Intraoperative Driving Pressure-Guided High PEEP vs Standard Low PEEP for Postoperative Pulmonary Complications.
Writing and Steering Committees for the DESIGNATION–Investigators, Dorland G, Gama de Abreu M, Hemmes SNT, Hol L, Hollmann MW, van Meenen DMP, Nijbroek SGLH, Schultz MJ, Serpa Neto A, Vermeulen TD
- DOI
- 10.1001/jama.2025.23373
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
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How this rating was calculated
- IntegrityIntegrity concern−0.5★
- ReportingData & code availability partially met−0.25★
- CitationsUnresolved reference−0.25★
- No data or code availability links were detected to verify.
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
This is a well-conducted, well-reported multicenter randomized trial with rigorous design, clear ethics, and transparent reporting. The main weakness is the vague data sharing statement, and there are minor copyedit inconsistencies in Figure 1 and the abstract.
Both reviewers independently scored all eight dimensions and agreed on every status; no divergence to reconcile. The statistics verification recomputed only 1 reported test (consistent), so the broader statistical analysis is not fully machine-verified. The citation check flagged 1 reference not found in any registry.
Numerical inconsistencies
1 finding · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
Recomputed 1 test: 1 consistent, 0 inconsistent; 1 via agent-written checks.
- CONSISTENTreported p = .230 · recomputed p = .215Reviewers 1, 2Primary outcome p-value from absolute difference and 95% CI
“absolute difference, 2.5% [95% CI, −1.5% to 6.4%]; P = .23”
Taken as given: The absolute difference is 0.025 (2.5%); The 95% CI is -0.015 to 0.064; The CI is two-sided at 95%; The p-value is two-sidedMethod: Recomputed p-value from the estimate and 95% CI using normal approximation.How we recomputed it: pCI(0.025, -0.015, 0.064, 0)
- lowinternal contradictionFigure 1 legend states 734 patients randomized to high PEEP and 734 to low PEEP, but the text and Table 1 state 718 and 717, respectively.
734 Randomized to undergo individualized high PEEP and recruitment maneuvers ... 734 Randomized to undergo standard low PEEP without recruitment maneuvers
Figure 1reviewer’s wording
Overstated conclusions
None foundConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
Checked — nothing surfaced.
7 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewers 1, 2Driving pressure-guided high PEEP did not reduce postoperative pulmonary complications compared with standard low PEEP.The primary outcome result directly supports this claim.Evidence: Primary outcome: 142/718 (19.8%) vs 125/717 (17.4%), absolute difference 2.5% (95% CI -1.5% to 6.4%), P = .23.
“the primary outcome occurred in 142 of 718 patients (19.8%) in the driving pressure–guided high PEEP group compared with 125 of 717 patients (17.4%) in the low PEEP group (absolute difference, 2.5% [95% CI, −1.5% to 6.4%]; P = .23)”
Abstract - supportedReviewer 1The high PEEP strategy was associated with increased hypotension and vasopressor use.Secondary outcomes show higher rates of hypotension and vasoactive agent use in the high PEEP group, with statistically significant differences.Evidence: Hypotension: 382 (54.0%) vs 317 (45.0%); use of vasoactive agents: 224 (32.0%) vs 130 (18.8%).
“The incidence of hypotension (382 [54.0%] vs 317 [45.0%]) and use of vasoactive agents (224 [32.0%] vs 130 [18.8%]) was higher in the high PEEP group”
Abstract - supportedReviewers 1, 2The incidence of intraoperative desaturation was higher in the low PEEP group.Secondary outcome data support this claim.Evidence: Desaturation: 6 (0.8%) vs 20 (2.8%).
“the incidence of intraoperative desaturation (6 [0.8%] vs 20 [2.8%]) was higher in the low PEEP group”
Abstract - supportedReviewer 1The intervention achieved its physiologic target of higher PEEP and lower driving pressure.Ventilation characteristics in Table 2 show higher PEEP and lower driving pressure in the high PEEP group.Evidence: Table 2: PEEP after first hour 10 (10-12) vs 5 (5-5); driving pressure after first hour 8 (7-10) vs 10 (8-12).
Intervention Protocol adherence was high and resulted in higher PEEP, peak pressure, plateau pressure, and SpO2, and a lower driving pressure in the high PEEP group compared with the low PEEP group
Resultsreviewer’s wording - supportedReviewer 1The findings are consistent with a 2025 trial evaluating individualized compliance-guided high PEEP as part of a perioperative bundle.The discussion cites the 2025 trial and notes consistency, which is a reasonable interpretation.Evidence: Discussion cites a 2025 randomized clinical trial.
