Review Article

The Historical Development of Obstetric Anesthesia and Its Contributions to Perinatology

Matthew L. Edwards, AB1 Anwar D. Jackson, MD2

1 School of Medicine, University of Texas Medical Branch at Galveston, Address for correspondence Matthew L. Edwards, AB, 301 University Galveston, Texas Boulevard, University of Texas Medical Branch at Galveston, School of 2 Department of Obstetrics and Gynecology, Michigan State University Medicine, Galveston, TX 77555 (e-mail: [email protected]). College of Human Medicine, Hurley Medical Center, Flint, Michigan

Am J Perinatol

Abstract Scottish obstetrician James Young Simpson first introduced the use of ether and Keywords chloroform anesthesia for labor in 1847, just 1 year after William Morton’s first ► obstetric anesthesia successful public demonstration of ether anesthesia at the Massachusetts General ► perinatology Hospital. The contemporaneous development of surgical anesthesia and obstetrics ► drugs enabled obstetric anesthesia to address the pain of childbirth. Shortly after its ► placental transport introduction, obstetricians raised concerns regarding placental transport, or the idea ► Virginia Apgar that drugs not only crossed the placenta, but exerted detrimental effects on the ► James Young Simpson neonate. The development of regional anesthesia and clinical work in obstetric ► history anesthesia and perinatology addressed issues of the safety of the neonate, enabling ► regional anesthesia obstetric anesthesia to safely and dramatically reduce the pain of childbirth. ► twilight sleep

It is remarkable that Boston dentist William T. G. Morton Obstetric Anesthesia and Concepts of (1819–1868) gave the first successful public demonstration of Placental Transport ether anesthesia at the Massachusetts General Hospital in 1846, several centuries after the discovery of ether. Certainly, At a time when 6 out of every 100 British mothers died during ether and other anesthetic agents have expanded the bound- childbirth, and even more suffered complications from the aries of surgery, aided the process of childbirth, and codified event, the development of obstetrics promised to increase the Downloaded by: Cornell. Copyrighted material. the medical treatment of pain. By 1847, just 1 year after safety of women and children during the perinatal period.4 Morton’ssuccessfuldemonstration,Scottishobstetrician Relatedly, James Young Simpson believed that mitigating the James Young Simpson (1811–1870) first introduced the use pain of childbirth was necessary for improving its safety.5 One of ether and chloroform anesthesia for labor.1–3 of Simpson’speersdescribedhimashavingthe“head of Jove” This article reviews the history of obstetric anesthesia and the and the “body of Bacchus,” while others described him as social responses to the management of pain during childbirth. gregarious and charming.6 Although these characteristics no Drawing on the historical and medical literatures between the doubt enabled him to advocate for the use of anesthesia mid-19th and 20th centuries, we discuss the major agents, during labor, the public had other reasons to adopt the use achievements and figures in obstetric anesthesia. Of particular of gases in labor. importance to perinatology, we also discuss the effect of the Feminism emerged during the mid-19th century and development of ideas about drugs in general (and anesthetics in many of its proponents believed that the pain of repetitive particular) on the neonate, ideas which arose among obstetri- childbirth was largely responsible for propagating the cians around 1880. Clinical work with the neonate came rather oppression of women.6,7 Leading feminists shared Simpson’s late in the history of obstetric anesthesia, in part from the work of desire for medical advancement and transmogrified it into anesthesiologist Virginia Apgar (1909–1974). the quest for female empowerment.1 While early recipients of

