To celebrate 100 years of the publication of Anesthesia & Analgesia (A&A), we examine the incalculable impact of the International Anesthesia Research Society (IARS) and A&A on the scholarship, clinical practice, and professionalization of pediatric anesthesiology.
Before the turn of the 20th century, there was little reference in the literature to anesthetizing pediatric patients. Two A&A articles from the 1920s demonstrate a progressive shift toward child-centered anesthetics. An article in the second issue of Current Researches in Anesthesia and Analgesia, published in October 1922 by Frances E. Haines, AM, MD, considered endotracheal, neuraxial, and intravenous (IV) anesthetics unsafe for children.1 The article “Anesthesia in Children: Safest Methods and Agents” did presage a later focus by acknowledging the advantages of reducing preoperative anxiety for a smoother induction. However, this ray of more modern thinking was quashed by this quintessential “children are just small adults” quote by the renowned nitrous oxide expert Elmer I. McKesson, MD, “in regard to the use of nitrous oxid-oxygen [sic] in children, age has no influence at all in the selection of anesthesia and besides there is not much variation in the technic of administering a babe and anesthetic from the technic for adults.”1
Three years later, “Anesthesia in Children” by Charles H. Robson, MD, presented a more advanced perspective.2 Robson2 practiced at The Hospital for Sick Children in Toronto, Canada, and was one of the first anesthesiologists known to dedicate his practice exclusively to pediatrics. He discussed the need for anesthesia in neonates, specialized equipment, preoperative fasting, monitoring of breath sounds/rapid deterioration of children’s status, and the recognition of specific techniques for congenital pathologies like pyloric stenosis and cleft lip and palate. Current Researches was beginning to rescue children from being “small adults.”
Over the next several decades, A&A reported important progress in original articles by emerging specialists, M. Digby Leigh, MD, and M. Kathleen Belton, MD, CM, who were advocates of experienced anesthesiologists caring for children, premedication, and endotracheal intubation in pediatric ear, nose, and throat (ENT) procedures.3–5 Margery van N. Deming, MD, Chief of Anesthesia at Children’s Hospital of Philadelphia (1946–1955); Robert M. Smith, MD, Chief of Anesthesia at Children’s Hospital Boston (1946–1980); M. Digby Leigh, MD, Anesthetist-in-Chief at the Children’s Memorial Hospital in Montreal (1940–1947); and C. Ronald Stephen, MD, FFARCS, at that time, Chief of Anesthesia at Children’s Memorial Hospital, Montreal, Canada (1947–1950) represented rising stars at leading children’s hospitals throughout the United States and Canada. This esteemed group was published on the fundamentals of pediatric anesthesia for the general anesthesiologist in A&A, providing resources for those who had less experience with children.6–10 T. Philip Ayre, MRCS, is a notable exception of an anesthesiologist who cared for adults and children making a significant contribution. His 1937 article in A&A introduced his eponymous “T-piece” allowing an “open” anesthetic technique free of high-resistance expiratory valves and rebreathing bags that caused “suboxygenation” in children (Figure).11 Before the Ayre’s T-piece, high-resistance “closed-circuit” breathing systems led to respiratory fatigue in small infants and significant rebreathing of expired air. With the “open” technique, “Pallor, sweating, and other signs of shock were absent.”11
Figure.: Ayre’s T-Piece connected to endotracheal tube in use for cleft lip and palate operation. Photograph from Ayre’s original 1937 A&A article. A&A indicates Anesthesia & Analgesia.
Children’s hospitals created collaborative environments for the maturation of pediatric medicine. In addition to advancements in pediatric anesthesia, the fields of neonatology and pediatric intensive care emerged in the middle of the 20th century. The Director of the Division of Anesthesia at Babies Hospital Virginia Apgar, MD, developed the appearance, pulse, grimace, activity, and respiration (APGAR) score for evaluation of newborn infants and collaborated with other physicians at Babies Hospital to establish a specialized unit for neonates.12 Apgar’s12 paper was doubly supported by presentation at the joint IARS and International College of Anesthetists meeting in 1952 then publication in Current Researches in Anesthesia & Analgesia in 1953. Committed to proper assessment and care of newborn infants, Apgar achieved one of the most impactful contributions of anesthesiology to the field of medicine.
