Critically IllFRACASNCT02841943
Fluid Responsiveness After CArdiac Surgery Study
An observational study of Critically Ill and Hypovolemia, run by South West Sydney Local Health District at 1 site in Australia.
Trial summary
Study Design: Prospective observational study Study Location: Liverpool Hospital Intensive Care Unit, South Western Sydney Local Health District, Sydney, Australia. Target study size: 100 patients Ethics: Approved by the local Human Research and Ethics Council (HREC) at Liverpool Hospital (LPOOL) as a Low Negligible… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critically Ill, Hypovolemia
- How many people
- 102 participants
- Where
- 1 siteAustralia
- Study dates
- Mar 2016to Dec 2016
- 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: All adult patients electively admitted to the Intensive Care Unit following cardiac surgery
Who may be able to join
- Admitted following elective cardiac surgery
- Adult (>18 years of age)
- Pulmonary artery, central venous and arterial catheters inserted
Who cannot join
- Emergency Patients (surgery immediately or within 12 hours of admission to hospital)
- Children (< 18 years of age)
- Patients admitted to ICU with ongoing extracorporeal circulatory support
- Patients re-admitted to ICU within same index hospital admission
Trial locations and contacts
1 site in 1 country.
Australia1 site
Intensive Care Unit, Liverpool Hospital, South Western Sydney Local Health District
Liverpool, New South Wales, 1871
About this study
Official title: Fluid Responsiveness After Cardiac Surgery (FRACAS) Study
Study Design: Prospective observational study
Study Location: Liverpool Hospital Intensive Care Unit, South Western Sydney Local Health District, Sydney, Australia.
Read more
Target study size: 100 patients
Ethics: Approved by the local Human Research and Ethics Council (HREC) at Liverpool Hospital (LPOOL) as a Low Negligible Risk (LNR) project [HREC/LNR/14/LPOOL/295, HREC/LNR/15/LPOOL47, HREC/LNR/14/LPOOL/150]
Participants: Post cardiac surgical patients admitted to the Intensive Care Unit between March-October 2016
Aims:
- to determine the descriptive and predictive value of variables (outlined below) related to oxygen delivery/consumption in regards to the effects of intravascular volume expansion
- to assess correlations between central and peripheral variables (outlined below) relevant to oxygen delivery/consumption
- to assess correlations between a set of variables (outline below) and patient centred outcomes in ICU and in hospital
Main variables collected:
- Tissue oxygen saturation by peripheral Near-Infrared Spectroscopy (NIRS)
- Common carotid arterial Doppler
- Arterial/mixed venous/central venous blood gas analyses
- Haemodynamic parameters
- Organ support measures
Data collection time points:
- ICU admission (within 30 minutes)
- Before administration of a fluid bolus
- After administration of a fluid bolus
- 6 hours after ICU admission
- Morning of first postoperative day (12-24 hours)
Outcome measures:
- the response to intravascular volume expansion
- ICU mortality, morbidity and length of stay and hospital mortality and length of stay
Data analysis:
- Clinical data are collected bedside using an electronic case record form
- Descriptive statistics
- Paired and unpaired comparative
- Correlative and predictive statistics
Read the detailed description
This prospective observational study program has a set of objectives within three major domains that will be analysed separately and synergistically:
Peripheral near infra-red spectroscopy (NIRS)
Aims:
- to describe the effects of non-sanguineous intravascular volume expansion on systemic oxygen delivery
- to describe how changes in systemic oxygen delivery impact on peripheral oxygen kinetics as measured by tissue oxygen saturation (StO2) in the thenar and forearm regions at rest and using a vascular occlusion test
- to determine the clinical applicability of using thenar and forearm NIRS to guide haemodynamic optimisation following cardiac surgery
- to assess the relation between systemic and peripheral oxygen kinetics vs. onset of organ dysfunction and need for extended stay in ICU following cardiac surgery
Hypotheses:
- Peripheral oxygen kinetics using NIRS offer more specific guidance for haemodynamic optimisation post cardiac surgery compared to using systemic variables only
- Impaired peripheral oxygen kinetics as assessed using NIRS can be used to identify patients at risk for developing organ dysfunction or needing extended period of ICU support an earlier stage compared to traditional systemic variables
Main measurements:
- peripheral near infrared spectroscopy (NIRS) measuring tissue oxygen saturation (StO2) at the thenar eminence and forearm during a 3 minute vascular occlusion test at 50mmHg above systolic pressure, following the establishment of a baseline (an StO2 average over 3 minutes with less than 5% variability)
- StO2 measurements are repeated at 30 minutes intervals during the first 6 hours following admission to ICU.
