Effect of Deep Versus Moderate Neuromuscular Block During Sevoflurane Anesthesia on Intraoperative Surgical Conditions.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Deep Versus Moderate Neuromuscular Block During Sevoflurane Anesthesia on Intraoperative Surgical Conditions. (NCT03170661), a randomized phase 4 study. The primary outcome is Leiden Surgical Rating Scale.

2. Clinical Question

The trial addresses whether the contrast between the two block depths observed in other anesthetic circumstances would also be seen with sevoflurane. The registry rationale notes that sevoflurane itself produces some degree of muscle relaxation, so results from propofol anesthesia might not apply. That rationale motivates the comparison; it does not establish what the trial would find.

The primary measure rates surgical conditions on a 5-point scale, from 1 for poor to 5 for optimal. The surgeon assessed conditions at 15 minute intervals during surgery, and the reported outcome is the average of those ratings for each participant. Thus, the primary question concerns an average rating across the procedure, rather than a single assessment or a direct measure of a postoperative outcome.

3. Trial Design

The registry record describes a completed, randomized, triple-masked, parallel-group phase 4 trial sponsored by Leiden University Medical Center. Enrollment was 98. The listed study dates are 2017-06-14 for study start and 2020-04-01 for primary completion. The posted primary outcome includes 49 participants in the moderate-block group and 49 in the deep-block group.

Participants were assigned to moderate or deep neuromuscular block while receiving sevoflurane anesthesia for laparoscopic renal surgery. The moderate-block target was 1-2 twitches train of four; the deep-block target was 1-2 twitches post tetanic count. These are the target descriptions in the registry record. Further details about how the targets were maintained or how departures from them were handled are not reported in the registry record.

Triple masking is recorded, but which people were masked and how masking was maintained are not reported in the registry record. The registry lists one intervention as a drug, named deep neuromuscular block, while also describing both comparison groups by their block depth. The specific drug or drugs and their dosing details are not reported in the registry record.

The record lists postoperative pain scores, sedation levels, and saturation, as well as intraoperative hemodynamic conditions and nociception level, among secondary outcomes. Numeric results are posted for pain scores, sedation levels, and saturation. Numeric results for intraoperative hemodynamic conditions and nociception level are not reported in the registry record. The record does not report further participant eligibility details, recruitment flow, or reasons for any exclusions from an analysis.

4. Participant Flow and Accounting

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

Overall Study

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Leiden Surgical Rating Scale, measured over during surgery.

The primary endpoint is the Leiden Surgical Rating Scale, a surgeon-rated measure of intraoperative surgical conditions. It uses a 5-point scale: 1 is poor and 5 is optimal. Ratings were made at 15 minute intervals during the on average 3 hour procedure, and the registry says the reported value is the mean and standard deviation of each participant’s average across the ratings.

A repeated set of ratings can capture conditions across an operation rather than relying on one moment. Averaging those ratings gives a continuous outcome that can be compared between groups using group means and a mean difference. The scale’s direction matters for interpretation: higher scores correspond to more optimal ratings, while lower scores correspond to poorer ratings. The posted group means are both 4.8.

The endpoint represents the surgeon’s rating of surgical conditions as defined by this scale. It is not, by itself, a measure of recovery, pain, complications, or overall clinical benefit. The registry record does not report a threshold for a clinically important difference on the scale, nor does it report how the scale was validated for this trial. Those omissions limit what can be said about the practical meaning of a difference, apart from describing its size and uncertainty.

7. Results Posted in the Registry

• Deep Neuromuscular Block: mean 4.80 versus 4.80 on control; difference 0.00 (95% CI -0.14 to 0.14), standardized effect d = 0.00; z-test p = 1.000.

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.

Postoperative Measurements and Outcomes; Pain Scores

• 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:
  • Deep Neuromuscular Block: mean 3.20 versus 2.90 on control; difference 0.30 (95% CI -0.43 to 1.03), standardized effect d = 0.16; z-test p = 0.422.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Deep Neuromuscular Block and the control. The interval gives the range of effects that remain compatible with the data.

Postoperative Measurements and Outcomes; Sedation Levels

• 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:
  • Deep Neuromuscular Block: mean 1.00 versus 0.90 on control; difference 0.10 (95% CI -0.14 to 0.34), standardized effect d = 0.17; z-test p = 0.409.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Deep Neuromuscular Block and the control. The interval gives the range of effects that remain compatible with the data.

Postoperative Measurements and Outcomes; Saturation

• 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:
  • Deep Neuromuscular Block: mean 98.00 versus 98.00 on control; difference 0.00 (95% CI -0.40 to 0.40), standardized effect d = 0.00; z-test p = 1.000.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Deep Neuromuscular Block and the control. The interval gives the range of effects that remain compatible with the data.

