- Wiley Online Library

Pediatric Anesthesia ISSN 1155-5645
REVIEW ARTICLE
Near-infrared spectroscopy: exposing the dark (venous) side
of the circulation
John P. Scott & George M. Hoffman
Departments of Anesthesiology and Pediatrics, Medical College of Wisconsin, Pediatric Anesthesiology and Critical Care Medicine, Children’s
Hospital of Wisconsin, Milwaukee, WI, USA
Keywords
spectroscopy; near-infrared; regional blood
flow; shock; monitoring; physiologic;
hypoxia–ischemia; hemodynamics
Correspondence
George M. Hoffman, Anesthesiology 735,
Children’s Hospital of Wisconsin, 9000 W
Wisconsin Ave, Milwaukee, WI 53226, USA
Email: [email protected]
Section Editor: Andy Wolf
Accepted 5 October 2013
Summary
The safety of anesthesia has improved greatly in the past three decades. Standard perioperative monitoring, including pulse oximetry, has practically eliminated unrecognized arterial hypoxia as a cause for perioperative injury.
However, most anesthesia-related cardiac arrests in children are now cardiovascular in origin, and standard monitoring is unable to detect many circulatory abnormalities. Near-infrared spectroscopy provides noninvasive
continuous access to the venous side of regional circulations that can approximate organ-specific and global measures to facilitate the detection of circulatory abnormalities and drive goal-directed interventions to reduce end-organ
ischemic injury.
doi:10.1111/pan.12301
Introduction
As standards for monitoring were articulated by the
American Society of Anesthesiologists (1–3) and applied
in most developed countries, anesthesia care has been
generally recognized as a victory for patient safety (4,5).
These standards, particularly the wide deployment of
pulse oximetry, were adopted without rigorous evidence
for efficacy but have virtually eliminated unrecognized
arterial hypoxemia, and strategies to avoid or manage
critical respiratory events have greatly reduced the incidence of perioperative injury due to arterial hypoxemia
(6–13), while the workload and rates of alarms and
intervention have increased (6). While the Cochrane
Collaborative has determined that ‘the value of pulse
oximetry is questionable’ in improving complications
(14), a gap still exists in the developing world for basic
monitoring, such that a call for universal application of
intraoperative pulse oximetry is a world health initiative (15,16) with evidence for improved outcomes when
applied (17). As adoption of pulse oximetry and airway
algorithms in westernized countries, anesthesia complications are more related to cardiovascular events (9).
Although healthy patients can be predictably anesthetized for relatively short surgical procedures with an
74
exceedingly low rate of complication, the risk of organ
injury is independently related to the duration of anesthesia (9). Moreover, the risk of both intraoperative and
perioperative mortality for neonates and infants remains
high, cardiac arrest remains a perioperative risk, and
ischemic injuries to brain, gut, and kidneys are significant causes of morbidity (10,11,18–23). The major
causes of cardiac arrest in anesthetized children are now
cardiovascular, including underestimation of hypovolemia and hemorrhage (8).
Limitations of standard domain measurements
Measurement of arterial blood pressure, or organ perfusion pressure (PP) (mean arterial minus central venous
pressure), provides an indirect measure of the output
from the heart and the input to the systemic circulation.
Organ PP is a function of both cardiac output and systemic vascular resistance (PP = CI*SVRI); thus, only
when one factor is constant, will blood pressure directly
reflect changes in the other. Blood pressure targets during anesthesia and critical care have been defined empirically from population data (24), but there is wide
disagreement between clinicians about what hypotension is significant (25). Although hypotension is
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J.P. Scott and G.M. Hoffman
common (26), the incidence of hypotension is highly
dependent on the definition (27) and reporting is related
to the occurrence of complications (28). There is little
evidence that moderate hypotension is harmful and a
lower safe limit could not be determined (29) except in
the extreme (30). Conversely, serious hemorrhage and
organ hypoperfusion can occur without significant
change in blood pressure, even in anesthetized patients
(31,32), and moderate hypotension may even improve
outcome in resuscitation from shock (33).
Inferences about blood flow from measures of blood
pressure are unreliable (34) and may be counterintuitive
(35). As measures of the relationship between blood
pressure and organ perfusion reveal large inter- and
intra-individual variations (36), it is not surprising that
outcomes are largely unrelated to changes in blood pressure. The model of PP = CI*SVRI also implies that
SVRI is a scalar variable, although the total resistance is
actually composed of the inverse of sums of regional
conductances, which are not clinically measurable and
which are somewhat independent of each other. Thus,
PP does not measure global or specific organ perfusion;
with relatively fixed cardiac output, an increase in blood
pressure will occur through a net increase in SVRI which
is not likely to be evenly distributed across all vascular
beds and thus will result from a change in the distribution of blood flow across organs. This implies that
increasing blood pressure occurs through a reduction in
blood flow to some regions. We need to measure more
than blood pressure to improve outcomes related to
circulation and organ perfusion.