- vascular occlusion tests are repeated before and after volume expansion.
Cardiac output and common carotid Doppler sonography
Aims:
- to apply computerised algorithms to derive advanced haemodynamic information (mean systemic filling pressure, heart efficiency, vascular compliance) in patients requiring fluid boluses following cardiac surgery
- to correlate changes in cardiac output, cardiac power and estimates of fluid responsiveness using the pulmonary artery catheter with the variables mean systemic filling pressure and heart efficiency
- to characterise indices of fluid responsiveness by measuring volume efficiency
- to determine the impact of changes in vascular resistance state on the assessment of changes in volume state in the post-operative cardiac surgery period
- to assess the relation between fluid responsiveness, fluid management and clinical outcomes in ICU following cardiac surgery
- to evaluate the potential for carotid Doppler blood flow measurements as a surrogate parameter for cardiac output, including incorporation into computerised algorithms
Hypotheses:
- the derived measures of mean systemic filling pressure and heart efficiency are superior to identify fluid responsiveness compared to cardiac output measurements alone in patients following cardiac surgery
- carotid Doppler blood flow measurements can be used as a surrogate parameter for cardiac output and in particular for changes in cardiac output when fluid responsiveness is investigated
Main measurements:
- Pulmonary arterial thermodilution studies (for cardiac output, stroke volume, cardiac index) by at least triplicate injections within a ± 10% range
- Computerised algorithms are used to derive an analogue mean systemic filling pressure, heart efficiency, volume efficiency based on cardiac output, central venous pressure and mean arterial pressure
- Common carotid Doppler sonography to measure vessel diameter, cross sectional area and time average mean velocity to generate blood flow as well as respirophasic peak flow velocity variation
Oxygen and carbon dioxide gradients
Aims:
- to assess any insufficiency of oxygen delivery to match the oxygen consumption, resulting in anaerobic metabolism, by determining i) arteriovenous concentration gradients for lactate, ii) the venoarterial carbon dioxide tension gradient [P(v-a)CO2] and the arteriovenous oxygen content gradient ([C(a-v)O2]
- to assess whether central venous blood gas analyses can substitute pulmonary arterial (mixed venous) blood gas analyses in the [P(v-a)CO2] and [C(a-v)O2] gradients and ratio
- to assess whether arteriovenous O2 and CO2 gradients are more specific and contemporaneous measures of anaerobic metabolism compared to serum lactate
Hypotheses:
- Changes in [C(a-v)O2] and [P(v-a)CO2] gradients can be used as prognostic markers with persistently abnormal values correlating with the presence and degree of organ failure
- Changes in [C(a-v)O2] and [P(v-a)CO2] gradients can be used as targets during haemodynamic optimisation
- Cumulative measurements of [C(a-v)O2] and [P(v-a)CO2] gradients to generate an area under the curve value can be used to assess and target the presence of an oxygen debt
Main measurements
- Central venous, pulmonary arterial (mixed venous) and arterial blood gas analyses (pO2, pCO2, bicarbonate and lactate concentrations)
A fluid bolus will be administered as 250ml or 500ml of fluid (crystalloid or colloid) at 1500ml/hour. Measurements will be conducted immediately before fluid administration and 10 minutes post fluid cessation.
The following risk scores will be calculated: Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II and III), Simplified Acute Physiology Score (SAPS2), Australian New Zealand Risk of Death (ANZROD), Euroscore 2.
Routine biochemical tests will be recorded including electrolytes, renal function tests, liver function tests.
