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Adrenaline - A Therapeutic History - Anesth Int Care 2017

The document discusses the historical use of adrenaline in medical treatments, particularly in resuscitation and the management of shock and anaphylaxis. It highlights key figures such as George Crile, who conducted pioneering research on adrenaline's efficacy, and Dudley Buxton, who emphasized its importance in anaesthesia. The evolution of adrenaline administration methods, from intracardiac to intravenous and inhalation routes, is also outlined, showcasing its critical role in emergency medicine by the 1950s.

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27 views3 pages

Adrenaline - A Therapeutic History - Anesth Int Care 2017

The document discusses the historical use of adrenaline in medical treatments, particularly in resuscitation and the management of shock and anaphylaxis. It highlights key figures such as George Crile, who conducted pioneering research on adrenaline's efficacy, and Dudley Buxton, who emphasized its importance in anaesthesia. The evolution of adrenaline administration methods, from intracardiac to intravenous and inhalation routes, is also outlined, showcasing its critical role in emergency medicine by the 1950s.

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Internos Urgencias
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We take content rights seriously. If you suspect this is your content, claim it here.
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Anaesth Intensive Care 2017 | 45:5 Cover note

Cover note

Adrenaline—a therapeutic history


Buxton’s work was based almost entirely on the
contemporary research of the American surgeon, George
Crile. Crile conducted extensive experiments on animals,
confirming the efficacy of adrenaline in the treatment of
shock and cardiac arrest3. He too noted the impracticalities,
stressing that some animals died from inadequate dosing
and others from too rapid an infusion. He also observed
that direct injection of adrenaline into the heart could lead
to ventricular fibrillation. Crile’s work was so revolutionary
it frequently made the local papers; his experiments with
decapitated dogs kept alive for hours with adrenaline
infusions were reported on the front page of the New York
Image courtesy of Geoffrey Kaye Museum, Australian and New Zealand Times4. In 1909, after some success with adrenaline in clinical
College of Anaesthetists.
situations, he prepared a protocol for resuscitation, the first
Intravenous medication is still in its infancy. Used with discretion to include the administration of adrenaline. Once again, this
it has a great future before it… attracted considerable attention in the press. The publicity
J.L. Marjoribanks, MD, DPH, Lieut-Colonel IMS prompted a flurry of correspondence, including a letter from
13 March 19211. a woman who asked if he could resuscitate her husband who
had died during an accident some years earlier and was still
The 1909 meeting of the Section of Anaesthetics of the entombed in a glacier5,6.
Royal Society of Medicine was devoted to the recognition, Latzko is thought to have been the first to use intracardiac
prevention and treatment of surgical shock, a problem adrenaline in humans. He presented his experiences at
that had attracted greater attention since the introduction a meeting in Vienna in 1909, stating he had been using
of blood pressure measurement. The principal speaker at intracardiac adrenaline with some success for five years7,8. In
the meeting, Dudley Buxton, outlined his observations, 1923, Carl Bodon, a US medical officer stationed in Budapest,
noting that adequate depth of anaesthesia was required published a review of the use of intracardiac drugs after
to prevent “psychic shock…irregular nervous explosions successfully resuscitating a man who arrested in the lounge
causing respiratory and circulatory storms which always room of their shared boarding house. Bodon used undiluted
make for danger”2. But he appreciated that excessively adrenaline and noted that, while many other drugs such as
deep anaesthesia could cause or exacerbate hypotension, camphor oil, caffeine, strophanthin and strychnine had been
compounding shock when other surgical variables, such as used, “adrenalin has lately, and deservedly, taken the lead
haemorrhage or visceral traction were present. in intracardiac injections when there is no time to be lost”7.
Describing the therapies he had been investigating, Buxton He also observed that the indications listed by the various
noted: “since I have employed oxygen with the anaesthetic, authors were grouped broadly into three categories of shock:
there has been less shock…”2. As well as proposing the free surgical (including anaesthesia), obstetric, and internal
and somewhat novel administration of oxygen, Buxton made diseases. He thought the list unsatisfactory and incomplete,
mention of pharmaceuticals. He dismissed the fashionable remarking: “So far as I know, nobody has thought of extending
injections of ether, alcohol and strychnine, offered some the indications to include the very promising and vast field of
support for digitalis in the failing heart and promoted the new idiosyncrasies against drugs, and anaphylaxis”7.
pharmaceutical, adrenaline, which: “if continuously applied, Anaphylaxis was a relatively newly understood condition,
offers much hope”2. Continuous application was not easy its pathophysiology discovered largely by accident. On July
though; intravenous infusions required surgical insertion 1905, a steamer sailed from France on a 2½ month voyage
of a cannula, were difficult to control and impractical for of discovery, one of a series of scientific voyages initiated
prolonged periods. Mr Lockhart Mummery, who had also by Prince Albert of Monaco9. Among the scientists on board
been experimenting with the drug, noted that “clinically were Paul Portier, a medical doctor from the department of
adrenalin was useless...it was necessary to keep up the physiology at the University of Paris, and the doctor, author
infusion of it into the veins, and watch the pressure by means and playwright, Charles Richet, also from Paris. Their mission
of a manometer”2. was to study the Portuguese man-of-war, the long tentacled

