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Table of Contents
Year : 2021  |  Volume : 5  |  Issue : 4  |  Page : 223-229

Blood transfusion and venous cannulation — medical publication and innovation across 350 years of history: A narrative review

1 Faculty of Medicine, The University of Queensland, Brisbane, Australia; Department of Anaesthesia and Perioperative Medicine, Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia; Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia
2 Faculty of Medicine, The University of Queensland, Brisbane, Australia
3 Faculty of Medicine, The University of Queensland, Brisbane, Australia; Department of Anaesthesia and Perioperative Medicine, Royal Brisbane and Women’s Hospital, Herston, Queensland, Australia
4 Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia; Department of Anesthesia, Onze-Lieve-Vrouw Hospital, Aalst, Belgium
5 Faculty of Medicine, Udayana University, Sanglah General Hospital, Bali, Indonesia; Faculty of Medicine, University of New South Wales, Kensington, NSW, Australia

Date of Submission29-Mar-2021
Date of Decision26-Jun-2021
Date of Acceptance06-Jul-2021
Date of Web Publication13-Aug-2021

Correspondence Address:
Dr. Andre Van Zundert
Faculty of Medicine, The University of Queensland, Brisbane. 20, Weightman St, Herston QLD, 4006.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjoa.BJOA_39_21

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This article reviews historical milestones during the last 350 years starting with early experiments in intravenous injections of drugs and blood transfusion conducted in a climate of scientific discovery rather than clinical application. Technical problems encountered during attempts of vascular cannulation and a lack of knowledge of physiology resulted in complications related to intravenous access, sometimes fatal, which resulted in a complete ban on blood transfusion in Europe for 150 years. Meticulous documentation of these first 17th century experiments was published in Britain, in the “Philosophical Transactions of the Royal Society of London,” the oldest continuously published scientific journal still in existence, and in France, in the “Journal des Sçavans.” These journals became the primary means of communication of scientific research and letters amongst the community of scientists. Intravenous therapy marked the start of the first primitive anesthetic and laid the foundations for anesthesia and blood transfusion, although their clinical application came centuries later. Successful intravenous anesthesia was established around the turn of the 19th century. Brave men in the 17th century endeavored to awaken the spirit of inquiry and research among their peers at the Royal Society of London. Thanks to these bold medical men acting at a time of accelerated change, there was a great impact on clinical practice in many medical fields. Anesthesia now bears the fruits of these initial experiments so that, ultimately, anesthetists can provide safe and effective anesthesia while delivering anesthetic drugs, intravenous fluids, and blood transfusions for the benefit of patients.

Keywords: Anesthesia, blood transfusion, cannula, history, intravenous

How to cite this article:
Van Zundert A, Wiepking FS, Roets M, Van Zundert TC, Gatt SP. Blood transfusion and venous cannulation — medical publication and innovation across 350 years of history: A narrative review. Bali J Anaesthesiol 2021;5:223-9

How to cite this URL:
Van Zundert A, Wiepking FS, Roets M, Van Zundert TC, Gatt SP. Blood transfusion and venous cannulation — medical publication and innovation across 350 years of history: A narrative review. Bali J Anaesthesiol [serial online] 2021 [cited 2022 May 26];5:223-9. Available from: https://www.bjoaonline.com/text.asp?2021/5/4/223/330961

  From Humoural Medicine to Modern Medicine Top

Since the Golden Age of Greece (400 BC), Hippocrates, Aristotle and later, Galen of Pergamon (129-210AD) had a strong belief in the primacy of blood. Their theories would determine the boundaries of medicine until the advent of modern medical research. For millennia, it was assumed that blood did not circulate, but, rather, moved in a slow ebb and flow sequence. Blood was considered important as ingested food was transformed in the liver into blood, distributed into veins, and ultimately turned into the flesh or tissues. Blood contained not only nutrients but also heat and vital spirits. In the left ventricle, blood was mixed with air, heated, and disseminated to tissues via arteries, according to the body’s needs. Blood contained four “humours” (black bile, yellow bile, phlegm, and blood), determining a person’s unique humoral composition and temperament, with linked mental and physical processes.

Good health was a balance of the humors. For more than two millennia, the common belief persisted that a variety of physical diseases and mental ailments were the results of an imbalance of “bad humours” or “poisons” in the blood. A patient could be cured by removal of the bad blood (bloodletting) in exchange of pure blood from animals or young boys. Transfusion with “cool” blood could restore the order of mind of the mentally unstable. These were the underlying reasons why early experiments focused on the intravenous (IV) administration of several medications and “poisons” that eventually led to the transfusion of blood. In the 17th century, the focus was not the clinical practice of blood replacement following severe blood loss but on the popular concept of alterability of personality, vigor, vitality, or youth.