- Conditions
- Critically Ill, Hypovolemia
- Keywords
- Fluid responsiveness, Near-infrared spectroscopy, Thoracic surgery, Hypovolemia, veno-arterial carbon dioxide gradient, arterio-venous oxygen gradient, hypercarbia, Carotid artery, ultrasonography, Doppler
- Medical subject headings
- Critical Illness, Hypovolemia, Hypercapnia
What is being measured
The primary outcome is the main question the study is designed to answer.
Fluid bolus responsiveness
Fluid responsiveness will be determined by any increase in cardiac output (continuous outcome) or by a 10-15% increase in cardiac output (dichotomous outcome) following bolus volume expansion
Measured: Approximately 30 minutes
Volume management responsiveness
Responders will be defined as patients with an improvement (change towards normal physiological values) following cumulative volume expansion in any variable(s) used to assess oxygen delivery/consumption balance
Measured: Approximately 6 hours
Secondary outcomes (2)
Morbidity
Use and extent of measures to support organ function such as mechanical ventilation, mechanical and pharmacological cardiovascular interventions, renal replacement therapy whilst admitted to ICU as well as length of admission to ICU.
Measured: At ICU discharge, an average of 4 days
Mortality
Vital status censored at discharge from ICU and hospital
Measured: Up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study startMar 2016
- Primary completionNov 2016
- Study completionDec 2016
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 Critically IllStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- South West Sydney Local Health District
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anders Aneman, South West Sydney Local Health District
- Investigators
- Anders Aneman, MD, PhD, Study director, Liverpool Hospital, South Western Sydney Local Health District
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02841943
- Sponsor's protocol ID
- LIVICU001
- Acronym
- FRACAS
- Status last verified
- Mar 2017
- First submitted
- 15 Jul 2016
- Last updated
- 21 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Gupta K, Sondergaard S, Parkin G, Leaning M, Aneman A. Applying mean systemic filling pressure to assess the response to fluid boluses in cardiac post-surgical patients. Intensive Care Med. 2015 Feb;41(2):265-72. doi: 10.1007/s00134-014-3611-2. Epub 2015 Jan 8.
PubMed 25567379Sondergaard S, Parkin G, Aneman A. Central venous pressure: soon an outcome-associated matter. Curr Opin Anaesthesiol. 2016 Apr;29(2):179-85. doi: 10.1097/ACO.0000000000000305.
PubMed 26825283Rangappa R, Sondergaard S, Aneman A. Improved consistency in interpretation and management of cardiovascular variables by intensive care staff using a computerised decision-support system. Crit Care Resusc. 2014 Mar;16(1):48-53.
PubMed 24588436
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluid Responsiveness After Cardiac Surgery (FRACAS) Study
- ClinicalTrials.gov ID
- NCT02841943
- Acronym / sponsor ID
- FRACAS / LIVICU001
- Conditions
- Critically Ill, Hypovolemia
- Keywords
- Fluid responsiveness, Near-infrared spectroscopy, Thoracic surgery, Hypovolemia, veno-arterial carbon dioxide gradient, arterio-venous oxygen gradient, hypercarbia, Carotid artery
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- South West Sydney Local Health DistrictUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- Nov 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 22 Jul 2016 (estimated)
- 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.
Study Design: Prospective observational study
Study Location: Liverpool Hospital Intensive Care Unit, South Western Sydney Local Health District, Sydney, Australia.