Newly conceived to battle the polio epidemic in the early 1950s, intensive care units (ICUs) were specialized hospital wards for high acuity patients. In the 1960s, pediatric critical care grew out of this tradition to provide skilled postoperative care to children receiving cutting-edge general and cardiothoracic surgeries. Pediatric anesthesiologists who built these critical care units contributed specialized knowledge of infant respiratory care and pharmacology translating their skills from the odds ratios (ORs) to the ICUs. A&A supported innovators like John Downes, MD, contributing to the administrative and clinical development of pediatric intensive care medicine through the 1967 article “Organization of an Intensive Care Unit in a Children’s Hospital.”13
As the pediatric intensive care units (PICUs) and neonatal intensive care units (NICUs) were established, pediatric surgeons and anesthesiologists collaborated on increasingly complex surgeries for sicker pediatric patients. With specialized intraoperative and postoperative care developing, advances in congenital cardiac surgery pushed the limits of medicine in the mid to late 20th century.14 In contrast to previous decades where pediatric anesthesiologists shared the fundamental and technical aspects of pediatric anesthesia for general practice, the pediatric research published by A&A in the 1950s and forward was increasing for the dedicated pediatric anesthesiologist performing complex cases and providing cutting edge anesthetics.15 Zindler and Deming16 wrote from extensive experience on the complex anesthetics required for tracheal esophageal fistula (TEF) repair in 1953, something only possible in a specialized pediatric hospital. A&A published advances such as modified equipment, fluid management, and the appropriate use of new pharmacologic agents like rocuronium, ketamine, and chloral hydrate.17–24
As the field matured in the 1980s, pediatric anesthesiologists remained leaders in patient safety, while A&A supported these topical conversations in the pediatric anesthesiology literature. Of particular significance is pulse oximetry, which was rapidly adopted as a standard ASA monitor in 1986.25 Charles J. Cote, MD, demonstrated its utility to minimize periods of intraoperative hypoxemia in pediatric patients only 2 years later.26,27 Building on the concept of early intervention for hypoxemia through the use of pulse oximetry, A&A published several articles supporting the extension of pulse oximetry monitoring into the postanesthesia care units (PACUs).28–30
The pediatric section in A&A has led the charge in advancing pediatric pain management with articles ranging from the pharmacokinetics of medication in children to the safety of patient-controlled analgesia (PCA).31–35 The journal has furthered the practice of pediatric regional anesthesia first providing a primer of pediatric regional anesthesia in 1989, following with consistent research and commentary from experts, and later by publishing outcomes from the Pediatric Regional Anesthesia Network (PRAN), which studies the practice, risks, and complications of regional anesthesia in children.36–39A&A published a report from the first 3 years of PRAN registry data in 2012, which supported the use of regional anesthetics in children after finding minimal complications within the large data base.40,41
To this point, we have demonstrated how A&A documented and spurred the development of equipment, pharmacology, and delivery techniques in pediatric anesthesiology. Management of perioperative anxiety stands out from the other advances as a distinctly patient-centered approach in pediatric anesthesia practice. The early articles hold astute observations about the nature of fear and attempt to control it through behavioral or pharmacological means. Haines1 in 1922 and Robson2 in 1925 addressed the effects of distress of induction of anesthesia and encouraged building a rapport with the child. In 1935, Leech42 dedicated an entire article to preanesthetic medication in children, and Smith, Leigh, and Belton continued the discussion on chemical control of preoperative anxiety including barbiturates and opioids into the 1950s.5,43 Beginning in the 1990s and continuing today, Zeev Kain, MD, MBA, picked up the torch and elevated the discussion by developing a standardized assessment tool to provide evidence-based practice. Through his work, predominantly published in A&A, Kain et al44–46 drove the agenda on premedication, preoperative anxiety, postoperative behavioral outcomes, emergence delirium, anxiety measurement tools, and specific interventions.47 Most notably, Kain et al48 developed the validated perioperative anxiety scale, Yale Pre-Operative Anxiety Scale, which is now considered the gold standard for scholarly work on perioperative anxiety. From Robson’s astute clinical observations of children’s anxiety to Kain’s qualitative and quantitative work on perioperative anxiety, the field of pediatric anesthesiology recognized the disproportionate stress and lasting psychological effects of perioperative anxiety.
