<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03285269</url>
  </required_header>
  <id_info>
    <org_study_id>ERUSH-001</org_study_id>
    <nct_id>NCT03285269</nct_id>
  </id_info>
  <brief_title>Extension of the RUSH Protocol for Volume Responsiveness</brief_title>
  <official_title>Extension of the Rapid Ultrasound for Shock and Hypotension to Evaluate Volume Responsiveness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kaiser Permanente</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kaiser Permanente</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The current study plants to create a patient registry of patients who present to the&#xD;
      emergency department with signs and symptoms of shock and evaluate the ability of a&#xD;
      multi-step cardiopulmonary ultrasound protocol to determine the need for fluid therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background &amp; Motivation: Non-traumatic shock accounts for millions of emergency department&#xD;
      visits every year and is a significant burden on the health care system making rapid&#xD;
      identification and treatment essential. For decades the Rapid Ultrasound in Shock and&#xD;
      Hypotension (RUSH) exam has been employed to help determine the etiology of non-traumatic&#xD;
      shock in the ED setting. The RUSH exam does not answer other critical questions such as the&#xD;
      need for additional fluid resuscitation. The current study hypothesizes that by include a&#xD;
      step-wise cardiopulmonary algorithm the RUSH exam can be extended (E-RUSH) to accurately&#xD;
      determine the need for additional fluid therapy.&#xD;
&#xD;
      Study Design: Prospective Observational Study in two urban Emergency Departments with a&#xD;
      combined annual census of &gt;111,000.&#xD;
&#xD;
      Population: ED patients exhibiting signs of shock definied by a systolic blood pressure &lt; 100&#xD;
      mmhg, MAP &lt; 65, persistent tachycardia, mottled skin, or lactate &gt;2mmol either at&#xD;
      presentation or during ED stay will be included. Exclusion criteria will be inability to&#xD;
      consent, external factors preventing ultrasound examination, age less than 18, pregnancy,&#xD;
      incarceration, arrhythmia, cardiac arrest, or treating physician gestalt that the patient is&#xD;
      not in shock.&#xD;
&#xD;
      Protocol: The E-RUSH protocol will include ultrasound exams of the IVC, heart and lungs as&#xD;
      described in the RUSH protocol but will also evaluate cardiac output, IVC collapsibility, and&#xD;
      presense of B-lines on lung ultrasound. At the time of ultrasound measuresments a&#xD;
      bioreactance device will be applied. Bioreactance measurements and ultrasound measurement of&#xD;
      cardiac output will be recorded pre and post a passive straight leg raise test. All charts&#xD;
      will be reviewed by two experts who are blinded to ultrasound and bioractance measurements.&#xD;
      When possible the protocol will be repeated 1-2 hours later or after initial interventions in&#xD;
      order to provide trend data.&#xD;
&#xD;
      Data Analysis: Volume responsivness as assessed by the E-RUSH will be defined a priori using&#xD;
      a step-wise flow diagram that combines IVC, lung and cardiac ejection fraction and output&#xD;
      measurements (see research plan for details). Determination of volume responsiveness by the&#xD;
      bioreactance device will be defined by manufacturer protocal. Determination of volume&#xD;
      responsiveness by expert review will be by a standard abstraction form with agreement of both&#xD;
      expert reviewers. Descriptive statistics will be performed to determine the test&#xD;
      characteristics of the ultrasound protocol to predict volume responsiveness. Given the lack&#xD;
      of a universally agreed upon gold standard for volume responsiveness, we will determine test&#xD;
      characteristics for E-RUSH using the bioreactance device as a reference standard and using&#xD;
      expert review as a second reference standard separately.&#xD;
&#xD;
      FACILITY RESOURCES The study facilities are in San Diego California, with a combined&#xD;
      emergency department census of over 111,000 patients per year. The emergency departments of&#xD;
      the facilities are equipped with portable bedside ultrasound machines, CT and MRI, 24 hour&#xD;
      laboratory testing and an integrated electronic medical record system. Emergency medicine and&#xD;
      family medicine residents rotate through both emergency departments. Both departments are&#xD;
      stroke receiving centers and level 3 trauma centers.&#xD;
&#xD;
      Research Databases An important aspect of the KPSC managed care environment is its integrated&#xD;
      approach to the delivery of medical care. This approach depends on, and therefore&#xD;
      facilitates, the development and maintenance of a large number of databases, linkable through&#xD;
      a unique identification key. These databases include those that track membership, encounters,&#xD;
      laboratory, claims, pharmaceutical dispensations and others. The address information is&#xD;
