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Near-Infrared Spectroscopy (NIRS):Principles, Evidence and Clinical Applications

KrisaVanMeurs,MDRosemarie Hess Professor ofNeonatal and Developmental Medicine

Stanford University School ofMedicineMedical Director, NeuroNICU

LucilePackardChildren’s Hospital Stanford

XSimpósio Internacional deNeonatologia doRio de JaneiroHotel RoyalTulip, Rio de Janeiro

23de Junho 2016

What is Near Infrared Spectroscopy (NIRS) ?

§ NIRScanbeusedasanon-invasivemonitoringtechniqueforcerebralandsomaticoxygenationandhemodynamics.

§ Data isacquiredfromvascularbeds(cerebral,renal,andsplanchnic)withvariedflowsandextractionratios.

§ Whilepulseoximetryprovidesameasureofarterialoxygensaturationreflectingoxygensupplytothetissues,NIRS-measuredregionaloximetrymeasuresthebalancebetweenlocaloxygendeliveryandconsumptionbeneaththesensor.

§ Itprovidesanon-invasivemeasureofend-organoxygenationandperfusion.

NIRS Principles

§ Biologictissuesabsorblightinthenearinfraredspectrum(700-900nm).Thisiscalledthe“windowintolivingorganisms”

§ Absorptionoflightintheinfraredspectrumismainlybyoxygenatedanddeoxygenatedhemoglobin.

§ ThechangeinoxyHb anddeoxyHb concentrationcanbecalculatedbymeasuringthechangeinabsorptionat2ormorewavelengths.

How a NIRS sensor works

PlacementofNIRSsensoronForehead.Thetwoblackcirclesarethelightsourceanddetector.

Lightpassesfromlightsourcethroughthescalp,skull,andbraintissuethentothedetector.

Cerebralsaturation(rSO2)reflectsaratioofarterialtovenousbloodof25%:75%

Interrogationdepthofthesensorisestimatedtobe½oflightsourcetodetectorseparationdistance.

Cerebral and Somatic oximetry

Cerebral high-flowandhighextractioncompensatorymechanismsandautoregulationcerebraldesaturationisalate indicatorofshockifautoregulation ispresent

Somatic variable-flow,lowerextractionflowishighlyinfluencedbysympathetictonesomaticdesaturationisearly indicatorofshock

Two-siteNIRScanprovideongoingindicationsofoxygenationandperfusionchangesincerebralandsomaticcirculations

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Regional saturation reflects oxygen balance

• rSO2increaseswithmoreoxygendeliveryorlessdemandwhilerSO2decreaseswhendeliveryfallsorriseindemand

• Oxygendeliveryisinfluencedby:HemoglobinconcentrationHemoglobinsaturationCardiacoutput(HR,preload,contractilityandafterload)

⬆ Oxygendemandfever,shivering,coldstress,infection,seizures,pain

⬇ Oxygendemandhypothermia,sedation/paralysis,decreasedextraction

Cerebral NIRS measures

§ Regionalmixedcerebraloxygensaturation(rScO2)

HHb =deoxy hemoglobinHbO2 =oxyhemoglobin

§ Cerebralfractionaltissueoxygenextraction(FTOE)

SaO2 =arterial oxygensaturation

rScO! =HbO!

HbO! + HHb

FTOE = SaO! − rScO!SaO!

Validation of cerebral oximetry measures

Direct comparison of the cerebral blood saturations measuredby i-Stat method vs the IL-682 co-oximeter, revealed that thecorrelation between the two commonly used blood analyzers werepoor for 10 blood sample pairs (Figure 6) where the bias andprecision was 9.5±6.0%. Therefore, for subjects 8-17, cephald bloodsamples were analyzed by the IL-682 to obtain SjvO2.Demographic information: 17 neonate subjects were studied,

nine males and eight females, with weights ranging from 2.5 to4.7 kg. Race breakdown: five subjects were Caucasian, six subjectswere Hispanic and 6 subjects were African American. Diagnosis:nine subjects had meconium aspiration syndrome, seven subjectshad primary pulmonary hypertension, and one subject had totalanomalus pulmonary venous return. For the 17 subjects, theprototype CAS cerebral oximeter collected 1718 h (i.e. 71.6 days)

of data, ranging from 24 to 218 h per subject. Two hundred andtwenty-five blood samples were drawn from the cephalad catheterfor co-oximetry analysis, ranging from five to 28 samples persubject.

Discussion

While NIRS technology based monitors have become a usefulresearch tool for monitoring the brain, their clinical applicationhas been hampered by accuracy, reliability and clinicalinterpretation of the measurements. One concern regardingaccuracy of adult cerebral oximetry is the issue of signalcontamination by the extracranial tissue layers. Compared toadults, neonates have a much thinner skull and scalp thickness,

SpO2

NIRS SctO2

NIRS SvO2

SpO2NIRS SctO2NIRS SvO2Ref SctO2Co-ox SjvO2

9.598.587.576.565.554.543.532.521.5Hour Marker

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Figure 2 A representative recording of pulse oximetry SpO2 (top trace), cerebral oximetry SctO2 (middle trace) and cerebral oximetry SvO2 (lowertrace) over an 8 h period. Two co-oximetry measurements for the reference SctO2 and SjvO2 indicated by squares and triangles, respectively, are alsoshown.

10090807060504030201001009080706050403020100

Co-ox ref SctO2 % (0.3*SpO2 + 0.7*SjvO2)Co-ox ref SctO2 % (0.3*SpO2 + 0.7*SjvO2)

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i-STAT IL-682

y = 0.65 + 28.9R = 0.73, p < .001

y = 0.73 + 20.8

7 Subjects

R = 0.67, p < .001

a b

n = 89 samplesBias = 0.26Precision = 5.09

10 Subjectsn = 136 samplesBias = 0.40Precision = 5.08

Figure 3 Scatter plots of cerebral oximetry SctO2 vs the reference SctO2 derived from co-oximetry SjvO2 and pulse oximetry SpO2: (a) i-STAT asreference; and (b) IL-682 as reference.

Validation of a noninvasive neonatal optical cerebral oximeterK Rais-Bahrami et al

631

Journal of Perinatology

Rais-Bahrami Ketal., JPerinatol (2006)

Objective:Tovalidatecerebraloximetrymeasurementswithcerebraloxygensaturationdirectlyfromblooddrawnfromcephalad catheterininternaljugularveininneonatesonveno-venousECMO

Results:Thereisahighlevelofagreementbetweencerebraloximetryandco-oximetrymeasuredbyjugularvenoussaturation.

Normal NIRS values in newborns

rSO2 Term PretermCerebral(%) 66-89 66-83Renal (%) 75-97 64-87Mesenteric(%) 63-87 32-66

Valuesdifferbysensor typewithneonatalsensors reading10%higher

Alderliesten T,etal. PedRes (2016)

Cerebral saturation varies with gestational age and chronologic age

Copyright © 2016 International Pediatric Research Foundation, Inc.

NIRS: reference values in 999 preterms Articles

Conversion DiagramsA strict linear model provided the best fit to convert data  obtained by the SAFB-SM (adult) sensor to the CNN (neonatal) sensor: rScO2-neo = 0.8481 * rScO2-adult + 19.11, R2 = 0.65. Figure 5 is a conversion of Figure 2 by using this equation.

