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Simple Intensive Care Studies I (SICS-I) (SICS-I)

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ClinicalTrials.gov Identifier: NCT02912624
Recruitment Status : Completed
First Posted : September 23, 2016
Last Update Posted : April 19, 2018
Sponsor:
Collaborator:
Copenhagen Trial Unit, Center for Clinical Intervention Research
Information provided by (Responsible Party):
I.C.C. van der Horst, University Medical Center Groningen

Brief Summary:

Circulatory shock is a condition of generalized inadequate blood flow through the body, leading to insufficient tissue perfusion and inadequate delivery of oxygen and other nutrients, to the extent that tissues are damaged. Four basic mechanisms of circulatory failure are distinguished, caused by a scale of underlying illnesses: distributive, hypovolemic, obstructive and cardiogenic shock. The last three types are characterized by a low cardiac output and hypovolemia. Distributive shock is characterized by peripheral circulation failure, with a low systemic vascular resistance, a disturbed microcirculation and a high cardiac output. Frequently, these forms overlap.

Shock is a common problem in the intensive care unit (ICU) as it affects about one third of the patients. Septic shock appears to be the most common type, followed by cardiogenic and hypovolemic shock. The diagnosis of shock is based on clinical examination with use of well-known circulatory parameters such as blood pressure and heart rate; biochemical parameters such as lactate and direct (semi-)invasive measurement of cardiac output and other variables.

Since cardiac output is an important determinant of oxygen delivery, many different methods of measuring cardiac output have been suggested. These methods range from non-invasive to invasive measurements with central lining. The most invasive method, the pulmonary artery catheter (PAC) has long been considered the optimal form of monitoring cardiac output by using thermodilution. However, this technique is associated with adverse events, such as bleeding, and there is no clear evidence of improved outcome. Therefore, numerous other techniques have been proposed, ranging from systems that use the dilution technique but only require central venous and peripheral artery lines; to less invasive tools that estimate cardiac output based on the arterial pressure waveform; and to non-invasive echocardiography.

Despite technical advances, much remains unknown about the value of conventionally used hemodynamic parameters for estimating cardiac output. A distinction between macro- and microcirculatory parameters can be made. Commonly used macro-circulatory parameters are heart rate, systolic and diastolic blood pressure, mean arterial pressure and central venous pressure. Lactate is used as a proxy for microcirculatory status. Over the years several other measurements have been suggested to improve insight in the hemodynamics of a certain patient or a group of patients. Skin temperature, capillary refill, mottling score and urinary output are used for hemodynamic assessment of the peripheral circulation and tissue perfusion. Most of these parameters have not been evaluated in a large prospective study and especially a combination of all these parameters has not directly been correlated to cardiac output.

More knowledge on the predictive value of all hemodynamic parameters in estimating cardiac output could assist physicians in earlier detection of impaired hemodynamics without the need for invasive or advanced methods. In this study the investigators aim to evaluate all hemodynamic parameters in a large unselected population of critically ill patients and to correlate them to cardiac output.

Purpose:

The purpose of this study is to create an infrastructure for a registry flexible to incorporate temporarily added specific research questions on the outcome of critically ill patients.


Condition or disease
Critical Illness Acute Disease Shock

  Show Detailed Description

Study Type : Observational [Patient Registry]
Actual Enrollment : 1090 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 90 Days
Official Title: Combining Conventional With Advanced Hemodynamic Parameters for Predicting the Outcome of Critically Ill Patients: a Pilot for a Registry
Actual Study Start Date : March 27, 2015
Actual Primary Completion Date : July 22, 2017
Actual Study Completion Date : November 1, 2017



Primary Outcome Measures :
  1. The association of a single or combination of clinical examination findings with cardiac index measured with transthoracic ultrasonography [ Time Frame: Immediately ]

    Primary outcome of the basic study, answering our diagnostic research question

    We calculated cardiac index, which was derived from cardiac output. Cardiac output has been measured with the cardiac probe M3S of M4S with default cardiac imaging setting of the General Electric Vivid-S6 mobile ultrasound machine. Two views were obtained: the parasternal long axis (PLAX) and the apical five chamber view (AP5CH). The PLAX was used as the primary view to measure the left ventricular outflow tract (LVOT) diameter. The AP5CH view was used to measure the velocity time integral (VTI) using the pulse wave Doppler signal in the LVOT. Cardiac output was calculated on the ultrasound machine according to the formula: Cardiac output (L/min)=heart rate ∙VTI∙π∙(1/2∙LVOT)^2

    Clinical examination findings have been collected during a one-time physical examination, which is further specified at the study description section.


