Cardiac output-guided haemodynamic therapy for patients undergoing major gastrointestinal surgery: OPTIMISE II randomised clinical trial.
OPTIMISE II Trial Group
- DOI
- 10.1136/bmj-2024-080439
- Record issued
- 2026-08-16
- Engine
- 7.39.0
- Exported
- 2026-09-22
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/7dd2308a-731f-46a7-a31a-54a0b6d151e7 is authoritative.
How this rating was calculated
- StatisticsPrinted percentage does not match its own count (capped) ×3−0.25★
- ReportingData & code availability partially met−0.25★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 10 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.
- 01Printed percentage does not match its own count
92.6% does not match the reported count 1156/1251
“1156 (92.6)”
Table 2 - 02Printed percentage does not match its own count
80.5% does not match the reported count 1005/1251
“1005 (80.5)”
Table 2 - 03Printed percentage does not match its own count
73.1% does not match the reported count 908/1247
“908 (73.1)”
Table 2
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 multicentre randomised controlled trial. The main methodological strengths are the rigorous design, clear reporting of statistical methods, and comprehensive ethical approvals. The primary weakness is the vague data availability statement, which lacks a concrete access mechanism.
Both reviewers classified the study as interventional, and this was adopted. The evaluation covered all eight dimensions; several sub-criteria were not applicable (e.g., animal-related items) and were excluded. The reviewers agreed on all dimensions except for minor discrepancies in key resources (software identification) and reporting transparency (reporting guideline), which were resolved by adopting the more specific evidence.
Numerical inconsistencies
1 finding · worst mediumValues 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.
- Printed percentage does not match its own countRecomputed
Recomputed 6 tests: 6 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 5 via agent-written checks. 3 printed percentages that do not match their own count.
- PERCENT92.6% does not match the reported count 1156/1251
“1156 (92.6)”
Table 2 - PERCENT80.5% does not match the reported count 1005/1251
“1005 (80.5)”
Table 2 - PERCENT73.1% does not match the reported count 908/1247
“908 (73.1)”
Table 2
- CONSISTENTreported p = .810 · recomputed p = .771Recomputed adjusted odds ratio 1.03 (95% CI 0.84–1.25), reported p=0.81
“adjusted odds ratio 1.03 (95% confidence interval 0.84 to 1.25); P=0.81”
Taken as given: 0.84–1.25 is a two-sided 95% confidence interval for the adjusted odds ratio of 1.03, not a range, an IQR, or a different interval level; the adjusted odds ratio is a RATIO measure, so the interval is symmetric on the log scale; p=0.81 is the p for THIS estimate, not for another comparison in the same sentenceMethod: back the two-tailed p out of the log-scale CI width and compare it against the printed pHow we recomputed it: pCI(1.03, 0.84, 1.25, 1) - CONSISTENTreported p = .810 · recomputed p = .771Reviewers 1, 2Primary outcome: postoperative infection within 30 days, intervention vs usual care.
“In 2498 patients (mean age 74 (standard deviation 6) years, 57% women), the primary outcome occurred in 289/1247 (23.2%) intervention patients and 283/1247 (22.7%) usual care patients (adjusted odds ratio 1.03 (95% confidence interval 0.84 to 1.25); P=0.81).”
Taken as given: The odds ratio is 1.03.; The 95% confidence interval is 0.84 to 1.25.; The p-value is derived from this odds ratio and CI.Method: P-value calculated from reported odds ratio and 95% confidence interval.How we recomputed it: pCI(1.03, 0.84, 1.25, 1) - CONSISTENTreported p = .030 · recomputed p = .030Reviewer 1Safety outcome: acute cardiac events within 24 hours, intervention vs usual care.
“Acute cardiac events within 24 hours occurred in 38/1250 (3.0%) intervention patients and 21/1247 (1.7%) usual care patients (adjusted odds ratio 1.82 (1.06 to 3.13); P=0.03).”
Taken as given: The odds ratio is 1.82.; The 95% confidence interval is 1.06 to 3.13.; The p-value is derived from this odds ratio and CI.Method: P-value calculated from reported odds ratio and 95% confidence interval.How we recomputed it: pCI(1.82, 1.06, 3.13, 1) - CONSISTENTreported p = .710 · recomputed p = .724Reviewer 1Safety outcome: acute cardiac events within 30 days, intervention vs usual care.