The posted numeric secondary results cover pain scores, sedation levels, and saturation during the post-anesthetic care unit stay. Their group summaries and unadjusted comparisons are descriptive extensions of the primary analysis. Across these outcomes, the estimates do not show a consistent pattern of clearly separated group means. This broad pattern is compatible with the primary comparison’s lack of a visible mean difference, but secondary outcomes do not independently establish the primary finding.

The registry also lists intraoperative hemodynamic conditions and nociception level as secondary outcomes, but numeric results for these are not reported in the registry record. The record lists five secondary outcomes overall, while numeric summaries are posted for three. Their absence from the posted numeric results should not be interpreted as a null finding or as evidence of no difference.

Unadjusted secondary comparisons carry less inferential weight when multiple outcomes are examined. In general, the more comparisons considered, the greater the chance that an apparently notable result arises by chance, even if there is no underlying effect. Adjustments or a prespecified hierarchy can address that issue, but a multiplicity strategy is not reported in the registry record. The available secondary calculations should therefore be read as exploratory descriptions, not as a set of independent confirmatory tests.

The registry does not report whether these secondary outcomes were prespecified in a detailed analysis plan, how missing observations were handled, or whether any adjustment was made for repeated measurements. Without those details, the secondary estimates cannot be given the same confirmatory status as a clearly specified primary analysis. They can indicate what the posted summaries look like, but they do not replace the primary comparison or resolve its limitations.

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

• Postoperative Measurements and Outcomes; Pain Scores
• Intraoperative Hemodynamic Conditions
• Postoperative Measurements and Outcomes; Sedation Levels
• Postoperative Measurements and Outcomes; Saturation
• Intraoperative Nociception Level

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is a mean score on a scale. The registry reports each group’s mean and standard deviation, then a mean difference for deep versus moderate block. A mean difference expresses the contrast on the original score scale. A value of 0.0 indicates that the posted group means are equal at the displayed precision. Its units remain score points on the Leiden Surgical Rating Scale, rather than a standardized measure.

What does a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimated effect under the statistical method used to construct it. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The recalculated primary interval is -0.14 to 0.14. Since it includes zero, the calculation is compatible with no mean difference and with small differences in either direction. It does not assign probabilities to particular values within the interval, and it does not show that all clinically important differences have been ruled out. The registry record does not state a clinically important difference threshold for this scale.

How should the p values be read?

In general, a p value describes how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions held. It is not the probability that the null model is true. The recalculated unadjusted p value is 1.0, while the sponsor-reported p value is 0.94. These arise from different reported analysis descriptions: the recalculation is a simple unadjusted comparison of posted summary statistics, and the registry identifies GEEGLM for the sponsor’s analysis. The record does not supply enough detail to reproduce the GEEGLM analysis.

Why might a generalized estimating equation analysis be used?

In general, generalized estimating equations can account for correlation among repeated observations from the same participant. That can be relevant when outcomes are measured repeatedly, as the scale ratings were taken at 15 minute intervals and averaged for the posted summary. However, the registry record does not say exactly which observations entered the sponsor’s model, what correlation structure was selected, or what link and variance specification were used. It is therefore not possible to attribute the difference between the sponsor’s p value and the simple recalculation to any particular modeling choice.

What does over-dispersion mean in general?

For count or binary outcomes, over-dispersion means that the observed variability exceeds what a model assumes. Accounting for it can change uncertainty estimates. The primary endpoint is reported as a continuous score, and the registry does not report an over-dispersion assessment. Over-dispersion should not be assumed to explain the primary result. More generally, selecting a model that reflects the outcome and the dependence structure is important because standard errors and confidence intervals depend on those assumptions.

What is the role of the recalculation?

The recalculated comparison uses posted means, standard deviations, and group sizes to produce a simple unadjusted estimate and interval. Such a calculation is a useful check on the scale and direction of the reported summaries, but it is not a replacement for the trial’s prespecified or sponsor-conducted analysis. The registry record does not report the full statistical analysis plan, so it is not possible to establish whether the sponsor’s model followed a particular prespecified specification. The record does identify the sponsor method as GEEGLM and reports p = 0.94; that reported analysis remains the trial’s own inferential result.

What do sample-size illustrations mean?

In general, a planning calculation estimates how many participants might be needed under stated assumptions to detect a selected effect with a chosen power and significance level. It is not an observed property of a completed trial and is not observed power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect set to a stated fraction of the observed effect. The posted planning illustrations relate to secondary outcomes. They are retrospective illustrations based on observed effects, not evidence that the original study was designed using those effects. The trial’s own sample-size justification is not reported in the registry record.