Standard hemodynamic monitors provide a minimal
data set that crudely characterizes the circulation.
Repetitive measurement and recording of heart rate,
arterial blood pressure, and, recently, arterial oxygen
saturation have been the basis for safety monitoring of
the circulation in anesthesia and critical care, but in
many instances, these parameters do not have adequate
predictive or heuristic value. These supply-side measures
are to the circulation what the fiO2 and breathing rate
are to the respiratory system. For the circulation, the
venous (postsystemic extraction) oxygen saturation provides a downstream signal about how the heart and circulatory system have functioned in systemic gas
exchange. Near-infrared spectrometry (NIRS) is the
‘pulse ox for the circulation’ providing real-time, continuous, noninvasive, organ-specific, and quasi-global
postextraction monitoring.
Physiologic rationale
Shock is the most common cause of pediatric cardiac
arrest (37). Global, regional, or intraregional alteration
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NIRS: exposing the circulatory dark side
in oxygen delivery (DO2) creates a state of oxygen debt
and anaerobic metabolism with failure to meet metabolic demand (oxygen consumption, VO2) (38–40). The
severity and duration of oxygen debt in critical illness is
directly linked to the development of end-organ ischemia, multiorgan failure and death (40,41). Prompt interventions directed at reversing oxygen debt are
associated with improved outcomes (22,42,43). Delayed
recognition and treatment of oxygen debt cause preventable morbidity and mortality (44). The anesthetized
child is not immune from these principles and may be at
higher risk because of surgical and anesthetic effects.
Standard vital sign parameters are not highly predictive of the degree of circulatory failure and often underestimate the magnitude of oxygen debt (34,35).
Biochemical indicators of organ hypoperfusion such as
blood lactate, unmeasured anions, and base deficit correlate with the severity of oxygen debt and mortality
(39,45), but cannot be continuously measured and lag
circulatory changes. Systemic venous oxygen saturation
(SvO2) monitoring provides an estimate of global oxygen balance according to the Fick equation SvO2 =
SaO2 VO2/DO2 (35). Venous saturation may be sampled intermittently or continuously monitored via an
oximetric catheter, and SvO2-guided resuscitation is
associated with improved outcomes in shock (22,42).
However, central venous line placement is invasive and
often technically challenging in infants and small children, adding significant delay in both assessment and
treatment. More importantly, SvO2 represents the flowweighted averages of individual organ saturations and
may be insensitive to maldistribution of regional blood
flows. In shock, elevated sympathetic tone redistributes
blood flow away from splanchnic and mesenteric regions
(35,46–49). Thus, regional ischemia may be clinically
silent until organ dysfunction occurs, resulting in
increased morbidity and mortality.
Continuous noninvasive organ-specific perfusion
monitoring is possible with infrared spectroscopy. NIRS
is a completely noninvasive methodology now commonly
used to measure regional tissue oxygenation and perfusion. The regional oxygen saturation (rSO2) approximates regional venous saturation, and in combination
with arterial oxygen saturation allows for the estimation
of regional oxygen economy. Manipulation of the regional Fick equation (rSO2 = SaO2 VO2/DO2) is often
performed to derive regional arterio-venous difference
(DarSO2 = SaO2 rSO2) or fractional oxygen extraction (fOE = [SaO2 rSO2]/SaO2), both of which are
proportional to blood flow when hemoglobin concentration and metabolism are constant (35,50). Thus, NIRS
opens a window for regional circulation monitoring that
can drive organ-specific goal-directed treatments.
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NIRS: exposing the circulatory dark side
Technology
Near-infrared spectrometry technologies derive estimates of physiologic measures by the application of
modifications of the Beer Lambert law relating photon
transmission to concentration of absorbers and scatterers in biologic suspensions. Near-infrared light passes
through tissues, such as skin and bone, with minimal
absorption. Significant biologic absorbers include
heme-containing (hemoglobin) and nonheme-containing
(bilirubin, myoglobin, cytochrome oxidase) chromophores, with oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) being the primary absorbers of nearinfrared light in blood (51–54). NIRS devices use laser
or diode light sources to emit multiple wavelengths of
near-infrared light (700–1000 nm). Because HbO2 and
HbR have different absorption spectra, their concentrations can be derived by solution of multiple equations.