“Acute cardiac events within 30 days occurred in 85/1249 (6.8%) intervention patients and 79/1247 (6.3%) usual care patients (adjusted odds ratio 1.06 (0.77 to 1.47); P=0.71).”
Taken as given: The odds ratio is 1.06.; The 95% confidence interval is 0.77 to 1.47.; The p-value is derived from this odds ratio and CI.Method: P-value calculated from reported odds ratio and 95% confidence interval.How we recomputed it: pCI(1.06, 0.77, 1.47, 1) - CONSISTENTreported p = .030 · recomputed p = .030Reviewer 2Acute cardiac event <24h odds ratio p-value
“adjusted odds ratio 1.82 (1.06 to 3.13); P=0.03”
Taken as given: The odds ratio is 1.82 with 95% CI 1.06 to 3.13.; The CI is two-sided at 95%.; The p-value is two-sided.Method: Recomputed p-value from the reported odds ratio and 95% CI using the normal approximation for the log odds ratio.How we recomputed it: pCI(1.82, 1.06, 3.13, 1) - CONSISTENTreported p = .710 · recomputed p = .724Reviewer 2Acute cardiac event <30d odds ratio p-value
“adjusted odds ratio 1.06 (0.77 to 1.47); P=0.71”
Taken as given: The odds ratio is 1.06 with 95% CI 0.77 to 1.47.; The CI is two-sided at 95%.; The p-value is two-sided.Method: Recomputed p-value from the reported odds ratio and 95% CI using the normal approximation for the log odds ratio.How we recomputed it: pCI(1.06, 0.77, 1.47, 1)
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.
6 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewer 1This clinical effectiveness trial in patients undergoing major elective gastrointestinal surgery did not provide evidence that cardiac output-guided intravenous fluid therapy with low dose inotrope infusion could reduce the incidence of postoperative infections.The primary outcome analysis showed no statistically significant difference in postoperative infection rates between the intervention and usual care groups (adjusted OR 1.03, 95% CI 0.84 to 1.25; P=0.81).Evidence: Results section, primary outcome analysis (adjusted odds ratio 1.03 (95% confidence interval 0.84 to 1.25); P=0.81).
“This clinical effectiveness trial in patients undergoing major elective gastrointestinal surgery did not provide evidence that cardiac output-guided intravenous fluid therapy with low dose inotrope infusion could reduce the incidence of postoperative infections.”
ConclusionFind in source - supportedReviewer 1The intervention was associated with an increased incidence of acute cardiac events within 24 hours, in particular tachyarrhythmias.The results show a statistically significant increase in acute cardiac events within 24 hours in the intervention group (adjusted OR 1.82, 95% CI 1.06 to 3.13; P=0.03), primarily due to arrhythmias.Evidence: Results section, safety outcome analysis (adjusted odds ratio 1.82 (1.06 to 3.13); P=0.03) and statement 'This difference was primarily due to an increased incidence of arrhythmias among intervention patients.'
“The intervention was associated with an increased incidence of acute cardiac events within 24 hours, in particular tachyarrhythmias.”
ConclusionFind in source - supportedReviewers 1, 2Based on these findings, the routine use of this treatment approach in unselected patients is not recommended.Given the lack of benefit for the primary outcome and the increased risk of early cardiac events, the conclusion that routine use is not recommended is directly supported by the trial's findings.Evidence: Overall findings of no reduction in infection and increased cardiac events.
“Based on these findings, the routine use of this treatment approach in unselected patients is not recommended.”
ConclusionFind in source - supportedReviewer 1Use of fixed, low dose inotrope infusions within such algorithms should be avoided owing to the risk of arrhythmias.The trial found an increased incidence of arrhythmias in the intervention group, which received inotrope infusions, directly supporting the recommendation to avoid their use.Evidence: Results showing increased arrhythmias in the intervention group and discussion linking this to dobutamine.
“Use of fixed, low dose inotrope infusions within such algorithms should be avoided owing to the risk of arrhythmias”
What this study addsFind in source - supportedReviewer 2The intervention did not reduce postoperative infections within 30 days.The primary outcome analysis shows no significant difference, with an adjusted odds ratio of 1.03 (95% CI 0.84 to 1.25; P=0.81), directly supporting the claim.Evidence: Primary outcome result: 289/1247 (23.2%) vs 283/1247 (22.7%), adjusted OR 1.03 (0.84-1.25), P=0.81.
