Semin Neurol 2008; 28(5): 690-702
DOI: 10.1055/s-0028-1105968
© Thieme Medical Publishers

Intracranial Hypertension

Eric M. Bershad1 , William E. Humphreis1 , Jose I. Suarez1
  • 1Department of Neurology, Baylor College of Medicine, Houston, Texas
Further Information

Publication History

Publication Date:
29 December 2008 (online)


Intracranial hypertension implies profoundly disturbed intracranial physiology. Although a shared manifestation of myriad neurological disorders of patients admitted in the intensive care unit (ICU), the pathways leading to intracranial hypertension vary by etiology. Acute elevation of the intracranial pressure is an emergency and may rapidly lead to brain death or a devastating neurological outcome if left untreated. Fortunately, with a firm grasp of the underlying pathophysiology and available treatments, one can optimize ICU-based management. Several integrated management paradigms have been used to treat intracranial hypertension. Regrettably, there is a dearth of randomized clinical trials to confirm the efficacy of even our most routine therapeutic strategies.


  • 1 Kshettry V R, Mindea S A, Batjer H H. The management of cranial injuries in antiquity and beyond.  Neurosurg Focus. 2007;  23(1) E8
  • 2 Steiner L A, Andrews P J. Monitoring the injured brain: ICP and CBF.  Br J Anaesth. 2006;  97(1) 26-38
  • 3 Rangel-Castillo L, Robertson C S. Management of intracranial hypertension.  Crit Care Clin. 2006;  22(4) 713-732 , abstract ix
  • 4 Davson H, Hollingsworth G, Segal M B. The mechanism of drainage of the cerebrospinal fluid.  Brain. 1970;  93(4) 665-678
  • 5 Czosnyka M, Richards H K, Czosnyka Z et al.. Vascular components of cerebrospinal fluid compensation.  J Neurosurg. 1999;  90(4) 752-759
  • 6 Langfitt T W, Weinstein J D, Kassell N F. Cerebral vasomotor paralysis produced by intracranial hypertension.  Neurology. 1965;  15 622-641
  • 7 Stoyka W W, Frankel D Z, Kay J C. The linear relation of cerebral blood flow to arterial oxygen saturation in hypoxic hypoxia induced with nitrous oxide or nitrogen.  Can Anaesth Soc J. 1978;  25(6) 474-478
  • 8 Klatzo I. Presidential address. Neuropathological aspects of brain edema.  J Neuropathol Exp Neurol. 1967;  26(1) 1-14
  • 9 Black K. Blood-brain barrier. In: Youmans JR Neurological Surgery. Philadelphia; Saunders 1995: 482-490
  • 10 Carpenter J, Weinstein S, Myseros J, Vezina G, Bell M J. Inadvertent hyponatremia leading to acute cerebral edema and early evidence of herniation.  Neurocrit Care. 2007;  6(3) 195-199
  • 11 Ropper A H. Lateral displacement of the brain and level of consciousness in patients with an acute hemispheral mass.  N Engl J Med. 1986;  314(15) 953-958
  • 12 Bingaman W E, Frank J I. Malignant cerebral edema and intracranial hypertension.  Neurol Clin. 1995;  13(3) 479-509
  • 13 Kishore P R, Lipper M H, Becker D P, Domingues da Silva A A, Narayan R K. Significance of CT in head injury: correlation with intracranial pressure.  AJR Am J Roentgenol. 1981;  137(4) 829-833
  • 14 Lee K R, Hoff J T. Intracranial Pressure. In: Youmans JR Neurological Surgery. Philadelphia; Saunders 1996: 491-518
  • 15 Lyons M K, Meyer F B. Cerebrospinal fluid physiology and the management of increased intracranial pressure.  Mayo Clin Proc. 1990;  65(5) 684-707
  • 16 Lang E W, Chesnut R M. Intracranial pressure. Monitoring and management.  Neurosurg Clin N Am. 1994;  5(4) 573-605
  • 17 Jordan K G. Neurophysiologic monitoring in the neuroscience intensive care unit.  Neurol Clin. 1995;  13(3) 579-626
