Proactive vs Reactive Treatment of Hypotension During Surgery: The PRETREAT Randomized Clinical Trial.
Kant M, van Klei WA, Hollmann MW, de Klerk ES, Otterspoor LC, Besselink MG, Kappen TH, Veelo DP, PRETREAT study group
- DOI
- 10.1001/jama.2025.18007
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/a126e71c-92c8-49ce-86a1-baf1741d5503 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern−0.5★
- ReportingData & code availability partially met−0.25★
- Statistics were not checked: no recomputable values were found in this text — no test statistic reported with its degrees of freedom, no effect estimate printed with both a 95% CI and a p-value, and no percentage printed with both its count and its denominator.
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 8 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
- 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 and well-reported randomized clinical trial with rigorous design, clear ethics approval, and transparent reporting. The main weakness is the vague data availability statement, which lacks a concrete repository or access mechanism.
Both reviewers independently scored all eight dimensions and agreed on all statuses. The study type is interventional (RCT). Non-applicable sub-criteria (e.g., animal housing, cell lines) were excluded. The statistics verification component checked 0 tests, so no statistical errors were found, but this does not confirm the correctness of unreported analyses.
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
- lowinternal contradictionThe abstract states the trial was stopped after 3247 patients, but the results section states 3522 were randomized. This discrepancy is explained by the fact that the abstract reports the number at the time of the futility analysis, while the results report the final number after continued recruitment during the analysis period.
The trial was stopped early for futility after 3247 of 5000 planned patients... were enrolled. ... bringing the total enrollment to 3522 of the planned 5000.
Abstractreviewer’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.
5 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewers 1, 2Proactive blood pressure management did not improve functional disability at 6 months.The primary outcome analysis shows a mean difference of -0.5 with a 95% CrI crossing zero, supporting the null result.Evidence: Primary outcome: mean difference -0.5 (95% CrI -1.9 to 0.9)
“At 6 months, mean (SD) WHODAS scores were 17.7 (20.1) in the proactive group and 18.2 (20.5) in the standard group (mean difference, –0.5; 95% credible interval, –1.9 to 0.9).”
Abstract - supportedReviewer 1The intervention increased vasopressor initiation according to guidelines.The odds ratio of 3.73 with 95% CrI 3.21-4.31 clearly shows increased vasopressor use.Evidence: Secondary outcome: vasopressor initiation OR 3.73 (95% CrI 3.21-4.31)
Compared with the control group, vasopressors were administered more frequently according to the clinical guidelines in the intervention group (odds ratio [OR], 3.73; 95% CrI, 3.21-4.31)
Resultsreviewer’s wording - supportedReviewers 1, 2The intervention reduced intraoperative hypotension.The area under the threshold for MAP <65 mm Hg was significantly reduced, with a 48.4% relative reduction.Evidence: Area under the threshold: 28.5 vs 70.6 mm Hg × minutes, relative reduction -48.4%
The area under the threshold for MAP less than 65 mm Hg was 28.5 mm Hg × minutes in the intervention group vs 70.6 mm Hg × minutes in the control group, corresponding to a 48.4% relative reduction (95% CrI, –55.5% to –41.1%).
Resultsreviewer’s wording - supportedReviewers 1, 2There were no significant differences in any of the 23 secondary outcomes.All secondary outcomes show credible intervals crossing the null, supporting the claim.Evidence: Table 3 lists all secondary outcomes with CrIs crossing zero or including 1 for ORs.
“There were no significant differences in any of the 23 secondary outcomes.”
Results - supportedReviewer 1The trial was stopped early for futility.The DSMB recommended early termination based on futility criteria, and the trial was stopped.Evidence: Interim analysis showed posterior probability of MCID <5%.
“Based on these results the DSMB concluded there was no harm, but recommended early termination of the trial for futility, so the trial was stopped.”
Methods
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 studies on intraoperative hypotension and notes their limitations (small sample sizes, failure to achieve blood pressure differences). The rationale for risk-stratified MAP targets is clearly linked to the hypothesis. The paper does not explicitly describe how limitations of prior research are addressed beyond the design features mentioned in the discussion.
Randomization used concealed computer-generated permuted blocks, stratified by risk. Blinding was partial: patients and outcome assessors were blinded, but treating anesthesiologists were not (unavoidable). Power analysis was performed with a prespecified MCID and sample size. Inclusion/exclusion criteria were clearly defined. Outlier handling is addressed through the analysis population and missing data imputation. Controls are appropriate (usual care). Independent replication is not applicable for a single pivotal trial.
“patients completed outcome questionnaires digitally, ensuring that outcome assessment remained blinded to treatment allocation.”
Sex is reported for both groups. Age and health status (ASA classification, comorbidities) are reported. Demographics include age, sex, and comorbidities. Species/strain and housing are not applicable. Sex justification is not applicable because both sexes were enrolled.
“Sex, No. (%) Men 764 (47.2) 745 (45.7) Women 854 (52.8) 884 (54.3)”
“Age, median (IQR), y 59 (44-69) 59 (45-69)”
“Preexisting conditions, No. (%) a Hypertension 470 (29.0) 480 (29.5)”
“Age, median (IQR), y 59 (44-69) 59 (45-69) Sex, No. (%) Men 764 (47.2) 745 (45.7) Women 854 (52.8) 884 (54.3)”
The trial was approved by a named ethics committee (Medical Ethics Committee of the University Medical Center Utrecht, reference No. 20-749). Written informed consent was obtained from all participants. Regulatory compliance is implied through adherence to CONSORT and Dutch regulations, though not explicitly named.
