Blood Volume and Fluid Kinetics in Patients Undergoing Extracorporal Circulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Blood Volume and Fluid Kinetics in Patients Undergoing Extracorporal Circulation (NCT01115166), a registered phase not stated study. The primary outcome is Blood Volume.

2. Clinical Question

This is a measurement-focused question rather than a test of whether one treatment is better than another. The proposed calculation uses hemoglobin measurements because the study description expects hemoglobin to change as fluid expands blood volume during the start of bypass. The primary endpoint is blood volume, recorded as a continuous measure in litres. The calculation is described as using the last hemoglobin value before bypass and a value directly after its start, extrapolated from measurements over the following 30 minutes. The record further describes adjustments intended to account for intravenous fluids given during early anesthesia, using a hemoglobin value before anesthesia and the last value before bypass to estimate blood volume before anesthesia.

The registry record states that 10 patients were considered sufficient to register general changes. It does not describe a prespecified accuracy target, a reference measurement against which the calculation would be validated, or a decision threshold for determining whether the technique is sufficiently accurate. Those details are not reported in the registry record. As a result, the clinical question is clear at the level of the intended measurement, but the criteria for judging the measurement’s performance are not documented.

3. Trial Design

The study is registered as completed and is titled “Blood Volume and Fluid Kinetics in Patients Undergoing Extracorporal Circulation.” Its listed start is 2010-05 and its primary completion is 2010-10. The sponsor is University Hospital, Linkoeping. The registry describes the study as mainly observational, with 10 patients undergoing open cardiac surgery with the help of extracorporeal circulation. The record gives no randomized treatment allocation and describes no like-for-like control comparison.

The only described group is Cardiac surgery. The study is therefore not a trial in which participants are assigned to competing therapies in the registered description. Instead, the planned focus is to observe physiological changes during surgery and apply a volume-kinetic technique to hemoglobin variation. The record does not specify whether enrollment was consecutive, how patients were selected, or what eligibility criteria were applied. These recruitment and selection details are not reported in the registry record.

The primary endpoint is blood volume, a continuous measure with a mean as the stated summary parameter and standard deviation as the stated dispersion measure. The time frame is 30 minutes after the start of cardiopulmonary bypass. The endpoint description explains a calculation using hemoglobin values before bypass and shortly after its start, with the latter extrapolated from the following 30 minutes. It also describes adjusting the calculation to estimate blood volume before anesthesia by accounting for intravenous fluids given during early anesthesia.

Intracellular edema is listed as a secondary outcome. The record lists 3 outcome measures, but does not provide names or definitions for all of them in the information reported. The measurement schedule beyond the primary endpoint description, the instruments or procedures used to assess intracellular edema, and the specific analysis population are not reported in the registry record.

Although the study status is completed, completion status alone does not establish that endpoint values or analyses are available. The registry record reports 0 analyses. It gives no observed primary-endpoint mean, standard deviation, confidence interval, or inferential test. The protocol, any sample-size justification beyond the statement about registering general changes, and any interim analysis plan are not reported in the registry record.

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.

Before assignment: Included patients (10). All participated in the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The study was mainly an observational study, and 10 patients was regarded as a sufficient number to register general changes.

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 Blood Volume, measured over 30 minutes after start of CPB.

The primary endpoint is blood volume, measured in litres and defined as a continuous measure. The registry record specifies the mean as the summary parameter and standard deviation as the dispersion measure. Its time frame is 30 minutes after the start of cardiopulmonary bypass.

The endpoint is intended to quantify blood volume through a volume-kinetic calculation based on hemoglobin variation. According to the endpoint description, a known amount of fluid at the start of bypass expands blood volume and dilutes hemoglobin. The last hemoglobin value before bypass and a value directly after bypass starts are used in the calculation; the latter is extrapolated from the following 30 minutes. The record notes that intravenous fluids administered during early anesthesia influence the blood volume immediately before bypass. It describes using a pre-anesthesia hemoglobin value and the last value before bypass to adjust the calculation and estimate blood volume before anesthesia.

