Ionized Calcium and Bleeding in Cardiac Surgery

Plasma Ionized Calcium and Perioperative Bleeding in Cardiac Surgery.

This retrospective study investigates the association between perioperative plasma ionized calcium concentration and perioperative bleeding in open-heart surgery. Excluding patients who meet exclusion criteria, the study will include all applicable adult patients who underwent cardiac surgery at Helsinki University Hospital between January 2021 and March 2026. As clinical routine, during both cardiac surgery and the subsequent intensive care period, multiple blood gas analyses were performed, including measurements of plasma ionized calcium concentration. Time-weighted averages of all measurements will be calculated across different phases of surgery (pre-CPB, on -CPB, post-CPB) and the first 24 hours of ICU stay (0-6 h, 6-12 h, 12-24 h). Perioperative bleeding will be assessed using the Universal Definition of Perioperative Bleeding (UDPB) classification validated for cardiac surgery. In addition to chest drain output, this classification accounts for blood products administered to treat bleeding (red blood cells, platelets, and fresh frozen plasma), pharmacological coagulation factor concentrates (fibrinogen/cryoprecipitate, PCC, aFVIIa) and surgical interventions (open sternum, resternotomy). The association between plasma ionized calcium and UDPB class will be assessed with regression models. The primary analysis will be the association between time-weighted mean plasma ionized calcium level during the post-CPB phase as a continuous variable and dichotomous UDPB (UDPB 3-4 vs. UDPB 0-2) in patients who did not receive blood products during the post-CPB phase. One secondary and two sensitivity analyses will be performed

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Surgery Subjects

Detailed Description

PERIOPERATIVE TIME STAMPS: The perioperative phase is divided into the following time periods: the operating room phase before cardiopulmonary bypass (pre-CPB), cardiopulmonary bypass (on-CPB), the operating room phase after cardiopulmonary bypass (post-CPB), 0-6 hours in the intensive care unit (ICU-0-6h), 6-12 hours in the intensive care unit (ICU-6-12h), and 12-24 hours in the intensive care unit (ICU-12-24h). If the patient is transferred from the intensive care unit to the ward earlier than 24 hours after surgery, the final time period ends at the time of transfer.

PRIMARY ANALYSIS: The association between time-weighted mean plasma ionized calcium concentration during the post-CPB phase as a continuous variable and dichotomous UDPB (UDPB 3-4 vs. UDPB 0-2) in patients who did not receive blood products during the post-CPB phase. SECONDARY ANALYSIS: The association between time-weighted mean plasma ionized calcium concentration during the post-CPB phase as a continuous variable and the original five-grade UDPB in patients who did not receive blood products during the post-CPB phase. SENSITIVITY ANALYSES: The corresponding analyses to the primary and secondary analyses including all patients.

STATISTICAL ANALYSES: Differences in continuous variables between two groups will be tested using Student's t-test, and correlations between continuous variables will be assessed using Pearson's correlation test. The association between two dichotomous variables will be analyzed using Pearson's chi-square test. Temporal changes in plasma ionized calcium concentration across the entire study population will be analyzed using one-way analysis of variance (ANOVA). Post hoc comparisons will be performed using Dunnett's test, in which perioperative plasma ionized calcium concentrations will be compared with pre-CPB values. The association between plasma ionized calcium and UDPB class will be assessed with regression models. In addition to the primary, secondary and sensitivity analyses, corresponding multivariable analyses will be performed adjusted for clinical risk factors for bleeding. The clinical risk factors included in the model will be those previously identified by the research group among cardiac surgery patients at Meilahti Hospital. Multicollinearity among explanatory variables in the multivariable models will be considered present if the variance inflation factor (VIF) exceeds 5. In the presence of multicollinearity, the variable considered more clinically relevant for the model will be prioritized, and secondarily, the variable showing the stronger univariable association with the outcome will be selected. Otherwise, all predefined explanatory variables will be included in the multivariable model regardless of their statistical significance in univariable analyses. If needed, the five-grade UDPB will be modified to meet the assumption for proportional odds in ordinal regression models. Linearity will be tested. If needed, non-linear modeling will be used. The extent of missing data is not known at the time of writing the study protocol. The need for imputation of missing data and the specific imputation methodology will be evaluated after the study dataset has been obtained. Results will be presented as means and standard deviations, frequencies and proportions, or odds ratios with 95% confidence intervals (CI). A two-sided p-value < 0.05 will be considered statistically significant.

• Study Type: Observational
• Enrollment (Estimated): 4300

Contacts and Locations

• Study Contact: Name: Eero Juhani Pesonen, MD, PhD, docent; Phone Number: +358-40-5880781; Email: eero.pesonen@hus.fi

Study Locations

• Finland
  • Helsinki, Finland, 00029 HUS
    • Helsinki University Hospital, Meilahti Hospital
    • Contact: Eero Pesonen, MD, PhD, docent; Phone Number: +358-40-5880781; Email: eero.pesonen@hus.fi
    • Principal Investigator: Eero Pesonen, MD, PhD, docent
    • Sub-Investigator: Minna Ilmakunnas, MD, PhD, docent
    • Sub-Investigator: Peter Raivio, MD, PhD, docent
    • Sub-Investigator: Erika Wilkman, MD, PhD, docent
    • Sub-Investigator: Liisa Petäjä, MD, PhD
    • Sub-Investigator: Lotta Joenpolvi, medical student

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All adult (age 18-100 years) patients who underwent open-heart surgery with cardiopulmonary bypass (surgery with a main procedure code in the NCSP classification F category, "Heart and Great Vessels of the Thorax", performed on extracorporeal perfusion, procedure code FXA00) in Helsinki University Hospital between January 2021 and March 2026.

