- 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: ghoffman@mcw.edu
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.
References
1 Eichhorn JH. Prevention of intraoperative
anesthesia accidents and related severe
injury through safety monitoring. Anesthesiology 1989; 70: 572–577.
2 Eichhorn JH, Cooper JB, Cullen DJ et al.
Anesthesia practice standards at Harvard:
a review. J Clin Anesth 1988; 1: 55–65.
3 Keats AS. Anesthesia mortality in perspective. Anesth Analg 1990; 71: 113–119.
4 Barach P, Small SD. Reporting and preventing medical mishaps: lessons from nonmedical near miss reporting systems. BMJ
2000; 320: 759.
5 Gaba DM. Anaesthesiology as a model for
patient safety in health care. BMJ 2000;
320: 785.
6 Cooper JB, Cullen DJ, Nemeskal R et al.
Effects of information feedback and pulse
oximetry on the incidence of anesthesia
complications. Anesthesiology 1987; 67:
686–694.
7 Moller JT, Johannessen NW, Espersen K
et al. Randomized evaluation of pulse
oximetry in 20,802 patients; II: perioper-
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
8
9
10
11
ative events and postoperative complications. Anesthesiology 1993; 78: 445–453.
Bhananker SM, Ramamoorthy C,
Geiduschek JM et al. Anesthesia-related
cardiac arrest in children: update from the
Pediatric Perioperative Cardiac Arrest
Registry. Anesth Analg 2007; 105:
344–350.
Cheney FW, Posner KL, Lee LA et al.
Trends in anesthesia-related death and
brain damage: a closed claims analysis.
Anesthesiology 2006; 105: 1081–1086.
Morray JP, Geiduschek JM, Ramamoorthy C et al. Anesthesia-related cardiac
arrest in children: initial findings of the
Pediatric Perioperative Cardiac Arrest
(POCA) Registry. Anesthesiology 2000;
93: 6–14.
Ramamoorthy C, Haberkern CM, Bhananker SM et al. Anesthesia-related cardiac
arrest in children with heart disease: data
from the Pediatric Perioperative Cardiac
Arrest (POCA) registry. Anesth Analg 2010;
110: 1376–1382.
12 Shah A, Shelley KH. Is pulse oximetry an
essential tool or just another distraction?
The role of the pulse oximeter in modern
anesthesia care. J Clin Monit Comput 2013;
27: 235–242.
13 Cote CJ, Goldstein EA, Cote MA et al. A
single-blind study of pulse oximetry in children. Anesthesiology 1988; 68: 184–188.
14 Pedersen T, Møller AM, Hovhannisyan K.
Pulse oximetry for perioperative monitoring. Cochrane Database Syst Rev 2009; 4:
CD002013.
15 Merry A, Eichhorn J, Wilson I. Extending
the WHO ‘Safe Surgery Saves Lives’ project
through global oximetry. Anaesthesia 2009;
64: 1045–1048.
16 Merry AF, Cooper JB, Soyannwo O et al.
International standards for a safe practice
of anesthesia 2010. Can J Anaesth 2010; 57:
1027–1034.
17 Kwok AC, Funk LM, Baltaga R et al.
Implementation of the World Health Organization surgical safety checklist, including
introduction of pulse oximetry, in a
83
NIRS: exposing the circulatory dark side
18
19
20
21
22
23
24
25
26
27
28
29
84
resource-limited setting. Ann Surg 2013;
257: 633–639.
Hoffman GM. Outcomes of pediatric anesthesia. Semin Pediatr Surg 2008; 17: 141–
151.
Peddy SB, Hazinski MF, Laussen PC et al.
Cardiopulmonary resuscitation: special
considerations for infants and children with
cardiac disease. Cardiol Young 2007; 17
(Suppl 2): 116–126.
Goepfert MS, Richter HP, zu Eulenburg C
et al. Individually Optimized Hemodynamic
Therapy Reduces Complications and
Length of Stay in the Intensive Care Unit.
2013.
Hamilton MA, Cecconi M, Rhodes A. A
systematic review and meta-analysis on
the use of preemptive hemodynamic
intervention to improve postoperative
outcomes in moderate and high-risk
surgical patients. Anesth Analg 2011; 112:
1392–1402.
de Oliveira CF, de Oliveira DS, Gottschald
AF et al. ACCM/PALS haemodynamic
support guidelines for paediatric septic
shock: an outcomes comparison with and
without monitoring central venous oxygen
saturation. Intensive Care Med 2008; 34:
1065–1075.
Rivers EP, Coba V, Whitmill M. Early
goal-directed therapy in severe sepsis and
septic shock: a contemporary review of the
literature. Curr Opin Anaesthesiol 2008; 21:
128–140.
Haque IU, Zaritsky AL. Analysis of the evidence for the lower limit of systolic and
mean arterial pressure in children. Pediatr
Crit Care Med 2007; 8: 138–144.
Nafiu OO, Voepel-Lewis T, Morris M et al.
How do pediatric anesthesiologists define
intraoperative hypotension? Pediatr Anesth
2009; 19: 1048–1053.
Nafiu OO, Kheterpal S, Morris M et al.
Incidence and risk factors for preincision
hypotension in a noncardiac pediatric
surgical population. Pediatr Anesth 2009;
19: 232–239.
Bijker JB, van Klei WA, Kappen TH et al.
Incidence of intraoperative hypotension as
a function of the chosen definition: literature definitions applied to a retrospective
cohort using automated data collection.
Anesthesiology 2007; 107: 213–220.
