Cerebral Blood Perfusion Changes After General Anesthesia for Craniotomy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cerebral Blood Perfusion Changes After General Anesthesia for Craniotomy (NCT01642147), a randomized na study. The primary outcome is Mean Blood Flow Velocity in Middle Cerebral Artery.

2. Clinical Question

3. Trial Design

The registry record describes a completed, randomized, parallel-group study sponsored by Huashan Hospital. It lists an enrollment of 60 and records the study period as starting in 2012-11, with primary completion in 2013-01. The record gives no further description of the study timeline, follow-up, or recruitment process.

The groups are patients undergoing craniotomy for selective supratentorial tumor removal and patients undergoing selective abdominal surgery. The record labels allocation as randomized and masking as none. It does not describe the randomization sequence, allocation concealment, or the mechanism by which participants were assigned to the surgical groups. Because the groups are defined by different surgeries, the label alone does not clarify whether surgery itself was assigned or whether participants were randomly selected within the groups.

The listed procedures include transcranial Doppler, radial artery catheterization, and surgery under general anesthesia in both groups. Jugular venous bulb catheterization is listed for the craniotomy group. The arm descriptions are incomplete in the registry record, so they do not provide a full account of measurement schedules or all study procedures.

The primary measure is baseline mean blood flow velocity in the middle cerebral artery, assessed before general anesthesia. The registry lists 12 outcome measures and 6 analyses, but the details of outcomes beyond the primary measure described in the posted results are not reported in the registry record. The trial’s original design assumptions and the detailed statistical analysis plan are also not reported in the registry record. Its stated sample-estimation description refers to a cohort-study equation using hyperemia frequency from literature and a pre-study, without further information about the equation or assumptions.

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.

Before assignment: Transcranial doppler (TCD) and head CT-scan was used to exclude patients with intracranial hypertension,cerebrovascular diseases, or metastatic brain tumor.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The number of participants for analysis was determined by sample estimation equation of cohort study. In the equation, the hyperemia frequency from literature and pre-study was used.

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.

6. Primary Endpoint

The registry lists the primary outcome as Mean Blood Flow Velocity in Middle Cerebral Artery, measured over before general anesthesia.

The primary endpoint is mean blood flow velocity in the middle cerebral artery, measured in cm/s before general anesthesia. It is a continuous measurement, and the registry describes the endpoint as the baseline mean velocity. The posted group summaries give a mean and standard deviation for each surgical group: 63.7 cm/s with a standard deviation of 6.7 in the craniotomy group, and 61.8 cm/s with a standard deviation of 8.1 in the abdominal surgery group. Each group has 30 participants in the posted endpoint summary.

Transcranial Doppler is listed as a study measure. In general, a continuous blood-flow velocity measure can describe the distribution of baseline values and support a comparison of group averages. A baseline measure can also provide context for interpreting measurements taken later, if those are collected and reported. However, this registry endpoint is explicitly before general anesthesia. It therefore does not itself measure a change during emergence or establish whether such a change occurred.

The study summary describes an aim to examine cerebral blood flow changes during emergence using jugular venous bulb oxygen saturation and transcranial Doppler. The posted results summarized for the primary endpoint do not provide emergence measurements or a before-and-after estimate. Those results are not reported in the registry record.

7. Results Posted in the Registry

• Abdominal Surgery Group: mean 61.80 versus 63.70 on control; difference -1.90 (95% CI -5.66 to 1.86), standardized effect d = -0.26; z-test p = 0.322.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean difference represent?

A mean is the arithmetic average of values within a group. For a continuous measure such as blood flow velocity, the mean summarizes the group’s central value, while the standard deviation describes how spread out individual measurements are around that mean. The registry reports a mean of 63.7 cm/s and standard deviation of 6.7 for the craniotomy group, and a mean of 61.8 cm/s and standard deviation of 8.1 for the abdominal surgery group.

The recalculated mean difference is oriented as abdominal surgery minus craniotomy. Its estimate is -1.9 cm/s. A negative value in this ordering means the posted mean is lower in the abdominal surgery group than in the craniotomy group. This is a descriptive contrast in the posted baseline means; it does not establish why the means differ or whether the contrast is important for a clinical purpose.

Why are there two p-values?

The recalculation uses the posted group means and standard deviations to estimate a difference between means. It reports an unadjusted p-value of 0.322. The sponsor’s reported test is Wilcoxon (Mann-Whitney), with p = 0.554. In general, a mean-based comparison focuses on average values, while the Wilcoxon (Mann-Whitney) test compares the relative ordering of observations between groups. The rank-based test does not simply test the same mean contrast using a different formula. The registry does not give the individual observations or further details of the sponsor’s analysis, so the reported rank-based result cannot be reconstructed from the posted summary statistics.