      annually geo-coded to the census block level, providing linkage to census-based group-level&#xD;
      information about socio-economic status.&#xD;
&#xD;
      Each of the KPSC clinical operations systems are updated in real-time, facilitating our&#xD;
      ability to create near real-time research databases. Our Membership database captures&#xD;
      demographic (e.g., name, date of birth, gender, race/ethnicity, etc.) and benefit information&#xD;
      for over 12 million active and former members, and is updated on a weekly basis. The&#xD;
      utilization database captures outpatient and hospital encounters (e.g., diagnoses,&#xD;
      procedures, etc.), member claims submitted from outside hospitals (usually with up to 3-month&#xD;
      delay), and care provided at home, skilled nursing and hospice facilities. This database is&#xD;
      updated weekly. Outpatient and inpatient pharmacy databases track medication orders and&#xD;
      dispenses, and are updated either daily or monthly depending on the source system. Death&#xD;
      information is derived from multiple sources including KP hospital and membership data, as&#xD;
      well as two external sources from California State and Social Security Administration death&#xD;
      files. The state death records lag about one to two years for date and underlying cause of&#xD;
      death and between two and three years for all causes listed on the death certificate.&#xD;
&#xD;
      SCIENTIFIC ENVIRONMENT Biostatistical expertise is provided by a Biostatistics Unit that&#xD;
      consists of statisticians, programmers, natural language specialists, database developers and&#xD;
      administrators. The Unit provides services including statistical consultation, data analysis,&#xD;
      data extraction, disease identification based on free-texts and data management for research&#xD;
      projects. In addition, the Unit is responsible for creating many of the research data bases&#xD;
      used. All Unit employees have SAS programming skills and years of experience in conducting&#xD;
      broad and varied research. The Biostatistics Unit supports more than 300 research projects&#xD;
      annually.&#xD;
&#xD;
      Oversight of Research at KPSC KPSC has an Institutional Review Board (IRB) under the Medical&#xD;
      Director of Operations for the Southern California Permanente Medical Group. The IRB is&#xD;
      charged with the protection of human subjects through the oversight of all investigators and&#xD;
      their research projects in Kaiser Permanente Southern California. Compliance with the minimum&#xD;
      Federal standards for the protection of human subjects in research is demonstrated by a&#xD;
      Federal Wide Assurance (FWA) held through the Kaiser Foundation Research Institute. The IRB&#xD;
      also acts as the KPSC HIPAA privacy board.&#xD;
&#xD;
      Ethics Kaiser Permanente - Southern California (KPSC) shall obtain written evidence of review&#xD;
      and approval from our independent ethics committee (IRB) of the protocol, informed consent&#xD;
      forms, evidence of partial waiver, and all other documents requiring IRB review and approval&#xD;
      prior to the initiation of the project.&#xD;
&#xD;
        1. RISKS TO THE SUBJECTS&#xD;
&#xD;
             1. Human Subjects Involvement and Characteristics Describe the proposed involvement of&#xD;
                human subjects in the work outlined in the Research Design and Methods section.&#xD;
&#xD;
                The study population are ED patients exhibiting signs of shock definied by a&#xD;
                systolic blood pressure &lt; 100 mmhg, MAP &lt; 65, persistent tachycardia, mottled skin,&#xD;
                or lactate &gt;2mmol either at presentation or during ED stay will be included.&#xD;
                Exclusion criteria will be inability to consent, external factors preventing&#xD;
                ultrasound examination, age less than 18, pregnancy, incarceration, traumatic&#xD;
                mechanism, arrhythmia, cardiac arrest, or treating physician gestalt that the&#xD;
                patient is not in shock. Our goal is to enroll a total of 50 patients.&#xD;
&#xD;
                This study will not recruit subjects defined as vulnerable populations. Individuals&#xD;
                age less than 18 and pregnant women will be excluded as noted in the exclusion&#xD;
                criteria.&#xD;
&#xD;
             2. Sources of Materials&#xD;
&#xD;
           The following data will be obtained from the patient:&#xD;
&#xD;
             -  Consent Form&#xD;
&#xD;
             -  ultrasound will be used to perform visual assessment of the patient's inferior vena&#xD;
                cava&#xD;
&#xD;
             -  Variables including but not limited to: systolic blood pressure, MAP, persistent&#xD;
                tachycardia, mottled skin, or lactate status, age, pregnancy status, arrhythmia,&#xD;
                cardiac arrest,&#xD;
&#xD;
             -  &quot;Electronic Health Data&quot; - All charts will be reviewed by two experts who are&#xD;
                blinded to ultrasound and bioractance measurements.&#xD;
&#xD;
             -  Bioreactance measurements and ultrasound measurement of cardiac output will be&#xD;
