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Cerebral edema and its management

CEREBRAL EDEMA AND ITS MANAGEMENT

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Cerebral edema and its management

  1. 1. CEREBRAL EDEMA
  2. 2. TYPES 1. CYTOTOXIC 2. VASOGENIC 3. HYDROSTATIC 4. OSMOTIC 5. HYDROCEPHALIC • EDEMA IN TRAUMA • EDEMA IN TUMOUR
  3. 3. 1. Cytotoxic • In cytotoxic edema, the BBB remains intact. • It occurs due to a disruption in cellular metabolism that impairs functioning of the sodium and potassium pump in the glial cell membrane, leading to cellular retention of sodium and water. • Swollen astrocytes occur in gray and white matter • This interfere with neuronal and oligoendrocyte function • This edema occurs through intra cellular hyperosmolarity and extra cellular hypotonicity with deranged ATP dependant Na K pump
  4. 4. Causes • various toxins, including – dinitrophenol, – triethyltin, – hexachlorophene, and – isoniazid. It can occur in • Reye's syndrome, • severe hypothermia • early ischemia, • encephalopathy, • early stroke or hypoxia, • cardiac arrest, and pseudotumor cerebri.
  5. 5. • During an ischemic stroke, a lack of oxygen and glucose leads to a breakdown of the sodium-calcium pumps on brain cell membranes, • which in turn results in a massive build up of sodium and calcium intracellularly. • This causes a rapid uptake of water and subsequent swelling of the cells. • It is this swelling of the individual cells of the brain that is seen as the main distinguishing characteristic of cytotoxic edema, as opposed to vasogenic wherein the influx of fluid is typically seen in the interstitial space rather than within the cells themselves
  6. 6. Vasogenic edema • Vasogenic edema occurs due to a breakdown of the tight endothelial junctions which make up the blood–brain barrier (BBB). • Swollen astrocyte foot processes reflecting initial glial cytotoxicity( clossed barrier to open barrier edema) • Interendothelial fenestration widened • Trans endothelial trafficking increased • This allows intravascular proteins and fluid to penetrate into the parenchymal extracellular space. • Once plasma constituents cross the BBB, the edema spreads; this may be quite rapid and extensive • As water enters white matter it moves extracellularly along fiber tracts and can also affect the gray matter.
  7. 7. Causes • trauma, • tumors, • focal inflammation, • late stages of cerebral ischemia and • hypertensive encephalopathy.
  8. 8. 3. HYDROSTATIC EDEMA • This form of cerebral edema is seen in acute, malignant hypertension. SYST >160 • It is thought to result from direct transmission of pressure to cerebral capillaries with • transudation of fluid from the capillaries into the extravascular compartment. • Occurs inter-endothelially and trans endothelially • TRANSIENT OPENING OF BBB • Later extracellular protein osmotic gradient draws fluid from vascular compartment
  9. 9. causes Accelerated hypertention Mountain sickness Nitric oxide
  10. 10. Osmotic • Normally, the osmolality of cerebral-spinal fluid (CSF) and extracellular fluid (ECF) in the brain is slightly lower than that of plasma. • Plasma dilution decreases serum osmolality, resulting in a higher osmolality in the brain compared to the serum. • This creates an abnormal pressure gradient and movement of water into the brain, causing edema • BBB IS relatively intact • Then edema is interstitial in location
  11. 11. Causes • Plasma can be diluted by several mechanisms, including • excessive water intake (or hyponatremia), • syndrome of inappropriate antidiuretic hormone secretion (SIADH) • Hemodialysis • rapid reduction of blood glucose in hyperosmolar hyperglycemic state (HHS),
  12. 12. Hydrocephalic edema • Interstitial edema occurs in obstructive hydrocephalus due to a rupture of the CSF-brain barrier. • This results in trans-ependymal flow of CSF, causing CSF to penetrate the brain and spread to the extracellular spaces and the white matter. • Interstitial cerebral edema differs from vasogenic edema as CSF contains almost no protein.
  13. 13. Cerebral edema from brain tumour • Cancerous glial cells (glioma) of the brain can increase secretion of vascular endothelial growth factor (VEGF), • New and weak vessel formation • which weakens the junctions of the blood– brain barrier
  14. 14. Edema in trauma • Vasogenic d/t breach in BBB • Cytotoxic d/t inflammatory mediators • Osmotic brain edema d/t extra vasation of plasma products • Hydrocephalic d/t obstruction of csf flow
  15. 15. • CEREBRAL edema, simply defined as an increase in brain water content (above the normal brain water content of approximately 80%).