The first organized pediatric anesthesiology fellowships appeared in the 1970s, although the Accreditation Council of Graduate Medical Education (ACGME) accreditation would not happen until the 1990s. Increased pediatric training opportunities arrived in the 1980s when the embedded training third categorical (CA3) year allowed for 6 months of focused subspecialty training and a growing number of pediatric anesthesiology fellowships. Over the next 2 decades, these pediatric anesthesiologists would organize professionally into the American Academy of Pediatrics Anesthesiology Section, the American Society of Anesthesiologists Pediatric Anesthesia Committee, and the Society for Pediatric Anesthesia. In 1991 as part of recognizing the growing communities of subspecialists in anesthesiology, A&A created a pediatric anesthesia subspecialty section with a pediatric editor and formal affiliation with the Society for Pediatric Anesthesia by 1996.49
With a robust academic community of clinical and laboratory research, pediatric anesthesiology sought ACGME accreditation for their fellowship in the mid-1990s. Indirectly, A&A played an early role in the ACGME accreditation for pediatric anesthesiology fellowship. A central argument for accreditation of a pediatric anesthesiology subspecialty was that enforcing a standardized curriculum would, in the end, improve patient care, and A&A had a long and consistent history of publishing morbidity and mortality data on pediatric anesthesia.7,50–54 In recognition of the clinical expertise and complex care of sick children, in 1997, the ACGME recognized a set of national standards for pediatric anesthesiology training, including exposure to pediatric pain medicine, pediatric cardiac anesthesia, and intensive care. Some parts of this contentious debate spilled onto the pages of A&A.55,56 The professional discussion in addition to the morbidity and mortality data in A&A may have supported the formalization of pediatric anesthesia fellowships and eventually recognition as an American Board of Anesthesiology subspecialty.
Pediatric anesthesiologists in the 21st century have opportunities for advanced fellowships and combined residencies to provide further specialized training. In recent years, A&A has provided a forum for the evolution of these aspects of pediatric anesthesiology. The Congenital Cardiac Anesthesia Society (CCAS) communicates position statements through A&A including pediatric cardiac anesthesia fellowship training milestones and coronavirus disease 2019 (COVID-19)–related recommendations.57,58 Most recently, the CCAS applied to the ACGME in October 2021 for a 1-year accredited advanced fellowship in pediatric cardiac anesthesia was approved in February 2021. Similarly, formative discussion regarding pediatric critical care occurs on the pages of A&A.59,60 Although pediatric critical care was born of pediatric surgery and anesthesiology, the pathway to a pediatric critical care fellowship is now restricted through a pediatric residency track. Combined pediatric and anesthesia residencies exist allowing residents with an interest in anesthesiology a route to the pediatric critical care fellowship. Recent discussions in A&A highlight the challenges of this system and how it has limited the presence of anesthesiology trained pediatric critical care specialists due to the extensive length of training required.61
While A&A continues to discuss timely topics and progress in pediatric anesthesia, the IARS is pivotal in addressing a central question of potential cognitive consequences of anesthesia in children. The questions of neurotoxicity raised in the early 2000s led to the IARS partnering with the Food and Drug Administration (FDA) to initiate the SmartTots initiative in 2010. Its mission is “to coordinate and fund research with the goal of ensuring safe surgery for the millions of infants and young children who undergo anesthesia and sedation each year.”62 SmartTots funds “research in the fields of anesthesiology, pediatrics, neuroscience, and epidemiology and supports studies of existing anesthetic drugs and their effects on childhood development.”62 Investigators like Lena Sun, MD, from well-known pediatric anesthesia neurotoxicity research initiatives like the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) Study received grants from SmartTots.63 Recent publications in A&A continue the conversation on pediatric anesthetic neurotoxicity including work from SmartTots grant recipients on prenatal exposure to general anesthesia, dexmedetomidine and clonidine effects on sevoflurane-induced neurophysiologic changes, and cognitive impairment in mice, and whether exposure to a single anesthetic before age 3 has lasting neuropsychological effects.64–66
A&A provided a platform for the evolution of the clinical, academic, and professional growth of pediatric anesthesiology over the past 100 years. Organizations like the IARS provide the necessary community for professional development. Pediatric anesthesiologists have discussed the challenges of practice, introduced new research, and debated organizational and administrative issues in the pages of A&A. The journal provided the crucial and game-changing forum for pediatric anesthesiologists to publish their research, culminating in the pediatric subspecialty section and support of the Society for Pediatric Anesthesia.
