Medical Management of Intracranial Hypertension. Joao A. Gomes, MD FAHA Head, Neurointensive Care Unit Cerebrovascular Center

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Medical Management of Intracranial Hypertension Joao A. Gomes, MD FAHA Head, Neurointensive Care Unit Cerebrovascular Center

Anatomic and Physiologic Principles

Intracranial compartments Brain 80% (1,400 cc) CSF 75-150 cc (10%): 50% intraventricular and 50% subarachnoid compartment Blood 75-150 cc (10%): 70% venous, 30% arterial

Monro-Kelly doctrine An increase in the volume of one compartment must be accompanied by an approximately equal decrease in the volume of the other compartments to maintain normal ICP

Compensation Shift of CSF from the intracranial to the spinal thecal compartment Dural sinus collapse and arterial vasoconstriction: decreased CBV Brain herniation

Cerebral Perfusion Pressure CBF determinations difficult to perform. CPP is a helpful guide to estimate adequacy of cerebral circulation. CPP is the blood pressure of the brain CPP= MAP - ICP Normal CPP 60-100 CPP < 30-40 typically leads to ischemia

Compliance: pressure-volume response CSF added to the craniospinal space Pressure-volume curve follows a hyperbolic function (rather than linear) Reflection of the elastic properties of the craniospinal system (elastance)

Compliance: zones I, II, III Ratio of the change in volume to the resulting change in pressure (ΔV/ΔP) Measure of the distensibility of the intracranial cavity Zone II: normal ICP, poor compliance

ICP Monitoring

The choroid plexus is credited as the site of transfer of the arterial pulse to the CSF Pressure gradient exists along the craniospinal axis in a rostro-causal fashion (about 60% lower in the lumbar space) Facilitates the movement of CSF from the ventricles into the subarachnoid space ICP waveforms

Intraventricular monitoring Percussive wave (P1): choroidal plexus pulse Tidal wave (P2): intracranial compliance Dicrotic wave (P3):closure of aortic valve Poor compliance: peaked P2

Pathophysiology

Treatment

Principles of Treatment General - Avoid shivering, agitation or fever - Euvolemia to slight hypervolemia - Pressors as needed to maintain CPP - Facilitate venous outflow (head elevation > 30 degrees, midline position)

Specific - Controlled hyperventilation (PaCO2 25-30 mmhg) - External CSF drainage - Osmotic therapy - Metabolic suppression (propofol, barbiturates) - Decompressive surgery - Hypothermia

ICP Treatment Algorithm Insert ICP monitor and maintain CPP >65 mm Hg (ventriculostomy preferred) Consider repeat CT scan Yes Yes Yes CSF drainage (if available) Sedation/Analgesia Consider mild hyperventilation (P a CO 2 30-35 mm Hg); further sedation; neuromuscular blockade Yes ICP >20-25 mm Hg? Yes ICP >20-25 mm Hg? Yes No No Hypertonic saline (23.4% 30 cc bolus) Mannitol bolus (0.5-1.0 g/kg) ICP >20-25 mm Hg? Yes ICP >20-25 mm Hg? Yes No No Stepwise withdrawal of ICP therapies Second-tier therapies such as hypothermia, decompressive craniectomy, barbiturate coma.

23.4% Hypertonic Saline Bullet Standard dose: 30 ml (120 meq - 8008 mosm/l) given over 15-20 minutes May repeat once at discretion of MD (i.e. another dose of 30 ml) MD or APRN/PA may administer 23.4% slow via central line if indicated at 2 cc/min Appropriate for initial or adjunct emergency treatment of acute intracranial hypertensive crisis or herniation