A p-value describes how compatible the data are with a specified null model under the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result will replicate. A p-value also does not describe the size of an effect. The two reported values should be read alongside the estimates and their uncertainty, with attention to the different methods used.

What does a confidence interval add?

A confidence interval gives a range of estimates compatible with the data under a specified procedure and its assumptions. The recalculated 95% confidence interval for the mean difference extends from -5.662 to 1.862 cm/s. It includes values in both directions relative to no difference. This means the posted summary statistics do not tightly determine whether the underlying mean contrast is below or above no difference. The interval is for the recalculated mean contrast, not for the sponsor’s Wilcoxon test; an interval for the sponsor’s analysis is not reported in the registry record.

In general, interval width reflects both the variability in measurements and the amount of information available. A narrower interval indicates greater precision for the particular estimate, while a wider interval leaves a broader range of plausible values. An interval should not be interpreted as a range containing every individual participant’s measurement.

What does the standardized difference mean?

The recalculated standardized mean difference is -0.256. In general, standardization puts a mean contrast on a scale relative to pooled variability, rather than retaining the original cm/s units. It can help describe the size of a contrast when measurement units differ, but it is not a replacement for the original-unit estimate. It also does not correct for possible confounding, selection, measurement differences, or other design concerns.

The recalculation uses posted summary statistics and is unadjusted. The registry does not report the underlying data, an adjusted model, or the detailed analysis plan. The analysis therefore cannot assess individual-level distributions, whether assumptions were checked, or whether other planned analyses were conducted as intended. The registry’s stated primary endpoint and the sponsor’s reported rank-based comparison remain important context when interpreting the recalculated mean-based result.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a model assumes. If an analysis assumes less variability than is present, uncertainty can be understated and intervals may be too narrow. For a continuous outcome summarized by standard deviations, the reported spread helps characterize variability; however, the registry does not report an over-dispersion assessment or a model-based analysis of the endpoint. There is no basis in the record to claim that over-dispersion was present or that it affected the reported analysis.

More generally, statistical results depend on the analysis method and assumptions. A mean comparison and a rank-based test answer related but not identical questions, and both require careful interpretation in light of study design and data availability. The posted summary supports a descriptive comparison of baseline means and a recalculated interval, but it cannot reproduce the sponsor’s test or establish the study’s full analysis strategy.

10. Confidence Intervals and Precision

The recalculated mean difference is -1.9 cm/s, with a 95% confidence interval from -5.662 to 1.862 cm/s. The interval is centered around the estimated contrast and expresses uncertainty about the mean difference under the recalculation’s assumptions. Because the interval includes no difference and extends to either side, the direction and magnitude of the baseline contrast remain uncertain.

The interval also makes clear why a point estimate should not be read alone. The estimate of -1.9 cm/s is one value, but the data are compatible with a range of contrasts extending from a larger negative difference to a positive difference. The interval does not show the distribution of individual measurements, and it is not a prediction interval for future participants. It also does not specify whether any value in the interval is clinically important; the registry record gives no threshold for that judgment.

This interval belongs to the unadjusted recalculation of the difference in means based on posted summary statistics. The sponsor’s reported Wilcoxon (Mann-Whitney) analysis gives p = 0.554, but its estimate and confidence interval are not reported in the registry record. The two methods target related comparisons but are not interchangeable, so the recalculated interval should not be attributed to the sponsor’s rank-based analysis.

In general, confidence intervals communicate precision more directly than a significance label alone. Here, the interval’s width indicates that the baseline mean contrast is not estimated with enough precision to support a narrow statement about its size. It describes uncertainty in this specific comparison and does not resolve the limitations of the study design or answer the emergence-related question.

11. 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 illustration gives participants per arm, not a total number of events. Its entries are planning illustrations based on the observed effect, not the trial’s original design assumptions. The listed 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 a stated fraction of the observed effect. The trial’s own detailed sample-size assumptions are not reported in the registry record.

For planning for 100% of the observed effect, the illustration gives 241 participants per arm for 80% power and 322 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 428 participants per arm for 80% power and 572 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 961 participants per arm for 80% power and 1,287 participants per arm for 90% power.

In general, power is the chance that a study will identify an effect of the specified size under the planning assumptions if that effect is present. The 80% power column and the 90% power column describe different planning targets: the latter seeks a greater chance of detecting the chosen effect under those assumptions. The figures are not observed power for this trial.

The rows illustrate that smaller effects require more participants per arm to achieve the stated power targets, given the same planning framework. These values should not be read as a recommendation or as evidence that the completed trial was designed around the recalculated effect. They are hypothetical planning quantities based on the observed effect and the stated assumptions.

