The history of therapeutic hypothermia and its use in neurosurgery

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Despite an overwhelming history demonstrating the potential of hypothermia to rescue and preserve the brain and spinal cord after injury or disease, clinical trials from the last 50 years have failed to show a convincing benefit. This comprehensive review provides the historical context needed to consider the current status of clinical hypothermia research and a view toward the future direction for this field. For millennia, accounts of hypothermic patients surviving typically fatal circumstances have piqued the interest of physicians and prompted many of the early investigations into hypothermic physiology. In 1650, for example, a 22-year-old woman in Oxford suffered a 30-minute execution by hanging on a notably cold and wet day but was found breathing hours later when her casket was opened in a medical school dissection laboratory. News of her complete recovery inspired pioneers such as John Hunter to perform the first complete and methodical experiments on life in a hypothermic state. Hunter’s work helped spark a scientific revolution in Europe that saw the overthrow of the centuries-old dogma that volitional movement was created by hydraulic nerves filling muscle bladders with cerebrospinal fluid and replaced this theory with animal electricity. Central to this paradigm shift was Giovanni Aldini, whose public attempts to reanimate the hypothermic bodies of executed criminals not only inspired tremendous scientific debate but also inspired a young Mary Shelley to write her novel Frankenstein. Dr. Temple Fay introduced hypothermia to modern medicine with his human trials on systemic and focal cooling. His work was derailed after Nazi physicians in Dachau used his results to justify their infamous experiments on prisoners of war. The latter half of the 20th century saw the introduction of hypothermic cerebrovascular arrest in neurosurgical operating rooms. The ebb and flow of neurosurgical interest in hypothermia that has since persisted reflect our continuing struggle to achieve the neuroprotective benefits of cooling while minimizing the systemic side effects.

ABBREVIATIONS BRL = Brain Research Laboratory; SCI = spinal cord injury; TBI = traumatic brain injury.

Article Information

Correspondence Mark C. Preul: Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ. neuropub@barrowneuro.org.

INCLUDE WHEN CITING Published online May 25, 2018; DOI: 10.3171/2017.10.JNS171282.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

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    Engraving of Hippocrates (c. 460–c. 370 bce) on the frontispiece of his famous work translated by Francis Clifton, “Upon Air, Water and Situation: Upon Epidemical Diseases: and upon Prognosticks, in Acute Cases Especially,” London, 1734. Image engraved by G. Van der Gucht from a drawing by Peter Paul Rubens of a bust of Hippocrates; the engraved image is a rendering of Hippocrates according to the artists’ imaginations. Figure is in the public domain.

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    Left: A woodcut from c. 1651 depicting the hanging of Anne Greene. A militiaman is depicted beating on her chest with the stock of his musket, and relatives pull on her feet in hopes of ending her misery more quickly. The upper left corner of the image depicts her resuscitation and rewarming. Right: William Petty (May 26, 1623–December 16, 1687) at the time of his election as professor of anatomy at Oxford. (Portrait by Isaac Fuller c. 1651.) Left panel: public domain. Right panel: © National Portrait Gallery, London. Used with permission.

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    A portrait of John Hunter (February 13, 1728–October, 16 1793), who may be regarded as the father of modern scientific surgery. He carried out one of the first experiments to study the effects of hypothermia on live organisms and made many of the earliest discoveries in body temperature regulation and the physiological effects of hypothermia. Portrait by John Jackson, after Sir Joshua Reynolds, oil on canvas, 1813; copy of portrait by Sir Joshua Reynolds, made in 1786. © National Portrait Gallery, London. Used with permission.

