Brain injury results from ischemia, tissue hypoxia, and a cascade of secondary events. The cornerstone of neurocritical care management is optimization and maintenance of cerebral blood flow (CBF) and oxygen and substrate delivery to prevent or attenuate this secondary damage. New techniques for monitoring brain tissue oxygen tension (PtiO2) are now available. Brain PtiO2 reflects both oxygen delivery and consumption. Brain hypoxia (low brain PtiO2) has been associated with poor outcomes in patients with brain injury. Strategies to improve brain PtiO2 have focused mainly on increasing oxygen delivery either by increasing CBF or by increasing arterial oxygen content. The results of nonrandomized studies comparing brain PtiO2-guided therapy with intracranial pressure/cerebral perfusion pressure-guided therapy, while promising, have been mixed. More studies are needed including prospective, randomized controlled trials to assess the true value of this approach. The following is a review of the physiology of brain tissue oxygenation, the effect of brain hypoxia on outcome, strategies to increase oxygen delivery, and outcome studies of brain PtiO2-guided therapy in neurocritical care.
RosenthalGHemphillJCIIISoraniM. Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen delivery and metabolism in patients with traumatic brain injury. Crit Care Med. 2008;36(6):1917–1924.
2.
KroghA. The rate of diffusion of gases through animal tissues, with some remarks on the coefficient of invasion. J Physiol. 1919;52(6):391–408.
3.
KreuzerF. Oxygen supply to tissues: the Krogh model and its assumptions. Experientia. 1982;38(12):1415–1426.
4.
MenonDKColesJPGuptaAK. Diffusion limited oxygen delivery following head injury. Crit Care Med. 2004;32(6):1384–1390.
5.
EllsworthMLEllisCGPopelASPittmanRN. Role of microvessels in oxygen supply to tissue. NIPS. 1994;9:119–123.
6.
GoldmanDPopelAS. A computational study of the effect of capillary network anastomoses and tortuosity on oxygen transport. J Theor Biol. 2000;206(2):181–194.
7.
EllsworthMLEllisCGGoldmanDStephensonAHDietrichHHSpragueRS. Erythrocytes: oxygen sensors and modulators of vascular tone. Physiology (Bethesda). 2009;24:107–116.
8.
DulingBRBerneRM. Longitudinal gradients in periarteriolar oxygen tension. A possible mechanism for the participation of oxygen in local regulation of blood flow. Circ Res. 1970;27(5):669–678.
9.
TsaiAGJohnsonPCIntagliettaM. Oxygen gradients in the microcirculation. Physiol Rev. 2003;83(3):933–963.
10.
LubbersDWBaumgartlH. Heterogeneities and profiles of oxygen pressure in brain and kidney as examples of the pO2 distribution in the living tissue. Kidney Int. 1997;51(2):372–380.
MaasAIFleckensteinWde JongDAvan SantbrinkH. Monitoring cerebral oxygenation: experimental studies and preliminary clinical results of continuous monitoring of cerebrospinal fluid and brain tissue oxygen tension. Acta Neurochir Suppl (Wien). 1993;59:50–57.
13.
MeixensbergerJDingsJKuhnigkHRoosenK. Studies of tissue PO2 in normal and pathological human brain cortex. Acta Neurochir Suppl (Wien). 1993;59:58–63.
14.
ZaunerABullockRDiXYoungHF. Brain oxygen, CO2, pH, and temperature monitoring: evaluation in the feline brain. Neurosurgery. 1995;37(6):1168–1176; discussion 1176-1167.
15.
SarrafzadehASKieningKLBardtTFSchneiderGHUnterbergAWLankschWR. Cerebral oxygenation in contusioned vs. nonlesioned brain tissue: monitoring of PtiO2 with Licox and Paratrend. Acta Neurochir Suppl. 1998;71:186–189.
16.
DoppenbergEMZaunerAWatsonJCBullockR. Determination of the ischemic threshold for brain oxygen tension. Acta Neurochir Suppl (Wien). 1998;71:166–169.