DISCUSSIONThis is the first study to report reference values of rScO2 and cFTOE obtained using NIRS during the first 72 h of life in a large cohort of preterm neonates born at a GA <32 wk.

Four factors should be taken into account when comparing the work reported here to work of others: (i) GA, (ii) PA, (iii) sample size, and (iv) the sensor and device that were used (see discussion below). Values found in the literature agree quite well with the values reported here (Table 3, mean difference: −0.9%). The differences are likely explained by the character-istics of the reported populations (e.g., GA, PA, specific mor-bidity), duration of measurements, and small sample sizes (9–11,17–20). It seems likely that the rScO2 will either stabi-lize or may even increase again after 72 h (12,13,15,21). Note that van Hoften et al. collected data with a pediatric sensor

and Pocivalnik et al. and Pichler et al. with a neonatal sensor (15,20,21).

It is noteworthy how close the −2 SD bands (i.e., p2.3) are to the rScO2 threshold (i.e., 33–44%) reported to be associ-ated with functional impairment of the brain (22,23). A lower CBF, either regional or global, in infants with a lower GA is the most plausible explanation for the positive association between GA and rScO2. Roche-Labarbe et al., while using a frequency domain NIRS system, also demonstrated lower levels of cerebral oxygenation during the first 7 wk of life in infants with a GA <31 wk compared to infants with a GA >31 wk (24). Furthermore, their data show that infants with a GA of 24–27 wk have the lowest blood flow index, support-ing lower CBF as an explanation for lower cerebral oxygen-ation in younger infants. No associations were found between head circumference and rScO2, and SaO2 and GA. This makes the influence of head circumference (i.e., different curvature of the head influencing NIRS from a technical point of view) or SaO2 unlikely. Furthermore, a similar (inverse) association was found between GA and cFTOE. An increased metabolic demand in neonates of lower GA seems unlikely as cerebral activity increases with GA (25).

Female neonates had lower rScO2 as compared to male neonates. This gender difference was also observed by the Pichler et al. during transition from fetal to neonatal life (per-sonal communication, data not published). Again, this could not be explained by a difference in SaO2 or head circumfer-ence. Therefore, possible explanations are a higher (regional) CBF or lower metabolic demand. A hsPDA can cause a ductal steal phenomenon with a surplus of pulmonary flow at the cost of systemic perfusion and thus CBF (26). Although nota-bly increasing with PA, the effect of a hsPDA seems rather limited during the first 3 d of life. The most plausible expla-nation for this is the fact that most hsPDAs become clini-cally apparent from day 3 onward. In addition, an objectively present hsPDA (i.e., confirmed by cardiac ultrasound) does not necessarily decrease CBF, and thus rScO2, as the mag-nitude of systemic steal depends on shunt volume and left ventricular output. Moreover, in this study, the PA at diag-nosis was dichotomized (i.e., ≤84 h); therefore, the exact PA of the individual at diagnosis and start of treatment was not taken into account. In previous publications, we took a differ-ent approach with case–control designs and the start of indo-methacin or surgery as time reference, at median postnatal days 2 and 7, respectively (26,27).

Higher rScO2 values in infants born SGA demonstrate the brain-sparing effect with a compensatory higher CBF. This has been demonstrated previously with other techniques (28). The difference in rScO2 between SGA and AGA infants dimin-ishes over time, suggesting that the CBF returns to normal after day 3. Interestingly, unlike in AGA infants, rScO2 val-ues in SGA infants were slightly lower at 72-h PA compared to rScO2 values shortly after birth. This suggests downregula-tion of compensatory mechanisms instead of a relative lack of hemodynamic development in SGA infants as an explanation for values converging toward AGA values. The limited number

Figure 1. Boxplots of the raw data are displayed for four gestational age groups: white boxes indicate 24–25 wk, light gray boxes indicate 26–27 wk, dark gray boxes indicate 28–29 wk, and black boxes indicate 30–31 wk for (a) regional cerebral oxygen saturation (rScO2) and (b) cerebral fractional tissue oxygen extraction (cFTOE). Data are displayed in 6-h periods for 0–24 h after birth and in 12-h periods for 24–72 h after birth.

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a

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Volume 79 | Number 1 | January 2016 Pediatric RESEARCH 57

Alderliesten T,etal. JPediatr (2016)

*Usedsmalladultsensorwith INVOS5100or4100

White– 24-25weeksLightgray– 26-27weeksDarkgray– 28-29weeksBlack– 30-31weeks

AveragerScO2was65%atadmission,increasedwithGAby1%perweekandalsowithchronologicagepeakingataround36hoursofage.

Normal cerebral saturation during transition

neonates in no need of medical support during immediatetransition. Higher crSO2 values, measured with the NIRS de-vice FORE-SIGHT (Casmed, Branford, Connecticut), in pre-term neonates in need of respiratory support andsupplemental oxygen compared with term neonates hasbeen previously reported.15,16,29

cFTOE reflects cerebral tissue oxygen extraction and/orconsumption.18-21 Thus, cFTOE is inversely correlated to ox-ygen delivery in CDPreterm during the first 2 days of life.30,31

However, we did not observe any significant difference incFTOE between the groups. We observed a trend to lower

cFTOE values in the CDTerm group compared with the VDTerm

group, which is in accordance to recently published data.20

The most widely used NIRS devices in neonates are theNIRO 300 and 200NX(Hamamatsu Photonics, Hamamtsu,Japan), the Invos cerebral/somatic oximeter monitor (withneonatal, pediatric, and adult sensors), and the FORE-SIGHT. Measurements in the present study were performedwith the Invos 5100 monitor using the neonatal sensor.Compared with the use of the NIRO 300 and the Invos adultsensor the tissue oxygenation index and rSO2 values are about10% higher.32,33 However, no difference was observed using

Figure 1. The 10th, 25th, 50th, 75th, and 90th percentiles of crSO2 in neonates requiring no medical support after birth. A, Allneonates. B, VDTerm. C, CDTerm. D, CDPreterm.

Table II. The 10th. 50th, and 90th percentiles of cFTOE using the LMSmethod of neonates requiring nomedical support

Minute

All neonates VDTerm CDTerm CDPreterm

Percentile Percentile Percentile Percentile

10th 50th 90th 10th 50th 90th 10th 50th 90th 10th 50th 90th

2 0.11 0.33 0.70 0.19 0.40 0.69 0.09 0.32 0.74 0.16 0.34 0.613 0.09 0.29 0.61 0.15 0.33 0.59 0.08 0.28 0.64 0.13 0.29 0.564 0.08 0.25 0.53 0.11 0.27 0.50 0.07 0.24 0.54 0.10 0.25 0.505 0.06 0.21 0.45 0.09 0.22 0.42 0.06 0.20 0.46 0.07 0.21 0.466 0.05 0.18 0.39 0.07 0.19 0.36 0.05 0.17 0.39 0.06 0.18 0.417 0.05 0.16 0.34 0.06 0.17 0.33 0.04 0.15 0.34 0.05 0.16 0.378 0.04 0.15 0.32 0.06 0.16 0.32 0.04 0.14 0.31 0.04 0.15 0.359 0.04 0.15 0.31 0.05 0.16 0.32 0.04 0.14 0.30 0.04 0.14 0.3410 0.05 0.15 0.31 0.05 0.16 0.33 0.04 0.14 0.30 0.03 0.14 0.3411 0.05 0.15 0.31 0.06 0.17 0.34 0.05 0.15 0.30 0.03 0.14 0.3412 0.05 0.16 0.32 0.06 0.17 0.35 0.05 0.16 0.31 0.03 0.15 0.3513 0.06 0.17 0.33 0.06 0.18 0.36 0.06 0.17 0.31 0.03 0.15 0.3514 0.06 0.17 0.33 0.06 0.19 0.38 0.07 0.17 0.32 0.03 0.15 0.3615 0.07 0.18 0.34 0.07 0.19 0.39 0.08 0.18 0.32 0.03 0.15 0.36

December 2013 ORIGINAL ARTICLES

Reference Ranges for Regional Cerebral Tissue Oxygen Saturation and Fractional Oxygen Extraction in Neonates duringImmediate Transition after Birth

1561

Downloaded from ClinicalKey.com at Stanford University June 08, 2016.For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.

