1. CEREBRAL RESUSCITATION FROM ACUTE CATASTROPHIC NEUROLOGIC INJURY: THE BRAIN CODE / ACUTE ICP MANAGEMENT Navaz Karanjia, MD Director, Neurocritical Care Assistant Professor of Neurosciences, Anesthesiology, and Surgery University of California-San Diego

2. Disclosures  No financial disclosures  Off-label use: propofol for ICP control

3. Objectives  To discuss the physiology of herniation and cranial vault mechanics  To explain the specific protocols for a “brain code”  To discuss the evidence behind the specific interventions in a “brain code”  To discuss the outcomes of patients that have been “brain coded”  To take you through a brain code/ICP emergency case

4. Cerebral Resuscitation: acute catastrophic neurologic injury  Catastrophic neurologic injury:  ICP  herniation

5. Why do I want you to understand acute ICP management?

6. Cerebral Resuscitation: herniation

9. Cerebral resuscitation: herniation Subfalcine Herniation  Cerebral cortex under falx  Leg weakness   mental status Central/Upward Herniation  Brainstem down/up through tentorium   mental status  Dilated pupil, eye “down and out” (CN3)  Weakness/posturing  Basilar stroke Tonsillar Herniation  Cerebellar tonsils in foramen magnum  Awake, pharynx weakness, quadriparesis  Arrhythmia/cardiac arrest  Respiratory arrest Uncal Herniation  Uncus over tentorial notch   mental status  Sluggish -> Dilated pupil -> eye “down and out” (CN3)  Weakness/posturing

10. Cerebral Resuscitation: tonsillar herniation MEDULLA -CN 9, 10—throat sensation/muscles, vagus -CN 11—shoulder shrug, head turn -CN12—tongue muscles -Pyramids—all motor tracts -Respiratory control, HR, BP Tonsillar Herniation  Cerebellar tonsils in foramen magnum  Awake, pharynx weakness, quadriparesis  Arrhythmia/cardiac arrest  Respiratory arrest GAME OVER

11. Cerebral resuscitation: tonsillar herniation

12. Cerebral resuscitation: herniation Subfalcine Herniation  Cerebral cortex under falx  Leg weakness   mental status Central/Upward Herniation  Brainstem down/up through tentorium   mental status  Dilated pupil, eye “down and out” (CN3)  Weakness/posturing  Basilar stroke Tonsillar Herniation  Cerebellar tonsils in foramen magnum  Awake, pharynx weakness, quadriparesis  Arrhythmia/cardiac arrest  Respiratory arrest Uncal Herniation  Uncus over tentorial notch   mental status  Dilated pupil, eye “down and out” (CN3)  Weakness/posturing  PCA stroke

13. Cerebral Resuscitation: uncal herniation Uncal Herniation  Uncus over tentorial notch   mental status  Dilated pupil, eye “down and out” (CN3)  Weakness/posturing  PCA stroke GAME OVER

14. Cerebral resuscitation: herniation Subfalcine Herniation  Cerebral cortex under falx  Leg weakness   mental status Central/Upward Herniation  Brainstem down/up through tentorium   mental status  Dilated pupil, eye “down and out” (CN3)  Weakness/posturing  Basilar stroke Tonsillar Herniation  Cerebellar tonsils in foramen magnum  Awake, pharynx weakness, quadriparesis  Arrhythmia/cardiac arrest  Respiratory arrest Uncal Herniation  Uncus over tentorial notch   mental status  Dilated pupil, eye “down and out” (CN3)  Weakness/posturing  PCA stroke

15. Cerebral Resuscitation: cranial vault mechanics 80% 12% 8%8% 92% 4%4% 4%4% 79%20% Monroe Kellie Doctrine  Skull is a rigid container (1600 cc)  Cranial contents (brain, blood, CSF) are incompressible  Additional volume (pathologic or expansile) will lead to displacement of normal cranial contents Normal ICP = 5-20 cm H20 CSF Blood Brain Blood Tumor Brain Normal Cerebral edema Tumor Saunders NR, Habgood MD, Dziegielewska KM (1999). "Barrier mechanisms in the brain, I. Adult brain". Clin. Exp. Pharmacol. Physiol. 26 (1): 11–9.

16. Cerebral Resuscitation: cranial vault mechanics

17. HV, mannitol, 23% Brain Volume No blood = BAD FOR BRAIN 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.

18. Cerebral Resuscitation: cranial vault mechanics CPP = MAP - ICP CBF = CPP/CVR CD02 = CBF x Ca02

19. Cerebral Resuscitation: cranial vault mechanics Rosner M J, Rosner S D & Johnson A H. "Cerebral perfusion: management protocol and clinical results." J.Neurosurgery 1985; 83: 949-962. Bratton SL et al. J Neurotrauma 24 (S1): S59-S64, 2007 Narotam 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 TBI: ICP 60 = mortality reduction by > 50% HOWEVER, CPP>70 = increased mortality Healthy human subjects: normal CPP = 50-70 CPP<50 = ischemia/decreased EEG amplitude AIM FOR CPP>60, ICP<20

20. Cerebral Resuscitation: acute catastrophic neurologic injury

21. Cerebral Resuscitation: when to brain code  When there are clinical signs of herniation  When ICP is sustained >20cm H20 >3 minutes

22. Cerebral Resuscitation: herniation

23. Cerebral Resuscitation: compartment approach to ICP management Venous blood  HOB up 60 deg  Neck straight  No IJ lines, do not lay flat for lines  Do no use venodilating BP agents CSF  Place IVC  Change popoff Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Lesion  Blood, tumor, pus -> surgery  Air-> 100% NRB, surgery Arterial blood  Hyperventilate  Avoid hyperemia: MAP target 80, Pa02>50  Decrease metabolism: sedation, cooling

24. Cerebral Resuscitation: venous compartment Venous blood  HOB up 60 deg  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.