17.
ValadkaABGopinathSPContantCFUzuraMRobertsonCS. Relationship of brain tissue PO2 to outcome after severe head injury. Crit Care Med. 1998;26(9):1576–1581.
18.
JohnstonAJSteinerLAChatfieldDA. Effect of cerebral perfusion pressure augmentation with dopamine and norepinephrine on global and focal brain oxygenation after traumatic brain injury. Int Care Med. 2004;30(5):791–797.
19.
ScheuflerKMLehnertARohrbornHJNadstawekJTheesC. Individual value of brain tissue oxygen pressure, microvascular oxygen saturation, cytochrome redox level, and energy metabolites in detecting critically reduced cerebral energy state during acute changes in global cerebral perfusion. J Neurosurg Anesthesiol. 2004;16(3):210–219.
20.
ValadkaABGoodmanJCGopinathSPUzuraMRobertsonCS. Comparison of brain tissue oxygen tension to microdialysis-based measures of cerebral ischemia in fatally head-injured humans. J Neurotrauma. 1998;15(7):509–519.
21.
MeixensbergerJKunzeEBarcsayEVaethARoosenK. Clinical cerebral microdialysis: brain metabolism and brain tissue oxygenation after acute brain injury. Neurol Res. 2001;23(8):801–806.
22.
FleckensteinWWeissC. A comparison of Po2 histograms from rabbit hind-limb muscles obtained by simultaneous measurements with hypodermic needle electrodes and with surface electrodes. Adv Exp Med Biol. 1984;169:447–455.
23.
PurinsKEnbladPSandhagenBLewenA. Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors. Acta Neurochir (Wien). 2010;152(4):681–688.
24.
HoelperBMAlessandriBHeimannABehrRKempskiO. Brain oxygen monitoring: in-vitro accuracy, long-term drift and response-time of Licox- and Neurotrend sensors. Acta Neurochir (Wien). 2005;147(7):767–774.
25.
KieningKLHartlRUnterbergAWSchneiderGHBardtTLankschWR. Brain tissue pO2-monitoring in comatose patients: implications for therapy. Neurol Res. 1997;19(3):233–240.
26.
ColesJPFryerTDSmielewskiP. Defining ischemic burden after traumatic brain injury using 15O PET imaging of cerebral physiology. J Cereb Blood Flow Metab. 2004;24(2):191–201.
27.
LonghiLPaganFValerianiV. Monitoring brain tissue oxygen tension in brain-injured patients reveals hypoxic episodes in normal-appearing and in peri-focal tissue. Int Care Med. 2007;33(12):2136–2142.
28.
PonceLLPillaiSCruzJ. Position of probe determines prognostic information of brain tissue PO2 in severe traumatic brain injury. Neurosurgery. 2012;70(6):1492–1502; discussion 1502-1493.
29.
Kett-WhiteRHutchinsonPJAl-RawiPGGuptaAKPickardJDKirkpatrickPJ. Adverse cerebral events detected after subarachnoid hemorrhage using brain oxygen and microdialysis probes. Neurosurgery. 2002;50(6):1213–1221; discussion 1221-1212.
30.
VäthAKunzeERoosenKMeixensbergerJ. Therapeutic aspects of brain tissue pO2 monitoring after subarachnoid hemorrhage. Acta Neurochir Suppl. 2002;81:307–309.
31.
ChenHIStiefelMFOddoM. Detection of cerebral compromise with multimodality monitoring in patients with subarachnoid hemorrhage. Neurosurgery. 2011;69(1):53–63; discussion 63.
32.
BardtTFUnterbergAWHartlRKieningKLSchneiderGHLankschWR. Monitoring of brain tissue PO2 in traumatic brain injury: effect of cerebral hypoxia on outcome. Acta Neurochir Suppl. 1998;71:153–156.
