Perioperative optimization of spatially resolved near-infrared spectroscopy determined cerebral frontal lobe oxygenation (scO2) may reduce postoperative morbidity. Norepinephrine is routinely administered to maintain cerebral perfusion pressure and, thereby, cerebral blood flow, but norepinephrine reduces the scO2. We hypothesized that norepinephrine-induced reduction in scO2 is influenced by cutaneous vasoconstriction.


Fifteen healthy male subjects (25 ± 5 yr, mean ± SD) were studied during: hyperventilation (1.5 kPa end-tidal PcO2 reduction), whole-body heating, administration of norepinephrine (0.15 μg · kg · min; with and without end-tidal carbon dioxide correction), and hypoxia (FiO2: 0.12%). Arterial (saO2), skin, and internal jugular venous oxygen saturations (sjO2) were recorded, and the average cerebral capillary oxygen saturation (scapO2) was calculated.


This study indicates that scO2 is influenced by skin oxygen saturation because whole-body heating increased scO2 by 3.6% (2.1-5.1%; 95% CI) and skin oxygen saturation by 3.1% (1.3-4.9%), whereas scapO2 remained unaffected. Conversely, hyperventilation decreased scO2 by 2.1% (0.4-3.7%) and scapO2 by 5.3% (3.8-6.9%), whereas skin oxygen saturation increased 1.8% (0.5-3.1%). In response to hypoxia, scO2 (10.2%; 6.6-13.7%), scapO2 (7.9%; 6.4-9.4%), and skin oxygen saturation (8.9%; 6.3-11.6%) all decreased. With administration of norepinephrine there was a 2.2% (1.0-4.3%) decrease in skin oxygen saturation and scO2 decreased 6.2% (4.2-8.0%), with scapO2 remaining unaffected.


The results confirm that spatially resolved near-infrared spectroscopy detects cerebral deoxygenation with systemic hypoxic exposure and hyperventilation. However, a commonly used vasopressor norepinephrine disturbs skin oxygen saturation to an extent that influences scO2.

  • Cerebral oximetry by spatially resolved near-infrared spectroscopy is used to monitor and optimize cerebral oxygenation during procedures that might impair cerebral perfusion

  • Changes in cutaneous perfusion could interfere with the accuracy of cerebral oximetry

  • The effects of hypocapnia, hyperthermia, hypoxia, and norepinephrine on cerebral and forehead skin blood flow and oxygenation were studied in human volunteers

  • Cerebral oximetry accurately detected cerebral deoxygenation produced by hypoxia and hyperventilation, but hyperthermia and norepinephrine affected skin oxygenation and directionally influenced cerebral oximetry readings

IT is crucial to maintain cerebral blood flow (CBF) during anesthesia, but it is difficult to determine CBF in clinical settings. On the other hand, it is straightforward to monitor frontal lobe oxygenation (scO2) by noninvasive near-infrared spectroscopy (NIRS) that provides real-time assessment and is reported to monitor scO2correctly.1Thus, perioperative optimization may be directed to preserve scO22and maintained scO2secures rapid postoperative recovery in both cardiac3and elderly patients.4For example, vasopressors are administered to prevent reductions in mean arterial pressure (MAP) that could affect CBF and in turn scO2. However, vasopressors appear to affect scO2differently. Phenylephrine reduces scO2in anesthetized patients,5but that is not the case for ephedrine.6In healthy subjects the administration of norepinephrine reduces scO27with a concomitant reduction in blood flow velocity in the middle cerebral artery (MCA vmean) and internal jugular venous saturation (sjO2), suggesting that sympathetically mediated cerebral vasoconstriction reduces CBF to an extent that affects scO2. But sympathetic innervation of the cerebral vasculature remains controversial, and whether administration of norepinephrine reduces MCA vmeanremains debated.8Alternatively, the reduction in scO2following administration of norepinephrine is influenced by cutaneous vasoconstriction.9Also both CBF and scO2are sensitive to changes in PaCO210,11and an increase in ventilation provoked by administration of norepinephrine could contribute to the reduction in scO2.12 

