The Critically Ill Neurological Patient:

Why Neuro ICU Matters

Julia Durrant, MDDivision of Neurosciences Critical Care

Department of NeurologyOregon Health and Science University

Disclosures

No external sources of financial support to disclose

Outline

• The Dedicated Neuro ICU• The Art of the Neuro ICU

– Cerebral edema/ICP management– Fever control– Seizure control

• Does it work?

Neuro ICU at OHSU

• Founded in 2005• 17 bed unit• 24 hour CT/MRI access• 24 Hour access to EEG techs, Epilepsy faculty• Proximity to OR and Angio suites• 24-7 Neuro-Intensivist coverage with 8 faculty

Patient Population

• Severe ischemic stroke: at risk for cytotoxic edema

• Ischemic stroke following thrombolysis with tPA or thrombectomy

• Cerebral venous thrombosis

Who should be admitted?

• ICU admission:– Stroke complicated by respiratory failure,

myocardial decompensation or uncontrollable hypertension.

– Large mismatch between core infarction and territory

• complex hemodynamic management.

Patient Population

• Intracerebral and intraventricular hemorrhage

• Subdural and epidural hematoma

Patient Population

• Subarachnoid hemorrhage

• Cerebral aneurysms• Cerebral and spinal

vascular malformations

• Brain tumors

Patient Population

• Status epilepticus• Meningitis and

encephalitis• Neuromuscular

disorders in crisis (myasthenia gravis, Guillain-Barre syndrome) and acute myelopathies

Neuroprotection: the goal of neurocritical care

• Assessment of end organ perfusion – No direct laboratory measurements– Physical exam– MRI/CT imaging

• Interval to end-organ failure under adverse conditions can be rapid.

• Further injury to even small regions of brain can have devastating consequences.

What Can We Offer?

• Cerebral resuscitation– “The Brain Code”

• Disease-specific management

• Full complement of subspecialists

• Cutting-edge technology

Cerebral Resuscitation: acute catastrophic neurologic injury

• Catastrophic neurologic injury: ICP herniation

Cranial Vault Mechanics

• Monroe and Kellie– Skull is a rigid container– Cranial contents (brain,

blood, CSF) are viscous gel and incompressible

– Additional volume (pathologic or expansion of the 3 normal contents) will lead to the displacement of another content

87%1400 mL4%

75mL9%150mL

92%4% 4%

79%1%

20%

Saunders NR, Habgood MD, Dziegielewska KM (1999). "Barrier mechanisms in the brain, I. Adult brain". Clin. Exp. Pharmacol. Physiol. 26 (1): 11–9

csf blood brainnormal

abnormal

abnormalmass

Cranial vault mechanics

CPP = MAP - ICP

Rosner M J, Rosner S D & Johnson A H. "Cerebral perfusion: management protocol and clinical results." J.Neurosurgery 1985; 83: 949-962.

CBF = CPP/CVR

CD02 = CBF x Ca02

Bratton SL et al. J Neurotrauma 24 (S1): S59-S64, 2007Narotam P, Morrison J et al. Brain tissue oxygen monitoring in traumatic brain injury and major

trauma: outcome analysis of a brain tissue oxygen-directed therapy. JNS (2009) 111 (4): 672-682

ICP<20, CPP>60 = mortality reduction by> 50% in TBI

Cerebral Resuscitation: herniation syndromesSubfalcine HerniationCerebral cortex under falx•Ipsi/contra leg weakness• mental status

Upward HerniationBrainstem up through tentorium• mental status •Dilated pupil (CNIII), ophthalmoplegia•Ipsi paresis/posturing (contra cerebral crus)

Central HerniationBrainstem down through tentorium• mental status •Dilated pupil (CNIII), ophthalmoplegia•Ipsi paresis/posturing (contra cerebral crus) •Basilar stroke

Tonsillar HerniationCerebellar tonsils in foramen magnum•Awake, quadriparesis•Arrhythmia/cardiac arrest•Respiratory arrest

Uncal Herniation mental statusUncus over tentorial notch•Dilated pupil (CNIII), ophthalmoplegia•Ipsi paresis/posturing (contra cerebral crus)• PCA stroke

