Lidocaine and Ketamine in Abdominal Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lidocaine and Ketamine in Abdominal Surgery (NCT00721110), a randomized na study. The primary outcome is The Effects of Lidocaine and Ketamine on Functional Recovery Assessed by 6 Minute Walk Test on Postoperative Day Two.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, quadruple-masked, factorial study of lidocaine and ketamine in abdominal hysterectomy. It lists four treatment groups: intravenous lidocaine, placebo, intravenous ketamine, and intravenous ketamine plus lidocaine. Lidocaine and ketamine were administered throughout surgery and for the 24 hours following surgery; the placebo description specifies a lidocaine placebo over the same period. The factorial structure is consistent with evaluating the two drugs as separate treatment factors, but the registry record does not report the allocation procedure in further detail or describe an interaction analysis.

Enrollment was 64. The study status is recorded as terminated. The start is listed as 2008-07 and primary completion as 2010-10. The phase is not reported in the registry record. The sponsor is The Cleveland Clinic. The record does not state why the trial was terminated, whether the planned enrollment was reached, or whether recruitment or follow-up ended as intended.

Recovery assessments included the six-minute walk test and measures of pain, opioid consumption, nausea and vomiting, and fatigue. The brief description also mentions walking tests, questionnaires, and blood tests. The listed secondary outcomes specify verbal response pain scores at several recovery time points, opioid consumption at specified times, nausea and vomiting after two hours in the post-anesthesia care unit and on the first postoperative day, and a verbal response fatigue score on postoperative day one. Further details of the study procedures and analysis populations are not reported in the registry record.

Although masking is recorded as quadruple, the registry record does not identify which roles were masked or describe how masking was maintained. It also does not report a statistical analysis plan, a sample-size justification for the trial, or the reason for termination. These omissions limit how completely the study’s conduct and intended comparisons can be reconstructed from the registry record alone.

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: This is a factorial study design with 64 patients randomized to 2 treatments each: lidocaine or placebo and ketamine or placebo. Each treatment was analyzed separately (i.e., lidocaine versus placebo and ketamine versus placebo separately). Though there are 4 distinct groups, the same 64 patients are in both lidocaine and ketamine analyses.

Overall Study

Reasons for not completing this period:

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 The Effects of Lidocaine and Ketamine on Functional Recovery Assessed by 6 Minute Walk Test on Postoperative Day Two, measured over postoperative day 2.

The primary endpoint is the mean distance on the six-minute walk test on postoperative day two, measured in meters. The registry describes it as an assessment of functional recovery after hysterectomy and says it measures return to ambulation after surgery. The test expresses walking capacity as a continuous measurement, allowing group averages and the spread of individual results to be described.

As a functional measure, walking distance addresses an aspect of recovery that is different from pain ratings or opioid use. It can reflect the ability to resume movement after surgery, while still being influenced by many features of recovery and testing conditions. The registry record does not report details such as the walking-test protocol, encouragement procedures, or how incomplete tests were handled, so those aspects cannot be evaluated from the posted record.

The posted primary outcome gives group means, standard deviations, and analysis counts. The means describe the average distance within each reported group; the standard deviations describe the variability of measurements within those groups. The registry also reports adjusted analyses. These summaries address differences in measured walking distance, but do not by themselves establish whether any difference would be important to participants. The registry record does not report a threshold for a clinically important change in walking distance.

7. Results Posted in the Registry

• Nonlidocaine: mean 202.00 versus 202.00 on control; difference 0.00 (95% CI -34.64 to 34.64), standardized effect d = 0.00; z-test p = 1.000.
• Ketamine: mean 193.00 versus 202.00 on control; difference -9.00 (95% CI -45.04 to 27.04), standardized effect d = -0.13; z-test p = 0.625.
• Nonketamine: mean 210.00 versus 202.00 on control; difference 8.00 (95% CI -23.41 to 39.41), standardized effect d = 0.13; z-test p = 0.618.

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.

Verbal Response Fatigue Score on Postoperative Day 1

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Nonlidocaine: mean 7.20 versus 7.20 on control; difference 0.00 (95% CI -1.34 to 1.34), standardized effect d = 0.00; z-test p = 1.000.
  • Ketamine: mean 7.40 versus 7.20 on control; difference 0.20 (95% CI -1.22 to 1.62), standardized effect d = 0.08; z-test p = 0.782.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Nonlidocaine 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 Ketamine and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering pain, opioid consumption, nausea and vomiting, and fatigue. It reports a fatigue measure on postoperative day one with group summaries and a sponsor analysis. Numerical results for the other listed secondary outcomes are not reported in the registry record. Thus, the secondary outcome record does not provide a complete numerical account of every recovery measure named in the study description.

