Cerebral edema and intracranial hypertension after traumatic brain injury can be managed through various interventions to control increased intracranial pressure. These include cerebral resuscitation, intracranial pressure monitoring, hyperosmolar therapy with mannitol or hypertonic saline, mild hyperventilation, CSF drainage, temperature control, surgical decompression, and in refractory cases high-dose barbiturates or calcium channel blockers. Nutritional support and anti-seizure prophylaxis may also be considered as part of the management approach.

1. Cerebral Edema A Review and Management PJ Papadakos MD FCCP FCCM Professor Anesthesiology, Surgery and Neurosurgery Director Critical Care Medicine University of Rochester

2. HOW DO PATIENTS PRESENT ? Obvious--motor vehicle accident, car vs pedestrian, fall from height, etc Less obvious--sports injuries (football), delayed deterioration (epidural) Hidden--shaken baby syndrome, older child maltreatment Post Surgical Post Cardiac Arrest, Hypoxic Injury Electrolyte Imbalance

3. CAVEATS IN BRAIN INJURY Neurologic examination - the most important information you have Accurate history is often unavailable or inaccurate Potential for associated injuries or illness (cardiovascular, respiratory, cervical spine)

4. CEREBRAL RESUSCITATION Primary survey - airway, breathing, and circulation Neurologic evaluation Secondary survey - “head to toe” Neuroradiologic evaluation Ongoing evaluation and transport

5. MECHANISMS OF INJURY-PRIMARY Impact: epidural, subdural, contusion, intracerebral hemorrhage, skull fractures Inertial: concussion, diffuse axonal injury Hypoxic\ Ischemic

6. MECHANISMS OF 2 nd INJURY Global Hypoxia and ischemia of brain Decreased cerebral blood flow due to increased intracranial pressure Local impairment of cerebral blood flow or extra cellular milieu due to the presence of injured brain

7. PATHOPHYSIOLOGY Primary damage – the only treatment is by prevention . Secondary damage – multifactorial and time dependent.

8. Brain trauma BBB disruption diffuse axonal injury edema formation Eicosanoids endocannabinoids necrosis energy failure cytokines SOME of the SECONDARY EVENTS IN TRAUMATIC BRAIN INJURY apoptosis inflammation ROS polyamines Calcium Acetyl Choline ischemia Shohami, 2000 Green – pathophysiological processes; Yellow – various mediators

9. Time is Important

10. Hours Dynamic Changes Following Stroke/Trauma Days Weeks / Months Weeks/Months Ca , Na + Glut, ROS 8 hrs 7 Necrosis Apoptosis Repair Remodeling Plasticity Functional Recovery I N J U R Y 14 2 Inflammation Barone &Feuerstein JCBF, 1999

11. Pathophysiology

12. MONRO-KELLIE DOCTRINE V intracranial vault =V brain +V blood + V csf

13. BRAIN: CEREBRAL EDEMA-VASOGENIC (Caused mainly by activation of NMDA receptors by glutamate)

14. BRAIN: CEREBRAL EDEMA-CYTOTOXIC (Caused mainly by activation of cytokines, ROS and other pro-inflammatory mediators)

15. The brain has the ability to control its blood supply to match its metabolic requirements Chemical or metabolic byproducts of cerebral metabolism can alter blood vessel caliber and behavior BLOOD: CEREBRAL BLOOD FLOW

16. BLOOD: CEREBRAL BLOOD FLOW (VOLUME) Increases in cerebral metabolic rate Hyperthermia Seizures Pain, anxiety

17. CSF: CEREBROSPINAL FLUID 10% of intracranial volume Initial displacement of CSF from ventricles Ventriculostomy to drain CSF

18. Intracranial Compliance Calvarium is composed of three fluid compartments: Cerebral Blood Volume, CSF, and cerebral parenchyma

20. GUIDELINES – GENERAL ASPECTS Standards: accepted principles of patient management that reflect a high degree of clinical certainty Guidelines: strategies that reflect moderate clinical certainty Options: unclear clinical certainty

21. Prehospital

22. PREHOSPITAL AIRWAY MANAGEMENT Hypoxia must be avoided, and correct immediately . 13%-27%  O 2 Supplemental oxygen should be administered No advantage of ETI (ET intubation) Vs. BVM (Bag / valve / mask) ventilation for the pre-hospital airway in pediatric TBI 420 TBI; 115 BVM; 177 ETI  no change ( Gausche, JAMA 2000 ) TBI + ETI  ETCO 2