received Copyright © by Thieme Medical DOI http://dx.doi.org/ May 10, 2016 Publishers, Inc., 333 Seventh Avenue, 10.1055/s-0036-1585409. accepted after revision New York, NY 10001, USA. ISSN 0735-1631. June 5, 2016 Tel: +1(212) 584-4662. History of Obstetric Anesthesia Edwards et al. ether and chloroform included Emma Darwin (1808–1896) in 1834. Conversely, W. S. Savory found that strychnine (the wife of Charles Darwin [1809–1882]) and Queen Victoria injected into the fetal dogs’ circulation subsequently caused (1819–1901),8 these agents were generally out of reach for the mothers to convulse. In 1850, obstetrician C. C. Hüter the average laboring woman. Cognizant of this disparity, devised a chemical test that identified chloroform in neonatal philanthropists helped establish the National Birthday Trust cord blood. in 1928. The trust was an organization dedicated to making Nearly a quarter-century passed before the issue of placen- anesthesia available to every laboring woman in the British tal transport was resumed in 1876, however, when the Swiss Isles.1 By the turn of the 20th century, ether and chloroform obstetrician Paul Zweifel (1848–1927) demonstrated that were ubiquitous in childbirth on both sides of the Atlantic chloroform used in labor accumulated significantly in the fetal Ocean, and James Simpson was regarded in Europe as one of blood and urine.1,7,8 This third-generation physician who the era’smostinfluential physicians.6 pioneered the study of fetal-placental metabolism found a While Simpson gained fame and notoriety in the eyes of synthetic reducing agent in the urine of infants whose mothers the British public, his medical contemporaries in Europe and were treated with chloroform anesthesia for labor.1,9 Zweifel North America approached ether and chloroform with heavy believed that this metabolic “reaction resembled that pro- skepticism.6,8 Many British obstetricians argued that ether, a duced by glucose1” and hypothesized that chloroform altered volatile gas whose medical applications had only been dem- the fetal metabolism of carbohydrates.1 Using placental tissue, onstrated months before Simpson used it in childbirth, had he determined that the substance was not glucose, but rather unproven safety and efficacy in labor. The British medical chloroform.1 Fellow physicians and scientists questioned the establishment feared ether and chloroform not only significance of his study, however, arguing that the chloroform increased the risk of hemorrhage and infection, but also present in placental tissue might represent “contamination by had detrimental effects on the newborn.8 These criticisms maternal blood adherent to the placental membranes.”1 Zwei- were among the earliest expressing concerns about the fel used the same chemical reaction to demonstrate chloro- placental transport of drugs from mother to fetus. form in the umbilical artery and neonatal urine.1,9 His findings Some physicians feared that a drug strong enough to definitively proved that ether and chloroform quickly crossed sedate an adult would have even greater effects on neonates. the placenta. To be sure, Zweifel only demonstrated placental Simpson himself had experienced the potency of chloroform, transport; he did not test for the amount of drug that was and it was only after this experience that he became con- transported, or its effects on the neonate. vinced of chloroform’sanestheticsuperiorityandintroduced Issues of placental transport were not the only challenges it into his obstetric practice.5 Without extensive data, how- to obstetric anesthesia during Simpson’stime.Whenanes- ever, fears regarding the effects of chloroform on neonates thesia began to shape obstetrics in the mid-19th century, were nothing more than unproven suspicions. As the use of religious opposition became a formidable challenge.10 Resis- ether and chloroform became more widespread in labor, the tance became so strong that Simpson and another London complications of their use also became better known. John obstetrician Protheroe Smith (1809–1889), had to address the Snow (1813–1858), a British general practitioner who anes- issue of religion and obstetric anesthesia in publications by thetized Queen Victoria during the birth of her eighth child, arguing that the scriptural text “in sorrow thou shalt bring also expressed concerns about ether and chloroform.8 Snow forth children” was not congruent with the idea of intended Downloaded by: Cornell. Copyrighted material. noticed that neonates born to mothers who had received suffering of women during childbirth, and that moreover, the ether in labor came out with respiratory depression and pain experienced during childbirth could be directly decreased motor activity.8,9 Snow also smelled ether on the explained by anatomy and science rather than punishment breath of these neonates,8 thus supporting the idea of intra- from God.1 Simpson’s1847publicationcoincidedwithQueen uterine transport of the drug. Victoria’swillingnesstohaveetherasamedicalanestheticin In spite of mounting evidence about ether and chloro- her two subsequent births.1 form’seffectsonnewborns,ferventproponentsoflabor analgesia continued to dismiss their colleagues’ clinical find- 1 The Emergence of Twilight Sleep and ings. Walter Channing (1786–1876), a Harvard professor and Regional Anesthesia obstetrician, was one such proponent. A leading physician who cofounded the predecessor of the Brigham and Women’s Simpson was not indifferent to the effects of ether and Hospital in Boston, MA, Channing asserted that ether did not chloroform on newborns. He died in 1870, six years before cross the placenta.8 For Channing, this belief was supported Zweifel’slandmarkdiscovery.Hadhelivedlonger,hemayhave by the fact that he never smelled ether at the cut ends of seen the evidence of ether and chloroform’sdetrimental umbilical cords.8 Unlike Snow, he did not mention smelling effects on neonates and sought other means of mitigating the newborn’sexhalations.Thus,hedidnotdetectthestrong the pain of childbirth. Even so, however, Simpson’s odor of ether on the newborn’sbreath.1 contemporaries and immediate successors who benefited Clinical evidence between 1834 and 1850 supported the from Zweifel’sdiscoveryfailedtofind suitable replacements concept of placental transmission of drugs. Noted French for the volatile gases. physiologist François Magendie’s(1783–1855) famous exper- As the evidence for chloroform’seffectsonnewbornsgrew, iment demonstrating the placental transmission of camphor the discovery of safer anesthetic alternatives did not progress from pregnant dogs to their fetuses was translated to English at nearly as quick a pace. In fact, ether and chloroform