The available secondary reporting does not change the central interpretation of the primary walk-test result: the posted findings leave substantial uncertainty about treatment differences. A secondary measure addresses a different aspect of recovery, and agreement or disagreement across outcomes would not by itself settle the primary functional-recovery question. The registry’s fatigue summaries and reported comparisons do not supply a consistent basis for claiming a broad recovery effect across all outcomes.

Secondary outcomes generally carry less evidential weight when many measures or time points are examined and no adjustment strategy is reported. In general, testing multiple outcomes creates more opportunities for apparently notable results to arise by chance. The registry record lists several secondary outcomes and multiple assessment times for some of them, but does not report a multiplicity plan. The statistical relationship among these measures and the sponsor’s approach to interpreting them are also not reported.

Accordingly, secondary findings are best treated as supportive or exploratory unless the registry record establishes a prespecified hierarchy and an appropriate analysis strategy. No such hierarchy or multiplicity adjustment is reported. This does not make the secondary outcomes uninformative; rather, it means that isolated results should not outweigh the uncertain primary result or be generalized to all aspects of recovery. The absence of numerical postings for several listed outcomes also prevents a balanced comparison of the full secondary-outcome pattern.

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

• Verbal Response Pain Scores (VRS) at PACU Admission and Discharge as Well as Mornings and Afternoons of Postoperative Days 1 and 2
• Total Opioid Consumption at PACU Admission and Discharge as Well as Mornings of Postoperative Days 1 and 2
• Presence of Nausea and Vomiting After Two Hours in the PACU and the First Postoperative Day
• Verbal Response Fatigue Score on Postoperative Day 1

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: each participant’s six-minute walk test is recorded as a distance, and the registry reports a mean for each group. The posted standard deviation describes how dispersed individual distances are around a group mean. A standard deviation is not the uncertainty in the mean difference; it describes variation among measurements. The recalculation uses the group means, standard deviations, and analysis counts to estimate unadjusted differences between group means.

What does a mean difference represent?

In general, a mean difference expresses the distance between two group averages in the outcome’s original units. For the walk test, the unit is meters. A value of zero means the two averages are the same in that comparison; a positive or negative value indicates the direction of the estimated difference according to the order of the groups. The recalculated estimates are not adjusted for other variables. They summarize the posted group-level statistics and should not be treated as a replacement for the sponsor’s reported analysis.

For the Lidocaine and Nonlidocaine primary comparison, the recalculated mean difference is 0.0 meters. For Ketamine compared with the listed Lidocaine group, it is -9.0 meters. For Nonketamine compared with Lidocaine, it is 8.0 meters. The registry’s reported adjusted analyses use different group pairings for the second comparison: Ketamine and Nonketamine. Consequently, estimates should be interpreted with their comparison labels in view rather than treated as interchangeable results.

Why do the intervals matter?

In general, a confidence interval describes the uncertainty around an estimated effect under a statistical model. A narrower interval indicates greater precision, while a wider interval indicates less precision. An interval that includes zero is compatible with no average difference under the analysis, but it can also be compatible with effects on either side of zero. It does not establish equivalence. The recalculated intervals are presented with the posted recalculations; the registry record does not identify their confidence level. The sponsor’s intervals are explicitly labeled 97.5% confidence intervals.

The intervals around the primary recalculated estimates are broad in relation to the point estimates. This means the observed averages alone do not pin down the direction or size of the underlying group difference with much precision. General statistical interpretation should distinguish the point estimate, which is the best single summary under the analysis, from the interval, which indicates uncertainty about that estimate.

What does the p-value say?

In general, a p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that null hypothesis and the statistical model were correct. It is not the probability that the null hypothesis is true, nor does it measure the probability that a treatment works. The unadjusted p-values for the recalculated primary comparisons are 1.0, 0.625, and 0.618. The sponsor’s adjusted p-values are 0.96 and 0.54. These values do not provide strong evidence against no difference for their respective comparisons, but they do not prove that the effects are zero.

What does ANCOVA add?

The registry identifies ANCOVA as the method for the sponsor’s primary comparisons. In general, analysis of covariance estimates a group contrast while accounting for one or more covariates. Adjustment can produce an estimate that differs from a simple comparison of group means, because the calculation incorporates the model and covariate information. The registry record does not identify the covariates, model specification, or handling of missing observations. The adjusted estimates therefore can be reported as posted, but their full modeling details cannot be assessed from the registry record.