                recorded pre and post a passive straight leg raise test.&#xD;
&#xD;
           The data collected will be linked/coded using a study identification number (SID) and&#xD;
           only KPSC study team members and persons directly involved in recruitment will have&#xD;
           access to the key that identifies individual subjects.&#xD;
&#xD;
        2. ADEQUACY OF PROTECTION AGAINST RISKS&#xD;
&#xD;
             1. Recruitment and Informed Consent We will obtain a waiver to access and use the EHR&#xD;
                data for case/patient identification. The waiver will be used to identify patients&#xD;
                in order approach patients regarding the study and to obtain consent. Study&#xD;
                personnel will screen the ED tracking board and communicate with ED providers to&#xD;
                find patients meeting inclusion criteria. Upon identification study personnel, will&#xD;
                approach patient in the private exam room to obtain informed consent in person.&#xD;
&#xD;
                The study will not recruit anyone less than 18 or women who are pregnant. However,&#xD;
                due to the rich diversity of Kaiser Permanente's membership in Southern California,&#xD;
                Spanish speakers will be recruited. All materials and forms will be translated to&#xD;
                Spanish to include all Spanish speaking/reading potential participants. Consent&#xD;
                forms will be stored securely onsite and a study database will be maintained. All&#xD;
                patients will be provided a copy of the consent form.&#xD;
&#xD;
             2. Protection Against Risk Names and other identifying information on participants&#xD;
                will be obtained for record keeping purposes only and no participants will be&#xD;
                identified in any forms or reports from this study. Survey and clinical data will&#xD;
                only be shared internally among KPSC study team members and only persons directly&#xD;
                involved in recruitment will have access to the key that identifies individual&#xD;
                subjects. Transfer of data if needed will be via encrypted email.&#xD;
&#xD;
        3. POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS The immediate&#xD;
           benefit to the participant is none. However, If the E-RUSH protocol proves accurate and&#xD;
           useful, it has the potential to improve patient care and safety and a vulnerable and&#xD;
           high risk population. There are no high-risk aspects of the proposed work.&#xD;
&#xD;
        4. IMPORTANCE OF THE KNOWLEDGE TO BE GAINED There are no high-risk aspects of the proposed&#xD;
           work. The importance of the current study presents an innovative algorithm that my&#xD;
           further demonstrate the ability of ultrasound to be useful in the shock patient to&#xD;
           determine fluid needs. If an algorithmic approach using bedside ultrasound proves&#xD;
           accurate in titrating fluid resuscitation, it could reduce complications of under&#xD;
           resuscitation (organ failure) and over resuscitation (pulmonary edema, third spacing and&#xD;
           abdominal compartment syndrome). Avoidance of complications would have downstream&#xD;
           benefits such as reduced length of stay, reduced mortality, and reduced burden on the&#xD;
           healthcare system.&#xD;
&#xD;
        5. DATA AND SAFETY MONITORING PLAN Our study will not be a clinical trial. All the&#xD;
           information and/or databases will be password protected to ensure security of the PHI&#xD;
           contained in the data systems. Study data access that would identify participants will&#xD;
           be tightly controlled and limited to authorized individuals using the follow safeguards:&#xD;
           roles and privileges, defined data owners, automatic log off and lockouts, field level&#xD;
           hide, read only, or read-write permission at user level, encryption of data transfers,&#xD;
           and limited/controlled delete capabilities. Standard backup procedures will be employed&#xD;
           at Kaiser Permanente, where data will be backed up nightly to a secured disk based&#xD;
           storage system and then offloaded to a robotic tape library system, with tapes rotated&#xD;
           offsite for additional level of protection. This ensures against data loss in the event&#xD;
           of a local systems failure or natural disaster.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study was not initiated because it was not approved by KPSC IRB.&#xD;
  </why_stopped>
  <start_date type="Anticipated">November 2017</start_date>
  <completion_date type="Anticipated">November 2018</completion_date>
  <primary_completion_date type="Anticipated">November 2018</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>1 Month</target_duration>
  <primary_outcome>
    <measure>Test Characteristics of the E-RUSH Protocol to Predict Fluid Responsiveness</measure>
    <time_frame>1 year</time_frame>
    <description>Will determine sensitivity and specificity of a step-wise cardiopulmonary approach to determine fluid responsivness.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">0</enrollment>
