Ventilation Strategy During General Anesthesia for Orthopedic Surgery: A Quality Improvement Project: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ventilation Strategy During General Anesthesia for Orthopedic Surgery: A Quality Improvement Project (NCT03657368), a non-randomized na study. The primary outcome is Time-weighted Average SaO2/FiO2 Ratio in the Postanesthesia Care Unit (PACU).

2. Clinical Question

3. Trial Design

This completed project is described as a quality-improvement study of ventilation strategies during general anesthesia for orthopedic surgery. The registry lists a factorial model and four arms formed by combining two tidal volume settings with two PEEP settings. The low and high tidal volumes are 6 ml/kg and 10 ml/kg predicted body weight, respectively; the low and high PEEP settings are 5 cm H2O and 8 cm H2O, respectively. The record does not describe whether or how the two factors were analyzed jointly, or whether an interaction between them was assessed.

Allocation is nonrandomized, and masking is listed as single. The registry record does not specify who was masked, how the ventilation strategy was selected for each patient, or what allocation procedures were used. As a result, the listed arms should not be interpreted as randomized groups. Differences in outcomes could be associated with the ventilation combinations, but the design alone cannot rule out differences in patient characteristics, clinical practice, or other factors across groups.

The sponsor is The Cleveland Clinic. The record gives a start date of 2018-09-03, a primary completion date of 2020-10-23, and a status of completed. Enrollment is listed as 2860. These are registry design and conduct details, not outcome findings. The registry record does not report the planned sample-size justification, detailed eligibility criteria, or a complete statistical analysis plan.

The primary endpoint is a PACU oxygenation measure. Listed secondary outcomes include a composite of serious postoperative pulmonary complications, ward oxygenation defined by a time-weighted average of the SaO2/FiO2 ratio, and postoperative hospital stay in days. The record lists six outcome measures and eight analyses, but does not provide a full account of the analyses associated with each measure.

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

Analysis population for the primary outcome, as defined in the registry: The mean difference was estimated from a linear mixed regression model with surgeries from same patient as repeated measures, after propensity score weighting.

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 Time-weighted Average SaO2/FiO2 Ratio in the Postanesthesia Care Unit (PACU), measured over After surgery until discharged from PACU or up to 90 minutes.

The primary endpoint is the time-weighted average SaO2/FiO2 ratio in the postanesthesia care unit (PACU). The timeframe is after surgery until discharge from the PACU or up to 90 minutes. The registry description defines the oxygenation measure using peripheral oxygen saturation divided by the fraction of inspired oxygen, written there as the SpO2/FiO2 ratio, and identifies it as a validated measure of acute lung injury. The title uses SaO2/FiO2 terminology, while the description uses SpO2/FiO2; the record does not explain this difference in notation.

A ratio that accounts for inspired oxygen can describe oxygenation in relation to the oxygen concentration being delivered, rather than relying on oxygen saturation alone. In general, a time-weighted average combines measurements over a specified observation period while accounting for the time represented by those measurements. The registry does not report the measurement schedule, weighting details, or handling of observations after PACU discharge.

The endpoint is a continuous measure, with the mean and standard deviation identified as the summary type and dispersion. The registry describes estimating a mean difference using a linear mixed regression model, with surgeries from the same patient treated as repeated measures and propensity score weighting applied. The actual mean difference, its uncertainty, and any inferential result are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry identifies its summary as a mean with standard deviation. A mean describes the central value of a quantitative measure; a standard deviation describes the spread of individual measurements around that mean. These summaries do not, on their own, show the uncertainty in a comparison between groups. A confidence interval, if reported, would indicate a range of values compatible with the data and the analysis assumptions. The registry record does not report the primary comparison estimate or its confidence interval.

Why use a linear mixed regression model?

The primary population description says that the mean difference was estimated with a linear mixed regression model and that surgeries from the same patient were treated as repeated measures. In general, repeated measurements from one person may be related to one another. A mixed model can account for this within-person structure rather than treating every surgery as wholly independent. This matters because ignoring correlation can affect the estimated uncertainty of a comparison. The registry does not state the model’s fixed or random effects, its covariates, or the specific method used to calculate uncertainty.

The record gives enrollment as 2860, but this is not a reported count of observations contributing to the primary endpoint. Nor does the record describe how many patients had repeated surgeries or whether every enrolled patient contributed a PACU oxygenation measurement. The number analyzed for the primary endpoint and the approach to observations that were unavailable are not reported in the registry record.

What does propensity score weighting do?

In general, a propensity score represents the estimated likelihood of receiving a particular treatment or strategy based on observed characteristics. Weighting based on propensity scores can be used to make groups more comparable on characteristics included in that model. This is an adjustment for measured information, not a substitute for randomization. It cannot balance factors that were not measured or not included, and its performance depends on the model and the data. The registry states that propensity score weighting was used, but does not report the variables used to estimate the scores, the weighting procedure, balance after weighting, or any sensitivity analyses.

