Nitrous Oxide Induction Induces Amnesia in Pediatric Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nitrous Oxide Induction Induces Amnesia in Pediatric Patients (NCT02050152), a randomized na study. The primary outcome is Explicit Memory.

2. Clinical Question

The study addressed a dose-response question: whether memory differed across the 0%, 33%, and 66% concentrations before induction of anesthesia. The registered intervention description places the mask exposure alongside pictures and jokes; the primary endpoint description focuses on recall of an odor. These are registry descriptions of the study procedures and outcome, not evidence about the mechanism of any observed difference.

The posted primary counts were 7 participants in the 0% group, 1 in the 33% group, and 2 in the 66% group. The comparisons are each against the 0% group. The registry record does not report a direct comparison between the 33% and 66% groups, nor does it report a formal test of a dose-response trend. Therefore, the posted comparisons address each concentration relative to the control group, rather than establishing whether the two active concentrations differ from one another.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group study and lists the status as completed. Enrollment is recorded as 90. The registry identifies the sponsor as State University of New York at Buffalo. The study start is recorded as 2013-05, and primary completion as 2013-10. The phase is listed as NA.

Three groups received nitrous oxide at 0%, 33%, or 66%. Each exposure lasted 2 minutes while participants were shown pictures and told jokes. The registry’s brief summary describes the study as prospective, double-blinded, and placebo controlled, with the aim of investigating the amnestic effects of two concentrations before induction of anesthesia. The registered design also includes the 0% group as the comparator.

The posted primary outcome counts are 7 of 30 for 0%, 1 of 29 for 33%, and 2 of 31 for 66%. Those group-specific denominators are the ones used in the posted comparisons. The record does not report details of the randomization sequence, concealment procedures, or which study personnel were masked. It also does not report the ages or other baseline characteristics of participants, or whether all randomized participants contributed to each outcome.

The primary outcome was assessed after full recovery from anesthesia and before discharge; the timeframe says this was generally by 2 hours after termination of anesthesia. The registry also lists three secondary outcomes assessed at different timeframes. The specific original sample-size justification, trial protocol, and prespecified statistical analysis plan are not reported in the registry record. No analysis records are listed, so the posted comparison calculations should not be mistaken for a detailed report of the trial’s original analysis procedures.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Children 6-12 years, ASA physical status 1 or 2

6. Primary Endpoint

The registry lists the primary outcome as Explicit Memory, measured over After full recovery from anesthesia (generally by 2 hours after termination of anesthesia), but before discharge from hospital all variables will be assessed.

The primary endpoint is explicit memory, measured as a count of participants. During recovery, after a child had fully recovered from anesthesia and before discharge, a blinded observer was to ask whether the child smelled an odor while breathing through the mask. The timeframe notes that assessment was generally by 2 hours after anesthesia termination. The registry does not describe a scored memory scale or report additional criteria for classifying a response.

This is a binary outcome at the participant level: each participant is counted according to whether the specified memory was recorded. For the primary endpoint, the posted counts are 7 of 30 in the 0% group, 1 of 29 in the 33% group, and 2 of 31 in the 66% group. The comparison statistic is a risk difference, which expresses the difference between the proportions with the endpoint in two groups. Negative estimates indicate a lower observed proportion in the nitrous oxide group than in the 0% group.

As a general measurement point, a memory task offers an observable way to assess recall of a study experience. Its interpretation depends on the exact question, timing, and outcome definition. The registry record identifies the question about an odor but does not report details such as how unclear responses were handled or whether any validation procedure was used. The endpoint therefore describes recall as recorded under this task; it does not, by itself, measure every aspect of memory or establish why a participant did or did not recall the experience.

7. Results Posted in the Registry

• Nitrous Oxide 33%: 3.4% (1/29) versus 23.3% (7/30) on control; risk difference -19.9 percentage points (95% CI -36.4 to -3.4), risk ratio 0.15 (0.02–1.13); unadjusted two-proportion z-test p = 0.026.
• Nitrous Oxide 66%: 6.5% (2/31) versus 23.3% (7/30) on control; risk difference -16.9 percentage points (95% CI -34.3 to 0.5), risk ratio 0.28 (0.06–1.23); unadjusted two-proportion z-test p = 0.063.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Explicit Memory