Measurement of the light intensity at the isobestic point
(the wavelength at which HbO2 and HbR absorb nearinfrared light equally) allows for an estimation of total
Hb content. Although the concentrations of nonheme
absorbers can degrade precision of absolute measurements, the ratio of HbO2/(HbO2 + HbR) is more robust
(55–57). This estimate of field oxyhemoglobin saturation is termed regional saturation (rSO2) or tissue
oxygenation index (TOI). For the validation of regional
oxygen saturation, this field is modeled as lying between
the arterial and regional venous blood. As 75–90% of
the blood in tissue is postarteriolar, the rSO2 value is an
estimate of regional venous saturation (54,55,58–61),
NIRS devices provide saturation that is regional and
optically weighted (rSO2), while intravascular catheters
provide saturation that is regional and flow-weighted
(SvO2); thus, the two measures are highly related but
not equivalent.
The clinical feasibility of NIRS derives from technologic optimization of the competing constraints of reflectance spectroscopy. While the absolute light path of an
individual photon in suspension cannot be determined,
the average photon path is an ellipse from light source
to detector. The depth of this light path is approximately
one-half of the source-detector distance. Larger sourcedetector separation yields deeper tissue interrogation
but less photon recovery; these trade-offs are optimized
with 4–5 cm source-detector separation. Most current
(spatially resolved continuous wave) devices also include
a near light path, and employ subtraction algorithms to
reject measures from shallow tissue, effectively focusing
the measure on deeper tissue (62). The resulting monitored field is 2–3 cm deep, making neonates, infants and
children the ideal candidates for organ-specific circulation monitoring with NIRS.
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J.P. Scott and G.M. Hoffman
Animal and pediatric studies demonstrate good
correlation between the rSO2C and jugular venous bulb
saturation (SjvO2) (60,63–68). In all studies, the withinpatient trends were good, but absolute agreement is better in smaller heads, because the same sensor geometry
interrogates a tissue field that is proportionally larger
and deeper (69). Sensor location will be sensitive to heterogeneity within organs, but in the absence of cortical
pathology, there is little difference between left, right, or
midline forehead placement (57,70). Currently available
devices are highly correlated with each other but do not
show absolute equivalence (61,71). Unlike pulse oximetry, NIRS does not depend on a pulsatile signal, and
thus, continuous oxygenation measures are available
during all alterations of perfusion, including nonpulsatile cardiopulmonary bypass (CPB) and circulatory
arrest, planned or otherwise (72–77).
Normal measures
In acyanotic humans, cerebral saturation (rSO2C)
ranges between 60% and 80% (60,78–87). The regional
blood flow/metabolism relationship can be better
expressed by the arterial-NIRS difference (DarSO2) or
the fOE, with normal cerebral fOE of 20–40%, and
somatic fOE of 10–30%. The cerebral fOE drops in the
minutes after birth, while the somatic fOE remains elevated for a longer period of time, perhaps related to
later closure of the ductus arteriosus (83). In normal
newborns in the first week of life (85), the average resting cerebral rSO2C was 77 8%, resting somatic-renal
(rSO2S) 86 8%, and somatic-renal to cerebral difference (DrSO2SC) was 9 9%. Somatic measures showed
greater variability within than between patients, indicating the state dependence of these measures (Figure 1).
Cerebral oximetry
Near-infrared spectrometry was initially developed to
monitor the cerebral circulation. In adults, bilateral
frontal cerebral oximetry is used to monitor perfusion to
at risk areas of grey matter within cerebral cortex in the
watershed areas between the anterior and middle cerebral arteries (88). The smaller head circumference of
neonates and children permits greater depth of penetration of and assessment of subcortical tissue oxygenation
(Figure 2) (69).
Experimental data reveal a threshold for cerebral oxygen debt at rSO2C in the 35–45% range, which correspond to the 50% reduction in cerebral blood flow that
produces injury (89). In animals, neuronal ATP depletion and development of cerebral anaerobic metabolism
occurred with RSO2C <45%, hypoxic ischemic injury
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
J.P. Scott and G.M. Hoffman
NIRS: exposing the circulatory dark side
Figure 1 Normal values for cerebral and somatic (renal) regional saturation (rSO2) measures, derived from 25 normal newborns over the
first 5 days of life. Individual measures were obtained at 10-s intervals
over a 5-h period that included resting and feeding. Individual patient
medians and ranges shown. Shaded regions are 95%CI for patient
and population. Deeply shaded regions are mean and SD of patient
means. The cerebral extraction was 20%, and the somatic extraction
was 11%, with an average somatic-cerebral rSO2 difference was 9%.
