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Perioperative Medicine  |   August 2012
Cutaneous Vasoconstriction Affects Near-infrared Spectroscopy Determined Cerebral Oxygen Saturation during Administration of Norepinephrine
Author Affiliations & Notes
  • Henrik Sørensen, M.Sc.
    *
  • Niels H. Secher, M.D., D.M.Sc.
  • Christoph Siebenmann, M.Sc.
  • Henning B. Nielsen, M.D., D.M.Sc.
    §
  • Matthias Kohl-Bareis, Ph.D.
  • Carsten Lundby, Ph.D.
    #
  • Peter Rasmussen, Ph.D.
    **
  • *Medical Student, **Postdoctoral Fellow, Department of Anesthesia, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, and Zürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland. Professor, §Research Fellow, Department of Anesthesia, Rigshospitalet, University of Copenhagen. Ph.D. Student, #Professor, Zürich Center for Integrative Human Physiology, University of Zürich. Professor, RheinAhr Campus Remagen, University of Applied Sciences Koblenz, Germany.
Article Information
Perioperative Medicine / Cardiovascular Anesthesia / Central and Peripheral Nervous Systems / Radiological and Other Imaging / Respiratory System
Perioperative Medicine   |   August 2012
Cutaneous Vasoconstriction Affects Near-infrared Spectroscopy Determined Cerebral Oxygen Saturation during Administration of Norepinephrine
Anesthesiology 8 2012, Vol.117, 263-270. doi:10.1097/ALN.0b013e3182605afe
Anesthesiology 8 2012, Vol.117, 263-270. doi:10.1097/ALN.0b013e3182605afe
What We Already Know about This Topic
  • 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

What This Article Tells Us That Is New
  • 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.1 Thus, perioperative optimization may be directed to preserve scO22 and maintained scO2secures rapid postoperative recovery in both cardiac3 and elderly patients.4 For 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,5 but that is not the case for ephedrine.6 In healthy subjects the administration of norepinephrine reduces scO27 with 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.8 Alternatively, the reduction in scO2following administration of norepinephrine is influenced by cutaneous vasoconstriction.9 Also both CBF and scO2are sensitive to changes in PaCO210,11 and 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.13,14 In a hot environment, skin blood flow (SBF) increases, especially over the forehead,15 whereas there is no change in CBF or muscle blood flow. However, the NIRS-determined muscle oxygenation increases during whole-body heating.13 For evaluation of cerebral oxygen saturation in a hot environment, it appears important that hyperthermia elicits a hyperventilation-induced lowering of PaCO216,17 and, in turn, CBF.18 Thus, when scO2is unaffected by hyperthermia19 while the internal jugular venous-derived cerebral oxygenation is reduced,20 the 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.
Materials and Methods
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.21,22 A 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 tissues23 using 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.24 Although the algorithm of the instrument is not disclosed, the apparatus is widely used in clinical cerebral monitoring2,3,10,25 and 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.26,27 We 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.30,31 Gas is exchanged linearly along the entire vascular pathway from the arteries to the veins.32,33 Thus, 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 
Protocol
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 PaCO2,7 the 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,7,8,34 a 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.
Results
Hyperventilation
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
Image not available
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.
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.
×
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
Image not available
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.
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.
×
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
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.
Discussion
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.29 Others have proposed a 3:1 ratio primarily based on anatomical evidence between arterial and venous blood for validation of NIRS.35 The 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.1,36 The NIRS-derived arterial-to-venous ratios are somewhat contradicted by positron emission tomography data,37 but 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.24 The 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 heating13 and with intradermal injections of epinephrine.14 Here, 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.1 Core 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.
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.
×
Vasoconstriction of the Skin
Previous studies suggest that administration of vasopressors exert a negative impact on scO2.5  7 It is debated whether the reduction in scO2is because of a decrease in cardiac output,38 sympathetically mediated cerebral vasoconstriction, or changes in SBF.34 It is less ambiguous how α-adrenergic drugs affect the microcirculation of the skin.39 The 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 PaCO2.34 We 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  7 One 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 scO2,40 but 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.40 It 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,41 but 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 NIRS11 and 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.
Perspective
Despite the influence of SBF for the NIRS signal, it remains useful for perioperative optimizing to improve patient outcome after anesthesia,2,25 although 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.
Conclusion
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.
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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.
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.
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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.
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.
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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.
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.
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Table 1. Systemic and Cerebral Hemodynamics
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Table 1. Systemic and Cerebral Hemodynamics
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Table 2. Skin-derived Variables
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Table 2. Skin-derived Variables
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