Reduce Cranial Contents:Blood – vasodilation to constriction

Venous ReturnHyperventilationReduction of CMR02

Brain waterOsmolar therapy for edema

Medical Interventions

Drain CSF Surgical removal of mass

Break the rigid skull - craniectomy

Surgical Interventions

Airway: O2 sat>90%Breathing: normal CO2Circulation CPP> 60mmHg

Head of Bed: • 30 degree, midline

Hyperventilation: • pCO2 30 +/- 2 mmHg

Hyperosmolar therapy• Mannitol IV 1 gm/kg IV• Hypertonic saline (CVL)

o 3% NaCl or 23.4% NaClNormothermia/?HypothermiaPharmacologic Coma

Brain Code

Cerebral Resuscitation: compartment approach to ICP management

Venous blood-HOB up-Neck straight-No IJ lines, do not lay flat for lines-Do no use venodilating BP agents

CSF-Place IVC-Change popoff

Lesion-Blood, tumor, pus -> surgery-Air-> 100% NRB, surgery

Arterial blood-Hyperventilate-Avoid hyperemia: MAP target 60, Pa02>50-Decrease metabolism: sedation, cooling

Brain parenchyma-Osmotherapy (mannitol, hypertonic saline)-Steroids only if appropriate (Vasogenic edema)

Cerebral Resuscitation: arterial compartment

Arterial blood-Hypervent -Avoid hyperemia: MAP target 60, Pa02>50-Decrease metabolism: sedation, cooling

Kramer A, Zygun D. Anemia and red cell transfusion in neurocritical care. Critical Care 2009 13:R89

Cerebral Resuscitation: compartment approach to ICP management

Venous blood-HOB up-Neck straight-No IJ lines, do not lay flat for lines-Do no use venodilating BP agents

CSF-Place IVC-Change popoff

Lesion-Blood, tumor, pus -> surgery-Air-> 100% NRB, surgery

Arterial blood-Hyperventilate-Avoid hyperemia: MAP target 60, Pa02>50-Decrease metabolism: sedation, cooling

Brain parenchyma-Osmotherapy (mannitol, hypertonic saline)-Steroids only if appropriate (Vasogenic edema)

Cerebral Resuscitation: venous compartment

Venous blood-HOB up-Neck straight-No IJ lines, do not lay flat for lines-Do no use venodilating BP agents

If CVP exceeds ICP, CPP = MAP - CVP

Ropper: n=19. 52% had ICP when HOB increased from 0->60°. 2% had ICP.Davenport: n=8. Median ICP from 18->15 with 20° elevation, no in CPP until > 60°. Lee: n=30. Trendelenburg positioning ICP from 20->24, but ICP in 20% of pts. (!)

Davenport A, Will EJ, Davison AM. Effect of posture on intracranial pressure and cerebral perfusion pressure. Crit Care Med 1990; 18(3):286-289.

Lee ST. Intracranial pressure changes during positioning of patients with severe head injury. Heart Lung 1989; 18(4):411-414.

Ropper AH, O'Rourke D, Kennedy SK. Head position, intracranial pressure, and compliance. Neurology 1982; 32(11):1288-1291.

Cerebral Resuscitation: compartment approach to ICP management

Venous blood-HOB up-Neck straight-No IJ lines, do not lay flat for lines-Do no use venodilating BP agents

CSF-Place IVC-Change popoff

Lesion-Blood, tumor, pus -> surgery-Air-> 100% NRB, surgery

Arterial blood-Hyperventilate-Avoid hyperemia: MAP target 60, Pa02>50-Decrease metabolism: sedation, cooling

Brain parenchyma-Osmotherapy (mannitol, hypertonic saline)-Steroids only if appropriate (Vasogenic edema)

Cerebral Resuscitation: CSF compartment

CSF-Place IVC-Change popoff

Cerebral Resuscitation: compartment approach to ICP management

Venous blood-HOB up-Neck straight-No IJ lines, do not lay flat for lines-Do no use venodilating BP agents

CSF-Place IVC-Change popoff

Lesion-Blood, tumor, pus -> surgery-Air-> 100% NRB, surgery

Arterial blood-Hyperventilate-Avoid hyperemia: MAP target 60, Pa02>50-Decrease metabolism: sedation, cooling

Brain parenchyma-Osmotherapy (mannitol, hypertonic saline)-Steroids only if appropriate (Vasogenic edema)

Cerebral Resuscitation: Brain parenchyma

Brain parenchyma-Osmotherapy (mannitol, hypertonic saline)-Steroids only if vasogenic edema- Surgery (hemicrani, SOC)

