• Pulmonary Dysfunction or COPD 
• Asthma
• Chronic Disorders

• Improving Outcomes in Mechanically Ventilated Patients
• Weaning from Prolonged Mechanical Ventilation
• Role of 20-HETE on Vasospasm-Induced Ischemia after SAH
• Advanced Nurse Training: Trauma/Emergency Preparedness
• The Role of 20-Hete in the Pathogenesis of Stroke

Hoffman, L.

04/01/99-01/31/09
5 NR004339-05A1-06 NIH

Role of 20-HETE on Vasospasm-Induced Ischemia after SAH

This is a competitive renewal of the NIH funded study "Methods of Predicting Delayed Cerebral Ischemia (DCI) in subarachnoid hemorrhage (SAH)". In our current study, we found that 33% of SAH patients develop symptomatic vasospasm (SV) and DCI, and have nearly twice the mortality rate than patients that do not develop SV. We found the sensitivity and specificity of alternative, noninvasive techniques to identify SV and DCI in this population disappointing., We now wish to extend our work and examine a biomarker specific for vasospasm, (20-HETE), that has not been tested in humans. Several well known vasoactive agents [norepinephrine (NE), nitric oxide (NO), endothelin (ET-1)] depend on the formation of 20-HETE to elicit the majority of their vasoconstrictive effects. Independently these vasoactive agents have not proven to be sufficiently sensitive for early detection of SV, but their cumulative effect through 20-HETE formation hold promise as a clinical indicator of SV and DCI.
 

The specific aims are to:

1) Characterize the individual recovery curves of norepinephrine (NE), nitric oxide (NO), endothelin (ET-1), and 20-HETE in the CSF within the first 14 days after SAH.

2) Define the time dependent relationship between 20-HETE and outcomes [acute complication (SV, DCI) and function 3 months post SAH].

3) Define the relationship between NE, NO and ET-1 in the CSF and outcomes. This study will use a prospective, longitudinal, within-subject between-group repeated measure design to compare 20-HETE, NE, NO, and ET-1 (during the first 14 days following SAH) between individuals who do and do not develop SV or DCI. We will recruit 180 patients with SAH (ages 21-75) in order to achieve a final sample of 150 subjects available at the three-month follow-up. All subjects will undergo serial sampling of cerebrospinal fluid, serum and urine samples, concurrent with intense neurophysiologic monitoring and clinical examinations, to detect early markers of SV and DCI. The independent variables are the CSF levels of NE, NO, ET-1 and 20-HETE. The acute dependent variable outcomes are: SV, DCI and functional outcomes at 3 months post hemorrhage. Hierarchical linear modeling (HLM) (i.e., multilevel modeling or growth curve modeling) analysis will be used to examine the recovery curves of 20 HETE, NE, NO, and ET-1.
 

Improving Outcomes in Mechanically Ventilated Patients

The provision of critical care has changed markedly since its inception. Intensive care units (ICUs), developed to provide highly skilled care during a brief illness, now also provide care for substantial numbers of patients who require extended support due to inability to wean from mechanical ventilation (MV). Acute care nurse practitioners (ACNP) are prepared to perform a wide range of nursing functions, as well as certain functions traditionally performed by physicians, including diagnosis, management, and interpreting diagnostic studies. These competencies make the ACNP and excellent candidate to test an intervention designed to facilitate recovery from critical illness. The primary aim of this study is to test ability of an intervention (ACNP-managed care versus usual care) to improve outcomes in patients dependent on MV admitted to a SD-ICU and in the post discharge period.

The secondary aim is to identify factors which promote weaning progression and weaning success in this population. The study will use a 2x2 non-randomized, repeated measures, equivalent time-samples design. During the intervention, an ACNP will manage subjects admitted to a SD-ICU, and provide consultation to these patients and their families for one month after discharge. Usual care subjects will be managed by physicians-in-training and followed for the same time period, but will not receive post discharge consultation. Dependent variable will be: 1) weaning progress (hours off full MV support); 2) recovery trajectory (rapid, shallow breathing ratio [f/Vt], pulmonary capillary wedge pressure estimated noninvasively [ePCWP], acute physiology and chronic health evaluation [APACHE] III scores; 4) information needs (Patient/Family Information Needs Scale); 5) ICU resources consumption (ratio of cost to charges); 6) health-related quality of life (Health Assessment Questionnaire, Medical Outcomes Study SF-36); 7) medical record documentation; and 8) disposition. Measures will be obtained at SD-ICU admission, when weaning occurs or the subject is discharged from the SD-ICU and 1, 6, and 12 months after discharge. During weaning trials, f/Vt and ePCWP will be also measured at 3-day intervals. Data will be analyzed using logistic regression, analysis of covariance, proportional hazards regression, and linear mixed effect models. To accomplish our Secondary Aims, we will construct weaning patterns for each subject, identify the proportion of weaning patterns which can be reliably differentiated as consist weaning progress, and use stepwise multiple logistic regression to identify variables which predict weaning consistent progress, irrespective of group.

