Adverse effects of nitrous oxide 
Brodsky JB, Cohen EN.
Med Toxicol. 1986 Sep-Oct;1(5):362-74 


Although once considered completely devoid of complications, it is now recognised that the misuse or inappropriate use of nitrous oxide (N2O) often results in adverse side effects. 

Hypoxia, particularly the entity 'diffusion hypoxia', can occur with the administration of inadequate amounts of oxygen during or immediately after a N2O anaesthetic. N2O will diffuse into air-containing cavities within the body faster than nitrogen diffuses out. This results in a temporary increase in either the pressure and/or volume of the cavity depending upon the distensibility of its walls. The magnitude of the effect is proportional to the blood supply of the cavity, the concentration of N2O inhaled and the length of time the patient is exposed to N2O. 

Significant morbidity or even death can result from this phenomenon. A property unique to N2O is its ability to oxidise and inactivate the vitamin B12 components of certain enzymes in both animals and man. One such enzyme, methionine synthetase is essential for normal DNA production. Animal and human studies have demonstrated that the haematological, immune, neurological and reproductive systems are each affected. These adverse effects of N2O can occur after both acute (surgical) or long term (occupational) exposure to the gas. 

Because of its effects on the pressure and volume characteristics of air-containing spaces, N2O should not be used for patients with bowel obstruction, pneumothorax, middle ear and sinus disease, and following cerebral air-contrast studies. Many anaesthesiologists feel that use of N2O should be restricted during the first two trimesters of pregnancy because of its effects on DNA production and the experimental and epidemiological evidence that N2O causes undesirable reproductive outcomes. 

Since N2O affects white blood cell production and function, it has been recommended that N2O not be administered to immunosuppressed patients or to patients requiring multiple general anaesthetics. Many anaesthesiologists believe that the potential dangers of N2O are so great that it should no longer be used at all for routine clinical anaesthesia. However, the continued use of N2O remains a controversial topic since, at present, a suitable substitute gas is not available.

Neurologic Problems

Mental confusion is a Nitrous Oxide side effect that is almost never mentioned, yet it happens with more frequency than many would like to admit. This mental confusion occurs as a result of the nitrous oxide depleting the Vitamin B12 stores in the body. While most people have plenty of vitamin b12 stored in their liver, those who are at high risk for vitamin b12 deficiency:

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While hyperhomocysteinemia does not sound like something you should be worried about, it actually occurs to Everyone every single time that they are given the nitrous oxide drug. Hyperhomocysteinemia is a condition where a substance in the blood called 'homocysteine' becomes elevated. While researchers don't agree on the consequences of having high homocysteine levels, some studies have shown higher rates of heart disease and Alzheimer's Disease with higher homocysteine levels.

One study showed that every single patient who participated in a study of Nitrous Oxide Side Effects had higher levels of homocysteine for the entire one month that the study lasted after ONE dose of the nitrous oxide drug. It begs the question of how long these high homocysteine levels persist after being given this drug. Unfortunately no studies on this have been done on this to find out. 

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for most people, a high homocysteine level is not likely to be dangerous nitrous oxide side effects, but for some people, it could be deadly. There is a condition called Methyltetrafolate Reductase Disorder that often occurs in families with high numbers of people with heart disease or Alzheimer's Disease.

There have been people who have died as a result of being given Dental Nitrous Oxide when they had an undiagnosed Methyltetrafolate Reductase Disorder. In these sad cases, asking a few questions about family history of heart disease or a medical need to take Vitamin B12 and Folic Acid supplements could have prevented these deaths for Nitrous Oxide Side Effects.

Hearing and Other Ear Problems

Since nitrous oxide is a gas that is generally given using a mask over the mouth and the nose, it has been shown to raise the pressure inside the middle ear in a large percentage of patients.

"Many children complain of difficulty hearing
in the

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first 24 hours after nitrous oxide anaesthesia."
Negative pressure in the middle ear in children 
after nitrous oxide anaesthesia

While most people will not even notice this, there ARE a small number of people who have had serious problems because of this increase in middle ear pressure. There have been cases of:

  • Typanic Membrane Rupture
  • Sudden Hearing Loss
  • Blood in the ear

and other ear related problems- even in children. Again, while these are NOT common problems, no one is warned about them beforehand. And those who have had any prior surgeries, implants or chronic ear problems should inform their doctor of this ahead of time and potentially use another form of relaxation for the procedure.

Alternatives to Nitrous Oxide

If you have any of the risk factors that may cause you to become severely Vitamin B12 Deficient or you simply wish to not risk the high homocysteine levels that are ALWAYS one of the nitrous oxide side effects, you may want to speak to your doctor about simply getting numbing injections for your dental work. Even many complicated dental procedures can be done with numbing injections and do not always require nitrous oxide.

If, however, you are extremely nervous about your procedure and feel that dental nitrous oxide is the best choice for you, then some researchers recommend simply taking a dose of Vitamin B12 before your procedure in order to avoid any problems. In studies, Vitamin B12 has been safely taken in dosages up to 40 milligrams per day for extended periods of time.

While that is likely to be excessive to prevent nitrous oxide side effects from a single administration, there are no guidelines as to the 'right' amount to take or the amount that will counteract the Vitamin B12 deficiency that will be experienced during your treatment.