33.
van den BrinkWAvan SantbrinkHSteyerbergEW. Brain oxygen tension in severe head injury. Neurosurgery. 2000;46(4):868–876; discussion 876-868.
34.
Maloney-WilenskyEGraciasVItkinA. Brain tissue oxygen and outcome after severe traumatic brain injury: a systematic review. Crit Care Med. 2009;37(6):2057–2063.
35.
ErikssonEABarlettaJFFigueroaBE. The first 72 hours of brain tissue oxygenation predicts patient survival with traumatic brain injury. J Trauma Acute Care Surg. 2012;72(5):1345–1349.
OddoMLevineJMMackenzieL. Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independently of intracranial hypertension and low cerebral perfusion pressure. Neurosurgery. 2011;69(5):1037–1045; discussion 1045.
38.
RohlwinkUKZwaneEFieggenAGArgentACle RouxPDFigajiAA. The relationship between intracranial pressure and brain oxygenation in children with severe traumatic brain injury. Neurosurgery. 2012;70(5):1220–1230; discussion 1231.
39.
RadolovichDKCzosnykaMTimofeevI. Transient changes in brain tissue oxygen in response to modifications of cerebral perfusion pressure: an observational study. Anesth Analg. 2010;110(1):165–173.
40.
StocchettiNChieregatoADe MarchiMCrociMBentiRGrimoldiN. High cerebral perfusion pressure improves low values of local brain tissue O2 tension (PtiO2) in focal lesions. Acta Neurochir Suppl. 1998;71:162–165.
41.
JaegerMSchuhmannMUSoehleMMeixensbergerJ. Continuous assessment of cerebrovascular autoregulation after traumatic brain injury using brain tissue oxygen pressure reactivity. Critical Care Medicine. 2006;34(6):1783–1788.
42.
CzosnykaMSmielewskiPKirkpatrickPLaingRJMenonDPickardJD. Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery. 1997;41(1):11–17; discussion 17-19.
43.
CzosnykaMBalestreriMSteinerL. Age, intracranial pressure, autoregulation, and outcome after brain trauma. J Neurosurg. 2005;102(3):450–454.
44.
JaegerMSchuhmannMUSoehleMNagelCMeixensbergerJ. Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage by brain tissue oxygen pressure reactivity and its relation to delayed cerebral infarction. Stroke. 2007;38(3):981–986.
45.
JaegerMSoehleMSchuhmannMUMeixensbergerJ. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke. 2012;43(8):2097–2101.
46.
RadolovichDKCzosnykaMTimofeevI. Reactivity of brain tissue oxygen to change in cerebral perfusion pressure in head injured patients. Neurocritical Care. 2009;10(3):274–279.
47.
DenglerJFrenzelCVajkoczyPHornPWolfS. The oxygen reactivity index and its relation to sensor technology in patients with severe brain lesions. Neurocritical Care. 2013;19(1):74–78.
JaegerMSoehleMMeixensbergerJ. Effects of decompressive craniectomy on brain tissue oxygen in patients with intracranial hypertension. J Neurol Neurosurg Psychiatry. 2003;74(4):513–515.
50.
StiefelMFHeuerGGSmithMJ. Cerebral oxygenation following decompressive hemicraniectomy for the treatment of refractory intracranial hypertension. J Neurosurg. 2004;101(2):241–247.
51.
OddoMLevineJMFrangosS. Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension. J Neurol Neurosurg Psychiatry. 2009;80(8):916–920.
52.
ChenHIMalhotraNROddoMHeuerGGLevineJMLeRouxPD. Barbiturate infusion for intractable intracranial hypertension and its effect on brain oxygenation. Neurosurgery. 2008;63(5):880–886; discussion 886-887.
53.
ReischRMauerDRingelKPerneczkyA. The effect of intra-arterial infusion of papavarine hydrochloride on brain tissue oxygen pressure and cerebral blood flow in the management of severe vasospasm following aneurysmal subarachnoid hemorrhage. Zentralbl Neurochir. 1999;60:33–54.