  <condition>Shock</condition>
  <arm_group>
    <arm_group_label>Shock Group</arm_group_label>
    <description>Patients presenting with signs and symptoms of shock will undergo the E-RUSH ultrasound protocol and bioreactance before and after a passive leg raise maneuver.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Ultrasound Protocol</intervention_name>
    <description>Ultrasound of the inferior vena cava, heart and lungs.</description>
    <arm_group_label>Shock Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Bioreactance</intervention_name>
    <description>Bioreactance assessment using Cheetah Bioreactance Device (FDA Approved). Bioreactance is a non-invasive measure of cardiac output.</description>
    <arm_group_label>Shock Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Passive Leg Raise</intervention_name>
    <description>A passive leg raise involves placing the patient supine and raising the legs to simulate an intravenous fluid bolus.</description>
    <arm_group_label>Shock Group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients presenting to the one of two urban emergency department with signs and symptoms of&#xD;
        shock.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ED patients exhibiting signs of shock definied by a systolic blood pressure &lt; 100&#xD;
             mmhg, MAP &lt; 65, persistent tachycardia, mottled skin, or lactate &gt;2mmol either at&#xD;
             presentation or during ED stay will be included&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Exclusion criteria will be inability to consent, external factors preventing&#xD;
             ultrasound examination, age less than 18, pregnancy, incarceration, arrhythmia,&#xD;
             cardiac arrest, or treating physician gestalt that the patient is not in shock.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason M Fields, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaiser Permanenete</affiliation>
  </overall_official>
  <reference>
    <citation>Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.</citation>
    <PMID>11445675</PMID>
  </reference>
  <reference>
    <citation>Bentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT. Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids? JAMA. 2016 Sep 27;316(12):1298-309. doi: 10.1001/jama.2016.12310.</citation>
    <PMID>27673307</PMID>
  </reference>
  <reference>
    <citation>Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011 Feb;39(2):259-65. doi: 10.1097/CCM.0b013e3181feeb15.</citation>
    <PMID>20975548</PMID>
  </reference>
  <reference>
    <citation>Corl KA, George NR, Romanoff J, Levinson AT, Chheng DB, Merchant RC, Levy MM, Napoli AM. Inferior vena cava collapsibility detects fluid responsiveness among spontaneously breathing critically-ill patients. J Crit Care. 2017 Oct;41:130-137. doi: 10.1016/j.jcrc.2017.05.008. Epub 2017 May 12.</citation>
    <PMID>28525778</PMID>
  </reference>
  <reference>
    <citation>Monnet X, Marik PE, Teboul JL. Prediction of fluid responsiveness: an update. Ann Intensive Care. 2016 Dec;6(1):111. doi: 10.1186/s13613-016-0216-7. Epub 2016 Nov 17.</citation>
    <PMID>27858374</PMID>
  </reference>
  <reference>
    <citation>Oord M, Olgers TJ, Doff-Holman M, Harms MP, Ligtenberg JJ, Ter Maaten JC. Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild sepsis in the emergency department: a pilot study. BMJ Open. 2017 Jan 27;7(1):e013465. doi: 10.1136/bmjopen-2016-013465.</citation>
    <PMID>28132006</PMID>
  </reference>
  <reference>
    <citation>Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.</citation>
    <PMID>11794169</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>January 6, 2022</last_update_submitted>
  <last_update_submitted_qc>January 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>shock</keyword>
  <keyword>ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Shock</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Not planning to share IPD</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03285269
org study id: ERUSH-001
nct id: NCT03285269
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The current study plants to create a patient registry of patients who present to the
      emergency department with signs and symptoms of shock and evaluate the ability of a
      multi-step cardiopulmonary ultrasound protocol to determine the need for fluid therapy.
Background & Motivation: Non-traumatic shock accounts for millions of emergency department
      visits every year and is a significant burden on the health care system making rapid
      identification and treatment essential. For decades the Rapid Ultrasound in Shock and
      Hypotension (RUSH) exam has been employed to help determine the etiology of non-traumatic
      shock in the ED setting. The RUSH exam does not answer other critical questions such as the
      need for additional fluid resuscitation. The current study hypothesizes that by include a
      step-wise cardiopulmonary algorithm the RUSH exam can be extended (E-RUSH) to accurately
      determine the need for additional fluid therapy.

