IRB-HSR# 14299: The Use of the Intrathoracic Pressure Regulator (ITPR) to Improve Cerebral Perfusion Pressure in Patients With Altered Intracranial Elastance

September 17, 2010 updated by: University of Virginia

Patients who have a functioning intracranial pressure-monitoring device (either a subarachnoid bolt, or an intraventricular catheter) in place, and are either sedated, intubated, and mechanically ventilated (i.e. in the NNICU), or are scheduled to undergo an operation or interventional neuroradiological procedure at the University of Virginia. Patients with a contraindication to TTE will be excluded.

For patients in the NNICU, basic hemodynamic variables (systemic blood pressure, central venous pressure, etc.) will be collected. In addition, left ventricular performance (including estimates of LVEDV, LVESV, EF, FAC, and SV) will be assessed using TTE. Once these baseline data are recorded, the ITPR will be inserted in the ventilator circuit and activated to provide either -5 mm Hg or -9 mm Hg endotracheal rube pressure (ETP) (based on a randomization scheme). After the ITPR has been active for at least five minutes, the same intracranial, hemodynamic, and TTE data obtained above will be gathered. The ITPR will then be turned off for five minutes, and intracranial, hemodynamic, and TTE data will again be recorded. The ITPR will be activated a second time (-9 mm Hg or -5 mm Hg ETP, i.e. whichever value was not used previously), and after five minutes of use data will be recorded again. The ITPR will then be disconnected, data will be collected after waiting two minutes, and no further interventions will be made.

ABG's will be obtained before and during the use of the device at each setting.

This is a proof of concept/feasibility study designed to test the primary hypothesis that use of the ITPR will result in decreased intracranial pressure and increased cerebral perfusion pressure. The effect of the ITPR on secondary indicators of cardiac performance will also be examined. These include but are not limited estimates of ventricular end diastolic volume and pressure (LVEDV/P), ejection fraction (EF), left ventricular end systolic volume and pressure (LVESV/P), fractional area change (FAC), all of which will be assessed by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

The ITPR is an FDA-approved device intended to increase circulation and blood pressure in hypovolemic and cardiogenic shock. The device is inserted within a standard respiratory circuit between the patient and the ventilator. It functions by decreasing intrathoracic pressure during the expiratory phase to subatmospheric levels after each positive pressure ventilation. This decrease in intrathoracic pressure creates a vacuum within the thorax relative to the rest of the body, thereby enhancing venous return to the heart and consequently increasing cardiac output and blood pressure. Activation of the device is also accompanied by a decrease in SVR. The end result is a device that simultaneously improves cardiac output by increasing LVEDV and decreasing SVR while increasing coronary perfusion pressure by increasing blood pressure and decreasing LVESP/LVESV.1-8

Interestingly, while the ITPR was developed as a non-invasive mechanism to increase preload in hypovolemic patients, its mechanism of action (generation of subatmospheric intrathoracic pressure) has been shown to reduce intracranial pressure6. This is critical in brain-injured patients, because elevated intracranial pressure is strongly associated with poor outcome in traumatic brain injury (TBI) patients - in a recent study of 846 TBI patients, those with ICP < 20 mm Hg by 48 hours had a mortality rate of 14%, whereas those with ICP > 20 mm Hg had a mortality rate of 34%9. Particularly interesting are the ITPR's combined benefits of increased MAP and decreased ICP, as hypotension is a well-known poor prognostic indicator in this patient population.

In fact, according to the Brain Trauma Foundation Guidelines, "Hypotension, occurring at any time from injury through the acute intensive care course, has been found to be a primary predictor of outcome from severe head injury for the health care delivery systems within which prognostic variables have been best studied. Hypotension is repeatedly found to be one of the five most powerful predictors of outcome and is generally the only one of these five that is amenable to therapeutic modification. A single recording of a hypotensive episode is generally associated with a doubling of mortality and a marked increase in morbidity from a given head injury10."

