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Intracranial Hypertension and Cerebral Perfusion Pressure Insults in Adult Hypertensive Intraventricular Hemorrhage: Occurrence and Associations With Outcome

Ziai, Wendy C. MD, MPH1,2; Thompson, Carol B. MS, MBA3; Mayo, Steven PharmD4; McBee, Nichol MPH5; Freeman, William D. MD6; Dlugash, Rachel MSPH5; Ullman, Natalie MD, MPH1,2; Hao, Yi PhD5; Lane, Karen CMA, CCRP5; Awad, Issam MD7; Hanley, Daniel F. MD5; for the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III) Investigators

doi: 10.1097/CCM.0000000000003848
Neurologic Critical Care
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Objectives: Elevated intracranial pressure and inadequate cerebral perfusion pressure may contribute to poor outcomes in hypertensive intraventricular hemorrhage. We characterized the occurrence of elevated intracranial pressure and low cerebral perfusion pressure in obstructive intraventricular hemorrhage requiring extraventricular drainage.

Design: Prospective observational cohort.

Setting: ICUs of 73 academic hospitals.

Patients: Four hundred ninety-nine patients enrolled in the CLEAR III trial, a multicenter, randomized study to determine if extraventricular drainage plus intraventricular alteplase improved outcome versus extraventricular drainage plus saline.

Interventions: Intracranial pressure and cerebral perfusion pressure were recorded every 4 hours, analyzed over a range of thresholds, as single readings or spans (≥ 2) of readings after adjustment for intracerebral hemorrhage severity. Impact on 30- and 180-days modified Rankin Scale scores was assessed, and receiver operating curves were analyzed to identify optimal thresholds.

Measurements and Main Results: Of 21,954 intracranial pressure readings, median interquartile range 12 mm Hg (8–16), 9.7% were greater than 20 mm Hg and 1.8% were greater than 30 mm Hg. Proportion of intracranial pressure readings from greater than 18 to greater than 30 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 70 mm Hg were associated with day-30 mortality and partially mitigated by intraventricular alteplase. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and intracranial pressure greater than 20 mm Hg in spans were associated with both 30-day mortality and 180-day mortality. Proportion of cerebral perfusion pressure readings from less than 65 to less than 90 mm Hg and combined intracranial pressure greater than 20 plus cerebral perfusion pressure less than 60 mm Hg were associated with poor day-30 modified Rankin Scale, whereas cerebral perfusion pressure less than 65 and less than 75 mm Hg were associated with poor day-180 modified Rankin Scale.

Conclusions: Elevated intracranial pressure and inadequate cerebral perfusion pressure are not infrequent during extraventricular drainage for severe intraventricular hemorrhage, and level and duration predict higher short-term mortality and long-term mortality. Burden of low cerebral perfusion pressure was also associated with poor short- and long-term outcomes and may be more significant than intracranial pressure. Adverse consequences of intracranial pressure-time burden and cerebral perfusion pressure-time burden should be tested prospectively as potential thresholds for therapeutic intervention.

1Division of Neurocritical Care, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

2Division of Neurocritical Care, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.

3Biostatistics Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

4Emissary International LLC, Austin, TX.

5Division of Brain Injury Outcomes, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

6Mayo Clinic, Jacksonville, FL.

7Section of Neurosurgery and the Neurovascular Surgery Program, University of Chicago Pritzker School of Medicine, Chicago, IL.

A full list of the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III) Investigators are available in Appendix 1 (Supplemental Digital Content 9, http://links.lww.com/CCM/E727).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by the National Institutes of Health grants 5U01NS062851 for Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III). Genentech assisted by donating the study drug.

Dr. Ziai received funding from C. R. Bard, Headsense, and NINDS. Drs. Ziai, Thompson, and Mayo, Ms. McBee, Dr. Ullman, Ms. Lane, and Drs. Awad and Hanley received support for article research from National Institutes of Health (NIH). Drs. Thompson’s and Award’s institutions received funding from the NIH. Ms. McBee’s, Ms. Lane’s, and Dr. Hanley’s institutions received funding from NIH/NINDS 5U01NS062851, NIH/NINDS 1U01NS08082, and Genentech (drug donation). Ms. McBee, Dr. Ullman, Ms. Lane, and Drs. Awad and Hanley disclosed off-label product use of alteplase. Dr. Ullman’s institution received funding from NIH/NINDS. Dr. Awad received funding from expert reviews and medicolegal opinions. Dr. Hanley received funding from BrainScope, Neurotrope, Portola Pharmaceuticals, Op2Lysis, HeadSense, and Medtronic. Dr. Ziai, Ms. McBee, Ms. Lane, and Drs. Awad and Hanley are supported by grant 5U01NS062851. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail:weziai@jhmi.edu

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