William Harvey (1578—1657) would eventually replace the Galenic system of physiology through observation and lay the foundation of modern medicine. He described the circulatory system, first in Latin (1628), then later in English (1653) in his 72-page book, “Exercitatio Anatomica de Motu Cordis et Sanguinis Animalibus/An Anatomical Exercise on the Motion of the Heart and Blood in Animals.” Harvey showed that blood flowed through a systemic circulation of blood vessels in one direction, pumped through the body by the heart. This discovery disproved Ancient Greeks’ theory that blood (manufactured by the liver) was “washed” forward and backward in the blood vessels, like “the tides of the sea.”[1],[2] Harvey further described that drainage of blood is best achieved by putting an IV cannula in the peripheral vein in the opposite direction to the administration of fluids and drugs, as valves in veins prevent flow down the limb.[3]

  The Royal Society of London for Improving Natural Knowledge Top

Three hundred and fifty years ago, a group of scientists in Oxford, England, gathered together in “the Invisible College” with the motto “Nullius in verba” (take nobody’s word for it) to verify all statements by considering the facts determined by experiments [Figure 1]a. During apothecaries’ meetings, medical and chemical experiments took place based on trial and error, performed by “learned physicians.” At their weekly meetings, three to four experiments were performed, ranging from an animal dissection (e.g., a dolphin or an otter) to transfusing blood from one animal (e.g., a sheep) to another animal or a human, and examining slides under their newly-designed microscopes. Christopher Wren (1632—1723) and Robert Hooke (1635—1703), two founding members of the Royal Society, organized the first meeting at the Gresham College, London, on November 28, 1660. The group of scientists received royal approval and encouragement by King Charles II in two Charters (1662—1663) and became known as “The Royal Society of London for Improving Natural Knowledge” [Figure 1]b. The King himself was one of the first 150 fellows.
Figure 1: (a) The Royal Society’s logo “Nullius in Verba” (first meeting on 28 November 1660); (b) The Royal Society’s First Royal Charter by King Charles II (1662); (c) Volume I of the Philosophical Transactions covering 1665-1666 (First Edition 6th March 1665); (d) Henry Oldenburg, founder of the world’s first scientific journal “Philosophical Transactions;” (e) “Experiment of transfusion, practised upon a man in London,” performed on November 23, 1667 (Philosophical Transactions, 9th December 1667) — Panels A-E are reprinted with permission from the Royal Society of London; (f) Early blood transfusion from lamb to man (reprinted with permission from the Wellcome Library, London); (g) Blundell J. Blood transfusion technique for severe postpartum hemorrhage. Observations on transfusion of blood, The Lancet II, June 13, 1829 (reprinted with permission from Elsevier)

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  The Philosophical Transactions of the Royal Society of London Top

The mid-17th century’s novel approach to medicine with observations, new experiments, and documentation, an increasing number of university-trained physicians and the replacement of English as the modern Latin in medical work, contributed to speeding the progress in medicine. This replaced a medical arena of chaos and confusion which fed on ignorance and superstition. Revolutionary advancements in the conduct and communication of science were the result. It was the normal practice of the time that experiments first were demonstrated in front of colleagues and peers. Subsequently, the experiment was written down and published, often as “Letters.” 17th-century experiments in England were documented in “Philosophical Transactions” of the Royal Society of London [Figure 1]c, the world’s first peer-reviewed scientific journal (first issue on March 6, 1665). It is the oldest continuously published scientific journal still in existence,[4] founded by the visionary editorship of the German scholar Heinrich (Henry) Oldenburg [Figure 1]d, despite several disruptions in the early years, such as the plague (1665), the Great London Fire (1666), and the Second Anglo-Dutch War (1667). Oldenburg put up the money to publish the Philosophical Transactions on the first Monday of every month and was able to sell it for profit. Twelve monthly parts were bound into a single volume with a title page and index. This is the era when Robert Boyle (1627—1691) discovered the pressure—volume—temperature relationship (Boyle’s law), while Robert Hooke gained credit for discovering the cell and he published his book “Micrographia,” in which he recorded all his drawings and observations made through the magical world of the microscope. With consummate technical skill, Hooke created × 50 magnifications, enabling him to view the previously undiscovered world of the cell. Robert Hooke’s appointment as curator of experiments to the Royal Society resulted in a staggering number and variety of experiments at the weekly meetings.[5]