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • 33% N2O: 72.4% (21/29) versus 70.0% (21/30) on control; risk difference 2.4 percentage points (95% CI -20.7 to 25.5), risk ratio 1.03 (0.75–1.43); unadjusted two-proportion z-test p = 0.838.
  • 60% N2O: 45.2% (14/31) versus 70.0% (21/30) on control; risk difference -24.8 percentage points (95% CI -48.8 to -0.8), risk ratio 0.65 (0.41–1.02); unadjusted two-proportion z-test p = 0.050.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 33% N2O and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for 60% N2O than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Explicit Memory if the Child Remembered Being Shown an Animal in a Photo

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • 33% N2O: 72.4% (21/29) versus 90.0% (27/30) on control; risk difference -17.6 percentage points (95% CI -37.1 to 1.9), risk ratio 0.80 (0.62–1.04); unadjusted two-proportion z-test p = 0.083.
  • 60% N2O: 45.2% (14/31) versus 90.0% (27/30) on control; risk difference -44.8 percentage points (95% CI -65.4 to -24.3), risk ratio 0.50 (0.33–0.75); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 33% N2O and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for 60% N2O than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Explicit Memory of the Name of a Food That Begins With the Letter "b"

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Explicit Recall a Food That Started With a "b" With 33% N2O: 51.7% (15/29) versus 33.3% (10/30) on control; risk difference 18.4 percentage points (95% CI -6.4 to 43.2), risk ratio 1.55 (0.84–2.87); unadjusted two-proportion z-test p = 0.153.
  • Explicit Recall a Food That Started With a "b" With 66% N2O: 22.6% (7/31) versus 33.3% (10/30) on control; risk difference -10.8 percentage points (95% CI -33.1 to 11.6), risk ratio 0.68 (0.30–1.55); unadjusted two-proportion z-test p = 0.349.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Explicit Recall a Food That Started With a "b" With 33% N2O and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Explicit Recall a Food That Started With a "b" With 66% N2O and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary memory question to other recall tasks: explicit memory after recovery, recall of seeing an animal in a photo, and recall of a food name beginning with the letter b. Across these outcomes, the posted comparisons do not form one uniform pattern. The estimates vary in direction and uncertainty across tasks and concentrations. That variation makes it important to interpret each outcome in its own terms rather than treating all memory measures as interchangeable.

Some secondary findings point in a direction similar to the primary comparison, while others do not. The animal-photo outcome has lower posted counts in the nitrous oxide groups than in the 0% group, with a more pronounced estimated difference for the 60% label. For the food-name task, the 33% group has a higher posted count than the comparator, while the 66% group has a lower count. These are descriptive patterns across different tasks; they do not establish a coherent dose-response relationship.

The secondary outcomes are related to the primary result because they concern memory after anesthesia, but they do not measure exactly the same recall content or necessarily use identical timeframes. The primary endpoint asks about an odor, while the secondary outcomes include a general explicit-memory measure and task-specific recall. Their estimates therefore provide context rather than direct replication of the primary measure.

The reported secondary comparisons are unadjusted, and the registry lists multiple outcomes and pairwise comparisons. As a general statistical concern, testing multiple outcomes increases the chance that some results may appear notable by chance. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting the secondary endpoints. Accordingly, these comparisons carry less inferential weight than a clearly prioritized primary analysis, and the secondary pattern should be considered exploratory. The record also lists no reported analyses, limiting insight into the intended handling of these outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Explicit Memory
• Explicit Memory if the Child Remembered Being Shown an Animal in a Photo
• Explicit Memory of the Name of a Food That Begins With the Letter "b"

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference express?

The primary outcome is binary: a participant either had the specified memory recorded or did not. A risk difference compares the proportions with that outcome in two groups by subtracting the comparator-group proportion from the other group’s proportion. A negative value means the observed proportion was lower in the nitrous oxide group. For the primary comparisons, the risk differences are -0.199 for 33% versus 0%, and -0.169 for 66% versus 0%.

Risk differences are expressed on the absolute scale. They describe the difference in observed outcome frequency, rather than a relative change. The registry also contains relative measures, but a risk difference is the stated comparison metric for the posted primary results. As a general statistical point, absolute measures can be useful for understanding how far apart two observed group proportions are, while relative measures answer a different question about proportional association.

What does the confidence interval add?

A confidence interval gives a range of estimates compatible with the data under the calculation method and its assumptions. It communicates uncertainty around the point estimate, rather than identifying a range in which the true value is guaranteed to lie. For the 33% primary comparison, the interval runs from -0.364 to -0.034. For the 66% comparison, it runs from -0.343 to 0.005. The latter interval includes zero, a value representing no risk difference. Interval width also matters: wider intervals indicate less precision than narrower ones under the same scale and method.