      Study Design: Prospective Observational Study in two urban Emergency Departments with a
      combined annual census of >111,000.

      Population: ED patients exhibiting signs of shock definied by a systolic blood pressure < 100
      mmhg, MAP < 65, persistent tachycardia, mottled skin, or lactate >2mmol either at
      presentation or during ED stay will be included. Exclusion criteria will be inability to
      consent, external factors preventing ultrasound examination, age less than 18, pregnancy,
      incarceration, arrhythmia, cardiac arrest, or treating physician gestalt that the patient is
      not in shock.

      Protocol: The E-RUSH protocol will include ultrasound exams of the IVC, heart and lungs as
      described in the RUSH protocol but will also evaluate cardiac output, IVC collapsibility, and
      presense of B-lines on lung ultrasound. At the time of ultrasound measuresments a
      bioreactance device will be applied. Bioreactance measurements and ultrasound measurement of
      cardiac output will be recorded pre and post a passive straight leg raise test. All charts
      will be reviewed by two experts who are blinded to ultrasound and bioractance measurements.
      When possible the protocol will be repeated 1-2 hours later or after initial interventions in
      order to provide trend data.

      Data Analysis: Volume responsivness as assessed by the E-RUSH will be defined a priori using
      a step-wise flow diagram that combines IVC, lung and cardiac ejection fraction and output
      measurements (see research plan for details). Determination of volume responsiveness by the
      bioreactance device will be defined by manufacturer protocal. Determination of volume
      responsiveness by expert review will be by a standard abstraction form with agreement of both
      expert reviewers. Descriptive statistics will be performed to determine the test
      characteristics of the ultrasound protocol to predict volume responsiveness. Given the lack
      of a universally agreed upon gold standard for volume responsiveness, we will determine test
      characteristics for E-RUSH using the bioreactance device as a reference standard and using
      expert review as a second reference standard separately.

      FACILITY RESOURCES The study facilities are in San Diego California, with a combined
      emergency department census of over 111,000 patients per year. The emergency departments of
      the facilities are equipped with portable bedside ultrasound machines, CT and MRI, 24 hour
      laboratory testing and an integrated electronic medical record system. Emergency medicine and
      family medicine residents rotate through both emergency departments. Both departments are
      stroke receiving centers and level 3 trauma centers.

      Research Databases An important aspect of the KPSC managed care environment is its integrated
      approach to the delivery of medical care. This approach depends on, and therefore
      facilitates, the development and maintenance of a large number of databases, linkable through
      a unique identification key. These databases include those that track membership, encounters,
      laboratory, claims, pharmaceutical dispensations and others. The address information is
      annually geo-coded to the census block level, providing linkage to census-based group-level
      information about socio-economic status.

      Each of the KPSC clinical operations systems are updated in real-time, facilitating our
      ability to create near real-time research databases. Our Membership database captures
      demographic (e.g., name, date of birth, gender, race/ethnicity, etc.) and benefit information
      for over 12 million active and former members, and is updated on a weekly basis. The
      utilization database captures outpatient and hospital encounters (e.g., diagnoses,
      procedures, etc.), member claims submitted from outside hospitals (usually with up to 3-month
      delay), and care provided at home, skilled nursing and hospice facilities. This database is
      updated weekly. Outpatient and inpatient pharmacy databases track medication orders and
      dispenses, and are updated either daily or monthly depending on the source system. Death
      information is derived from multiple sources including KP hospital and membership data, as
      well as two external sources from California State and Social Security Administration death
      files. The state death records lag about one to two years for date and underlying cause of
      death and between two and three years for all causes listed on the death certificate.