“the primary outcome occurred in 289/1247 (23.2%) intervention patients and 283/1247 (22.7%) usual care patients (adjusted odds ratio 1.03 (95% confidence interval 0.84 to 1.25); P=0.81)”
AbstractFind in source - supportedReviewer 2The intervention was associated with an increased incidence of acute cardiac events within 24 hours.The safety outcome shows a statistically significant increase in acute cardiac events within 24 hours (adjusted OR 1.82, 95% CI 1.06-3.13; P=0.03), supporting the claim.Evidence: Safety outcome: 38/1250 (3.0%) vs 21/1247 (1.7%), adjusted OR 1.82 (1.06-3.13), P=0.03.
“Acute cardiac events within 24 hours occurred in 38/1250 (3.0%) intervention patients and 21/1247 (1.7%) usual care patients (adjusted odds ratio 1.82 (1.06 to 3.13); P=0.03)”
AbstractFind in source
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 previous studies and meta-analyses suggesting benefits of cardiac output-guided therapy while acknowledging controversies and limitations such as high risk of bias in older trials. The rationale for targeting postoperative infections is well-articulated, linking the intervention to improved tissue perfusion and inflammatory pathways.
“Cardiac output-guided therapy has proved controversial at times, and excessive early pulmonary artery catheter use generated safety concerns.”
“Our previous studies described the physiological and pharmacological basis of this effect, including the role of low dose inodilators, finding beneficial changes in inflammatory pathways and improved tissue perfusion and oxygenation.”
“Meta-analyses further suggest a reduction in postoperative infections and other complications, and shorter hospital stays, but they are limited by the inclusion of many older, single centre trials with a high risk of bias.”
“Meta-analyses further suggest a reduction in postoperative infections and other complications, and shorter hospital stays, but they are limited by the inclusion of many older, single centre trials with a high risk of bias.”
“We hypothesised that this intervention would reduce postoperative infections compared with usual clinical care.”
Randomisation used minimisation with a random component via a central online service. Blinding of outcome assessors is described, with a note that blinding of participants was not possible. A priori sample size calculation is provided. Inclusion/exclusion criteria are detailed. The analysis population (ITT) and missing-data approach (mean imputation) are defined.
“participants were randomised in a 1:1 ratio by minimisation with a random component (80% probability to be allocated to the group that minimises the between group differences in the minimisation factors), using a central online service, which concealed the allocation sequence.”
“Research staff collecting and assessing clinical outcomes were not involved in the participants’ care and were unaware of study group allocation. Self-assessment of assessor blinding was performed after follow-up visits.”
“We determined that a sample size of 2502 participants (1251 in each group) would allow detection of a reduction in postoperative infection rate within 30 days, from 30% to 24% with >90% power, using a two sided test with significance level α=0.05.”
“participants were randomised in a 1:1 ratio by minimisation with a random component (80% probability to be allocated to the group that minimises the between group differences in the minimisation factors), using a central online service, which concealed the allocation sequence.”
“Research staff collecting and assessing clinical outcomes were not involved in the participants’ care and were unaware of study group allocation.”
“We determined that a sample size of 2502 participants (1251 in each group) would allow detection of a reduction in postoperative infection rate within 30 days, from 30% to 24% with >90% power, using a two sided test with significance level α=0.05.”
The study reports the mean age, sex distribution (57% women), BMI, ASA physical status classification, and a detailed list of comorbidities for both intervention and usual care groups. This provides a clear picture of the study population.
“In 2498 patients (mean age 74 (standard deviation 6) years, 57% women)”
“Table 1 Baseline characteristics of participants. Values are number (percentage) unless stated otherwise”
“Mean age was 74 (standard deviation 6) years and 1432/2498 (57.3%) participants were women.”
“Table 1 Baseline characteristics of participants. Values are number (percentage) unless stated otherwise”
The trial protocol was approved by the UK National Research Ethics Service (IRAS ID 209688) and by responsible ethics committees in all participating countries. All participants provided written informed consent. Regulatory compliance is implied through adherence to ethical standards.
“The trial protocol (see supplement 1) was approved by the UK National Research Ethics Service (ID 209688) and by responsible ethics committees in all participating countries.”
“All participants provided written informed consent.”
“The trial protocol (see supplement 1) was approved by the UK National Research Ethics Service (ID 209688) and by responsible ethics committees in all participating countries.”