Hoffman, L.
12/01/03-11/30/08

Loyola University

Weaning From Prolonged Mechanical Ventilation

Patients requiring mechanical ventilation (MV) for more than 21 days account for more than 37% of all ICU costs. As such, these patients are now transferred to centers that specialize in weaning from MV, so called long-term acute care (LTAC) facilities. Despite the proliferation of LTAC facilities, research on methods of expediting weaning and tests that can reliably identify patients that have a likelihood for weaning at these facilities is lacking. In addition, little or no information is available regarding the health-related quality of life (AOL) of patients several months after being discharged from a facility specializing in long-term MV. Thus, the aim of this study is to determine the efficient way to wean patients at an LTAC facility and to identify which patients are likely to benefit from such weaning strategies.

The secondary aim is to determine the QOL 6 and 12 months after discharge from an LTAC facility and patients’ preference toward MV. The accuracy of family members serving as proxies in estimating QOL in these patients will also be assessed. To address these aims, a prospective, randomized trial in patients who are transferred to an LTAC facility will be done to compare the efficacy of two techniques—pressure support and spontaneous breathing trials—in weaning the patients from prolonged MV. Measurements of frequency and tidal volume in combination with an initial trial of spontaneous breathing will be obtained prior to randomization to examine the accuracy of such measurements in predicting weaning out come. Health related WOL measurements will be obtained from patients and their families, serving as proxies, at the LTAC facility and patients’ place of residents at 6 and 12 months after discharge. Findings from this study will provide novel insights into the most reliable way for predicting which patients will be weaned, the most efficient method of weaning patients, and the impact of prolonged MV on QOL months after discharge from an LTAC facility. Such information will for the first time help health care providers in formulating objective guidelines in the management of patients who are weaned at an LTAC center.

Hoffman, L.

07/01/04-06/30/07

HRSA/AENP

Advanced Nurse Training: Trauma/Emergency Preparedness

The overall purpose of this project is to enhance the Acute Care Practitioner (ACNP) and Clinical Nurse Specialist (CNS) Programs by implementing a new clinical emphasis in Trauma/Emergency Preparedness (TEP). The project will also introduce innovative methods of providing high fidelity human simulation (HFHS) instruction in TEP training and extend it to rural areas.

The clinical emphasis in TEP will prepare graduates to function as principal providers of care for adults involved in trauma or emergency situations or prepare systems experts in TEP. The clinical emphasis is designed to meet current and emerging TEP needs in an innovative manner that will link program preparation with local, regional, and national needs in trauma and emergency care. These needs include the necessity to increase the number of emergency trained providers who can respond to divers threats, better integrate trauma and emergency trained providers  who can respond to diverse threats, better integrate trauma and emergency preparedness systems across all levels of emergency care (rural through urban), and implement rapid facility and patient volume expansion. The clinical emphasis in TEP is designed to meet unique needs of Pennsylvania that involve the care of patients who reside in rural, western and central portions of the state and large numbers of elderly patients. The proposed project will add additional coursework and clinical and laboratory experiences to provide graduates with the prerequisite knowledge and skills needed to become expert, culturally competent health care providers. The project incorporates a systematic plan to recruit minority applicants and those from rural settings and increase placement of students in medically underserved areas. Finally, it will build on the educational technologies currently in place at the University of Pittsburgh to facilitate distance learning, and, thereby, recruitment of students from rural areas.

Hoffman, L. (Horowitz)

07/01/05-04/30/06

R01 NS052315-01 NIH

The Role of 20-Hete in the Pathogenesis of Stroke

Decreasing tissue infarction in the ischemic penumbra is the primary therapeutic target after stroke.  The degree of tissue damage in the ischemic penumbra is a function of the severity of the ischemic insult, which is partially regulated by the cerebral microvascular resistance.  Recent studies have shown that the monohydroxylated metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE) is an important regulator of cerebrovascular resistance and is an important regulator of the vasoactive effects of nitric oxide.