Detection of Cerebral Ischemia With a Noninvasive Neurometabolic Optical Monitor (NNOM)

The goals of the project are to evaluate a noninvasive monitor of brain metabolism and blood flow in critically ill humans. If validated, such a reliable noninvasive brain blood flow and metabolism monitor, by allowing physiologic and pharmacologic decisions based on real-time brain physiology, potentially will become an important tool for clinicians in their efforts to prevent additional brain tissue death in patients admitted with stroke, brain hemorrhage and traumatic brain injury.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke; Traumatic Brain Injury; Subarachnoid Hemorrhage; Intracerebral Hemorrhage; Acute Anoxic Encephalopathy
• Intervention / Treatment: Drug: Indocyanine Green

Detailed Description

Many critically ill patients are admitted to the hospital with no infarcted brain tissue and yet, after a period of extremely intense and expensive critical care, the patients are discharged with new hospital-acquired dead brain tissue, with associated life-long disability or brain death. This situation arises from the critical barrier of there being no straightforward bedside methods to monitor cerebral blood flow (CBF) and its adequacy during progression of post-insult secondary brain damage. This is important because of the expectation that decrements in CBF in dangerous excess of decrements in cerebral metabolic rate for oxygen (CMRO2), if detected early, can be treated to avert brain infarction. Clinical examples of this issue, among many others, include post ischemic stroke edema, post thrombolysis hyperemia or occlusion, post SAH vasospasm, hyperemic and oligemic intracranial hypertension after traumatic brain injury or stroke, ICH associated global ischemia, and intra and post carotid endarterectomy oligemia and hyperperfusion.

Critical care physicians need a bedside monitor of CBF coupled to CMRO2. The CMRO2 data will allow delineation of adequacy of CBF as occasionally CBF decrements are simply matching changes in CMRO2. The lack of such monitoring capability has resulted in clinicians making often not helpful therapeutic decisions directed to non-neurologic endpoints, e.g., blood pressure, PaCO2 and so on, "hoping" that such interventions will have a desired effect on brain perfusion and metabolism.

Diffuse Correlation Spectroscopy (DCS) and Diffuse Optical Spectroscopy (DOS) are promising NNOM optical techniques under development at UPenn (Dr. Arjun Yodh) which can provide continuous bedside quantitative CBF, CMRO2 and oxygen extraction fraction (OEF) information. Determination of capability to detect anaerobic conditions, as the investigators propose doing, will make feasible the notion of individualized CBF, CMRO2, and OEF measurement and brain-directed therapeutic optimization by bedside caregivers. This will eventually support a significant change in the way Neurocritical Care is practiced, titrating therapy to neurophysiologic rather than cardiovascular/ pulmonary endpoints. UPenn research techniques presently provide information on relative quantitative changes in CBF and CMRO2 from baseline. The investigators propose also developing a method for measurement of absolute CBF and CMRO2 and further validating the absolute CBF against invasive thermodilution (ThD) CBF techniques. The investigators' long range goal and overall objective is to prevent in-hospital brain tissue death through development of improved bedside CBF/ CMRO2/OEF (NNOM) monitoring techniques.

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennylvania Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH, TBI, ICH, and/or PIAE after cardiac arrest (post cardiac arrest coma) with GCS less than or equal to 8 (coma- clinical indications for invasive neuromonitoring), endotracheal intubation, clinical indications for invasive neuromonitoring, and family/guardian informed consent.

Description

Inclusion Criteria:

Inclusion criteria will be age greater than or equal to 18 years, the diagnosis of SAH, TBI, ICH, and/or (PIAE) after cardiac arrest (post cardiac arrest coma) with GCS less than or equal to 8, endotracheal intubation, clinical indications for invasive Neuromonitoring, and family/guardian informed consent.

Exclusion Criteria:

1. coagulation or platelet problems which cannot be corrected based on clinical indications
2. anatomic abnormalities in skull or brain tissue precluding appropriate placement of an invasive brain monitor
3. ongoing CNS or scalp infection,
4. allergy to indocyanine green dye
5. pregnancy
6. lactation or pumping breast milk for the purpose of feeding an infant
7. increased bilirubin suggestive of cholestasis or biliary obstruction, (8) allergy to iodide

(9) severity of injury which leads the team or family to conclude that further advance medical care would be futile and limitation of the level of support is requested.

Woman of childbearing potential will be excluded by urine or serum pregnancy test prior to conducting any study related procedures. . There is not a risk of pregnancy during this study as comatose patients will be monitored 24 hours a day in Intensive Care Units which have full visibility of patients.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Non-Invasive Monitoring; One non-invasive optode patch will be placed adjacent to the area of invasive monitoring and the second patch will be placed contralaterally. (12 hrs. daily is chosen primarily for budgetary reasons). The information for the non-invasive technology will be compared to the invasive technology. ICG (Indocyanine Green) will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable).

Drug: Indocyanine Green; ICG will be injected to derive absolute CBF and calibrate the DCS monitor to yield continuous absolute CBF. During each 12-hour monitoring session, for up to 14 days, the ICG will be injected at baseline(0.2 mg/kg,(4), every four hours (or less if signal is stable).; Other Names: Indocyanine Green Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The outcome variable will be the degree of correlation of ThD (thermodilution) CBF with optical CBF (cerebral blood flow).	Determine if the optical monitoring device's assessment of CBF is valid.	12 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The outcome variable will be whether the optical monitoring system detects an anaerobic condition based on specific criteria of low ThD CBF, low brain PO2(PbrO2), and high microdialysis lactate pyruvate ratio ( LPR).	Determine if the optical monitoring system can detect an anaerobic adverse condition in the brain which might lead to neural injury.	12 Days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The outcome variable will be a determination of characteristics of trends in systemic and neurophysiologic data which predict the later development of an anaerobic condition in the brain.	Predict the later onset of a brain anaerobic condition.	12 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: W. Andrew Kofke, MD, University of Pennsylvania Health System

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (ACTUAL): October 1, 2018
• Study Completion (ACTUAL): May 25, 2022

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 1, 2016
• First Posted (ESTIMATE): December 6, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 2, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Signs and Symptoms, Respiratory; Infarction; Stroke; Brain Infarction; Intracranial Hemorrhages; Hypoxia; Ischemic Stroke; Brain Ischemia; Ischemia; Brain Injuries; Hemorrhage; Brain Injuries, Traumatic; Brain Diseases; Cerebral Infarction; Subarachnoid Hemorrhage; Cerebral Hemorrhage; Hypoxia, Brain
• Other Study ID Numbers: 819681

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No, study data only remains with the study team. update reports will be submitted to the NIH, however individual patient data will not be included.