Importantly, cerebral perfusion pressure (mean arterial pressure - the greater of ICP or CVP) is only a surrogate marker for cerebral blood flow. The function of hypotension as a useful clinical variable is dependent on two factors - first, its correlation with the true variable of interest (cerebral blood flow) and second, the ability of clinicians to manipulate the underlying variable of interest (cerebral blood flow) based on the surrogate marker (cerebral perfusion pressure).

The acceptable level of hypotension in patients with brain injuries has not been determined, and the Brain Trauma Foundation (BTF) Guidelines recommend maintaining systolic blood pressures > 90 mm Hg, but acknowledge that this number is relatively arbitrary and not based on any high-level studies (thus assigning it a designation of Level II evidence) 11. The BTF Guidelines further state that because hypotension is such a poor prognostic variable, it would be unethical to randomize patients to various blood pressure goals, and therefore Level I evidence is not forthcoming. Further complicating the situation is the lack of agreement on how to increase blood pressure (with the hopes of increasing cerebral perfusion pressure)12-15. Many of the pharmacologic agents used to increase mean arterial pressure have significant vasoconstrictive effects, which could counteract any increase blood pressure and lead to unchanged, or even reduced cerebral blood flow.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 1. patients who have a functioning intracranial pressure-monitoring device (either a subarachnoid bolt, or an intraventricular catheter) in place, and are either sedated, intubated, and mechanically ventilated (i.e. in the NNICU)and have an arterial line in place, or are scheduled to undergo an operation or interventional neuroradiological procedure at the University of Virginia.

    2. age 18 years of age and older 3. informed consent/ surrogate consent has been obtained

Exclusion Criteria:

  • 1. pneumothorax 2. hemothroax 3. uncontrolled bleeding 4. uncontrolled hypertension defined as SBP > 180 mmHg at the time of surgery 5. known respiratory disease such as chronic emphysema, COPD, or Cystic Fibrosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ITPR -9 & then -5 mm Hg
the ITPR will be inserted in the ventilator circuit and activated to provide either -5 mm Hg or -9 mm Hg endotracheal tube pressure (ETP) Each subject will have all measurements recorded at both -5 & -9 mm Hg
Device: ITPR -9 & then -5mm Hg
the ITPR will be inserted in the ventilator circuit and activated to provide either -5 mm Hg or -9 mm Hg endotracheal tube pressure (ETP) Each subject will have all measurements recorded at both -5 & -9 mm Hg
Experimental: ITPR -5 & then _9 mm HG
the ITPR will be inserted in the ventilator circuit and activated to provide either -5 mm Hg or -9 mm Hg endotracheal tube pressure (ETP) Each subject will have all measurements recorded at both -5 & -9 mm Hg
Device: ITPR -5 mm Hg then -9 mm Hg
the ITPR will be inserted in the ventilator circuit and activated to provide either -5 mm Hg or -9 mm Hg endotracheal tube pressure (ETP) Each subject will have all measurements recorded at both -5 & -9 mm Hg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemodynamic variables
Time Frame: baseline, 5 minutes after device activation & 5 minutes after device turned off
hemodynamic variables (systemic blood pressure, central venous pressure, ICP) will be collected at baseline, 5 minutes after device activation & 5 minutes after device turned off
baseline, 5 minutes after device activation & 5 minutes after device turned off

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
cardiac performance
Time Frame: baseline, 5 minutes after device activation & 5 minutes after device turned off
cardiac performance will also be examined. These include but are not limited estimates of ventricular end diastolic volume and pressure (LVEDV/P), ejection fraction (EF), left ventricular end systolic volume and pressure (LVESV/P), fractional area change (FAC)
baseline, 5 minutes after device activation & 5 minutes after device turned off

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Investigators

  • Principal Investigator: Edward C Nemergfut, MD, University of Virginia Anesthesiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Study Registration Dates

First Submitted

September 17, 2010

First Submitted That Met QC Criteria

September 17, 2010

First Posted (Estimate)

September 20, 2010

Study Record Updates

Last Update Posted (Estimate)

September 20, 2010

Last Update Submitted That Met QC Criteria

September 17, 2010

Last Verified

September 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14299

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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