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Title Hematopoietic Disruption Due to Chronic Nitrous Oxide Exposure
Clinical Question Does prolonged exposure to nitrous oxide of 24 hours or more cause hematopoietic changes in exposed providers, staff, or patients in comparison to those with no exposure?
Clinical Bottom Line Exposure to nitrous oxide for periods of 24 hours can result in megaloblastic changes in hematopoiesis and preoperative administration of B12 can prevent these abnormalities. (See Comments on the CAT below)
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 79709Amess/197822 Patients undergoing cardiac bypass surgery, 8 were exposed to N2O for 24 hours, 9 were exposed only during their operation, and 5 were given only oxygen exposure for 24 hours.Randomized Control Trial
Key resultsAll of the patients in group A (24 hour N2O exposure) showed signs of abnormal megaloblastic anemia, while only 3 members of group B (N2O exposure during operation only) showed megaloblastic changes, and no members of group C (no N2O exposure in 24 hours) displayed such changes. These changes were measured with a deoxyuridine suppression test to gauge changes in DNA synthesis. No p value or Confidence Interval was given comparing the differing groups.
#2) 19439331Wronska-Nofer/200984 health care workers who had been working for at least 5 years in an environment with varying levels of N2O, 83 unexposed health care workers.Case Control Study
Key resultsGenotoxicity was assessed using comet test. Concentrations of nitrous oxide, sevoflurane and isoflurane monitored by gas chromatography and mass spectrometry made possible to relate the extent of DNA damage to the level of exposure in both groups. Their results document a positive correlation between the DNA damage and the N2O levels in the ambient air. They conclude that occupational exposure to N2O is associated with increased DNA damage and that the level of exposure plays a critical role in this regard.
#3) 6975588O'Sullivan/1981One group was exposed for under 6 h, the next for between 12 and 24 h and a control group who received no nitrous oxide.Cohort Study
Key resultsBone marrow function in patients receiving nitrous oxide was assessed by the deoxyuridine (dU) suppression test and morphologic changes in the bone marrow were also studied. The control group and the short exposure group showed no abnormality of bone marrow function, while the long exposure group had abnormal dU supression tests and a megaloblastic hematopoiesis. The changes observed could be prevented by the preoperative administration of folinic acid.
Evidence Search Randomized Controlled Trial, Search "Hematopoiesis"[Mesh]Search "Nitrous Oxide"[Mesh]
Comments on
The Evidence
In the randomized controlled trial, and cohort study, the dissimilar groups of patients in each study had over 90% completion rate and had adequate follow up. In all three articles, compliance was adequate and there were no competing interests.
Applicability The patient pool in the study were undergoing either valve replacement or a cardiac bypass surgery with the use of nitrous oxide – oxygen as a part of the general anesthesia during surgery and as a component of recovery.
Specialty/Discipline (General Dentistry) (Oral Surgery)
Keywords Nitrous Oxide, Hematopoiesis
ID# 561
Date of submission: 05/14/2010spacer
E-mail poppm@livemail.uthscsa.edu
Author Matthew Popp
Co-author(s) e-mail
Faculty mentor/Co-author Ernest Valdez, DDS
Faculty mentor/Co-author e-mail VALDEZE@uthscsa.edu
Basic Science Rationale
(Mechanisms that may account for and/or explain the clinical question, i.e. is the answer to the clinical question consistent with basic biological, physical and/or behavioral science principles, laws and research?)
post a rationale
None available
Comments and Evidence-Based Updates on the CAT
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by Christopher Walker and Inna Piskorska (San Antonio, TX) on 08/08/2013
We searched PubMed in August 2013 and found a case report from January 2013 by Trivette et al. (PMID 23569553 ) supporting that, “Nitrous oxide exposure, including use as an inhalant, over 12 hours can lead to bone marrow abnormalities such as megaloblastic hematopoiesis.” The report reviewed blood count values of an admitted 20-year-old pregnant female who abused nitrous after an episode of binge use of nitrous oxide. However, this report’s evidence is not as strong as the other studies cited in this CAT, due to the singularity of the case, and that the patient had a history of multiple types of drug abuse.

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