PichlerG,etalJPediatr (2013)

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Hemispheric differences in cerebral oximetry

and right-determined rScO2 and cFTOE after extraction of 22hypoxemic and/or hyperoxemic periods. Values now were !7.8to "8.2 and !0.088 to "0.084, respectively, indicating animprovement of the limits of agreement during stable systemicSaO2 (p # 0.05). The longitudinal 2-h patterns of rScO2 andcFTOE at day 1 and day 3, extracted from tracings duringstable SaO2 values which were always within normal limits(i.e., 85–95%) showed a not significant difference with

higher rScO2 and cFTOE values at day 3 compared withday 1 of life. On day 1, no left-to-right asymmetry wasfound (Fig. 4).

There was no correlation between rScO2 and mean arterialblood pressure or cFTOE and mean arterial blood pressure(r $ 0.05 and r $ 0.04, respectively).

DISCUSSION

The present study shows a symmetrical cerebral oxygen-ation of the immature brain during stable arterial oxygensaturation within expected limits (2) during the first 3 d in thevery preterm infant, as indicated by the similar values ofNIRS-monitored left and right fronto-parietal rScO2, althoughour small longitudinal study is showing a slight tendency forhigher rScO2 values at the right fronto-parietal position atday 3. This pattern changes during an unstable arterial oxy-genation pattern with substantial drops of SaO2 with or with-out subsequent hyperoxemia, when extra oxygen was addedfor a quick recovery of arterial saturation. Then differencesbetween left and right SaO2 values up to more than 10% couldbe detected. Mostly a symmetrical cerebral oxygenation pat-tern reappeared when arterial saturation remained stable andwithin normal limits for another 10–15 min.

These results are important when one relies on NIRS-determined cerebral oxygenation using rScO2. We assume thatthe difference between left and right rScO2 values during theseunstable arterial saturations was not an artifact but indeedindicate an uneven cerebral oxygenation in those regions ofthe brain from where the rScO2 is derived. We can onlyspeculate what the reasons are for this apparent uneven oxy-genation of the brain, in particular during unstable arterialsaturations. Despite the findings of Chiron et al. (12) whoreported a functional dominance of the right brain hemispherein the young infant and making it conceivable that duringrecovery from an arterial saturation drop the right hemisphericoxygenation should recover more quickly than the oxygen-ation of the left hemisphere, we could not confirm this. Asclearly indicated by the Bland-Altman plots (Fig. 3), nopreference for the right or left measurement side was detected

Figure 2. (a) Representative pattern of 2 h of left (blue line) and of right(green line) regional cerebral oxygen saturation (rScO2) during all systemicarterial oxygen saturations (SaO2; orange line); (b) left and right rScO2

patterns during stable SaO2. Note differences in left and right rScO2 valuesduring substantial decreases in SaO2.

Figure 3. Limits of agreement accordingto Bland and Altman (16) in 36 infantsbetween left and right near-infrared spec-troscopy (NIRS)-monitored regional cere-bral oxygen saturation (rScO2) (a) and ofNIRS-monitored cerebral fractional tissueoxygen extraction (cFTOE) (b) obtainedwhen all simultaneously monitored sys-temic oxygen saturations (SaO2s) were in-cluded; (c) and (d) obtained when onlyrScO2 and cFTOE determinations were in-cluded during stable SaO2s within the nor-mal range (p # 0.05).

228 LEMMERS AND VAN BEL

Lemmers P, vanBel F, Ped Res(2009)

Purpose: To determine if cerebraloximetry is symmetrical

Results: Duringstable andnormalarterial saturations, there wereonlyminor differences in rScO2values.

During periods ofunstable saturation,<85% and>98%, transient differencesin rScO2valuesof~10%were seenbetween RandL.

What rScO2 values injure the brain?

• Mitochondrial damage in CA1 region ofhippocampus innewborn pigletssubjected togradedanoxia. Hou Xetal. ,Physiol Meas 2007rScO2<40%

• Neworworse ischemia onMRI in infants with hypoplastic leftheartsyndrome (HLHS).DentCetal. , JThorac Cardiovasc Surg 2002

rScO2<45%for>180 minutes

• Functional impairments innewborn piglets. Kurth, Ped Res 2007

rScO2 ranging 33-44%

• Abnormal high energyphosphates measured byMRI spectroscopy inbrainsofnewborn piglets. (Kusaka T, Ped Res 2009)

rScO2<40%

Target rScO2 ranges for newborns

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Dix etal., Pediatr Res(2014);Alderliesten etal., Pediatr Res2015

Safezone

Dangerzone

What can you do if the rScO2 is abnormal?

Ifcerebralsaturationistoolow:

• Hypocarbia (decreaseventilation)

• Hypotension(treatwithfluidorinotropes)

• Anemia(givepackedredbloodcelltransfusion)

• Lowarterialsaturation(increaseFiO2)

Ifcerebralsaturationistoohigh:

• Supranormal arterialsaturation(weanFiO2)

• Hypercarbia (increaseventilation)

Two-site NIRS monitoring

12

Cerebral and Mesenteric Sensor Application

Recommend placement of the hydrocolloid adhesive-backed NIRS sensor directly onto a trimmed Mepitel (MoInlycke) or other translucent skin dressing. Place the sensor with skin dressing onto the central forehead of the infant to assess cerebral oxygen saturation levels. Place a second NIRS sensor with skin dressing on the infant’s left-lower abdominal quadrant.for monitoring of mesenteric saturation levels. A central infra-umbilical location is also acceptable for sensor placement. The sensors should be plugged into the correct ports on the amplifier box (port 1 for cerebral monitoring and port 2 for mesenteric saturation monitoring). Check to make sure that signal strength bars are green. If in study mode, the INVOS monitor will not display numeric values.

NIRS sensor on forehead with CPAP in place Mesenteric NIRS sensor over Mepitel dressing

Once monitoring is set-up in study mode, NIRS values are obscured to blind clinicians.

Renal/FlankCerebral

Renal sensor onposterior flankbelowcostal marginandabove iliaccrest(T10-L2)

Cerebral sensor canbeplaced on rightor left sideof forehead

Mesenteric or Splanchnic saturation monitoring

12

Cerebral and Mesenteric Sensor Application

Recommend placement of the hydrocolloid adhesive-backed NIRS sensor directly onto a trimmed Mepitel (MoInlycke) or other translucent skin dressing. Place the sensor with skin dressing onto the central forehead of the infant to assess cerebral oxygen saturation levels. Place a second NIRS sensor with skin dressing on the infant’s left-lower abdominal quadrant.for monitoring of mesenteric saturation levels. A central infra-umbilical location is also acceptable for sensor placement. The sensors should be plugged into the correct ports on the amplifier box (port 1 for cerebral monitoring and port 2 for mesenteric saturation monitoring). Check to make sure that signal strength bars are green. If in study mode, the INVOS monitor will not display numeric values.

