The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction (NCT02554253), a randomized phase 2 study. The primary outcome is Number of Patients With Postoperative Cognitive Dysfunction.

2. Clinical Question

The clinical question is a comparison of two induction strategies in an older cardiac-surgery population, with postoperative cognitive change as the primary outcome. It is not simply a comparison of anesthetic exposure in general: the registry identifies ketamine and propofol as the two study arms. The primary endpoint is based on a prespecified threshold across neurocognitive tests, rather than a single test score or a general impression of cognitive status.

The registry summary frames the question around potential postoperative complications associated with inflammation. That is the rationale recorded for conducting the comparison, not a result of the trial. The posted outcomes allow the cognitive endpoint to be considered alongside the two secondary clinical outcomes, while the registry record does not report results for the hemodynamic investigation mentioned in the summary.

3. Trial Design

This was a randomized, parallel-group Phase 2 trial, with no masking reported. Mayo Clinic is listed as the sponsor, and the record status is completed. The recorded start is 2015-09 and primary completion is 2020-12. Enrollment is listed as 52.

The two arms were ketamine induction and propofol induction. The record reports 25 participants in the ketamine arm and 24 in the propofol arm for the primary outcome. Those are the outcome denominators, and the registry does not explain how they relate to total enrollment. The allocation ratio and details of the randomization procedure are not reported in the registry record.

The primary outcome is the number of participants with postoperative cognitive dysfunction. Acute kidney injury and postoperative delirium are the two posted secondary outcomes. Each is counted over the interval from baseline preoperative cognitive tests to hospital discharge or 10 days postoperatively, whichever came first. The primary outcome description also gives this timeframe.

The registry identifies the primary outcome population as intent to treat. The analysis population definitions for the secondary outcomes, the handling of participants with incomplete outcome data, and the original design assumptions are not reported in the registry record. The record lists three outcome measures and three analyses. It does not describe interim analyses or a stopping rule.

The absence of masking means the study was unmasked as registered. The record does not state whether outcome assessors were masked, or give further details about treatment administration or the randomization process. These omissions limit what can be inferred about trial conduct from the registry entry alone; they do not establish that any particular procedure was or was not used.

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: Of the 265 patients assessed for eligibility, 52 were randomized to study groups. 8 did not meet inclusion criteria, 97 declined to participate, 96 were unable to be contacted before surgery, and 12 were unable to coordinate preoperative testing before surgery.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat population

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: 52 patients were enrolled. 3 patients did not complete the study. 1 patient was found to be ineligible after enrollment, 1 patient transitioned to a procedure that was in the exclusion criteria, and one patient received both the induction medications. This resulted in 25 patients for analysis in the ketamine group and 24 patients in the Propofol group.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Postoperative Cognitive Dysfunction, measured over Baseline (preoperative cognitive tests) to hospital discharge or 10 days postoperatively whichever came first..

The primary endpoint counts participants who met the registry's definition of postoperative cognitive dysfunction (POCD). It compares preoperative with postoperative cognitive testing, with follow-up ending at hospital discharge or 10 days after surgery, whichever came first. The registry describes the population as intent to treat.

POCD was defined in advance as a decline of more than 1 standard deviation on at least 2 neurocognitive tests. The named tests are Trail Making Test A, Trail Making Test B, Hopkins Verbal Learning Test-Revised Learning trials, Hopkins Verbal Learning Test-Revised Delayed Recall, Digit Span, Controlled Oral Word Association Test, Stroop color/word test, and the Mini Mental Status Examination. Thus, the endpoint is a threshold-based classification using multiple tests, not a comparison of mean scores on one measure.

As a general statistical point, a prespecified threshold makes the outcome rule explicit and supports consistent classification. It also compresses detailed test-score information into a participant count, so the count does not show the size or pattern of cognitive change among individuals. The registry gives the definition but does not report how missing test results, practice effects, or differing test completion patterns were handled. Those details matter for interpreting a multi-test endpoint and are not reported in the registry record.

7. Results Posted in the Registry

• Propofol: 41.7% (10/24) versus 64.0% (16/25) on control; risk difference -22.3 percentage points (95% CI -49.6 to 4.9), risk ratio 0.65 (0.37–1.14); unadjusted two-proportion z-test p = 0.117.

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.