An influence from skin oxygenation to the NIRS signal has been identified.13,14In a hot environment, skin blood flow (SBF) increases, especially over the forehead,15whereas there is no change in CBF or muscle blood flow. However, the NIRS-determined muscle oxygenation increases during whole-body heating.13For evaluation of cerebral oxygen saturation in a hot environment, it appears important that hyperthermia elicits a hyperventilation-induced lowering of PaCO216,17and, in turn, CBF.18Thus, when scO2is unaffected by hyperthermia19while the internal jugular venous-derived cerebral oxygenation is reduced,20the maintained scO2indicates that scO2is influenced by SBF, and this hypothesis was tested in the present study. For this purpose we assessed cerebral perfusion and oxygenation while PaCO2and PaO2were manipulated with separate assessment of SBF and skin hemoglobin and oxygenation.

Fifteen healthy males (age 25 ± 5 yr [mean ± SD], height 182 ± 7 cm, and mass 76 ± 8 kg) participated in the study. The study was approved by the local ethics committee (H-4–2010–132, Copenhagen, Denmark) in accordance with Declaration of Helsinki including oral and written informed consent.

After arrival to the laboratory at 8:00 AM, the subjects were resting supine for 20 min before catheterization. Under local anesthesia (2% lidocaine), a catheter (Edwards Life Sciences, Irvine, CA) was inserted retrograde in the right internal jugular vein by Seldinger technique guided by ultrasound, and the tip of the catheter was placed at its bulb. The position of the catheter at the jugular bulb was verified during placement if the subjects reported a slight pain behind the ear. The placement was also confirmed by quick infusion of saline if the subject experienced an auditory response.21,22A 20 G catheter was placed in the brachial (n = 12) or radial artery (n = 3) of the nondominant arm and a central venous catheter (Cavafix MT134, Braun, Melsungen, Germany) was advanced through an arm vein. Catheters were connected to transducers (Edwards Life Sciences) placed at the level of the heart (fourth intercostal space; Dialogue-2000; IBC-Danica Electronic, Copenhagen, Denmark) to monitor MAP and heart rate. Data were analog-digital converted and sampled at 200 Hz (DI-720; Dataq Instruments Inc., Akron, OH) by computer software (Windaq; Dataq Instruments Inc.).

To assess scO2we used a spatially resolved NIRS (INVOS; Somanetics, Troy, MI), meaning that it records differences in absorption of photons returning from deep and superficial tissues23using light at 703 and 808 nm and an emitter-detector separation of 3 and 4 cm with the depth sensitivity corresponding to approximately one-third of the emitter-detector separation.24Although the algorithm of the instrument is not disclosed, the apparatus is widely used in clinical cerebral monitoring2,3,10,25and evaluation of its performance is therefore important. The general approach of this instrumentation is that by analyzing the signals from the two emitter-detector separations, the signal of superficial tissue layers is suppressed, providing an estimate of deep tissue, e.g. , the frontal lobe oxygenation. We assumed that frontal lobe activation was unchanged throughout the protocol and therefore did not influence cerebral metabolic rate of oxygen and, in turn, the NIRS signal. To avoid any influences from the frontal or sagittal sinuses to the NIRS signal, the sensor was placed high on the forehead in randomized and balanced order. The SBF was monitored by LDF (moorVMS-LDF; Moor Instruments, Axminster, United Kingdom) using light at 785 nm. The LDF sensor was integrated with a tissue oxygenation sensor (moorVMS-OXY; Moor Instruments) that uses white light spectroscopy (wavelength range, 400–700 nm) to assess skin oxygen saturation,skin hemoglobin concentrations, and temperature. The instrument self-calibrates when turned on prior and LDF and white light spectroscopy are established as valid measurements of the microcirculation of the skin.26,27We assumed that changes in SBF beneath the LDF sensor reflected that beneath the NIRS sensor, with the two sensors placed ipsilateral and distanced 3 to 4 cm apart.

To evaluate whether the interventions affected CBF, MCA vmeanwas determined by transcranial Doppler sonography (2 MHz probe, Multi-Dop, DWL, Singen, Germany). Using adhesive ultrasound gel, the best signal-to-noise ratio was obtained at the temporal insonation window. Placement of the probe was randomized and balanced across subjects with respect to hemisphere, and eight subjects had the probe placed on the right side. Previous reports exclude influence of PaCO2on the diameter of the MCA and we, therefore, assumed that changes in MCA vmeanreflect those in CBF.28 

Transcranial Doppler, SBF, NIRS, and skin oxygenation in addition to the blood pressure signals were all analog-digital converted and sampled on the DI-720. Following recording, values were averaged over at least 30 s before entering the statistical analysis.