NIRS sensor on forehead with CPAP in place Mesenteric NIRS sensor over Mepitel dressing

Once monitoring is set-up in study mode, NIRS values are obscured to blind clinicians.

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NIRS Devices

Monitor SpecificationsAbsolute Tissue Oxygen Saturation Range: 0 to 99%Dimensions: 29.7 cm (11.7 in) X 32.5 cm (12.8 in) X 17.0 cm (6.7 in)Weight: 6.0 kg (13.3 lbs)

Desaturation events may defy logic, they don’t have to defy detection.

CASMED reserves the right to make changes to this sheet and the product at any time without notice. All rights reserved. CASMED, FORE-SIGHT and FORE-SIGHT ELITE are registered trademarks of CAS Medical Systems, Inc.All other trademarks belong to the companies indicated. U.S. Patents information at www.casmed.com/patents

ISO 13485 Certificate Number FM 72259

44 East Industrial Road, Branford, CT 06405 USA 800.227.4414 | www.casmed.com

Call our Customer Service toll-free number 800.227.4414 to contact your local sales representative.

Experience the enhanced performance and ease of use with FORE-SIGHT ELITE to optimize brain protection

f r o m

First and only FDA cleared tissue oximeter utilizing a 5th wavelength of near-infrared light to reduce patient variability

Enhanced FORE-SIGHT algorithm improves accuracy to unprecedented levels (3.05% Arms)1

Eliminates the need for pre-induction baseline reading

Detects otherwise unnoticed cerebral desaturation events

Wide range of connectivity options with VGA output, Philips IntelliBridge, and EMR Systems

Large SensorP/N: 01-07-2103 (20 sensors/case)Adult Cerebral: ≥ 40kg

Preamp CableP/N: 01-06-3100

21-05-0240 Rev 04

MarkedProduct is

1) MacLeod D, Ikeda K, Cheng C, Shaw A. Validation of the next generation FORE-SIGHT ELITE Tissue Oximeter for adult cerebral tissue oxygen saturation. Anesth Analg 2013;116(SCA Suppl):1-182,#40

SenSmart x-100,Nonin

Fore-sight,Casmed

INVOS5100C,Somanetics/Medtronic

NIRS Sensors

Articles Dix et al.

used NIRS devices in the NICU—the INVOS 5100C (Covidien), the Equanox model 7600, and the Fore-Sight systems—were compared.

The INVOS 5100C (Covidien) sensors use light-emitting diodes to emit near-infrared light of two wavelengths (730 and 810 nm). The nature and quantity of the recaptured near-infrared light reflects the amount of HHb and O2Hb, used to calculate rScO2. Two detectors are located next to the light-emitting diodes. By subtracting the shal-low (shorter) signal from the deeper (further) signal, surface inter-ference contamination is minimized (31,32). Clinical applicability of the INVOS device in neonates has been researched (33). The INVOS 5100C (Covidien) can be used with three different sensors: the adult (SomaSensor SAFB-SM), pediatric (SomaSensor SPFB), and neonatal sensor (Oxyalert CNN). As the adult sensor has been exclusively used at the Wilhelmina Children’s Hospital in the clinical setting, this sen-sor serves as reference measurement.

The Equanox model 7600 uses two light-emitting diodes (Classic Sensor 8000CA), sending out a near-infrared signal composed of three wavelengths (730, 810, and 880 nm). The two light-emitting diodes are in the middle of the sensor, flanked by two photo diodes to capture the reflected light. Double detectors reduce intervening tissue and surface effects. At the time of the study, no neonatal sensor for the Equanox device was available. The Equanox device has thus far only one (adult) sensor.

The Fore-Sight tissue oximeter and its neonatal sensor (small sen-sor) use four different wavelengths in the near-infrared light spectrum (from 670–780–805–850 nm). One light emitting source is placed next to an absorbing diode. An overview of the different devices and their sensors is shown in Table 4.

Study DesignFive different NIRS sensors from the three NIRS devices were com-pared (Figure 4). Two sensors at the time were applied to the fronto-parietal part of the head of the neonate, one on each side symmetri-cally. Sensors were fixated with an opaque elastic bandage to shield the optodes from ambient light. After a period of at least 1 h, sensors were switched to the contralateral side to collect two periods of 60 min of a

stable clinical episode, without interference due to, for example, feed-ing or care. The INVOS (Covidien) adult sensor was used as refer-ence measurement. However, in the course of this research, a practical limitation occurred in comparing the Equanox sensor to the INVOS (Covidien) adult sensor. Strong interference between the two sensors resulted in unreliable results. We therefore adjusted the study design and compared the Equanox sensor with the Fore-Sight neonatal sen-sor, where the interference problem did not occur. The resulting com-binations were as follows:

• INVOS (Covidien) adult sensor (SomaSensor SAFB-SM) vs. INVOS (Covidien) neonatal sensor (Oxyalert CNN)

• INVOS (Covidien) adult sensor (SomaSensor SAFB-SM) vs. INVOS (Covidien) Somanetics pediatric sensor (SomaSensor SPFB)

• INVOS (Covidien) adult sensor ((SomaSensor SAFB-SM) vs. Fore-Sight neonatal sensor (small sensor)

• Equanox sensor (Classic Sensor 8000CA) vs. Fore-Sight neona-tal sensor (small sensor)

To correct for the 7% difference between left and right positions, we measured both the devices bilaterally resulting in two measuring periods (34). Of the 55 included neonates, 10 resulted in only one monitoring period of an hour. In our experience, it usually takes 5 min to produce a reliable signal after application. We therefore did not include the first 5 min into the analysis of the results. Signal Base (a program especially designed at the Wilhelmina Children’s Hospital for NIRS signal analysis) was used to convert and to analyze the obtained rScO2 signals.

Statistical AnalysisData were summarized as mean values ± SD or as median values and ranges where appropriate. Simple linear regression analysis was used to analyze the correlation between the different obtained rScO2 signals. Bland–Altman statistics compares the difference between the signals with the average rScO2 (35). Representative rScO2 signals were converted in median values with a sampling rate of one value per minute, because the different NIRS devices use different sampling rates and to exclude the influence of ‘0’-values (artifacts). Sixty suc-cessive values of each sensor (and if representative of both sides) were analyzed with the Signal Base program. No signals were removed or given less weight during the calculations. We used SPSS 17.0 (SPSS, Chicago, IL) for statistical analysis.

REFERENCES1. Wolf M, Greisen G. Advances in near-infrared spectroscopy to study the

brain of the preterm and term neonate. Clin Perinatol 2009;36:807–34, vi.2. van Bel F, Lemmers P, Naulaers G. Monitoring neonatal regional cere-

bral oxygen saturation in clinical practice: value and pitfalls. Neonatology 2008;94:237–44.

3. Naulaers G, Meyns B, Miserez M, et al. Use of tissue oxygenation index and fractional tissue oxygen extraction as non-invasive parameters for cerebral oxygenation. A validation study in piglets. Neonatology 2007;92:120–6.