In France, private lawyer Denis de Sallo established, the “Journal des Sçavans” (later renamed Journal des Savants) on Monday January 5, 1665, the earliest academic journal published in Europe. Its content included obituaries of famous men, church history, and legal reports. During the French Revolution, the journal ceased publication until 1816 under the “Institut de France,” and in 1908, the “Académie des Inscriptions et Belles-Lettres” took over patronage. However, from 1816, the journal ceased to carry scientific material and became more of a literary journal.[6]

  The first intravenous injections of drugs Top

Sir Christopher Wren, the “British Leonardo,” was a mathematician, professor of astronomy, constructor of the first “weather clock,” improver of cutting-edge microscopes, and one of the most acclaimed English architects in history, responsible for rebuilding 52 churches after the Great London Fire (1666), including his grand masterpiece St. Paul’s Cathedral.[7],[8],[9] Wren was the illustrator of Thomas Willis’ (1621—1675) book of the “Circle of Willis” and understood that blood circulation could be used to receive injected liquid medicine and “poisons” directly into the bloodstream to study their effects.[10] Two early members of the Royal Society, Francis Potter and Francis Glisson, devised new techniques for various IV injections of drugs and were concerned to perfect hollow tubes which could be inserted into veins.[8] It was only a short step from the Glisson’s injection experiments and Potter’s transfusion techniques, to Wren’s injections of drugs.[11] Wren was the first to perform, in 1656, an IV injection by venous cut down over large vessels in a hind limb, with a “slender pipe of a syringe,” injecting a warm solution of “Opium in Sack,” i.e., opium fortified wine, into a dog. The dog became drunk but survived the experiment and was later even stolen.[2],[12],[13],[14] Christopher Wren can rightfully be considered to have administered the first IV anesthetic.[3],[12]

These first IV injections took place in Oxford, either at the lodgings of aristocrat Robert Boyle at Deep Hall (now University College), owned by Christ Church,[13] or at the home of the French Ambassador, the Duc de Bordeaux.[7]

  The first intravenous blood transfusion has many fathers Top

One of Oxford’s finest doctors, Richard Lower (1631—1691), is credited with performing, in England in 1665, the first animal-to-animal (dog to dog and sheep to dog) blood transfusion through tubes. He first transfused dogs by connecting the jugular veins of two animals; this failed due to intravascular clotting. The Philosophical Transactions Number 30 from Monday December 9, 1667, reports in detail, the human blood transfusion experiment, performed by Dr. Richard Lower on November 23, 1667 [Figure 1]e on a man with a mental disease (Arthur Coga), with the aim to change his character.[9],[15],[16],[17] The carotid artery of a sheep was connected with the man’s cubital vein using a silver pipe in a quill, after removing 6—7 ounces of blood through bloodletting [Figure 1]f. Twelve ounces of the sheep’s blood were infused into the man. Lower’s instruments consisted of a lancet for venesection and an apparatus for transfusion: (a) a tapered silver tube placed into the blood vessel; (b) a groove in the pipe for the placement of the connector from the infusion; (c) a flange to fix the tube with a suture; (d) a connector or emissary tube; and (e) a wooden rod to close the emissary tube while preparing the infusion. In many respects, this device laid the basis of modern syringes with needles.[12],[13],[15],[18]

German graduate of Padua University, professor of physics at Kiel and early member of the Academia Naturae Curiosorum, Johann-Daniel Major (1634—1693), is believed to have given medications to humans intravenously and suggested a method of animal-to-human transfusion with a cannula made of silver. Unfortunately, the first patient died. Major’s best-known composition is a work concerning therapeutic injections in “Prodromus inventae a SE chirurgiae infusoriae” (Leipzig, 1664). Major and many others since ancient times believed that illnesses might arise from corrupted blood. Cures could be realized by either injecting a healing medicament directly into the blood or transfusing the blood of a healthy person directly into the sick body. In his trials, Major used tiny silver pipes rather than the more common feather quills, to be “infusoria salubris” (i.e., healing injections) as opposed to the purely experimental “infusoria curiosa.”[19],[20] Johan Sigismund Elsholtz (1623—1688) described extensively on his own animal experiments in Berlin using different “poisons” and on experiments of other Europeans.[21]

In France, Jean-Baptiste Denis (1643—1704), personal physician to King Louis XIV, performed, on June 15, 1667, the first medical blood transfusion in humans in a 15-year-old boy, who suffered from a fever for many months and who had been bled so much by his doctor using leeches 20 times, that he required an infusion of blood for which Denis used blood from a lamb. The boy recovered. Denis repeated several transfusions on other patients with mixed (sometimes fatal) results. One of them resulted in the first transfusion reaction. Denis’ experiments with animal blood provoked a heated controversy in France and in the late 1660s, the procedure was banned; other bans were soon followed from England and the Vatican.