Arterial and jugular venous blood samples were obtained simultaneously in preheparinised syringes. Atmospheric air was immediately removed from the syringe. The samples were analyzed for PaO2and PaCO2, oxygen saturation (saO2; sjO2), and total hemoglobin (ABL700; Radiometer, Copenhagen, Denmark). To express the oxygen content in the arterial or venous blood, CO2= 0.0031 · PO2+ Hb · SO2  was used. The arterial to venous difference (avdO2) for the brain was calculated. With the assumption that CMRO2was constant, changes in CBF were calculated using the Fick equation,

The cerebrovascular resistance index was calculated as MAP divided by MCAvmeanand the skin vascular resistance index was MAP divided by SBF. Using a simplified equation, scapO2was calculated:1,29 

The calculation of scapO2is based on the cerebral oxygen extraction and motivated by the assumption that oxygen extraction remains constant along the capillary network.30,31Gas is exchanged linearly along the entire vascular pathway from the arteries to the veins.32,33Thus, it can be assumed that sO2decreases linearly from the arterial to the venous end of the capillary and average cerebral oxygen saturation is then the midway point between arterial and venous saturations.29 


Following catheterization, the subjects rested supine for 30 min with elevated head rest with room temperature kept constant (22–24°C). The experiment included three trials performed in randomized and balanced order, followed by a hypoxic trial. Before each trial resting values were obtained with 43 ± 14 min rest between the trials. The trials included the following.

(1) The subjects were asked to hyperventilate to reduce the end-tidal pressure of carbon dioxide (PETCO2; INNOCOR, Odense, Denmark) by 1.5 kPa. Blood samples were collected after 7 ± 2 min reflecting when the targeted PETCO2was established.

(2) To increase skin temperature, the subjects were exposed to whole-body heating. The subjects were covered with a heat-isolating aluminum blanket together with a dedicated heating blanket (Bair Hugger 505; Arizant Healthcare, Eden Prairie, MN) that was inflated by air at 42°C. Linens covered and isolated the head. Blood samples were obtained after 26 ± 7 min, reflecting when there was no further increase in SBF (skin temperature increased by 1.7 ± 0.7°C) and it was confirmed that PaCO2remained stable.

(3) Norepinephrine (0.15 μg · kg−1· min−1) was infused through the central venous catheter for 15 min; blood samples were collected afterward. To avoid potential effects of norepinephrine on PaCO2,7the subjects were instructed to restrain the ventilatory depth for 11 ± 5 min in order to maintain the arterial carbon dioxide. If the subject was not able to control PETCO2in this way,a tube was added to the inspired gas mixture and thus increased the ventilatory death space. Administration of norepinephrine with and without PETCO2correction was performed in randomized order.

(4) After these trials, the subjects were exposed to hypoxia (FiO2: 0.12%) for which the inspired air was balanced by N2(Altitrainer, SMTEC, Nyon, Switzerland) for 10 min, while blood samples were collected.

Statistical Methods

Based on similar studies,7,8,34a sample size of 15 subjects was assumed to provide β < 0.20. One-way ANOVA followed by a Tukey post hoc  test on repeated measures evaluated variables. To express relationships between variables we used Pearson's correlation. The results are presented as changes from baseline and variables are provided with their 95% CI. We performed a two-tailed hypothesis testing and the statistically significant level was set to P < 0.05 with data analyzed in SAS 9.2 (SAS Institute Inc., Cary, NC). Because of insufficient signal quality, MCV vmeanwas excluded in one subject during hyperventilation and in another subject during the control before whole-body heating. Similarly, scO2was excluded in one subject during whole-body heating.


As intended, hyperventilation induced a 1.1 kPa decrease in PaCO2whereas PaO2increased (table 1). Skin oxygen saturation increased by 1.8% (0.5% to 3.1%), although there were no changes in skin hemoglobin concentrations, skin vascular resistance index, or SBF.