4. Nagdyman N, Fleck T, Schubert S, et al. Comparison between cerebral tis-sue oxygenation index measured by near-infrared spectroscopy and venous jugular bulb saturation in children. Intensive Care Med 2005;31:846–50.

5. Weiss M, Dullenkopf A, Kolarova A, Schulz G, Frey B, Baenziger O. Near-infrared spectroscopic cerebral oxygenation reading in neonates and infants is associated with central venous oxygen saturation. Paediatr Anaesth 2005;15:102–9.

6. Yoshitani K, Kawaguchi M, Tatsumi K, Kitaguchi K, Furuya H. A compari-son of the INVOS 4100 and the NIRO 300 near-infrared spectrophotom-eters. Anesth Analg 2002;94:586–90.

7. Greisen G. Is near-infrared spectroscopy living up to its promises? Semin Fetal Neonatal Med 2006;11:498–502.

8. Petrova A, Mehta R. Near-infrared spectroscopy in the detection of regional tissue oxygenation during hypoxic events in preterm infants undergoing critical care. Pediatr Crit Care Med 2006;7:449–54.

9. Toet MC, Lemmers PM. Brain monitoring in neonates. Early Hum Dev 2009;85:77–84.

Table 4. NIRS devices and sensors

NIRS devices Sensors

INVOS oximetera Small adult SomaSensor (SAFB-SM) (standard)

Pediatric SomaSensor (SPFB)

OxyAlert Neonatal Sensor (CNN)

Fore-Sight oximeterb Neonatal Sensor (small sensor)

Equanox model 7600c Adult sensor (Classic Sensor 8000 CA)

NIRS, near-infrared spectroscopy.aINVOS 5100C (Covidien). bFore-Sight (CAS Medical Systems). cEquanox model 7600 (NONIN Medical).

Figure 4. The different NIRS sensors used for comparison. (a) INVOS adult sensor (SomaSensor SAFB-SM) (Covidien). (b) INVOS neonatal sensor (Oxyalert CNN) (Covidien). (c) INVOS pediatric sensor (SomaSensor SPFB) (Covidien). (d) Fore-Sight neonatal sensor (small sensor) (CAS Medical Systems). (e) Equanox sensor (Classic Sensor 8000CA) (NONIN Medical).

a b c d e

562 Pediatric RESEARCH Volume 74 | Number 5 | November 2013 Copyright © 2013 International Pediatric Research Foundation, Inc.

a.INVOSAdultsensor,Covidien,2wavelengthsb. INVOSneonatalsensor,Covidienc. INVOSpediatricsensor,Covidiend. Fore-sightneonatalsensor,CASMed,5wavelengthse. Equanox sensor,NONIN,4wavelengths

Sensor application procedure

1. RecommendplaceNIRSsensorontoMepitel orothertranslucentskindressingpositioned.Donotapplypressure(e.g.headbands,wrap,tape).

2. Makesuresignalstrengthbarisgreen

3. Checkforerythemaorirritationofskinaroundthesensoratleastevery24hours.Avoidliftingupsensorunlessremoving.

4. Sensorinstructionsstateleaveinplacefor48hourshoweverwekeepinplacefor4-7days.

5. Useadhesiveremoverorwarmmoistclothtoremove.

Who may benefit from NIRS monitoring

§ Preterminfants<29weeksgestation

§ InfantswithsuspectedhemodynamicallysignificantPDA

§ Hypoxicischemicencephalopathy

§ GradeIII/IVintraventricular hemorrhage

§ ComplexCongenitalheartdisease

§ Congenitaldiaphragmatichernia

§ Criticallyillinfantswithhemodynamicinstability(pre-ECMOorECMO)

Hypocarbia during mechanical ventilationArtificial Ventilation can influence cerebral Oxygenation

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pCO2 (mmHg)

♀ 26 4/7 wks; 925 g; SMIV; chorioamnionitis; day 1;

rScO2

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Change in rScO2 and FTOE with red blood cell transfusion

Although NIRS seems promising for assessing splanchnic ox-ygen saturation, study-specific, device-specific, and location-specific characteristics may interfere with the reliability of themeasurements [21]. Schat et al. monitored simultaneously sRSO2

over the liver and infra-umbilical regions in preterm neonateswith suspect or proven NEC. Although median sRSO2 values overthe liver (51e62%) were not significantly different from thosemeasured in the infra-umbilical region (49e56%), values werehighly variable in time with poor correlation between sites. Largergroups of patients are required to determine the potential valueof sRSO2 to predict the onset and course of NEC in preterminfants.

5.13. NIRS as a biomarker for need for red blood cell transfusions(RBCT) and response to RBCT

Several studies have reported a temporal association betweenRBCTs and NEC in preterm neonates; this has been refuted byothers [19,62]. These conflicting reports pose a dilemma for neo-natologists in determining the need for RBCTs, predicting risk forNEC following transfusion, and decision to feed in the peri-RBCTperiod. An improvement in cRSO2, sRSO2, and rRSO2 and a reduc-tion in cFTOE have been reported following RBCT in small numbersof preterm infants [19] (Fig. 5). Some investigators reported lack ofcorrelation of pre-RBCT hematocrit with cRSO2 and sRSO2, sug-gesting that hematocrit level alone is a poor predictor of tissueoxygenation. Van Hoften et al. reported that cRSO2 may be at riskwhen hemoglobin levels decrease to <9.7 g/dL [63]. A significantimprovement in cRSO2, pRSO2, perfusion, and symptoms of anemiawas described following transfusion in infants with cRSO2 <55%compared to infants with cRSO2 !55% [64]. Symptomatic preterminfants with anemia were reported to have higher peripheral FTOE

Fig. 4. Daily mean splanchnic regional saturation of oxygen (sRSO2) ± SD. demon-strating interindividual daily variability at for two gestational age groups. n ¼ 6 foreach GA group. *Significant difference from 32 to 33 weeks (P < 0.05). (Adapted withpermission by Macmillan Publishers from: McNeill S, Gatenby JC, McElroy S, Engel-hardt B. Normal cerebral, renal and abdominal regional oxygen saturations using near-infrared spectroscopy in preterm infants. J Perinatol 2011;31:51e7.)

Fig. 5. Profiles of splanchnic and cerebral oxygenation during transfusion. Red cross-hatched boxes between vertical blue lines represent red blood cell transfusion (RBCT). On the x-axis, ‘0’ represents time of start of RBCT, ‘e12’ to ‘0’ represents 12 h pre-RBCT, ‘0’ to ‘3’ represents duration of RBCT and ‘4’ to ‘26’ represents 24 h post RBCT. Panels present data for(a) Splanchnic regional oxygen saturation (sRSO2, %), (b) Splanchnic fractional tissue oxygen extraction ratio (sFTOE), (c) cerebral regional oxygen saturation (cRSO2, %), and (d)cerebral fractional tissue oxygen extraction ratio (cFTOE). (Adapted with permission by IM Publications from Sood BG, Cortez J, McLaughlin KL, et al. Near infrared spectroscopy as abiomarker for necrotizing enterocolitis following red blood cell transfusion. J Near InfraRed Spectrosc 2014;22:375e88.)

B.G. Sood et al. / Seminars in Fetal & Neonatal Medicine 20 (2015) 164e172 169

Downloaded from ClinicalKey.com at Stanford University June 08, 2016.For personal use only. No other uses without permission. Copyright ©2016. Elsevier Inc. All rights reserved.