54.
CharbelFTDuXHoffmanWEAusmanJI. Brain tissue PO(2), PCO(2), and pH during cerebral vasospasm. Surg Neurol. 2000;54(6):432–437; discussion 438.
55.
DeshaiesEMJacobsenWSinglaALiFGorjiR. Brain tissue oxygen monitoring to assess reperfusion after intra-arterial treatment of aneurysmal subarachnoid hemorrhage-induced cerebral vasospasm: a retrospective study. AJNR Am J Neuroradiol. 2012;33(7):1411–1415.
56.
StiefelMFSpiottaAMUdoetukJD. Intra-arterial papaverine used to treat cerebral vasospasm reduces brain oxygen. Neurocrit Care. 2006;4(2):113–118.
57.
StuartRMHelbokRKurtzP. High-dose intra-arterial verapamil for the treatment of cerebral vasospasm after subarachnoid hemorrhage: prolonged effects on hemodynamic parameters and brain metabolism. Neurosurgery. 2011;68(2):337–345; discussion 345.
58.
OddoMNduomEFrangosS. Acute lung injury is an independent risk factor for brain hypoxia after severe traumatic brain injury. Neurosurgery. 2010;67(2):338–344.
59.
ReinprechtAGreherMWolfsbergerSDietrichWIllievichUMGruberA. Prone position in subarachnoid hemorrhage patients with acute respiratory distress syndrome: effects on cerebral tissue oxygenation and intracranial pressure. Crit Care Med. 2003;31(6):1831–1838.
60.
HlatkyRValadkaABGopinathSPRobertsonCS. Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain. J Neurosurg. 2008;108(1):53–58.
61.
LonghiLValerianiVRossiSDe MarchiMEgidiMStocchettiN. Effects of hyperoxia on brain tissue oxygen tension in cerebral focal lesions. Acta Neurochir Suppl. 2002;81:315–317.
62.
FigajiAAZwaneEGraham FieggenAArgentACLe RouxPDPeterJC. The effect of increased inspired fraction of oxygen on brain tissue oxygen tension in children with severe traumatic brain injury. Neurocrit Care. 2010;12(3):430–437.
63.
van SantbrinkHvd BrinkWASteyerbergEWCarmona SuazoJAAvezaatCJMaasAI. Brain tissue oxygen response in severe traumatic brain injury. Acta Neurochir (Wien). 2003;145(6):429–438; discussion 438.
64.
FloydTFClarkJMGelfandR. Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA. J Appl Physiol (1985). 2003;95(6):2453–2461.
65.
NakajimaSMeyerJSAmanoTShawTOkabeTMortelKF. Cerebral vasomotor responsiveness during 100% oxygen inhalation in cerebral ischemia. Arch Neurol. 1983;40(5):271–276.
66.
JaegerMLangEW. Cerebrovascular pressure reactivity and cerebral oxygen regulation after severe head injury. Neurocrit Care. 2013;19(1):69–73.
67.
MagnoniSGhisoniLLocatelliM. Lack of improvement in cerebral metabolism after hyperoxia in severe head injury: a microdialysis study. J Neurosurg. 2003;98(5):952–958.
68.
DiringerMNAiyagariVZazuliaARVideenTOPowersWJ. Effect of hyperoxia on cerebral metabolic rate for oxygen measured using positron emission tomography in patients with acute severe head injury. J Neurosurg. 2007;106(4):526–529.
69.
OddoMMilbyAChenI. Hemoglobin concentration and cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2009;40(4):1275–1281.
70.
ChangJJYounTSBensonD. Physiologic and functional outcome correlates of brain tissue hypoxia in traumatic brain injury. Criti Care Med. 2009;37(1):283–290.
71.
SmithMJStiefelMFMaggeS. Packed red blood cell transfusion increases local cerebral oxygenation. Crit Care Med. 2005;33(5):1104–1108.
72.