Table 1. Systemic and Cerebral Hemodynamics

Table 1. Systemic and Cerebral Hemodynamics
Table 1. Systemic and Cerebral Hemodynamics

There were no changes in MAP, but MCA vmean, sjO2, and CBFFickall decreased. Also, the NIRS-determined scO2was reduced by 2.1% (0.4–3.7%; fig. 1) and scapO2was reduced by 5.3% (3.8–6.9%).

Fig. 1. Changes in cerebral oxygen saturation, skin oxygen saturation, and calculated average cerebral oxygen saturation during whole-body heating, hyperventilation, and hypoxia. Error bars  represent 95% CI limits. P  values for the intervention are presented. scO2= cerebral oxygen saturation; scapO2= calculated average cerebral oxygen saturation; sskinO2= skin oxygen saturation.

Fig. 1. Changes in cerebral oxygen saturation, skin oxygen saturation, and calculated average cerebral oxygen saturation during whole-body heating, hyperventilation, and hypoxia. Error bars  represent 95% CI limits. P  values for the intervention are presented. scO2= cerebral oxygen saturation; scapO2= calculated average cerebral oxygen saturation; sskinO2= skin oxygen saturation.

Close modal

Whole-body Heating

With exposure to whole-body heating there was an increase in skin temperature by 1.6°C (0.7–2.6°C) (table 2) and a concomitant increase in SBF by 23.5 AU (10.4–36.6) and skin oxygen saturation by 3.1% (1.3–4.9%).

Table 2. Skin-derived Variables

Table 2. Skin-derived Variables
Table 2. Skin-derived Variables

We did not observe any changes in MAP, MCA vmean,sjO2, or CBFFickin response to whole-body heating (table 1). Yet, there was an increase by 3.6% (2.1–5.1%; fig. 1) in scO2, whereas scapO2remained unchanged.

Administration of Norepinephrine

With administration of norepinephrine, skin vascular resistance index increased while total hemoglobin of the skin decreased (table 2). Thus, skin oxygen saturation was reduced by 2.2% (1.0–4.3%).

Administration of norepinephrine induced in average 22 mmHg increase in MAP, whereas MCA vmean,sjO2, and CBFFickwere unaffected. Yet, the scO2was reduced by 6.2% (4.2–8.0%; fig. 2), although scapO2remained unchanged.

Fig. 2. (A ) Changes in cerebral oxygen saturation, skin oxygen saturation, and calculated average cerebral oxygen saturation during administration of norepinephrine (0.15 μg · kg−1· min−1) with and without PETCO2correction. Error bars  represent 95% CI limits and P  values for the intervention are presented. (B ) Correlation of cerebral oxygen saturation with both calculated average cerebral oxygen saturation and skin oxygen saturation, during administration of norepinephrine with and without PETCO2correction. scO2= cerebral oxygen saturation; scapO2= calculated average cerebral oxygen saturation; sskinO2= skin oxygen saturation.

Fig. 2. (A ) Changes in cerebral oxygen saturation, skin oxygen saturation, and calculated average cerebral oxygen saturation during administration of norepinephrine (0.15 μg · kg−1· min−1) with and without PETCO2correction. Error bars  represent 95% CI limits and P  values for the intervention are presented. (B ) Correlation of cerebral oxygen saturation with both calculated average cerebral oxygen saturation and skin oxygen saturation, during administration of norepinephrine with and without PETCO2correction. scO2= cerebral oxygen saturation; scapO2= calculated average cerebral oxygen saturation; sskinO2= skin oxygen saturation.

Close modal

Administration of Norepinephrine with PETCO2Correction

The subjects managed to keep PaCO2at the level established before administration of norepinephrine, eventually with enlargement of the ventilatory dead space (n = 6). Under these circumstances there was a tendency for a reduction in skin oxygen saturation (−3.8–0.5%; P = 0.066), but no changes in SBF or skin temperature, although skin hemoglobin concentrations and skin vascular resistance index were affected (table 2).

The MCA vmeanincreased by 6.9 cm/s. With PETCO2correction, scO2remained reduced by 4.2% (2.2–6.0%; fig. 2) with no change in scapO2(−3.7–4.9%).