Taffe P, Sicard N, Pittet V et al. The
occurrence of intra-operative hypotension
varies between hospitals: observational
analysis of more than 147,000 anaesthesia. Acta Anaesthesiol Scand 2009; 53:
995–1005.
Bijker JB, van Klei WA, Vergouwe Y et al.
Intraoperative hypotension and 1-year mortality after noncardiac surgery. Anesthesiology 2009; 111: 1217–1226.
J.P. Scott and G.M. Hoffman
30 Walsh M, Devereaux PJ, Garg AX et al.
Relationship between intraoperative mean
arterial pressure and clinical outcomes after
noncardiac surgery: toward an empirical
definition of hypotension. Anesthesiology
2013; 119: 507–515.
31 Pizov R, Eden A, Bystritski D et al.
Hypotension during gradual blood loss:
waveform variables response and absence
of tachycardia. Br J Anaesth 2012; 109:
911–918.
32 Stricker PA, Lin EE, Fiadjoe JE et al.
Absence of tachycardia during hypotension
in children undergoing craniofacial reconstruction surgery. Anesth Analg 2012; 115:
139–146.
33 Li T, Zhu Y, Fang Y et al. Determination
of the optimal mean arterial pressure for
postbleeding resuscitation after hemorrhagic shock in rats. Anesthesiology 2012;
116: 103–112.
34 Tibby SM, Hatherill M, Marsh MJ et al.
Clinicians’ abilities to estimate cardiac
index in ventilated children and infants.
Arch Dis Child 1997; 77: 516–518.
35 Hoffman GM, Ghanayem NS, Tweddell JS.
Noninvasive assessment of cardiac output.
Semin Thorac Cardiovasc Surg Pediatr Card
Surg Annu 2005: 12–21.
36 Brady K, Hogue CW. Intraoperative
hypotension and patient outcome: does”
one size fit all?”. Anesthesiology 2013;
119: 495–497.
37 Kleinman ME, Chameides L, Schexnayder
SM et al. Pediatric advanced life support:
2010 American Heart Association Guidelines for cardiopulmonary resuscitation and
emergency cardiovascular care. Pediatrics
2010; 126: e1361–e1399.
38 Barbee RW, Reynolds PS, Ward KR.
Assessing shock resuscitation strategies by
oxygen debt repayment. Shock 2010; 33:
113–122.
39 Rixen D, Siegel JH. Bench-to-bedside
review: oxygen debt and its metabolic correlates as quantifiers of the severity of hemorrhagic and post-traumatic shock. Crit Care
2005; 9: 441–453.
40 Shoemaker WC, Appel PL, Kram HB. Role
of oxygen debt in the development of organ
failure sepsis, and death in high-risk surgical
patients. Chest 1992; 102: 208–215.
41 Shoemaker WC, Appel PL, Kram HB. Tissue oxygen debt as a determinant of postoperative organ failure. Prog Clin Biol Res
1989; 308: 133–136.
42 Rivers E, Nguyen B, Havstad S et al. Early
goal-directed therapy in the treatment of
severe sepsis and septic shock. N Engl J
Med 2001; 345: 1368–1377.
43 Tweddell JS, Hoffman GM, Mussatto KA
et al. Improved survival of patients undergoing palliation of hypoplastic left heart
44
45
46
47
48
49
50
51
52
53
54
55
56
57
syndrome: lessons learned from 115 consecutive patients. Circulation 2002; 106(12 Suppl 1): 182–189.
Rivers EP. Early goal-directed therapy in
severe sepsis and septic shock: converting
science to reality. Chest 2006; 129: 217–218.
Balasubramanyan N, Havens PL, Hoffman
GM. Unmeasured anions identified by the
Fencl-Stewart method predict mortality
better than base excess, anion gap, and lactate in patients in the pediatric intensive care
unit. Crit Care Med 1999; 27: 1577–1581.
Ruokonen E, Takala J, Kari A. Regional
blood flow and oxygen transport in patients
with the low cardiac output syndrome after
cardiac surgery. Crit Care Med 1993; 21:
1304–1311.
Ruokonen E, Takala J, Kari A et al. Regional blood flow and oxygen transport in septic shock. Crit Care Med 1993; 21: 1296.
Marik PE. Gastric intramucosal pH. A better predictor of multiorgan dysfunction
syndrome and death than oxygen-derived
variables in patients with sepsis. Chest 1993;
104: 225–229.
Meier-Hellmann A, Hannemann L, Specht
M et al. Relationship Between Mixed
Venous and Hepatic Venous O2 Saturation
in Patients with Septic Shock. Oxygen
Transport to Tissue XV. New York, NY:
Plenum Press, 1994: 701–707.
Ghanayem NS, Wernovsky G, Hoffman
GM. Near-infrared spectroscopy as a hemodynamic monitor in critical illness. Pediatr
Crit Care Med 2011; 12(4 Suppl.): S27–S32.
Jobsis FF. Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science
1977; 198: 1264–1267.
Wahr JA, Tremper KK, Samra S et al.
Near-infrared spectroscopy: theory and
applications. J Cardiothorac Vasc Anesth
1996; 10: 406–418.
Kurth CD, Steven JM, Benaron D et al.
Near-infrared monitoring of the cerebral
circulation. J Clin Monit 1993; 9: 163–170.
Kurth CD, Thayer WS. A multiwavelength frequency-domain near-infrared
cerebral oximeter. Phys Med Biol 1999;
44: 727–740.
Boushel R, Langberg H, Olesen J et al.
Monitoring tissue oxygen availability with
near infrared spectroscopy (NIRS) in health
and disease. Scand J Med Sci Sports 2001;
11: 213–222.