  2. The association of all measured clinical examination findings, biochemical values and hemodynamic variables measured with transthoracic echocardiography with 90-day mortality [ Time Frame: 90 days ]

    Primary outcome of the basic study, answering our prognostic research question.

    Clinical examination findings, as well are specified at the study description section.

    Biochemical values are serum lactate, creatinine and hemoglobine (see study description).

    Hemodynamic variables are obtained from advanced patient monitoring devices, such as invasive central venous or arterial blood pressures, echocardiographic measurements, etc.

    Follow-up on all-cause mortality will be obtained from the municipal personal records database. Analysis of mortality will be performed using time-to-event data (patients were censored at 90-days of follow-up).



Secondary Outcome Measures :
  1. The diagnostic test accuracy of a single or a combination of clinical examination findings to diagnose a low, normal and high cardiac index measured with transthoracic echocardiography [ Time Frame: Immediately ]

    Secondary outcome of the basic study, answering our diagnostic research question.

    For this outcome, we will determine the cut-offs as follows:

    1. Use a cardiac index cut-off of 2.2 L/min/m2
    2. Identify the optimal cut-off(s) for cardiac index. We will use dot plots to assess the distribution of cardiac index stratified by the presence or absence of each (combination of) clinical examination finding(s) that indicate hypoperfusion. We will conduct a logistic regression with the dichotomised clinical examination finding as dependent variable and cardiac index as independent variable, including the assumed covariate(s) of each finding, and compute receiver operating characteristic (ROC)-curves to identify the optimal cut-off(s).

  2. The association and diagnostic test accuracy of a single or combination of clinical examination findings with cardiac index in clinically different patient subgroups [ Time Frame: Immediately ]

    Secondary outcome of the basic study, answering our diagnostic research question.

    If the sample size permits, we will conduct subgroup analysis in different subpopulations. We will create the following subgroups in the basic study and test both our prognostic and diagnostic hypotheses on:

    • Subgroup 1: subdivide the population into three groups: no shock, shock associated with a low cardiac output, shock associated with a high cardiac output.
    • Subgroup 2: subdivide the population by underlying pathologies that could influence the haemodynamic measurements in a patient: Patients admitted due to cardiac arrest, myocardial infarction, after liver transplantation or liver failure, and severe sepsis. Patients admitted or known with heart failure, central nervous system pathologies, and severe chronic cardiovascular disease.

  3. The association of clinical examination, biochemical and haemodynamic variables and 7- and 30-day mortality [ Time Frame: 30 days ]

    Secondary outcome of the basic study, answering our prognostic research question.

    This will be a sensitivity analyses on different follow-up times of mortality.


  4. The association of clinical examination, biochemical and haemodynamic variables that are not visible to caregivers with 90-day mortality [ Time Frame: 90 days ]

    Secondary outcome of the basic study, answering our prognostic research question.

    Variables not visible to caregivers are some of our clinical examination findings and cardiac index measurements. Clinical examination findings that were not shared with caregivers, were: capillary refill times, mottling scores and peripheral temperature measurements.


  5. The association of clinical examination, biochemical and haemodynamic variables with 90-day mortality in clinically different patient subgroups [ Time Frame: 90 days ]

    Secondary outcome of the basic study, answering our prognostic research question.

    If the sample size permits, we will conduct subgroup analysis in different subpopulations. We will create the following subgroups in the basic study and test both our prognostic and diagnostic hypotheses on:

    • Subgroup 1: subdivide the population into three groups: no shock, shock associated with a low cardiac output, shock associated with a high cardiac output.
    • Subgroup 2: subdivide the population by underlying pathologies that could influence the haemodynamic measurements in a patient: Patients admitted due to cardiac arrest, myocardial infarction, after liver transplantation or liver failure, and severe sepsis. Patients admitted or known with heart failure, central nervous system pathologies, and severe chronic cardiovascular disease.