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    A: Luigi Aloisio Galvani, Italian physician, physicist, and biologist, who studied bioelectricity (September 9, 1737–December 4, 1798). Anonymous painting, 18th century, University of Bologna. B: Galvani’s rival, a famous Italian physicist and pioneer of electricity, Alessandro Giuseppe Antonio Anastasio Volta (February 18, 1745–March 5, 1827). C: Galvani’s nephew, Giovanni Aldini (April 10, 1762–January 17, 1834). Aldini was a professor of physics who carried out animal and human experiments on galvanism, popularizing his uncle’s invention for the English-speaking public. Portrait by William Brockedon, chalk and pencil, 1830. D and E: Illustrations from Giovanni Aldini’s treatise on galvanism depicting his animal cadaver and human cadaver experiments with electricity (Aldini J: Essai Theorique et Experimental sur Le Galvanisme, Avec une Serie D’Experiences. Paris: De L’Imprimerie de Fournier Fils, 1804). Panels A and B: public domain. Panel C: © National Portrait Gallery, London. Used with permission. Panels D and E: Wellcome Library, London; copyrighted work available under Creative Commons Attribution only license CC BY 4.0 (http://catalogue.wellcomelibrary.org/record=b1119983).

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    Newspaper cartoon depicting Aldini’s alleged resurrection of George Forster. Aldini’s public experiments are thought to have inspired Mary Shelley’s infamous Dr. Frankenstein. Printed and published by H. R. Robinson, 1836. Library of Congress, Prints & Photographs Division, reproduction number LC-USZ62-11916.

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    A painting by Tony Robert-Fleury showing Pinel unchaining women in a Parisian asylum in 1795 (painted in 1875). Figure is in the public domain.

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    Temple Fay (January 9, 1895–August 19, 1963) in 1940 at the time of his most intense activity in hypothermia research. Publicly, Fay was perhaps more notorious for his support of the Doman-Delacato “patterning” treatment. Photograph courtesy of Special Collections Research Center, Temple University Libraries, Philadelphia, PA.

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    Schutzstaffel (SS) doctors at Dachau conducting the immersion-hypothermia experiments in 1942. Sigmund Rascher appears in the front in the left photograph. Note the ice chunks in the tub of water. After the conclusion of the official study, Rascher was apparently involved in the murders of more prisoners to enhance his contribution for a scientific conference and to expand his later postdoctoral thesis with the additional autopsy findings. “I take the liberty to enclose the final report on the hypothermia experiments in Dachau.… Also not included in this report is the microscopic pathological examination of the brain stem of the deceased.… Till the conference I will conduct more experiments and hope to be able to present further results in this period.” [Rascher S: Final report from Dr. Sigmund Rascher sent to Heinrich Himmler, Oct. 16, 1942, Staatsarchiv Nürnberg, Germany]. Himmler replied to Rascher: “I view those people who today still reject these human experiments, preferring instead to let courageous German soldiers…die, as guilty of high treason and as traitors…” [Himmler H: Letter to Sigmund Rascher, Oct. 24, 1942, Staatsarchiv Nürnberg, Germany]. The German military leadership was unable to influence or take control of the project. Rascher and his wife, Karoline, who was 16 years older than Rascher and who also promoted his career along with Himmler, came to ironic deaths. After learning that they had committed fraud with regard to the false reporting of births when instead they had kidnapped their 4 “Aryan” children, the deceived Himmler exacted the ultimate revenge. Rascher’s wife was sent to the Ravensbrück concentration camp and executed in 1945, while Rascher was sent to the Buchenwald concentration camp and then transferred to Dachau in April 1945, where he was executed. Used with permission from Bildarchiv Preussischer Kulturbesitz. Rights provided by US-based partner, Joyce Faust, Permissions Associate, Art Resource, Inc. www.artres.com.

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    Robert J. White (January 21, 1926–September 16, 2010), a neurosurgeon and scientist at Case Western Reserve University, who carried out a series of studies of hypothermia and undertook full head transplant experiments on animals. From the archives of The MetroHealth System, Cleveland, Ohio. Used with permission.

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    Intraoperative photograph taken during hypothermic cardiac arrest at Barrow Neurological Institute, 1986, showing the operating neurosurgeon Robert F. Spetzler explaining details of the surgery to journalists. Copyright Barrow Neurological Institute. Used with permission.

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