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The attack on Nitrous Oxide

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Planktonmd

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There is a study in this month's Anesthesiology implying that avoiding Nitrous Oxide decreases Post op complications although it does not increase the duration of hospital stay.
The problem with this study is the design:
One group got N2O 70% and O2 30 % while the second group got Nitrogen 20% and O2 80 %.
Obviously the second group got a much higher FIO2 which makes it difficult to say if the decrease in complications was due to avoiding Nitrous or giving more Oxygen.
any opinions?

Here is the link: http://www.anesthesiology.org/pt/re...Lz!-362743511!181195628!8091!-1!1187565806882
 

fakin' the funk

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There is an Editorial View at the begnning of the issue that addresses that topic. Here's an excerpt. Sounds like the gist is "It doesn't matter; give high oxygen."
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The authors of the current study intended to examine the value of avoidance of nitrous oxide in reducing postoperative complications. The difficulty in designing such a study is that you cannot change the concentration of nitrous oxide without replacing the gas with another, such as nitrogen, oxygen, or helium. The nitrous oxide avoidance group also received 80% oxygen, previously suggested to be of benefit in preventing surgical site infection and postoperative nausea and vomiting, whereas the 70% nitrous oxide group received only 30% oxygen. Therefore, it is impossible to determine whether the beneficial effects reported resulted from high inspired oxygen, avoiding nitrous oxide, or a combination of the two. Fleischmann et al. found no difference in surgical site infection rate when comparing 70% nitrogen-30% oxygen versus 70% nitrous oxide-30% oxygen as the intraoperative gas mixture, but did not include an 80% oxygen group. These results suggest that avoidance of nitrous oxide may be less important than high inspired oxygen.

In the end, it may not matter to clinicians whether the benefits found in the study by Myles et al. resulted from avoidance of nitrous oxide or administration of high inspired oxygen, because administration of high inspired oxygen by necessity requires avoidance of 70% nitrous oxide. There is certainly plentiful evidence that nitrous oxide use is associated with an increased incidence of postoperative nausea and vomiting. Conversely, a randomized controlled trial in colon surgery patients demonstrated that high inspired oxygen reduced postoperative nausea and vomiting, suggesting that the reduced incidence in the study by Myles et al. could also result from high inspired oxygen. A number of other potential adverse effects of nitrous oxide have been reported in the literature, although their clinical relevance is not clear. There is some evidence for lack of harm from nitrous oxide (the study by Fleischmann et al.), but there is little evidence for benefit. Myles et al. add a compelling argument for eliminating nitrous oxide use in patients undergoing major surgery by showing potential harm from nitrous oxide (whether directly or through reducing the capacity to provide a high inspired oxygen concentration).
 

InductionAgent

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It would be nice to know whether a 40%O2 60%nitrogen mix showed equal benefit over 70%N2O/ 30%O2 as compared to 80%O2 20%nitrogen, but like the editorial states, it wouldn't change management much. If I'm concerned about the high O2 content in instances such as potential atelectasis or higher risk of airway fire, I'm going to avoid nitrous anyway.

There's still times when I'm inclined to use N2O, such as in a simple I&D. I don't want to paralyze the patient, yet post-induction (& pre-incision) his BP won't tolerate an adequate level of volatile agent to keep him from moving once the procedure starts. It's a short case, so I don't want to over-narcotize him. The risks of serious N2O toxicity are reduced by the fact that it's a short case. I give him PONV prophylaxis.
 

Mman

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It would be nice to know whether a 40%O2 60%nitrogen mix showed equal benefit over 70%N2O/ 30%O2 as compared to 80%O2 20%nitrogen, but like the editorial states, it wouldn't change management much. If I'm concerned about the high O2 content in instances such as potential atelectasis or higher risk of airway fire, I'm going to avoid nitrous anyway.

There's still times when I'm inclined to use N2O, such as in a simple I&D. I don't want to paralyze the patient, yet post-induction (& pre-incision) his BP won't tolerate an adequate level of volatile agent to keep him from moving once the procedure starts. It's a short case, so I don't want to over-narcotize him. The risks of serious N2O toxicity are reduced by the fact that it's a short case. I give him PONV prophylaxis.


I think most studies showing detrimental effects of N20 (at least a biochemical level) look at > 6 hours of exposure to 60% or more and I think they were all > 2 hours.