  16. 16. MONITORING ICP • The Brain Trauma Foundation guidelines recommend ICP monitoring in patients with TBI, – a GCS score of less than 9, and abnormal CT scans, – in patients with a GCS score less than 9 and normal CT scans in the presence of two or more of the following: 1. age greater than 40 years 2. unilateral or bilateral motor posturing 3. systolic blood pressure greater than 90 mmHg. • No such guidelines exist for ICP monitoring in other brain injury paradigms (ischemic stroke, ICH, cerebral neoplasm
  17. 17. General Measures for Managing Cerebral Edema 1. Optimizing Head and Neck Positions 2. Ventilation and Oxygenation 3. Intravascular Volume and Cerebral Perfusion 4. Seizure Prophylaxis 5. Management of Fever and Hyperglycemia 6. Nutritional Support
  18. 18. Specific Measures for Managing Cerebral Edema 1. Controlled Hyperventilation 2. Osmotherapy 3. Corticosteroid Administration 4. Pharmacological Coma 5. Therapeutic Hypothermia 6. Other Adjunct Therapies
  19. 19. Optimizing Head and Neck Positions • 30̊elevation of the head in patients is essential for 1. avoiding jugular compression and impedance of venous outflow from the cranium 2. for decreasing CSF hydrostatic pressure. • to avoid the use of restricting devices and garments around the neck (such as devices used to secure endotracheal tubes), which may impair cerebral venous outflow via compression of the internal jugular veins. • Head position elevation may be detrimental in ischemic stroke, because it may compromise perfusion to ischemic tissue at risk.
  20. 20. Ventilation and Oxygenation • Hypoxia and hypercapnia are potent cerebral vasodilator • Pt should be intubated in: 1. GCS scores less than or equal to 8 2. Patients with poor upper airway reflexes be intubated preemptively for airway protection. 3. aspiration pneumonitis 4. pulmonary contusion 5. acute respiratory distress syndrome.
  21. 21. • Levels of PaCO2should be maintained that support adequate rCBF or CPP to the injured brain, and a value of approximately 35 mmHg is a generally accepted target in the absence of ICP elevations or clinical herniation syndromes. • Avoidance of hypoxemia and maintenance of PaO2 at approximately 100 mmHg are recommended. • Delivery of PEEP greater than 10 cm H2O in patients with severe TBI has resulted in elevated ICP which resulted from elevations in central venous pressures and impedance of cerebral venous drainage.
  22. 22. • Therefore, careful monitoring of clinical neurological status, ICP, and CPP (mean arterial pressure – ICP) is recommended in mechanically ventilated patients with cerebral edema with or without elevations in ICP. • Blunting of upper airway reflexes (coughing) with endobronchial lidocaine before suctioning, sedation, or, rarely, pharmacological paralysis may be necessary for avoiding increases in ICP.
  23. 23. Intravascular Volume and Cerebral Perfusion • Maintenance of CPP using adequate fluid management in combination with vasopressors is vital in patients with brain injury • Hypotonic fluids should be avoided at all cost) • Euvolemia or mild hypervolemia with the use of isotonic fluids (0.9% saline) should always be maintained through rigorous attention to daily fluid balance, body weight, and serum electrolyte monitoring.
  24. 24. • The recommended goal of a CPP level greater than 60 mmHg should be adhered to in patients with TBI, and simultaneously, sharp rises in systemic blood pressure should be avoided. • CBF=CPP/CVR ( CBF-Cerebral blood flow, CPP-Cerebral perfusion pressure, CVR-Cerebrovascular resistance ) • NORMAL CPP= 70 TO 90 mm of Hg • CPP=MAP-ICP (IF ICP>JVP) (MAP-mean arterial pressure ) • CPP=MAP-JVP (IF JVP>ICP) • MAP=DP-1/3PP (PP-Pulse pressure ,where PP= SBP-DBP) • Normal MAP is between 70 to 110 mmHg
  25. 25. TREATING HYPERTENSION • Judicious use of antihypertensives 1. Labetalol 2. Enalaprilate 3. Nicardipine – is recommended for treating systemic hypertension. • Potent vasodilators are to be avoided – Nitroglycerine – Nitroprusside – as they may exacerbate cerebral edema via accentuated cerebral hyperemia and CBV due to their direct vasodilating effects on cerebral vasculature.