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Anaesth Intensive Care 2017 | 45:5 Cover note

jellyfish which inflicted extreme pain and disability on its more prominent”16. Even in these early days of intravenous
hapless victims. Portier and Richet were hopeful that isolating medication, the potential for errors was all too apparent.
a toxin would lead to potential treatments. By the 1950s, adrenaline had a well-established place in
Continuing their work back on shore, they injected animals the treatment of many life-threatening conditions. Despite
with repeated low doses of various toxins, hoping to create the development of many other sympathomimetic amines, it
an immunological treatment. To their surprise, the animals remains a crucial part of all resuscitation protocols.
previously exposed to large doses of the toxin died when
reinjected with subsequent low doses. Richet’s ongoing work C. M. Ball
in this area led to the understanding of the condition and Department of Anaesthesia and Perioperative Medicine,
ultimately, a Nobel Prize. He named the condition ‘aphylaxis’ Alfred Hospital and Monash University, Melbourne, Victoria
(without protection, from the Greek), later changed to
anaphylaxis because it was easier to say. P. J. Featherstone
The discovery was well timed. While the condition had Addenbrooke's Hospital, Cambridge, UK
been described since ancient times, it was emerging as a
more frequent problem due to the development of antitoxins References
to diphtheria and tetanus. Antitoxins, while saving the lives 1. Marjoribanks J. Adrenaline for resuscitation. Br Med J 1921;
of many, were also causing isolated deaths. In 1919, T. Harris 1:544.
Boughton reviewed a number of deaths in asthmatics with 2. Buxton D. Treatment of shock during anaesthesia. Proc R Soc
known allergies to horses10. These patients had all died Med 1909; 2 (Sect Anaesth):55-70.
following administration of antitoxins made with horse 3. Crile G. Blood-pressure in surgery. An experimental and clinical
serum. While Boughton correctly identified the problem research. The Cartwright prize essay for 1903. Philadelphia and
London: J B Lippincott Company; 1903.
as anaphylaxis, there was no mention of treatment. The
4. Brought dead dog to life. New York Times. 1903; Sect. Column 4.
following year Will Walter reported a near fatal anaphylactic 5. Surgeon tells how he brings back life. New York Times. 1909
reaction to pollen inoculation noting “it being a well- February 14; Sect. Column 3.
established principle that anaphylatoxic poisoning is best 6. Crile GW, Crile G. George Crile, an Autobiography. Philadelphia
met by increasing blood alkalinity… we adopted an alkaline and New York: Lippincott; 1947.
dietary regimen”11. 7. Bodon C. The intracardiac injection of adrenalin. Lancet 1923;
Bodon was not the first to suggest adrenaline for the 1:586-590.
treatment of anaphylaxis but in the years following his 8. Latzko. Discussion d. Gesells, d. Aerzto in Wein. Vien M Wschr.
1923 publication, there was a marked increase in the use 1909.
9. Cohen SG, Zelaya-Quesada M. Portier, Richet, and the discovery
of adrenaline for this condition, by both the intracardiac
of anaphylaxis: a centennial. J Allergy Clin Immunol 2002;
and intravenous routes. Adrenaline was also discovered to 110:331-336.
have bronchodilatory properties in 1903 and by the 1920s 10. Boughton T. Anaphylactic death in asthmatics. JAMA 1919;
had widespread application in the treatment of asthma12,13. 73:1912-1915.
Given subcutaneously, it was often self-administered by 11. Walter W. Inoculation against hay-fever: an experience, a
the patient during acute attacks14. As the intravenous route warning and a suggestion. JAMA 1920; 75:670-671.
became more practical with the development of better 12. Bullowa J, Kaplan D. Treatment of asthmatic attacks: on the
equipment, it was realised that intravenous administration hypodermatic use of adrenalin chloride in the treatment of
was more effective for status asthmaticus15. For less severe asthmatic attacks. Med News 1903; 83:787-790.
13. Davidson M. Asthma. Postgrad Med J 1928; 4:1-6.
attacks, the subcutaneous route was eventually supplanted
14. Graeser J, Rowe A. Inhalation of epinephrin for the relief of
by inhaled adrenaline. James Graeser and Albert Rowe were asthmatic symptoms. J Allergy 1935; 6:415-419.
the first to suggest oral inhalations of adrenaline. Using a 1 in 15. Ross J. Intravenous adrenaline in asthma. Br Med J 1946; 2:242.
100 solution, they demonstrated that it was more effective 16. Preparations and appliances. Adrenaline preparation for asthma.
than injections and had less side-effects in many of their Br Med J 1938;2:709.
patients14. As a result, several companies began making
special preparations, formulated to work in commercially
available atomisers. These solutions were more concentrated
than the intravenous preparations raising new safety
concerns. The release of Burroughs Wellcome and Co’s 1%
vaporole prompted an editorial in the British Medical Journal
stating: “The bottles of vaporole solution and their containers
are labelled “Caution—Not for injection,” but we would
suggest the advantage of making this warning somewhat

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