“The trial protocol (see supplement 1) was approved by the UK National Research Ethics Service (IRAS ID 209688) and by responsible ethics committees in all participating countries.”
“All participants provided written informed consent.”
The cardiac output monitoring system (Edwards Lifesciences EV1000/HemoSphere with ClearSight or FloTrac) is identified with manufacturer. Inotropes (dobutamine, dopexamine) are named with doses. Statistical software is identified (Stata, version 17). Bench criteria are not applicable as this is a clinical trial without wet-lab assays.
“Cardiac output and associated haemodynamic variables were monitored using an Edwards Lifesciences (Irvine, CA) system comprising an EV1000 or HemoSphere monitor with either ClearSight (non-invasive) cuff or FloTrac (invasive arterial pressure) sensor depending on clinician choice.”
“Intervention group participants also received a fixed, low dose, equipotent infusion of either dobutamine (2.5 µg/kg/min) or dopexamine (0.5 µg/kg/min), chosen based on clinician preference and local availability, and started after the first fluid bolus.”
“Cardiac output and associated haemodynamic variables were monitored using an Edwards Lifesciences (Irvine, CA) system comprising an EV1000 or HemoSphere monitor with either ClearSight (non-invasive) cuff or FloTrac (invasive arterial pressure) sensor depending on clinician choice.”
The paper names mixed-effects logistic regression models, specifies covariates, and uses restricted cubic splines for continuous variables. It reports adjusted odds ratios with 95% confidence intervals and exact p-values. Data presentation includes per-group Ns and percentages. The statistical analysis plan was publicly available and finalized before unblinding.
“The primary outcome was analysed using a mixed effects logistic regression model with a random intercept for country and fixed effects: surgical procedure category, age, sex, ASA class, and baseline haemoglobin and creatinine levels.”
“adjusted odds ratio 1.03 (95% confidence interval 0.84 to 1.25); P=0.81”
“Postoperative infection <30 days of randomisation (primary outcome) | 1247 (99.7) | 1247 (100) | 289 (23.2) | 283 (22.7) | 1.03 (0.84 to 1.25) | 0.81 | 0.4 (−3.4 to 4.2) | 1.03 (0.85 to 1.25) | 0.75 | 0.5 (−3.3 to 4.3)”
“The primary outcome was analysed using a mixed effects logistic regression model with a random intercept for country and fixed effects: surgical procedure category, age, sex, ASA class, and baseline haemoglobin and creatinine levels.”
“adjusted odds ratio 1.03, 95% confidence interval (CI) 0.84 to 1.25; P=0.81”
The data availability statement indicates that deidentified data will be shared with authenticated researchers who guarantee confidentiality, but it does not name a specific repository, data access committee, or detailed request procedure. No custom code is mentioned as being developed or shared.
“Deidentified data will be shared with other authenticated researchers for further research and research publications on this topic, but only if they guarantee to preserve the confidentiality of the information requested. Requests for data sharing will be considered by the data sharing committee o”
“Deidentified data will be shared with other authenticated researchers for further research and research publications on this topic, but only if they guarantee to preserve the confidentiality of the information requested. Requests for data sharing will be considered by the data sharing committee”
Trial registration number is provided (ISRCTN39653756). Methods are comprehensive. Limitations are explicitly discussed. Conclusions are proportional to the results. Funding sources and competing interests are declared.
“Trial registration ISRCTN Registry ISRCTN39653756.”
“Supplement 3 provides details of the trial’s standard operating procedures for the care of participants in the intervention and usual care groups.”
“Our trial also has some limitations. It was not possible to conceal group allocation during administration of this complex intervention.”
“Funding: The trial was funded by Edwards Lifesciences (Irvine, CA, USA) and the UK National Institute for Health and Care Research (NIHR).”
“Trial registration ISRCTN Registry ISRCTN39653756.”
“Our trial also has some limitations. It was not possible to conceal group allocation during administration of this complex intervention.”
Registered (1 ID: ISRCTN). No reporting guideline cited.
Broken references and links
None foundReferences 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.
Checked — nothing surfaced.
Checked 42 references by DOI: 42 verified.
Every extracted reference resolved against Crossref/OpenAlex with no retraction flags.
1 data/code link checked; 1 live.
- codehttps://optimiseii.org/documentsLIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
8 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 8 minor suggestions below.
8 copyedit issues flagged: mostly punctuation, consistency, clarity.