12. 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.900; pooled standard deviation σ = 7.433.
2. n = 2 × (1.96 + 0.842)² × 7.433² / -1.900² = 240.2, rounded up to 241 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
delta <- -1.90000000000001                      # observed difference in means
sigma <- 7.43303437365925                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1642147)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 241 (80% power), 322 (90% power)
 75% of observed effect: n per arm = 428 (80% power), 572 (90% power)
 50% of observed effect: n per arm = 961 (80% power), 1,287 (90% power)
power.t.test: 241.2 
Simulated power at n = 241 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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.

13. Analyses Reported by the Sponsor

The sponsor’s posted analysis compares the groups using a Wilcoxon (Mann-Whitney) test and reports p = 0.554. The analysis does not report a test estimate or confidence interval in the registry record. This is the sponsor’s own reported result and should be distinguished from the unadjusted recalculation based on the posted group means and standard deviations.

The recalculation estimates the difference in means as -1.9 cm/s, with a 95% confidence interval from -5.662 to 1.862 cm/s and an unadjusted p-value of 0.322. It uses a mean-based comparison of summary statistics, whereas the sponsor’s rank-based test compares the ordering of observations. The two p-values therefore arise from different methods and need not match. The registry does not provide individual observations or enough methodological detail to reproduce the sponsor’s test.

The record does not flag a discrepancy between its reported result and the recalculation. The methods nevertheless answer related, not identical, statistical questions. The sponsor’s p-value should be cited as the reported rank-based analysis, and the recalculated estimate should be described as an unadjusted mean difference derived from posted summaries. Neither should be presented as the other method’s result.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 6 analyses, but the full set of outcome definitions, analysis details, and results is not reported in the registry record. The primary endpoint described in the posted results is baseline mean blood flow velocity in the middle cerebral artery. The details of secondary outcomes are not reported in the registry record.

When several outcomes or statistical tests are examined, the chance of finding at least one apparently unusual result can increase. In general, multiplicity adjustments or a prespecified hierarchy can address some of that concern, but the registry record does not report whether any adjustment, hierarchy, or other multiplicity strategy was used. The recalculated p-value is unadjusted. The record does not establish whether the sponsor’s reported p-value was adjusted for multiple analyses.

The record describes the primary endpoint population in terms of sample estimation, referring to a cohort-study equation and hyperemia frequency from literature and a pre-study. It does not report a detailed analysis population definition. Information about intention-to-treat, per-protocol, or other analysis sets is not reported in the registry record. The criteria for including or excluding participants from the endpoint analysis are also not reported.

Missing-data handling, the amount of missing endpoint data, and any imputation or sensitivity analyses are not reported in the registry record. The posted endpoint summary gives 30 participants in each group, but that alone does not establish how missing measurements or deviations were handled. A complete assessment of the analysis population and robustness of results is therefore not possible from the registry entry.

The registry’s randomized allocation label does not supply the missing details of sequence generation, allocation concealment, or participant assignment. The record also does not describe interim analyses or stopping rules. These items should be treated as unreported rather than assumed to have been absent or conducted in a particular way.

15. Safety Results

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

Other (non-serious) adverse events

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

The serious adverse event figures list 30 participants at risk in the abdominal surgery group and 30 in the craniotomy group, with 0 affected in each group. The other adverse event figures also list 30 at risk in each group, with 0 affected in each group. No serious adverse event terms are listed.

These figures mean that no affected participants are recorded in the listed serious or other adverse event categories during the registry’s reported accounting. They do not establish that no events occurred outside the categories or observation period captured in the record. The registry does not report the duration or detail of safety follow-up, definitions of adverse events, or completeness of event collection.

Deaths are not reported in the registry record. The listed zero counts should not be interpreted as evidence of no risk, nor do they allow a comparison of safety between the surgical groups beyond the recorded figures. Safety results require the context of event definitions, follow-up, and completeness, which is not available in the posted entry.

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

The primary result describes baseline middle cerebral artery blood flow velocity before general anesthesia. The group means are 63.7 cm/s for patients undergoing craniotomy and 61.8 cm/s for patients undergoing abdominal surgery. The unadjusted recalculation estimates a mean difference of -1.9 cm/s for abdominal surgery minus craniotomy, with a 95% confidence interval from -5.662 to 1.862 cm/s. The sponsor’s reported Wilcoxon (Mann-Whitney) test has p = 0.554.

These statistics do not show that the groups are identical. A confidence interval containing no difference indicates that the data do not precisely distinguish a range of possible mean contrasts from no contrast under the recalculation’s assumptions. A non-small p-value is not proof that there is no effect, and it does not establish equivalence. The record reports no equivalence margin or clinical threshold for the endpoint.