Other Outcome Measures:
  1. The association between clinical, biochemical and haemodynamic variables and tissue (muscle) StO2 at the knee measured by near-infrared spectroscopy (NIRS) with the Inspectra StO2 tissue oxygenation monitor [ Time Frame: Immediately ]

    Substudy 1 - primary outcome

    StO2 was measured by NIRS with the Inspectra StO2 tissue oxygenation monitor, model 650 (Hutchinson Technology, Inc., Hutchinson, Minnesota, USA). We used a 15-mm probe to measure the StO2 at a depth of 14mm at two sites: the thenar eminence and the distal end of the vastus medialis muscle. The average StO2 value was calculated over 30 seconds after one minute of signal stabilisation.


  2. The association between clinical, biochemical and haemodynamic variables and tissue (muscle) StO2 at the thenar muscle measured by near-infrared spectroscopy (NIRS) with the Inspectra StO2 tissue oxygenation monitor [ Time Frame: Immediately ]
    Substudy 1 - secondary outcome

  3. The association between tissue (muscle) StO2 measured by NIRS and 90-day mortality [ Time Frame: Immediately ]
    Substudy 1 - secondary outcome

  4. The diagnostic test accuracy of a B-profile measured with pulmonary ultrasonography compared to pulmonary oedema diagnosed by chest radiography [ Time Frame: Immediately ]

    Substudy 2 - primary outcome

    Pulmonary ultrasound was conducted with the cardiac probe M3S of M4S with default cardiac imaging and maximal frequency (3.6 MHz) setting of the General Electric Vivid-S6 mobile ultrasound machine. We measured the presence or absence of B-lines at the six locations specified in the BLUE-protocol. The presence of a B-profile was defined by three or more B lines observed in at least three of the six BLUE points, or in two of the four lower BLUE points.

    Pulmonary oedema was diagnosed by the radiologist who reviewed chest radiographs as part of daily care. The radiologist was blinded for the variables collected in our study.


  5. The diagnostic test accuracy of pulmonary crackles assessed with auscultation compared to pulmonary oedema diagnosed by chest radiography [ Time Frame: Immediately ]
    Substudy 2 - primary outcome

  6. The statistically and clinically significant difference in CO between patients with and without a B-profile measured with pulmonary ultrasonography [ Time Frame: Immediately ]

    Substudy 2 - secondary outcome

    The presence of a B-profile was defined by three or more B lines observed in at least three of the six BLUE points, or in two of the four lower BLUE points.


  7. The association between PEEP increase and cardiac output measured with transthoracic echocardiography [ Time Frame: Immediately ]

    Substudy 3 - primary outcome

    Cardiac output was measured using the same ultrasound machine, probes, views and formulas as described in the primary outcome of the basic study.

    During the PEEP-challenge, an additional 10 cm H2O of PEEP was temporarily applied when supervised by the treating ICU physician. The PEEP was elevated for a maximum duration of 5 minutes during which the changes in cardiac output, heart rate, blood pressures and central venous pressure were recorded.


  8. The association between RV-function measured by TAPSE or RV s' with transthoracic echocardiography and 90-day mortality [ Time Frame: 90 days ]

    Substudy 4 - primary outcome

    TAPSE and RV s' have been measured with the cardiac probe M3S of M4S with default cardiac imaging setting of the General Electric Vivid-S6 mobile ultrasound machine. Both measurements were obtained in the AP4CH view. TAPSE was assessed in M-mode, after placing the cursor on the junction of the tricuspid valve and the RV free wall. RV s' was assessed in the tissue velocity imaging mode highlighting the area of interest. The pulsed Doppler sample volume was placed at the tricuspid level of the RV free (i.e. lateral) wall and the longitudinal velocity of excursion was measured.


  9. The association between RV-function measured by TAPSE or RV s' with transthoracic echocardiography and clinical examination findings and cardiac output measured with transthoracic echocardiography [ Time Frame: Immediately ]
    Substudy 4 - secondary outcome

  10. The association between peripheral blood flow measured at the common carotid, subclavian, and common femoral arteries and cardiac output, all measured with (transthoracic) echocardiography [ Time Frame: Immediately ]

    Substudy 5 - primary outcome

    Common carotid artery, subclavian artery, and common femoral artery flows have been measured with the linear probe 8L or 9L and default carotid setting of the General Electric Vivid-S6 mobile ultrasound machine.