Hypoxia was associated with a reduction in skin oxygen saturation by 8.9% (6.3–11.6%; fig. 2). There was an increase in skin vascular resistance index because SBF decreased (table 2), but, on the other hand, skin hemoglobin concentrations remained unaffected.

With hypoxic exposure, PaO2and saO2were reduced. Neither MCA vmeannor CBFFickchanged. Also scO2(by 10.2%; 6.6–13.7%) and scapO2(by 7.9%; 6.4–9.4%; fig. 1) were reduced.

The results provide, in our opinion, compelling evidence that skin oxygen saturation affects the applied spatially resolved INVOS NIRS-determined evaluation of scO2. Whole-body heating and administration of norepinephrine provide a discrepancy between scO2and scapO2. On the other hand, during hyperventilation and hypoxia, there were corresponding reductions in scO2and scapO2. Thus, the reduction in scO2during administration of norepinephrine can be explained by cutaneous vasoconstriction, whereas the increase in scO2during whole-body heating seems because of an increase in skin oxygen saturation. These observations have implications for use of NIRS clinically and for preservation of scO2and in turn CBF with administration norepinephrine during anesthesia.

The calculation of cerebral oxygenation from arterial and jugular bulb saturation is of importance to this study. Here, we used an approach based on cerebral oxygen extraction and defined the average cerebral blood hemoglobin oxygenation as the midway point between the arterial and jugular venous saturations.29Others have proposed a 3:1 ratio primarily based on anatomical evidence between arterial and venous blood for validation of NIRS.35The contribution ratio may be different between NIRS devices and it is unlikely that the composition of cerebral blood volume remains stable at different levels of PcO2and, consequently, CBF.1,36The NIRS-derived arterial-to-venous ratios are somewhat contradicted by positron emission tomography data,37but contribution from skin may have influenced NIRS validation of the cerebral blood volume distribution. Importantly, using a 3:1 ratio between arterial and venous blood, or sjugO2alone, does not change the conclusion that skin has a significant contribution to the NIRS signal.

Vasodilation of the Skin

The penetration depth sensitivity of NIRS light is proportional to the emitter-detector separation.24The presented results raise the question whether a separation distance of 3 or 4 cm is enough to secure spatial resolution and thereby exclude crosstalk between scO2and skin oxygen saturation. With whole-body heating, we obtained an increase in scO2and skin oxygen saturation, whereas calculated scapO2remained stable (fig. 1). Thus, the increase in scO2associated with whole-body heating can be explained by the increase in skin oxygen saturation. Nonspatially resolved NIRS is affected by skin oxygen saturation with local and whole-body heating13and with intradermal injections of epinephrine.14Here, with spatially resolved NIRS, we observed a correlation between scO2and skin oxygen saturation during administration of norepinephrine with and without PETCO2correction(fig. 2) and a similar correlation was observed during whole-body heating (fig. 3). In support for an influence of skin oxygen saturation on scO2, a marked increase in SBF and reduced skin vascular resistance index were observed. Marked hyperthermia can elicit hyperventilation, but PaCO2was maintained during whole-body heating and therefore did not affect cerebrovascular resistance index and sjO2as previously described.1Core temperature was not recorded, but the results show no changes in PaCO2, MCA vmean, or CBFFick, typically seen during whole-body heating.9 

Fig. 3. Correlation of skin oxygen saturation and cerebral oxygen saturation during administration of norepinephrine with and without PETCO2correction, represented as red dots , and whole-body heating presented as blue dots . For all data in the plot, r = 0.64 (P < 0.0001), with r = 0.6 (P < 0.0001) for administration of norepinephrine and r = 0.4 (P = 0.15) for whole-body heating. scO2= cerebral oxygen saturation; sskinO2= skin oxygen saturation.

Fig. 3. Correlation of skin oxygen saturation and cerebral oxygen saturation during administration of norepinephrine with and without PETCO2correction, represented as red dots , and whole-body heating presented as blue dots . For all data in the plot, r = 0.64 (P < 0.0001), with r = 0.6 (P < 0.0001) for administration of norepinephrine and r = 0.4 (P = 0.15) for whole-body heating. scO2= cerebral oxygen saturation; sskinO2= skin oxygen saturation.