American Journal of Perinatology History of Obstetric Anesthesia Edwards et al. remained the only labor anesthetics available at the turn of raised the same concerns about twilight sleep that their the 20th century.7 Ether and chloroform’shalf-centurydom- predecessors had raised about ether and chloroform a half- inance ended in 1902, when an Austrian obstetrician named century earlier. They believed that twilight sleep halted labor, Richard von Steinbüchel (1862–1952) implemented “Dam- failed to provide adequate pain relief and was harmful to the merschlaff,” or twilight sleep for the first time.8,11 Twilight neonate.11 Physicians in the early 1900s, however, had a sleep combined morphine and scopolamine, a concoction different understanding of labor physiology. During that that resulted in a comfortable and amnesic labor experience. time, the central nervous system was regarded as the domi- While von Steinbüchel introduced twilight sleep to obstetrics, nant regulator of labor, and agents that depressed the central aGermanobstetriciannamedCarlGauss(1875–1957) popu- nervous system would therefore suppress labor.11 The endo- larized the method through public lectures and publica- crine system’scontroloverlaborwouldnotbeunderstood tions.8,11 Physicians were familiar with the analgesic until later in the 20th century. Physicians now know that properties of opioids several decades before von Steinbüchel’s opioids can potentially suppress contractions in the early innovation. The crude extracts available, however, made phase of labor, but cannot stop the active phase of labor. consistent results difficult to obtain. Morphine and codeine While morphine had minimal effect on the progression of were finally isolated from opium in 1809, and the introduc- labor, other concerns of twilight sleep arose. The initial dose of tion of the syringe and hollow metal needle in 1853 made morphine often failed to provide proper anesthesia. In response, opiates a practical form of anesthesia. Physicians were still obstetricians frequently ignored Gauss’ recommendation by hesitant about administering opioids to laboring patients, giving their patients 40 to 50 mg of morphine, in part spurred however, until the Austrians’ anesthetic revolution. by their patients’ expectation of painless labor.8 Obstetricians Similar to ether andchloroform 50years earlier, themedical also noticed that twilight sleep had serious effects on thefetus. In establishment also initially opposed twilight sleep. J. Whit- the decades preceding twilight sleep, opioids were a common tridge Williams (1866–1931) (►Fig. 1), a prominent Johns component in medications. Even though many obstetricians did Hopkins obstetrician who wrote the first editions of obstetrics’ not directly administer opioids to their patients, they were seminal textbook, repudiated twilight sleep in the 1908 and steadily gaining experience taking care of patients who had 1912 editions of his book.11 Gauss considered twilight sleep to become addicted to the analgesics. When these obstetricians be a double-edged sword. He recommended that no more than attempted to wean their patients off of opioids, they noticed the 10 mg of morphine be administered during one labor, and signs of withdrawal, including violent fetal movements and evaluated the effects of the dose of scopolamine by giving his sudden neonatal death.8,11 The effect of the opioid on the fetus patients memory tests during labor.8,11 Prominent physicians was inferred when “[it] again became quiet” after patients resumed their original dose.1 The National Twilight Sleep Association was formed in 1915 to spread literature and rally support for the technique. One example of such literature is the book The Sleeping Car,whichwaspublishedin1915byRussellK. Carter (1849–1928) (►Fig. 2). By 1923, even J. Whittridge Downloaded by: Cornell. Copyrighted material.