Target study size: 100 patients
Ethics: Approved by the local Human Research and Ethics Council (HREC) at Liverpool Hospital (LPOOL) as a Low Negligible Risk (LNR) project [HREC/LNR/14/LPOOL/295, HREC/LNR/15/LPOOL47, HREC/LNR/14/LPOOL/150]
Participants: Post cardiac surgical patients admitted to the Intensive Care Unit between March-October 2016
Aims:
- to determine the descriptive and predictive value of variables (outlined below) related to oxygen delivery/consumption in regards to the effects of intravascular volume expansion
- to assess correlations between central and peripheral variables (outlined below) relevant to oxygen delivery/consumption
- to assess correlations between a set of variables (outline below) and patient centred outcomes in ICU and in hospital
Main variables collected:
- Tissue oxygen saturation by peripheral Near-Infrared Spectroscopy (NIRS)
- Common carotid arterial Doppler
- Arterial/mixed venous/central venous blood gas analyses
- Haemodynamic parameters
- Organ support measures
Data collection time points:
- ICU admission (within 30 minutes)
- Before administration of a fluid bolus
- After administration of a fluid bolus
- 6 hours after ICU admission
- Morning of first postoperative day (12-24 hours)
Outcome measures:
- the response to intravascular volume expansion
- ICU mortality, morbidity and length of stay and hospital mortality and length of stay
Data analysis:
- Clinical data are collected bedside using an electronic case record form
- Descriptive statistics
- Paired and unpaired comparative
- Correlative and predictive statistics
Detailed description
This prospective observational study program has a set of objectives within three major domains that will be analysed separately and synergistically:
Peripheral near infra-red spectroscopy (NIRS)
Aims:
- to describe the effects of non-sanguineous intravascular volume expansion on systemic oxygen delivery
- to describe how changes in systemic oxygen delivery impact on peripheral oxygen kinetics as measured by tissue oxygen saturation (StO2) in the thenar and forearm regions at rest and using a vascular occlusion test
- to determine the clinical applicability of using thenar and forearm NIRS to guide haemodynamic optimisation following cardiac surgery
- to assess the relation between systemic and peripheral oxygen kinetics vs. onset of organ dysfunction and need for extended stay in ICU following cardiac surgery
Hypotheses:
- Peripheral oxygen kinetics using NIRS offer more specific guidance for haemodynamic optimisation post cardiac surgery compared to using systemic variables only
- Impaired peripheral oxygen kinetics as assessed using NIRS can be used to identify patients at risk for developing organ dysfunction or needing extended period of ICU support an earlier stage compared to traditional systemic variables
Main measurements:
- peripheral near infrared spectroscopy (NIRS) measuring tissue oxygen saturation (StO2) at the thenar eminence and forearm during a 3 minute vascular occlusion test at 50mmHg above systolic pressure, following the establishment of a baseline (an StO2 average over 3 minutes with less than 5% variability)
- StO2 measurements are repeated at 30 minutes intervals during the first 6 hours following admission to ICU.
- vascular occlusion tests are repeated before and after volume expansion.
Cardiac output and common carotid Doppler sonography
Aims:
- to apply computerised algorithms to derive advanced haemodynamic information (mean systemic filling pressure, heart efficiency, vascular compliance) in patients requiring fluid boluses following cardiac surgery
- to correlate changes in cardiac output, cardiac power and estimates of fluid responsiveness using the pulmonary artery catheter with the variables mean systemic filling pressure and heart efficiency
- to characterise indices of fluid responsiveness by measuring volume efficiency
- to determine the impact of changes in vascular resistance state on the assessment of changes in volume state in the post-operative cardiac surgery period
- to assess the relation between fluid responsiveness, fluid management and clinical outcomes in ICU following cardiac surgery
- to evaluate the potential for carotid Doppler blood flow measurements as a surrogate parameter for cardiac output, including incorporation into computerised algorithms
Hypotheses:
- the derived measures of mean systemic filling pressure and heart efficiency are superior to identify fluid responsiveness compared to cardiac output measurements alone in patients following cardiac surgery
- carotid Doppler blood flow measurements can be used as a surrogate parameter for cardiac output and in particular for changes in cardiac output when fluid responsiveness is investigated
Main measurements:
- Pulmonary arterial thermodilution studies (for cardiac output, stroke volume, cardiac index) by at least triplicate injections within a ± 10% range
- Computerised algorithms are used to derive an analogue mean systemic filling pressure, heart efficiency, volume efficiency based on cardiac output, central venous pressure and mean arterial pressure