Number of Patients With Acute Kidney Injury

• 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:
  • Propofol: 50.0% (12/24) versus 24.0% (6/25) on control; risk difference 26.0 percentage points (95% CI -0.1 to 52.1), risk ratio 2.08 (0.93–4.66); unadjusted two-proportion z-test p = 0.059.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Propofol and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients Who Develop Postoperative Delirium

• 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:
  • Propofol: 4.2% (1/24) versus 0.0% (0/25) on control; risk difference 4.2 percentage points (95% CI -3.8 to 12.2); unadjusted two-proportion z-test p = 0.302.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Propofol and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes add context to the primary cognitive endpoint, but they do not produce one uniform pattern across all outcomes. Acute kidney injury was recorded more often in the propofol arm, while postoperative delirium was uncommon and recorded in only one arm. The primary outcome's observed counts also point in a different direction from the acute kidney injury counts. These variations across endpoints are a reason to avoid reducing the results to a single treatment narrative.

The reported secondary comparisons are unadjusted. The registry lists three outcome measures and three analyses, but does not report a procedure to account for testing multiple outcomes. When several outcomes are examined, chance can contribute to apparently noteworthy findings even when there is no underlying difference. This general issue means an isolated nominal p-value should carry less weight than a pattern supported by a prespecified analysis and adequate precision.

The acute kidney injury sponsor result is p = 0.08, and its unadjusted re-calculation is p = 0.059. The delirium sponsor result is p = 0.31, and its unadjusted re-calculation is p = 0.302. Those values do not resolve the uncertainty in the primary comparison. The registry does not report a formal joint interpretation of primary and secondary outcomes, a hierarchy among outcomes, or multiplicity adjustment.

Secondary outcomes can be useful for describing the range of outcomes recorded during the trial, but they should not be treated as independent confirmation of the primary result. Event counts, definitions, follow-up, and analysis procedures all affect how much weight each comparison can bear. The registry provides the stated outcome interval but does not report further details about outcome ascertainment or missing-data handling for the secondary endpoints.

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

• Number of Patients With Acute Kidney Injury
• Number of Patients Who Develop Postoperative Delirium

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a Fisher Exact analysis for the primary comparison and for acute kidney injury. For postoperative delirium, it reports a Chi-squared analysis. The posted analyses are labelled as superiority analyses. The registry does not report additional details such as the exact statistical test settings, a confidence-interval method, covariate adjustment, or a more complete statistical analysis plan.

What does a risk difference express?

As a general statistical explanation, a risk difference subtracts the event proportion in one group from the event proportion in another. The re-calculated comparisons use propofol relative to ketamine. A negative value therefore points toward a lower observed event proportion in propofol, while a positive value points toward a higher one. The direction alone is not evidence of a reliable difference: the uncertainty interval and analysis method also matter. The posted comparison is unadjusted, so it describes the group contrast without adjustment for other variables.

The risk difference is an absolute measure. It keeps the contrast on the event-proportion scale, which can be easier to relate to the observed participant counts than a relative measure. General statistical interpretation still depends on the study population, outcome definition, follow-up period, and uncertainty around the estimate. The registry also includes relative measures for some outcomes, but those do not remove the uncertainty in a small sample.

Why use exact and chi-squared tests?

Fisher Exact and Chi-squared are methods for comparing categorical outcomes. In general, Fisher Exact calculates a test result from the possible allocations of observed counts under a no-association assumption. The Chi-squared method uses an approximation based on the difference between observed and expected counts. Sparse event data can make large-sample approximations less dependable, so the number of events and the test used are relevant context. The registry reports a Chi-squared test for delirium, where the posted counts are sparse, but does not explain the choice or give further test details. No claim about the suitability of a particular analysis can be established from the registry description alone.

The re-calculated comparisons use posted summary counts and are simple unadjusted calculations. They are not a substitute for the sponsor's reported analysis. Differences in test methods can yield different p-values even when the underlying group counts are the same. A p-value describes how unusual data at least as extreme as those observed would be under a specified null model and its assumptions; it is not the probability that the null hypothesis is true, nor a measure of clinical importance.

How should the confidence interval be read?

As a general explanation, a confidence interval gives a range of effect values compatible with the data under the interval procedure's assumptions. For the primary re-calculation, the interval crosses zero, the value corresponding to no risk difference. The interval therefore indicates that the posted counts do not precisely distinguish a positive contrast from a negative one. It should be read together with the point estimate and the participant counts, rather than as a guarantee that the true effect lies within a fixed range.