Fig. 1 The Sleeping Car “Twilight,” or, Motherhood Without Pain was published in 1915 to dispel “the whole truth about ‘Twilight Sleep’.” Its publication coincided with the formation of the National Twilight Sleep Association. (Carter R. The Sleeping Car “Twilight” or Motherhood Without Pain. The whole truth about “Twilight Sleep” and the New Fig. 2 J. Whittridge Williams (1866–1931). Williams was an obste- Anesthesia; the marvelous French discovery, the most wonderful of all; trician at the Johns Hopkins University Hospital and author of the and a special chapter for every man on the Conquest of Pain. Boston, seminal textbook Williams Obstetrics. (Image courtesy of the National MA: Chapple Publishing Company; 1915.) Library of Congress, Washington, DC.)

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Williams acquiesced to twilight sleep’smassappealandtriedthe means of analgesia to evaluate the efficacy of their technique.14 technique.11 Hingson and Edwards found that continuous caudal anesthesia As twilight sleep rose to prominence, another form of outperformed other forms of pain control in several key areas, anesthesia was slowly introduced into obstetric practice. including the incidences of neonatal anoxia, stillborn births Regional anesthesia was introduced in 1884, when the Austrian and neonatal mortality. They also identified several short- ophthalmologist Carl Köller (1857–1944) administered cocaine comings with their technique, including fetal anoxia due to to anesthetize the eye of a patient with glaucoma.8 During the hypotension from vasomotor blockade, increased incidence of subsequent decades, obstetricians adopted regional anesthesia operative deliveries and occasional fetal hypersensitivity to the concomitant with their increasing understanding of labor phys- anesthetic. Although the incidences of stillbirth and neonatal iology. Moreover, studies of pregnancy and delivery following mortality were easy to quantify, a consistent measure of spinal cord transection shed doubt about the notion that labor is neonatal hypoxia and other indicators of neonatal morbidity dependent on central nervous system control. In the first three had yet to be discovered. That changed in 1953, when Virginia decades of the 20th century, several articles were published on Apgar introduced a neonatal scoring system. the uses of spinal, lumbar, epidural, paravertebral, parasacral, ’ and pudendal nerve blocks in labor. While regional anesthesia s Virginia Apgar’sConcernsfortheNeonate minimal effect on the neonate was a distinct advantage over inhalation anesthesia and twilight sleep, the dearth of suitable Virginia Apgar completed her surgical residency at Columbia agents for regional anesthesia limited its widespread adoption. University College of Physicians and Surgeons during an era As a result, inhalation agents, and opioids remained the domi- when few women entered the medical profession, and popular nant options for pain control during labor, while regional opinion held that the rigors of being a surgeon were too anesthesia was typically reserved for delivery. demanding on women. At the insistence of her chairman, Robert Andrew Hingson (1913–1996), Waldo B. Edwards Apgar diverted her attention from surgery to anesthesiology, (1905–1981), and James L. Southworth (1913–1970), three and began her training with some of the field’spreeminent physicians employed by the United States Marine Hospital on minds.8 When Apgar returned to Columbia in 1938, she Staten Island, were the first doctors to administer continuous became the director of the Division of Anesthesiology in the caudal anesthesia in 1941. Hingson and Southworth intro- Department of Surgery. She remained in this position until duced their technique in a bilateral phlebectomy; the