As a general interpretation, an interval that includes zero does not establish that the groups are identical. It indicates that the data and calculation do not exclude zero at the interval’s stated confidence level. Conversely, an interval that excludes zero does not establish clinical importance, eliminate bias, or prove a causal mechanism. The size and uncertainty of the estimate both need consideration.

How should the p-values be read?

The unadjusted p-values for the primary comparisons are 0.026 for 33% versus 0%, and 0.063 for 66% versus 0%. A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be, under that hypothesis and the statistical assumptions. It is not the probability that the null hypothesis is true, nor is it a measure of the size or importance of an effect.

These values are unadjusted. The registry record does not report an adjustment for testing multiple outcomes or comparisons, and no reported analysis records are listed. When multiple comparisons are made, the chance of finding at least one apparently unusual result can increase. As a general principle, interpretation should account for the number and priority of comparisons, rather than treating each p-value as if it were the only test. The original trial plan for addressing multiplicity is not reported in the registry record.

What does randomized, double-blind, parallel-group mean?

In general, random assignment is intended to reduce systematic differences between groups at the point of assignment, masking is intended to limit the influence of knowledge about assigned treatment, and a parallel-group design assigns participants to one group for comparison. The registry labels this study randomized, double-blind, and parallel. It does not report the sequence-generation or concealment details, or specify which people were blinded. These design labels therefore provide a broad description, not enough information to assess every protection against bias.

The study enrolled groups with posted outcome denominators of 30, 29, and 31. The registry does not report whether those denominators represent everyone randomized, whether any participants lacked outcome data, or the analysis population used in the original trial. It also does not report an intention-to-treat or per-protocol analysis. Those missing details limit assessment of how closely the posted outcome counts reflect the randomized groups.

What analyses are documented?

The registry lists no reported analyses. The comparisons presented in the statistical results are unadjusted recalculations from the posted outcome counts. This means they describe simple group comparisons based on the available summary statistics; they are not evidence that the trial’s original investigators used the same calculation or testing procedure. The registry does not report the original statistical plan, covariate adjustments, interim analyses, or sample-size justification. None should be inferred from the recalculated estimates.

As a general matter, an adjusted analysis can account for specified factors, whereas an unadjusted comparison does not make such an adjustment. Whether adjustment is appropriate depends on the design and analysis plan. Because baseline information and the original plan are not reported, it is not possible to assess whether an adjusted analysis was planned or whether it would alter the estimates.

The outcome is a count of participants with an event, not a continuous measurement. The primary comparison thus concerns proportions and risk differences. As a general statistical concept, methods for binary outcomes rely on assumptions about the sampling and comparison procedure; the registry record does not identify the precise method used for the sponsor’s original analysis. The posted results are best interpreted as count-based descriptive comparisons with the stated uncertainty estimates and unadjusted p-values.

11. Confidence Intervals and Precision

The primary risk-difference estimate for 33% versus 0% is -0.199, with a 95% confidence interval from -0.364 to -0.034. The estimate for 66% versus 0% is -0.169, with a 95% confidence interval from -0.343 to 0.005. Both intervals span a substantial range of possible risk differences relative to their point estimates, so the point estimates should not be read as exact descriptions of the underlying group differences.

The interval for the 33% comparison lies below zero, while the interval for 66% extends across zero. The 66% interval is compatible with values ranging from a negative difference to a small positive difference under the reported calculation. This uncertainty is relevant even though the observed count in that group was lower than the comparator count. The 33% interval also has meaningful width: excluding zero does not mean the magnitude is known precisely.

As a general statistical explanation, precision depends in part on the amount of information in the data and on how frequently the event occurs. When counts are limited, estimates can be sensitive to individual observations, and intervals may be wide. Here, the primary outcome counts are 7, 1, and 2 in groups with denominators of 30, 29, and 31, respectively. These small counts make careful attention to uncertainty especially important.

A confidence interval is not a guarantee that the true difference lies within its endpoints, and it does not address every source of uncertainty. It reflects uncertainty under the statistical method, but not necessarily issues such as outcome measurement, missing data, or departures from the recorded design. The registry record does not report enough analysis detail to assess those issues fully. The estimates therefore provide a useful but limited account of precision for the posted comparisons.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size planning figures are illustrations based on the observed effect, not the trial’s original design assumptions. The registry’s original sample-size justification is not reported. For these binary outcomes, the planning figures are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect.