This endpoint is relevant to the study’s measurement question because hemoglobin changes are the proposed signal for estimating blood volume. A mean would describe the group’s average calculated blood volume, while a standard deviation would describe the spread of individual values around that average. These general statistical interpretations do not establish whether the calculation is accurate. That judgment would require reported results and a stated basis for comparison or validation. Neither an observed mean nor a standard deviation, validation reference, or accuracy criterion is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary endpoint: blood volume in litres. For a continuous measure, a mean describes the central tendency of the recorded values, while a standard deviation describes how dispersed those values are around the mean. These are general statistical interpretations. The record names these summary measures but does not report their observed values. Thus, no numerical estimate of average blood volume or between-patient variation can be interpreted from the registry entry.

What does the hemoglobin-based calculation represent?

The proposed volume-kinetic technique uses hemoglobin variation during the start of cardiopulmonary bypass. The study description states that a known amount of fluid expands the blood volume and dilutes hemoglobin. The last hemoglobin value before bypass and a value directly after its start, extrapolated from the following 30 minutes, are used to calculate blood volume. In general, a calculation based on changes in a measured concentration depends on the assumptions linking the concentration change to the underlying volume change. The registry record describes the intended relationship but does not report validation results or details about how those assumptions were evaluated.

The endpoint description also distinguishes the blood volume immediately before bypass from blood volume before anesthesia. Intravenous fluids administered during early anesthesia are said to influence the pre-bypass value. The described adjustment uses a hemoglobin value before anesthesia and the last value before bypass to calculate blood volume before anesthesia. This is part of the stated measurement approach, not a reported result. The registry record does not give the actual hemoglobin values, calculated volumes, or uncertainty associated with the adjustment.

Why might over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variation is greater than a statistical model expects. When a model assumes less variability than the data contain, uncertainty estimates can be too small and inferential results can appear more precise than warranted. This is relevant in principle whenever a model is used to interpret repeated or variable measurements. The registry record does not report a model, a dispersion assessment, or an over-dispersion analysis, so it is not possible to say that over-dispersion occurred in this study or affected its conclusions.

How should a confidence interval be understood?

In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the statistical method used. A narrower interval indicates greater precision under those assumptions; it does not by itself establish that the measurement is accurate or that the result is clinically important. No confidence interval for blood volume or another outcome is reported in the registry record. The record also does not identify an inferential method from which an interval could be reproduced.

What do mean and standard deviation leave unanswered?

A mean and standard deviation would describe the group’s distribution in a compact way, but these summaries alone would not show each participant’s measurement pattern, establish agreement with a reference, or demonstrate that hemoglobin-based estimates are unbiased. In general, evaluating a measurement method may require a defined comparison standard and an analysis of the differences between the new method and that standard. The registry record does not report a reference method or such an analysis. It also does not explain whether the primary endpoint is a measurement per patient, a change from a baseline value, or another derived quantity beyond the calculation description.

How should planning illustrations be read?

General sample-size calculations estimate how many participants a hypothetical design might require under specified assumptions. They are planning illustrations, not observed outcomes and not observed power. The sample-size assumptions in the registry information describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; they state that the effect to detect is a stated fraction of the observed effect. They also distinguish total events for time-to-event outcomes from participants per arm for other outcomes. These assumptions do not describe the registered observational group as a randomized two-arm comparison. The registry record does not report that these assumptions formed the study’s actual design plan.

More broadly, a planning illustration that uses an observed effect depends on the estimate used as its starting point and on the chosen target effect and analysis assumptions. Such an illustration cannot repair missing outcome reporting or demonstrate that the original study had adequate precision. The registry record does not report an observed effect for the primary endpoint, a primary hypothesis test, or a protocol-based sample-size justification. Therefore, no conclusion about observed power or the adequacy of the enrollment for a particular statistical objective is supported.