Sood Betal.,J NearInfraRed Spectrosc (2014)

ScO2increasesandFTOEdecreasesfollowingtransfusioninpreterminfants.

A poorcorrelationofpre-transfusionhematocritwithrScO2isseensuggestingthathematocritaloneisapoorpredictoroftissueoxygenation.

rScO2,perfusionandsymptomsofanemiaimproveininfantswithrScO2<55%butnotininfantswithrScO2≥55%

rScO2orFTOEmaybebetterindicatorsofneedfortransfusion

Hypotension in preterm infants

Objective: Tocompareneurodevelopmental(ND)outcome,meanarterial BP,andrScO2betweenneonatestreatedforlowmeanarterialpressure(MAP)andcontrols

Results:Infantstreated forlowMAPspentmoretimewithMAP< gestationalage thancontrols(9versus0%,p<0.001)buttherewerenodifferencesinNDoutcomeorrScO2

rSO2<50%for>10%timewasassociatedwithlowerNDoutcome

Conclusion:ThissuggeststhatrScO2isasurrogatemarkerforcerebralbloodflowandcouldbeusedinhypotensiontreatmentprotocols.

Alderliesten T etal.,J Pediatr (2014)

NIRS and the PDA

AhemodynamicallysignificantPDAisassociatedwithincreasedpulmonarybloodflowanddecreasedsystemicbloodflowduetoductalsteal.

Thisisassociatedwithlowerbloodpressureaswellasdecreasedbrainandotherorganperfusion.

NIRShasbeenusedtostudycerebralandsomaticeffectsofPDAaswellasresponsetomedicalandsurgicaltreatment.

rScO2 and hemodynamically significant PDA

Variable hsPDA (n=20) Controls (n=20) PvalueMeanbloodpressure(mmHg) 33 38 <0.05MeanrScO2(%) 629 7210 <0.05FTOE 0.340.1 0.250.1 <0.05

Lemmers Petal., Pediatrics (2008)

Conclusions: IninfantswithPDA,meanbloodpressureandcerebralsaturationwerelowerandFTOEhighercomparedwithcontrolinfantswithoutaPDA.

Renal saturation and hemodynamically significant PDA

Variable hsPDA (n=21) NoPDA(n=14) PvalueRenalsaturation (%) 613 703 0.03

ChockVYet al., E-PAS2015:1569.508

Lowrenal saturation isassociatedwith hs PDA.Also see increasedvariability of tracing.

Renal saturation <66% wasassociatedwith hsPDA with sensitivity of81%andspecificity of77%, AUC =0.786,p<0.0001.

Is the PDA significant in this infant?

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What about the PDA in this infant?

.

NIRS and response to medical management of PDA

Lemmers PMAet al., Pediatrics(2008)

Cerebral saturation (blue) andmeanblood pressure in infant with PDAbeingtreated with indomethacin.

rScO2 isextremely low withPDA anddecreases with eachdose of indomethacin.

Median rScOs forbabies with PDA(white bars) andcontrols (blackbars).

rScO2returned tonormal valuesafter treatment.

Renal saturation changes with medical management

BeforeTreatment:Renalsatssignificantlydepressedatbaselinewithextremevariability

After Treatment:Renalsatshigherwithlessvariability

CerebralautoregulationBrainmaintainsconstantperfusionpressuredespitefluctuationsinsystemicbloodpressure

ImpairedcerebralautoregulationPressurepassivecirculationMeasuredasconcordance(r>0.5)betweenmeanarterial bloodpressure(MAP)andrSO2

• Common inpreterm infants. Souletal. ,Pediatr Res 2007

• Associated with mortality, severe IVH/PVL. Tsuji etal. , Pediatrics 2000

PDA and cerebral autoregulation

IntactAutoregulation

ImpairedAutoregulation

Concordancebetween MAP andrSO2, r=0.82

ChockVYet al.,JPediatr 2012

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PDA and loss of cerebral autoregulation

ChockVYet al.,JPediatr 2012

*p=0.04

N=28 VLBWPPI=PressurePassivityIndex

Average PPIininfantsfollowingPDAligationisincreasedfor2hoursandthennormalizesby6hours.

Use of cerebral oximetry to predict outcome in HIE

NIRS, aEEG, hypothermia, and outcome Articlesat admission was not different between infants with favorable outcome and infants with adverse outcome, and all had a core temperature of 33.5 °C at 6 h of life. Table 1 provides the patient characteristics of favorable and adverse outcome groups. There were no significant differences between the groups, except for the Thompson score on admission and presence of lesions on magnetic resonance imaging (MRI). The MRI scores of infants with adverse outcome were significantly higher com-pared with the favorable outcome group (median (range) 6 (3–10) vs. 2 (0–7), P < 0.001). MRI was not performed in seven infants of the adverse outcome group, as they were too unstable to be transported to the MRI unit and died before the fourth day after birth. These infants had extensive abnormali-ties on sequential cranial ultrasound examinations with inac-tive aEEG recordings and/or seizures that were unresponsive to several antiepileptic drugs (confirmed with (repeated) stan-dard EEG examinations). In seven of the 12 infants who died, permission for postmortem investigation was obtained. All showed severe generalized brain damage (extensive hypoxic–ischemic brain injury) with histological signs of cell death and cytotoxic edema.

NIRS and aEEG PatternsAt admission, before starting total body cooling, rScO2 values were not different between the groups (mean ± SD: 63 ± 10 vs. 68 ± 14% in the adverse and favorable outcome group, respec-tively). rScO2 values for both outcome groups increased over postnatal age, but this increase was modest in the group with favorable outcome and normalized after reaching normal body temperature again at 84 h of age. In the group with an adverse outcome, rScO2 reached high values from 24 h of life onward (Figure 1a). rScO2 values were significantly higher in this group as compared with the favorable outcome group at 24, 36, 48, and 84 h postnatally (mean ± SD: 82 ± 7 vs. 72 ± 9%, 83 ± 9 vs. 75 ± 8%, 83 ± 10 vs. 76 ± 8%, 79 ± 10 vs. 72 ± 9%, P < 0.001, P < 0.01, P < 0.05, and P < 0.02, respectively). The mean cFTOE value mirrored the patterns of rScO2 of both groups and became very low from 24 h of age onward in the adverse outcome group as compared with the favorable outcome group

Table 1. Important patient characteristics

Characteristic

Favorable outcome

Adverse outcome

P valuen = 26 n = 13

Gestational age, weeks (mean ± SD)

40.32 ± 1.50 40.21 ± 1.26 ns

Birth weight, grams (mean ± SD)

3,744 ± 644 3,831 ± 603 ns

Gender ns

Male (n (%)) 16 (62) 8 (62)

Female (n (%)) 10 (38) 5 (38)

5 min Apgar (median (range)) 3 (1–6) 3 (0–7) ns

First pH (mean ± SD) 6.97 ± 0.2 6.90 ± 0.3 ns

First base excess (mean ± SD) −16.4 ± 6.4 −13.1 ± 8.3 ns

Lactate (mean ± SD) 14.3 ± 6.9 12.1 ± 8.5 ns

Ventilation support (n (%)) 23 (88) 13 (100) ns

Inotropics (n (%)) 21 (80) 12 (92) ns

Nitric oxide ventilation (n (%)) 10 (38) 3 (23) ns

PPHN (n (%)) 10 (38) 4 (30) ns

Seizures (n (%)) 15 (59) 13 (100) ns

Thompson score (median (range))

10 (7–13) 12 (8–14) 0.04

CUS

Increased periventricular echogenicity (n (%))

14 (53) 5 (38) ns

Subcortical densities (n (%)) 15 (57) 8 (61) ns

Basal ganglia/thalamus (n (%)) 12 (46) 9 (69) ns

MRI n = 26 n = 6

Total MR score (median (range)) 2 (0–7) 6 (3–10) <0.001

CUS, cranial ultrasound; MRI, magnetic resonance imaging; ns, not significant; PPHN, persistent pulmonary hypertension of the neonate.