The registry’s other reported primary analysis information includes mean differences in final values, confidence intervals, and p-values. The adjusted Lidocaine versus Nonlidocaine estimate is 0.93, with a 97.5% confidence interval from -52 to 54 and p = 0.96. The Ketamine versus Nonketamine estimate is -11, with a 97.5% confidence interval from -65 to 44 and p = 0.54. The recalculations are simple unadjusted comparisons, whereas these sponsor estimates are adjusted. Differences between their point estimates do not by themselves indicate an error; the methods and, for some contrasts, the comparison groups differ.

How should the planning illustrations be read?

In general, a sample-size calculation estimates how many participants per arm a hypothetical study might need under stated assumptions to detect a specified effect with a chosen power and significance level. Here the illustrations are based on the observed effect, assume two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. They show planning for fractions of the observed effect. For the primary Ketamine comparison, the registry lists 995 participants per arm for 80% power and 1,331 participants per arm for 90% power when planning for 100% of the observed effect. For 75% of the observed effect, the corresponding figures are 1,768 and 2,366 participants per arm. These figures are hypothetical planning illustrations, not observed power, and are not evidence about the power of the completed trial.

Small estimated effects can yield large planning requirements, and planning for a smaller fraction of an observed effect increases the required group size in these illustrations. Such calculations inherit uncertainty from the observed effect used to construct them. They do not establish what effect is clinically important, and the registry record does not report that the original trial was designed using these assumptions or calculations.

Finally, the factorial design concerns two treatment factors, lidocaine and ketamine, but the registry record does not report a factorial interaction estimate or the full analysis plan. A factorial trial can be analyzed to estimate separate factor effects and, when specified, whether the effect of one factor depends on the other. Without the reported model details and interaction results, conclusions about the combined treatment should remain limited to the posted comparisons rather than inferred from the design label alone.

11. Confidence Intervals and Precision

The primary outcome estimates are imprecise enough that the observed averages do not settle the direction or size of the treatment differences. The recalculated Lidocaine versus Nonlidocaine mean difference is 0.0 meters, with an interval from -34.64 to 34.64. The interval spans values on both sides of zero. The Ketamine comparison against Lidocaine has an estimate of -9.0 meters and an interval from -45.04 to 27.04. The Nonketamine comparison against Lidocaine has an estimate of 8.0 meters and an interval from -23.41 to 39.41. Each interval includes zero and allows for effects in either direction.

The sponsor’s adjusted estimates are also uncertain. The Lidocaine versus Nonlidocaine estimate is 0.93 meters, with a 97.5% confidence interval from -52 to 54. The Ketamine versus Nonketamine estimate is -11 meters, with a 97.5% confidence interval from -65 to 44. The ranges are broad, so the posted results do not narrowly identify a single effect size. Their inclusion of zero is consistent with the reported p-values, but does not demonstrate equivalence or rule out differences that could matter.

In general, precision depends on the amount of outcome variability, the analysis count, and the method used to estimate the contrast. The posted standard deviations indicate variation in walking distances within the groups, while the analysis counts for the primary summaries range from 30.0 to 32.0. These are the counts reported for the outcome summaries; they should not be confused with the enrollment figure of 64 or treated as a complete account of participant flow. The registry record does not explain the differences in analysis counts.

The registry does not report a clinical-importance threshold for the walk-test distance. As a result, statistical uncertainty can be described, but the intervals cannot be classified against a prespecified threshold for a meaningful functional difference. The sample-size illustrations suggest that detecting effects as small as the observed estimates would require much larger groups under the stated assumptions, but those illustrations are not a measure of the trial’s observed power and do not resolve the uncertainty in the treatment effects.

12. Analyses Reported by the Sponsor

The registry reports sponsor analyses for two primary contrasts. An ANCOVA comparison of Lidocaine and Nonlidocaine gives a mean difference in final values of 0.93, a 97.5% confidence interval from -52 to 54, and p = 0.96. An ANCOVA comparison of Ketamine and Nonketamine gives a mean difference of -11, a 97.5% confidence interval from -65 to 44, and p = 0.54. Both adjusted intervals include zero, and neither reported p-value indicates strong evidence of a difference under that analysis.