Murkin JM, Arango M. Near-infrared spectroscopy as an index of brain and tissue
oxygenation. Br J Anaesth 2009; 103(Suppl
1): i3–i13.
Menke J, Voss U, Moller G et al. Reproducibility of cerebral near infrared spectroscopy in neonates. Biol Neonate 2003; 83:
6–11.
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
J.P. Scott and G.M. Hoffman
58 Ewert P, Kretschmar O, Peters B et al.
Transcatheter closure of congenital ventricular septal defects. Z Kardiol 2004; 93:
147–155. Interventioneller Verschluss angeborener Ventrikelseptumdefekte. Breitere
Indikationsstellung dank neuer Implantate.
59 Watzman HM, Kurth CD, Montenegro
LM et al. Arterial and venous contributions
to near-infrared cerebral oximetry. Anesthesiology 2000; 93: 947–953.
60 Nagdyman N, Fleck T, Schubert S et al.
Comparison between cerebral tissue oxygenation index measured by near-infrared
spectroscopy and venous jugular bulb saturation in children. Intensive Care Med 2005;
31: 846–850.
61 Nagdyman N, Ewert P, Peters B et al.
Comparison of different near-infrared spectroscopic cerebral oxygenation indices with
central venous and jugular venous oxygenation saturation in children. Pediatr Anesth
2008; 18: 160–166.
62 Davie SN, Grocott HP. Impact of extracranial contamination on regional cerebral
oxygen saturation: a comparison of three
cerebral oximetry technologies. Anesthesiology 2012; 116: 834–840.
63 Abdul-Khaliq H, Troitzsch D, Berger F
et al. Regional transcranial oximetry with
near infrared spectroscopy (NIRS) in comparison with measuring oxygen saturation
in the jugular bulb in infants and children
for monitoring cerebral oxygenation [Regionale transkranielle Oxymetrie mit Nahinfrarot-Spektroskopie (NIRS) im Vergleich
zur Messung der Sauerstoffsattigung im
Bulbus jugularis bei Sauglingen und Kindern als Monitoring der zerebralen Oxygenierung]. Biomed Tech (Berl) 2000; 45: 328–
332.
64 Daubeney PE, Pilkington SN, Janke E et al.
Cerebral oxygenation measured by nearinfrared spectroscopy: comparison with jugular bulb oximetry. Ann Thorac Surg 1996;
61: 930–934.
65 Pollard V, Prough DS, DeMelo AE et al.
Validation in volunteers of a near-infrared
spectroscope for monitoring brain oxygenation in vivo. Anesth Analg 1996; 82: 269–
277.
66 Leyvi G, Bello R, Wasnick JD et al. Assessment of cerebral oxygen balance during
deep hypothermic circulatory arrest by continuous jugular bulb venous saturation and
near-infrared spectroscopy. J Cardiothorac
Vasc Anesth 2006; 20: 826–833.
67 Ricci M, Lombardi P, Schultz S et al. Nearinfrared spectroscopy to monitor cerebral
oxygen saturation in single-ventricle physiology. J Thorac Cardiovasc Surg 2006; 131:
395–402.
68 Kreeger RN, Ramamoorthy C, Nicolson
SC et al. Evaluation of pediatric near-infra-
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
NIRS: exposing the circulatory dark side
69
70
71
72
73
74
75
76
77
78
79
80
81
red cerebral oximeter for cardiac disease.
Ann Thorac Surg 2012; 94: 1527–1533.
Hoffman GM. Neurologic monitoring on
cardiopulmonary bypass: what are we obligated to do? Ann Thorac Surg 2006; 81:
S2373–S2380.
Kishi K, Kawaguchi M, Yoshitani K et al.
Influence of patient variables and sensor
location on regional cerebral oxygen
saturation measured by INVOS 4100
near-infrared spectrophotometers. J Neurosurg Anesthesiol 2003; 15: 302–306.
Dix LM, van Bel F, Baerts W et al. Comparing near-infrared spectroscopy devices
and their sensors for monitoring regional
cerebral oxygen saturation in the neonate.
Pediatr Res 2013; doi: 10.1038/pr.2013.133.
[Epub ahead of print].
Abdul-Khaliq H, Troitzsch D, Schubert S
et al. Cerebral oxygen monitoring during
neonatal cardiopulmonary bypass and deep
hypothermic circulatory arrest. Thorac Cardiovasc Surg 2002; 50: 77–81.
Daubeney PE, Smith DC, Pilkington SN
et al. Cerebral oxygenation during paediatric cardiac surgery: identification of vulnerable periods using near infrared
spectroscopy. Eur J Cardiothorac Surg
1998; 13: 370–377.
Kurth CD, Levy W, Chance B. Oxygen
metabolism during circulatory arrest. J
Neurosurg 1994; 81: 330–331.
Kurth CD, Steven JM, Nicolson SC. Cerebral oxygenation during pediatric cardiac
surgery using deep hypothermic circulatory
arrest. Anesthesiology 1995; 82: 74–82.
Kurth CD, Steven JM, Nicolson SC et al.
Kinetics of cerebral deoxygenation during
deep hypothermic circulatory arrest in neonates. Anesthesiology 1992; 77: 656–661.
Nagdyman N, Fleck TP, Ewert P et al.
Cerebral oxygenation measured by nearinfrared spectroscopy during circulatory
arrest and cardiopulmonary resuscitation.
Br J Anaesth 2003; 91: 438–442.
Kim MB, Ward DS, Cartwright CR et al.