Study findings are consistent with a 2025 randomized clinical trial that evaluated individualized compliance-guided high PEEP as part of a perioperative bundle aimed at reducing postoperative pulmonary complications.
Discussion ¶4reviewer’s wording - supportedReviewer 2Hypotension and vasopressor use were higher in the high PEEP group.Secondary outcome results support this claim.Evidence: Hypotension: 382 (54.0%) vs 317 (45.0%); vasoactive agents: 224 (32.0%) vs 130 (18.8%).
“The incidence of hypotension (382 [54.0%] vs 317 [45.0%]) and use of vasoactive agents (224 [32.0%] vs 130 [18.8%]) was higher in the high PEEP group”
Abstract - supportedReviewer 2The intervention achieved its physiologic target of lower driving pressure.Ventilation characteristics show lower driving pressure in the high PEEP group.Evidence: Driving pressure after first hour: 8 (7-10) vs 10 (8-12) cm H2O.
resulted in higher PEEP, peak pressure, plateau pressure, and SpO2, and a lower driving pressure in the high PEEP group compared with the low PEEP group
Resultsreviewer’s wording
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
1 finding · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
The introduction cites prior trials on lung-protective ventilation, PEEP, and driving pressure, and notes limitations of previous individualized PEEP trials (complex designs, bundled interventions). The rationale linking driving pressure to outcomes and the need for a trial isolating intraoperative PEEP titration is clearly stated.
“Driving pressure, a marker of lung strain, is independently associated with postoperative pulmonary complications.”
Randomization used a computer-generated allocation sequence with permuted block sizes and stratification by site and BMI. Blinding of outcome assessors was implemented. A priori power analysis was provided. Inclusion/exclusion criteria were detailed. The analysis population (primary analysis population) and per-protocol analysis were defined, addressing missing data and dropouts.
The paper reports age, sex, weight, BMI, ARISCAT score, ASA status, functional status, coexisting disorders, smoking status, and procedure types in Table 1. Both sexes are included, so sex justification is not applicable. Species/strain and housing conditions are not applicable for a human trial.
“Female 360 (50.1) 390 (54.4)”
“Age, median (IQR), y 66.0 (57.0-73.0) 65.0 (57.0-73.0)”
“Coexisting disorders Diabetes 84 (11.7) 85 (11.9)”
“patients were a median (IQR) age of 66 (57-74) years”
“Diabetes 84 (11.7) 85 (11.9)”
The study was approved by the institutional review board of Amsterdam University Medical Centers, and written informed consent was obtained from all participants. The trial was registered and conducted per CONSORT guidelines.
“The study was approved by the institutional review board of Amsterdam University Medical Centers, Academic Medical Center location.”
“Written informed consent was obtained from all participants.”
“The trial was conducted and reported according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”
“The study was approved by the institutional review board of Amsterdam University Medical Centers, Academic Medical Center location.”
“Written informed consent was obtained from all participants.”
“The trial was conducted and reported according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”
The trial uses a non-pharmacological intervention (ventilation strategy) with detailed protocol descriptions. No drugs, biologics, or devices are used as investigational products. Statistical software (R version 4.3.3) is identified. Other resource criteria are not applicable.
“Analyses were performed using R version 4.3.3 (R Foundation).”
“Analyses were performed using R version 4.3.3 (R Foundation).”
The primary analysis used a mixed-effect generalized linear model with binomial distribution and identity link, with site as random effect. P-values are reported as exact values (e.g., P = .23). Effect sizes are reported as absolute differences with 95% CIs. Statistical software is identified. Data presentation includes per-group n and appropriate figures. Mathematical plausibility checks were not applicable due to large N and continuous outcomes.
“The effect of high PEEP compared with low PEEP on the incidence of postoperative pulmonary complications was assessed using a mixed-effect generalized linear model with binomial distribution and identity link.”
“absolute difference, 2.5% [95% CI, −1.5% to 6.4%]; P = .23”
“absolute difference, 2.5% [95% CI, −1.5% to 6.4%]”
“The effect of high PEEP compared with low PEEP on the incidence of postoperative pulmonary complications was assessed using a mixed-effect generalized linear model with binomial distribution and identity link.”