Other key analysis details are also absent. The registry record does not report the analysis population, handling of missing observations, covariate adjustments, or a detailed account of the primary model. These details matter because the interpretation of an estimate depends on who was included and how repeated or incomplete measurements were treated.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 0.0, with a 95% confidence interval from -0.14 to 0.14. This interval gives a sense of the precision of the simple unadjusted comparison: differences of modest size in either direction remain compatible with the calculation. Its width should be interpreted on the original score scale, whose ratings run from 1 for poor to 5 for optimal.

Precision is not the same as importance. The interval does not identify what difference would matter to patients, surgeons, or trial decision-makers. A clinically important difference threshold is not reported in the registry record. Nor does the interval establish equivalence: an equivalence conclusion requires a prespecified margin and an analysis designed to assess whether the interval lies within that margin, neither of which is reported.

The group means are rounded to one decimal place, while the recalculated interval is reported to two decimal places. The two means are both 4.8 as posted, and the mean difference is 0.0. The spread measures are 0.4 for moderate block and 0.3 for deep block. The registry record does not provide individual participant data or the distribution of ratings, so the effect of rounding and the shape of the score distributions cannot be assessed from the posted summaries alone.

The sponsor’s analysis reports p = 0.94 but does not report an effect estimate or confidence interval in the registry record. Its precision therefore cannot be compared directly with the recalculated interval. A p value alone does not show the range of effect sizes compatible with that model. The sponsor’s model and the simple recalculation should be kept distinct when considering the evidence.

12. Analyses Reported by the Sponsor

The registry record reports the sponsor’s primary analysis as GEEGLM, with p = 0.94 for the superiority comparison. It does not report the model-based effect estimate or its confidence interval. The simple recalculation from the posted group summaries gives a mean difference of 0.0, a 95% confidence interval from -0.14 to 0.14, and p = 1.0. The recalculation is unadjusted and should not be presented as though it were the sponsor’s model result.

The analyses are close in their broad description: both report little evidence of a mean separation in the posted primary outcome. But the methods and p values differ, so they are not interchangeable estimates. The GEEGLM result is the trial’s reported inferential analysis; the recalculation is a transparent summary-statistic check. The registry record does not give enough model details to explain the difference or to reproduce the sponsor’s analysis. No discrepancy is flagged in the registry record, but that does not supply the missing model specifications or an unreported sponsor confidence interval.

13. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and lists secondary outcomes, but a detailed multiplicity strategy is not reported in the registry record. In general, testing multiple outcomes increases the chance of at least one apparently notable result occurring by chance. A prespecified testing hierarchy or adjustment can help control that risk. Without a reported approach, unadjusted secondary p values, where calculated, should be treated cautiously and should not be used as if each were an isolated confirmatory test.

Details about missing data are not reported in the registry record. The posted primary summaries include 49 participants in each arm, matching the enrollment total, but the record does not establish from those summaries whether every randomized participant contributed all scheduled ratings or how incomplete measurements were handled. It also does not report imputation, complete-case rules, or sensitivity analyses for missing data. These methods can affect estimates when observations are incomplete, so the posted group summaries alone cannot answer those questions.

The analysis population is not reported in the registry record. Although the trial is described as randomized and the primary outcome summaries show 49 participants per arm, the record does not specify whether the primary analysis followed intention-to-treat, per-protocol, or another population definition. It does not describe post-randomization exclusions or how deviations from target block depth were treated.

The sponsor’s primary method is identified as GEEGLM, but model specifications and adjustment details are not reported. The record does not state whether any covariates were included or how repeated ratings were represented in that analysis. It also does not report an adjustment for multiple testing. These omissions limit independent reproduction of the sponsor’s inference and make the simple recalculation useful only as an unadjusted comparison of posted summaries.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: prolonged hospital stay (6.1%), hospital readmission (4.1%).

The registry reports serious adverse events affecting 5 participants in the moderate-block group and 2 in the deep-block group. Other adverse events affected 3 participants in the moderate group and 2 in the deep group. No deaths are reported in either group. The record lists prolonged hospital stay at 6.1% and hospital readmission at 4.1% among the top serious-event terms.

These are descriptive counts from a trial with 49 participants in each group. The registry record does not provide event-level details, timing, severity grading beyond the serious-event classification, or information about whether participants experienced more than one event. The top serious-event terms should not be assumed to account for all events or to be mutually exclusive. The figures alone do not establish that the groups differ in safety, and the record does not report a comparative statistical analysis of adverse events.

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

The primary result describes surgeon-rated surgical conditions during laparoscopic renal surgery under sevoflurane anesthesia. Both groups had a posted mean Leiden Surgical Rating Scale score of 4.8. The unadjusted recalculation estimates a mean difference of 0.0, with a 95% confidence interval from -0.14 to 0.14. The sponsor’s reported analysis gives p = 0.94. These statistics describe the observed trial results; they do not prove that the two strategies have identical effects.