  26. 26. Seizure Prophylaxis • Phenytoin are widely used empirically in clinical practice in patients with acute brain injury • Early seizures in TBI can be effectively reduced by prophylactic administration of phenytoin for 1 or 2 weeks.
  27. 27. Management of Fever • fever has deleterious effects of on outcome following brain injury, • increases in oxygen demand, • normothermia is strongly recommended in patients with cerebral edema, irrespective of underlying origin. • Acetaminophen (325–650 mg orally, or rectally every 4–6 hours) is the most common agent used, • Other surface cooling devices have demonstrated some efficacy
  28. 28. Hyperglycemia • Hyperglycemia can also exacerbate brain injury and cerebral edema • current evidence suggests that rigorous glycemic control may be beneficial in all patients with brain injury.
  29. 29. Nutritional Support • Unless contraindicated, the enteral route of nutrition is preferred. • Special attention should be given to the osmotic content of formulations, to avoid free water intake that may result in a hypoosmolar state and worsen cerebral edema.
  30. 30. Specific Measures for Managing Cerebral Edema Controlled
  31. 31. Controlled Hyperventilation • controlled hyperventilation remains the most efficacious therapeutic intervention for cerebral edema, • particularly when the edema is associated with elevations in ICP. • A decrease in PaCO2 by 10 mmHg produces proportional decreases in rCBF resulting in rapid and prompt ICP reduction. • The vasoconstrictive effect of respiratory alkalosis on cerebral arterioles has been shown to last for 10 to 20 hours, • beyond which vascular dilation may result in exacerbation of cerebral edema and rebound elevations in ICP. • Prolonged hyperventilation has been shown to result in worse outcomes in patients with TBI
  32. 32. • Overaggressive hyperventilation may actually result in cerebral ischemia. • maintain PaCO2 by 10 mmHg to a target level of approximately 30–35 mmHg for 4 to 6 hours, although • controlled hyperventilation is to be used as a rescue or resuscitative measure for a short duration until more definitive therapies are instituted and maintained that are tailored toward the particular patient (osmotherapy, surgical decompres- sion, and others). • Caution is advised when reversing hyperventilation judiciously over 6 to 24 hours to avoid cerebral hyperemia and rebound elevations in ICP secondary to effects of reequilibration.
  33. 33. Osmotherapy • Weed and McKibben observed that intravenous administration of a concentrated salt solution resulted in an inability to withdraw CSF from the lumbar cistern due to a collapse of the thecal sac. • Concentrated urea was the first agent to be used clinically as an osmotic agent. Its use was short-lived due to its side effects (nausea, vomiting, diarrhea, and coagulopathy) • Glycerol was possibly the second osmotic agent to be used clinically and is, interestingly, still used by some physicians in continental Europe because of tradition.
  34. 34. MANNITOL • Mannitol, an alcohol derivative of simple sugar mannose, was introduced in 1960 and has since remained the major osmotic agent of choice in clinical practice. • Its long duration of action (4–6 hours) and relative stability in solution have enhanced its use over the years. • The extra- osmotic properties of mannitol provide additional beneficial effects in brain injury, 1. Decreases in blood viscosity, 2. Resulting in increases in rCBF and CPP 3. and a resultant cerebral vasoconstriction leading to decreased CBV 4. free radical scavenging 5. Inhibition of apoptosis
  35. 35. MANNITOL • Mannitol is a nonelectrolyte of low molecular weight that is pharmacologically inert— • can be given in large quantities sufficient to raise osmolarity of plasma and tubular fluid. • It is not metabolized in the body; • freely filtered at the glomerulus and undergoes limited reabsorption: • therefore excellently suited to be used as osmotic diuretic. • Mannitol appears to limit tubular water and electrolyte reabsorption in a variety of ways: • excretion of all cation and anions is also enhanced
  36. 36. • IN PROXIMAL TUBULE: – Retains water isoosmotically in PT dilutes luminal fluid which opposes NaCl reabsorption. • IN LOOP OF HENLE: – Inhibits transport processes in the thick AscLH by an unknown mechanism. – Major site of action is LOOP OF HENLE • MEDULLARY OSMOTIC GRADIENT & RENAL BLOOD FLOW: – By extracting water from intracellular compartments, osmotic diuretics expand the extracellular fluid volume, decrease blood viscosity, and inhibit renin release. – These effects increase RBF. – and the increase in renal medullary blood flow removes NaCl and urea from the renal medulla, thus reducing medullary tonicity.