A&A documented and enabled the maturation of pediatric anesthesiology; pediatric anesthesia and pediatric anesthesiologists would be far poorer without A&A.
DISCLOSURES
Name: Melissa L. Coleman, MD.
Contribution: This author helped define the research question, research and analyze primary sources, and write the manuscript.
Name: David B. Waisel, MD.
Contribution: This author helped define and guide the research question, write the manuscript, and provide comments and edits to the manuscript.
This manuscript was handled by: Douglas R. Bacon, MD, MA.
REFERENCES
1. Haines FE. Anesthesia in children: safest methods and agents. Curr Res Anesth Analg. 1922;1:50–54.
2. Robson C. Anesthesia in children. Curr Res Anesth Analg. 1925;4:235–240.
3. Leigh MD, Fitzgerald RR. Endotracheal anesthesia supplementing avertin in cleft palate operations. Curr Research Anesth Analg. 1937;16:64–65.
4. Leigh MD, Belton MK. Anesthesia for ear, nose and throat operations in infants and children. Curr Res Anesth Analg. 1948;27:41–48.
5. Belton MK, Leigh MD. Premedication in pediatric anesthesia. Curr Res Anesth Analg. 1950;29:68–76.
6. Leigh MD, Belton MK, Lewis GB. Pediatric anesthesia. Curr Res Anesth Analg. 1956;35:1–17.
7. Smith RM. Complications of anesthesia in pediatrics. Curr Res Anesth Analg. 1948;27:227–231.
8. Stephen CR, Slater HM. Agents and techniques employed in pediatric anesthesia. Curr Res Anesth Analg. 1950;29:254–262.
9. Deming MV. Agents and techniques for induction of anesthesia in infants and young children. Curr Res Anesth Analg. 1952;31:113–119.
10. Smith RM. Indications for endotracheal intubation in pediatric anesthesia. Curr Res Anesth Analg. 1954;33:107–114.
11. Ayre P. Endotracheal anesthesia for babies with special reference to hare-lip and cleft palate operations. Curr Res Anesth Analg. 1937;16:330–333.
12. Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg. 1953;32:260–267.
13. Bachman L, Downes JJ, Richards CC, Coyle D, May E. Organization and function of an intensive care unit in a children’s hospital. Anesth Analg. 1967;46:570–574.
14. Smith RM, Engineer EH. Problems related to openheart operations on children: part 2. Anesth Analg. 1960;39:267–272.
15. Austin S. Anesthesia for bronchoscopy and bronchography in children. Anesth Analg. 1963;42:632–639.
16. Zindler M, Van Deming MN. The anesthetic management of infants for the surgical repair of congenital atresia of the esophagus with tracheo-esophageal fistula. Curr Res Anesth Analg. 1953;32:180–190.
17. Bachman L, Nightingale A, Paymaster N. Neuromuscular blockade in infants and children. Anesth Analg. 1964;43:744–747.
18. Mojdehi E, Mauro AL, Labartino L, Reynolds B. Clinical evaluation of hydroxyzine hydrochloride in pediatric anesthesia and its effect on arousal time. Anesth Analg. 1968;47:685–688.
19. Maguire HT, Saint Pierre MM. A method for heating and humidification of gases for use of the Bird ventilator in neonate anesthesia. Anesth Analg. 1974;53:1014–1015.