23. RESUSCITATION OF BP AND O 2 AND PREHOSPITAL BRAIN-SPECIFIC TX’S FOR SPTBI PATIENTS Hypotension should be identified and corrected as rapidly as possible with fluid resuscitation. (G) Hypotension on arrival to ER (Pigula, J Ped Surg 1993) 18% ER: mortality 61% Vs. 22%, ↓ BP+ ↓ O 2 – mortality  85% ! Levine (Neurosurg 1992) : TBI 0-4y ↓ BP – 32% poor outcome. Laurssen (J Neurosurg 1988) : ↑ BP  ↓ EX; White (CCM 2001) : syst BP > 135  X19 in survival !

24. PREHOSPITAL TREATMENTS No evidence of efficacy: sedation, NMB, Mannitol, saline 3%, hyperventilation. The prophylactic administration of mannitol is not recommended. Mannitol may be considered for use in euvolemic patients who show signs of cerebral herniation or acute neurological deterioration.

25. PREHOSPITAL TREATMENTS Mild prophylactic hyperventilation is not recommended . Hyperventilation may be considered in patients who show signs of Imminent cerebral herniation or acute neurological deterioration After correcting hypotension or hypoxemia

26. CT SCANS and X-rays

27. Skull fracture

29. Intracranial Hemorrhage

31. Coup-Contrecoup focal injury consisting of contusions and hematoma at the site of the blow, opposite side of the brain

33. Reversible high T2 signal abnormalities in pre-eclampsia

34. Monitoring

35. INDICATIONS FOR ICP MONITORING IN PATIENTS WITH SEVERE TBI ↑ ICP ≡ ↓ Outcome; Aggressive Tx ≡ ↑ Outcome Intra-cranial pressure monitoring (ICP) is appropriate in all patients with severe traumatic brain injury (TBI) (Glasgow Coma [GCS] score ≤ 8) The presence of open fontanels and/or sutures in an infant with severe TBI does not preclude the development of intracranial hypertension or negate the utility of ICP monitoring.

36. INTRACRANIAL PRESSURE MONITORING STBI (GCS ≤ 8) + Abnormal CT ≡ 53-63% ↑ ICP (adult data). Intra-cranial pressure monitoring is not routinely indicated in infants and children with mild or moderate head injury. However, a physician may choose to monitor ICP in certain conscious patients with traumatic mass lesions or serial neurological examination is precluded by sedation, neuromuscular blockade, or anesthesia.

37. THRESHOLD FOR TREATMENT OF INTRA-CRANIAL HYPERTENSION ICP>20-40mmHg ≡ Mort. 28%; ICP>40mmHg ≡ 100% Treatment for intracranial hypertension, defined as a pathologic elevation in intracranial pressure (ICP), should begin at an ICP ≥ 20 mm Hg. (O) Patients may herniate at ICP < 20-25mmHg. Is there a lower ICP threshold for younger children ? Interpretation and treatment of ↑ ICP based on any ICP threshold should be corroborated by frequent clinical examination monitoring of physiologic variables (CPP, Compliance) cranial imaging.

38. INTRACRANIAL PRESSURE MONITORING TECHNOLOGY ICP monitoring: a ventricular catheter; external strain gauge transducer (??); catheter tip pressure transducer device  All accurate & reliable (O) Ventricular cath. device most accurate, reliable, low cost + enables therapeutic (CSF) drainage . No report of meningitis  ICP monitoring. Jensen: 7% +tip; positive > 7.5 days

39. CEREBRAL PERFUSION PRESSURE (CPP) A cerebral perfusion pressure (CPP) >40 mm Hg

40. THE ROLE OF CSF DRAINAGE Cerebrospinal fluid (CSF) drainage can be considered as an option in the management of elevated ICP Drainage: Ventriculostomy ± Lumber puncture.