  37. 37. • some circumstances, prostaglandins may contribute to the renal vasodilation and medullary washout induced by osmotic diuretics. • A reduction in medullary tonicity causes a decrease in the extraction of water from the DTL, which, in turn, limits the concentration of NaCl in the tubular fluid entering the ATL. • This latter effect diminishes the passive reabsorption of NaCl in the ATL.
  38. 38. • Effects on Urinary Excretion – Osmotic diuretics increase the urinary excretion of nearly all electrolytes, including Na+, K+, Ca2+, Mg2+, Cl-, HCO3 and phosphate. • Effects on Renal Hemodynamics – Osmotic diuretics increase RBF by a variety of mechanisms. – Osmotic diuretics dilate the afferent arteriole, which increases PGC and dilute the plasma, which decreases PGC – These effects would increase GFR were it not for the fact that osmotic diuretics also increase PT – In general, superficial SNGFR is increased, but total GFR is little changed.
  39. 39. PHARMACOKINETICS • Administration Mannitol is not absorbed orally. • has to be given i.v. as 10–20% solution. • It is excreted with a t½ of 0.5–1.5 hour.
  40. 40. USES • Decreases intracranial or intraocular tension – (acute congestive glaucoma, head injury, stroke, etc.): – by osmotic action it encourages movement of water from brain parenchyma, CSF and aqueous humour; – 1–1.5 g/kg is infused over 1 hour as 20% solution to transiently raise plasma osmolarity. – It is also used before and after ocular/brain surgery to prevent acute rise in intraocular/intracranial pressure
  41. 41. • To maintain g.f.r. and urine flow in impending acute renal failure, – e.g. in shock, severe trauma, cardiac surgery, haemolytic reactions: 500–1000 ml of the solution may be infused over 24 hours. – If acute renal failure has already set in, kidney is incapable of forming urine even after an osmotic load; mannitol is contraindicated: it will then expand plasma volume → pulmonary edema and heart failure may develop. • To counteract low osmolality of plasma/e.c.f. – due to rapid haemodialysis or peritoneal dialysis (dialysis disequilibrium).
  42. 42. • Forced diuresis: – Mannitol along with large volumes of saline was infused i.v. to produce ‘forced diuresis’ in acute poisonings in the hope of enhancing excretion of the poison. – However, this has been found to be ineffective and to produce electrolyte imbalances. Not recommended now.
  43. 43. CONTRAINDICATION 1. Acute tubular necrosis, 2. Anuria 3. Pulmonary edema; 4. Acute left ventricular failure 5. CHF 6. Cerebral haemorrhage.
  44. 44. SIDE EFFECTS • When given orally causes osmotic diarrhoea • DEHYDRATION, HYPERKALEMIA, AND HYPERNATREMIA – Excessive use of mannitol without adequate water replacement can ultimately lead to severe dehydration, free water losses, and hypernatremia. – As water is extracted from cells, intracellular K+ concentration rises, leading to cellular losses and hyperkalemia. – These complications can be avoided by careful attention to serum ion composition and fluid balance.
  45. 45. • EXTRACELLULAR VOLUME EXPANSION – Mannitol is rapidly distributed in the extracellular compartment and extracts water from cells. – Prior to the diuresis, this leads to expansion of the extracellular volume and hyponatremia. – This effect can complicate heart failure and may produce florid pulmonary edema. • Headache, nausea, and vomiting are commonly observed in patients treated with osmotic diuretics.
  46. 46. OTHER OSMOTIC DIURETICS • Isosorbide and glycerol – These are orally active osmotic diuretics which may be used to reduce intraocular or intracranial tension. – Intravenous glycerol can cause haemolysis. • Dose: 0.5–1.5 g/kg as oral solution.