Estimation of jugular venous O2 saturation
from cerebral oximetry or arterial O2 saturation during isocapnic hypoxia. J Clin Monit Comput 2000; 16: 191–199.
Tina LG, Frigiola A, Abella R et al.
Near infrared spectroscopy in healthy
preterm and term newborns: correlation
with gestational age and standard monitoring parameters. Curr Neurovasc Res
2009; 6: 148–154.
Dani C, Pratesi S, Fontanelli G et al.
Blood transfusions increase cerebral,
splanchnic, and renal oxygenation in
anemic preterm infants. Transfusion 2010;
50: 1220–1226.
Petrova A, Mehta R. Near-infrared spectroscopy in the detection of regional tissue
82
83
84
85
86
87
88
89
90
91
92
93
94
oxygenation during hypoxic events in preterm infants undergoing critical care. Pediatr Crit Care Med 2006; 7: 449–454.
Dave V, Brion L, Campbell D et al.
Splanchnic tissue oxygenation, but not
brain tissue oxygenation, increases after
feeds in stable preterm neonates tolerating
full bolus orogastric feeding. J Perinatol
2008; 29: 213–218.
Binder C, Urlesberger B, Avian A et al.
Cerebral and peripheral regional oxygen
saturation during postnatal transition in
preterm neonates. J Pediatr 2013; 163: 394–
399.
Pichler G, Binder C, Avian A et al. Reference ranges for regional cerebral tissue
oxygen saturation and fractional oxygen
extraction in neonates during immediate
transition after birth. J Pediatr 2013; doi:
10.1016/j.jpeds.2013.07.007.
Bernal NP, Hoffman GM, Ghanayem NS
et al. Cerebral and somatic near-infrared
spectroscopy in normal newborns. J Pediatr
Surg 2010; 45: 1306–1310.
Nagdyman N, Fleck T, Barth S et al.
Relation of cerebral tissue oxygenation
index to central venous oxygen saturation
in children. Intensive Care Med 2004; 30:
468–471.
Misra M, Stark J, Dujovny M et al. Transcranial cerebral oximetry in random normal
subjects. Neurol Res 1998; 20: 137.
Roesner JP, Koch A, Bateman R et al.
Accurate and continuous measurement of
oxygen deficit during haemorrhage in pigs.
Resuscitation 2009; 80: 259–263.
Ginsberg MD. Adventures in the pathophysiology of brain ischemia: penumbra,
gene expression, neuroprotection: the 2002
Thomas Willis Lecture. Stroke 2003; 34:
214–223.
Kurth CD, Levy WJ, McCann J. Nearinfrared spectroscopy cerebral oxygen saturation thresholds for hypoxia-ischemia in
piglets. J Cereb Blood Flow Metab 2002; 22:
335–341.
Kurth CD, McCann JC, Wu J et al. Cerebral oxygen saturation-time threshold for
hypoxic-ischemic injury in piglets. Anesth
Analg 2009; 108: 1268–1277.
Levy WJ, Levin S, Chance B. Near-infrared
measurement of cerebral oxygenation. Correlation with electroencephalographic ischemia during ventricular fibrillation.
Anesthesiology 1995; 83: 738–746.
Austin EH 3rd, Edmonds HL Jr, Auden
SM et al. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg 1997; 114: 707–715, 17;
discussion 15-6.
Nollert G, Mohnle P, Tassani-Prell P et al.
Postoperative neuropsychological dysfunction and cerebral oxygenation during
85
NIRS: exposing the circulatory dark side
95
96
97
98
99
100
101
102
103
104
86
cardiac surgery. Thorac Cardiovasc Surg
1995; 43: 260–264.
Edmonds HL Jr, Ganzel BL, Austin EH
3rd. Cerebral oximetry for cardiac and vascular surgery. Semin Cardiothorac Vasc
Anesth 2004; 8: 147–166.
Dent CL, Spaeth JP, Jones BV et al. Brain
magnetic resonance imaging abnormalities
after the Norwood procedure using regional
cerebral perfusion. J Thorac Cardiovasc
Surg 2006; 131: 190–197.
Kussman BD, Wypij D, Laussen PC et al.
Relationship of intraoperative cerebral oxygen saturation to neurodevelopmental outcome and brain magnetic resonance
imaging at 1 year of age in infants undergoing biventricular repair. Circulation 2010;
122: 245–254.
Hoffman GM, Brosig CL, Mussatto KA
et al. Perioperative cerebral oxygen saturation in neonates with hypoplastic left
heart syndrome and childhood neurodevelopmental outcome. J Thorac Cardiovasc
Surg 2013; 146: 1153–1164.
Kraut A, Barbiro-Michaely E, Mayevsky
A. Differential effects of norepinephrine on
brain and other less vital organs detected by
a multisite multiparametric monitoring system. Med Sci Monit 2004; 10: 220.
Mandelbaum M, Barbiro-Michaely E,
Tolmasov M et al., eds. Effects of severe
hemorrhage in in-vivo brain and small intestine mitochondrial NADH and microcirculatory blood flow. advances in biomedical
photonics and imaging. Proceedings of the
6th International Conference on Photonics
and Imaging in Biology and Medicine (Pibm
2007) Wuhan, China, 4–6 November 2007;
2008: World Scientific.
Booth EA, Dukatz C, Ausman J et al. Cerebral and somatic venous oximetry in adults
and infants. Surg Neurol Int 2010; 1: 75.
Wong JK, Smith TN, Pitcher HT et al.