The registry does not identify the confidence-interval procedure used for the re-calculated estimates. The sponsor's reported analyses list p-values but no confidence limits. The methods used to derive those sponsor p-values are identified by test name, but the registry does not provide enough additional detail to reconstruct every aspect of the sponsor's analysis.

What does the primary definition add?

The primary outcome uses a threshold across multiple neurocognitive tests. As a general point, a threshold can make the endpoint easier to interpret as a count of participants meeting a defined criterion. It also discards information about the amount of change above or below that threshold, and the count may depend on how test scores are standardized and how incomplete testing is treated. The registry gives the threshold and test list, but those implementation details are not reported in the registry record.

The intent-to-treat label is reported for the primary endpoint. In general, an intent-to-treat analysis aims to retain participants in their randomized groups, but the label by itself does not explain how missing outcomes were handled or confirm the exact analytic dataset. The registry does not report the missing-data method, the analysis population for each secondary endpoint, or whether adjustments were made for multiple comparisons. These unknowns should remain separate from the results that are posted.

11. Confidence Intervals and Precision

The primary re-calculation includes a confidence interval for the risk difference between propofol and ketamine. That interval crosses zero. In practical terms, the data are compatible with a range of contrasts that includes no difference, as well as values in either direction. The point estimate has a direction, but the interval indicates that the estimate is not precise enough to establish that direction with confidence.

The sponsor's reported primary Fisher Exact result is p = 0.23 and does not include a confidence interval in the registry record. The unadjusted re-calculation reports p = 0.117. A p-value alone does not show the range or size of plausible effects, and it cannot replace an interval estimate. The two p-values should be kept distinct because they come from different analyses.

For acute kidney injury, the re-calculated risk-difference interval reaches across zero, and the sponsor reports p = 0.08. For delirium, the re-calculated interval also crosses zero, with a sponsor-reported p = 0.31. The sparse observed counts, especially for delirium, limit the precision of those comparisons. These interval patterns do not prove equivalence or absence of an effect; they indicate uncertainty in the estimated group differences.

As a general statistical principle, a wider interval means that the data distinguish among a broader range of possible effects. Sample size, event frequency, and variability in the data influence precision. The enrollment and event counts in this trial are modest, and the registry does not provide a sponsor-reported confidence interval for the primary comparison. Consequently, readers should avoid treating a point estimate or a p-value threshold as a complete account of the evidence.

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 planning figures are participants per arm, not total events. The outcomes are counts of participants with events, and the planning display uses participant counts for these comparisons. Each entry is an illustration based on the observed effect, not the trial's original design calculation.

The stated assumptions for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is set to a stated fraction of the observed effect: 100%, 75%, or 50%. The registry record does not report the trial's own original sample-size assumptions or justification.

The 80% power column gives the estimated number of participants per arm for a planning scenario designed to have an 80% chance of detecting the specified effect under the assumptions. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. In general, higher target power requires more participants. The displayed values increase as the assumed effect becomes a smaller fraction of the observed effect, because smaller differences are harder to distinguish from random variation.

These figures are planning illustrations, not observed power. They should not be read as evidence about what the completed trial was capable of detecting under its original design, because that design rationale is not reported in the registry record. They also do not show that a stated effect is true or clinically important. Their purpose is to demonstrate how participant requirements change under the specified assumptions and effect scenarios.

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 = 0.640; treatment proportion p₁ = 0.417; average p̄ = 0.528.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7060 = 1.3837.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6881 = 0.5791.
4. n = (1.3837 + 0.5791)² / (-0.2233)² = 77.2, rounded up to 78 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 <- 0.64                          # control proportion
p1 <- 0.416666666666667                          # 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(2554253)
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 = 78 (80% power), 103 (90% power)
 75% of observed effect: n per arm = 137 (80% power), 183 (90% power)
 50% of observed effect: n per arm = 305 (80% power), 408 (90% power)
power.prop.test: 77.2 
Simulated power at n = 78 per arm: 0.796 (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. Analyses Reported by the Sponsor

The sponsor's own primary analysis is reported as a Fisher Exact test with p = 0.23. The unadjusted re-calculation from the posted summary counts reports p = 0.117 and gives a risk-difference estimate with a confidence interval. The registry does not flag a discrepancy between the posted results and the re-calculation. The distinction between the analyses remains important: the reported p-value and the re-calculated estimate are not the same statistical output.

