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Goerig M, Schulte am Esch J. 
“[Early contributions for the development of nitrous oxide-oxygen anesthesia in central Europe]”. 
Anaesthesiol Reanim. 2002 Jun 05;27(2):42-53.
The American dentist Horace Wells was the first to administer nitrous oxide for pain relief during painful tooth extractions. Since, however, an official demonstration of the pain-relieving properties of the gas at Massachusetts General Hospital in Boston ended in failure, use of the drug was abandoned. A few years later, Gardner Quincey Colton, a former coworker of Wells, took up Wells\' idea to use nitrous oxide for pain relief and this was instrumental in its reintroduction into daily practice. Colton\'s publications on the advantageous use of nitrous oxide caused Stanislav Klikovitch from St. Petersburg, Russia, to administer the drug for pain relief during labour. In order to minimize the risk of asphyxia during the inhalation of the gas, he used an anaesthetic mixture consisting of 80% nitrous oxide and 20% oxygen. Moreover, it is to Klikovitch that we owe the first description of effective self-administration of nitrous oxide mixtures for pain relief. He recommended that inhalation should start 30-60 seconds before the expected pain and said between 2 and 6 inhalations would give the expected effect. Additionally, he suggested taking deep breaths and doing so at the beginning of subsequent pains. This is the first description of patient-controlled analgesia. Klikovitch reported his experiences with the new anaesthetic method in several German-language publications. Among those who were fascinated by his pain-relieving concept was Paul Zweifel from Leipzig, one of the leading obstetricians of his time in Germany. Together with numerous of his pupils, he popularized the method, using new apparatus for a safer kind of administration. Further technical developments in the early twenties, such as the introduction of the circle system or the clinical use of oxygen-monitoring devices, were additional milestones in nitrous oxide/oxygen anaesthesia.
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