Exclusion Criteria: Organ transplants (procedure code FQ), hemophilia, von Willebrand disease, or platelet function disorders (ICD-10 codes D65-D69) and essential thrombocythemia (ICD-10 code D75.2).

Description

Inclusion Criteria:

• age 18-100 years
• open-heart surgery with cardiopulmonary bypass (surgery with a main procedure code in the NCSP classification F category, "Heart and Great Vessels of the Thorax", performed on extracorporeal perfusion, procedure code FXA00)
• between January 2021 and March 2026

Exclusion Criteria:

• organ transplants (procedure code FQ)
• hemophilia, von Willebrand disease, or platelet function disorders (ICD-10 codes D65-D69)
• essential thrombocythemia (ICD-10 code D75.2)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

adult patients undergoing cardiac surgery with cardiopulmonary bypass; All adult (age 18-100 years) patients who underwent open-heart surgery with cardiopulmonary bypass (surgery with a main procedure code in the NCSP classification F category, "Heart and Great Vessels of the Thorax", performed on extracorporeal perfusion, procedure code FXA00) in Helsinki University Hospital between January 2021 and March 2026. Exclusion Criteria: Organ transplants (procedure code FQ), hemophilia, von Willebrand disease, or platelet function disorders (ICD-10 codes D65-D69) and essential thrombocythemia (ICD-10 code D75.2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted plasma ionized calcium concentration during the post-CPB phase in OR for the primary and secondary analyses.	Time-weighted plasma ionized calcium concentration as a continuous parameter during the post-CPB phase in OR (i.e., the time interval between the cessation of CPB and the exit from OR) in the patients who did not receive blood products during the post-CPB phase.	The time interval between the cessation of CPB and the exit from OR.
Dichotomized UDPB (Universal Definition of Perioperative Bleeding).	UDPB (Universal Definition of Perioperative Bleeding) as a measure of perioperative bleeding and dichotomized into UDPB 0-2 vs. UDPB 3-4 in the patients who did not receive blood products during the post-CPB phase.	From the cessation of CPB till the end of the first 24 postoperative hours in ICU or till the exit from ICU, whichever occurred first.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Original five-grade UDPB (Universal Definition of Perioperative Bleeding).	Five-grade UDPB (Universal Definition of Perioperative Bleeding) as a measure of perioperative bleeding in the patients who did not receive blood products during the post-CPB phase.	From the cessation of CPB till the end of the first 24 postoperative hours in ICU or till the exit from ICU, whichever occurred first.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted plasma ionized calcium concentration during the post-CPB phase in OR for both sensitivity analyses of all patients.	Time-weighted plasma ionized calcium concentration as a continuous parameter during the post-CPB phase in OR (i.e., the time interval between the cessation of CPB and the exit from OR) in all patients.	The time interval between the cessation of CPB and the exit from OR.
Sensitivity analysis for dichotomized UDPB (Universal Definition of Perioperative Bleeding) in all patients.	UDPB (Universal Definition of Perioperative Bleeding) as a measure of perioperative bleeding and dichotomized into UDPB 0-2 vs. UDPB 3-4 in all patients.	From the cessation of CPB till the end of the first 24 postoperative hours in ICU or till the exit from ICU, whichever occurred first.
Sensitivity analysis for original five-grade UDPB (Universal Definition of Perioperative Bleeding) in all patients.	Five-grade UDPB (Universal Definition of Perioperative Bleeding) as a measure of perioperative bleeding in all patients.	From the cessation of CPB till the end of the first 24 postoperative hours in ICU or till the exit from ICU, whichever occurred first.

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital

Publications and helpful links

General Publications

• Dyke C, Aronson S, Dietrich W, Hofmann A, Karkouti K, Levi M, Murphy GJ, Sellke FW, Shore-Lesserson L, von Heymann C, Ranucci M. Universal definition of perioperative bleeding in adult cardiac surgery. J Thorac Cardiovasc Surg. 2014 May;147(5):1458-1463.e1. doi: 10.1016/j.jtcvs.2013.10.070. Epub 2013 Dec 9.
• Talvasto A, Ilmakunnas M, Raivio P, Vlasov H, Hiippala S, Suojaranta R, Wilkman E, Petaja L, Helve O, Juvonen T, Pesonen E. Albumin Infusion and Blood Loss After Cardiac Surgery. Ann Thorac Surg. 2023 Aug;116(2):392-399. doi: 10.1016/j.athoracsur.2023.03.041. Epub 2023 Apr 27.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: cardiac surgery; bleeding; cardiopulmonary bypass; perioperative bleeding; plasma ionized calcium
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hemorrhage
• Other Study ID Numbers: 04934

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: EU and national legislation restrict the distribution of personal health data. No data is available outside the authorized use within the HUS Acamedic or Findata platforms.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No