Figure 1. (a) Regional cerebral oxygen saturation (rScO2) (%) and (b) cerebral fractional tissue oxygen extraction (cFTOE) (mean and 95% confidence interval) of neonates with hypoxic–ischemic encephalopathy (HIE) with favorable outcome (solid line) and adverse outcome (death or adverse neurodevelopmental outcome at 18 mo of life (dashed line) during the first 84 h after birth (*P < 0.001 (24 h), P < 0.01 (36 h), P < 0.05 (48 h), P < 0.02 (84 h); and P < 0.001 (24 h), P < 0.02 (36 h), P < 0.02 (84 h), respectively)).

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Copyright © 2013 International Pediatric Research Foundation, Inc. Volume 74 | Number 2 | August 2013 Pediatric RESEARCH 181

Lemmers P, etal. Ped Res(2013)

Cerebral saturation(rScO2)ishigher andfractionaltissueoxygenextraction(FTOE)islower by24hoursandonwardinneonateswithHIEwithadverseoutcomes

FTOE=SaO2– rScO2/SaO2

HighrScO2andlowFTOEreflectssecondaryenergy failurewithreducedoxygenconsumptionbyseverelyinjuredneuronalcells

Solid line =good outcomeDashed line=pooroutcome

High rScO2 at 24 hours is associated with poor neurodevelopmental outcome NIRS Monitoring in Congenital Heart Disease

§ Whatcanpre-operativeNIRSmonitoringtellus?

§ IndirectmeasureofQp:Qs• Regardless of systemic oxygenation (SpO2), cerebral or somaticoxygenation maybe inadequate

• HowdoNIRSvalues correlate with other indicators ofpoor systemicperfusion (e.g.high lactate,prolonged capillary refill, coldextremities, low urine output)

§ Effectivenessorneedforadditionalnterventions• Ventilator changes, diuretics, change inPGEdose, need forbloodtransfusion, earlier surgical intervention

Infant with Juxtaductal Aortic Coarctation

SpO2 stable- 95%pre-ductaland71%post-ductal

PGErestarted

Cerebral sats dropped to35-45%

3-dayold31weekinfantwithhypoplastic leftheart

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SpO2 86%

SpO2 99%

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NIRS and Necrotizing Enterocolitis (NEC)

pattern similar to ‘A’ but with relatively higher rsSO2 in thefirst 7 days of life followed by signal dropout on D8–D9(Figure 3e).

On the basis of the patterns observed on hourly rsSO2

recordings, we classified enrolled infants as those withoutfeeding intolerance (n¼ 8), with feeding intolerance(n¼ 8), with clinically diagnosed NEC (n¼ 2) and sepsis(n¼ 1).

Infants without feeding intolerance (n¼ 8)

Clinical characteristics of infants without feeding intoler-ance are presented in Table II. Significant time trends ofmean daily rsSO2 were noted with a decline from D2 to D9followed by an increase to D2 value by D14 (Figure 2b,Table III). Longitudinal data analysis revealed significantlylower rsSO2 during D3–D10 compared to D2 (p5 0.05);rsSO2 during D11–D14 was not different from D2. Meandaily rsSO2 showed a significant correlation with SBP(r2¼70.326, p¼ 0.015) and SaO2 (r2¼ 0.226, p¼ 0.018)but not with SD of rsSO2.

Infants with feeding intolerance (n¼ 8)

Clinical characteristics of infants with and without feedingintolerance were comparable (Table II). The feedingprotocol, route, type of milk, and caloric supplementationwere comparable between the two groups. Feeds wereadministered over 30 min to 2.5 h depending on thevolume of feeds and feeding tolerance. The mean+SDage at the onset of feeding intolerance was 7.4+ 2.9 days.The mean+SD duration for which feeds were held was2.1+ 1.1 days (range 1.1–4.8 days). Abdominal radio-graphs (AXR) were obtained in two infants; both wereunremarkable. The mean+SD volume per feed at 14days, 5.8+ 6.0 ml, was significantly lower in infants withfeeding intolerance (p¼ 0.000).

Significant time trends of mean daily rsSO2 were notedwith decline for the first 10 days followed by an increase(Figure 2b, Table III). Longitudinal data analysis revealedthat rsSO2 during D3–D14 was significantly lower when

compared to D2 (p5 0.01). Mean daily rsSO2 showed asignificant correlation with SBP (r2¼70.219, p¼ 0.029)and SD of mean daily rsSO2 (r2¼ 0.411, p¼ 0.000) but notwith SaO2.

On adjusted mixed model analyses, daily mean rsSO2

was significantly lower in infants with feeding intolerancewhen compared to those without (p¼ 0.0043), and therewas a significant difference between the groups over time(p5 0.05) with significant differences on days 5, 9, 10, 12,and 13 (p5 0.05) (approximate t-test generated frommixed models). GA, gender, hemoglobin, SBP, and SaO2

were not significant predictors of rsSO2.

Infants with clinically diagnosed NEC (n¼ 2)

Two infants (twins delivered at 24 weeks GA) werediagnosed with NEC during the study. The first, a femaleinfant, required PPV from birth. Umbilical catheters werepresent for the first 4 days. Vasopressors were adminis-tered till 23 h of age. A bile stained aspirate was recordedon D2; the abdominal examination was unremarkable,and an AXR showed minimal bowel gas. On D7, ibu-profen was initiated for treatment of patent ductusarteriosus (PDA) and trophic feeds were initiated withbreast milk. A second course of ibuprofen was initiated onD10. On D11, the infant had worsening respiratory andmetabolic acidosis, hyperglycemia, bile-stained emesisand greenish-blue discoloration of the abdomen. AnAXR revealed paucity of bowel gas without evidence offree air, portal venous gas or pneumatosis. Over the nextfew hours, the infant needed escalating ventilatory andhemodynamic support and the abdomen became dis-tended and tender. The infant was transferred out to theneighboring Children’s Hospital where peritoneal drainswere placed.

Hourly mean rsSO2 and SaO2 for this infant arepresented in Figure 3c. Hourly rsSO2 readings over thefirst 4 days of life were marked by high mean values(450%) and/or exaggerated variability (SD4 24) (‘luxuryperfusion’). Starting on D5, there was an abrupt decreasein rsSO2 accompanied by decrease in variability withprogressively increasing high signal dropout rate despite

Figure 2. Daily mean rsSO2 over the first 14 days of life. Error bars represent+ 1 SD. (a) Data for all 19 infants. (b), dotted line represents

infants without feeding intolerance (n¼8); dashed line represents infants with feeding intolerance (defined as feeds being held for "1 day bythe blinded clinical staff) (n¼ 8); black line represents infants with suspected necrotizing enterocolitis in the first 14 days of life (n¼2).