The 80% power column gives the planned number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect is the true one. The 90% power column gives the corresponding number per arm for a design with a 90% chance. These are planning targets, not descriptions of the power of the completed trial.

Rows labeled as planning for 100%, 75%, or 50% of the observed effect ask how many participants per arm would be needed to target the full observed effect or a smaller fraction of it. A smaller effect is harder to distinguish from random variation, so the planning figures rise as the assumed effect becomes smaller. For example, the primary 33% comparison lists 45 participants per arm for 80% power when planning for 100% of the observed effect, and 237 per arm when planning for 50% of the observed effect. The corresponding 90% figures are 60 and 317.

These calculations use the observed effect as their starting point, which can make them unstable as planning evidence when the observed estimate is imprecise. They are not an independent estimate of the effect that a future study should expect. This is not observed power: the figures describe hypothetical planning under stated assumptions, not a retrospective measure of what the completed study achieved.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.233; treatment proportion p₁ = 0.034; average p̄ = 0.134.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4816 = 0.9439.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4606 = 0.3877.
4. n = (0.9439 + 0.3877)² / (-0.1989)² = 44.8, rounded up to 45 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.233333333333333                          # control proportion
p1 <- 0.0344827586206897                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2050152)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 45 (80% power), 60 (90% power)
 75% of observed effect: n per arm = 94 (80% power), 125 (90% power)
 50% of observed effect: n per arm = 237 (80% power), 317 (90% power)
power.prop.test: 44.8 
Simulated power at n = 45 per arm: 0.861 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes, with comparisons of each nitrous oxide group against the 0% group. This creates multiple opportunities for a result to appear unusual by chance. As a general statistical principle, the more hypotheses tested, the more important it is to specify in advance which outcome is primary and how other tests will be interpreted. The record does identify a primary endpoint, but it does not report a multiplicity adjustment, testing hierarchy, or other procedure for controlling error across comparisons.

The unadjusted p-values should therefore be understood as applying to their individual comparisons, not as evidence that the chance of a false-positive finding across all outcomes has been controlled. The original analysis plan is not reported. The posted comparisons are recalculations from summary statistics, and the registry lists no reported analyses. It is not possible to determine from the registry whether the trial investigators used a different approach or how they addressed multiple testing.

Missing-data handling is also not reported. The record gives group-specific denominators for outcomes, but does not say whether these are all randomized participants, whether any outcome assessments were unavailable, or how missing responses were treated. It does not report whether the analysis followed an intention-to-treat, per-protocol, or other population definition. These omissions matter because outcome availability and analysis-population choices can affect a comparison.

The registry does not report interim analyses, stopping rules, or a prespecified statistical analysis plan. These details should not be assumed from the completed status or the posted p-values. Overall, the available record supports interpretation of the posted counts and unadjusted estimates, but it does not establish how multiplicity, missing data, or analysis populations were addressed in the original trial.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry’s adverse-event figures report zero serious adverse events and zero other adverse events in each group. The group-specific numbers at risk are 30 for the 0% group, 29 for the group labeled 30%, and 31 for the group labeled 60%. Deaths are reported as zero in each group. These are the posted counts; they should not be interpreted as evidence that no adverse events could occur.

The adverse-event group labels list 30% and 60%, whereas the intervention and primary outcome records identify the active concentrations as 33% and 66%. The registry record does not explain this label difference. It is therefore appropriate to report the adverse-event labels as recorded and avoid assuming the reason for the discrepancy.

As a general statistical point, observing no events in a study does not establish that the underlying risk is zero. The registry does not provide further detail about event definitions, duration of safety follow-up, or methods for collecting adverse events. These figures summarize only the safety counts posted in the record and do not support broader conclusions about safety beyond those observations.

16. What the Result Does, and Does Not, Mean

The posted primary counts show fewer recorded odor-memory events in both nitrous oxide groups than in the 0% group. The unadjusted risk-difference estimate for 33% is -0.199, with a confidence interval that excludes zero; the estimate for 66% is -0.169, with a confidence interval that includes zero. These results describe the observed groups and the uncertainty around their comparisons under the reported calculations.

They do not show whether 33% and 66% differ from each other, because that direct comparison is not reported. Nor do they establish a dose-response trend. A pattern across separate comparisons against a shared control is not equivalent to a formal test of trend. The endpoint is also specific: it records a child’s response to a question about an odor after anesthesia. It cannot stand in for every form of memory or establish the reason that a child did or did not recall the experience.