25. Cerebral Resuscitation: compartment approach to ICP management Venous blood  HOB up 60 deg  Neck straight  No IJ lines, do not lay flat for lines  Do no use venodilating BP agents CSF  Place IVC  Change popoff Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Lesion  Blood, tumor, pus -> surgery  Air-> 100% NRB, surgery Arterial blood  Hyperventilate  Avoid hyperemia: MAP target 80, Pa02>50  Decrease metabolism: sedation, cooling

26. Cerebral Resuscitation: arterial compartment Arterial blood  Mild hypervent (RR 18) target pC02 30-35  Avoid hyperemia: MAP target 80-130  Avoid hypoxia: Pa02>50  Decrease metabolism: propofol IVP, propofol/pentoba rb gtt, hypothermia 32- 34 C Kramer A, Zygun D. Anemia and red cell transfusion in neurocritical care. Critical Care 2009 13:R89 35 60150 25 20 50

27. Cerebral Resuscitation: arterial compartment Blood gas values and hemodynamic data at different respiratory rates 10 breaths/m13 breaths/m16 breaths/m PaCO 2 (mmHg)45.5 ± 9.939.7 ± 7.9*35.9 ± 7.9 †‡ Δ CO 2 (mmHg)4.2 ± 1.86.6 ± 2.87.6 ± 1.7 † pH7.29 ± 0.067.32 ± 0.06*7.35 ± 0.07 †‡ Bicarbonate (mmol/l)21.2 ± 2.520.7 ± 2.520 ± 2.5 Δ CO 2 ≤6 mmHg, n (%)10 (100)4 (40)*2 (20) † ScvO 2 (%)77.9 ± 4.174.7 ± 7.472.6 ± 7.1 † Cardiac index (l/m 2 )2.37 ± 0.52.36 ± 0.62.36 ± 0.6 Mean arterial pressure (mmHg)71.7 ± 13.368 ± 14.571.4 ± 13.2 Temperature (°C)36.9 ± 0.936.9 ± 0.936.8 ± 0.9 Δ CO 2, venous-arterial difference in carbon dioxide tension; PaCO 2, arterial partial pressure of carbon dioxide; ScvO 2, central venous oxygen saturation. *P <0.05 (respiratory rate 10 vs. 13 breaths/minute), † P <0.05 (respiratory rate 10 vs. 16 breaths/minute), ‡ P <0.05 (respiratory rate 13 vs. 16 breaths/minute). Morel et al. Critical Care 2011 15:456 doi:10.1186/cc10528

28. Cerebral Resuscitation: compartment approach to ICP management Venous blood  HOB up 60 deg  Neck straight  No IJ lines, do not lay flat for lines  Do no use venodilating BP agents Arterial blood  Hyperventilate  Avoid hyperemia: MAP target 80, Pa02>50  Decrease metabolism: sedation, cooling CSF  Place IVC  Change popoff Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Lesion  Blood, tumor, pus -> surgery  Air-> 100% NRB, surgery

29. Cerebral Resuscitation: CSF compartment CSF  Place IVC  Change popoff Situations in which IVC drainage is unlikely to be helpful:  cerebral edema with significant midline shift and no hydrocephalus  posterior fossa pathology Situations in which IVC drainage may be dangerous:  unsecured aneurysm  posterior fossa pathology

30. Cerebral Resuscitation: compartment approach to ICP management Venous blood  HOB up 60 deg  Neck straight  No IJ lines, do not lay flat for lines  Do no use venodilating BP agents CSF  Place IVC  Change popoff Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Lesion  Blood, tumor, pus -> surgery  Air-> 100% NRB, surgery Arterial blood  Hyperventilate  Avoid hyperemia: MAP target 80, Pa02>50  Decrease metabolism: sedation, cooling

31. Cerebral Resuscitation: Brain parenchyma Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) CytotoxicVasogenic Stroke Tumor Abscess

32. Cerebral Resuscitation: Brain parenchyma Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Intact BBB Damaged BBB particles blood brain Permeable Semi-Permeable

33. Cerebral Resuscitation: Brain parenchyma Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Sodium=1.0 Mannitol=0.9 Glycerol=0.5Sodium=0.6 Sodium=0.97 Mannitol=0.9 Glycerol=0.5Urea=0.6 Reflection Coefficient

34. Cerebral Resuscitation: Brain parenchyma Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Sodium=1.0 Mannitol=0.9 Glycerol=0.5Sodium=0.6

35. Cerebral Resuscitation: Brain parenchyma Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Sodium=1.0 Mannitol=0.9 Glycerol=0.5Sodium=0.6  N=8. 22 episodes of elevated ICP occurred, refractory to mannitol.  Bolus of 75cc of 10% saline normalized ICP in all.  ICP  10. Na  5.6 mmol/L. Serum osm  9 mmol/L.  No unexpected side effects.