“absolute difference, 2.5% [95% CI, −1.5% to 6.4%]”
The paper mentions a Data Sharing Statement in Supplement 6, but the specific content is not provided in the text. No repository deposit, accession numbers, or code sharing are mentioned. For a clinical trial, managed access is acceptable, but the statement is not detailed in the main text.
“Data Sharing Statement: See Supplement 6.”
“Data Sharing Statement: See Supplement 6.”
The trial is registered (NCT03884543). Methods are detailed. CONSORT guidelines are followed. All outcomes are reported, including non-significant ones. Limitations are explicitly discussed. Funding and conflicts of interest are disclosed.
“TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03884543”
“Funding/Support: This study was supported by a research grant from ZonMw (852001922).”
“TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03884543”
“The trial was conducted and reported according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”
Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.
Broken references and links
1 finding · worst lowReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
- References not resolvable to a published paperRecomputed
Checked 26 references by DOI: 25 verified — 1 DOI unresolved.
- UNRESOLVED10.3969/j.issn.1672-7347.2013.01.015Effect of lung protection mechanical ventilation on respiratory function in the elderly undergoing spinal fusion (in Chinese)Cited DOI does not resolve to any Crossref record.
Copyediting
4 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 4 minor suggestions below.
4 copyedit issues flagged: mostly typo, consistency.
- MINORtypoFigure 1 legend“734 Randomized to undergo individualized high PEEP and recruitment maneuvers”→ Should be 718 to match the text and Table 1.The figure legend appears to have a typo in the number of patients randomized to high PEEP.
- MINORconsistencyFigure 1“734 Randomized to undergo standard low PEEP without recruitment maneuvers”→ Should be 717 to match the text and Table 1.The figure legend appears to have a typo in the number of patients randomized to low PEEP.
- MINORtypoFigure 1 legend“ARISCAT a score <26”→ Remove the stray 'a' or format as superscript.The 'a' appears to be a footnote marker that is misplaced.
- MINORconsistencyAbstract vs Results“Among 1468 adults, 1435 (98%) completed the trial”→ Ensure the denominator is consistently stated as 'randomized' or 'enrolled'.The abstract says 'completed the trial' but the results section says '1435 were included in primary analysis'.
The published work is methodologically robust and transparent; an informed reader should weigh the minor reporting gaps (vague data sharing statement, Figure 1 number inconsistencies) and the one unresolved reference. No erratum is warranted for the rigor dimensions, but the Figure 1 discrepancies should be corrected.
- 1.HIGHdata codeIn the Data Sharing Statement (Article Information / Supplement 6), specify the data access mechanism (e.g., data access committee, conditions, timeline, contact) instead of only referencing Supplement 6.A vague data sharing statement is a reporting gap that limits reproducibility and is the only non-pass dimension.
- 2.HIGHdata codeDeposit the statistical analysis code in a public repository (e.g., Zenodo) with a DOI and include the link in the Data Sharing Statement.Providing code enhances reproducibility and addresses the 'code_sharing' not_reported gap.
- 3.HIGHotherVerify or correct the reference 'Effect of lung protection mechanical ventilation on respiratory function in the elderly undergoing spinal fusion (in Chinese)' (DOI 10.3969/j.issn.1672-7347.2013.01.015), which was not found in any registry.An unresolved reference may be fabricated or contain an incorrect DOI; it must be verified or replaced.
- 4.MEDIUMcopyeditIn Figure 1 legend, correct the number randomized to high PEEP from 734 to 718 to match the text and Table 1.The internal contradiction between the figure and text undermines data integrity and reader trust.
- 5.MEDIUMcopyeditIn Figure 1 legend, correct the number randomized to low PEEP from 734 to 717 to match the text and Table 1.Same as above; the figure must be consistent with the reported numbers.
- 6.MEDIUMcopyeditIn Figure 1 legend, remove the stray 'a' in 'ARISCAT a score <26' or format it as a proper footnote marker.This is a typographical error that could confuse readers.
- 7.MEDIUMcopyeditIn the Abstract and Results, ensure the denominator for the primary analysis is consistently stated (e.g., 'randomized' vs 'included in primary analysis').Inconsistent denominators between abstract and results can mislead readers about the analysis population.
- 8.LOWdata codeIf any non-identifiable aggregate data are available, deposit them in a public repository and provide an accession number in the Data Sharing Statement.This would strengthen the data availability statement beyond a mere reference to a supplement.
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- Statistics · Integrity · Claimseach serious problem−1★
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- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
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