The sponsor analysis is the analysis reported in the registry; the re-calculation is a simple, unadjusted comparison based on the group counts. The registry does not provide an analysis plan or enough detail to reconcile every methodological choice between them. It would therefore be inappropriate to present the re-calculated p-value as if it were the sponsor's reported result, or to treat the two values as interchangeable.

For the secondary outcomes, the sponsor reports Fisher Exact p = 0.08 for acute kidney injury and Chi-squared p = 0.31 for delirium. The re-calculated unadjusted p-values are 0.059 and 0.302, respectively. As with the primary outcome, these are outputs from different analyses. The posted sponsor results should be identified as such, with re-calculations used only to describe the direct unadjusted contrasts from the summary counts.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes, with three outcome measures and three reported analyses. It does not report a multiplicity adjustment, a hierarchy for interpreting the outcomes, or a plan specifying how secondary findings would affect conclusions. Without such information, the sponsor-reported p-values should be read as endpoint-specific results rather than as an adjusted family of tests.

As a general statistical point, testing several outcomes increases the opportunity for a nominally unusual result to occur by chance across the set. Adjustment procedures can address that issue, but they can also change the interpretation and precision of individual comparisons. No adjustment procedure is reported in the registry record, so none should be assumed. This is especially relevant when interpreting secondary outcomes alongside the primary endpoint.

The primary outcome is labeled as an intent-to-treat population. The registry does not explain how participants with missing postoperative tests were handled, whether all randomized participants were included in the analysis, or how missingness was assessed. It also does not report missing-data procedures for acute kidney injury or delirium. The primary outcome denominators are 25 and 24, whereas enrollment is listed as 52; the record does not reconcile those figures. That information gap is not enough to determine why the denominators differ.

The statistical analysis plan, covariate adjustment strategy, sensitivity analyses, and interim-analysis procedures are not reported in the registry record. Nor does the record specify whether outcome definitions or analysis choices changed over time. These omissions limit assessment of how robust the reported findings are to alternative analytic decisions. They do not establish that missing data, multiplicity, or interim analyses were handled in a particular way; they mark details that cannot be evaluated from the registry entry.

16. 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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: complete heart block (4.2%), rv failure (4.0%), respiratory failure (4.0%), intestinal perforation (4.0%), acute kidney injury (4.0%).

The adverse-event record lists 25 participants at risk in the ketamine arm and 24 in the propofol arm. One participant in each arm is recorded as having a serious adverse event. No other adverse events are recorded as affecting participants in either arm, and deaths are recorded as zero in both arms.

The registry also lists serious-event terms with percentages: Complete heart block, 4.2%; RV failure, 4.0%; Respiratory failure, 4.0%; Intestinal perforation, 4.0%; and Acute kidney injury, 4.0%. The record does not explain how these term-level percentages relate to the arm-level serious-event counts or give further event-level detail. They should not be treated as a complete description of event timing, severity, attribution, or recurrence.

These are descriptive safety counts from a trial with limited enrollment. The registry entry does not provide a formal comparative safety analysis, and the counts alone do not establish whether an event was caused by a study drug. They also do not determine the frequency of uncommon events in a broader population.

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

The posted results describe a randomized comparison of ketamine and propofol induction in older patients undergoing cardiac surgery. For the primary cognitive endpoint, the observed counts differ between arms, but the unadjusted re-calculated confidence interval crosses zero and the sponsor's Fisher Exact analysis reports p = 0.23. Taken together, these results leave considerable uncertainty about the size and direction of the population difference.

The result does not establish that either induction strategy changes postoperative cognitive dysfunction. Nor does it establish that the strategies are equivalent. An uncertain estimate can be compatible with no difference and with effects in either direction; it is not affirmative evidence for any one of those possibilities. The trial's observed counts should not be converted into a claim of benefit or harm without considering the uncertainty and limitations of the record.

The secondary outcomes broaden the description but do not settle the primary question. The endpoints have different observed patterns, and the record does not report multiplicity adjustment. The secondary p-values therefore do not constitute independent confirmation of a treatment effect. The reported follow-up also ends at discharge or 10 days after surgery, so the outcomes do not describe longer-term cognitive status.

