The Volatile Discovery of Fluorine Anesthetics

As paraphrased from,

Dr. John C. Krantz Jr’s Historical Medical Classics Involving New Drugs, 1974

This book was given to me by the first pharmacist I worked under when I made the commitment to pursue pharmacy school. This pharmacist, and these stories, inspired me. I hope this paraphrased historical recalling of the discovery of fluorine anesthetics leaves you grateful for the progress that our pharmacological predecessors accomplished.

Fluorine, as an element, was first discovered in 1810 by Ampere of France. It was not used in a human patient until 1953. One of the three leading anesthetics at the time, ether, was to become the backbone of Fluromar, the first fluorine anesthetic. Ether was highly volatile and flammable, making it extremely dangerous to work with.

“Apparently unaware of the explosive nature of mixtures of ethylene and oxygen, the surgeon attempted electric cautery on the patient, a prominent Baltimore merchant. A violent explosion ensued, eviscerating the patient, injuring the surgeon and demolishing the operating room furnishing.” Pg 117

Thankfully, a century of work began to unravel the connection between introducing fluorine to ethers, and the substantial decrease in flammability. Replacement of all hydrogen atoms within ether did prove to inhibit the flammability, but it was unfortunately also efficient in ceasing any anesthetic ability of the substance. The solution was to compromise with partial fluorination:

C2H5 – O – C2H5 : ether vinyl ether – Vinamar

CF3 ∙ CH2 – O – CH = CH : trifluoroethyl vinyl ether – Fluoromar

John C. Krantz Jr, was a part of the team that discovered Fluoromar as a Professor of Pharmacology, at the University of Maryland. Their team had succeeded with many animal studies, showing the safety and efficacy of Fluoromar in small animals. Human patients were not to be considered for a trial until one brazen former student of Dr. Krantz’s walked into his office for a casual reunion in the winter of 1953. This former student, now a Professor of Anesthesiology at the University of Illinois, brazenly demanded that he should willingly submit himself to be the first human subject. This Dr. Max S. Sadove claimed that as the president of the Walter Reed Society, he should be given the first ever human dose of a fluorinated anesthetic.

Notably, the Walter Reed Society was a group of scientists who emulated the virtues of Walter Reed and therefore were so inclined to use even their own bodies to further the advances of medicine.

Thus, it was agreed; The two Professors met at the university’s research hospital. When met with the newly advanced - and formidable - anesthesia delivery machine, Dr. Krantz politely declined its use and opted for the open drip method. Dr. Sadove laid on the surgery table while Dr. Krantz prepared the concoction and when they were ready, began to drip the liquid onto the mask that lay over Dr. Sadove’s face… He made it to only 32 counts. When Dr. Sadove awoke after six minutes, he was alert and unaffected by the induced slumber. The team then decided this was satisfactory evidence of its success:

“Thirty minutes later Dr. Sadove administered Fluoromar by the open drip method to a middle-aged woman for anesthesia for rectal surgery.” Pg 117

Krantz, John C. (John Christian). Historical Medical Classics Involving New Drugs. Baltimore: Williams & Wilkins, 1974. Print.