  • 18 King W A, Martin N A. Critical care of patients with subarachnoid hemorrhage.  Neurosurg Clin N Am. 1994;  5(4) 767-787
  • 19 Lundberg N. Continuous recording and control of ventricular fluid pressure in neurosurgical practice.  Acta Psychiatr Scand Suppl. 1960;  36(149) 1-193
  • 20 Andrews B T, Chiles III B W, Olsen W L, Pitts L H. The effect of intracerebral hematoma location on the risk of brain-stem compression and on clinical outcome.  J Neurosurg. 1988;  69(4) 518-522
  • 21 Feen E S, Suarez J I. Raised intracranial pressure.  Curr Treat Options Neurol. 2005;  7(2) 109-117
  • 22 Frank J I. Management of intracranial hypertension.  Med Clin North Am. 1993;  77(1) 61-76
  • 23 Winkelman C. Effect of backrest position on intracranial and cerebral perfusion pressures in traumatically brain-injured adults.  Am J Crit Care. 2000;  9(6) 373-380 quiz 381-372
  • 24 Mitchell P H, Ozuna J, Lipe H P. Moving the patient in bed: effects on intracranial pressure.  Nurs Res. 1981;  30(4) 212-218
  • 25 Bratton S L, Chestnut R M, Ghajar J et al.. Guidelines for the management of severe traumatic brain injury. I. Blood pressure and oxygenation.  J Neurotrauma. 2007;  (24 Suppl 1) S7-S13
  • 26 Rosner M J, Becker D P. Origin and evolution of plateau waves. Experimental observations and a theoretical model.  J Neurosurg. 1984;  60(2) 312-324
  • 27 Bratton S L, Chestnut R M, Ghajar J et al.. Guidelines for the management of severe traumatic brain injury. IX. Cerebral perfusion thresholds.  J Neurotrauma. 2007;  (24 Suppl 1) S59-S64
  • 28 Robertson C S, Valadka A B, Hannay H J et al.. Prevention of secondary ischemic insults after severe head injury.  Crit Care Med. 1999;  27(10) 2086-2095
  • 29 Nordstrom C H. Physiological and biochemical principles underlying volume-targeted therapy–the “Lund concept”.  Neurocrit Care. 2005;  2(1) 83-95
  • 30 Yundt K D, Diringer M N. The use of hyperventilation and its impact on cerebral ischemia in the treatment of traumatic brain injury.  Crit Care Clin. 1997;  13(1) 163-184
  • 31 Bratton S L, Chestnut R M, Ghajar J et al.. Guidelines for the management of severe traumatic brain injury. XIV. Hyperventilation.  J Neurotrauma. 2007;  (24 Suppl 1) S87-S90
  • 32 McGuire G, Crossley D, Richards J, Wong D. Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure.  Crit Care Med. 1997;  25(6) 1059-1062
  • 33 Cooper K R, Boswell P A, Choi S C. Safe use of PEEP in patients with severe head injury.  J Neurosurg. 1985;  63(4) 552-555
  • 34 Castillo J, Davalos A, Marrugat J, Noya M. Timing for fever-related brain damage in acute ischemic stroke.  Stroke. 1998;  29(12) 2455-2460
  • 35 Hajat C, Hajat S, Sharma P. Effects of poststroke pyrexia on stroke outcome: a meta-analysis of studies in patients.  Stroke. 2000;  31(2) 410-414
  • 36 Oliveira-Filho J, Ezzeddine M A, Segal A Z et al.. Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome.  Neurology. 2001;  56(10) 1299-1304
  • 37 Jiang J Y, Gao G Y, Li W P, Yu M K, Zhu C. Early indicators of prognosis in 846 cases of severe traumatic brain injury.  J Neurotrauma. 2002;  19(7) 869-874
  • 38 Rossi S, Zanier E R, Mauri I, Columbo A, Stocchetti N. Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage.  J Neurol Neurosurg Psychiatry. 2001;  71(4) 448-454
  • 39 Capes S E, Hunt D, Malmberg K, Pathak P, Gerstein H C. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview.  Stroke. 2001;  32(10) 2426-2432