20. Hollister GR, Burn JM. Side effects of ketamine in pediatric anesthesia. Anesth Analg. 1974;53:264–267.
21. Orkin LR, Siegel IM, Rovenstine EA. Resistance to breathing apparatus used in anesthesia: endotracheal equipment. Anesth Analg. 1954; 33:217–224.
22. Herbert WI, Scott EB, Lewis GB Jr. Fluid management of the pediatric surgical patient. Anesth Analg. 1971;50:376–380.
23. From RP, Scamman FL. Ventilatory frequency influences accuracy of end-tidal CO2 measurements. Analysis of seven capnometers. Anesth Analg. 1988;67:884–886.
24. Bissonnette B, Sessler DI, LaFlamme P. Intraoperative temperature monitoring sites in infants and children and the effect of inspired gas warming on esophageal temperature. Anesth Analg. 1989;69:192–196.
25. Eichhorn JH. ASA 1986 monitoring standards launched new era of care, improved patient safety. ASPF Newsletter. 2020;35:71–75.
26. Coté CJ, Goldstein EA, Coté MA, Hoaglin DC, Ryan JF. A single-blind study of pulse oximetry in children. Anesthesiology. 1988;68:184–188.
27. Coté CJ, Goldstein EA, Fuchsman WH, Hoaglin DC. The effect of nail polish on pulse oximetry. Anesth Analg. 1988;67:683–686.
28. Motoyama EK, Glazener CH. Hypoxemia after general anesthesia in children. Anesth Analg. 1986;65:267–272.
29. Soliman IE, Patel RI, Ehrenpreis MB, Hannallah RS. Recovery scores do not correlate with postoperative hypoxemia in children. Anesth Analg. 1988;67:53–56.
30. Kataria BK, Harnik EV, Mitchard R, Kim Y, Admed S. Postoperative arterial oxygen saturation in the pediatric population during transportation. Anesth Analg. 1988;67:280–282.
31. Rusy LM, Houck CS, Sullivan LJ, et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg. 1995;80:226–229.
32. Lynn A, Nespeca MK, Bratton SL, Strauss SG, Shen DD. Clearance of morphine in postoperative infants during intravenous infusion: the influence of age and surgery. Anesth Analg. 1998;86:958–963.
33. Monitto CL, Greenberg RS, Kost-Byerly S, et al. The safety and efficacy of parent-/nurse-controlled analgesia in patients less than six years of age. Anesth Analg. 2000;91:573–579.
34. Møiniche S, Rømsing J, Dahl JB, Tramèr MR. Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review. Anesth Analg. 2003;96:68–77.
35. Maxwell LG, Kaufmann SC, Bitzer S, et al. The effects of a small-dose naloxone infusion on pain management for pediatric patients on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled study. Anesth Analg. 2005;100:953–958.
36. Dalens B. Regional anesthesia in children. Anesth Analg. 1989;68:654–672.
37. Berde C. Regional anesthesia in children: what have we learned? Anesth Analg. 1996;83:897–900.
38. Meyer MJ, Krane EJ, Goldschneider KR, Klein NJ. Case report: neurological complications associated with epidural analgesia in children: a report of 4 cases of ambiguous etiologies. Anesth Analg. 2012;115:1365–1370.
39. Pediatric Regional Anesthesia Network. Accessed December 22, 2021.
https://pranetwork.org/.
40. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia. Anesth Analg. 2012;115:1353–1364.
41. Berde C, Greco C. Pediatric regional anesthesia: drawing inferences on safety from prospective registries and case reports. Anesth Analg. 2012;115:1259–1262.
42. Leech BC. Preanesthetic medication in children. Curr Res Anesth Analg. 1935;14:283.
43. Smith RM, Jeffries M. The evaluation of sedative agents for preoperative use in children. Anesth Analg. 1959;38:166–172.
44. Kain ZN, Mayes LC, Bell C, Weisman S, Hofstadter MB, Rimar S. Premedication in the United States: a status report. Anesth Analg. 1997;84:427–432.