  47. 47. • In a prospective series of patients with elevated ICP and diverse intracranial diseases, bolus mannitol decreased ICP, with a mean reduction of 52% of pretreatment values. • in an uncontrolled series of patients with TBI, 0.25g/kg of an intra venous bolus of mannitol was sufficient to attenuate elevated ICP. • high-dose mannitol treatment may be preferable to conventional doses for acute TBI.
  48. 48. • DOSE OF MANNITOL: – The conventional osmotic agent mannitol, when administered at a dose of 0.25 to 1.5 g/kg by intravenous bolus injection, usually lowers ICP, with maximal effects observed 20 to 40 minutes following its administration. – Repeated dosing of Mannitol may be instituted every 6 hours and should be guided by serum osmolality to a recommended target value of approximately 320 mOsm/L; higher values result in renal tubular damage
  49. 49. HYPERTONIC SALINE • Hypertonic saline solutions reappeared in the 1980s – Its use resulted in lower ICP – decreased cerebral edema – increased rCBF – improved oxygen delivery • prehospital restoration of intravascular volume improved morbidity and mortality rates and physiological parameters (such as systemic blood pressure, cardiac index, and tissue per- fusion) in this subset of patients.
  50. 50. • unique extraosmotic properties of hypertonic saline 1. Modulation of CSF production resorption 2. Accentuation of tissue oxygen delivery. 3. May modulate inflammatory and neurohumoral responses (arginine-vasopressin and atrial natriuretic peptide) 4. Following brain injury that may act together to ameliorate cerebral edema. • FORMULATIONS OF HYPERTONIC SALINE – 2% – 3% NaCl has 513 mEq/L of Na and Cl. – 5% NaCl has 856 mEq/L of Na and Cl. – 7% (1200 mEq/L) and – 7.5% – 10% – 23.4% (approx 4000 mEq/L),
  51. 51. • 23.4% hypertonic saline produced both a greater and more sustained reduction in ICP (?8 hours of observation) than did equiosmolar doses of mannitol. • Boluses of 7.5% hypertonic saline reduced ICP and cerebral edema to the same extent as mannitol. • a mixture of 7.2% NaCl and 10% dextran-60 produced similar reductions in ICP, compared with equimolar doses of 20% mannitol. • 30% saline can be used to reduce icp refractory to mannitol or even to hyperventilation/barbiturates • hypertonic saline produces longer duration of ICP lowering with than with mannitol.
  52. 52. • hypertonic saline with hydroxyethyl starch (for more prolonged action), hypertonic saline was shown to be more effective than equiosmolar doses of mannitol in lowering elevated ICP and augmenting CPP in patients with ischemic stroke. • the literature supports the use of hypertonic saline as a therapy to decrease ICP in patients following TBI and stroke and to optimize intravascular fluid status in patients with SAH-induced vasospasm.
  53. 53. • Hypertonic saline solutions of 2, 3, or 7.5% contain equal amounts of sodium chloride and sodium acetate (50:50) to avoid hyperchloremic Acidosis. • Potassium supplementation (20–40 meq/L) is added to the solution as needed. • Continuous intravenous infusions are begun through a central venous catheter at a variable rate to achieve euvolemia or slight hypervolemia (1–2 ml/ kg/hr). • A 250-ml bolus of hypertonic saline can be administered cautiously in select patients if more aggressive and rapid resuscitation is warranted. • The goal in using hypertonic saline is to increase serum sodium concentration to a range of 145 to 155 mEq/L (serum osmolality approximately 300–320 mOsm/L)
  54. 54. • This level of serum sodium is maintained for 48 to 72 hours until patients demonstrate clinical improvement or there is a lack of response despite achieving the serum sodium target. • During withdrawal of therapy, special caution is emphasized due to the possibility of rebound hyponatremia and cerebral edema • Serum sodium and potassium are monitored every 4 to 6 hours, during both institution and withdrawal of therapy • other serum electrolytes are monitored daily (particularly calcium and magnesium)
  55. 55. • Chest radiographs are obtained at least once every day to try and find evidence of pulmonary edema from congestive heart failure, especially in elderly patients with poor cardiovascular reserve. • Intravenous bolus injections (30 ml) of 23.4% hypertonic saline have been used in cases of intracranial hypertension refractory to conventional ICP-lowering therapies; • repeated injections of 30 ml boluses of 23.4% saline may be given if needed to lower ICP. • Administration of this osmotic load, to lower ICP and maintain CPP, may allow extra time for other di-agnostic or therapeutic interventions (such as decompressive surgery) in critically ill patients.