Because allocation was nonrandomized, residual confounding remains a concern even when propensity score weighting is used. In general, balance diagnostics help readers assess whether measured characteristics became more similar after weighting. No such diagnostics are reported in the registry record. It is also not reported whether weights were stabilized, trimmed, or otherwise modified, so no claim about those details is warranted.

How should the factorial structure be understood?

The four strategies arise from crossing the listed low and high settings for tidal volume and PEEP. In general, a factorial design can be used to study the contributions of more than one intervention factor and whether the factors may interact. Here, however, the registry only identifies the model as factorial and lists the combinations. It does not report whether the statistical analysis estimated separate main effects, a joint effect, or an interaction between tidal volume and PEEP. The absence of that information means the factorial label should not be treated as evidence that a particular factorial contrast was estimated.

The statistical method described for the primary outcome is a mean-difference analysis. The record does not report the precise contrasts, reference group, covariate adjustment beyond propensity score weighting, or whether the estimates were adjusted for both intervention factors. These details are necessary to interpret a numerical estimate, but no numerical estimate is reported.

What do planning illustrations represent?

Any sample-size illustrations associated with this analysis are planning exercises, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They use a chosen fraction of the observed effect as the effect to detect. For time-to-event outcomes, the stated convention is to report the total number of events; for other outcomes, it is participants per arm. These assumptions describe how a planning illustration is constructed, not the original project’s design or a result from the study.

The registry record does not report the project’s own sample-size justification. It also does not report the observed primary effect needed to interpret an illustration based on a fraction of that effect. A planning sample size is not evidence that the study had a particular probability of detecting an effect, and it should not be described as observed power.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("TV = 6 ml/kg", "TV = 10 ml/kg", "PEEP = 5cmH2O", "PEEP = 8cmH2O")
n   <- c(1362, 1498, 1526, 1334)
m   <- c(355, 350, 353, 352)
sp  <- c(46, 47, 46, 47)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  TV = 6 ml/kg  1362  355.000  46.000  352.555  357.445
CARM  TV = 10 ml/kg  1498  350.000  47.000  347.618  352.382
CARM  PEEP = 5cmH2O  1526  353.000  46.000  350.690  355.310
CARM  PEEP = 8cmH2O  1334  352.000  47.000  349.476  354.524

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and eight analyses. The named primary outcome is the time-weighted average SaO2/FiO2 ratio in the PACU. Listed secondary outcomes include a composite of serious postoperative pulmonary complications, ward oxygenation defined as a time-weighted average of the SaO2/FiO2 ratio, and length of postoperative hospital stay in days. The record does not explain the remaining outcome measures or map each analysis to a specific outcome and comparison.

When a study examines multiple outcomes or comparisons, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for multiplicity. In general, prespecified outcome hierarchy and adjustment procedures help readers understand how multiple tests were handled. The registry record does not report whether any multiplicity adjustment was used, which comparisons were prespecified, or whether analyses were exploratory. The presence of a named primary endpoint does not by itself establish how other analyses were treated.

Missing-data handling is not reported in the registry record. In general, missing outcome measurements can affect an estimate if the reasons for missingness are related to patient characteristics or outcomes. Readers would need information on the amount and pattern of missingness, any imputation or other handling strategy, and the analysis population to evaluate this issue. The record does not specify whether the primary analysis included all enrolled patients, only patients with available endpoint measurements, or another defined population.

The primary population description does state that surgeries from the same patient were treated as repeated measures and that propensity score weighting was applied. It does not provide the analysis sample, the number of observations included, or details of exclusions. The planned statistical analysis, interim analyses, and complete approach to defining analysis populations are not reported in the registry record.

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 0% reporting threshold.

The registry lists serious adverse events, other adverse events, and deaths for each of the four ventilation combinations. In each group, the recorded number affected is 0 for serious adverse events, 0 for other adverse events, and 0 for deaths. The numbers listed at risk are 727 for low tidal volume and low PEEP, 635 for high tidal volume and low PEEP, 799 for low tidal volume and high PEEP, and 699 for high tidal volume and high PEEP.

These are the registry’s recorded counts; they should not be interpreted as proof that no adverse events occurred outside the reporting captured by the record. The record does not provide serious adverse event terms, and no serious adverse event terms are listed. It does not describe the event-collection procedures, reporting completeness, or whether the at-risk counts correspond to every safety outcome’s follow-up population.

The allocation was nonrandomized, and the registry does not report comparative safety estimates or uncertainty. The recorded zero counts therefore do not establish equivalence among the strategies or quantify differences in risk. They describe what was entered in the registry’s adverse-event fields, not a definitive comparison of safety.

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

This record defines a clinically focused comparison: ventilation during general anesthesia for elective orthopedic surgery, with tidal volume and PEEP set at the listed low or high levels. It also identifies a primary oxygenation measure in the PACU and describes an analysis using a linear mixed regression model, repeated measures for surgeries from the same patient, and propensity score weighting. These details explain what the project set out to examine and how its primary mean difference was described as being estimated.