Cytotoxic Vasogenic Hydrostatic

Cerebral Resuscitation: Brain parenchyma

Reflection Coefficient

Osmotic Load

Hinson et al, J Intensive Care Med (2011)

Solution Concentration Sodium Concentration (mEq/L) Osmolarity (mOsm/L)

Ringer's lactate 130 2750.90% 154 3082.00% 242 6843.00% 513 1062

Mannitol 20% n/a 1098Mannitol 25% n/a 1375

7.50% 1283 256623.40% 4004 8008

P.S. 1L of NS is 3.5g of Na+ in 1 liter of free water

Cerebral Resuscitation: Brain parenchyma

• Both improve rheology of erythrocytes increases deformability through small capillaries

•Mannitol easier to give: no central line

•HS increases vascular volume improves CBF up to 23%

HS reduces inflammatory response by reducing PMN adhesion to microvasculature

Pascual J et al. Hypertonic saline resuscitation of hemorrhagic shock diminishes neutrophil rolling and adherence to endothelium and reduces in vivo vascular leakage. Ann Surg. 2000 Nov; 236 (5): 634-642

Tseng M, Pippa G et al. Effect of hypertonic saline on cerebral blood flow in poor grade patients with subarachnoid hemorrhage. Stroke 2003;34:1389-1396

Recent Trials

Hinson et al, J Intensive Care Med (2011)

Author/Year Type of Prospective Trial Agent

Condition(s) Treated

Number of Patients? Outcome

Ichai/2009Randomized Controlled

3% sodium lactate v. 20% mannitol TBI 34

HS>Mannitol for êICP, éGOS

Francony/2008Randomized Controlled

7.5% HS v. 20% mannitol

TBI + Stroke 20 Both êICP

similarly

Battison/2005Randomized Controlled

20mL 20% mannitol v. 100mL 7.5% HS dextran TBI + SAH 9 HS>mannitol

for êICP

Harutjunyan/2005Randomized Controlled

7.2% HS + 6% HES v. 15% mannitol

Neurosurgpatients 40 HS>mannitol

for êICP

Vialet/2003Randomized Controlled

7.5% HS v. 20% mannitol TBI 20

HS>Mannitol for reducing elevated ICP episodes

Adverse Effects

Hinson et al, J Intensive Care Med (2011)

Complication Mannitol Hypertonic Saline

Renal FailureAvoid continuous infusion, repeat high dosing

Avoid prolonged hypernatremia >160mEq/L

ReboundAllow clearance prior to repeat dosing

Allow clearance prior to repeat dosing

Metabolic Acidosis n/aReduce chloride in admixture

Hypokalemia n/a Add potassium to fluids

HypovolemiaConcurrent volume resuscitation n/a

Cerebral Resuscitation: compartment approach to ICP management

Venous blood-HOB up-Neck straight-No IJ lines, do not lay flat for lines-Do no use venodilating BP agents

CSF-Place IVC-Change popoff

Lesion-Blood, tumor, pus -> surgery-Air-> 100% NRB, surgery

Arterial blood-Hyperventilate-Avoid hyperemia: MAP target 60, Pa02>50-Decrease metabolism: sedation, cooling

Brain parenchyma-Osmotherapy (mannitol, hypertonic saline)-Steroids only if appropriate (Vasogenic edema)

Cerebral Resuscitation: Lesion

• Surgical evacuation: STICH– Subjects with ICH (≥2cm) randomized to early (<24 hours)

surgical evacuation v. medical management– No benefit to early surgery in general– Superficial lesions, large cerebellar lesions (≥3cm) may

benefit– Summary: “Except for possibly those with superficial

ICHs, craniotomy at 1 day or longer after onset is not better than initial conservative medical treatment with or without later craniotomy for patients who have deterioration.”

Mendelow AD, et. al. STICH investigators. Lancet. 2005; 365 (9457): 387–97.

Malignant Middle Cerebral Artery Stroke

• 1-10% of patients with supratentorial infarcts– life-threatening edema with

peak edema on day 2-5• Mortality of entire MCA

territory is 78%, thus “malignant MCA infarction”– Including maximal medical

intervention• Midline shift peaked after 2-4

days for those who died,– 3-7 days for survivors.