Close modal

Vasoconstriction of the Skin

Previous studies suggest that administration of vasopressors exert a negative impact on scO2.5,,7It is debated whether the reduction in scO2is because of a decrease in cardiac output,38sympathetically mediated cerebral vasoconstriction, or changes in SBF.34It is less ambiguous how α-adrenergic drugs affect the microcirculation of the skin.39The present results demonstrate a decrease in skin oxygen saturation with administration of norepinephrine (fig. 2) and lower skin hemoglobin concentrations and increased skin vascular resistance index. At the same time, scO2decreased whereas calculated scapO2was unaffected, suggesting that cutaneous vasoconstriction affects the NIRS-determined scO2. In support, when PETCO2was maintained, the reductions in scO2and skin oxygen saturation remained and the reduction in scO2during administration of norepinephrine could illustrate the influence of skin oxygen saturation considering that scapO2was stable.

Administration of phenylephrine provokes a marked reduction in scO2despite unaffected internal carotid artery flow, PaO2and PaCO2.34We acknowledge that a decrease in scO2with administration of norepinephrine could be because of an alteration in the arterial and venous contributions to the NIRS signal, but also, cutaneous vasoconstriction could be responsible for the reduction in scO2. Administration of ephedrine, on the other hand, does not affect scO2.5,,7One explanation for this discrepancy could be that ephedrine does not have the same vasoconstrictive effects on smooth muscles in skin vasculature as norepinephrine. Reduction in cardiac output has a negative impact on scO2,40but the present results suggest that the reduction in scO2is explained by a reduction in skin oxygen saturation. The stability of MCA vmeanand CBFFickalso emphasize that cerebral blood flow is not challenged, which would have been the case if cardiac output was lowered.40It remains unknown to what extent the cerebral vasculature is influenced by sympathetic innervation, but the results do not support sympathetic vasoconstriction in brain (table 1).

Hypoxia and Hypocapnia

With systemic hypoxic exposure, scapO2was reduced by 7.9% and scO2by 10.2% (P < 0.0001). Therefore, it seems that NIRS estimates brain oxygen saturation correctly during systemic hypoxic exposure. The influence of the skin oxygen saturation is minimal with hypoxia, but we cannot exclude that the 2.3% discrepancy between scO2and scapO2can be explained by the 8.9% reduction of skin oxygen saturation (P = 0.03) because of cutaneous vasoconstriction (table 2). The threshold for hypoxemia-induced arterial dilatation was not reached,41but we cannot exclude cerebral vasodilatation because of hypoxic exposure. On the other hand, such vasodilation was likely counterbalanced by hypocapnia, because MCV vmeandid not change significantly (table 1).

Because of the higher oxygen pressure during hyperventilation, skin oxygen saturation increased, whereas scapO2and scO2decreased (fig. 1 ).  The inverse relationship between scO2and skin oxygen saturation with hyperventilation could explain why scO2underestimates scapO2by 3.2%, however, systematic errors because of a low signal-noise ratio cannot be excluded. These findings support that PaCO2has an influence on cerebral oxygen saturation as assessed by NIRS11and more so than the influence of the skin oxygen saturation. Regardless of the crosstalk between skin oxygen saturation and scO2, INVOS is sensitive to changes in cerebral oxygen saturation during hyperventilation and systemic hypoxic exposure.


Despite the influence of SBF for the NIRS signal, it remains useful for perioperative optimizing to improve patient outcome after anesthesia,2,25although administration of α-agonists as vasopressors may confound interpretation of NIRS. Further studies are needed to evaluate whether difference in emitter-detector separation of more than 3 and 4 cm can avoid crosstalk between skin oxygen saturation and spatially resolved scO2. Alternatively, different algorithms for the analysis of NIRS data are required to suppress skin artifacts. In a multiple regression analysis, skin oxygenation contributes approximately 30% to the NIRS signal; however, further investigations are needed to quantify in details the contribution from the different components beneath the NIRS sensor. Furthermore, it is needed to evaluate whether administration of norepinephrine is associated with reduction in scO2in situations with low cardiac out or hypotension.