Cerebral and lower limb near-infrared spectroscopy in adults on extracorporeal membrane oxygenation. Artif Organs 2012; 36:
659–667.
Hoffman GM, Wider MD. Organ specificity
of rSO2 measurements during regional
ischemia in piglets. Anesthesiology 2008;
109: A272. [Internet] Available at: http://
www.asaabstracts.com/strands/asaabstracts/abstract.htm?
year=2008&index=6&absnum=1980.
Accessed 5 January, 2011.
Hoffman GM, Wider MD. Changes in
regional oxygenation by NIRS during global ischemia in piglets. Anesthesiology 2008;
109: A1512. [Internet]. Available at: http://
www.asaabstracts.com/strands/asaabstracts/abstract.htm?
year=2008&index=9&absnum=1984.
Accessed 5 January, 2011.
J.P. Scott and G.M. Hoffman
105 Hoffman GM, Tweddell JS. Regional blood
flow monitoring in the perioperative period.
In: Kleinman CS, Seri I, eds. Hemodynamics and Cardiology: Neonatology Questions
and Controversies, 2nd edn. Philadelphia:
W.B. Saunders, 2012: 473–487.
106 Nahum E, Skippen PW, Gagnon RE et al.
Correlation of transcutaneous hepatic nearinfrared spectroscopy readings with liver
surface readings and perfusion parameters
in a piglet endotoxemic shock model. Liver
Int 2006; 26: 1277–1282.
107 Nahum E, Skippen PW, Gagnon RE et al.
Correlation of near-infrared spectroscopy
with perfusion parameters at the hepatic
and systemic levels in an endotoxemic shock
model. Med Sci Monit 2006; 12: BR313–
BR317.
108 Ortmann LA, Fontenot EE, Seib PM
et al. Use of near-infrared spectroscopy
for estimation of renal oxygenation in
children with heart disease. Pediatr Cardiol 2011; 32: 748–753.
109 Pigula FA, Gandhi SK, Siewers RD et al.
Regional low-flow perfusion provides
somatic circulatory support during neonatal
aortic arch surgery. Ann Thorac Surg 2001;
72: 401–406; discussion 6-7.
110 Pigula FA, Nemoto EM, Griffith BP et al.
Regional low-flow perfusion provides cerebral circulatory support during neonatal
aortic arch reconstruction. J Thorac Cardiovasc Surg 2000; 119: 331–339.
111 Andropoulos DB, Diaz LK, Fraser CD
Jr et al. Is bilateral monitoring of cerebral oxygen saturation necessary during
neonatal aortic arch reconstruction?
Anesth Analg 2004; 98: 1267–1272; table
of contents.
112 Andropoulos DB, Stayer SA, Diaz LK
et al. Neurological monitoring for congenital heart surgery. Anesth Analg 2004; 99:
1365–1375; table of contents.
113 Hoffman GM, Stuth EA, Jaquiss RD et al.
Changes in cerebral and somatic oxygenation during stage 1 palliation of hypoplastic
left heart syndrome using continuous regional cerebral perfusion. J Thorac Cardiovasc
Surg 2004; 127: 223–233.
114 Berens RJ, Stuth EA, Robertson FA et al.
Near infrared spectroscopy monitoring during pediatric aortic coarctation repair. Pediatr Anesth 2006; 16: 777–781.
115 Baumgartl H, Zimelka W, Lubbers DW.
Evaluation of PO(2) profiles to describe the
oxygen pressure field within the tissue.
Comp Biochem Physiol A Mol Integr Physiol
2002; 132: 75–85.
116 Lubbers DW, Baumgartl H. Heterogeneities
and profiles of oxygen pressure in brain and
kidney as examples of the pO2 distribution
in the living tissue. Kidney Int 1997; 51:
372–380.
117 McQuillen PS, Nishimoto MS, Bottrell CL
et al. Regional and central venous oxygen
saturation monitoring following pediatric
cardiac surgery: concordance and association with clinical variables. Pediatr Crit
Care Med 2007; 8: 154–160.
118 Furck AK, Hansen JH, Uebing A et al. The
impact of afterload reduction on the early
postoperative course after the Norwood
operation - a 12-year single-centre
experience. Eur J Cardiothorac Surg 2010;
37: 289–295.
119 Uebing A, Furck AK, Hansen JH et al.
Perioperative cerebral and somatic oxygenation in neonates with hypoplastic left heart
syndrome or transposition of the great
arteries. J Thorac Cardiovasc Surg 2011;
142: 523–530.
120 Hoffman GM, Ghanayem NS, Stuth EA
et al. NIRS-derived somatic and cerebral
saturation difference provides non-invasive real-time hemodynamic assessment of
cardiogenic shock and risk of anaerobic
metabolism. Anesthesiology 2004; 99:
A1448. [Internet]. Available at: http://
www.asaabstracts.com/strands/asaabstracts/abstract.htm?
year=2004&index=16&absnum=2206.
Accessed 5 January, 2011.
121 Hoffman GM, Ghanayem NS, Mussatto
KA et al. Postoperative two-site NIRS predicts complications and mortality after
stage 1 palliation of HLHS. Anesthesiology
2007; 107: A234. [Internet]. Available at:
http://www.asaabstracts.com/strands/asaabstracts/abstract.htm?
year=2007&index=16&absnum=1585.
Accessed 5 January, 2011.
122 Dyess DL, Powell RW, Swafford AN Jr
et al. Redistribution of organ blood flow
after hemorrhage and resuscitation in fullterm piglets. J Pediatr Surg 1994; 29: 1097–
1102.
