Impact of Opioid Free Anesthesia on Outcome After DIEPflap Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Impact of Opioid Free Anesthesia on Outcome After DIEPflap Surgery (NCT03202134), a registered phase not stated study. The primary outcome is Number of Patients With One or More Complications.

2. Clinical Question

The clinical question is whether the recorded outcomes differed between patients who received opioid-free anesthesia (OFA) and those who received opioid anesthesia (OA) during Deep Inferior Epigastric Perforator free flap surgery. The registry describes transfer of abdominal tissue to the breast using microsurgery. It notes that flap blood flow decreases during the first hours and that anesthetic and perioperative factors can affect perfusion. It also identifies postoperative nausea and vomiting (PONV) as a relevant outcome.

The registry also lists PONV, postoperative pain measured with a visual analog scale, morphine use, skin temperature, and length of hospital stay as secondary outcomes. The record does not give results for those outcomes in the registry record for this analysis. The clinical question is therefore descriptive and comparative, but the record does not support a conclusion about the size or precision of differences in the primary outcome.

3. Trial Design

Despite the registry title referring to a study of anesthesia impact, the official title identifies this as a retrospective observational cohort study. Participants were not randomly assigned. According to the registry summary, the attending anesthesiologist selected opioid or opioid-free anesthesia based on the availability of competence. This makes the study a nonrandomized comparison of treatment groups rather than a randomized trial.

The registry reports enrollment of 204 and a study status of completed. The study start is recorded as 2014-01, and primary completion is recorded as 2019-11-15. The sponsor is AZ Sint-Jan AV. Further details about the setting, eligibility criteria, recruitment process, and how the retrospective cohort was assembled are not reported in the registry record.

The two approaches are described in broad terms. OFA involved dexmedetomidine loading doses and an infusion, and lidocaine loading and maintenance infusion. The entry also begins to describe a ketamine loading dose but is truncated, so the full OFA regimen is not reported in the registry record. OA is described as induction with sufentanil and continued anesthesia using additional boluses or a continuous remifentanil infusion. Other details needed to reproduce either regimen are not reported in the registry record.

The primary outcome was the number of participants with one or more complications, with assessment at one month postoperatively. The registry defines the complication outcome as counting minor and major complications and names CLAVIEN and DINDOO. Secondary outcomes were PONV, visual-analog-scale postoperative pain, morphine use, skin temperature, and length of hospital stay. Details of how these secondary measures were defined and analyzed are not reported in the registry record.

Because treatment choice was linked to clinician assignment and competence availability, the groups may differ in ways related to treatment selection or outcomes. The record does not report a randomization procedure, and it does not report whether statistical adjustment was used to address potential confounding. The posted information therefore supports describing the design as observational, not interpreting the groups as exchangeable by design.

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 Number of Patients With One or More Complications, measured over One month postoperative.

The primary endpoint is the number of participants with one or more complications during the one-month postoperative period. The registry describes the complications as minor and major and refers to CLAVIEN and DINDOO. In practical terms, this endpoint is a participant-level count: a participant is counted as having the endpoint if at least one qualifying complication is recorded. The detailed rules for qualifying events, including how multiple complications in one participant are handled, are not reported in the registry record.

A combined complication endpoint can capture a broad range of postoperative outcomes in one measure. It may be useful when the clinical concern includes several types or severities of complications rather than one narrowly defined event. However, a combined measure can conceal differences among its components. The total does not by itself show which complication types occurred, how severe they were, or whether the groups differed on particular components.

The endpoint is distinct from the serious and other adverse-event counts listed in the registry. Those counts should not be treated as the primary outcome unless the record explicitly establishes that they use the same definitions and participants; such a link is not reported in the registry record. The primary endpoint results by group, including the number of participants with complications, are not reported in the registry record. Consequently, neither the direction nor the magnitude of the primary comparison can be described from these registry entries.