- MINORpunctuationAbstract, Objectives“surgery: OPTIMISE II randomised clinical trial”→ surgery: OPTIMISE II Randomised Clinical TrialConsistency in capitalization for trial names.
- MINORconsistencyAbstract, Results“mean age 74 (standard deviation 6) years”→ mean age 74 (SD 6) yearsUse consistent abbreviation (SD) as used elsewhere.
- MINORpunctuationMethods, Procedures, paragraph 3“after surgery ().”→ after surgery (Figure 1).Reference to figure is missing.
- MINORpunctuationResults, paragraph 3“control group experienced an acute cardiac event within 24 hours (38/1250 (3.0%) v 21/1247 (1.7%); adjusted odds ratio 1.82, 1.06 to 3.13; P=0.03) ( and ).”→ control group experienced an acute cardiac event within 24 hours (38/1250 (3.0%) v 21/1247 (1.7%); adjusted odds ratio 1.82, 1.06 to 3.13; P=0.03) (Table 3 and Figure 2).Missing references to table and figure.
- MINORpunctuationResults, paragraph 4“did not differ between the two groups ( and figure S1 in supplement 3).”→ did not differ between the two groups (Table 3 and figure S1 in supplement 3).Missing reference to table.
- MINORpunctuationResults, paragraph 5“minimally adjusted analysis ().”→ minimally adjusted analysis (Table 3).Missing reference to table.
- MINORconsistencyAbstract, Results“57% women”→ Consider using '57.3%' for consistency with the Results section.Abstract states 57% while Results state 57.3%.
- MINORclarityMethods, Statistical analysis“We included ASA class and procedure as categorical variables using the same categories used in the minimisation algorithm.”→ Consider rephrasing for clarity: 'ASA class and procedure were included as categorical variables using the same categories as in the minimisation algorithm.'Minor grammatical improvement.
The published work is robust and generally well-reported. An informed reader should weigh the vague data availability statement and the minor reporting inconsistencies (e.g., missing figure/table references) as areas that could warrant clarification or a correction. The statistical verification found some inconsistencies, but without specific details, these do not undermine the overall conclusions.
- 1.HIGHdata codeIn the Data availability statement, specify a concrete access route: name the data sharing committee, provide a contact email or a platform (e.g., YODA, Vivli), and state the conditions and expected timeframe for data requests.The current statement is vague and does not provide a clear mechanism for researchers to request data, which is a common requirement for reproducibility.
- 2.HIGHdata codeAdd a statement about code sharing: if any custom analysis code was used, deposit it in a public repository (e.g., Zenodo) with a DOI and link it in the manuscript.Sharing analysis code enhances transparency and allows others to reproduce the statistical analyses.
- 3.MEDIUMreportingAdd a CONSORT flow diagram as a figure (if not already included) to improve reporting transparency.A CONSORT flow diagram is a standard requirement for reporting randomised trials and helps readers track participant flow.
- 4.MEDIUMreportingIn the Methods, explicitly state that the trial was reported according to CONSORT guidelines and provide the checklist as supplementary material.Explicitly stating adherence to CONSORT and providing the checklist demonstrates compliance with reporting standards.
- 5.MEDIUMcopyeditFix missing references to tables and figures in the Results section: add 'Figure 1' after 'after surgery ()', add 'Table 3 and Figure 2' after 'acute cardiac event within 24 hours', add 'Table 3' after 'did not differ between the two groups', and add 'Table 3' after 'minimally adjusted analysis'.Missing cross-references reduce clarity and make it harder for readers to locate the supporting data.
- 6.MEDIUMcopyeditStandardize the abbreviation for standard deviation: use 'SD' consistently instead of 'standard deviation' in the Abstract.Consistent terminology improves readability and professionalism.
- 7.MEDIUMcopyeditAlign the percentage of women in the Abstract (57%) with the Results (57.3%) for consistency.Inconsistent numbers between the abstract and results can confuse readers and may be flagged during review.
- 8.LOWcopyeditCapitalize 'Randomised Clinical Trial' in the Abstract for consistency with trial naming conventions.Consistent capitalization of trial names is a minor but professional detail.
- 9.LOWcopyeditRephrase the sentence in Methods, Statistical analysis for clarity: 'ASA class and procedure were included as categorical variables using the same categories as in the minimisation algorithm.'The current phrasing is slightly awkward; the suggested rephrasing is clearer.
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.