pair 1949, when the Division of Anesthesiology became its own deviated from the conventional practice by leaving the caudal freestanding department. Despite leading her colleagues for needle in place after administering the initial anesthetic.12 over a decade, Apgar did not become the department’sinau- This allowed the two physicians to administer continuous gural chairman. She was, however, promoted to full professor, analgesia throughout the operation. Hingson then collabo- the first woman at Columbia to earn the title. Her newfound rated with Edwards, the hospital’schiefobstetrician,and freedom from bureaucratic management also afforded her modified the technique for obstetric use. Hingson and more time to dedicate to obstetric anesthesia.15 Edwards employed a malleable stainless steel needle through Apgar was appalled by the lack of effort placed in resusci- which they could continuously bathe the nerve trunks of the tating infants deemed too apneic, too small or too malformed sacral and lumbar plexuses in the epidural space.8,13 The two to survive. These infants were often labeled stillborn and Downloaded by: Cornell. Copyrighted material. physicians’ technique was tested in January 1942, when a were left to die. Apgar began resuscitating these infants and patient presented to their Staten Island hospital in need of an developed a scoring system that could objectively assess and emergency cesarean delivery. The expecting mother suffered document the neonatal viability within the first few minutes from rheumatic heart disease, and her physicians feared that of life.16 Her scoring system, published in 1953, enabled she would neither tolerate labor nor survive general anes- physicians to objectively assess neonatal wellbeing immedi- thesia due to her condition.13 Nonetheless, she was anesthe- ately following delivery, as well as evaluate the neonatal tized successfully with caudal anesthesia, and she and her effects of labor analgesia. With these measurements (i.e., baby survived the surgery. By 1944, Hingson and Edwards heart rate, respirations, color, tone, and reflex irritability), had successfully replicated their technique in 600 deliveries, Apgar and her colleagues demonstrated superior neonatal and the aptly named Hingson–Edwards technique was rap- and maternal outcomes with regional anesthesia compared idly adopted throughout the United States.12 with general anesthesia.15 These findings additionally sup- Hingson and Edwards developed their anesthetic technique ported the transition to regional anesthesia for childbirth.15 in a vastly different medical climate than their predecessors. Virginia Apgar shifted the focus of childbirth from maternal While the effects of anesthesia on neonates had concerned safety to neonatal safety, a shift that was not isolated to some prominent physicians since the mid-19th century, physi- medical professionals. Ever since James Simpson introduced cians became increasingly aware of the potential harm of labor chloroform to obstetrics, the general public and women in analgesics during the first half of the 20th century. Hingson particular have played a pivotal role in advancing labor anal- and Edwards distinguished themselves as innovators of labor gesia. Even as evidence of the neonatal effects of chloroform, analgesia by actively studying the effects their continuous twilight sleep and other agents mounted, the public believed caudal analgesia had on newborns. Their study, published in that the agents’ benefits outweighed their detrimental effects. 1948, was one of the few that not only described negative This perception evolved during a time when childbirth still had neonatal outcomes, but also utilized control groups and other ahighmaternalmorbidityandmortalitybytoday’sstandards.