36. Cerebral Resuscitation: Brain parenchyma Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC)  Increased vascular volume-> improves CBF up to 23%  Dehydration of erythrocytes increases deformability through small capillaries  Reduces inflammatory response by reducing PMN adhesion to microvasculature (unclear clinical significance) 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

37. Cerebral Resuscitation: Brain parenchyma Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Sodium=1.0 Mannitol=0.9 Glycerol=0.5Sodium=0.6 Create a GRADIENT, DON’T dehydrate your patient!

38. Cerebral Resuscitation: compartment approach to ICP management Venous blood  HOB up 45 deg  Neck straight  No IJ lines, do not lay flat for lines  Do no use venodilating BP agents CSF  Place IVC  Change popoff Brain parenchyma  Osmotherapy (mannitol, hypertonic saline)  Steroids only if appropriate (tumor, HACE, some infections)  Surgery (hemicrani, SOC) Lesion  Blood, tumor, pus -> surgery  Air-> 100% NRB, surgery Arterial blood  Hyperventilate  Avoid hyperemia: MAP target 80, Pa02>50  Decrease metabolism: sedation, cooling

39. MA Koenig, M Bryan, JL Lewin, III, MA Mirski, RG Geocadin and RD Stevens Neurology 2008;70;1023-1029; originally published online Feb 13, 2008  253 cases transtentorial herniation  30cc 23.4% saline bolus reversed clinical signs of TTH in 75%  Transient hypotension in 17%, no CPM on MRI at 17 days Emergency ICP management

40. Cerebral Resuscitation: outcomes ?

41. 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

42. Cerebral Resuscitation: outcomes  Hemicraniectomy for hemispheric stroke (AHA IB)  Indication: 50-66% infarction of MCA territory  Age: <50-60 yo  Dominance: no difference in functional outcome between L and R (Vahedi, Lancet Neurology 2007)  When: Early (<24-48 hrs)  How: >12cm hemicraniectomy  Outcomes: 43% vs 21% independent (SOC for cerebellar decompression: 40% independent)

43. Cerebral Resuscitation: herniation

44. Brain Code Pager and Brain Code Box Webpage Brain, Code (or Hillcrest pharmacy code pager 2619) Code pharmacist will arrive in <3 minutes with brain code box Contains: 100g 20% mannitol, 30 cc 23% saline, 500 cc 3% saline, phenylephrine premixed syringes (100mcg/1mL), syringes, filters Code sheet for documentation 34 episodes of herniation treated using BrainCodeBox at Hillcrest in 4 months 18 episodes herniation clinically reversed or partially reversed Cerebral Resuscitation: herniation

45. Patient TG  32M w/ colloid cyst w/ nl exam went into MRI at OSH at 0815 -> emerged from MRI 0900 w/ BP 200/100, pupils blown, extensor posturing, weak B corneals, + cough/gag -> intubated/versed+vecuronium+nipride gtt  MRI w acute obstructive hydrocephalus  JHH called at 1200; OSH instructed to stop versed/vec, give mannitol 1g/kg bolus (no hypertonic saline available), sedate with propofol, nicardipine only for SBP>220, insert femoral central line in reverse Trendelenburg if possible  None of these interventions were implemented

46. Patient TG  Pt arrives at JHH at 1400  Exam:  Temp 38.2, BP 220/110, HR 40-120 w/ runs of SVT, 02 sat 100%  AC 450/12/5/5/40%  Dilated nonreactive pupils  +R corneal, -L corneal  +cough/gag  Overbreathing vent @ RR32  Extensor posturing R, flaccid L  No central or arterial line

47. Patient TG

48.  1400-1410  Pt examined, pacer pads placed, labs drawn  Mannitol 1g/kg, 1L 2% saline bolus, 1L NS@100/h  Hyperventilation  Radial arterial line, femoral line placed  -> heart rate stabilized, no change in neuro exam  1410-1414  30cc 23.4% saline bolus -> ? regained L corneal  1414-1417  30cc 23.4% saline bolus -> pupils reactive, pt localizing  1443  Coags back, IVC placed and draining

49. Cerebral Resuscitation: outcomes

50.  My Cell: 650-906-9521  My Email: nkaranjia@ucsd.edu

51. Acknowledgements  Bill Mobley, MD  Bob Carter, MD  Alex Khalessi, MD  Jeffrey Gertsch, MD  Brian Lemkuil, MD  Bill Wilson, MD  Tom Hemmen, MD  Kim Kerr, MD  Peter Fedullo, MD  Patricia Graham RN, Laura Dibsie RN, and Cassia Chevillon RN  Romer Geocadin, MD  Marek Mirski, MD  COL Geoffrey Ling, MD