General: a clear endpoint definition helps readers understand what is counted and when it is assessed. A time window matters because events outside it may not contribute to the outcome, and event-classification rules affect which observations are included. The one-month postoperative timeframe is reported, but further operational details are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what this registry record can show from what it cannot establish. The first is the distinction between a study design and a statistical analysis. The registry describes a retrospective observational cohort and says that anesthesia choice was made by the attending anesthesiologist according to competence availability. That describes how the comparison groups arose. The specific analysis used to compare them is not reported in the registry record.

What does an observational comparison mean?

General: random assignment aims to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline characteristics. In an observational cohort, treatment selection can be related to patient characteristics, clinician decisions, or the circumstances of care. Those same factors may also be related to outcomes. This creates the possibility of confounding: an observed group difference may reflect treatment, differences between the groups, or both.

The registry names clinician assignment and competence availability as the basis for treatment selection. It does not report whether group characteristics were compared, whether adjustment was performed, or which variables were considered. An adjusted analysis can address measured confounders only to the extent that those variables are recorded and the analytic approach is suitable. It cannot automatically remove bias from factors that were not measured or were handled inadequately. The record does not provide enough information to assess these issues.

How should participant counts be read?

The primary endpoint is a binary participant-level outcome: having one or more complications within the stated postoperative period. A participant either meets that endpoint definition or does not, according to the event rules. The registry identifies the endpoint as counting participants, rather than reporting the total number of separate complications. The rules for adjudicating events and handling more than one complication per participant are not reported in the registry record.

The adverse-event entries also give participants at risk and participants affected for serious and other events. These are descriptive counts. They do not alone give a complete comparison of clinical outcomes, and they should not be substituted for the primary endpoint. The record does not report how adverse events were defined, whether event ascertainment was equivalent between groups, or whether the serious and other categories overlap with the primary complication definition.

What would uncertainty measures add?

General: an effect estimate describes the size and direction of a comparison, while a confidence interval describes its statistical uncertainty under the chosen model and assumptions. A p-value addresses compatibility of the data with a specified null hypothesis under the analysis assumptions; it is not a measure of clinical importance and does not establish causality. The registry entries do not include a primary comparison estimate, confidence interval, or p-value. The statistical significance and precision of the primary outcome therefore cannot be assessed from the registry record.

General: binary outcomes can be analyzed using several approaches, including comparisons of proportions or regression models. The appropriate choice depends on the study question, data structure, and adjustment strategy. No specific model or test is reported in the registry record, so none should be attributed to this study. Likewise, no claim about multiplicity adjustment, interim analysis, or a prespecified analysis plan can be made from the record.

Why does sample-size planning need careful interpretation?

The registry entries describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The illustration uses a stated fraction of the observed effect to define the effect to detect, and participant counts are expressed per arm for non-time-to-event outcomes. These are planning assumptions, not evidence that the study was designed with those assumptions, and not a measure of observed power. The trial’s own sample-size justification is not reported in the registry record.

General: sample-size calculations depend on assumptions about the effect to detect, outcome variability or event frequency, allocation, and the chosen statistical procedure. A planning illustration can show how required sample size changes under its assumptions, but it cannot establish that an observed result is reliable or that the study had a particular probability of detecting an effect after data collection. No additional planning results or assumptions beyond those described are reported in the registry record.

What is missing for a reproducible analysis?

The registry does not report the primary outcome values by group, the statistical model, covariate handling, missing-data methods, or analysis populations. It also does not report outcome definitions beyond the brief description, an analysis plan, or whether outcome assessment was blinded. These omissions limit reproducibility and make it impossible to evaluate whether the reported adverse-event counts answer the primary question. General: clear reporting of estimands, endpoint definitions, analysis populations, missing-data handling, and uncertainty helps readers judge how well an analysis addresses its stated question.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Opioid Free Anesthesia (OFA)", "Opioid Anesthesia (OA)")
n      <- c(55, 149)
events <- c(10, 85)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Opioid Free Anesthesia (OFA)  55  10  18.2  9.1  30.9  10.2  30.3  10.2  30.4
ARM  Opioid Anesthesia (OA)  149  85  57.0  48.7  65.1  49.0  64.7  49.0  64.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and several secondary outcomes: PONV, postoperative pain measured by a visual analog scale, morphine use, skin temperature, and length of hospital stay. It reports six outcome measures and five analyses. The specific analyses associated with those counts, and whether the listed outcomes were all analyzed as planned, are not reported in the registry record.

