Cardiac Output, LowCONNIENCT03444545
Continous Cardiac Output - Non-Invasive Evaluation (CONNIE)
An observational study of Cardiac Output, Low and Cardiac Output, High, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
The capnodynamic method non-invasively calculates effective pulmonary blood flow (EPBF) continuously during surgery. In this study EPBF is compared to cardiac output (CO) measured with Transpulmonary Thermodilution (TPTD) att baseline and during hemodynamic changes in patients scheduled for open abdominal surgery at… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Output, Low, Cardiac Output, High
- What is being tested?
- Capnodynamic method and Transpulmonary thermodilution
- Type of treatment
- Medical device
- How many people
- 35 participants
- Where
- 1 siteSweden
- Study dates
- 29 Oct 2015to 31 Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients having major abdominal surgery requiring advanced hemodynamic monitoring
Who may be able to join
- Elective major abdominal surgery requiring advanced hemodynamic monitoring
Who cannot join
- Symptomatic coronary artery disease, chronic obstructive pulmonary disease with emphysema
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Performance of a Capnodynamic Method Compared to Transpulmonary Thermodilution in Open Abdominal Surgery
The capnodynamic method non-invasively calculates effective pulmonary blood flow (EPBF) continuously during surgery. In this study EPBF is compared to cardiac output (CO) measured with Transpulmonary Thermodilution (TPTD) att baseline and during hemodynamic changes in patients scheduled for open abdominal surgery at the Karolinska University Hospital, Solna, Sweden.
Read the detailed description
The capnodynamic method continuously calculates effective pulmonary blood flow (EPBF) with the help of a capnodynamic equation:
ELV x (FACO2(n) - FACO2(n-1)) = deltat(n) x EPBF (CvCO2 - CvCO2(n)) - VTCO2
ELV Effective lung volume [L] EPBF Effective pulmonary blood flow [L/min] n current breath n-1 previous breath FACO2 mean alveolar carbon dioxide fraction CvCO2 mixed venous carbon dioxide content [Lgas/Lblood] CcCO2n pulmonary end-capillary carbon dioxide content [Lgas/Lblood] VTCO2n volume [L] of carbon dioxide eliminated by the current, nth, breath delta t n current breath cycle time [min]
The equation above describes the mole balance between the CO2 delivered to lungs (EPBF), the volume taking part in the gas exchange (ELV) and CO2 excreted from the lungs (VTCO2). Normally there is no difference in CO2 between the actual and the preceding breath as the same amount of CO2 as delivered to the lungs as is excreted. When small changes in CO2 concentration are inserted into the equation obtained with short inspiratory or expiratory pauses in three out of nine breaths, nine different equations are obtained. The three unknown variables; ELV, EPBF and CvCO2can be solved with a linear least square optimization, a well-known numerical mathematical principle. The breathing pattern is automatically controlled by the ventilator which provides continuous calculations of EPBF where each value represents the average of the preceding nine breaths and renews with each breath as the newest replaces the oldest in the equation system.
At the day of surgery, included patients arrive 45 minutes earlier than otherwise at the surgical unit. After safe surgical checklist, vital signs are measured and epidural catheter inserted during a light sedation. Patients are anesthetized and muscle relaxed. An endotracheal tube is inserted in the trachea. Central arterial and vein catheters are inserted in sterile conditions with ultrasound guidance. Anesthesia is maintained with propofol in target controlled infusion and a short acting opioid is added as needed.
The protocol in the first 25 patients comprises simultaneous measurements of EPBF and CO at 1) Baseline (three measurments), 2) PEEP 15cmH2O, 3) PEEP 5cmH2O 4) before epidural activation, 5) 10-15 minutes after epidural activation 6) before volume infusion (when the patient is considered hypovolemic by the attending anaesthesiologist) and 7) shortly after volume infusion.
The attending anesthesiologist has the final responsibility on deciding the order of the protocol, for example if volume infusion should precede PEEP 15 cmH20 if hypovolemia is suspected.