45. Kain ZN, Wang SM, Mayes LC, Caramico LA, Hofstadter MB. Distress during the induction of anesthesia and postoperative behavioral outcomes. Anesth Analg. 1999;88:1042–1047.
46. Kain ZN, Caldwell-Andrews AA, Maranets I, et al. Preoperative anxiety and emergence delirium and postoperative maladaptive behaviors. Anesth Analg. 2004;99:1648–1654.
47. Fortier MA, Bunzli E, Walthall J, et al. Web-based tailored intervention for preparation of parents and children for outpatient surgery (WebTIPS): formative evaluation and randomized controlled trial. Anesth Analg. 2015;120:915–922.
48. Kain ZN, Mayes LC, Cicchetti DV, Bagnall AL, Finley JD, Hofstadter MB. The yale preoperative anxiety scale: how does it compare with a “gold standard”? Anesth Analg. 1997;85:783–788.
49. Craig DB, Martin JT. Anesthesia & Analgesia: seventy-five years of publication. Anesth Analg. 1997;85:237–247.
50. Stephen CR. Operating room fatalities in pediatric surgery. Curr Res Anesth Analg. 1952;31:36–44.
51. Smith RM. Some reasons for the high mortality in pediatric anesthesia. Anesth Analg. 1957; 36:105–112.
52. Ament R. Classification of operating room mortality: review of cases in a pediatric medical center during the 10-year period, 1949 to 1958. Anesth Analg. 1960;39:158–166.
53. Graff TD, Phillips OC, Benson DW, Kelley E. Baltimore anesthesia study committee: factors in pediatric anesthesia mortality. Anesth Analg. 1964;43:407–414.
54. Cohen MM, Cameron CB, Duncan PG. Pediatric anesthesia morbidity and mortality in the perioperative period. Anesth Analg. 1990;70:160–167.
55. Rockoff MA, Hall SC. Subspecialty training in pediatric anesthesiology: what does it mean? Anesth Analg. 1997;85:1185–1190.
56. Haberkern CM, Geiduschek JM, Sorensen GK, Bratton SL, Morray JP. Multi-institutional survey of graduates of pediatric anesthesia fellowship: assessment of training and current professional activities. Anesth Analg. 1997;85:1191–1195.
57. Nasr VG, Guzzetta NA, Miller-Hance WC, et al. Consensus statement by the congenital cardiac anesthesia society: milestones for the pediatric cardiac anesthesia fellowship. Anesth Analg. 2018;126:198–207.
58. Faraoni D, Caplan LA, DiNardo JA, et al. Considerations for pediatric heart programs during COVID-19: recommendations from the congenital cardiac anesthesia society. Anesth Analg. 2020;131:403–409.
59. Sanford EL. Pediatrics-anesthesia combined residency training: an applicant’s perspective. Anesth Analg. 2013;116:1386–1388.
60. Sanford EL. Pediatrics and anesthesiology combined residency: a graduate’s perspective and opinion on combined pediatric anesthesiology and critical care fellowship. Anesth Analg. 2019;129:634–635.
61. Longacre MM, Cummings BM, Bader AM. Building a bridge between pediatric anesthesiologists and pediatric intensive care. Anesth Analg. 2019;128:328–334.
62. SmartTots: Who We Are. Accessed November 2, 2021.
https://smarttots.org/about/who-we-are/.
63. SmartTots: Research and Grants. Accessed November 2, 2021.
https://smarttots.org/research-and-grants/.
64. Ing C, Landau R, DeStephano D, et al. Prenatal exposure to general anesthesia and childhood behavioral deficit. Anesth Analg. 2021;133:595–605.
65. Sun M, Dong Y, Li M, et al. Dexmedetomidine and clonidine attenuate sevoflurane-induced Tau phosphorylation and cognitive impairment in young mice via α-2 adrenergic receptor. Anesth Analg. 2021;132:878–889.
66. Warner DO, Hu D, Zaccariello MJ, et al. Association between behavioral and learning outcomes and single exposures to procedures requiring general anesthesia before age 3: secondary analysis of data from Olmsted County, MN. Anesth Analg. 2021;133:160–167.