Multiplicity arises when several outcomes, comparisons, time points, or analyses are examined. General: examining many statistical tests can increase the chance that at least one result appears notable by chance. Researchers may address this through a prespecified hierarchy, adjustment, or careful interpretation of secondary outcomes. The registry record does not report whether a multiplicity strategy was specified or used. No conclusions about adjustment should be inferred from the number of listed outcomes alone.

Missing-data methods are also not reported in the registry record. The record does not state whether all enrolled participants contributed to each outcome, how missing observations were handled, or whether any analysis used imputation or another method. It does not identify analysis populations, such as whether analyses included all eligible participants or only those with outcome data. The enrollment figure does not resolve these questions.

General: missing observations can affect an estimate when the availability of outcome data is related to treatment assignment or outcome status. The implications depend on how much data are missing, why they are missing, and the method used to handle them. Those details are unavailable. The registry also does not report interim analyses or stopping rules. Without the analysis plan and missing-data accounting, the relationship between the listed outcomes, the analyzed participants, and the intended comparisons cannot be fully evaluated.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: revision surgery (6.0%).

The registry reports serious and other adverse-event counts separately for the OFA and OA groups. For serious events, it lists 1 affected participant among 55 at risk in OFA and 9 among 149 at risk in OA. For other events, it lists 9 affected participants among 55 at risk in OFA and 67 among 149 at risk in OA. Deaths are listed as 0 in each group. These are counts from the posted record and do not, by themselves, explain the event definitions or establish why the groups differ.

The registry names revision surgery as the leading serious adverse-event term and gives 6.0%. The event count, the precise denominator for this term, and its relationship to the overall serious-event counts are not reported in the registry record. The term should not be interpreted as if it represented every complication, nor can it be assumed to define the primary endpoint.

General: safety counts are most informative when event definitions, follow-up completeness, ascertainment procedures, and denominators are clear and comparable between groups. A count is descriptive; it does not adjust for differences in patient characteristics or establish a causal effect. The registry record does not report a statistical comparison or uncertainty interval for these adverse-event figures. They should therefore be read as recorded events in the two observed groups, not as a definitive estimate of comparative safety.

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

The record describes a clinically relevant observational comparison in DIEPflap surgery. Its primary question concerns participants with at least one minor or major complication at one month postoperatively, and its secondary outcomes include PONV, pain, morphine use, skin temperature, and hospital stay. The registry also reports adverse-event counts for the two anesthesia groups.

What the record does not report is essential to judging the primary comparison: the number of participants meeting the primary endpoint in each group, an effect estimate, and an uncertainty interval. Without those results, the direction, magnitude, and precision of the primary outcome comparison cannot be characterized. The secondary outcome results and their statistical analyses are also not reported in the registry record.

The safety counts provide descriptive information, including the numbers at risk and affected participants, and the record lists no deaths in either group. They do not establish that one anesthesia approach caused more or fewer events. The study was not randomized, and treatment selection was determined by the attending anesthesiologist according to competence availability. Differences between groups could therefore reflect factors related to treatment selection as well as any association with anesthesia approach.

General: an association observed in an observational cohort is not equivalent to a causal treatment effect. A causal interpretation requires a credible account of confounding, outcome measurement, missing data, and the analysis used. Those details are not reported in the registry record. Even a statistically precise estimate, if one were available, would not by itself eliminate design-related bias.

Accordingly, the registry supports describing the study question, design, endpoint definition, and selected adverse-event counts. It does not support a conclusion that OFA or OA changed the primary complication outcome, nor a conclusion about comparative effects on the listed secondary outcomes. The absence of reported primary results is distinct from evidence that the groups had the same outcomes.