The succeeding 10 patients (patients 26 to 35) are PEEP optimized before start of protocol using a standardiazed open lung tool recruitment. During the PEEP elevation (step 2 in the protocol above) 10cmH2O is added to the optimal PEEP and then released back to the baseline optimal PEEP (step 3).
Each comparative measurement of CO and EPBF in the protocol includes as an average of three TPTD measured with PiCCO2 and and the average of EPBF registered in the beginning of the first TPTD and in the end of the last TPTD.
- Conditions
- Cardiac Output, Low, Cardiac Output, High
- Being tested
- Capnodynamic method, Transpulmonary thermodilution
- Keywords
- Cardiac output, Carbon dioxide, Intraoperative monitoring, Pulmonary blood flow
- Medical subject headings
- Cardiac Output, Low, Cardiac Output, High
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Capnodynamic methodDevice
Expired carbon dioxide is measured with a mainstream infrared sensor (Capnostat-3, Respironics Inc, Wallingford, CT, USA) and gas flow analysed with the flow sensor incorporated in the ventilator (Servo-i, Maquet Critical Care, Solna, Sweden) which was connected to a computer where all the mathematical analysis is carried out with a software written in Matlab™ (The Mathworks Inc, Natick, MA, USA).
Instead of a fixed ratio between inspiration and expiration, three breaths out of every nine are prolonged with a 3-4 seconds longer expiration creating small changes in end- expiratory CO2
Transpulmonary thermodilutionDevice
Also called PiCCO
Each cardiac output measurement comprises an average of three thermodilutions performed successively one after another. TPTD is performed with a PiCCO2 monitor (Pulsion Medical Systems SE, Feldkirchen, Germany)
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute values of EPBF compared to Cardiac output
Mean cardiac output as measured with transpulmonary thermodilution compared to mean effective pulmonary blood flow measured with the capnodynamic method at the start of first thermodilution and during the time interval zero to 4 hours.
Measured: Mean CO vs EPBF from zero to 4 hours perioperatively
Secondary outcomes (1)
Changes in EPBF compared to changes in Cardiac output
Measurement of cardiac output and EPBF as described in Outcome 1 before and after hemodynamic changes.
Measured: Mean CO vs mean EPBF from zero to 4 hours perioperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2018
- Study start29 Oct 2015
- Primary completion28 Sep 2018
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cardiac Output, LowStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Region Stockholm
- Responsible party
- Principal investigator, Anil Gupta, Karolinska Institutet
- Investigators
- Hakan Björne, PhD, Study director, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03444545
- Sponsor's protocol ID
- CONNIE 1
- Acronym
- CONNIE
- Status last verified
- Jan 2019
- First submitted
- 30 Jan 2018
- Last updated
- 11 Jan 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sigmundsson TS, Ohman T, Hallback M, Redondo E, Sipmann FS, Wallin M, Oldner A, Hallsjo Sander C, Bjorne H. Performance of a capnodynamic method estimating effective pulmonary blood flow during transient and sustained hypercapnia. J Clin Monit Comput. 2018 Apr;32(2):311-319. doi: 10.1007/s10877-017-0021-3. Epub 2017 May 11.
PubMed 28497180Sander CH, Sigmundsson T, Hallback M, Sipmann FS, Wallin M, Oldner A, Bjorne H. A modified breathing pattern improves the performance of a continuous capnodynamic method for estimation of effective pulmonary blood flow. J Clin Monit Comput. 2017 Aug;31(4):717-725. doi: 10.1007/s10877-016-9891-z. Epub 2016 Jun 1.
PubMed 27251701Sigmundsson TS, Ohman T, Hallback M, Suarez-Sipmann F, Wallin M, Oldner A, Hallsjo-Sander C, Bjorne H. Comparison between capnodynamic and thermodilution method for cardiac output monitoring during major abdominal surgery: An observational study. Eur J Anaesthesiol. 2021 Dec 1;38(12):1242-1252. doi: 10.1097/EJA.0000000000001566.