Blood injection fell out of favor for 150 years, halting human blood transfusion research.[2],[22] Transfusion reactions were often the cause of fatal outcome due to: (a) differences in the number of blood group type between humans (n = 4) and animals such as cats (n = 3), sheep (n = 7), dogs (n = 8), cows (n = 11), and horses (n > 30); (b) several donors were used during repeated blood transfusion, which increased the likelihood to develop intolerability; and (c) coagulation in blood vessels.

More than a 100 years later, the English obstetrician James Blundell (1791—1878), the “father of transfusion medicine,” known for his transfusion studies in both dogs and humans, saw many patients dying in childbirth from severe postpartum hemorrhage complications. He started successful human-to-human blood transfusions [Figure 1]g, using the woman’s husband as donor and equipment he designed himself.[18],[23],[24] This was at a time when bloodletting was still in widespread use and a recognized treatment for postpartum hemorrhage.[25]

However, it wasn’t until after Austrian-born American biologist Karl Landsteiner’s discovery of the ABO blood groups in 1901 that blood transfusions became safe and reliable, ending the high mortality rate due to incompatible blood group transfusions, and earning Landsteiner the Nobel Prize for Medicine and Physiology in 1930.[26],[27]

It was becoming rapidly apparent that the use of the venous system as a therapeutic conduit was clearly of great medical value.[23],[28] Furthermore, these early canine experiments raised many queries such as: Does blood transfusion induce mental and psychological changes in the animal receiving blood? Does transfusion change a dog of one breed into another? Does it alter a dog’s temperament? Will a dog with new blood still know his master? Can a “fierce” dog be made into a “cowardly” dog? Transmutational fears existed with cross-species transfusion, often drawing the ire of the public and rendering the researcher the subject to public mockery and scorn.

  Problems and lack of adequate equipment (syringes/needles) to access the vascular space Top

Originally, experiments in the 17th century (Wren, Major, Elsholtz) used imperfect tools to administer drugs intravenously. Soon, the drawbacks of these early systems were made clear, especially in areas such as inappropriate, nonfitting material used to access the vascular space, blood leakage, intravascular coagulation, clotting preventing re-infusion, and instability of the infusion system leading to dislodgment needing reinsertion. Moreover, the procedure was fraught with other difficulties, such as adverse transfusion reactions, air embolism, and transmission of blood-borne disease.

Later, three methods were used to administer IV fluids or drugs: (a) the cutdown of a vein; (b) the use of a hollow metal needle to gain venous access; and (c) threading a plastic tube into a vein through a previously inserted hollow (metal) needle, followed by withdrawal of the needle over the catheter. None of them were ideal due to the fact that (a) venous cutdowns required surgical skills and supplies, were time-consuming, and uncomfortable for the patient with many complications (e.g., sacrificing the vessel, high infection rate); (b) insertion of reusable metal needles caused discomfort, frequent dislodgments, and reinsertions; and (c) threading plastic tubes through hollow metal needles often resulted in leakage of fluid and inadvertent shearing off the catheter tip, causing it to embolize into the circulation.

Lack of adequate equipment (syringes and sharp needles), device fixation, lack of knowledge (blood groups, transfusion reactions, germ theory and sterility, addiction (to opium), infection), nonfamiliarity with monitoring of volume during infusion and bloodletting, needlestick injuries, reusing needles, catheter thrombosis/embolus, inability to anticoagulate blood, and inadequate care of IV treatment were some of the many problems encountered during early vascular attempts. No doubt, initially, blood transfusion was painful and messy, with many failures and severe complications.

  Early development of intravenous apparatus, syringes, and needles Top

For 1000 of years, rudimentary devices were produced for medical purposes and were used by physicians of antiquity. Until the 19th century, most medical devices were still basic. Through the 19th and into the early 20th century, when the medical technical industry introduced cutting-edge technology, probably as an extension of the then new practice of inoculation against disease, subcutaneous injecting was generally seen as a more valuable route of administration than IV injection. Early physicians did not realize that hypodermic (subcutaneous) substances that were injected would have a systemic effect. Alexander Wood (1817—1884) from Edinburgh believed that the action of opiates administered by subcutaneous injection was mainly localized into the region of peripheral nerves. The use of Wood’s new hypodermic syringe and hollow needle was thought to allow greater accuracy in administering the drug in close proximity to a nerve, facilitating better pain relief in “neuralgias.”[28] Wood’s treatment of neuralgia by subcutaneous injection was popularized in Europe by the French L. J. Béhier.[29]