The registry record does not report the primary outcome result. Without a reported group estimate or comparison estimate, there is no basis to state which combination had a higher or lower PACU oxygenation ratio, how large any difference was, or how precise it was. The listed goal of determining an optimal strategy is an objective, not a finding. The secondary outcome results are also not reported in the record.

Even if an outcome estimate were available, the nonrandomized allocation would need to be considered. In general, statistical adjustment can reduce bias from measured differences when the adjustment model is appropriate, but it cannot guarantee control of unmeasured differences. The registry reports propensity score weighting without the variables or diagnostics needed to assess how well it addressed measured imbalance.

The zero adverse-event counts are registry entries and should be read within that limited scope. They do not demonstrate that events are impossible, establish equal safety across strategies, or replace comparative estimates with uncertainty. Likewise, enrollment and study completion are not evidence of a particular clinical effect.

The appropriate interpretation is therefore bounded: the registry describes a completed nonrandomized quality-improvement project, its four ventilation combinations, its primary outcome definition, and part of its statistical approach. It does not report the numerical outcome findings needed to judge the direction, magnitude, or precision of the primary comparison.

14. Why This Trial Matters Statistically

This project raises a useful statistical question because it combines two ventilation settings rather than comparing only one intervention against a single control. The four combinations make it important to distinguish comparisons of the individual factors from comparisons of complete strategies. In general, a factorial structure can support questions about both factors and their possible interaction, but the registry record does not state which factorial contrasts were estimated. A clear analysis specification is necessary to connect the design to the clinical question.

The nonrandomized allocation also makes the distinction between association and causal interpretation especially important. Propensity score weighting is reported, but its value depends on what characteristics were measured and modeled, whether the weighted groups achieved balance, and whether important confounding remained. These details are not reported in the registry record. Readers therefore cannot assess from this record alone how much the adjustment supports a causal interpretation.

The outcome structure adds another consideration. The PACU endpoint is a time-weighted oxygenation ratio, and the registry also lists postoperative pulmonary complications, ward oxygenation, and hospital stay. Multiple outcomes and analyses call for transparent reporting of which comparisons were planned and how multiplicity was handled; those details are not reported. The record also does not describe missing-data methods or the population included in each analysis.

Finally, statistical interpretation depends on estimates and uncertainty, not only on the study objective or analytical method. The primary mean difference, its confidence interval, and its inferential result are not reported in the registry record. This limits assessment of both the observed pattern and its precision. The record remains informative about design, endpoint definition, and stated methods, while not supplying the outcome evidence needed to compare the strategies.

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 principal limitation for interpreting this record is that the primary outcome result is not reported. There is no group-specific PACU oxygenation summary, mean difference, confidence interval, or p-value. Secondary outcome findings are also not reported in the information. Accordingly, the registry record does not support a conclusion about the observed direction or magnitude of differences among strategies.

Nonrandomized allocation limits the extent to which group comparisons can be interpreted as causal. The record states that propensity score weighting was used, but does not identify the variables included, report balance diagnostics, or describe sensitivity analyses. It is therefore not possible to evaluate the quality of measured adjustment or the potential effect of unmeasured confounding from the registry record.

The record identifies a factorial model and four combinations, but does not explain the actual factorial contrasts, whether an interaction was evaluated, or the reference comparison. It also does not provide detailed model specifications, the analysis population, or information on missing outcome data. The six listed outcome measures and eight analyses are not fully mapped to analysis questions, and multiplicity procedures are not reported.

The primary endpoint description uses SaO2/FiO2 in its title and SpO2/FiO2 in its definition. The record does not clarify the difference in notation. Measurement schedules and the exact construction of the time-weighted average are also not reported. Finally, the zero adverse-event counts lack detail on event ascertainment and completeness. These limitations concern what the registry record documents; they do not establish that the study itself failed to address these issues in other materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ventilation Strategy During General Anesthesia for Orthopedic Surgery: A Quality Improvement Project — NCT03657368.
• Registry record last updated 2025-08-27; status last verified 2025-02.
• Results first posted 2025-08-27.
• 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 record describes a completed, nonrandomized, single-masked factorial quality-improvement project sponsored by The Cleveland Clinic. It lists enrollment of 2860, with a start date of 2018-09-03 and primary completion date of 2020-10-23. The study concerns ventilation during general anesthesia for orthopedic surgery and compares four combinations of tidal volume and PEEP.

The primary endpoint is the time-weighted average oxygenation ratio in the PACU, measured after surgery until discharge or up to 90 minutes. The stated analysis uses a linear mixed regression model, treats surgeries from the same patient as repeated measures, and applies propensity score weighting. The primary result, detailed model specifications, missing-data handling, and multiplicity procedures are not reported in the registry record. Adverse-event fields record zero affected for serious events, other events, and deaths in each arm.