  11. The association between a calculated proxy for abdominal organ blood flow and acute kidney injury (AKI) according to the KDIGO criteria or 90-day mortality [ Time Frame: 90 days ]

    Substudy 5 - secondary outcome

    A proxy for abdominal flow was calculated by subtracting flow over both left and right carotid, subclavian and femoral arteries from the cardiac output.

    AKI was established and classified following the kidney disease: improving global outcomes (KDIGO) criteria. Urine output and serum creatinine measurements from the first 72 hours of inclusion were analysed to establish and classify AKI for each patient.


  12. The level of agreement between cardiac output measured by the FloTrac and cardiac output measured with transthoracic echocardiography [ Time Frame: 24 hours ]

    Substudy 6 - primary outcome

    Cardiac output has been estimated with the FloTrac (Edwards Lifesciences, Irvine, California, USA) and a monitor to compute stroke volume and cardiac output (Vigileo, Edwards Lifesciences, Irvine, California, USA). The FloTrac analyses the arterial pressure waveform to compute stroke volume and cardiac output. The estimated cardiac output was compared to the cardiac output measured with the General Electric Vivid-S6 mobile ultrasound machine.


  13. The changes in levels of agreement when factors are present that might influence the FloTrac measurements of cardiac output [ Time Frame: 24 hours ]
    Substudy 6 - secondary outcome

  14. The association between changes in clinical examination findings over 24 hours and changes in cardiac output measured with transthoracic echocardiography [ Time Frame: 24 hours ]

    Substudy 7 - primary outcome

    We repeated the measurements of the variables collected in the basic study, sub-study 2, and sub-study 4. We performed these measurements 24 hours (minimum 22 to maximum 26 hours) after the first measurement and calculated differences. The sign of the variable indicates whether a variable has either increased (positive number) or decreased (negative number).


  15. The association between changes in clinical examination, biochemical, and hemodynamic variables over 24 hours and 90-day mortality [ Time Frame: 90 days ]
    Substudy 7 - secondary outcome

  16. The association between RV-volume overload measured by tricuspid insufficiency and RV-diameters measured with transthoracic echocardiography and AKI by the KDIGO criteria [ Time Frame: Immediately ]

    Substudy 8 - primary outcome

    Right ventricle diameters and tricuspid regurgitation velocity have been measured with the cardiac probe M3S of M4S with default cardiac imaging setting of the General Electric Vivid-S6 mobile ultrasound machine. The measurements were obtained in the AP4CH view with a right ventricle centred view.

    AKI was established and classified following the kidney disease: improving global outcomes (KDIGO) criteria. Urine output and serum creatinine measurements from the first 72 hours of inclusion were analysed to establish and classify AKI for each patient.


  17. The association between clinical, biochemical, and hemodynamic variables and the development of AKI according to the KDIGO criteria [ Time Frame: Immediately ]
    Substudy 8 - primary outcome

  18. The association between RV-volume overload measured by tricuspid insufficiency and RV diameters measured with transthoracic echocardiography and 90-day mortality [ Time Frame: 90 days ]
    Substudy 8 - secondary outcome

  19. The association between clinical, biochemical, and hemodynamic variables and the development of AKI regardless of the presence of pre-existent chronic kidney disease [ Time Frame: Immediately ]
    Substudy 8 - secondary outcome

  20. The diagnostic accuracy of fluid responsiveness assessed by changes in EtCO2, heart rate and blood pressure compared to the PLR test [ Time Frame: Immediately ]

    Substudy 9 - primary outcome

    Every passive leg raising manoeuvre was conducted for a maximum duration of 60 seconds during which the changes in cardiac output, heart rate, blood pressures, central venous pressure, and EtCO2 were recorded. Fluid responsiveness was diagnosed when cardiac output increased with 15% after the PLR-test.


  21. The diagnostic accuracy of fluid responsiveness assessed by a PLR test without lowering the head of the bed compared to the standard PLR test [ Time Frame: Immediately ]

    Substudy 9 - primary outcome

    During the fluid responsiveness study, two different PLR tests were applied when supervised by the treating ICU physician.