  • 40 Pulsinelli W A, Levy D E, Sigsbee B, Scherer P, Plum F. Increased damage after ischemic stroke in patients with hyperglycemia with or without established diabetes mellitus.  Am J Med. 1983;  74(4) 540-544
  • 41 Els T, Klisch J, Orszagh M et al.. Hyperglycemia in patients with focal cerebral ischemia after intravenous thrombolysis: influence on clinical outcome and infarct size.  Cerebrovasc Dis. 2002;  13(2) 89-94
  • 42 Kase C S, Furlan A J, Wechsler L R et al.. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke: the PROACT II trial.  Neurology. 2001;  57(9) 1603-1610
  • 43 Alberti O, Becker R, Benes L, Wallenfang T, Bertalanffy H. Initial hyperglycemia as an indicator of severity of the ictus in poor-grade patients with spontaneous subarachnoid hemorrhage.  Clin Neurol Neurosurg. 2000;  102(2) 78-83
  • 44 Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury.  Neurosurgery. 2000;  46(2) 335-342 discussion 342-333
  • 45 Yang S Y, Zhang S, Wang M L. Clinical significance of admission hyperglycemia and factors related to it in patients with acute severe head injury.  Surg Neurol. 1995;  44(4) 373-377
  • 46 Godoy D A, Pinero G R, Svampa S, Papa F, Di Napoli M. Hyperglycemia and short-term outcome in patients with spontaneous intracerebral hemorrhage.  Neurocrit Care. 2008;  9 217-229
  • 47 Kimura K, Iguchi Y, Inoue T et al.. Hyperglycemia independently increases the risk of early death in acute spontaneous intracerebral hemorrhage.  J Neurol Sci. 2007;  255(1–2) 90-94
  • 48 van den Berghe G, Wouters P, Weekers F et al.. Intensive insulin therapy in the critically ill patients.  N Engl J Med. 2001;  345(19) 1359-1367
  • 49 Van den Berghe G, Wilmer A, Hermans G et al.. Intensive insulin therapy in the medical ICU.  N Engl J Med. 2006;  354(5) 449-461
  • 50 Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters P J. Insulin therapy protects the central and peripheral nervous system of intensive care patients.  Neurology. 2005;  64(8) 1348-1353
  • 51 Bilotta F, Caramia R, Cernak I et al.. Intensive insulin therapy after severe traumatic brain injury: a randomized clinical trial.  Neurocrit Care. 2008;  9 159-166
  • 52 Vespa P M, Miller C, McArthur D et al.. Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis.  Crit Care Med. 2007;  35(12) 2830-2836
  • 53 Temkin N R, Dikmen S S, Wilensky A J et al.. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures.  N Engl J Med. 1990;  323(8) 497-502
  • 54 Rosengart A J, Huo J D, Tolentino J et al.. Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs.  J Neurosurg. 2007;  107(2) 253-260
  • 55 Sirven J I, Wingerchuk D M, Drazkowski J F, Lyons M K, Zimmerman R S. Seizure prophylaxis in patients with brain tumors: a meta-analysis.  Mayo Clin Proc. 2004;  79(12) 1489-1494
  • 56 Chen H J, Lee T C, Wei C P. Treatment of cerebellar infarction by decompressive suboccipital craniectomy.  Stroke. 1992;  23(7) 957-961
  • 57 Vahedi K, Hofmeijer J, Juettler E et al.. Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials.  Lancet Neurol. 2007;  6(3) 215-222
  • 58 Piek J. Decompressive surgery in the treatment of traumatic brain injury.  Curr Opin Crit Care. 2002;  8(2) 134-138
  • 59 Muizelaar J P, van der Poel H G, Li Z C, Kontos H A, Levasseur J E. Pial arteriolar vessel diameter and CO2 reactivity during prolonged hyperventilation in the rabbit.  J Neurosurg. 1988;  69(6) 923-927
  • 60 Marshall R S, Mayer S A. On Call Neurology. 2nd ed. New York; WB Saunders 2001
  • 61 Muizelaar J P, Marmarou A, Ward J D et al.. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial.  J Neurosurg. 1991;  75(5) 731-739