Statistical evidence is not the same as clinical importance. A p-value does not measure the magnitude or practical meaning of a difference, and a confidence interval does not account for every possible source of bias. The registry record does not report detailed baseline characteristics, missing-data handling, the original analysis plan, or the exact analysis population. Those omissions limit assessment of how robustly the observed estimates represent the randomized comparison.

The secondary outcomes offer additional, but not uniform, information about memory tasks. Because those comparisons are unadjusted and multiple outcomes are listed, they should not be treated as independent confirmation of the primary result. The safety record lists no adverse events, but the available counts cannot establish absence of risk.

Overall, the record documents a randomized comparison and a lower observed count for the primary memory task in both nitrous oxide groups than in the 0% group. It does not by itself establish a treatment effect beyond this measured outcome, demonstrate a particular mechanism, or settle questions that the registry does not report.

17. Why This Trial Matters Statistically

This trial is statistically instructive because its primary outcome is binary and the event counts are small. With only a few participants recorded as having the specified memory in each group, point estimates and intervals need to be read together. A single outcome observation can matter more to a proportion when the underlying count is limited, and that makes uncertainty particularly salient.

The two primary comparisons illustrate why an observed direction alone is not enough. Both risk-difference estimates are negative, yet their confidence intervals differ in whether they include zero. This is a useful distinction between the direction of the point estimate and the precision of the evidence. It also illustrates why a p-value should not be treated as a summary of effect size or certainty.

The record also highlights the importance of outcome hierarchy and multiplicity. It lists several memory measures and comparisons, but does not report a multiplicity plan or analysis protocol. A clearly specified primary outcome helps orient interpretation, while secondary measures can add context only when their distinct definitions and inferential status are kept in view.

Finally, the registry combines an explicit randomized, double-blind, parallel-group design description with limited detail about implementation and analysis. The trial labels help frame the comparison, but missing information about allocation procedures, analysis populations, and missing data constrains a fuller assessment. For biostatisticians and clinical researchers, the central lesson is to separate what the posted counts and estimates establish from what cannot be recovered from the registry record.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to this registry record. The primary endpoint is described as a question about smelling an odor, but the record does not explain response coding, the handling of uncertain answers, or whether the memory task was validated. The assessment is described as occurring after full recovery and before discharge, generally by 2 hours after anesthesia termination; variation in actual assessment timing is not detailed.

The intervention descriptions specify the concentration and a 2-minute mask exposure alongside pictures and jokes, but the record does not provide further procedural detail. It does not report participant ages, baseline characteristics, or details of anesthesia. These omissions limit assessment of the population and context to which the observed counts apply.

Although the study is labeled randomized and double-blind, allocation-sequence generation, concealment, and the identities of masked personnel are not reported. The record does not describe missing outcomes or define the analysis population. It also does not report the original analysis plan, multiplicity handling, or sample-size justification. The posted comparison statistics are unadjusted recalculations, and no reported analyses are listed.

The secondary outcomes use different recall tasks and timeframes, and the record does not explain whether all were prespecified or how they were prioritized. The adverse-event labels use 30% and 60%, unlike the 33% and 66% intervention labels, with no explanation in the registry. These details warrant caution when comparing outcomes across sections of the record. The limitations do not invalidate the posted counts, but they restrict how broadly and definitively those counts can be interpreted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Nitrous Oxide Induction Induces Amnesia in Pediatric Patients — NCT02050152.
• Registry record last updated 2026-06-30; status last verified 2026-05.
• Results first posted 2026-06-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

The registry record describes a completed, randomized, double-blind, parallel-group study of nitrous oxide concentrations before induction of anesthesia in children. It lists enrollment of 90 and interventions of 0%, 33%, and 66%, each administered for 2 minutes while pictures were shown and jokes were told.

The primary endpoint was explicit memory of an odor, assessed after recovery and before discharge. Posted counts were 7 of 30 for 0%, 1 of 29 for 33%, and 2 of 31 for 66%. The unadjusted risk differences versus 0% were -0.199 and -0.169, respectively; the confidence interval for the first excludes zero, while the second includes zero.

Three secondary memory outcomes are also posted. Registry analysis records, the original statistical plan, missing-data procedures, and sample-size justification are not reported. Adverse-event counts are zero in each group, with a difference in active-dose labels between the safety and intervention records.