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. 2011 Oct;113(4):843-8.
doi: 10.1213/ANE.0b013e31822402f5. Epub 2011 Jun 16.

Nitrous oxide anesthesia and plasma homocysteine in adolescents

Peter Nagele  1 , Danielle Tallchief, Jane Blood, Anshuman Sharma, Evan D Kharasch
Affiliations

Nitrous oxide anesthesia and plasma homocysteine in adolescents

Peter Nagele et al. Anesth Analg. 2011 Oct.

Abstract

Background: Nitrous oxide inactivates vitamin B(12), inhibits methionine synthase, and consequently increases plasma total homocysteine (tHcy). Prolonged exposure to nitrous oxide can lead to neuropathy, spinal cord degeneration, and even death in children. We tested the hypothesis that nitrous oxide anesthesia causes a significant increase in plasma tHcy in children.

Methods: Twenty-seven children (aged 10-18 years) undergoing elective major spine surgery were enrolled, and serial plasma samples from 0 to 96 hours after induction were obtained. The anesthetic regimen, including the use of nitrous oxide, was at the discretion of the anesthesiologist. Plasma tHcy was measured using standard enzymatic assays.

Results: The median baseline plasma tHcy concentration was 5.1 μmol/L (3.9-8.0 μmol/L, interquartile range) and increased in all patients exposed to nitrous oxide (n = 26) by an average of +9.4 μmol/L (geometric mean; 95% confidence interval, 7.1-12.5 μmol/L) or +228% (mean; 95% confidence interval, 178%-279%). Plasma tHcy peaked between 6 and 8 hours after induction of anesthesia. One patient who did not receive nitrous oxide had no increase in plasma tHcy. Several patients experienced a severalfold increase in plasma tHcy (maximum +567%). The increase in plasma tHcy was strongly correlated with the duration and average concentration of nitrous oxide anesthesia (r = 0.80; P < 0.001).

Conclusions: Pediatric patients undergoing nitrous oxide anesthesia develop significantly increased plasma tHcy concentrations. The magnitude of this effect seems to be greater compared with adults; however, the clinical relevance is unknown.

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Conflict of interest statement

Disclosures

Name: Peter Nagele, MD, MSc

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Peter Nagele has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Conflicts of Interest: Peter Nagele received research funding from Roche Diagnostics.

Name: Danielle Tallchief, BS, RN

Contribution: This author helped conduct the study.

Attestation: Danielle Tallchief has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: Danielle Tallchief reported no conflicts of interest.

Name: Jane Blood, BS, RN

Contribution: This author helped conduct the study.

Attestation: Jane Blood has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: Jane Blood reported no conflicts of interest.

Name: Anshuman Sharma, MD

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Anshuman Sharma has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Conflicts of Interest: Anshuman Sharma reported no conflicts of interest

Name: Evan D. Kharasch, MD, PhD

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Conflicts: Evan D. Kharasch reported no conflicts of interest.

Attestation: Evan D. Kharasch has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Figures

Figure 1
Figure 1
Response of plasma total homocysteine concentrations among individual study patients (n=27). tHcy = total homocysteine. Plasma tHcy concentrations exceeding 10 μmol/L are commonly considered abnormal. Red dotted line: patients who received nitrous oxide only during induction and emergence; red full line: no exposure to nitrous oxide.
Figure 2
Figure 2
Box plot representation of pooled average response of plasma total homocysteine at different timepoints. Boxes represent the interquartile range, the line the median and the whiskers the 5 – 95 percentile. tHcy = total homocysteine. Asterisks refer to statistical significance (P value :** 0.001 – 0.01; *** < 0.001)
Figure 3
Figure 3
Linear correlation of the increase in plasma total homocysteine and the cumulative nitrous oxide dose (N2O*min). tHcy = total homocysteine
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References

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