The earliest and most common syringe-type device was called a “clyster,” a device for giving enemas to purify the body, widely practised since ancient times.[21] At its most basic, a syringe for medical purposes is a type of simple pump, consisting of a plunger or piston that fits tightly within a cylindrical tube called a barrel, holding the fluid. The open end of the syringe may be fitted with a nozzle, a hypodermic needle, or a tubing to help direct the flow into (aspiration of fluids and blood) and out (administration of blood and drugs) of the barrel. Graduated marks on the syringe provide an indication of the volume of fluid in the reservoir. The connector provides a “fits-all” standard Lüer-Slip or Lüer-Lok system. In 1894, a German instrument maker working in France, Hermann Wülfing-Lüer, introduced the conical fitting with a 6% Lüer taper in the male for syringes and needles, which are still popular today. Lüer syringes became the standard syringe in the USA, while in Europe, the metal and glass Record syringe (10% taper nozzle) became popular following its production in 1906.[30] Since the International Organization of Standardization recommended the standard use of the Lüer-tipped syringe in 1995, the Lüer fittings are used worldwide for many medical applications.

Eventually, clinicians produced syringes with finger loops to enable injection for single hand injection.

The metal needles for injection (e.g., for heparin anticoagulation) were also fitted with fixation devices (e.g., Gordh needle).

Numerous catheter manufacturers produced medical equipment (tubes, needles, and catheters) using their own sizing system of tubing and various units of measures for various catheters. Nonstandardization of materials and dimensions caused many misconnections resulting in potential harm to the patient with the possibility of lethal consequences. At present, the most commonly used catheter sizing systems to ensure a secure connection are based on the outer diameter of the device using an ascending scale, i.e., The French metric scale (Fr, F, FG, or Ch) based on the Charrière system, and a descending scale, i.e., The British Standard Gauge (G or ga), which expresses the external diameter, based on a comparative standard using a defined set of sizes or thicknesses. Great Britain maintained the “Imperial Standard Yard” until 1963, when all gauges formally lost their legal existence, except within the field of anesthesia as a matter of convenience.[30]

James Blundell was among the first to use the term “syringe” for blood transfusion and described his method “the Impellor” in 1824.[31] It is likely that syringe-type devices, made from metal or glass, were described by many people who have been credited with their invention (Francis Rynd, Charles Gabriel Pravaz, and Alexander Wood). Syringes were produced by several instrument makers (e.g., in Paris: Charrière, Mathieu, and Lüer; in London: Ferguson, Solomon Maw, and Down Bros).[28],[29],[30],[31],[32]

David J. Massa (1923—1990) provided the first description of the modern over-the-needle IV catheter in 1949, also called the plastic Rochester needle, allowing plastic tubing attached to a shortened 16-G steel needle, threaded over a 19-G needle that acts as a stylet.[33] Australian toymaker Charles Rothauser (Adelaide, 1949) created the world’s first plastic disposable hypodermic syringe and produced the first injection-molded syringe from polypropylene. John Court from Melbourne introduced a winged infusion needle device, the “Court needle” or “butterfly,” with a plastic attachment that is connected to an IV giving set.[34]

Disposable syringes were introduced with standard Lüer fittings in the second half of the 20th century, solving the problem of sterility and mismatching fittings. The first completely disposable syringes were produced by Becton-Dickinson (Hypak® and Intracath®) and BBraun (Braunula®). Further improvements resulted in ported and nonported IV catheters, notched versions, safety catheters, and integrated needles to protect patients and users from needlestick injury and blood contact.[35]

IV cannulas were designed for short-term use (e.g., Hermann Strauss cannula in 1907), while indwelling IV cannulae saw many applications (such as the Olovson-Meyer needle (1940) for heparin therapy) and use in anesthesia, for example, the Gordh (1945), Domanig (1950), and Mitchell (1952) needles. Securing IV access was often problematic. For many years, anesthetists used syringes connected to the needle by a rubber tubing, with the needle and tubing securely taped to the volar surface of the outstretched arm or a syringe holder.[28],[36],[37],[38]

IV injections were by no means without incident or problems. Asepsis was a problem. Another challenge occurred when medication presented as a powder needed to be dissolved into a solution when the knowledge to ensure the safety of this process did not exist. Precision-made syringes were not available. This made correct dosage difficult. Syringes and needles were often mismatched with no standardization. The problem of inability to fix the syringe to the patient’s skin could result in dislocation, the piston occasionally got stuck, and reusable hypodermic needles often became dull and rusty from boiling and needed frequent sharpening.