“The trial protocol was approved by the Medical Ethics Committee of the University Medical Center Utrecht (reference No. 20-749) and has been published previously (Supplement 1).”
“The trial protocol was approved by the Medical Ethics Committee of the University Medical Center Utrecht (reference No. 20-749)”
The intervention is a clinical strategy, not a drug or device, but the MAP targets and vasopressor use are described. Software (Castor EDC, R, brms) is identified. No antibodies, cell lines, or organisms are used, so those are not applicable.
“Markov Chain Monte Carlo sampling was performed in R with the brms package (via Stan).”
“Markov Chain Monte Carlo sampling was performed in R with the brms package (via Stan).”
All tests are named (Bayesian linear/logistic regression). Assumptions are handled through Bayesian modeling with weakly informative priors. Exact p-values are not reported; instead, credible intervals and posterior probabilities are used, which is appropriate for Bayesian analysis. Effect sizes are reported with credible intervals. Software is identified. Data presentation includes per-group n and dispersion. Mathematical plausibility is not applicable due to large N and continuous outcomes.
“All analyses were conducted using a bayesian framework, which allowed us to estimate credible treatment effects given the observed data.”
“The between-group difference was –0.5% (95% CrI, –1.9% to 0.9%)”
“Markov Chain Monte Carlo sampling was performed in R with the brms package (via Stan).”
“All analyses were conducted using a bayesian framework, which allowed us to estimate credible treatment effects given the observed data.”
“The between-group difference was –0.5% (95% CrI, –1.9% to 0.9%)”
The paper states 'Data Sharing Statement: See Supplement 4.' This is vague and does not specify a concrete access route. No repository deposit or accession numbers are provided. Code sharing is not mentioned.
“Data Sharing Statement: See Supplement 4.”
“Data Sharing Statement: See Supplement 4.”
The trial is registered (NL-OMON55117). CONSORT guidelines are referenced. All prespecified outcomes are reported, including negative results. Limitations are discussed in detail. Conclusions are proportional to the evidence. Funding and conflicts of interest are disclosed.
“TRIAL REGISTRATION Overview of Medical Research in the Netherlands (CCMO): NL-OMON55117”
“The trial was registered with the Overview of Medical Research in the Netherlands registry (NL-OMON55117, first registration March 3, 2021).”
Registration stated in text, but no registry ID was detected. Reporting guideline cited: CONSORT.
Broken references and links
None found · partly checkedReferences 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.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Checked 30 references by DOI: 28 verified — 2 no DOI (shown, not verified).
- NO DOIThe effect of proactive versus reactive treatment of hypotension on postoperative disability and outcome in surgical patients under anesthesia (PRETREAT): an adaptive multicenter randomized controlled trialNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOICastor electronic data captureNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
Copyediting
3 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 3 minor suggestions below.
3 copyedit issues flagged: mostly consistency, typo.
- MINORtypoAbstract, Results“mean atrial pressure”→ mean arterial pressureTypo in the Key Points section.
- MINORconsistencyResults, Primary Outcome“–0.5% (95% CrI, –1.9% to 0.9%)”→ –0.5 (95% CrI, –1.9 to 0.9)Percentage sign may be misleading; the outcome is a score difference, not a percentage.
- MINORconsistencyResults, Trial Participants“Of the 3247 randomized patients who had received the allocated intervention”→ Of the 3247 patients who received the allocated interventionClarify that these are not all randomized patients.
The published work is robust and well-reported. An informed reader should weigh the vague data availability statement as a minor limitation, but it does not undermine the validity of the findings. No erratum or correction appears necessary based on the rigor review.
- 1.HIGHdata codeReplace the vague 'Data Sharing Statement: See Supplement 4' with a concrete statement specifying a repository (e.g., Dryad, Zenodo) or a managed-access platform with conditions and timeframe.A vague data availability statement does not meet reproducibility standards and is a common reviewer concern.
- 2.HIGHdata codeDeposit de-identified individual patient data in a public repository with a DOI or accession number, if permitted by consent and ethics.Providing a direct data access route enhances reproducibility and reader trust.
- 3.HIGHdata codeShare custom analysis code in a public repository (e.g., GitHub) with a permanent identifier, and describe the workflow in sufficient detail.Code sharing is essential for reproducibility of Bayesian analyses.
- 4.MEDIUMethicsExplicitly state compliance with a recognized regulatory framework (e.g., Declaration of Helsinki, ICH-GCP) in the Methods section.While ethics approval is documented, explicit regulatory compliance strengthens the ethics reporting.
- 5.MEDIUMcopyeditFix the typo 'mean atrial pressure' to 'mean arterial pressure' in the Abstract/Key Points.Correct terminology is essential for clarity and accuracy.
- 6.MEDIUMcopyeditClarify the primary outcome presentation: change '–0.5% (95% CrI, –1.9% to 0.9%)' to '–0.5 (95% CrI, –1.9 to 0.9)' if the outcome is a score difference, not a percentage.Misleading units can confuse readers about the effect size.
- 7.MEDIUMcopyeditClarify the participant flow statement: change 'Of the 3247 randomized patients who had received the allocated intervention' to 'Of the 3247 patients who received the allocated intervention'.The original phrasing is ambiguous about whether all randomized patients are included.
- 8.LOWreportingClarify the discrepancy between the abstract (3247 patients) and results (3522 randomized) by explicitly stating the timing of the futility analysis.The internal contradiction is explained but should be made explicit to avoid reader confusion.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.