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doi: 10.1097/ALN.0000000000000092

Vitamins in Nitrous Oxide Randomized Trial: A Few Concerns

Saikia, Priyam M.D.

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To the Editor:

WHETHER intraoperative use of nitrous oxide increases the risk of adverse perioperative cardiac event has been the topic of discussion in recent time.1 I congratulate Nagele et al.2 for addressing this very pertinent and controversial topic. However, I believe that apart from the limitations described in the discussion, there are two aspects of this study that should be addressed.
First, is this an intention-to-treat analysis in its strictest form? According to figure 1 in their article, among 557 patients randomized, only 500 patients were included in the intention-to-treat analysis, thus excluding 10.23% patients from final analysis.2 The intention-to-treat principle requires all the randomized participants to be included and analyzed according to their allocated group even though they may not have received the intended intervention.3 Moreover, in contrary to the calculation by the authors and their doubt whether a lager sample size would have influenced their study outcome, Myles1, in his editorial, has expressed uncertainty regarding their sample size.2 As the result of this study has wide impact on perioperative care, a response by the authors regarding the reasons for this exclusion and its influence on the final statistical outcome will be of much help to analyze the conclusion.
Second, although the authors concluded that high-sensitivity cardiac troponin T assay is the most sensitive method to detect perioperative myocardial injury and infarction, is it justifiable to use it to detect perioperative myocardial infarction?2 Nagele et al.2 has reported that 80% patients (with similar distribution in both the randomized groups) had measurable increase in high-sensitivity cardiac troponin T level in the postoperative period with overall incidence of myocardial infarction 4.4%. Because many nonthrombotic factors frequently encountered in perioperative period are associated with increased cardiac troponin level, considering this high percentage of patients with increased high-sensitivity cardiac troponin T, its use in perioperative period runs the risk of inflated rate of diagnosis of myocardial infarction unless analytical issues with it is given due consideration.4 Instead, its value may be more in ruling out myocardial ischemia.
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Competing Interests

The author declares no competing interests.
Priyam Saikia, M.D.,
Gauhati Medical College and Hospital, Guwahati, Assam.
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1. Myles PS. Nitrous oxide: Deep in the zone of uncertainty. ANESTHESIOLOGY. 2013;119:1–3

2. Nagele P, Brown F, Francis A, Scott MG, Gage BF, Miller JPVINO Study Team. . Influence of nitrous oxide anesthesia, B-vitamins, and MTHFR gene polymorphisms on perioperative cardiac events: The vitamins in nitrous oxide (VINO) randomized trial. ANESTHESIOLOGY. 2013;119:19–28

3. Sainani KL. Making sense of intention-to-treat. PM R. 2010;2:209–13

4. Daubert MA, Jeremias A. The utility of troponin measurement to detect myocardial infarction: Review of the current findings. Vasc Health Risk Manag. 2010;6:691–9

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