  Central venous access Top

German surgical resident Werner Forssmann intentionally punctured his own antecubital vein, passed a 4-Fr ureteric catheter, and confirmed placement of the tip of the catheter in the right atrium with an X-ray. In 1929, he was the first to document the intracardiac positioning of a catheter inserted percutaneously, which ultimately meant the start of new options for monitoring and therapy. In the 1940s, Forssmann’s technique was further improved by André Counard and Dickinson Richards as a useful clinical tool for cardiovascular research. The three researchers were awarded the Nobel Prize in Medicine in 1956 for their role in central venous access, which is an essential tool in modern medicine, in anesthesia, intensive care, cardiology, and radiology, with particular applications in hemodialysis, total parenteral nutrition, and blood transfusion.[39]

  Historical fallacy and misconception of physiologic 0.9% saline Top

The Indian Blue Cholera pandemic, raging over Europe and Britain causing many thousands of deaths, reached Sunderland (England) in 1831 and stimulated the first IV use of saline. Although there was no consensus on its management and many methods were tried, the contemporary belief was that a noxious substance in the bowel was the culprit causing cholera, which needed to be purged from the bowel by using venesection and bloodletting.[40] The Irish Dr. William Brooke O’Shaughnessy studied the disease by analyzing blood and excreta and observed that the victims lost large amounts of water, saline, and carbonate—alkali from the blood, suggesting to rectify the imbalance of the circulation and restoring the red color to the blood, by an IV injection of warm water with mild innocuous salts.[14],[40],[41],[42],[43],[44] However, the solutions first used by Edinburgh physician Thomas Aitchison Latta (1796—1833) and later by other pioneers in saline infusion in the 19th century, advocating some 76 different, ineffective, and often damaging treatments for cholera, showed little similarity to the 0.9% saline solution we use today.[14],[26],[41],[45],[46],[47],[48],[49] Their aim was not rehydration but restoration of the blood to its red color and its arterial qualities.

Although mixing common salt in water is an easy and convenient way to produce physiologic saline, it remains a mystery how it came into general use as an IV fluid. The development of “normal saline” was followed from experiments by Hartog Jacob Hamburger, a Dutch chemist at Utrecht veterinary school in 1888, who described the beneficial osmotic consequences of isotonic fluid such as 0.92% saline and went on to call this fluid “normal” saline.[27],[48],[49],[50],[51] Sydney Ringer (1835—1910) introduced additional substances of chloride, sodium, potassium, calcium, and magnesium, to an isolated frog’s heart, suspended in a 0.75% solution of sodium chloride, to keep the heart beating for long periods of time.[52] Ringer’s solution is the basis of modern solutions, such as Ringer’s lactate or Hartmann’s solution,[52],[53] and Ringer’s acetate solution, which are all on the World Health Organization’s List of Essential Medicines, internationally deemed effective and safe therapies in health systems.[54]

  Conclusion Top

Accurate description of the cardiovascular system and the ability to access the system by insertion of IV tubes to deliver medication has been one of the most prominent advances in health care and was the precursor to the true birth of modern anesthesia.[55] The IV route ensures the delivery of medication used in anesthesia directly into the systemic circulation, avoiding the vagaries of (mal) absorption of orally administered drugs, oral bioavailability, and drug inactivation by the gut and liver. IV access was the start of many meaningful therapies and allowed operative interventions to occur without pain, including the possibility of one human living as a result of receiving donated blood from another.

Meticulous documentation of the early experimental scientific with technical details made the experiments accessible and permitted scientists and physicians to communicate with one another. The “Philosophical Transactions of the Royal Society of London” meant the start of thousands of scientific periodicals today devoted to biomedical sciences and medicine transferring knowledge to future generations in the hope of advancing medical practice. The impact of 350 years of revolutionary developments in science and medicine, and publication of these changes is unmeasurable. Without the impetus of early IV access experiments, our current enviable position — and especially so in anesthesia and resuscitation — may not have been possible.