PubMed 34155171
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Performance of a Capnodynamic Method Compared to Transpulmonary Thermodilution in Open Abdominal Surgery
- ClinicalTrials.gov ID
- NCT03444545
- Acronym / sponsor ID
- CONNIE / CONNIE 1
- Conditions
- Cardiac Output, Low, Cardiac Output, High
- Keywords
- Cardiac output, Carbon dioxide, Intraoperative monitoring, Pulmonary blood flow
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Region Stockholm
- Study start
- 29 Oct 2015 (actual)
- Primary completion
- 28 Sep 2018 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 23 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The capnodynamic method non-invasively calculates effective pulmonary blood flow (EPBF) continuously during surgery. In this study EPBF is compared to cardiac output (CO) measured with Transpulmonary Thermodilution (TPTD) att baseline and during hemodynamic changes in patients scheduled for open abdominal surgery at the Karolinska University Hospital, Solna, Sweden.
Detailed description
The capnodynamic method continuously calculates effective pulmonary blood flow (EPBF) with the help of a capnodynamic equation:
ELV x (FACO2(n) - FACO2(n-1)) = deltat(n) x EPBF (CvCO2 - CvCO2(n)) - VTCO2
ELV Effective lung volume [L] EPBF Effective pulmonary blood flow [L/min] n current breath n-1 previous breath FACO2 mean alveolar carbon dioxide fraction CvCO2 mixed venous carbon dioxide content [Lgas/Lblood] CcCO2n pulmonary end-capillary carbon dioxide content [Lgas/Lblood] VTCO2n volume [L] of carbon dioxide eliminated by the current, nth, breath delta t n current breath cycle time [min]
The equation above describes the mole balance between the CO2 delivered to lungs (EPBF), the volume taking part in the gas exchange (ELV) and CO2 excreted from the lungs (VTCO2). Normally there is no difference in CO2 between the actual and the preceding breath as the same amount of CO2 as delivered to the lungs as is excreted. When small changes in CO2 concentration are inserted into the equation obtained with short inspiratory or expiratory pauses in three out of nine breaths, nine different equations are obtained. The three unknown variables; ELV, EPBF and CvCO2can be solved with a linear least square optimization, a well-known numerical mathematical principle. The breathing pattern is automatically controlled by the ventilator which provides continuous calculations of EPBF where each value represents the average of the preceding nine breaths and renews with each breath as the newest replaces the oldest in the equation system.
At the day of surgery, included patients arrive 45 minutes earlier than otherwise at the surgical unit. After safe surgical checklist, vital signs are measured and epidural catheter inserted during a light sedation. Patients are anesthetized and muscle relaxed. An endotracheal tube is inserted in the trachea. Central arterial and vein catheters are inserted in sterile conditions with ultrasound guidance. Anesthesia is maintained with propofol in target controlled infusion and a short acting opioid is added as needed.
The protocol in the first 25 patients comprises simultaneous measurements of EPBF and CO at 1) Baseline (three measurments), 2) PEEP 15cmH2O, 3) PEEP 5cmH2O 4) before epidural activation, 5) 10-15 minutes after epidural activation 6) before volume infusion (when the patient is considered hypovolemic by the attending anaesthesiologist) and 7) shortly after volume infusion.
The attending anesthesiologist has the final responsibility on deciding the order of the protocol, for example if volume infusion should precede PEEP 15 cmH20 if hypovolemia is suspected.
The succeeding 10 patients (patients 26 to 35) are PEEP optimized before start of protocol using a standardiazed open lung tool recruitment. During the PEEP elevation (step 2 in the protocol above) 10cmH2O is added to the optimal PEEP and then released back to the baseline optimal PEEP (step 3).