Although highly dynamic in the short term, the pattern of average
somatic rSO2 exceeding average cerebral rSO2 was observed in
24/25 neonates, and there were no consistent or important changes
in either measure in the transition from resting to feeding. From
source (85) with permission.
Figure 2 Areas of potential hypoxic–ischemic injury in the neonatal
brain include moderate and deep cortical structures. The light path
of a near-infrared (NIR) spectroscopy device applied to the frontal
forehead will traverse areas at risk between the short- and longpenetrating arteries. More of these regions will be in the monitored
field in neonates with small head dimensions. From source (69) with
permission.
Figure 3 Relation between near-infrared spectroscopy regional oxygen saturation (ScO2) and brain tissue lactate concentration in piglets. The lactate concentrate rose sharply at saturations <45%.
Modified from source (90) with permission.
occurred with rSO2C <40%, and neuronal cell death at
an RSO2C <30% (Figure 3) (90,91). These data are consistent with clinical studies documenting worse neurologic outcomes in infants and children who experience
prolonged normothermic cerebral saturation <40–50%
(92–95). In children with congenital heart disease
(CHD) requiring CPB, prolonged perioperative cerebral
desaturation <45% was associated with abnormal brain
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
magnetic resonance (MRI) imaging findings (96,97) and
worsened neurodevelopmental outcomes (97,98).
Multisite oximetry
Multisite oximetry can monitor the circulations in multiple organs, typically brain and a somatic organ such as
the kidney, liver, intestine, or muscle. Typically, the
cerebral circulation has tight flow-metabolism coupling
driven by local autoregulatory mechanisms, while the
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NIRS: exposing the circulatory dark side
somatic circulations (rSO2S) have sympathetically modulated resistances that can alter rapidly with changes in
autonomic outflow. A monitoring strategy that includes
a cerebral and a noncerebral organ can assess oxygen
delivery to organs with perfusion regulated by different
neurohormonal mechanisms and thus reveal changes in
the distribution of blood flow with changes in patient
state that are completely invisible to global circulatory
measures (99,100).
Somatic NIRS saturation data have been validated
for the detection of changes in perfusion of renal, hepatic, and mesenteric, and muscle circulations in animal
and human catheter-based vascular occlusion procedures (101). Skeletal muscle blood flow and metabolism
has been extensively interrogated with NIRS (55,102).
In piglet models of renal, hepatic, or mesenteric
ischemia, somatic NIRS values correlate well with
organ-specific measurements of oxygen delivery, venous
saturation, and lactate levels (103–107). Normothermic
desaturation kinetics detected by NIRS are congruent
with time dependence of ischemic injury of different
organs (Figure 4) (104,105). In human studies, the
greatest degree of agreement between somatic NIRS and
organ-specific venous saturation data occur infants
weighing <10 kg (101,108). The region specificity of
NIRS is most obvious during interventions that produce
major changes in the distribution of blood flow, including application of aortic cross-clamp during low-flow
CPB with selective cerebral perfusion or coarctation
repair (109–114).
The somatic-cerebral saturation gradient (DrSO2SC)
reflects differences in flow-metabolism ratios in each
region, and these NIRS data are congruent with
micropuncture measures of brain and kidney oxygen
tension distributions (115,116). The DrSO2SC is a
shorthand comparison of the arterial-somatic and
J.P. Scott and G.M. Hoffman
arterial-cerebral differences (or extractions) and is
about 10–15% in normals and well-supported patients
(35,85,105,117–119). The DrSO2SC narrows with activation of the sympathetic nervous system in response
to stressors including early shock. Increased systemic
vascular resistance maintains perfusion of heart and
brain, at the expense of perfusion to the kidneys and
mesenteric organs, with subsequent development of
organ
dysfunction
and
increased
mortality
(50,120,121). Two-site NIRS is valuable in the identification of somatic hypoperfusion in early compensated
shock, as reduced renal/mesenteric perfusion may be
clinically silent until organ dysfunction occurs (122–
124).
As the mixed venous oxygen saturation is the flowweighted average of regional venous saturations, mathematical reconstructions of SvO2 from a multiple-site
NIRS rSO2 measures perform better than single-site correlations (35,50,125–127). Two-site cerebral and renal
somatic saturation data correlate well in linear models
with SvO2 (35). For patients who do not have central
access, two-site NIRS provides a surrogate SvO2 for
rapid assessment and goal-directed treatment (Figure 5).
In conjunction with pulse oximetry, this technique
allows for a dynamic noninvasive estimate of regional
and global oxygen extraction with adequate accuracy
for clinical use (35,128).