14. Why This Trial Matters Statistically

This study matters statistically because its question concerns a broad postoperative complication outcome in a setting where the registry describes potential links between anesthesia, flap perfusion, and PONV. The primary endpoint counts participants with one or more complications, while the listed secondary outcomes span symptoms, medication use, skin temperature, and hospital stay. That range makes clear why precise definitions and a transparent analysis plan matter.

The design is equally important. Treatment was chosen by the attending anesthesiologist according to the availability of competence rather than by randomization. This means that statistical interpretation must account for the possibility that the groups differed before treatment. A group comparison is not automatically a treatment effect, and an analysis can address only the confounding factors that were measured and appropriately handled. Whether adjustment was performed is not reported in the registry record.

The available safety counts illustrate another reporting issue: event totals need clear definitions and a clear relationship to the primary endpoint. Serious and other adverse events are not necessarily interchangeable with a composite of minor and major complications. Without definitions and outcome-level results, readers cannot determine whether the safety counts represent the same events or answer the central study question.

General: good clinical-trial reporting makes the design, outcome definitions, analysis populations, missing-data handling, effect estimates, and uncertainty visible. These details allow readers to assess both statistical precision and the risk of bias. Here, the registry record identifies the intended outcomes and reports some adverse-event figures, but does not report the primary outcome results or key analytic details. That gap limits what can be learned from the comparison, regardless of the clinical interest of the question.

15. 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 main limitation for interpreting this record is that the primary outcome results are not reported in the registry record. Although the endpoint is defined as participants with one or more complications within one month postoperatively, no group-specific primary counts or comparative estimates are available in the registry record. The record likewise does not report results for the listed secondary outcomes.

The retrospective observational design limits causal interpretation. Anesthesia was selected by the attending anesthesiologist according to availability of competence, not through random assignment. The registry does not report baseline characteristics, group comparability, or whether adjustment for confounding was performed. It is therefore not possible to assess the extent to which differences in patient or care characteristics could explain any observed group differences.

Outcome and analysis details are limited. The record gives a brief description of minor and major complications and names CLAVIEN and DINDOO, but does not report complete event definitions or adjudication procedures. It does not report the statistical model, analysis populations, missing-data handling, multiplicity strategy, or interim analyses. The truncated OFA description also leaves the full intervention regimen unclear.

The adverse-event information is descriptive and does not include reported uncertainty intervals or statistical comparisons. The meaning and denominator of the 6.0% revision-surgery term are not fully specified. The relation between those adverse-event categories and the primary complication endpoint is not reported in the registry record.

Finally, the record’s planning illustration is not the trial’s own sample-size justification and cannot be treated as observed power. The registry does not report the study’s design justification or a complete statistical plan. These limitations restrict assessment of both the strength of the comparison and its reproducibility.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Impact of Opioid Free Anesthesia on Outcome After DIEPflap Surgery — NCT03202134.
• Registry record last updated 2021-02-23; status last verified 2021-02.
• Results first posted 2021-02-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes NCT03202134, titled “Impact of Opioid Free Anesthesia on Outcome After DIEPflap Surgery,” as a retrospective observational cohort study. The official title specifies complications after DIEPflap surgery. The study is listed as completed, with total enrollment of 204, a start recorded as 2014-01, and primary completion recorded as 2019-11-15. AZ Sint-Jan AV is the sponsor.

The primary outcome is the number of participants with one or more minor or major complications at one month postoperatively. Secondary outcomes include PONV, postoperative pain, morphine use, skin temperature, and length of hospital stay. The registry reports adverse-event counts for OFA and OA, but does not report the primary outcome results, secondary outcome results, or the statistical analysis needed to estimate comparative effects.

Treatment was not randomized; the attending anesthesiologist selected the approach according to competence availability. This limits causal interpretation. The record supports a description of the design, intended outcomes, and posted adverse-event counts, but the primary comparison cannot be quantified from the registry record.