The recalculated estimates are unadjusted comparisons based on the posted group means, standard deviations, and analysis counts. The recalculation for Lidocaine versus Nonlidocaine is close to the sponsor’s adjusted estimate. Other recalculated contrasts use Lidocaine as the reference group, whereas the sponsor’s second adjusted contrast compares Ketamine with Nonketamine. Differences in estimates should therefore be understood in light of both the adjustment and the groups being contrasted.

The registry discrepancy indicator is false. The sponsor’s adjusted analyses and the unadjusted recalculations are distinct summaries, not a flagged disagreement between two versions of the same analysis. The adjusted estimates are the registry’s reported sponsor results; the recalculations offer a transparent, simple comparison of posted summary statistics. The registry record does not give the covariates or full ANCOVA specification, which limits further assessment of how adjustment affected the estimates.

13. Multiplicity, Missing Data and Analysis Populations

The study lists a primary functional-recovery endpoint and several secondary outcomes, including pain, opioid consumption, nausea and vomiting, and fatigue. Some outcomes are assessed at more than one time point. The registry record reports 28 analyses, but does not explain how those analyses map to outcomes, time points, treatment contrasts, or model specifications. It does not report a multiplicity strategy, such as a prespecified hierarchy or adjustment for repeated testing. Without that information, the reported p-values should be interpreted as results for their individual analyses rather than as a set with controlled overall error.

Missing-data methods are not reported in the registry record. The primary outcome summaries list analysis counts of 31.0 for Lidocaine, 31.0 for Nonlidocaine, 30.0 for Ketamine, and 32.0 for Nonketamine. The reason these counts differ is not reported. The record does not describe how unavailable walk-test measurements were handled, whether participants with missing data were excluded, or whether any imputation or sensitivity analysis was used. Missingness could affect the interpretation of observed group summaries, but its extent and handling cannot be determined from the posted record.

The registry reports enrollment of 64, but does not describe the analysis population for the primary or secondary outcomes. It does not state whether analyses followed intention-to-treat principles, whether participants were analyzed according to randomized assignment, or whether a per-protocol population was used. The record also does not provide a participant flow accounting for enrollment, treatment receipt, follow-up, and inclusion in each analysis. These details are important for assessing whether the analyzed groups preserve the benefits of randomization and whether exclusions could have influenced results.

The registry does not report a statistical analysis plan or sample-size justification for the original study. The separate planning illustrations use the observed effects and stated assumptions; they should not be mistaken for the trial’s original design rationale. Without prespecified analysis details, missing-data methods, and a multiplicity plan, the precision and robustness of the reported findings are harder to evaluate than the numerical estimates alone suggest.

14. 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 adverse-event record lists zero serious events affecting participants in each group, with 16 at risk in Lidocaine, 16 at risk in Placebo, 15 at risk in Ketamine, and 15 at risk in Ketamine plus Lidocaine. It also lists zero other events affecting participants in those respective groups and gives the same at-risk counts for those event fields. No serious-event terms are listed.

The death fields in the registry record contain 16 for Lidocaine, 16 for Placebo, 15 for Ketamine, and 15 for Ketamine plus Lidocaine. These entries are not consistent with a straightforward reading of a count of deaths among the stated at-risk groups. The registry record does not explain how those fields were defined or populated, so they should not be interpreted as evidence that those numbers of deaths occurred. Clarification of the record is needed to understand them.

Zero reported affected participants in the event fields is not, by itself, proof that no adverse events occurred. The posted counts may reflect the registry’s collection and reporting conventions, and the record does not provide event definitions, follow-up details, or a fuller safety narrative. These safety entries should therefore be read as registry reporting, with the unexplained death fields kept distinct from the zero serious- and other-event counts.

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

The posted primary results show similar average walk-test distances for the Lidocaine and Nonlidocaine groups and modestly different averages in the other listed comparisons. The unadjusted intervals are broad and include zero. The sponsor’s adjusted comparisons also have intervals that include zero. Taken together, the registry results do not provide clear evidence of a difference in the reported primary comparisons, but they also do not establish that the treatments have identical effects.

A result that is not statistically persuasive is not a demonstration that a treatment has no effect. The intervals remain compatible with both positive and negative differences. Because the registry does not report a threshold for a clinically important difference in walking distance, it is not possible to determine from these results whether particular values inside the intervals would be meaningful to patients or clinicians.

The trial’s stated purpose includes assessing whether combined lidocaine and ketamine infusions improve recovery compared with a single infusion or placebo. The posted analyses do not provide a separate adjusted estimate for every such contrast, and the registry record does not report an interaction analysis for the factorial design. Therefore, the results should not be extended into a definitive conclusion about the combined infusion or all pairwise treatment comparisons.

