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

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.