Near-infrared spectrometry and oxygen debt in
congenital heart disease
Children with CHD are at risk for global and regional
oxygen debt. Ischemic neurologic injury and acute kidney injury (AKI) are the most common lasting manifestations of regional oxygen debt in survivors. Multisite
rSO2-monitoring aids in the detection of low cardiac
Figure 4 Near-infrared
spectrometryderived desaturation curves from cerebral,
mesenteric, renal, and skeletal muscle beds
in isoflurane-anesthetized neonatal piglets
during conditions of normothermic global
ischemia induced by acute cardiac arrest.
Data are expressed as the absolute change
in regional saturation (rSO2) from baseline.
Cerebral tissue has the most rapid desaturation during global ischemia, reflecting the
highest ratio of oxygen consumption. From
source (104) with permission.
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J.P. Scott and G.M. Hoffman
NIRS: exposing the circulatory dark side
Figure 5 Simultaneous measures of cerebral and somatic rSO2 and
optically measured saturation from the superior vena cava (SvO2), in
neonates following stage one palliation of hypoplastic left heart syndrome. A linear combination of both cerebral and renal rSO2 best fit
the SvO2, with approximately equal weighting of cerebral and
somatic sites. Adapted from source (35) with permission.
output and organ-specific oxygen debt. Consequently,
within our institution, two-site cerebral and renal NIRS
monitoring has become standard for all phases of care
in children with complex CHD (50,129,130).
Preoperative NIRS monitoring has resulted in
improved care delivery and decreased resource
utilization in neonates with unpalliated hypoplastic left
heart syndrome (HLHS). These infants have tenuous
parallel circulation with threats to oxygen delivery from
both arterial desaturation and low systemic perfusion.
As pulmonary vascular resistance (PVR) decreases during the first days of life, pulmonary blood flow (QP)
may increase at the expense of systemic blood flow (high
QP:QS), which can be calculated from a modified Fick
equation utilizing SaO2 and SvO2, and estimated with
SvO2 reconstructed from multisite NIRS (105,131).
Management without mechanical ventilation is enabled
in infants with high SaO2 and preserved systemic perfusion monitored by NIRS, while those with evidence of
systemic hypoperfusion received appropriate goal-directed interventions (132). We found that somatic blood
flow (assessed by DarSO2S) was consistently reduced
prior to stage one palliation but that these indices of perfusion were normalized by surgical palliation and support (Table 1). These neonates are extreme exemplars of
patients with circulatory vulnerability related to both
arterial hypoxemia and left to right shunts, demonstrating how NIRS monitoring provides continuous noninvasive diagnostic information to guide rational therapy.
For example, provision of respiratory support to preterm infants with large patent ductus can worsen mesenteric perfusion as detected by increased mesenteric fOE
(133).
Postoperatively, low cardiac output syndrome
(LCOS) is common, with the superimposition of ischemia reperfusion injury, myocardial edema and diastolic
dysfunction, and changes in oxygen consumption
(134,135). When combined with conventional pulse
oximetry, NIRS derived indices of systemic perfusion
have been successfully applied to identify neonates at
risk for shock and guide appropriate therapy. In neonates following stage 1 palliation (S1P), reduced rSO2S
and somatic-cerebral gradients were associated with
increasing risk of biochemical shock, multiple organ dysfunction, and mortality (113,121,125,126,130,131,136–
138). In acyanotic infants and children undergoing
biventricular repairs, average cerebral and somatic NIRS
rSO2 values were inversely related to the development
Table 1 Regional oxygenation by pulse oximetry (SaO2), cerebral (rSO2C), and renal somatic (rSO2S) Near-infrared spectrometry in normal newborns (85), and patients with HLHS before (132) and after (120) stage one palliation. Derived parameters are somatic-cerebral rSO2 difference
(ΔrSO2SC), arterial-cerebral difference (ΔarSO2C) and arterial-somatic difference (ΔarSO2S). Somatic hypoperfusion is evident before palliation
by a wide ΔarSO2S and a small somatic-cerebral difference (ΔrSO2SC). Although the absolute SaO2 and regional rSO2 after palliation is lower
than normal newborns, the regional blood flow parameters, as reflected by arterial-regional differences, are normalized
Parameters
SaO2
rSO2C
rSO2S
ΔrSO2SC
ΔarSO2C
ΔarSO2S
SvO2
Normal (N = 25,
n = 17690)
HLHS Pre-S1P
(N = 47, n = 1831)
98 4
77.7 7.9
86.7 7.6
9.0 8.9
20.3 7.9
11.2 7.6
92.3
66.8
68.4
1.6
25.1
23.5
5.4a
8.5a
8.8a
9.4a,b
9.0
9.1a,b
HLHS post-S1P
(N = 41, n = 1554)
84.8
66.4
78.4
11.9
18.2
6.3
64.2
6.1a
9.0a
7.7a
9.4
8.6
7.3
9.6
HLHS, hypoplastic left heart syndrome; S1P, stage 1 palliation.