  56. 56. Glycerol • Glycerol is another useful agent given in oral • Doses: – 30 ml every 4-6 hour or daily IV 50g in 500 ml of 2.5% saline solution – its effectiveness appears to decrease after few days. – It is used in a dose of 0.5-1.0 g/kg body weight. – In unconscious or uncooperative patients it is given by nasogastric tube
  57. 57. Therapeutic Basis and Goal of Osmotherapy • fundamental goal of osmotherapy is to create an osmotic gradient to cause egress of water from the brain extracellular (and possibly intracellular) compartment into the vasculature, • thereby decreasing intracranial volume (normal brain volume 80%, normal blood volume 10%, and normal CSF volume 10%) and improving intracranial elastance and compliance.
  58. 58. • In healthy individuals, serum osmolality (285–295 mOsm/L) is relatively constant, and the serum Na+ concentration is an estimate of body water osmolality. • Under ideal circumstances,serum osmolality is dependent on the major cations – (Na+ and K+) – plasma glucose – blood urea nitrogen. • Because urea is freely diffusible across cell membranes, serum Na+ and plasma glucose are the major molecules involved in altering serum osmolality
  59. 59. • The goal of using osmotherapy is to maintain a euvolemic or a slightly hypervolemic state. • A serum osmolality in the range of 300 to 320 mOsm/L has traditionally been recommended for patients with acute brain injury
  60. 60. An ideal osmotic agent 1. produces a favorable osmotic gradient, 2. Is inert 3. Nontoxic 4. is excluded from an intact BBB 5. has minimal systemic side effects. • REFLECTION COEFFICIENT : – The ability of the intact BBB to exclude a given compound has been quantified by biophysicists. – Very simplistically, compounds approaching 1is (completely impermeable) are considered to be better osmotic agents because they are completely excluded by an intact BBB, and conversely less likely to exhibit “rebound” cerebral edema during withdrawal of osmotherapy.
  61. 61. • With mannitol = 0.9 ,the potential for rebound cerebral edema exists as a result of a reversal of osmotic gradient • glycerol (= 0.48) and urea ( = 0.59) are less than ideal agents for osmotherapy because their osmotic effects are transient and they are only partly excluded by the intact BBB; • sodium chloride has a reflection coefficient of 1.0, it has been proposed to be a potentially more effective osmotic agent
  62. 62. Potential Complications of Osmotherapy. • Mannitol – Hypotension – Hemolysis – hy perkalemia – Renal insufficiency – pulmonary edema. • Side effect profile of hypertonic saline is superior to mannitol, but some theoretical complications that are possible with hypertonic saline therapy are notable (Table 2). – Myelinolysis, the most serious complication of hypertonic saline therapy, typically occurs when rapid corrections in serum sodium arise from a chronic hyponatremic state to a normonatremic or hypernatremic state.
  63. 63. Loop Diuretics • commonly furosemide for the treatment of cerebral edema, particularly when used alone, remains controversial. • Furosemide (0.7 mg/kg) has been shown to prolong the reversal of blood brain osmotic gradient established with the osmotic agents by preferentially excreting water over solute • Combining furosemide with mannitol produces a profound diuresis; however, the efficacy and optimum duration of this treatment remain • If loop diuretics are used, rigorous attention to systemic hydration status is advised, as the risk of serious volume depletion is substantial and cerebral perfusion may be compromised. • A common strategy used to raise serum sodium rapidly is to administer an intravenous bolus of furosemide (10 to 20 mg) to enhance free water excretion and to replace it with a 250- ml intravenous bolus of 2 or 3% hypertonic saline
  64. 64. Corticosteroid Administration • Used in vasogenic edema associated with brain tumors or accompanying brain irradiation and surgical manipulation. • steroids decrease tight-junction permeability and, in turn, stabilize the disrupted BBB. • Glucocorticoids, especially dexamethasone, are the preferred steroidal agents, due to their low mineralocorticoid activity • Steroids deleterious side effects are peptic ulcers, hyperglycemia, impairment of wound healing, psychosis, and immunosuppression.