The results suggest that the reduced INVOS NIRS-determined evaluation of scO2observed with administration of norepinephrine is because of skin vasoconstriction rather than cerebral deoxygenation. Thus, in situations with administration of norepinephrine and whole-body heating, an emitter-detector separation of 3 or 4 cm seems not to be large enough to avoid crosstalk between skin oxygen saturation and the INVOS NIRS-determined scO2, and further technical measures to eliminate the skin contribution should be considered. Nevertheless, the results confirm that spatial resolved NIRS is able to detect cerebral deoxygenation associated with hyperventilation and systemic hypoxic exposure.

Rasmussen P, Dawson EA, Nybo L, van Lieshout JJ, Secher NH, Gjedde A: Capillary-oxygenation-level-dependent near-infrared spectrometry in frontal lobe of humans. J Cereb Blood Flow Metab 2007; 27:1082–93
Murkin JM, Adams SJ, Novick RJ, Quantz M, Bainbridge D, Iglesias I, Cleland A, Schaefer B, Irwin B, Fox S: Monitoring brain oxygen saturation during coronary bypass surgery: A randomized, prospective study. Anesth Analg 2007; 104:51–8
Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM 3rd, Rodriguez AL, Magovern CJ, Zaubler T, Freundlich K, Parr GV: Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg 2009; 87:36–44
de Tournay-Jett é E, Dupuis G, Bherer L, Deschamps A, Cartier R, Denault A: The relationship between cerebral oxygen saturation changes and postoperative cognitive dysfunction in elderly patients after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2011; 25:95–104
Meng L, Cannesson M, Alexander BS, Yu Z, Kain ZN, Cerussi AE, Tromberg BJ, Mantulin WW: Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth 2011; 107:209–17
Nissen P, Brassard P, Jørgensen TB, Secher NH: Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension. Neurocrit Care 2010; 12:17–23
Brassard P, Seifert T, Secher NH: Is cerebral oxygenation negatively affected by infusion of norepinephrine in healthy subjects? Br J Anaesth 2009; 102:800–5
Moppett IK, Sherman RW, Wild MJ, Latter JA, Mahajan RP: Effects of norepinephrine and glyceryl trinitrate on cerebral haemodynamics: Transcranial Doppler study in healthy volunteers. Br J Anaesth 2008; 100:240–4
Wilson TE, Cui J, Zhang R, Crandall CG: Heat stress reduces cerebral blood velocity and markedly impairs orthostatic tolerance in humans. Am J Physiol Regul Integr Comp Physiol 2006; 291:R1443–8
Kety SS, Schmidt CF: The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 1948; 27:484–92
Madsen PL, Secher NH: Near-infrared oximetry of the brain. Prog Neurobiol 1999; 58:541–60
Moppett IK: Sympathetic activity and cerebral oxygenation. Br J Anaesth 2009; 103:769–70
Davis SL, Fadel PJ, Cui J, Thomas GD, Crandall CG: Skin blood flow influences near-infrared spectroscopy-derived measurements of tissue oxygenation during heat stress. J Appl Physiol 2006; 100:221–4
Buono MJ, Miller PW, Hom C, Pozos RS, Kolkhorst FW: Skin blood flow affects in vivo  near-infrared spectroscopy measurements in human skeletal muscle. Jpn J Physiol 2005; 55:241–4
Kondo N, Takano S, Aoki K, Shibasaki M, Tominaga H, Inoue Y: Regional differences in the effect of exercise intensity on thermoregulatory sweating and cutaneous vasodilation. Acta Physiol Scand 1998; 164:71–8
Haldane JS: The influence of high air temperatures. J Hyg 1905; 5:494–513
Cabanac M, White MD: Core temperature thresholds for hyperpnea during passive hyperthermia in humans. Eur J Appl Physiol Occup Physiol 1995; 71:71–6
Nybo L, Møller K, Volianitis S, Nielsen B, Secher NH: Effects of hyperthermia on cerebral blood flow and metabolism during prolonged exercise in humans. J Appl Physiol 2002; 93:58–64