I try hard to avoid long exposures to nitrous because of the effects on B12 and bone marrow suppression as well as PONV. However, I don't really bat an eye at 20-30 minutes at the end of a long case or during a quick case. I just can't imagine that such a short exposure would make that much of a difference.
 

Planktonmd

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There is an Editorial View at the begnning of the issue that addresses that topic. Here's an excerpt. Sounds like the gist is "It doesn't matter; give high oxygen."
---------------------------
The authors of the current study intended to examine the value of avoidance of nitrous oxide in reducing postoperative complications. The difficulty in designing such a study is that you cannot change the concentration of nitrous oxide without replacing the gas with another, such as nitrogen, oxygen, or helium. The nitrous oxide avoidance group also received 80% oxygen, previously suggested to be of benefit in preventing surgical site infection and postoperative nausea and vomiting, whereas the 70% nitrous oxide group received only 30% oxygen. Therefore, it is impossible to determine whether the beneficial effects reported resulted from high inspired oxygen, avoiding nitrous oxide, or a combination of the two. Fleischmann et al. found no difference in surgical site infection rate when comparing 70% nitrogen-30% oxygen versus 70% nitrous oxide-30% oxygen as the intraoperative gas mixture, but did not include an 80% oxygen group. These results suggest that avoidance of nitrous oxide may be less important than high inspired oxygen.

In the end, it may not matter to clinicians whether the benefits found in the study by Myles et al. resulted from avoidance of nitrous oxide or administration of high inspired oxygen, because administration of high inspired oxygen by necessity requires avoidance of 70% nitrous oxide. There is certainly plentiful evidence that nitrous oxide use is associated with an increased incidence of postoperative nausea and vomiting. Conversely, a randomized controlled trial in colon surgery patients demonstrated that high inspired oxygen reduced postoperative nausea and vomiting, suggesting that the reduced incidence in the study by Myles et al. could also result from high inspired oxygen. A number of other potential adverse effects of nitrous oxide have been reported in the literature, although their clinical relevance is not clear. There is some evidence for lack of harm from nitrous oxide (the study by Fleischmann et al.), but there is little evidence for benefit. Myles et al. add a compelling argument for eliminating nitrous oxide use in patients undergoing major surgery by showing potential harm from nitrous oxide (whether directly or through reducing the capacity to provide a high inspired oxygen concentration).

I think this is a weak study and was unable to neutralize other variables namely high FIO2.
All it does is show that If you give 80% Oxygen + 20% Nitrogen You get less complications than if you give 70% Nitrous and 30 % Oxygen.
So is it the high N2O, The low O2 or the higher Nitrogen causing the complications??
No one knows!
The problem with this kind of research is that people tend to forget the details of the study and only remember the faulty conclusion " Nitrous is bad"!
 

Mman

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Yes, it's a study with serious flaws. However, it's pretty well known that nitrous does have deleterious effects for the patient. We didn't need this study to figure it out.
 

fakin' the funk

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I think this is a weak study and was unable to neutralize other variables namely high FIO2.
All it does is show that If you give 80% Oxygen + 20% Nitrogen You get less complications than if you give 70% Nitrous and 30 % Oxygen.
So is it the high N2O, The low O2 or the higher Nitrogen causing the complications??
No one knows!

I believe the authors address this. Tricky, maybe, but it's a good point.
-------------------
The decreased risk of complications in the nitrous oxide-free group of our study could be explained by avoidance of nitrous oxide and/or administration of high inspired oxygen concentrations. We believe that, in a practical sense, this distinction is immaterial; regardless of whether the risk reduction is a result of nitrous oxide toxicity or direct benefits of supplemental oxygen, anesthesiologists should question the inclusion of nitrous oxide as part of their anesthetic regimen. We chose not to include a third group receiving 30% oxygen in 70% nitrogen, because this combination is not often used clinically and high inspired oxygen concentrations have been reported to be beneficial.

The problem with this kind of research is that people tend to forget the details of the study and only remember the faulty conclusion " Nitrous is bad"!
Did they say that?
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In conclusion, avoidance of nitrous oxide combined with supplementary oxygen in the gas mixture for anesthesia decreases the incidence of complications after major surgery but does not significantly affect duration of hospital stay. Whether the reduction in complications is due entirely to the known toxic effects of nitrous oxide, a possible beneficial effect of supplementary oxygen, or both, requires further study. In either case, the routine use of nitrous oxide in adult patients undergoing major surgery should be questioned.
 
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