  • 62 de los Reyes R A, Ausman J I, Diaz F G. Agents for cerebral edema.  Clin Neurosurg. 1981;  28 98-107
  • 63 Nau R. Osmotherapy for elevated intracranial pressure: a critical reappraisal.  Clin Pharmacokinet. 2000;  38(1) 23-40
  • 64 Ravussin P, Abou-Madi M, Archer D et al.. Changes in CSF pressure after mannitol in patients with and without elevated CSF pressure.  J Neurosurg. 1988;  69(6) 869-876
  • 65 Mendelow A D, Teasdale G M, Russell T et al.. Effect of mannitol on cerebral blood flow and cerebral perfusion pressure in human head injury.  J Neurosurg. 1985;  63(1) 43-48
  • 66 Burke A M, Quest D O, Chien S, Cerri C. The effects of mannitol on blood viscosity.  J Neurosurg. 1981;  55(4) 550-553
  • 67 Tan G, Zhou J, Yuan D, Sun S. Formula for use of mannitol in patients with intracerebral haemorrhage and high intracranial pressure.  Clin Drug Investig. 2008;  28(2) 81-87
  • 68 Cruz J, Minoja G, Okuchi K, Facco E. Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial.  J Neurosurg. 2004;  100(3) 376-383
  • 69 Garcia-Morales E J, Cariappa R, Parvin C A, Scott M G, Diringer M N. Osmole gap in neurologic-neurosurgical intensive care unit: Its normal value, calculation, and relationship with mannitol serum concentrations.  Crit Care Med. 2004;  32(4) 986-991
  • 70 Node Y, Nakazawa S. Clinical study of mannitol and glycerol on raised intracranial pressure and on their rebound phenomenon. In: Long DM Brain Edema: Pathogenesis, Imaging and Therapy Advances in Neurology. New York; Raven Press 1990: 359-363
  • 71 Domaingue C M, Nye D H. Hypotensive effect of mannitol administered rapidly.  Anaesth Intensive Care. 1985;  13(2) 134-136
  • 72 Wakai A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury.  Cochrane Database Syst Rev. 2007;  (1) CD001049
  • 73 Bereczki D, Fekete I, Prado G F, Liu M. Mannitol for acute stroke.  Cochrane Database Syst Rev. 2007;  (3) CD001153
  • 74 Qureshi A I, Suarez J I. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension.  Crit Care Med. 2000;  28(9) 3301-3313
  • 75 Qureshi A I, Suarez J I, Bhardwaj A et al.. Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: Effect on intracranial pressure and lateral displacement of the brain.  Crit Care Med. 1998;  26(3) 440-446
  • 76 Suarez J I. Hypertonic saline for cerebral edema and elevated intracranial pressure.  Cleve Clin J Med. 2004;  71(S1) S9-S13
  • 77 Koenig M A, Bryan M, Lewin III J L et al.. Reversal of transtentorial herniation with hypertonic saline.  Neurology. 2008;  70 1023-1029
  • 78 Harutjunyan L, Holz C, Rieger A et al.. Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol 15% in the treatment of increased intracranial pressure in neurosurgical patients: a randomized clinical trial.  Crit Care. 2005;  9(5) R530-R540
  • 79 Roberts I. Barbiturates for acute traumatic brain injury.  Cochrane Database Syst Rev. 2000;  (2) CD000033
  • 80 Albanese J, Arnaud S, Rey M et al.. Ketamine decreases intracranial pressure and electroencephalographic activity in traumatic brain injury patients during propofol sedation.  Anesthesiology. 1997;  87(6) 1328-1334
  • 81 Kolenda H, Gremmelt A, Rading S, Braun U, Markakis E. Ketamine for analgosedative therapy in intensive care treatment of head-injured patients.  Acta Neurochir (Wien). 1996;  138(10) 1193-1199
  • 82 Ubogu E E, Sagar S M, Lerner A J et al.. Ketamine for refractory status epilepticus: a case of possible ketamine-induced neurotoxicity.  Epilepsy Behav. 2003;  4(1) 70-75