Each comparative measurement of CO and EPBF in the protocol includes as an average of three TPTD measured with PiCCO2 and and the average of EPBF registered in the beginning of the first TPTD and in the end of the last TPTD.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients having major abdominal surgery requiring advanced hemodynamic monitoring
Key inclusion criteria (1 listed)
- Elective major abdominal surgery requiring advanced hemodynamic monitoring
Key exclusion criteria (1 listed)
- Symptomatic coronary artery disease, chronic obstructive pulmonary disease with emphysema
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Capnodynamic methodExpired carbon dioxide is measured with a mainstream infrared sensor (Capnostat-3, Respironics Inc, Wallingford, CT, USA) and gas flow analysed with the flow sensor incorporated in the ventilator (Servo-i, Maquet Critical Care, Solna, Sweden) which was connected to a computer where all the mathematical analysis is carried out with a software written in Matlab™ (The Mathworks Inc, Natick, MA, USA). Instead of a fixed ratio between inspiration and expiration, three breaths out of every nine are prolonged with a 3-4 seconds longer expiration creating small changes in end- expiratory CO2 | Device | – |
| Transpulmonary thermodilutionAlso: PiCCOEach cardiac output measurement comprises an average of three thermodilutions performed successively one after another. TPTD is performed with a PiCCO2 monitor (Pulsion Medical Systems SE, Feldkirchen, Germany) | Device | – |
Primary outcome
Absolute values of EPBF compared to Cardiac output
Time frame: Mean CO vs EPBF from zero to 4 hours perioperatively
Mean cardiac output as measured with transpulmonary thermodilution compared to mean effective pulmonary blood flow measured with the capnodynamic method at the start of first thermodilution and during the time interval zero to 4 hours.
1 secondary outcome
Changes in EPBF compared to changes in Cardiac output
Time frame: Mean CO vs mean EPBF from zero to 4 hours perioperatively
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2019.
- Background: PubMed 28497180Sigmundsson TS, Ohman T, Hallback M, Redondo E, Sipmann FS, Wallin M, Oldner A, Hallsjo Sander C, Bjorne H. Performance of a capnodynamic method estimating effective pulmonary blood flow during transient and sustained hypercapnia. J Clin Monit Comput. 2018 Apr;32(2):311-319. doi: 10.1007/s10877-017-0021-3. Epub 2017 May 11.
- Background: PubMed 27251701Sander CH, Sigmundsson T, Hallback M, Sipmann FS, Wallin M, Oldner A, Bjorne H. A modified breathing pattern improves the performance of a continuous capnodynamic method for estimation of effective pulmonary blood flow. J Clin Monit Comput. 2017 Aug;31(4):717-725. doi: 10.1007/s10877-016-9891-z. Epub 2016 Jun 1.
- Derived from this study: PubMed 34155171Sigmundsson TS, Ohman T, Hallback M, Suarez-Sipmann F, Wallin M, Oldner A, Hallsjo-Sander C, Bjorne H. Comparison between capnodynamic and thermodilution method for cardiac output monitoring during major abdominal surgery: An observational study. Eur J Anaesthesiol. 2021 Dec 1;38(12):1242-1252. doi: 10.1097/EJA.0000000000001566.
- Individual participant dataSharing planned: Undecided
Related trials for Cardiac Output, Low
RecruitingObservational study
Validation of Continuous Transcutaneous Carbon Dioxide Monitoring in VA-ECMO Patients
Carbon Dioxide
RecruitingObservational study
Post-Induction Low Cardiac Output Syndrome in Coronary Artery Bypass Graft Surgery
Cardiac Output, Low, Coronary Arterial Disease
RecruitingObservational study
Performance of Carbon Dioxide (CO2)-Derived Parameters in Predicting Low Cardiac Output Syndrome
Low Cardiac Output Syndrome Bypass Children
Recruiting
Assessment of Cardiac Function and Anesthesia Depth in Patients Undergoing Cardiac Surgery
Heart Disease
Enrolling by invitation
LBBP + CSP Versus LBBP Alone for Cardiac Resynchronization Therapy
Heart Failure Low Output
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hakan Björne, PhD study director
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Output, Low and Cardiac Output, High, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute values of EPBF compared to Cardiac output (time frame: Mean CO vs EPBF from zero to 4 hours perioperatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03444545, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2019.