From Ancient Arsenal to an Anesthetic: Historical Roles of Hyoscyamine and Aconitine in Anesthesia

Katsushika Ōi's painting from the 1840s (figure 1) poignantly captures Hua Tuo, a legendary 2nd–3rd century Chinese physician. This popular scene, drawn from the "Romance of the Three Kingdoms," depicts the Han dynasty general Guan Yu entrusting himself to the skilled hands of Hua Tuo after being struck by an aconite-poisoned arrow, a weapon notorious for its lethal use in warfare and hunting over millennia.Ōi's work, diverging from Utagawa Kuniyoshi's portrayal,1 features realistic details such as protruding veins on Guan Yu's hand and arm with tourniquets applied. The intricate and calming array of herbs and plant roots in the background is in stark contrast with the dripping blood onto the tray, and the blood collector's reaction of disbelief, mirrored in another bystander's face. Guan Yu's gallantry is further highlighted by his casual demeanor while playing Go after having refused Hua Tuo's pain relief offer.The aconite toxin, aconitine, disrupts sodium channels with high affinity, leading to acetylcholine depletion and potentially fatal cardiovascular effects.2 Hua Tuo's attempt to remove the toxin-infested bone was to prevent its spread to Guan Yu's heart.The cultural reverence for the episode of Hua Tuo and traditional Chinese medicine inspired not only Ōi but also Hanaoka Seishu (1760 to 1835). Despite the elusive details of Hua Tuo's anesthetic recipe, Hanaoka, having studied under distinguished traditional Chinese medicine practitioners in Kyoto, advanced the oral anesthetic technique.3 By 1804, he was able to perform lumpectomy surgeries. Hanaoka's recipe, Mafutsusan, used Datura extract containing hyoscyamine, also known as levo-atropine, which causes anticholinergic symptoms like delirium, cognitive decline, hallucinations, and disorientation. By combining Datura extract with attenuated cardio-depressant effects of aconitine, Hanaoka managed tachycardia from hyoscyamine overdose. His anesthetic technique allowed Hanaoka and his apprentices to perform surgeries on patients who would not have endured pain as Guan Yu did before ether and local anesthetics were widely available.3The creation of Ōi's artwork coincides with the period of emerging anesthetic techniques. Her canvas with her keen observational prowess and vibrant palette, invites reflection on the evolution of pain management and honors the resilience and courage of patients before the anesthetic revolution.The authors declare no competing interests.