  65. 65. Pharmacological Coma -Barbiturates • Barbiturates lower ICP, principally via a reduction in cerebral metabolic activity, resulting in a coupled reduction in rCBF and CBV. • In patients with TBI, barbiturates are effective in reducing ICP but have failed to show evidence of improvement in clinical outcome. • Agents used – Pentobarbital : a barbiturate with an intermediate physiological half life (approximately 20 hours) is the preferred agent – Phenobarbital : which has a much longer half- life (approximately 96 hours) – Thiopental : which has a much shorter half-life (approximately 5 hours)
  66. 66. • DOSAGE: – loading intravenous bolus dose of pentobarbital (3–10 mg/kg), – Followed by a continuous intravenous infusion (0.5–3.0 mg/Kg/hr, serum levels of 3 mg/dL), which is titrated to sustain reduction in ICP or achieve a “burst-suppression pattern” on continuous electroencephalographic monitoring. • It is recommended that a barbiturate coma be maintained for 48 to 72 hours, with gradual tapering by decreasing the hourly infusion by 50% each day. • Longer periods of induced coma may be necessary, however, to reverse the underlying disease causing cerebral edema and ICP elevation.
  67. 67. • ADVERSE EFFECTS OF BARBITURATES: 1. Sustained vasodepressor effect (lowering of systemic blood pressure and CPP), 2. Vasopressor support and ionotropic agent use are frequently required 3. Cardiodepression 4. Immunosuppression leading to increased risk of infection 5. Systemic hypothermia. 6. Inability to track subtle changes in a patient’s clinical neurological status, which necessitates frequent serial neuroimaging.
  68. 68. PROPOFOL • ADVANTAGES: – Propofol emerged as an appealing alternative, especially due to its extremely short half-life. – efficacy in controlling ICP in patients with TBI – it also has ANTISEIZURE properties – decreases cerebral metabolic rate. • SIDE EFFECTS: – HYPOTENSION can be the limiting factor to its use in the clinical setting. – HYPERTRIGLYCERIDEMIA – Cases of “propofol infusion syndrome” that can be fatal have been reported, particularly in children, when propofol is used over a long period of time at high doses. – Careful monitoring of serum triglycerides is recommended with its use. – Increased CO2 production due to the lipid emulsification vehicle.
  69. 69. Analgesia, Sedation and Paralysis. • Pain and agitation can worsen cerebral edema and raise ICP significantly, and should always be controlled. • Judicious intravenous doses of – bolus morphine (2–5 mg) – fentanyl (25– 100 ?cg) – continuous intravenous infusion of fentanyl (25–200 cg/hour) can be used for analgesia. • A NEUROMUSCULAR BLOCKADE: – can be used as an adjunct to other measures when controlling refractory ICP. – Nondepolarizing agents should be used, because a depolarizing agent (such as succinylcholine) can cause elevations in ICP due to induction of muscle contraction.
  70. 70. THERAPEUTIC HYPOTHERMIA • hyperthermia is deleterious to brain injury, achieving normothermia is a desirable goal in clinical practice. • The role of hypothermia in TBI is less clear • present consensus is that adverse effects of therapeutic hypothermia outweigh the benefits in TBI • external cooling devices – air-circulating cooling blankets – iced gastric lavage – surface ice packs
  71. 71. Other Adjunct Therapies • THAM: – a buffer (pKa ~ 7.8) introduced in the 1960s, which has been shown to ameliorate secondary neuronal injury and cerebral edema in experimental animal models, – as well as in patients with TBI (presumably by ameliorating tissue acidosis). – Role in TBI is clearly not eatablished • HYPERBARIC OXYGEN: – for the treatment of cerebral edema, based on a clinical trial (100% oxygen at 1.5 atmospheres for 1 hour every 8 hours) that demonstrated enhanced survival in patients with TBI • INDOMETHACIN: – Although the mechanisms are poorly understood, indomethacin treatment has been shown to attenuate increases in ICP in TBI diminishing rCBF and fever prevention have been postulated as plausible mechanisms for this beneficial action
  72. 72. • Adverse effects – systemic infection – Coagulopathy – electrolyte derangements. – Shivering, a common treatment accompaniment, can be controlled with pharmacological neuromuscular blockade or meperidine in combination with enteral buspirone

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