123 Reilly PM, Wilkins KB, Fuh KC et al. The
mesenteric hemodynamic response to circulatory shock: an overview. Shock 2001; 15:
329–343.
124 Ceppa EP, Fuh KC, Bulkley GB. Mesenteric
hemodynamic response to circulatory shock.
Curr Opin Crit Care 2003; 9: 127–132.
125 Chakravarti SB, Mittnacht AJ, Katz JC
et al. Multisite near-infrared spectroscopy
predicts elevated blood lactate level in children after cardiac surgery. J Cardiothorac
Vasc Anesth 2009; 23: 663–667.
126 Li J, Van Arsdell GS, Zhang G et al.
Assessment of the relationship between
cerebral and splanchnic oxygen saturations
measured by near-infrared spectroscopy
and direct measurements of systemic haemodynamic variables and oxygen transport
after the Norwood procedure. Heart 2006;
92: 1678–1685.
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
J.P. Scott and G.M. Hoffman
127 Redlin M, Koster A, Huebler M et al.
Regional differences in tissue oxygenation
during cardiopulmonary bypass for correction of congenital heart disease in neonates
and small infants: relevance of near-infrared
spectroscopy. J Thorac Cardiovasc Surg
2008; 136: 962–967.
128 Morey TE, Gravenstein N, Rice MJ. Let’s
think clinically instead of mathematically
about device accuracy. Anesth Analg 2011;
113: 89–91.
129 Ghanayem NS, Hoffman GM, Mussatto
KA et al. Perioperative monitoring in
high-risk infants after stage 1 palliation
of univentricular congenital heart disease.
J Thorac Cardiovasc Surg 2010; 140:
857–863.
130 Tweddell JS, Ghanayem NS, Hoffman GM.
Pro: NIRS is “standard of care” for postoperative management. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2010; 13:
44–50.
131 Hoffman GM, Tweddell JS, Ghanayem NS
et al. Alteration of the critical arteriovenous
oxygen saturation relationship by sustained
afterload reduction after the Norwood procedure. J Thorac Cardiovasc Surg 2004; 127:
738–745.
132 Johnson BA, Hoffman GM, Tweddell JS
et al. Near-infrared spectroscopy in neonates before palliation of hypoplastic left
heart syndrome. Ann Thorac Surg 2009; 87:
571–577; discussion 7-9.
133 Petrova A, Bhatt M, Mehta R. Regional
tissue oxygenation in preterm born
infants in association with echocardiographically significant patent ductus arteriosus. J Perinatol 2011; 31: 460–464.
134 Li J, Zhang G, Holtby HM et al. Inclusion
of oxygen consumption improves the accuracy of arterial and venous oxygen saturation interpretation after the Norwood
procedure. J Thorac Cardiovasc Surg 2006;
131: 1099–1107.
135 Li J, Zhang G, Holtby H et al. The influence of systemic hemodynamics and oxygen
transport on cerebral oxygen saturation in
neonates after the Norwood procedure. J
Thorac Cardiovasc Surg 2008; 135: 83–90,
e1-2.
136 Tweddell JS, Hoffman GM, Fedderly RT
et al. Phenoxybenzamine improves systemic
oxygen delivery after the Norwood procedure. Ann Thorac Surg 1999; 67: 161–167;
discussion 7-8.
137 Hoffman GM, Ghanayem NS, Kampine
JM et al. Venous saturation and the anaerobic threshold in neonates after the Norwood
procedure for hypoplastic left heart syndrome. Ann Thorac Surg 2000; 70: 1515–
1520; discussion 21.
138 Tweddell JS, Ghanayem NS, Mussatto KA
et al. Mixed venous oxygen saturation mon-
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88
NIRS: exposing the circulatory dark side
139
140
141
142
143
144
145
146
147
148
itoring after stage 1 palliation for hypoplastic left heart syndrome. Ann Thorac Surg
2007; 84: 1301–1310; discussion 10-1.
Kaufman J, Almodovar MC, Zuk J et al.
Correlation of abdominal site near-infrared
spectroscopy with gastric tonometry in
infants following surgery for congenital
heart disease. Pediatr Crit Care Med 2008;
9: 62–68.
Marino BS, Tibby SM, Hoffman GM.
Resuscitation of the patient with the functionally univentricular heart. Curr Pediatr
Rev 2013; 9: 148–157.
Hoffman GM, Ghanayem NS, Berens RJ
et al. Reduction in critical indicators of
shock by routine use of two-site NIRS in
pediatric ICU patients. Anesthesiology 2006;
106: A803. [Internet]. Available at: http://
www.asaabstracts.com/strands/asaabstracts/abstract.htm?
year=2006&index=6&absnum=1239.
Accessed 5 January, 2011.
Hoffman G, Groneck J, Mussatto K et al.
Modified pH startegy during antegrade
cerebral perfusion improves cerebral hemodynamics. Proceedings of the 2009 Annual
Meeting of the American Society Anesthesiologists [Internet]. 2009: A687. Available
from: http://www.asaabstracts.com/strands/
asaabstracts/abstract.htm?year=2009&
index=16&absnum=2022. Accessed 5
January, 2011.
Hoffman GM, Ghanayem NS. Perioperative neuromonitoring in pediatric cardiac
surgery: techniques and targets. Prog Pediatr Cardiol 2010; 29: 123–130.
Mutch WA, Ryner LN, Kozlowski P
et al. Cerebral hypoxia during cardiopulmonary bypass: a magnetic resonance
imaging study. Ann Thorac Surg 1997;
64: 695–701.