Different from normal neonates.
b
Different from post-S1P.
a
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NIRS: exposing the circulatory dark side
of organ hypoperfusion and anaerobic metabolism, with
postoperative lactic acidosis associated with an average
two-site NIRS saturation <65% (Figure 6) (125).
Somatic measures may be valid from probe placements
that target renal, mesenteric, or muscle beds (105,139).
The circulatory complexity of patients with CHD has
led to consensus recommendation for NIRS in single
ventricle patients at risk for or being resuscitated from
shock (37,50,140). In both cyanotic and acyanotic
infants, two-site NIRS monitoring has increased the
recognition of circulatory abnormalities and decreased
the incidence of shock in our ICU (105,141).
Hypoxic ischemic neurologic injury
Ischemic neurologic injury is the most common sequelae
of regional oxygen debt during and after pediatric heart
surgery (94). The etiology of peri-CPB ischemic neurologic injury is multifactorial, including impairment of
cerebral autoregulation, increased cerebral vascular
resistance, deep hypothermic circulatory arrest (DHCA),
and global LCOS (112,119,142,143). Cerebral oximetry
is a critical tool in the detection of CPB-associated cerebral dysoxia. Cerebral desaturation, during rewarming
and after CPB, is common and associated with cerebral
injury (97,113,143–146), with higher thresholds during
hypothermia (147,148). Although thresholds and intervention strategies based on cerebral NIRS that improve
outcome are incompletely validated (93), neurodevelopmental outcomes can be normal with application of cerebral goal-directed approaches (98,143,149).
CPB is associated with impaired cerebral autoregulation resulting in pressure-dependent flow, maldistribution of cerebral blood flow, and increased risk of
Figure 6 A linear combination of cerebral and somatic rSO2 was
highly related to blood lactate concentration in infants and children
following two-ventricle corrective surgery. Elevated lactate levels
were seen when the linear combination was <65%. Modified from
source (125) with permission.
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J.P. Scott and G.M. Hoffman
ischemic neurologic injury. Cerebral NIRS permits a
continuous assessment of the lower limits of cerebral
autoregulation. NIRS-derived indices of cerebral blood
flow correlate well with transcranial doppler (TCD)
measurements of the middle cerebral artery velocity and
cerebral PP (150). Online detection of the lower limit of
autoregulation, a concept fundamental to neurologic
protection but elusive in individual determination, is
apparent when changes in blood pressure and cerebral
rSO2 are coherent, and this effect can be quantitated
and automated to drive individualized targets for
management (150,151).
Deep hypothermic circulatory arrest is variably associated with adverse neurologic outcomes following cardiac surgery that are only loosely associated with total
duration of arrest (152). Risk factors for neurologic
insult during DHCA include the length of circulatory
arrest, temperature, hematocrit, and pH management
strategy. Cerebral NIRS monitoring has been utilized to
identify at risk states during DHCA (148,153–156).
With the degree of post-DHCA neurologic injury most
closely related to the time spent at the rSO2C nadir,
corresponding to a state of cerebral oxygen debt with
and no cerebral oxygen consumption (143,157,158).
NIRS-guided DHCA management strategies that
include identification of the rSO2C nadir and avoidance
of prolonged desaturation are associated with improved
outcomes (143,149,157).
The technique of selective antegrade cerebral pefusion
(ACP) of the brain via the right inominate artery can
reduce or eliminate the need for DHCA (110–113). Continuous rSO2C monitoring during ACP aids the detection of cerebral perfusion abnormalities and is critical to
ensuring optimal cerebral flow and adequate antegrade
flow. Animal and human data demonstrate improved
cerebral outcomes only if ACP flow is adequate to
normalize cerebral blood flow, detectable by TCD or
NIRS (143,149,159–161).
Early postoperative rSO2C depression following
cardiac surgery is consistent with elevated post-CPB
cerebral vascular resistance, which frequently occur following deep hypothermia (113,155). This phenomenon
occurs after repair of one and two ventricle lesions at
deep hypothermia (113,118,119). Abnormal cerebral
vascular resistance contributes to restricted cerebral perfusion and potential cerebral ischemia, with highest risk
in the first postoperative day (Figure 7) (98,118,119).
Severe intraoperative (162) and postoperative (98,114)
cerebral desaturation is associated with reduced
neurodevelopmental performance in early childhood
(Figure 8). The convergence of experimental and clincial
findings make cerebral rSO2 a rational target for
goal-directed therapy.