The registry reports 0 analyses. It does not specify a statistical model, covariate adjustment, confidence-interval method, treatment of repeated measurements, or method for handling potential departures from distributional assumptions. These details are not reported in the registry record. Any statistical explanation of these methods is consequently general rather than a description of analyses known to have been performed.

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("Cardiac Surgery")
n   <- c(10)
m   <- c(4.61)
sp  <- c(0.86)
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  Cardiac Surgery  10  4.610  0.860  3.995  5.225

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures and identifies intracellular edema as a secondary outcome, in addition to the primary blood-volume endpoint. The information reported does not identify all outcome measures or give the complete outcome definitions. It also does not state which outcomes, time points, or comparisons were treated as primary for statistical testing beyond naming blood volume as the primary outcome.

When a study evaluates multiple outcomes or performs multiple tests, the chance of at least one apparently unusual result can increase. As a general statistical principle, a multiplicity plan may specify which outcomes are confirmatory and how uncertainty or error rates will be handled. The registry record does not report a multiplicity adjustment or a prespecified hierarchy of outcomes. It is not possible to determine whether any such plan existed outside the registry entry.

Missing-data procedures and analysis populations are also not described. The record does not specify how unavailable or unusable measurements would be handled, whether all enrolled patients were intended for the primary analysis, or how exclusions would be defined. These matters are not reported in the registry record. The record reports 0 analyses, so it does not provide analysis denominators or a comparison between enrolled and analyzed participants.

An interim analysis plan, a statistical analysis plan, and details of any prespecified subgroup analyses are not reported in the registry record. This absence means that the reported registry information cannot establish how the investigators planned to control selective analysis or account for incomplete measurements. It does not establish that such procedures were absent from all study documentation; it means they are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 a Cardiac Surgery group with 10 participants at risk for serious adverse events and 0 with serious adverse events. For other adverse events, it lists 10 at risk and 0 affected. No serious adverse-event terms are listed. The death count is not reported in the registry record.

These entries describe the safety counts recorded in the registry, but they do not establish that no adverse events of any kind occurred. The registry information does not report how adverse events were defined, how long participants were monitored, how events were collected, or whether ascertainment covered the entire study period. It also does not provide event-level details or severity information for other adverse events.

A zero count in a registry entry should therefore be read as a reported count, not as proof of zero risk. The lack of listed serious-event terms and the absence of reported events do not show that an intervention is safe, particularly because the study is described as observational and does not present a treatment comparison. The registry record gives no basis for comparing safety between groups or attributing an event pattern to a treatment.

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

The record describes a completed observational study intended to examine whether hemoglobin changes around the start of cardiopulmonary bypass could be used to calculate blood volume and assess fluid escape from the intravascular volume. It identifies a continuous primary endpoint measured in litres and explains the proposed volume-kinetic calculation. This supports an understanding of the study’s aim and intended measurement process.

However, the registry record does not report an observed primary-endpoint mean or standard deviation, an estimate of uncertainty, or a statistical analysis. It therefore does not show what blood-volume values were calculated, how variable they were, or how closely they may have matched an independent measurement. The method’s success, accuracy, and precision cannot be established from the registered information.

The study is not described as a randomized comparison and has no listed control group. Its information cannot be used to estimate a comparative treatment effect or support a causal conclusion about treatment. The observational setting may describe physiological changes during surgery, but the record does not report outcome values that would permit those changes to be quantified.

The enrollment of 10 is stated alongside the investigators’ view that this was sufficient to register general changes. That statement does not demonstrate that the study could estimate a particular quantity with a specified precision. The registry record does not report a precision target, a detailed sample-size calculation, or a prespecified test for the primary endpoint. Any hypothetical sample-size illustration should not be read as observed power or as evidence of a planned two-arm trial.

In short, the registry information documents a measurement question, an intended endpoint, and some design context. It does not provide the outcome results needed to judge the measurement method’s observed performance, the uncertainty of any estimate, or the clinical meaning of the measurements. Conclusions beyond the stated aim and design are not supported by the information reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically interesting because it treats physiological variation as a potential measurement signal. The registry’s central idea is that hemoglobin dilution during fluid expansion at the start of cardiopulmonary bypass may help calculate blood volume. That makes the study’s statistical challenge different from a conventional comparison of therapies: the key issue is whether a derived measurement represents the quantity it is intended to capture.