Morrison SA, Sleivert GG, Neary JP, Cheung SS: Prefrontal cortex oxygenation is preserved and does not contribute to impaired neuromuscular activation during passive hyperthermia. Appl Physiol Nutr Metab 2009; 34:66–74
Rasmussen P, Nybo L, Volianitis S, Møller K, Secher N, Gjedde A: Cerebral oxygenation is reduced during hyperthermic exercise in humans. Acta Physiol 2010; 199:63–70
Rath GP, Bithal PK, Toshniwal GR, Prabhakar H, Dash HH: Saline flush test for bedside detection of misplaced subclavian vein catheter into ipsilateral internal jugular vein. Br J Anaesth 2009; 102:499–502
Nybo L, Secher NH, Nielsen B: Inadequate heat release from the human brain during prolonged exercise with hyperthermia. J Physiol 2002; 545:697–704
Benaron DA, Kurth CD, Steven JM, Delivoria-Papadopoulos M, Chance B: Transcranial optical path length in infants by near-infrared phase-shift spectroscopy. J Clin Monit 1995; 11:109–17
Germon TJ, Evans PD, Barnett NJ, Wall P, Manara AR, Nelson RJ: Cerebral near infrared spectroscopy: Emitter-detector separation must be increased. Br J Anaesth 1999; 82:831–7
Fedorow C, Grocott HP: Cerebral monitoring to optimize outcomes after cardiac surgery. Curr Opin Anaesthesiol 2010; 23:89–94
Choi CM, Bennett RG: Laser Dopplers to determine cutaneous blood flow. Dermatol Surg 2003; 29:272–80
Harrison DK, Evans SD, Abbot NC, Beck JS, McCollum PT: Spectrophotometric measurements of haemoglobin saturation and concentration in skin during the tuberculin reaction in normal human subjects. Clin Phys Physiol Meas 1992; 13:349–63
Serrador JM, Picot PA, Rutt BK, Shoemaker JK, Bondar RL: MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis. Stroke 2000; 31:1672–8
Gjedde A, Johannsen P, Cold GE, Ostergaard L: Cerebral metabolic response to low blood flow: Possible role of cytochrome oxidase inhibition. J Cereb Blood Flow Metab 2005; 25:1183–96
Kety SS: Determinants of tissue oxygen tension. Fed Proc 1957; 16:666–71
Weibel E: The Pathway for Oxygen. Cambridge: Harvard University Press; 1984
Sejersen P: Convection and diffusion of inert gases in cutaneous, subcutaneous and skeletal muscle tissue. In: Alfred Benzon Symposium III. Copenhagen: Munksgaard; 1970, pp 586–96
Torres Filho IP, Kerger H, Intaglietta M: pO2 measurements in arteriolar networks. Microvasc Res 1996; 51:202–12
Ogoh S, Sato K, Fisher JP, Seifert T, Overgaard M, Secher NH: The effect of phenylephrine on arterial and venous cerebral blood flow in healthy subjects. Clin Physiol Funct Imaging 2011; 31:445–51
Pollard V, Prough DS, DeMelo AE, Deyo DJ, Uchida T, Stoddart HF: Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo . Anesth Analg 1996; 82:269–77
Watzman HM, Kurth CD, Montenegro LM, Rome J, Steven JM, Nicolson SC: Arterial and venous contributions to near-infrared cerebral oximetry. ANESTHESIOLOGY 2000; 93:947–53
Ito H, Ibaraki M, Kanno I, Fukuda H, Miura S: Changes in the arterial fraction of human cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography. J Cereb Blood Flow Metab 2005; 25:852–7
Madsen P, Lyck F, Pedersen M, Olesen HL, Nielsen H, Secher NH: Brain and muscle oxygen saturation during head-up-tilt-induced central hypovolaemia in humans. Clin Physiol 1995; 15:523–33
Shibasaki M, Low DA, Davis SL, Crandall CG: Nitric oxide inhibits cutaneous vasoconstriction to exogenous norepinephrine. J Appl Physiol 2008; 105:1504–8
Van Lieshout JJ, Wieling W, Karemaker JM, Secher NH: Syncope, cerebral perfusion, and oxygenation. J Appl Physiol 2003; 94:833–48
Johnston AJ, Steiner LA, Gupta AK, Menon DK: Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity. Br J Anaesth 2003; 90:774–86