The endpoint is measured before general anesthesia, while the study summary describes interest in changes during emergence. A baseline comparison cannot establish what happened during emergence. The emergence-specific estimates and their uncertainty are not reported in the registry record, so this posted result does not answer whether cerebral blood flow changed over that period.

The comparison is between different surgical settings. The registry labels allocation randomized, but does not describe how participants were assigned to the groups. It also does not report an adjusted analysis or the details needed to assess possible differences between the groups. The result should therefore be read as a comparison of the posted summaries, not as proof that the type of surgery caused a difference or that the surgical groups are otherwise comparable.

The study record offers a limited statistical snapshot: baseline means and standard deviations, a recalculated mean comparison, and a sponsor-reported rank-based p-value. It does not provide individual participant data, full outcome reporting, or a complete analysis plan. The result is informative about the recorded baseline measure, but it does not settle broader questions about cerebral blood flow during anesthesia emergence.

17. Why This Trial Matters Statistically

This trial is statistically interesting because its study summary focuses on cerebral blood flow changes during emergence from general anesthesia, while the posted primary endpoint is a baseline velocity measurement taken before anesthesia. The distinction between a baseline description and a change over time is central to interpreting the result. A baseline comparison alone cannot quantify a later change or explain its timing.

The record also presents a useful example of why the named statistical method matters. The sponsor reports a Wilcoxon (Mann-Whitney) test, while the recalculation compares means using summary statistics. Both describe a contrast between groups, but they do not target exactly the same feature of the data. Their p-values should not be collapsed into a single result or treated as interchangeable.

The interval around the recalculated mean difference adds information beyond a p-value. It shows that uncertainty spans both directions around no difference, rather than supporting a narrow conclusion about the baseline contrast. Reporting the estimate, interval, and test method together makes the evidence easier to interpret without turning a statistical result into a clinical claim.

Finally, the record illustrates the importance of transparent reporting. Details about allocation, analysis populations, missing data, multiplicity, and outcomes beyond the posted primary result are not reported in the registry record. Those omissions limit what readers can infer about the study’s design and its broader questions, even when the posted group summaries and test result are clear.

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.

The primary limitation specific to the posted result is that it concerns baseline mean velocity before general anesthesia, not the emergence-related change named in the study summary. The registry does not report the emergence-specific estimates needed to evaluate that question. The primary result therefore addresses a narrower measurement than the study’s stated topic may suggest.

The comparison groups represent different surgical contexts: craniotomy for supratentorial tumor removal and abdominal surgery. Although the registry labels allocation randomized, the assignment process is not described. The record does not clarify whether surgery was assigned or how participants entered the comparison groups. The available information is insufficient to assess how group formation might affect interpretation.

The posted results do not include individual measurements, an adjusted analysis, or a confidence interval for the sponsor’s rank-based test. The recalculated mean difference is based on summary statistics and cannot show the shape of the distributions or support checks of individual-level assumptions. Further details about the measurement schedule and the incomplete arm descriptions are also not reported in the registry record.

Information about missing data, analysis populations, multiplicity, and the handling of protocol deviations is not reported in the registry record. The registry lists additional outcomes and analyses, but their detailed results are not included in the registry record for this interpretation. The record also gives no clinical threshold for judging the size of a velocity difference, which limits interpretation of practical importance.

The safety figures list no affected participants for the reported adverse-event categories, but event definitions and follow-up details are not reported. Deaths are not reported in the registry record. These omissions prevent a complete assessment of safety reporting from these figures alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Cerebral Blood Perfusion Changes After General Anesthesia for Craniotomy — NCT01642147.
• Registry record last updated 2013-06-24; status last verified 2013-05.
• Results first posted 2013-04-23.
• 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 identifies a completed randomized, parallel-group study sponsored by Huashan Hospital, with enrollment of 60. It compares patients undergoing craniotomy for selective supratentorial tumor removal with patients undergoing selective abdominal surgery. Masking is listed as none.

The primary endpoint is mean middle cerebral artery blood flow velocity before general anesthesia. The posted mean is 63.7 cm/s in the craniotomy group and 61.8 cm/s in the abdominal surgery group, with 30 participants reported in each group. The recalculated mean difference is -1.9 cm/s, with a 95% confidence interval from -5.662 to 1.862 cm/s. The sponsor’s reported Wilcoxon (Mann-Whitney) test gives p = 0.554.

The registry summary describes interest in cerebral blood flow changes during emergence, but those results and key details about analysis populations, missing data, and the full statistical plan are not reported in the registry record. The posted primary result is a baseline comparison and should be interpreted within that scope.