  22. The association between a temporary PEEP-increase and cardiac output measured with transthoracic echocardiography in fluid responders and fluid non-responders [ Time Frame: Immediately ]

    Substudy 9 - secondary outcome

    Fluid responsiveness was diagnosed when cardiac output increased with 15% after the PLR-test. The PEEP-challenge was conducted in a similar manner as described in sub-study 3.


  23. The diagnostic accuracy of a temporary PEEP-increase compared to the standard PLR test [ Time Frame: Immediately ]
    Substudy 9 - secondary outcome

  24. The diagnostic accuracy of a B-profile assessed with pulmonary ultrasonography compared to bilateral consolidations assessed on chest radiography for the diagnosis of ARDS [ Time Frame: Immediately ]

    Substudy 10 - primary outcome

    ARDS will be defined according to the Berlin ARDS criteria: 1) presence of acute hypoxemic respiratory failure defined by a PaO2/FiO2 ratio < 300 mm Hg and PEEP ≥ 5 cm H2O; 2) onset within one week of clinical insult or worsening respiratory symptoms; 3) bilateral consolidations on chest radiography or CT-thorax.


  25. The association between B-lines measured with pulmonary ultrasonography and clinical examination findings, biochemical values and hemodynamic variables [ Time Frame: Immediately ]

    Substudy 10 - secondary outcome

    Clinical examination findings, as well are specified at the study description section.

    Biochemical values are serum lactate, creatinine and hemoglobine (see study description).

    Hemodynamic variables are obtained from advanced patient monitoring devices, such as invasive central venous or arterial blood pressures, echocardiographic measurements, etc.


  26. The association between LV- and RV-myocardial strain measured by tissue Doppler imaging with transthoracic echocardiography and 90-day mortality [ Time Frame: 90 days ]

    Substudy 11 - primary outcome

    Myocardial strain and myocardial strain rates have been measured with the cardiac probe M3S of M4S with default cardiac imaging setting of the General Electric Vivid-S6 mobile ultrasound machine. The measurements were obtained in the AP4CH window with a left ventricle and right ventricle centred view for left and right myocardial strain, respectively.


  27. The association between LV- and RV-myocardial strain imaging and conventional CCUS measurements such as TAPSE, RV 's and cardiac output, all obtained with transthoracic echocardiography [ Time Frame: Immediately ]
    Substudy 11 - secondary outcome

  28. The level of agreement between myocardial strain measured by tissue Doppler imaging and myocardial strain rate measured by speckle tracking, both obtained with transthoracic echocardiography [ Time Frame: Immediately ]
    Substudy 11 - secondary outcome



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
The study will be conducted in the adult Critical Care of the University of Groningen, University Medical Center Groningen, a tertiary teaching hospital in the Northern part of the Netherlands.
Criteria

Inclusion Criteria:

  • Emergency admission
  • Expected stay > 24 hours

Exclusion Criteria:

  • Age < 18 years
  • Planned admission (either after surgery or for other reasons)
  • Withdrawn or unable to obtain informed consent
  • Continuous resuscitation efforts or mechanical circulatory support

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02912624


Locations
Netherlands
University Medical Center Groningen
Groningen, Netherlands, 9700 RB
Sponsors and Collaborators
University Medical Center Groningen
Copenhagen Trial Unit, Center for Clinical Intervention Research
Investigators
Principal Investigator: Iwan CC van der Horst, M.D., Ph.D. University of Groningen, University Medical Center Groningen
  Study Documents (Full-Text)

Documents provided by I.C.C. van der Horst, University Medical Center Groningen:
Statistical Analysis Plan  [PDF] April 3, 2018


Publications:
Responsible Party: I.C.C. van der Horst, Associate professor, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT02912624     History of Changes
Other Study ID Numbers: 201500144
First Posted: September 23, 2016    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by I.C.C. van der Horst, University Medical Center Groningen:
Physical Examination
Diagnostic Imaging
Ultrasonography
Hemodynamics
Patient Outcome Assessment
Mortality

Additional relevant MeSH terms:
Critical Illness
Acute Disease
Disease Attributes
Pathologic Processes