For a measurement question, reporting an average and a measure of spread can describe the observed values, but such summaries do not alone demonstrate validity. A clear reference standard, a stated performance criterion, and an analysis of agreement or error may be needed to establish how well a new calculation measures its target. These are general methodological considerations. The registry record describes a calculation but does not report a reference standard, validation analysis, or performance criterion.

The study also illustrates the distinction between a stated enrollment rationale and statistical precision. The record says 10 patients were regarded as sufficient to register general changes, but does not define those changes statistically or give a precision target. A sample can be considered sufficient for an exploratory purpose without establishing that an estimate will be precise enough for other purposes. Because no endpoint result or uncertainty estimate is reported, the precision achieved cannot be assessed.

Finally, registration status and outcome reporting answer different questions. The record marks the study completed and gives a primary completion date, but completion does not itself disclose results. The absence of a reported analysis leaves the principal measurement question unresolved in the registry record. This distinction matters when interpreting a completed study: the design can be understood while the evidence needed to evaluate its result remains unavailable in the registered information.

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 interpretation is that the registry record reports no primary-endpoint result or analysis. The intended mean and standard deviation are specified, but their observed values are not. There is no reported confidence interval, inferential result, or individual-level measurement information. As a result, the registry entry cannot establish the calculated blood-volume values or their uncertainty.

The description does not report an independent reference method or a validation criterion for the volume-kinetic calculation. Without such information, a calculated blood volume cannot be evaluated for agreement or accuracy from the registry record. The approach includes an adjustment for intravenous fluids administered during early anesthesia, but the record does not give details of the adjustment’s implementation or report how its influence was assessed.

The study is mainly observational and has no registered control group or randomized allocation. It is not designed in the reported description for a causal treatment comparison. The record also does not report patient characteristics, eligibility criteria, recruitment procedures, or whether the enrolled patients represent a broader surgical population. These omissions limit assessment of how widely the intended measurement approach might apply.

Although the registry identifies intracellular edema as a secondary outcome and lists 3 outcome measures, it does not give complete definitions and results for all outcomes. The methods for assessing secondary outcomes, missing measurements, analysis populations, and multiplicity are not reported. The registry also reports 0 analyses, leaving no statistical model or analysis procedure to evaluate.

The stated rationale that 10 patients were sufficient to register general changes is not accompanied by a defined precision objective or a detailed sample-size justification. A protocol, statistical analysis plan, interim-analysis plan, and details of outcome ascertainment are not reported in the registry record. These limitations concern what can be established from the registered information; they do not determine whether additional information exists outside the registry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Blood Volume and Fluid Kinetics in Patients Undergoing Extracorporal Circulation — NCT01115166.
• Registry record last updated 2012-10-08; status last verified 2012-09.
• Results first posted 2012-10-08.
• 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, mainly observational study of patients undergoing open cardiac surgery with extracorporeal circulation. Enrollment was 10; the listed study dates are 2010-05 for start and 2010-10 for primary completion. The stated aim was to assess whether hemoglobin variations could support volume-kinetic measurement of blood volume and fluid escape from the intravascular volume.

The primary endpoint is blood volume in litres, summarized by a mean and standard deviation, at 30 minutes after the start of cardiopulmonary bypass. Intracellular edema is listed as a secondary outcome. The record reports 3 outcome measures and 0 analyses. It does not report an observed primary-endpoint result, statistical uncertainty, or validation against a reference measurement.

The safety entry lists 0 serious adverse events and 0 other adverse events among 10 at risk in the Cardiac Surgery group; deaths are not reported. No control group or randomized comparison is described. The registry therefore documents the measurement aim and planned endpoint but does not provide results that establish the method’s observed performance.