The record also leaves important aspects of analysis conduct unclear: the covariates in ANCOVA, handling of missing measurements, analysis populations, multiplicity methods, and reason for termination are not reported. Secondary outcome postings are incomplete relative to the listed measures, and the safety death fields are unexplained. These gaps do not erase the posted estimates, but they limit how confidently the overall study can be interpreted.

In general, trial results describe evidence from a particular study population, treatment schedule, outcome definition, and analysis. They do not alone establish effects in other settings or answer questions not measured by the trial. Here, the registry record supports a cautious reading of uncertain differences in postoperative walking distance; it does not establish benefit, lack of benefit, equivalence, or safety beyond the reported registry fields.

16. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a factorial design with a functional primary outcome and multiple recovery measures. The treatment structure asks about two drugs, individually and together, while the primary endpoint summarizes postoperative walking distance. Interpreting the results requires attention to which groups are actually being compared, because an unadjusted comparison against Lidocaine is not interchangeable with a sponsor analysis comparing Ketamine and Nonketamine.

The example also shows why estimates and intervals are more informative than a binary reading of p-values. The posted means are close in some comparisons, but the intervals still cover a range of differences in both directions. A large p-value is not evidence that treatments are identical, and a nonsignificant comparison cannot establish equivalence without an appropriate design and margin, neither of which is reported in the registry record.

Another lesson is the distinction between a trial’s planned sample size and a later planning illustration. The registry’s illustrations use observed effects and explicit assumptions to show hypothetical participants per arm for specified power levels. They are not observed power and are not the trial’s original sample-size rationale. Using an observed estimate as a planning input can produce unstable requirements when the estimate itself is uncertain.

Finally, the registry record highlights the importance of reporting analysis populations, missing-data methods, multiplicity handling, and clear safety definitions. Their absence does not prevent readers from understanding the displayed estimates, but it constrains the strength of broader conclusions. Good statistical interpretation depends not only on calculated results, but also on transparent descriptions of how the results were obtained and which questions they address.

17. 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 posted primary outcome summaries contain relatively small analysis counts, and the registry record does not explain why the counts differ across outcome groups. It gives no participant flow diagram or account of exclusions, withdrawals, or missing walk-test measurements. Without missing-data methods or analysis-population definitions, it is not possible to assess whether the reported summaries represent all randomized participants or whether missingness could have affected the comparisons.

The sponsor reports ANCOVA estimates but does not identify the covariates or model specification in the registry record. The recalculations are unadjusted and use group-level summaries, so they cannot account for participant-level information or reproduce the adjusted analyses. The registry reports a factorial design but does not post an interaction estimate, leaving the combined-treatment question incompletely characterized by the reported contrasts.

Multiplicity is another limitation. The record lists numerous analyses and secondary measurements but does not report a strategy for controlling the consequences of multiple testing. Numerical results for several listed secondary outcomes are not reported in the registry record. That limits assessment of whether the primary pattern aligns with pain, opioid use, nausea and vomiting, and other aspects of recovery.

The record gives no clinical-importance threshold for the six-minute walk distance, no original sample-size justification, and no reason for the terminated status. The planning illustrations are based on observed effects and cannot resolve those uncertainties. Safety reporting also requires caution because the death fields are difficult to interpret and are not explained in the record. These limitations are specific to the information available in the registry record; they do not establish that the underlying study lacked procedures that were not reported there.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Lidocaine and Ketamine in Abdominal Surgery — NCT00721110.
• Registry record last updated 2017-07-26; status last verified 2017-04.
• Results first posted 2017-07-26.
• 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.

21. Record Summary

The registry record describes a randomized, quadruple-masked factorial study of perioperative intravenous lidocaine and ketamine for abdominal hysterectomy. The four groups were Lidocaine, Placebo, Ketamine, and Ketamine plus Lidocaine. Enrollment was 64; status is recorded as terminated. The primary endpoint was mean six-minute walk distance on postoperative day two.

Primary unadjusted recalculations and sponsor-reported ANCOVA comparisons do not show clear evidence of differences in the reported contrasts, while their intervals leave substantial uncertainty. The record lists secondary outcomes involving pain, opioid consumption, nausea and vomiting, and fatigue, but numerical reporting is incomplete. Missing-data handling, analysis populations, multiplicity methods, the reason for termination, and details of the adjusted models are not reported in the registry record. The adverse-event death fields are unexplained and should not be interpreted as straightforward counts of deaths.