The registry summary says the trial aimed to investigate hemodynamic impact, but no hemodynamic results are posted among the registry entries for this analysis. The registry record also does not report the original sample-size justification, detailed missing-data methods, or a complete statistical analysis plan. These limits constrain interpretation of both the results and the trial's ability to address broader questions.

As a general interpretation principle, a trial result is evidence about the enrolled sample under the outcomes and analyses reported, not a universal statement about all patients or settings. These data are most appropriately read as an imprecise comparison with descriptive secondary and safety information. They do not support medical advice or a definitive claim about clinical effectiveness.

18. Why This Trial Matters Statistically

This trial illustrates why an observed difference and a reliable conclusion are not the same thing. The primary event counts point in one direction, while the uncertainty interval spans the no-difference value and allows contrasts in either direction. Looking only at the point estimate would omit an important part of the evidence; looking only at a p-value would omit both effect magnitude and precision.

It also illustrates how the choice of analysis can matter. The registry reports a Fisher Exact primary test, while the simple unadjusted re-calculation uses the posted counts to describe a risk difference and reports a different p-value. These outputs address the same group data through distinct analyses and should be labeled accordingly. The record's limited methodological detail prevents a fuller account of how the sponsor's analysis was specified.

The trial has multiple outcomes, sparse event counts for delirium, and no reported multiplicity adjustment. This makes it useful to distinguish a primary endpoint from secondary observations and to avoid treating each nominal test as a separate confirmation. The cognitive outcome's threshold across multiple tests also shows how outcome definitions shape what a participant count represents.

Finally, the planning illustrations make clear that detecting a smaller effect generally requires more participants under the stated assumptions. Those illustrations are not a substitute for the trial's original design rationale, which is not reported in the registry record. Together, the endpoint definition, uncertainty, analysis choices, and planning assumptions offer a practical example of how biostatistical interpretation requires more than reading a single result in isolation.

19. 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 endpoint is a threshold classification based on multiple tests, and the registry does not report how incomplete testing or missing scores were handled. The threshold-based count does not show the degree of cognitive change or which tests contributed to each classification. The endpoint timeframe is limited to discharge or 10 days postoperatively, so later outcomes are not represented.

The total enrollment is 52, while the primary outcome denominators are 25 and 24. The registry does not explain this difference. Without a participant flow description or missing-data account, it is not possible to determine from this record why the analyzed denominators are as posted. The intent-to-treat label is recorded for the primary outcome, but the registry does not detail how it was implemented.

The record gives limited methodological information: randomization details, allocation ratio, original sample-size justification, statistical analysis plan, confidence-interval method, multiplicity procedures, and interim analyses are not reported. The record also does not report the hemodynamic results mentioned in the study summary. These gaps make it difficult to assess prespecification, robustness, or the rationale behind the reported analyses.

The observed event counts are limited, particularly for delirium, and the resulting comparisons are imprecise. The posted safety information is also brief and does not provide event-level timing, attribution, or a comparative safety analysis. These limitations mean the registry results are descriptive and should not be generalized beyond the outcomes, follow-up, and population recorded.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: The Impact of Ketamine on Postoperative Cognitive Dysfunction, Delirium, and Renal Dysfunction — NCT02554253.
• Registry record last updated 2022-02-15; status last verified 2022-01.
• Results first posted 2022-02-15.
• 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.

23. Record Summary

The registry record describes a completed, randomized, unmasked, parallel-group Phase 2 trial sponsored by Mayo Clinic. It enrolled 52 patients aged 75 years or older undergoing cardiac surgery and compared ketamine induction with propofol induction.

The primary outcome was the number of participants meeting a prespecified definition of postoperative cognitive dysfunction, assessed from preoperative testing through hospital discharge or 10 days postoperatively, whichever came first. Acute kidney injury and postoperative delirium were the posted secondary outcomes.

The primary counts differ between arms, but the re-calculated confidence interval crosses zero and the sponsor-reported Fisher Exact test is p = 0.23. Secondary results and safety counts add descriptive context but do not remove uncertainty. The registry record does not report the original sample-size justification, detailed missing-data procedures, multiplicity adjustment, or hemodynamic results.