Neonatal splanchnic tissue oxygenation 577

On adjusted mixed model analyses, rsSO2 was significantlyassociated with postnatal age (p5 0.0001). GA, gender,hemoglobin, SBP, and SaO2 were not significant pre-dictors of rsSO2.

Individual plots of mean hourly rsSO2 readings over thestudy period of all infants were annotated with clinicalevents and inspected closely for systematic trends. Threepatterns were identified:

A. rsSO2 in midrange with robust variability (defined asSD4 5% for this manuscript) (Figure 3a)B. rsSO2 in low range with maintained variability(Figure 3b) andC. Consecutive runs of extremely low rsSO2 for !12 hwith loss of variability (defined for this manuscript as SD"1.0) associated with high signal dropout despite good

sensor placement and preceded (Figure 3c, n¼ 1) orfollowed by a period of very high rsSO2 (Figure 3d,n¼ 1). We have designated periods of extremely lowrsSO2 with loss of variability and high signal drop out as‘abdominal silence’ and extremely high rsSO2 as ‘luxuryperfusion’.

Pattern ‘A’ was predominantly observed in pretermneonates without feeding intolerance (defined for thisstudy as the decision to hold feeds for at least 24 h byclinical staff in the absence of medical or surgical NEC).The most common clinical association with pattern ‘B’ wasthe presence of feeding intolerance. Pattern ‘C’ wasobserved in two infants with clinically diagnosed NEC.Another infant who died of septic shock and disseminatedintravascular coagulation (DIC) on D10 had an rsSO2

Table I. Maternal and neonatal characteristics.

Maternal characteristics, n (%) Neonatal characteristics in first 14 days of life, n (%)

Maternal age, yrs – mean+SD 26+ 6 Gestational age (wks) – mean+SD 28+2

Married 5 (26) Birth weight – mean+SD 1138+ 295

African-American race 18 (95) Male gender 11 (58)Received prenatal care 17 (89) 5-min Apgar "5 3 (16)

Preterm labor 16 (84) Positive pressure ventilation 14 (74)

PROM 10 (53) Umbilical artery catheter 5 (26)

PPROM 3 (16) Vasopressors – yes 2 (11)Clinical chorioamnionitis 3 (16) Caffeine 12 (63)

Maternal PIH 3 (16) PDA 5 (26)

Maternal antibiotics 8 (42) Indomethacin for PDA 1 (5)

Antenatal steroids 12 (63) Received blood transfusion 7 (37)MgSO4 tocolysis 7 (37) Grade III-IV IVH 3 (16)

Indomethacin tocolysis 1 (5) Age at first feed, days 2.7+ 1.8

Vaginal delivery 9 (47) Age at discharge, days – mean+SD 48.5+ 13.6

This table summarizes the maternal and neonatal characteristics of subjects enrolled in the study (n¼19)IVH, intraventricular hemorrhage; MgSO4, magnesium sulfate; PDA, patent ductus arteriosus; PIH, pregnancy-induced hypertension;

PROM, premature rupture of membranes; PPROM, prolonged premature rupture of membranes; SD, standard deviation.

Figure 1. Raw rsSO2 data obtained every 30 s for 24 h in one infant with an unremarkable NICU course.

576 J. Cortez et al.

CortezJetal.,J Matern FetalNeonatalMed (2011)

Splanchnicoximetryismorechallengingduetomarkedvariabilityinreadings(16%)whencomparedtorenal(6%),cerebral(3%)andpulseoximetry(1-2%).

SplanchnicoximetrymayhelpidentifybabieswithNEC.LowrSsO2isseenwithNECandfeedingintoleranceasshownhere.Dotted line=normal,dashed=feedingintolerance,solid=NEC

Can NIRS monitoring improve outcomes?

Prematureinfants

rScO2targetstoimproveoutcomes

Congenitalheartdisease

ManagementofHLHS

Infants enrolled in:

Lyon Madrid

Copenhagen Cork

Utrecht Graz

Milan Cambridge

SafeBoosC II: Phase 2 Study (Randomized)

Avoid: Hyperoxia:rScO2 >85% Hypoxia: rScO2< 55%

(SafeboosC II Group, BMJ 2015)

NIRS- monitored

Standard Treatment

<28 wks GA (n=166)

Sample Size: n=86/80

What could be done?

When cerebral rScO2 is low (<55%), consider:

• Low pCO2 (Increase pCO2)

• hsPDA (Close)

• Hypotension (treat)

• Anemia (Erytrocyte transfusion)

• Low arterial saturation (Increase FiO2)

When cerebral rScO2 is high (>85%), please consider:

• Supranormal Art Sat (Decrease FiO2 if possible)

• Too high pCO2 (Decrease pCO2)

• Low glucose (Treat low blood glucose)

N = 80 GA = 26.8 wks

N = 86 GA = 26.6 wks

p<0.001

(und

er p

repa

ratio

n)

Infants enrolled in:

Lyon Madrid

Copenhagen Cork

Utrecht Graz

Milan Cambridge

SafeBoosC II

81% hrs

36% hrs

Hyperoxia:rScO2 >85% Hypoxia: rScO2<55%

(No NIRS) (Yes NIRS)

(SafeboosC II Group, BMJ 2015)

Hypothesis:Pre-operativeuseofNIRSwouldreducetheneedforinvasivetherapiesincludingcontrolledventilationandinspiredgasmanipulation

Methods:Retrospectivereviewofinfantswhohadstage1palliationforHLHSfrom2000-2006

Historicalcohortfrom2000-2002withoutpre-opNIRSmonitoring(n=47)

NIRScohortfrom2003-2006hadcerebralandsomaticNIRSmeasuresrecordedhourly(n=45)

J

JohnsonBAetal.,AnnThorac Surg (2009)

Use of NIRS in pre-op newborns with HLHS

6/17/16

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NIRS in HLHS - Results

Control (n=47) NIRS(n=45) PvalueIntubatedn(%) 39(83) 27(60) 0.014Inspirednitrogen, n(%) 33(70) 7(16) 0.001Durationnitrogenuse,hours 3939 10 30 0.001Arterial saturation(%) 874.6 91.94.2 0.001Cerebralsaturation(%) 68.05.8Somaticsaturation(%) 70.35.7

HighersystemicsaturationinNIRSmonitoredgroupwasnotassociatedwithhypotension,acidosis,orworsenedrenalfunction.

JohnsonBAetal.,AnnThorac Surg (2009)

NIRS in HLHS - Conclusions

Routineuseofpre-op NIRS-monitoringresultedin:

§ Reducedmechanicalventilation(higherSaO2,lowerPaCO2)

§ Reduceduseofinspiredgases

§ Noimpactonmortalityorlengthofhospitalstay

JohnsonBAetal.,AnnThorac Surg (2009)

Conclusions

§ NIRSmonitoringisausefulnon-invasivemeasureofendorganoxygenationandperfusionprovidingcriticalinformationaboutthebalanceofoxygendeliveryandconsumption.

§ Whiletherearewiderangesonnormalvaluesinnewbornsdependingonthedeviceandsensorused,trendmonitoringprovidescriticalinformationinspecificclinicalscenarios.

§ FurtherstudiesareneededtodetermineifNIRScanimproveimportantpatientoutcomesinnewborninfants.

Thankyou!