We wish to acknowledge the contributions made by Oxford University Professor Keith Dorrington and Professor Jaideep Pandit, Nuffield Division of Anaesthetics, John Radcliffe Hospital, Oxford, UK, for their help in the preparation of this manuscript.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Aird WC. Discovery of the cardiovascular system: From Galen to William Harvey. J Thromb Haemost 2011;9:118-29.  Back to cited text no. 1
Learoyd P. The history of blood transfusion prior to the 20th century — Part 1. Transfus Med 2012;22:308-14.  Back to cited text no. 2
Dorrington KL, Aronson JK. Failed phlebotomy? Think William Harvey. BMJ 2014;349:g5232.  Back to cited text no. 3
Philosophical Transactions: Available from: http://rstl.royalsocietypublishing.org/. [Last accessed on 2020 Jan 21].  Back to cited text no. 4
Breathnach CS. Robert Hooke (1635-1703), in his own words. J Med Biogr 2003;11:218-25.  Back to cited text no. 5
Norman J. Journal des Sçavans: The First Scientific Journal Begins Publication (January 5, 1665). Available from: http://www.historyofinformation.com. [Last accessed on 2020 Jan 21].  Back to cited text no. 6
Keys TE. Historical vignettes. Sir Christopher Wren (1633-1723). Anesth Analg 1974;53:853.  Back to cited text no. 7
Gentili ME. Christopher Wren: From early transfusion to Saint-Paul Cathedral. Transfus Clin Biol 2014;21:328-9.  Back to cited text no. 8
Gibson WC. The bio-medical pursuits of Christopher Wren. Med Hist 1970;14:331-41.  Back to cited text no. 9
Bergman NA. Early intravenous anesthesia: An eyewitness account. Anesthesiology 1990;72:185-6.  Back to cited text no. 10
Wright AJ. The Strange Early Days of Blood Transfusion. Anesthesiology News. Available on: https://www.anesthesiologynews.com/PRN-/Article/01-15/The-Strange-Early-Days-of-Blood-Transfusion/29128/ses=ogst. [Last accessed on 2021 Jan 02].  Back to cited text no. 11
Webster C. The origins of blood transfusion: A reassessment. Med Hist 1971;15:387-92.  Back to cited text no. 12
Dorrington KL, Poole W. The first intravenous anaesthetic: How well was it managed and its potential realized? Br J Anaesth 2013;110:7-12.  Back to cited text no. 13
Rivera AM, Strauss KW, van Zundert A, Mortier E. The history of peripheral intravenous catheters: How little plastic tubes revolutionized medicine. Acta Anaesthesiol Belg 2005;56:271-82.  Back to cited text no. 14
Lower R. An account of the experiment of transfusion, practiced upon a man in London. 1667. Yale J Biol Med 2002;75:293-7.  Back to cited text no. 15
Coga A. An account of the experiment of transfusion, practised upon a man in London. Phil Trans 1667;2:557-9.  Back to cited text no. 16
Tubbs RS, Loukas M, Shoja MM, Ardalan MR, Oakes WJ. Richard Lower (1631-1691) and his early contributions to cardiology. Int J Cardiol 2008;128:17-21.  Back to cited text no. 17
Felts JH. Richard Lower: Anatomist and physiologist. Ann Intern Med 2000;132:420-3.  Back to cited text no. 18
Maluf NS. History of blood transfusion. J Hist Med Allied Sci 1954;9:59-107.  Back to cited text no. 19
Reinbacher WR. Leben, Arbeit und Umwelt des Arztes: Johann Daniel Major (1634—1693), Eine Biographie aus dem 17. Jahrhundert, mit neuen Erkenntnissen. Linsengericht: M. Kroeber; 1998.  Back to cited text no. 20
Gladstone E. Johann Sigismund Elsholtz: Clysmatica Nova (1665): Elsholtz’ Neglected Work on Intravenous Injection: Part I. Cal West Med 1933;38:432-4.  Back to cited text no. 21
Rudmann SV. Textbook of Blood Banking and Transfusion Medicine. 2nd ed. Philadelphia: Elsevier Saunders; 2005.  Back to cited text no. 22
Blundell J. Observations on transfusion of blood. Lancet 1829;2:321-4.  Back to cited text no. 23
Blundell J. Experiments on the transfusion of blood by the syringe. Med Chir Trans 1818;9:56-92.  Back to cited text no. 24
Welck M, Borg P, Ellis H. James Blundell MD Edin FRCP (1790-1877): Pioneer of blood transfusion. J Med Biogr 2010;18:194-7.  Back to cited text no. 25
Zarychanski R, Ariano RE, Paunovic B, Bell DD. Historical perspectives in critical care medicine: Blood transfusion, intravenous fluids, inotropes/vasopressors, and antibiotics. Crit Care Clin 2009;25:201-20, x.  Back to cited text no. 26