      SCIENTIFIC ENVIRONMENT Biostatistical expertise is provided by a Biostatistics Unit that
      consists of statisticians, programmers, natural language specialists, database developers and
      administrators. The Unit provides services including statistical consultation, data analysis,
      data extraction, disease identification based on free-texts and data management for research
      projects. In addition, the Unit is responsible for creating many of the research data bases
      used. All Unit employees have SAS programming skills and years of experience in conducting
      broad and varied research. The Biostatistics Unit supports more than 300 research projects
      annually.

      Oversight of Research at KPSC KPSC has an Institutional Review Board (IRB) under the Medical
      Director of Operations for the Southern California Permanente Medical Group. The IRB is
      charged with the protection of human subjects through the oversight of all investigators and
      their research projects in Kaiser Permanente Southern California. Compliance with the minimum
      Federal standards for the protection of human subjects in research is demonstrated by a
      Federal Wide Assurance (FWA) held through the Kaiser Foundation Research Institute. The IRB
      also acts as the KPSC HIPAA privacy board.

      Ethics Kaiser Permanente - Southern California (KPSC) shall obtain written evidence of review
      and approval from our independent ethics committee (IRB) of the protocol, informed consent
      forms, evidence of partial waiver, and all other documents requiring IRB review and approval
      prior to the initiation of the project.

        1. RISKS TO THE SUBJECTS

             1. Human Subjects Involvement and Characteristics Describe the proposed involvement of
                human subjects in the work outlined in the Research Design and Methods section.

                The study population are ED patients exhibiting signs of shock definied by a
                systolic blood pressure < 100 mmhg, MAP < 65, persistent tachycardia, mottled skin,
                or lactate >2mmol either at presentation or during ED stay will be included.
                Exclusion criteria will be inability to consent, external factors preventing
                ultrasound examination, age less than 18, pregnancy, incarceration, traumatic
                mechanism, arrhythmia, cardiac arrest, or treating physician gestalt that the
                patient is not in shock. Our goal is to enroll a total of 50 patients.

                This study will not recruit subjects defined as vulnerable populations. Individuals
                age less than 18 and pregnant women will be excluded as noted in the exclusion
                criteria.

             2. Sources of Materials

           The following data will be obtained from the patient:

             -  Consent Form

             -  ultrasound will be used to perform visual assessment of the patient's inferior vena
                cava

             -  Variables including but not limited to: systolic blood pressure, MAP, persistent
                tachycardia, mottled skin, or lactate status, age, pregnancy status, arrhythmia,
                cardiac arrest,

             -  "Electronic Health Data" - All charts will be reviewed by two experts who are
                blinded to ultrasound and bioractance measurements.

             -  Bioreactance measurements and ultrasound measurement of cardiac output will be
                recorded pre and post a passive straight leg raise test.

           The data collected will be linked/coded using a study identification number (SID) and
           only KPSC study team members and persons directly involved in recruitment will have
           access to the key that identifies individual subjects.

        2. ADEQUACY OF PROTECTION AGAINST RISKS

             1. Recruitment and Informed Consent We will obtain a waiver to access and use the EHR
                data for case/patient identification. The waiver will be used to identify patients
                in order approach patients regarding the study and to obtain consent. Study
                personnel will screen the ED tracking board and communicate with ED providers to
                find patients meeting inclusion criteria. Upon identification study personnel, will
                approach patient in the private exam room to obtain informed consent in person.

                The study will not recruit anyone less than 18 or women who are pregnant. However,
                due to the rich diversity of Kaiser Permanente's membership in Southern California,
                Spanish speakers will be recruited. All materials and forms will be translated to
                Spanish to include all Spanish speaking/reading potential participants. Consent
                forms will be stored securely onsite and a study database will be maintained. All
                patients will be provided a copy of the consent form.

             2. Protection Against Risk Names and other identifying information on participants
                will be obtained for record keeping purposes only and no participants will be
                identified in any forms or reports from this study. Survey and clinical data will
                only be shared internally among KPSC study team members and only persons directly
                involved in recruitment will have access to the key that identifies individual
                subjects. Transfer of data if needed will be via encrypted email.

        3. POTENTIAL BENEFITS OF THE PROPOSED RESEARCH TO THE SUBJECTS AND OTHERS The immediate
           benefit to the participant is none. However, If the E-RUSH protocol proves accurate and
           useful, it has the potential to improve patient care and safety and a vulnerable and
           high risk population. There are no high-risk aspects of the proposed work.