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
J.P. Scott and G.M. Hoffman
Figure 7 In neonates following stage, one palliation hypoplastic left
heart syndrome, an early postoperative period of cerebral desaturation was observed despite improving global hemodynamic measures, emphasizing the vulnerability of the cerebral circulation. The
contributions of cerebral and somatic saturation to the superior vena
cava saturation are also evident. From source (119) with permission.
Acute kidney injury
Post-CPB AKI remains a major source of morbidity in
children with CHD. Over 40% of children with CHD
develop AKI following bypass (163). The pathogenesis
of CPB-related AKI is not completely understood, but
renal ischemia is an important contributing factor to its
development (105,164–166). In animals, exposure to
CPB results in severe renal medullary hypoxia and
increased rates of AKI (167). Biochemical detection of
AKI includes measurement of serum creatinine and
urine output, but these parameters are insensitive and
lagging indicators of renal ischemia. Somatic-renal
desaturation is an early predictor of postoperative renal
dysfunction. In infants following biventricular repair,
2 h of rSO2R <50% was associated with a fourfold rate
of AKI (164). Similarly, following single ventricle repair,
rSO2R <60% for 1 h predicted an eightfold risk of AKI
(105,165). Recent studies of biomarkers of AKI demonstrate rSO2R <50% is predictive of elevated urinary
cystatin C, IL-18, and Kim-1, as well as increased morbidity and mortality (166). Somatic-renal regional oximetry can provide a target for intervention to reduce
ischemic injury.
Near-infrared spectrometry and sepsis-mediated
oxygen debt
Pediatric sepsis has high mortality when not rapidly
reversed. The ability to reverse oxygen debt in sepsis is
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
NIRS: exposing the circulatory dark side
Figure 8 Cerebral desaturation detected by near-infrared spectrometry in the 48 h following neonatal palliation of hypoplastic left heart
syndrome was associated with poorer performance on a robust
multi-domain neurodevelopmental measure (visual-motor integration
scale) when tested 4–5 years of age. Adapted from (98) with
permission.
associated with improved survival. Physiologic measures
associated with survival include the ability to increase
cardiac index, DO2, and VO2 (40,168). Animal models
of sepsis reveal a clear correlation between endotoxinmediated reductions in mesenteric perfusion, transcutaneous somatic NIRS, and invasive measures of mesenteric oxygen delivery (venous saturation, oxygen
delivery, and lactate measurements) (106,107). Outcomes in sepsis and septic shock are improved when
goal-directed treatments include circulatory optimization based on SvO2 measurement. Pediatric multisite
NIRS monitoring approximates SvO2 measurements
and allows goal-directed treatments to begin earlier, a
most important factor in improved outcome (22,42,44).
Failure to normalize both central and regional oxygen
measures is associated with poor outcome in resuscitation from shock (169,170).
Near-infrared spectrometry and oxygen debt in
prematurity
Regional oximetry in premature infants aids in the recognition of potentially devastating complications such
as hypoxic neurologic injury and necrotizing enterocolitis (NEC). Cerebral oximetry in premature infants has
been used to identify hypoxic and hyperemic states associated with adverse neurologic outcomes. In infants with
severe birth asphyxia, irreversible neurologic injury
resulting in neuronal cell death, loss of oxygen consumption and autoregulation was associated with abnormal
elevation in rSO2C (171). Transient episodes of pressure
passive cerebral blood flow are common in very low
81
NIRS: exposing the circulatory dark side
birth weight premature infants, detectable by continuous cerebral oximetry (172,173). Persistent blood-pressure-dependent and high rSO2C values in very
premature infants is indicative of loss of cerebral autoregulation and greater risk of peri-intraventricular hemorrhage (174).
Preterm, septic, and surgical neonates are at risk for
developing NEC. Mesenteric/splanchnic somatic oximetry has shown promise as a continuous noninvasive
monitor in the detection of mesenteric perfusion
(105,139,175). In piglets, anterior abdominal wall rSO2
values were significantly lower in animals who later
developed NEC (176). In preterm infants, reduced
splanchnic NIRS correlate with feeding intolerance and
NEC (177), and premature neonates with acute surgical
abdominal processes have reduced splanchnic to cerebral rSO2 gradients (178). This multisite approach has
also been exploited to individualize the need for and
response to blood transfusion (80,179,180). The recent
finding of higher rates of NEC, death, and disability
(but lower rates of retinopathy) in prematures subjected
to an oxygen-restrictive management strategy emphasizes the potential for differential end-organ injury in
vulnerable patients with otherwise-acceptable arterial
saturation (181).
