Gross DE, ed. Surgery of infants and children,  Philadelphia: WB Saunders; 1953.

Smith, 1952. Smith RM: Circulatory factors affecting anesthesia in surgery for congenital heart disease.  Anesthesiology  1952; 13:38.

Smith, 1991. Smith RM: Progress in paediatric anaesthesia in the United States.  Paediatr Anaesth  1991; 1:63.

Smith, 1953a. Smith RM: The prevention of tracheitis in children following endotracheal anesthesia.  Anesth Analg  1953; 32:102.

Smith et al., 1964. Smith RM, Crocker DC, Adams JG: Anesthetic management of patient under hyperbaric oxygenation.  Anesth Analg  1964; 43:766.

Smith, 1947. Smith SM: The use of curare in infants and children.  Anesthesiology  1947; 8:176.

Smith et al., 1947. Smith SM, Brown H, Toman J, et al: The lack of cerebral effects of d-tubocurarine.  Anesthesiology  1947; 8:1.

Snow, 1858. Snow J: On chloroform and other anesthetics,  London, John Churchill, 1858.

Snow, 1847. Snow J: On the inhalation of the vapour of ether,  London, John Churchill, 1847.

Stanley et al., 1994. Stanley CJ, Hirschl RB, Schumacher RE, et al: Extracorporeal life support for neonatal respiratory failure: 20 Year experience.  Ann Surg  1994; 220:269.

Starzl et al., 1963. Starzl TE, Marchioro TL, von Kaulla KN, et al: Homo-transplantation of the liver in human.  Surg Gynecol Obstet  1963; 117:659.

Stead, 1955. Stead AL: The response of the newborn infant to muscle relaxants.  Br J Anaesth  1955; 27:124.

Stehling, 1992. Stehling L: Common problems in pediatric anesthesia,  2nd ed.. St. Louis, Mosby-Year Book, 1992.

Stephen, 1954. Stephen CR: Elements of paediatric anaesthesia,  Springfield, IL, Charles C Thomas, 1954.

Stephen et al., 1958. Stephen CR, Lawrence JH, Fabian LW, et al: Clinical experience with fluothane—1,400 cases.  Anesthesiology  1958; 19:197.

Stephen and Slater, 1948. Stephen CR, Slater HM: A non-rebreathing, non-resisting valve.  Anesthesiology  1948; 9:550.

Steward, 1983. Steward DJ: History of pediatric anesthesia.   In: Gregory GA, ed. Pediatric anesthesia,  New York: Churchill Davidson; 1983.

Steward, 1982. Steward DJ: Preterm infants are more prone to complications following minor surgery than are term infants.  Anesthesiology  1982; 56:304.

Steward and Lerman, 2001. Steward DJ, Lerman J: Manual of pediatric anesthesia,  5th ed.. New York, Churchill Livingstone, 2001.

Stiles, 1974. Stiles CM: A flexible fiberoptic bronchoscope for endotracheal intubation of infants.  Anesth Analg  1974; 53:1017.

Sumner and Hatch, 1999. Sumner E, Hatch D: Paediatric anaesthesia,  2nd ed.. New York, Oxford University Press, 1999.

Task Force on Sedation by Non-Anesthesiologists, 1996. Task Force on Sedation by Non-Anesthesiologists : Practice guidelines for sedation and analgesia by non-anesthesiologists.  Anesthesiology  1996; 84:459.

Taussig, 1947. Taussig HB: Congenital malformations of the heart,  New York, The Commonwealth Fund, 1947.

Taylor and Towley, 1972. Taylor PA, Towley RM: The broncho-fiberscope as an aid to endotracheal intubation.  Br J Anaesth  1972; 46:611.

Telford and Keats, 1957. Telford J, Keats AS: Succinylcholine in cardiovascular surgery in infants and children.  Anesthesiology  1957; 18:841.

Tessier et al., 1967. Tessier P, Guiot G, Delbet JP, et al: Osteotomies cranio-naso-orbito-faciales hypertelorisme.  Ann Chir Plast Esthet  1967; 12:103.

Tiret et al., 1988. Tiret L, Nivoche Y, Hatton F, Desmonts JM, Vourc'h G: Complications related to anaesthesia in infants and children.  Br J Anaesth  1988; 61:263.

Tobias and Deshpande, 1996. Tobias JD, Deshpande JK: The pediatric pain handbook,  St. Louis, Mosby, 1996.

Todres and Fugate, 1996. Todres ID, Fugate JH: Critical care of infants and children,  Boston, Little, Brown, 1996.

Ungerleider et al., 1990. Ungerleider RM, Greeley WJ, Sheikh KH, et al: Routine use of intraoperative epicardial echocardiography and Doppler color flow imaging to guide and evaluate repair of congenital heart lesions: A prospective study.  J Thorac Cardiovasc Surg  1990; 100:297.

Virtue, 1955. Virtue RW: Hypothermic anesthesia,  Springfield, IL, Charles C Thomas, 1955.

Viscusi et al., 2004. Viscusi ER, Reynolds L, Chung F, et al: Patient-controlled transdermal fentanyl hydrochloride vs intravenous morphine pump for postoperative pain: A randomized controlled trial.  JAMA  2004; 291:1333.

Warren, 1847. Warren JM: Inhalation of ether.  Boston Med Surg J  1847; 36:160.

Waters, 1938. Waters RM: Pain relief for children.  Am J Surg  1938; 39:470.

Weinstein, 1939. Weinstein ML: Rectal pentothal sodium: A new pre- and basal anesthetic drug in the practice of surgery.  Anesth Analg  1939; 18:221.

Winston et al., 1987. Winston KR, Rockoff MA, Mullikan JB, et al: Surgical division of craniopagi.  Neurosurgery  1987; 21:782.

Yaster et al., 1985. Yaster M, Aranoff D, Kornhauser DM, et al: Pharmacokinetics of lidocaine during caudal anesthesia in children.  Anesthesiology  1985; 63:A465.

Yaster and Maxwell, 1989. Yaster M, Maxwell LG: Pediatric regional anesthesia.  Anesthesiology  1989; 70:324.

Zeltzer et al., 1989. Zeltzer LK, Jay SM, Fisher DM: The management of pain associated with pediatric procedures.  Pediatr Clin North Am  1989; 36:941.

Zindler and Deming, 1953. Zindler M, Deming MV: The anesthetic management of infants for repair of congenital atresia of the esophagus with tracheo-esophageal fistula.  Anesth Analg  1953; 32:180.

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