Dent CL, Spaeth JP, Jones BV et al. Brain
magnetic resonance imaging abnormalities
after the Norwood procedure using regional
cerebral perfusion. J Thorac Cardiovasc
Surg 2005; 130: 1523–1530.
Hoffman GM, Mussatto KA, Brosig CL
et al. Perioperative cerebral oxygen saturation in neonates with hypoplastic left heart
syndrome and childhood neurodevelopmental outcome. J Thorac Cardiovasc Surg
2013; 146: 1153–1164.
Kadoi Y, Kawahara F, Saito S et al. Effects
of hypothermic and normothermic cardiopulmonary bypass on brain oxygenation.
Ann Thorac Surg 1999; 68: 34–39.
Dexter F, Hindman BJ. Theoretical analysis
of cerebral venous blood hemoglobin oxygen saturation as an index of cerebral oxygenation during hypothermic
cardiopulmonary bypass. A counterproposal to the “luxury perfusion” hypothesis.
Anesthesiology 1995; 83: 405–412.
149 Andropoulos DB, Easley RB, Brady K
et al. Neurodevelopmental outcomes after
regional cerebral perfusion with neuromonitoring for neonatal aortic arch reconstruction. Ann Thorac Surg 2013; 95: 648–654;
discussion 54-5.
150 Brady KM, Mytar JO, Lee JK et al. Monitoring cerebral blood flow pressure autoregulation in pediatric patients during cardiac
surgery. Stroke 2010; 41: 1957–1962.
151 Brady KM, Lee JK, Kibler KK et al. Continuous measurement of autoregulation by
spontaneous fluctuations in cerebral perfusion pressure: comparison of 3 methods.
Stroke 2008; 39: 2531–2537.
152 Wypij D, Newburger JW, Rappaport LA
et al. The effect of duration of deep
hypothermic circulatory arrest in infant
heart surgery on late neurodevelopment:
the Boston Circulatory Arrest Trial. J
Thorac Cardiovasc Surg 2003; 126: 1397–
1403.
153 Greeley WJ, Ungerleider RM, Kern FH
et al. Effects of cardiopulmonary bypass on
cerebral blood flow in neonates, infants,
and children. Circulation 1989; 80: I209–
I215.
154 Greeley WJ, Ungerleider RM, Smith LR
et al. The effects of deep hypothermic cardiopulmonary bypass and total circulatory
arrest on cerebral blood flow in infants and
children. J Thorac Cardiovasc Surg
1989; 97: 737–745.
155 Greeley WJ, Kern FH, Meliones JN
et al. Effect of deep hypothermia and circulatory arrest on cerebral blood flow
and metabolism. Ann Thorac Surg 1993;
56: 1464–1466.
156 Sakamoto T, Zurakowski D, Duebener LF
et al. Interaction of temperature with
hematocrit level and pH determines safe
duration of hypothermic circulatory arrest.
J Thorac Cardiovasc Surg 2004; 128: 220–
232.
157 Kussman BD, Wypij D, DiNardo JA et al.
Cerebral oximetry during infant cardiac surgery: evaluation and relationship to early
postoperative outcome. Anesth Analg 2009;
108: 1122–1131.
158 Sakamoto T, Hatsuoka S, Stock UA et al.
Prediction of safe duration of hypothermic
circulatory arrest by near-infrared spectroscopy. J Thorac Cardiovasc Surg 2001; 122:
339–350.
159 Chen Y, Liu J, Ji B et al. The optimal flow
rate for antegrade cerebral perfusion during
deep hypothermic circulatory arrest. Artif
Organs 2012; 36: 774–779.
160 Pirzadeh A, Schears G, Pastuszko P et al.
Effect of deep hypothermic circulatory
arrest followed by low-flow cardiopulmonary bypass on brain metabolism in newborn piglets: comparison of pH-stat and
87
NIRS: exposing the circulatory dark side
161
162
163
164
165
166
167
168
169
170
88
alpha-stat management. Pediatr Crit Care
Med 2011; 12: e79–e86.
Hofer A, Haizinger B, Geiselseder G et al.
Monitoring of selective antegrade cerebral
perfusion using near infrared spectroscopy
in neonatal aortic arch surgery. Eur J Anaesthesiol 2005; 22: 293–298.
Simons J, Sood ED, Derby CD et al. Predictive value of near-infrared spectroscopy
on neurodevelopmental outcome after surgery for congenital heart disease in infancy.
J Thorac Cardiovasc Surg 2012; 143: 118–
125.
Parikh CR, Devarajan P, Zappitelli M et al.
Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery. J Am Soc Nephrol 2011;
22: 1737–1747.
Owens GE, King K, Gurney JG et al. Low
renal oximetry correlates with acute kidney
injury after infant cardiac surgery. Pediatr
Cardiol 2011; 32: 183–188.
Hoffman GM, Ghanayem NS, Mussatto
KA et al. Perioperative perfusion assessed
by somatic NIRS predicts postoperative
renal dysfunction. Anesthesiology 2005; 103:
A1327. [Internet]. Available at: http://www.
asaabstracts.com/strands/asaabstracts/
abstract.htm?year=2005&index=15&absnum=1769. Accessed 5 January, 2011.
Hazle MA, Gajarski RJ, Aiyagari R
et al. Urinary biomarkers and renal nearinfrared spectroscopy predict intensive
care unit outcomes after cardiac surgery
in infants younger than six months of
age. J Thorac Cardiovasc Surg 2013; 146:
861–867 e1.
Stafford-Smith M, Grocott HP. Renal medullary hypoxia during experimental cardiopulmonary bypass: a pilot study. Perfusion
2005; 20: 53–58.