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As neonatal mortality declined, physicians substituted the the new feminist movement that emerged in the mid-20th responsiveness of the neonate as an assessment of perinatal century, adopted the natural childbirth approach. care. Some mothers believed that suboptimal neonatal out- comes were a byproduct of the obstetric interventions that Conclusion impinged on the natural process of labor. Obstetric anesthesia has undergone many changes and chal- fi The Rise of the Natural Childbirth Movement lenges over the past 170 years. Perhaps the most signi cant change, however, has not been the technological innovation Ironically, as labor analgesia became safer for the newborns or the refinement of techniques of anesthetic administration. and neonatal resuscitation measures improved, many patients The field’sexpandedfocusonneonatalsafety,spurredby desired a return to “natural childbirth.” These notions were obstetricians’ concerns with the effects of drugs and anes- fueled by the work of Grantly Dick-Read (1889–1959). Born in thetics on the neonate during the late 19th century, has Suffolk, Dick-Read spent a portion of his early adulthood enabled successive generations of patients and physicians serving the British Empire in the trenches of the Great War. to receive the maternal and fetal benefits of labor analgesia It was during the war that Dick-Read became acquainted with without compromising the birth process. Though the quest an Indian soldier and learned several relaxation techni- for an ideal anesthetic agent continues to elude obstetricians ques.17,18 Following the war, Dick-Read completed his medical and anesthesiologists alike, patients can now benefitfrom education at the University of Cambridge and became an several safe procedures and agents to reduce the pain associ- obstetrician. He believed that childbirth was a physiological ated with childbirth. These neuraxial techniques include rather than a pathological process, and a “healthy childbirth spinal, epidural, and caudal anesthesia and analgesia. More- was never intended by the natural law to be painful.”17 He also over, there are now several safe and effective agents, includ- believed that the mental relaxation techniques he learned ing bupivacaine and ropivacaine.19 In light of this historical from his Indian colleague could be utilized to make labor development, the elimination of neonatal morbidity will painless. likely continue to drive innovations in obstetric anesthesia Christening his technique “natural childbirth,” Dick-Read’s and perinatology. goals extended beyond returning childbirth to its natural analgesic state. The Suffolk physician believed his technique would improve short-term and long-term neonatal outcomes. Disclosures Dick-Read combined his clinical experiences with his under- None. standing of the sympathetic nervous system to develop a theory called the “fear-tension-pain syndrome.” This theory held that pain triggered the sympathetic nervous system’s Note fight-or-flight response, which in turn released chemicals that Both the authors have contributed equally to this article. halted labor and caused hypoxic injury to the fetus.17,18 Dick- Read claimed that his technique not only prevented hypoxic insults to the neonate, but also strengthened the bond between Acknowledgments Downloaded by: Cornell. Copyrighted material. mothers and their newborn children. In a process he called The authors would like to thank Donald Caton, MD, Emeritus “motherlove,” Dick-Read believed that by making childbirth a Professor of Anesthesiology and Obstetrics and Gynecology, more pleasant experience, mothers more readily rendered University of Florida College of Medicine, Gainesville, FL, for love and adoration to their children. He believed that these reading several drafts of this article. The authors would also children, having grown up in a loving and caring environment, like to thank the Wood Library-Museum of Anesthesiology, were far less likely to spread hate and malice, and could Schaumburg, IL, for their assistance. potentially usher in a new era of peace.17,18 Like his fellow countryman James Simpson in the preced- ing century, Dick-Read spread his message with fiery passion and self-assuredness. The public responded well to the ob- References stetrician’sstyle,andhis1942bookRevelation of Childbirth 1 Caton D. What a Blessing She Had Chloroform: The Medical and became an international bestseller. Like Simpson, Dick-Read Social Response to the Pain of Childbirth from 1800 to the Present. New Haven, CT: Yale University Press; 1999 was also met with skepticism by his professional peers. 2 Sykes MK, Bunker JP. Anaesthesia and the Practice of Medicine: Although his beliefs about labor physiology had some merit, Historical Perspectives. London, United Kingdom: Royal Society of his flair for extravagant self-promotion irked many of his Medicine Press; 2007 physician colleagues. Dick-Read also never provided scientific 3 Keys T. The History of Surgical Anesthesia. New York, NY: Dover; data supporting his claims about the efficacy of natural 1945 childbirth, which further compromised his standing in the 4 Chamberlain G. British maternal mortality in the 19th and early 20th centuries. J R Soc Med 2006;99(11):559–563 medical community. Had Dick-Read relied more on scientific 5 Gordon LH. Sir James Young Simpson and Chloroform (1811– evidence, his natural childbirth technique may have been 1870). Honolulu, HI: University Press of the Pacific; 2002:88–133 regarded by the medical community as an acceptable form of 6 Caton D. Medical science and social values. Int J Obstet Anesth labor analgesia. Nonetheless, many women, some spurred by 2004;13(3):167–173

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