41. Mannitol ( 2 X Class III ) Vs. Hypertonic Saline ( 3 X Class II; 1 X Class III ). Mannitol is effective. Euvolemia + Folly catheter Accepted osmolarity: Mannitol < 320mOsm/L; Hyper NS < 360mOsm/L Mannitol   blood viscosity   arteriolar diameter and  osmotic effect. Hyper NS  Osmolar grad; membrane pot.; cellular volume;  ANP;  Inflammation;  C.O. USE OF HYPEROSMOLAR THERAPY

42. HYPEROSMOLAR THERAPY Hypertonic saline is effective for control of increased ICP after severe head injury Effective doses: cont. infusion of 3% saline 0.1 - 1.0 ml/kg/h, a sliding scale. Goal minimum dose maintain ICP <20 mmHg. Mannitol bolus dose: 0.25g/Kg – 1g/Kg.

43. USE OF HYPERVENTILATION in the ACUTE MANAGEMENT Mild or prophylactic hyperventilation (paco 2 <35 mm hg) should be avoided . Mild hyperventilation (paco 2 30-35 mm hg) may be considered for longer periods for intra-cranial hypertension refractory to Sedation and analgesia Neuromuscular blockade Cerebrospinal fluid drainage hyperosmolar therapy

44. HYPERVENTILATION Aggressive hyperventilation (Paco 2 < 30 mm Hg) may be considered as a second tier option in the setting of refractory hypertension (O). Cerebral blood flow (CBF), jugular venous oxygen saturation, or brain tissue oxygen monitoring is suggested to help identify cerebral ischemia in this setting. Aggressive hyperventilation therapy titrated to clinical effect may be necessary for BRIEF PERIODS in cases of cerebral herniation or acute neurologic deterioration.

45. THE USE of BARBITURATES in the CONTROL of INTRA-CRANIAL HYPERTENSION High-dose barbiturate therapy may be considered in hemodynamically stable patients with salvageable severe head injury and refractory intracranial hypertension. If high-dose barbiturate therapy is used, then appropriate hemodynamic monitoring (CVP, Swan-Ganz, repeated ECHOs) and cardiovascular support (Dopamine, Adrenaline) are essential.

46. THE USE of BARBITURATES in the CONTROL of INTRA-CRANIAL HYPERTENSION Gold standard – continuous EEG to achieve a state of burst suppression. Serum barbiturate levels are NOT GOOD for monitoring that therapy. Prophylactic therapy is not recommended (side effects).

47. THE ROLE OF TEMPERATURE CONTROL Extrapolated from the adult data, hyperthermia should be avoided in children with severe traumatic brain injury (TBI) (O). Despite the lack of clinical data in children, hypothermia may be considered in the setting of refractory intracranial hypertension

48. Calcium Channel Blockers

49. Ca2+ inf lux Voltag e- Operated Ca2+ specific Receptor- O perated Ca2+ / Cation Ligand-Operated Ca2+/Cation Plasma membrane channels Ca2+ Mitochondrial Ca Uptake Sarco-/Endo-plasmic reticulum Ca Uptake Ca/Mg pump Na-Ca exchg.

50. Calcium Channel blockers May be membrane protective Affect Vasospasm

51. Coronary/Cerebral Steal The detrimental redistribution of blood flow in patients with atherosclerotic disease from underperfused areas toward better perfused areas Before Vasodilator Stenosis After Vasodilator

52. Surgical Decompression

54. DECOMPRESSIVE CRANIECTOMY Decompressive craniectomy appears to be less effective in patients who have experienced extensive secondary brain insults Patients who experience Secondary deterioration on the Glasgow coma scale (GCS) and/or evolving cerebral herniation syndrome within the first 48 hrs after injury may represent a favorable group Unimproved GCS of 3 may represent an unfavorable group

55. THE USE OF CORTICOSTEROIDS IN THE TREATMENT TBI With the lack of sufficient evidence for beneficial effect and the potential for increased complications and suppression of adrenal production of cortisol, the routine use of steroids is not recommended for patients following severe traumatic brain injury.

56. NUTRITIONAL SUPPORT Replace 130-160% of resting metabolism expenditure after TBI in patients. Weight-specific resting metabolic expenditure guidelines can be found in Talbot's tables. Based on the adult guidelines, nutritional support should begin by 72 hrs with full replacement by 7 days.

57. THE ROLE of ANTI-SEIZURE PROPHYLAXIS FOLLOWING STBI Prophylactic anti-seizure therapy may be considered as a treatment option to prevent increased oxygen utilization

58. Thank You