- Common carotid Doppler sonography to measure vessel diameter, cross sectional area and time average mean velocity to generate blood flow as well as respirophasic peak flow velocity variation
Oxygen and carbon dioxide gradients
Aims:
- to assess any insufficiency of oxygen delivery to match the oxygen consumption, resulting in anaerobic metabolism, by determining i) arteriovenous concentration gradients for lactate, ii) the venoarterial carbon dioxide tension gradient [P(v-a)CO2] and the arteriovenous oxygen content gradient ([C(a-v)O2]
- to assess whether central venous blood gas analyses can substitute pulmonary arterial (mixed venous) blood gas analyses in the [P(v-a)CO2] and [C(a-v)O2] gradients and ratio
- to assess whether arteriovenous O2 and CO2 gradients are more specific and contemporaneous measures of anaerobic metabolism compared to serum lactate
Hypotheses:
- Changes in [C(a-v)O2] and [P(v-a)CO2] gradients can be used as prognostic markers with persistently abnormal values correlating with the presence and degree of organ failure
- Changes in [C(a-v)O2] and [P(v-a)CO2] gradients can be used as targets during haemodynamic optimisation
- Cumulative measurements of [C(a-v)O2] and [P(v-a)CO2] gradients to generate an area under the curve value can be used to assess and target the presence of an oxygen debt
Main measurements
- Central venous, pulmonary arterial (mixed venous) and arterial blood gas analyses (pO2, pCO2, bicarbonate and lactate concentrations)
A fluid bolus will be administered as 250ml or 500ml of fluid (crystalloid or colloid) at 1500ml/hour. Measurements will be conducted immediately before fluid administration and 10 minutes post fluid cessation.
The following risk scores will be calculated: Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II and III), Simplified Acute Physiology Score (SAPS2), Australian New Zealand Risk of Death (ANZROD), Euroscore 2.
Routine biochemical tests will be recorded including electrolytes, renal function tests, liver function tests.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All adult patients electively admitted to the Intensive Care Unit following cardiac surgery
Key inclusion criteria (3 listed)
- Admitted following elective cardiac surgery
- Adult (>18 years of age)
- Pulmonary artery, central venous and arterial catheters inserted
Key exclusion criteria (4 listed)
- Emergency Patients (surgery immediately or within 12 hours of admission to hospital)
- Children (< 18 years of age)
- Patients admitted to ICU with ongoing extracorporeal circulatory support
- Patients re-admitted to ICU within same index hospital admission
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Fluid bolus responsiveness
Time frame: Approximately 30 minutes
Fluid responsiveness will be determined by any increase in cardiac output (continuous outcome) or by a 10-15% increase in cardiac output (dichotomous outcome) following bolus volume expansion
Volume management responsiveness
Time frame: Approximately 6 hours
Responders will be defined as patients with an improvement (change towards normal physiological values) following cumulative volume expansion in any variable(s) used to assess oxygen delivery/consumption balance
2 secondary outcomes
Morbidity
Time frame: At ICU discharge, an average of 4 days
Mortality
Time frame: Up to 3 months
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 21 Mar 2017.
- Background: PubMed 25567379Gupta K, Sondergaard S, Parkin G, Leaning M, Aneman A. Applying mean systemic filling pressure to assess the response to fluid boluses in cardiac post-surgical patients. Intensive Care Med. 2015 Feb;41(2):265-72. doi: 10.1007/s00134-014-3611-2. Epub 2015 Jan 8.
- Background: PubMed 26825283Sondergaard S, Parkin G, Aneman A. Central venous pressure: soon an outcome-associated matter. Curr Opin Anaesthesiol. 2016 Apr;29(2):179-85. doi: 10.1097/ACO.0000000000000305.
- Background: PubMed 24588436Rangappa R, Sondergaard S, Aneman A. Improved consistency in interpretation and management of cardiovascular variables by intensive care staff using a computerised decision-support system. Crit Care Resusc. 2014 Mar;16(1):48-53.
- Individual participant dataSharing planned: No
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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.
Anders Aneman, MD, PhD study director
Liverpool Hospital, South Western Sydney Local Health District
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 Critically Ill and Hypovolemia, run by South West Sydney Local Health District at 1 site in Australia.
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 3 inclusion and 4 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 21 Mar 2017. 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 Australia. 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?
Fluid bolus responsiveness (time frame: Approximately 30 minutes). The study lists 2 primary outcomes in all. 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 NCT02841943, 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 21 Mar 2017.