Effects of anesthesia and interventions
Deliberate and inadvertant changes in arterial,
venous, and tissue pressure, body position, blood gas
composition, temperature, hemoglobin concentration,
and anesthetic depth occur routinely during anesthesia.
Most drugs in the anesthesiologist’s armamentarium
have direct or indirect effects on vascular tone, myocardial performance, and cerebral metabolism; these
effects can be additive, competing, or idiosyncratic,
and thus, the magnitude and direction of these effects
are difficult to predict. The potent cerebral vasodilator
J.P. Scott and G.M. Hoffman
effects of anesthetic vapors have been extensively
investigated in experimental settings (182) and are
obvious with NIRS monitoring. Cerebral rSO2 also
tends to increase with propofol and thiopental, but to
decrease with etomidate (183). The regional hyperemia
that accompanies sympathectomy with caudal or
major regional local anesthetic block can be readily
detected by NIRS (184,185). While the effect of
changes in arterial pCO2 and hydrogen ion concentration on the regional circulations are well known to
anesthesiologists, these remain only theoretic constructs without online measures. For example, hypercapnia dilates both cerebral and somatic arterioles,
causes a degree of sympathetic activation, and
increases PVR. In neonates and infants, the superimposition of these effects generally causes an increase in
cerebral blood flow, but a decrease in somatic blood
flow (Figure 9) (105,117,186,187).
The complexity of effects of vasoactive drugs on the
distribution of vascular resistances and myocardial
function makes prediction of specific organ effects
inaccurate. For example, the effects of epinephrine or
norepinephrine on renal blood flow depend on a
constellation of host and disease factors, and this
variation drives the need for individualized therapies.
Multisite NIRS monitoring allows observation of
patient-specific effects of complex interventions on
complex systems and provides more targets for individualized goal-directed treatment.
Sources of error
Errors in clinical application of NIRS devices are
largely related to misunderstanding of the optical
limitations, which are more significant in large
patients (52,101,188), in whom abdominal organspecific measures may be invalid, but almost all
patients have an accessible skeletal muscle field for
Figure 9 Changes in arterial carbon dioxide
tension (pCO2) can alter the distribution of
regional vascular resistance and blood flow.
In neonates, following stage one palliation of
hypoplastic left heart syndrome, and increase
in pCO2 causes an increase in cerebral blood
flow and oxygenation, but this is mirrored by
a reduction in renal-somatic blood flow and
oxygenation. From source (186) with permission.
82
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
J.P. Scott and G.M. Hoffman
NIRS: exposing the circulatory dark side
somatic monitoring. The optical field of current
4–5 cm source-detector distance devices will interrogate only about 1–2 cm3 of tissue, and both
individual anatomic variation and intra-organ
heterogeneity must be considered. Direct hyperbilirubinemia will cause a reduction in the rSO 2
relative to the regional venous measure, and this
effect needs further quantification (189,190).
Other sources of error are interpretive or inferential. The relationship between rSO2 and regional pO2
will depend on temperature, pCO2, and local factors,
and both overly high and overly low tissue pO2 are
associated with injury. Regional blood flow and saturation can change quickly, and overinterpretation of
a single regional rSO2 measure as a global or persistent characteristic may be misguided. Conversely, disregard of worrisome rSO2 information in the face of
normal blood pressure may not reflect understanding
of the complexity of circulatory physiology.
can be disruptive, challenging the anesthesiologist to
re-interpret the clinical state with more a complex
physiologic understanding. Noninvasive measurement
of regional oxygen saturation with NIRS can provide
a probe of organ-specific blood flow or oxygen supply/demand relationships that are good enough for
use in a wide variety of clinical scenarios, but the
current technology is more suitable for neonates,
infants and small children. Future developments will
permit more accurate measures in larger patients and
those with other optical confounders and will allow
greater spatial resolution. Through an understanding
of both the principles and limitations of current and
future devices and appropriate application of these
technologies, venous oximetry with NIRS can do for
the circulation monitoring what pulse oximetry has
done for respiratory monitoring: provide continuous
noninvasive information that can meaningfully
increase recognition of venous desaturation, organ
ischemia, and shock-like states.
Summary
The cardiovascular system is complex, and more multidimensional measures are necessary to describe and
monitor its characteristics and function. Measures in
both the pressure and oxygen domain can help
decode whole body and regional pressure and flow
changes, which are often in opposite directions; thus,
the continuous availability of information from NIRS
Acknowledgments
Sources of funding: Internal Medical College of
Wisconsin and Children’s Hospital of Wisconsin.
Conflicts of interest
No conflicts of interest declared.
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