Roets M, Sturgess DJ, Wyssusek K, van Zundert AA. Intraoperative cell salvage: A technology built upon the failures, fads and fashions of blood transfusion. Anaesth Intensive Care 2019;47:17-30.  Back to cited text no. 27
Ball C. The early development of intravenous apparatus. Anaesth Intensive Care 2006;34:22-6.  Back to cited text no. 28
Ball C, Westhorpe R. Intravenous equipment — The ongoing development of the syringe. Anaesth Intensive Care 2000;28:125.  Back to cited text no. 29
Pöll JS. The story of the gauge. Anaesthesia 1999;54:575-81.  Back to cited text no. 30
Blundell J. Dr. Blundell’s Physiological and Pathological Researches. Med Chir Rev 1825;2:400-12.  Back to cited text no. 31
Ball CM, Westhorpe RN. Intravenous equipment — Early syringes. Anaesth Intensive Care 2000;28:118-9.  Back to cited text no. 32
Southorn PA, Narr BJ. The Massa or Rochester plastic needle. Mayo Clin Proc 2008;83:1165-7.  Back to cited text no. 33
Ball C, Westhorpe R. Modern developments — Plastic cannulas and the court butterfly needle. Anaesth Intensive Care 2000;28:603.  Back to cited text no. 34
van Zundert A. New closed IV catheter system. Acta Anaesthesiol Belg 2005;56:283-5.  Back to cited text no. 35
Gordh T. A new, simple and practical needle for intravenous anesthesia. Anesthesiology 1945;6:258-60.  Back to cited text no. 36
Ball C, Westhorpe R. Intravenous cannulae. Anaesth Intensive Care 2000;28:467.  Back to cited text no. 37
Waisel DB. The role of World War II and the European theater of operations in the development of anesthesiology as a physician specialty in the USA. Anesthesiology 2001;94:907-14.  Back to cited text no. 38
Beheshti MV. A concise history of central venous access. Tech Vasc Interv Radiol 2011;14:184-5.  Back to cited text no. 39
Janakan G, Ellis H. Dr. Thomas Aitchison Latta (c1796-1833): Pioneer of intravenous fluid replacement in the treatment of cholera. J Med Biogr 2013;21:70-4.  Back to cited text no. 40
Bartecchi CE. Intravenous therapy: From humble beginnings through 150 years. South Med J 1982;75:61-4.  Back to cited text no. 41
MacGillivray N. Sir William Brooke O’Shaughnessy (1808—1889), MD, FRS, LRCS Ed: Chemical pathologist, pharmacologist and pioneer in electric telegraphy. J Med Biogr 2017;25:186-96.  Back to cited text no. 42
MacGillivray N. Dr Thomas Latta: The father of intravenous infusion therapy. J Inf Prev 2009;10:S3-6.  Back to cited text no. 43
Masson AH. Latta — Pioneer in saline infusion. Br J Anaesth 1971;43:681-6.  Back to cited text no. 44
Latta T. The first use of intravenous saline for the treatment of disease. Int J Epidemiol 2013;42:387-90.  Back to cited text no. 45
Cosnett JE. The origins of intravenous fluid therapy. Lancet 1989;1:768-71.  Back to cited text no. 46
Baskett TF. William O’Shaughnessy, Thomas Latta and the origins of intravenous saline. Resuscitation 2002;55:231-4.  Back to cited text no. 47
Awad S, Allison SP, Lobo DN. The history of 09% saline. Clin Nutr 2008;27:179-88.  Back to cited text no. 48
Featherstone PJ, Ball CM. Intravenous crystalloids in the late 19th and early 20th century. Anaesth Intensive Care 2017;45:651-3.  Back to cited text no. 49
Anon HJ. Hamburger (1859-1924). Nature 1959;183:648-9.  Back to cited text no. 50
Lazarus-Barlow WS. On the initial rate of osmosis of blood-serum with reference to the composition of “Physiological Saline Solution” in Mammals. J Physiol 1896;20:145-57.  Back to cited text no. 51
Ringer S. A third contribution regarding the Influence of the Inorganic Constituents of the Blood on the Ventricular Contraction. J Physiol 1883;4:222-5.  Back to cited text no. 52
Hartmann AF. Theory and practice of parenteral fluid administration. JAMA 1934;103:1249-54.  Back to cited text no. 53
WHO Model List of Essential Medicines 19th List (April 2015). Available from: http://www.who.int/medicines/publications/essentialmedicines/en/. [Last accessed on 2020 Jan 21].  Back to cited text no. 54
White PF. A history of intravenous anesthesia. In: Eger EI II, Edmond I, Saidman L, Westhorpe R, editors. The Wondrous Story of Anesthesia. Ch. 47. New York: Springer-Verlag; 2014.  Back to cited text no. 55


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1 Oddities in the Evolution of Syringes in Anesthesia
Floris S. Wiepking, André A. J. Van Zundert
Anesthesia & Analgesia. 2022; Publish Ah
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