ICP mmhg ICP mmhg Efficacy and Dose-Response Relationship of 23.4% Hypertonic Saline Administration and Intracranial Pressure (ICP) in Patients with Elevated ICP Samer Abubakr 1, MD, Riane Ghamrawi 2, PharmD, Simon Lam 2, PharmD, Christine L. Ahrens 2, PharmD, Joao A. Gomes 1, MD 1 Cerebrovascular Center; 2 Department of Pharmacy. Cleveland Clinic, Cleveland, OH, United States #188 Background Results Conclusions 23.4% hypertonic saline (HTS) is used for treatment of elevated intracranial pressure (ICP). Pharmacokinetic/pharmacodynamic studies are limited and dose-response curves in humans have not been reported. HTS 23.4% is traditionally dosed in 30 cc increments rather than based on patient s weight regardless of disease severity. We hypothesize that there is a correlation between weight-based dosing (mosm/kg) and ICP reduction. Study Objectives Total number of patients N=19 Male gender, n (%) 9 (47) Age (years)* 52 ± 18 Weight (kg)* 98 ± 26 ICU LOS (days)* 20 ± 28 GCS Pre* 6.6 ± 3 GCS Post* 8.7 ± 4 GCS change* 2 ± 2 Concomitant hypothermia 13 (68) and pentobarbital coma, n (%) Sodium pre 136 ± 6 Sodium post 146 ± 6 Dose Response Curve n= 18 doses 23.4% HTS was associated with a 67% reduction in ICP values in critically ill neurology/neurosurgery patients Time to clinical endpoint of ICP <20 mmhg was 41 minutes and in 75% of patients the duration of action was 127 minutes An improvement of 2 points in GCS was also observed The first description of a dose-response curve for 23.4% HTS in humans is reported While most patients received 2-4 mosm/kg of HTS, additional benefit may be derived from doses as high as 7 mosm/kg Primary Objective: Describe the onset, duration of action and maximum ICP lowering effect following administration of 23.4% HTS in critically ill patients with ICP crisis. Secondary Objectives: Develop a dose-response curve for 23.4% HTS. Research Design and Methods Retrospective chart review of patients admitted to the Neurocritical care unit from August 2010 to August 2011 who developed ICP crisis (>20 mm Hg sustained for >5 minutes) and were treated with 23.4% HTS. Only data for the first ever treatment with HTS were collected. Patient demographics, onset and duration of action, lowest ICP achieved and use of adjunctive therapies were recorded. Descriptive statistics and correlation analysis were performed. IRB approval and granted per institution policy. Admission diagnosis, n (%) *Data represented as mean + SD SAH 10 (52) 29.5 ± 11.5 pre ICH 6 (32) Other 3 (16) Absolute ICP Reduction ICP 10±12.5 Post P=0.0 05 ICP Change Over Time 30 29.5 25 20 20 19 15 10 5 0 0 41+25 127+99 Time in minutes Limitations Retrospective study Small number of patients. Confounding factors: hypothermia, hyperventilation, pentobarbital therapy Heterogeneous group of patients with different severities Some patients received concomitant hyperosmolar therapy (i.e. mannitol) within few hours prior to HTS Lack of continuous ICP documentation Bibliography Mayer SA, Chong J: Critical care management of increased intracranial pressure. J Intensive Care Med 2002;17:55-67 Qureshi AI, Wilson DA, Traystman RJ. Treatment of elevated intracranial pressure in experimental intracerebral hemorrhage: comparison between mannitol and hypertonic saline. Neurosurgery 1999;44:1055-63 Suarez JI, Qureshi AI, Bhardwaj A, et al. Treatment of refractory intracranial hypertension with 23.4% saline. Critical Care Medicine Author Disclosures: None 1998;26:1118-22

23.4% HTS was associated with a 67% reduction in ICP values in critically ill neurology/neurosurgery patients Time to clinical endpoint of ICP <20 mmhg was 41 minutes and in 75% of patients the duration of action was 127 minutes An improvement of 2 points in GCS was also observed The first description of a dose-response curve for 23.4% HTS in humans is reported While most patients received 2-4 mosm/kg of HTS, additional benefit may be derived from doses as high as 7 mosm/kg

HTS: side effects CPM SDH CHF Acid-base abnormalities Coagulopathies Hypotension with rapid infusion (decreases SVR)

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