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In a new randomized clinical trial by an Australian research team, adult patients who received nitrous oxide during major surgery were at increased risk of postoperative complications, including pneumonia, fever, severe nausea and wound infection. The findings, published in the journal Anesthesiology,1 attracted media attention in Australia2 and England,3,4 and additional coverage from Fox News5 in the United States.

While the study raises challenging questions regarding anesthesia for major surgery, it also cautions that “[e]xtrapolation of our findings to other situations, such as the use of nitrous oxide in minor surgery, pediatric surgery, or labor analgesia, should be avoided.”1 As for dentistry, an accompanying editorial6 and an interview of the study’s lead author7 emphasize that the findings are not applicable to dental procedures and other minor surgery. Additional perspectives on the Australian study are presented below.

The multi-center clinical trial recruited more than 2,000 patients over 18 years of age who were treated in hospitals based in the United Kingdom, Asia and Australia, and randomly assigned them to two study groups. Patients received either 70% nitrous oxide/30% oxygen or 80% oxygen/20% nitrogen. The study evaluated if removing nitrous oxide from the anesthetic mixture for major surgery, lasting at least two hours, reduced the incidence of postoperative complications within 30 days of surgery.

The study found that patients who received 70% nitrous oxide anesthesia were more likely to suffer pneumonia, fever and wound infections. Also, the nitrous oxide-free group had a significantly reduced rate of severe nausea or vomiting in the first 24 hours after surgery, but no significant differences were reported for the two patient groups’ duration of hospital stay.

While dentists commonly administer nitrous oxide to patients of all ages to reduce fear, anxiety, or uncooperativeness, the new Australian study did not represent or characterize how nitrous oxide is used for analgesia and sedation in dental practice. In general, dentistry does not administer the higher concentrations of nitrous oxide (70%) provided in the Australian study. This high level of nitrous oxide is required for anesthesia in major surgery because the gas is a weak general anesthetic agent. Nitrous oxide is most commonly used in general anesthesia as an adjunct to other, newer anesthetic agents. For dental applications, nitrous oxide is generally administered at lower concentrations, typically 50% or less with a correspondingly higher oxygen level.

As noted in an editorial6 accompanying the new study, “[n]itrous oxide is certainly useful for inhalational inductions in children, as well as for analgesia in laboring parturients or in patients having dental procedures." In addition, the study authors suggest the decreased risk for major post-operative complications could be attributed to either the avoidance of nitrous oxide and/or the administration of high inspired oxygen (note: the latter may have provided beneficial effects that were not possible in the group that received 70% nitrous oxide). Lastly, the study participants had significant medical problems and greater surgical stress, each of which may have influenced the postoperative outcomes. Further well-designed studies are required to determine whether routine use of 70% nitrous oxide in major surgery is associated with more postoperative complications.

Based on the available evidence, the use of conscious sedation, deep sedation and general anesthesia in dentistry is safe and effective when properly administered by trained individuals. These techniques may or may not include use of nitrous oxide. In accordance with ADA recommendations for controlling nitrous oxide exposure in the dental operatory, each office should have a properly installed nitrous oxide delivery system, including appropriate scavenging equipment with a readily visible and accurate flow meter (or equivalent measuring device); a vacuum pump with the capacity for up to 45 liters of air per minute per workstation; and a variety of sizes of masks to ensure proper fit for individual patients. Dentists who provide sedation and general anesthesia services in their dental office can obtain additional information in the ADA Guidelines for the Use of Sedation and General Anesthesia by Dentists (PDF) and the Council on Scientific Affairs’ recommendations for managing office emergencies.  


1. Myles PS, Leslie K, Chan MT, Forbes A, Paech MJ, Peyton P, Silbert BS, Pascoe E; the ENIGMA Trial Group. Avoidance of nitrous oxide for patients undergoing major surgery: a randomized controlled trial. Anesthesiology 2007 Aug;107(2):221-231. Abstract available at:;jsessionid=GLSf292jN1GNlth3ZC1QybHyzvCGGRXzBT9L2SXbbv27NJ18pjQ0!-362743511!181195628!8091!-1. Accessed August 21, 2007.

2. Safety of laughing gas no joke., August 9, 2007. Available at:,23599,22214158-29277,00.html. Accessed August 19, 2007.

3. Randerson J. Laughing gas increases risk of pneumonia and fever, says study. The Guardian, August 9, 2007. Available at: Accessed August 21, 2007.

4. Safety fears over laughing gas. news service, August 12, 2007. Available at: Accessed August 21, 2007.

5. Study: laughing gas dangerous, no joke., Health section, August 9, 2007. Available at:,2933,292690,00.html#. Accessed August 21, 2007.

6. Hopf HW. Is it time to retire high-concentration nitrous oxide? [editorial]. Anesthesiology 2007;107:200-1. Available at:;jsessionid=GTvNRJvympB4f7dTDtQGygb5dRgmQMZLlpkQ15JyrVYF23Jh5T3W!-79285651!181195629!8091!-1. Accessed August 24, 2007.

7. Miles J. Laughing gas frowned upon. The Courier-Mail, August 1, 2007. Accessed August 22, 2007.

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Science in the News is a service by the American Dental Association (ADA) to present current information about science topics in the news. The ADA is a professional association of dentists committed to the public's oral health, ethics, science and professional advancement; leading a unified profession through initiatives in advocacy, education, research and the development of standards. As a science-based organization, the ADA's evaluation of the scientific evidence may change as more information becomes available. Your thoughts would be greatly appreciated.

Document Posted August 2007