Nitrous Oxide: old anesthetic, new considerations. Or: to use or not to use?

to use?
Alexander Zlotnik MD, PhD
Professor and Chairman,
Soroka University Medical Center,
Ben

natural philosopher and chemist Joseph Priestley by heating iron filings

but published afterwards.
 Joseph Priestley is usually given priority in the

Airs" (i.e. nitrous oxide) and a novel "breathing apparatus" to

In 1799 Humphrey Davy discovered anesthetic properties of N20

in the treatment of a patient was when dentist Horace Wells

Chloroethane (ethyl chloride) 1922-1950s
Chloroform 1865-1932
Cryoflurane ?
Cyclopropane 1936-1980s
Diethylether 1846-1980s
Enflurane 1966-1980s
Ethylene 1920s-1940s
Fluroxene 1954-1974
Halothane 1956-2000s
Methoxyflurane 1960-1970s
Methoxypropane 1946-1957
Trichlorethylene 1930s-1970s
Vinyl ether 1933- 1960s

Impairement of endothelial function
Induction of oxidative stress
potentially destabilize coronary artery

received N2O were not more likely to develop stroke or

Nitrous oxide exposure does not seem to be associated with increased mortality, stroke, and myocardial infarction: a non-randomized subgroup analysis of the General Anaesthesia compared with Local Anaesthesia for carotid surgery 

BJA: British Journal of Anaesthesia, Volume 109, Issue 3, 1 September 2012, Pages 361–367

underwent non-cardiac surgery

Results:
N2O was not associated with an increased risk

anesthesia for noncardiac surgery
Of them: 16,961 were given N2O (45%)

RESULTS:
Inhalation of N2O was associated with decreased odds of 30-day mortality (odds ratio [OR]: 97.5% confidence interval, 0.67, 0.46-0.97; P = 0.02).
Nitrous patients had an estimated 17% (OR: 0.83, 0.74-0.92) decreased odds of experiencing major in-hospital morbidity/mortality than non-nitrous (P < 0.001)

Conclusion: the results of this study do not support eliminating N2O from anesthetic practice.

more than 2 h
nitrous oxide– based (70% nitrous oxide

ratio 0.98; 95% CI: 0.80 to 1.20; P0.82) .

Results:

2. Nitrous oxide did not increase the risk of stroke
(odds ratio1.01 (95% CI: 0.55 to 1.87;P0.97). Increasing age was the only significant predictor of
stroke

The adjusted odds ratio for myocardial infarction in patients
administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51;P0.04) Increasing age, higher ASA physical status, known coronary artery disease, anemia, and increasing duration of anesthesia were significant predictors of MI.

100% oxygen
Results:
No difference in postoperative SaO2
No difference in sputum production,

26 patients underwent resection of acoustic neurinoma
Surgery lasting at least

Results:
No difference in postoperative SaO2
No differnce in sputum production, cough and hypoxemia

at least 2 h
Nitrous oxide–free (80% oxygen , 20% nitrogen)

of DNA formation
inhibition of methionine production
inhibition of protein and

depression of chemotactic migration by monocytes

h
Randomization 65% intraoperative nitrous oxide (n=208) or nitrogen (n=206),
Lancet. 2005 Sep 24-30;366(9491):1101-7.
Nitrous oxide and risk

Results:
Infection rate was 15% (31/206) in patients given nitrous oxide and 20% (40/202) in those given nitrogen (p=0.205).
Additionally, the ASEPSIS wound healing score, wound collagen deposition, number of patients admitted to critical care unit, time to first food ingestion, duration of hospital stay, and mortality did not differ between treatment groups.

postoperative wound infection rate

therefore intracranial pressure
N2O is a known NMDA antagonist, it is

find any difference in delayed ischemic neurological deficit (20.1 %

side effects of bone marrow suppression, cobalamin deficiency, and folate

Hematologic system

Waldman (1990) measured RBC, Hb, mean RBCvolume, reticulocyte count, platelet count, mean platelet volume, blood leukocyte level, and
leukocyte differential in two groups of patients (a total of
49 patients), but did not show any clinical significance (within 2 weeks follow-up)

synthase
inhibition of methionine production
inhibition of protein and DNA
formation
Potential harm for

Reproductive system

Numerous animal studies have demonstrated a teratogenic effect of N2O

Potential for teratogenic effect

no statistically significant difference in the clinical pregnancy or delivery

While this result may be encouraging, the decision to include N2O as part of the anesthetic plan for each patient needs to be individualized, given the limited scientific evidence to support one technique over another.

Anaesthesia-II
British Journal of Anaesthesia, 2016
international, randomized, assessor-blinded trial
patients aged at

The primary outcome :
death and cardiovascular complications (non-fatal MI, stroke, PE, or cardiac arrest) within 30 days of surgery. 

oxide and in 296 (8%) patients not receiving nitrous oxide

Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61)

Severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001).

The findings support the safety profile of nitrous oxide use in major non-cardiac surgery.
Nitrous oxide did not increase the risk of death and cardiovascular complications or surgical-site infection

Conclusions:

Results:

year followup (medical record review and telephone interview)

Mixture for Anaesthesia (ENIGMA)-II trial.
Br J Anaesth. 2016 Dec;117(6):801-811.
Methods:
Telephone interview at

RESULTS:
12.2% patients reported chronic postsurgical pain at the wound site and 3.8% patients had severe pain and required regular analgesic interventions. 
Nitrous oxide did not affect the rate of chronic postsurgical pain (11.8% in nitrous oxide vs 12.5% no nitrous oxide group).
Moreover, in a planned subgroup analysis, nitrous oxide reduced the risk of chronic postsurgical pain in Asian patients.

206 (3.5%) had disability,
514 (8.8%) had a fatal or

Exposure to nitrous oxide did not increase the risk of:
primary outcome (odds ratio, 1.08; 95% CI, 0.94 to 1.25; P= 0.27),
disability (odds ratio, 1.07; 95% CI, 0.90 to 1.27; P= 0.44),
death (hazard ratio, 1.17; 95% CI, 0.97 to 1.43; P= 0.10),
MI (odds ratio, 0.97; 95% CI, 0.81 to 1.17; P= 0.78),
stroke (odds ratio, 1.08; 95% CI, 0.74 to 1.58; P= 0.70)

Conclusion:
These results support the long-term safety of nitrous oxide administration in noncardiac surgical patients with known or suspected cardiovascular disease.

does not support eliminating N2O from anesthetic practice.