  • 83 Minton M D, Grosslight K, Stirt J A, Bedford R F. Increases in intracranial pressure from succinylcholine: prevention by prior nondepolarizing blockade.  Anesthesiology. 1986;  65(2) 165-169
  • 84 Markewitz B A, Elstad M R. Succinylcholine-induced hyperkalemia following prolonged pharmacologic neuromuscular blockade.  Chest. 1997;  111(1) 248-250
  • 85 Clifton G L, Miller E R, Choi S C et al.. Lack of effect of induction of hypothermia after acute brain injury.  N Engl J Med. 2001;  344(8) 556-563
  • 86 Bernard S A, Gray T W, Buist M D et al.. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.  N Engl J Med. 2002;  346(8) 557-563
  • 87 Padosch S A, Kern K B, Bottiger B W. Therapeutic hypothermia after cardiac arrest.  N Engl J Med. 2002;  347(1) 63-65 author reply 63-65
  • 88 Poungvarin N, Bhoopat W, Viriyavejakul A et al.. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage.  N Engl J Med. 1987;  316(20) 1229-1233
  • 89 Qizilbash N, Lewington S L, Lopez-Arrieta J M. Corticosteroids for acute ischaemic stroke.  Cochrane Database Syst Rev. 2002;  (2) CD000064
  • 90 Norris J W, Hachinski V C. High dose steroid treatment in cerebral infarction.  Br Med J (Clin Res Ed). 1986;  292(6512) 21-23
  • 91 Anderson D C, Cranford R E. Corticosteroids in ischemic stroke.  Stroke. 1979;  10(1) 68-71
  • 92 Bauer R B, Tellez H. Dexamethasone as treatment in cerebrovascular disease. 2. A controlled study in acute cerebral infarction.  Stroke. 1973;  4(4) 547-555
  • 93 Chen D, Nishizawa S, Yokota N et al.. High-dose methylprednisolone prevents vasospasm after subarachnoid hemorrhage through inhibition of protein kinase C activation.  Neurol Res. 2002;  24(2) 215-222
  • 94 Chyatte D, Fode N C, Nichols D A, Sundt Jr T M. Preliminary report: effects of high dose methylprednisolone on delayed cerebral ischemia in patients at high risk for vasospasm after aneurysmal subarachnoid hemorrhage.  Neurosurgery. 1987;  21(2) 157-160
  • 95 Yamakawa K, Sasaki T, Tsubaki S et al.. Effect of high-dose methylprednisolone on vasospasm after subarachnoid hemorrhage.  Neurol Med Chir (Tokyo). 1991;  31(1) 24-31
  • 96 Edwards P, Arango M, Balica L et al.. Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months.  Lancet. 2005;  365(9475) 1957-1959
  • 97 Kullberg G, West K A. Influence of corticosteroids on the ventricular fluid pressure.  Acta Neurol Scand Suppl. 1965;  13(Pt 2) 445-452
  • 98 Miller J D, Sakalas R, Ward J D et al.. Methylprednisolone treatment in patients with brain tumors.  Neurosurgery. 1977;  1(2) 114-117
  • 99 Naredi S, Olivecrona M, Lindgren C et al.. An outcome study of severe traumatic head injury using the “Lund therapy” with low-dose prostacyclin.  Acta Anaesthesiol Scand. 2001;  45(4) 402-406
  • 100 Rosner M J, Rosner S D, Johnson A H. Cerebral perfusion pressure: management protocol and clinical results.  J Neurosurg. 1995;  83(6) 949-962
  • 101 Nordstrom C H. Volume-targeted therapy of increased intracranial pressure.  Acta Neurochir Suppl. 2003;  86 355-360
  • 102 Eker C, Asgeirsson B, Grande P O, Schalen W, Nordstrom C H. Improved outcome after severe head injury with a new therapy based on principles for brain volume regulation and preserved microcirculation.  Crit Care Med. 1998;  26(11) 1881-1886
  • 103 Brazis P W, Masdeu J C, Biller J. Coma. In: Brazis PW, Masdeu JC, Biller J Localization in Clinical Neurology. 4th ed. Philadelphia; Lippincott Williams and Wilkins 2001: 559-585

Jose I SuarezM.D. 

Department of Neurology, Baylor College of Medicine

One Baylor Plaza, NB 302, Houston, TX 77030