ZygunDANortjeJHutchinsonPJTimofeevIMenonDKGuptaAK. The effect of red blood cell transfusion on cerebral oxygenation and metabolism after severe traumatic brain injury. Crit Care Med. 2009;37(3):1074–1078.
73.
HebertPCWellsGBlajchmanMA. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group [see comment; erratum appears in N Engl J Med. 1999;340(13):1056]. N Engl J Med. 1999;340(6):409–417.
74.
RaoSVJollisJGHarringtonRA. Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes [see comment]. JAMA. 2004;292(13):1555–1562.
75.
SmithMJLe RouxPDElliottJPWinnHR. Blood transfusion and increased risk for vasospasm and poor outcome after subarachnoid hemorrhage [see comment]. J Neurosurg. 2004;101(1):1–7.
76.
TaylorRWManganaroLO'BrienJTrottierSJParkarNVeremakisC. Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient [see comment]. Crit Care Med. 2002;30(10):2249–2254.
77.
ShorrAFJacksonWL. Transfusion practice and nosocomial infection: assessing the evidence. Curr Opin Crit Care. 2005;11(5):468–472.
78.
ZallenGOffnerPJMooreEE. Age of transfused blood is an independent risk factor for postinjury multiple organ failure. Am J Surg. 1999;178(6):570–572.
79.
MooreFAMooreEESauaiaA. Blood transfusion. An independent risk factor for postinjury multiple organ failure. Arch Surg. 1997;132(6):620–624; discussion 624-625.
HeddleNMKlamaLNGriffithLRobertsRShuklaGKeltonJG. A prospective study to identify the risk factors associated with acute reactions to platelet and red cell transfusions. Transfusion. 1993;33(10):794–797.
82.
SillimanCCBoshkovLKMehdizadehkashiZ. Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. Blood. 2003;101(2):454–462.
83.
ToyPPopovskyMAAbrahamE. Transfusion-related acute lung injury: definition and review. Crit Care Med. 2005;33(4):721–726.
84.
CorwinHLGettingerAPearlRG. The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States [see comment]. Crit Care Med. 2004;32(1):39–52.
85.
StiefelMFSpiottaAGraciasVH. Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring. J Neurosurg. 2005;103(5):805–811.
86.
FletcherJJBergmanKBlosteinPAKramerAH. Fluid balance, complications, and brain tissue oxygen tension monitoring following severe traumatic brain injury. Neurocrit Care. 2010;13(1):47–56.
87.
ContantCFValadkaABGopinathSPHannayHJRobertsonCS. Adult respiratory distress syndrome: a complication of induced hypertension after severe head injury. J Neurosurg. 2001;95(4):560–568.
88.
SpiottaAMStiefelMFGraciasVH. Brain tissue oxygen-directed management and outcome in patients with severe traumatic brain injury. J Neurosurg. 2010;113(3):571–580.
89.
NarotamPKMorrisonJFNathooN. Brain tissue oxygen monitoring in traumatic brain injury and major trauma: outcome analysis of a brain tissue oxygen-directed therapy. J Neurosurg. 2009;111(4):672–682.
90.
GreenJAPellegriniDCVanderkolkWEFigueroaBEErikssonEA. Goal directed brain tissue oxygen monitoring versus conventional management in traumatic brain injury: an analysis of in hospital recovery. Neurocrit Care. 2013;18(1):20–25.
91.
MartiniRPDeemSYanezND. Management guided by brain tissue oxygen monitoring and outcome following severe traumatic brain injury. J Neurosurg. 2009;111(4):644–649.
92.
AdamidesAACooperDJRosenfeldtFL. Focal cerebral oxygenation and neurological outcome with or without brain tissue oxygen-guided therapy in patients with traumatic brain injury. Acta Neurochir. 2009;151(11):1399–1409.
93.
McCarthyMCMoncriefHSandsJM. Neurologic outcomes with cerebral oxygen monitoring in traumatic brain injury. Surgery. 2009;146(4):585–590; discussion 590-581.