Hayes MA, Timmins AC, Yau EH et al.
Oxygen transport patterns in patients with
sepsis syndrome or septic shock: influence
of treatment and relationship to outcome.
Crit Care Med 1997; 25: 926–936.
Sakr Y, Dubois MJ, De Backer D et al. Persistent microcirculatory alterations are associated with organ failure and death in
patients with septic shock. Crit Care Med
2004; 32: 1825–1831.
Lima A, van Bommel J, Jansen TC et al.
Low tissue oxygen saturation at the end of
early goal-directed therapy is associated
J.P. Scott and G.M. Hoffman
171
172
173
174
175
176
177
178
179
180
with worse outcome in critically ill patients.
Crit Care 2009; 13(Suppl 5): S13.
Toet MC, Lemmers PM, van Schelven
LJ et al. Cerebral oxygenation and electrical activity after birth asphyxia: their
relation to outcome. Pediatrics 2006; 117:
333–339.
Soul JS, Hammer PE, Tsuji M et al. Fluctuating pressure-passivity is common in the
cerebral circulation of sick premature
infants. Pediatr Res 2007; 61: 467–473.
Tsuji M, Saul JP, du Plessis A et al. Cerebral intravascular oxygenation correlates
with mean arterial pressure in critically ill
premature infants. Pediatrics 2000; 106:
625–632.
Alderliesten T, Lemmers P, Smarius JJ
et al. Cerebral oxygenation, extraction,
and autoregulation in very preterm
infants who develop peri-intraventricular
hemorrhage. J Pediatr 2013; 162: 698–
704. e2.
Gillam-Krakauer M, Cochran CM, Slaughter JC et al. Correlation of abdominal rSO2
with superior mesenteric artery velocities in
preterm infants. J Perinatol 2013; 33: 609–
612.
Gay AN, Lazar DA, Stoll B et al. Nearinfrared spectroscopy measurement of
abdominal tissue oxygenation is a useful
indicator of intestinal blood flow and necrotizing enterocolitis in premature piglets.
J Pediatr Surg 2011; 46: 1034–1040.
Cortez J, Gupta M, Amaram A et al. Noninvasive evaluation of splanchnic tissue oxygenation using near-infrared spectroscopy
in preterm neonates. J Matern Fetal Neonatal Med 2011; 24: 574–582.
Fortune PM, Wagstaff M, Petros AJ. Cerebro-splanchnic oxygenation ratio (CSOR)
using near infrared spectroscopy may be
able to predict splanchnic ischaemia in neonates. Intensive Care Med 2001; 27:
1401–1407.
Bailey SM, Hendricks-Mu~
noz KD, Mally
P. Splanchnic-cerebral oxygenation ratio
as a marker of preterm infant blood
transfusion needs. Transfusion 2012; 52:
252–260.
van Hoften JC, Verhagen EA, Keating P
et al. Cerebral tissue oxygen saturation and
extraction in preterm infants before and
after blood transfusion. Arch Dis Child
Fetal Neonatal Ed 2010; 95: F352–F358.
181 Boost I, Stenson B, Tarnow-Mordi W
et al. Oxygen saturation and outcomes in
preterm infants. N Engl J Med 2013;
368: 2094.
182 Szabo EZ, Luginbuehl I, Bissonnette B.
Impact of anesthetic agents on cerebrovascular physiology in children. Pediatr Anesth
2009; 19: 108–118.
183 Lovell AT, Owen-Reece H, Elwell CE et al.
Continuous measurement of cerebral oxygenation by near infrared spectroscopy during induction of anesthesia. Anesth Analg
1999; 88: 554.
184 Bettesworth J, Bhalla T, Barry ND et al.
Changes in tissue oxygenation following
caudal epidural blockade in infants and
children. Pediatr Anesth 2012; 22: 1068–
1071.
185 Tighe P, Elliott C, Lucas S et al. Noninvasive tissue oxygen saturation determined by
near-infrared spectroscopy following
peripheral nerve block. Acta Anaesthesiol
Scand 2011; 55: 1239–1246.
186 Hoffman GM, Ghanayem NS, Musa N
et al. Differential effects of carbon dioxide
tension on cerebral and somatic oxygenation assessed by near infrared spectroscopy
in postoperative neonates. Anesthesiology
2005; 103: A1374. [Internet]. Available at:
http://www.asaabstracts.com/strands/asaabstracts/abstract.htm?
year=2005&index=15&absnum=1852.
Accessed 5 January, 2011.
187 Li J, Zhang G, Holtby H et al. Carbon
dioxide–a complex gas in a complex circulation: its effects on systemic hemodynamics
and oxygen transport, cerebral, and
splanchnic circulation in neonates after the
Norwood procedure. J Thorac Cardiovasc
Surg 2008; 136: 1207–1214.
188 Germon TJ, Evans PD, Barnett NJ et al.
Cerebral near infrared spectroscopy: emitter-detector separation must be increased.
Br J Anaesth 1999; 82: 831–837.
189 Madsen PL, Skak C, Rasmussen A et al.
Interference of cerebral near-infrared oximetry in patients with icterus. Anesth Analg
2000; 90: 489–493.
190 Song JG, Jeong SM, Shin WJ et al. Laboratory variables associated with low nearinfrared cerebral oxygen saturation in
icteric patients before liver transplantation
surgery. Anesth Analg 2011; 112: 1347–
1352.
© 2013 John Wiley & Sons Ltd
Pediatric Anesthesia 24 (2014) 74–88