The trial asks a focused question about block depth in a particular surgical and anesthetic setting. Its findings should not automatically be extended to other operations, anesthetic approaches, patient groups, or outcomes. The registry rationale notes that sevoflurane itself produces some degree of muscle relaxation and that prior observations under propofol might not apply. The result is therefore specific to the comparison recorded for sevoflurane anesthesia, rather than a general test of every setting in which neuromuscular block is used.

The scale ranges from 1 for poor to 5 for optimal, and the observed group means are near the optimal end. This provides context for the scores, but it does not establish that differences near that end are unimportant or that the measure was unable to distinguish the groups. The record does not report a clinically meaningful threshold or an equivalence margin. Consequently, neither equivalence nor absence of a clinically relevant difference can be concluded from the reported p value alone.

The posted summaries also do not answer every question about outcomes. Numeric results for two listed secondary outcomes are not reported in the registry record, and key details about missing data, the analysis population, and the sponsor model are not available. The appropriate reading is bounded: the posted primary summaries show nearly indistinguishable rounded means, and the sponsor reports its own inferential result, while uncertainty about design and analysis details remains.

16. Why This Trial Matters Statistically

This trial illustrates why the statistical interpretation of a clinical result should distinguish an estimated effect from a p value. The posted means are equal at the displayed precision, while the recalculated interval communicates a range of differences compatible with the summary data. The sponsor-reported p value provides a separate result from the stated GEEGLM analysis. Neither the point estimate nor the p value alone supplies a complete account of effect size and precision.

The distinction between failure to detect a difference and evidence of equivalence is also important. A comparison framed as superiority does not establish that two strategies are equivalent when its result is not statistically notable. Equivalence requires a meaningful margin specified in advance and an analysis designed around that question. Such a margin is not reported in the registry record.

The repeated surgeon ratings also make the analysis structure relevant. Repeated measurements on one participant can be correlated, and general methods such as generalized estimating equations can address that dependence. Yet the registry identifies the method without enough detail to reproduce it. This is a practical example of why a method label is not a full statistical analysis plan.

Finally, the record illustrates how secondary outcomes, adverse events, and missing analysis details should be read alongside a primary result. Secondary comparisons need cautious interpretation when multiplicity handling is not reported, and descriptive safety counts are not a comparative safety test. Together, these issues show why transparent reporting of estimates, intervals, analysis populations, missing-data handling, and model specifications matters for clinical-trial interpretation.

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 registry record contains limited detail about the population beyond the setting of laparoscopic renal surgery under sevoflurane anesthesia. Further eligibility criteria and participant characteristics are not reported in the registry record, restricting assessment of how broadly the findings apply. The record also does not identify which people were masked, although the trial is labeled triple-masked.

The primary score is based on repeated surgeon ratings averaged across the procedure. The registry does not report the distribution of individual ratings, agreement among surgeons, or the extent to which ratings were missing. It also does not provide a threshold for a clinically important difference or an equivalence margin. Those omissions constrain interpretation of the score’s practical importance and of the near-equal group means.

The sponsor’s GEEGLM analysis is not fully specified, and its effect estimate and confidence interval are not reported. The analysis population, covariate adjustments, handling of missing data, and detailed model assumptions are also not reported in the registry record. The summary-statistic recalculation cannot fill those gaps, because it is an unadjusted analysis rather than a reconstruction of the sponsor’s model.

Numeric results are absent for two listed secondary outcomes, and the registry does not report a multiplicity strategy. Adverse-event reporting supplies counts and selected serious-event terms but not event-level detail or a comparative statistical analysis. Finally, the trial’s own sample-size justification is not reported in the registry record. These limitations do not erase the posted results, but they restrict what can be concluded from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Effect of Deep Versus Moderate Neuromuscular Block During Sevoflurane Anesthesia on Intraoperative Surgical Conditions. — NCT03170661.
• Registry record last updated 2021-05-13; status last verified 2021-04.
• Results first posted 2021-02-21.
• 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

NCT03170661 is a completed, randomized, triple-masked, parallel-group phase 4 trial sponsored by Leiden University Medical Center. It enrolled 98 participants undergoing laparoscopic renal surgery and compared deep with moderate neuromuscular block during sevoflurane anesthesia. The primary endpoint was the mean Leiden Surgical Rating Scale score during surgery.

The primary group means were 4.8 in both arms, with 49 participants per arm. The unadjusted recalculation gives a mean difference of 0.0 and a 95% confidence interval from -0.14 to 0.14. The registry reports a sponsor analysis using GEEGLM with p = 0.94. Numeric results are posted for three secondary outcomes; the other listed secondary outcomes are not reported numerically in the registry record. The record does not report a detailed analysis plan, missing-data approach, or sample-size justification.