        4. IMPORTANCE OF THE KNOWLEDGE TO BE GAINED There are no high-risk aspects of the proposed
           work. The importance of the current study presents an innovative algorithm that my
           further demonstrate the ability of ultrasound to be useful in the shock patient to
           determine fluid needs. If an algorithmic approach using bedside ultrasound proves
           accurate in titrating fluid resuscitation, it could reduce complications of under
           resuscitation (organ failure) and over resuscitation (pulmonary edema, third spacing and
           abdominal compartment syndrome). Avoidance of complications would have downstream
           benefits such as reduced length of stay, reduced mortality, and reduced burden on the
           healthcare system.

        5. DATA AND SAFETY MONITORING PLAN Our study will not be a clinical trial. All the
           information and/or databases will be password protected to ensure security of the PHI
           contained in the data systems. Study data access that would identify participants will
           be tightly controlled and limited to authorized individuals using the follow safeguards:
           roles and privileges, defined data owners, automatic log off and lockouts, field level
           hide, read only, or read-write permission at user level, encryption of data transfers,
           and limited/controlled delete capabilities. Standard backup procedures will be employed
           at Kaiser Permanente, where data will be backed up nightly to a secured disk based
           storage system and then offloaded to a robotic tape library system, with tapes rotated
           offsite for additional level of protection. This ensures against data loss in the event
           of a local systems failure or natural disaster.
observational model: Cohort
time perspective: Prospective
measure: Test Characteristics of the E-RUSH Protocol to Predict Fluid Responsiveness
time frame: 1 year
description: Will determine sensitivity and specificity of a step-wise cardiopulmonary approach to determine fluid responsivness.
arm group label: Shock Group
description: Patients presenting with signs and symptoms of shock will undergo the E-RUSH ultrasound protocol and bioreactance before and after a passive leg raise maneuver.
intervention type: Diagnostic Test
intervention name: Ultrasound Protocol
description: Ultrasound of the inferior vena cava, heart and lungs.
arm group label: Shock Group
intervention type: Device
intervention name: Bioreactance
description: Bioreactance assessment using Cheetah Bioreactance Device (FDA Approved). Bioreactance is a non-invasive measure of cardiac output.
arm group label: Shock Group
intervention type: Procedure
intervention name: Passive Leg Raise
description: A passive leg raise involves placing the patient supine and raising the legs to simulate an intravenous fluid bolus.
arm group label: Shock Group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jason M Fields, MD
role: Principal Investigator
affiliation: Kaiser Permanenete
citation: Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.
PMID: 11445675
citation: Bentzer P, Griesdale DE, Boyd J, MacLean K, Sirounis D, Ayas NT. Will This Hemodynamically Unstable Patient Respond to a Bolus of Intravenous Fluids? JAMA. 2016 Sep 27;316(12):1298-309. doi: 10.1001/jama.2016.12310.
PMID: 27673307
citation: Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011 Feb;39(2):259-65. doi: 10.1097/CCM.0b013e3181feeb15.
PMID: 20975548
citation: Corl KA, George NR, Romanoff J, Levinson AT, Chheng DB, Merchant RC, Levy MM, Napoli AM. Inferior vena cava collapsibility detects fluid responsiveness among spontaneously breathing critically-ill patients. J Crit Care. 2017 Oct;41:130-137. doi: 10.1016/j.jcrc.2017.05.008. Epub 2017 May 12.
PMID: 28525778
citation: Monnet X, Marik PE, Teboul JL. Prediction of fluid responsiveness: an update. Ann Intensive Care. 2016 Dec;6(1):111. doi: 10.1186/s13613-016-0216-7. Epub 2016 Nov 17.
PMID: 27858374
citation: Oord M, Olgers TJ, Doff-Holman M, Harms MP, Ligtenberg JJ, Ter Maaten JC. Ultrasound and NICOM in the assessment of fluid responsiveness in patients with mild sepsis in the emergency department: a pilot study. BMJ Open. 2017 Jan 27;7(1):e013465. doi: 10.1136/bmjopen-2016-013465.
PMID: 28132006
citation: Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.
PMID: 11794169
responsible party type: Sponsor
mesh term: Shock
sharing ipd: No
ipd description: Not planning to share IPD