Cerebral Resuscitation: Lesion

• Hemicraniectomy in stroke: DECIMAL, DESTINY, HAMLET– All small trials showed non-significant trend

toward benefit of hemicraniectomy– Meta-analysis suggests an absolute risk reduction

of 13%– Patient selection?

• Non dominant hemisphere• Age of patient

Jüttler E. Stroke. 2007 Sep;38(9):2518-25.

Disease Specific Management: Ischemic Stroke

• Hemorrhagic Transformation• CT study shows ~1-5% hemorrhagic

transformation– ranges from minor petechial bleeding to major

mass-producing hemorrhage• Use of antithrombotics, anticoagulants,

thrombolytics increase risk – NINDS ICH: 6.4% of tPA treated patients versus

0.6% in the placebo group, and mortality was 47%

Disease Specific Management: Subarachnoid Hemorrhage

• Feared Complications:– Hydrocephalus– Aneurysm re-rupture– Seizures– Vasospasm– Stressed myocardium– Neurogenic pulmonary edema

Disease Specific Management: Subarachnoid Hemorrhage

Blood pressure management Use of intermittent labetalol boluses or continuous infusion of

nicardipine to maintain SBP less than 140 mmHg (unsecured) Vasospasm prophylaxis

Nimodipine 60 mg every 4 hours for 21 days Vasospasm monitoring

Daily transcranial doppler sonography for 14 days Hydrocephalus treatment

Extraventricular Drain (EVD) placement

Cardiac Support after SAH

• Reduced Ejection Fraction or Symptomatic Vasospasm– Fluids, vasopressors– Hemodynamic monitoring

Fever

• ~50% of stroke patients develop fever1

• Body temp > 37.5°C significantly correlates with poor outcomes2

• Fever in first 24 hours linked to infarct volume3

• Induced normothermia may reduce metabolic stress4

1. Stroke 1998;29: 2455–60. 2. Stroke 1995;26:2040–3. 3. Acta Neuropathol 1991;81:615–25. 4. Stroke 2009;40:1913–16

Fever and Hypothermia

• Fever treatment– Acetaminophen– Cooling blankets– Intravascular cooling devices

• Hypothermia– Not Standard of Care– No clinical evidence yet to support its use– National Acute Brain Injury Study: Hypothermia II

terminated early for futility1

1. GL Clifton, A Valadka, D Zygun et al. Lancet Neurol, 10 (2011), pp. 131–139

Glucose• Elevated serum glucose increases tissue necrosis and edema.

• Hyperglycemia >200mg/dl is a predictor of poor outcome in ICU patients.

• Hypoglycemia (<60mg/dl) can result in focal neurological deficits.

• The goal of care is to achieve normoglycemia (80-140 mg/dl) with insulin infusion.

Seizures after Stroke

• Seizures occur in ~ 9% of patients1

– Greater risk after hemorrhagic stroke– ~2.5% have recurrent seizures– Stroke location modifies risk

• Routine prophylaxis not recommended2

• Seizure always on differential in depressed mental status– Continuous EEG helpful in making diagnosis

1. Arch Neurol. 2000 Nov;57(11):1617-22. 2. Stroke. 2010; 41: 2108-2129

Cardiac management

• ST-T changes can be seen in large ischemic strokes

• Diffuse or confined to a cardiovascular territory• Myocardial ischemia should always be excluded• “Brain T-wave changes” do not predict cardiac

morbidity• Autonomic reciprocal innervation to the

temporal lobes may produce arrhythmias in patients without pre-existing coronary disease

Does Neurocritical Care matter?

• Improved Mortality for ICH patients

Critical Care Medicine. 29(3):635-640, March 2001.

Does Neurocritical Care matter?

• Reduced Mortality

• Shorter LOS• More

discharges to home/rehab

Journal of Neurosurgical Anesthesiology. 13(2):83-92, April 2001.

Does Neurocritical Care matter?

• Reduction in mortality after Neuro-intensivist appointed

Critical Care Medicine. 32(11):2191-2198, November 2004.

Cerebral Resuscitation: outcomes

Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass lesions Qureshi,,Geocadin,Suarez, Ulatowski, CRITICAL CARE MEDICINE 2000;28:1556-1564

11/28 (40%) survived to discharge 7/11 (59%) survivors functionally independent

Does Neurocritical Care matter?

YES!

Thank you!

• Questions?