IRB-HSR# 14299: The Use of the Intrathoracic Pressure Regulator (ITPR) to Improve Cerebral Perfusion Pressure in Patients With Altered Intracranial Elastance
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|ClinicalTrials.gov Identifier: NCT01205607|
Recruitment Status : Unknown
Verified September 2010 by University of Virginia.
Recruitment status was: Enrolling by invitation
First Posted : September 20, 2010
Last Update Posted : September 20, 2010
|First Submitted Date ICMJE||September 17, 2010|
|First Posted Date ICMJE||September 20, 2010|
|Last Update Posted Date||September 20, 2010|
|Start Date ICMJE||May 2009|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||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
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
||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)
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||IRB-HSR# 14299: The Use of the Intrathoracic Pressure Regulator (ITPR) to Improve Cerebral Perfusion Pressure in Patients With Altered Intracranial Elastance|
|Official Title ICMJE||IRB-HSR# 14299: The Use of the Intrathoracic Pressure Regulator (ITPR) to Improve Cerebral Perfusion Pressure in Patients With Altered Intracranial Elastance|
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).
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 ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Health Services Research
|Condition ICMJE||Traumatic Brain Injury|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE||20|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01205607|
|Other Study ID Numbers ICMJE||14299|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Edward C., Nemergut MD, University of Virginia Anesthesiology|
|Study Sponsor ICMJE||University of Virginia|
|Collaborators ICMJE||Not Provided|
|PRS Account||University of Virginia|
|Verification Date||September 2010|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP