**5. Clinical events observed with NIRS**

To further demonstrate the extent of topics and studies, examples of some clinical scenarios are listed. Referenced articles date back to 2000. The articles quoted are found in the bibliography. They are representative of the scope of interest.

#### **5.1 Unstable neonates**

12 Infrared Spectroscopy – Life and Biomedical Sciences

Fig. 2. Two-site NIRS trends from a patient undergoing resuscitation from

changed.(Hoffman et al., 2007)

**4. Splanchnic (gut) NIRS** 

al., 2010, 2011)

suggest that total cardiac output was relatively limited but that the distribution

hypovolemic/septic shock. Early aggressive resuscitation with fluid and epinephrine to normal regional rSO2 values restored urine output. The effect of changes in pCO2 on cerebral blood flow are evident at 0700. The mirror changes in cerebral and somatic rSO2

Monitoring the GI tract as opposed to monitoring the brain or kidneys is more complex since the gut is a hollow or gas and stool filled, moving structure, in close proximity of stomach and bladder, which could affect its position and functioning. Proper probe placement may therefore be a challenge. In addition movements of the baby and pull on electrodes are more likely. A recent small study by Gillam-Krakauer et al. using Doppler confirmed that

McNeill's study of splanchnic/abdominal rSO2 in healthy preterm infants between day 0 and day 21 found that baseline changed over time. Overall abdominal rSO2 values were significantly lower than cerebral and renal values. The baseline increased over time. When comparing patients born at 32 and 33 weeks to those born at 29 and 30 weeks gestation, higher weekly means were observed in the 2nd week of life in the older group. (McNeill et

These changes too may indicate regional developmental maturation. For abdominal rSO2 long- and short-term variability is much higher and exceeds 20%. It may be associated with

splanchnic NIRS reflects bloodflow to the small intestine. (Gillam-Krakauer et al., 2011)

Respiratory distress (Lemmers et al., 2006; Meek et al., 1998)

ECMO (Benni et al., 2005; Rais-Bahrami et al., 2006)

Pediatric Surgery (Dotta et al., 2005)

Cardiac disease pre-, intra, post op (Abdul-Khaliq et al., 2002; Hoffman et al., 2003; Johnson, 2009; Kurth et al., 2001; Li et al., 2008; Redlin et al., 2008; Seri, 2006)

Patent Ductus Arteriosus (Hüning et a., 2008; Keating et al., 2010; Lemmers et al., 2008, 2010; Meier et al., 2006; Underwood et al., 2006, 2007; Vanderhaegen et al., 2008; Zaramella et al., 2006)

CNS abnormalities HIE, PVL, PIH (Caicedo et al., 2011; De Smet et al., 2010; Morren et al., 2003; Munro et al., 2004, 2005; Wolf & Greisen, 2009; Wong et al., 2008)

Greisen & Borch , 2001; Hou et al. 2007; O'Leary et al., 2009; Sorensen & Greisen, 2009; Toet, 2006; van Bel F et al., 2008; Vanderhaegen et al., 2009, 2010; Weiss, 2005; Verhaen et al. , 2010; Wolf & Greisen , 2009)

Mechanical Ventilation (Noone et al., 2003; van Alfen-van der Velden et al., 2006; Verhagen et al., 2010)

Apnea (Payer et al., 2003; Yamamota et al., 2003)

Intensive Care (Limperopoulos et al., 2008)

Resuscitation (Baerts et al., 2010, 2011; Fuchs , 2011)

#### **5.2 Care giving**

Delivery room (Baenziger et al. ; Urlesberger et al., 2010)

Feedings (Baserga et al., 2003; Dave et al., 2008, 2009)

Blood transfusion (Bailey et al., 2010; Dani et al., 2010; Hess, 2010; van Hoften et al., 2010) \*

Head ultrasound (van Alfen-van der Velden et al., 2008, 2009)

Use of Near-Infrared Spectroscopy in the Management of Patients in

studies.

easier:

generally available.

Neonatal Intensive Care Units – An Example of Implementation of a New Technology 15

been affected by coinciding with the era of limited research funding for large clinical

Studies are largely observational either observing a group of patients over time or following changes caused by therapeutic interventions (ECMO, heart surgery, transfusion, medications). Studies for the most part are small in patient numbers and short in time of observation. Study protocols observing the same phenomenon are often distinctly different from each other. Devices used may differ from trial to trial as well. All this can contribute to differences in study results. Due to the differences in study design meta-analysis, as an opportunity to obtain more robust results from a large number of trials and patients, may not be an option. Cerebral NIRS measurements are the most researched and incorporated into daily care. There is some consensus regarding critical lower limits of cerebral oxygenation (Wolf & Greisen, 2009; Wider, 2009). In addition the patient is accepted as his

For the future of NIRS monitoring in the NICU, it may be necessary for another NIH panel to be called to review the existing evidence obtained since the initial group met in 1999 and devise a hopefully low budget strategy to validate NIRS in the NICU further. Larger, randomized trials will be needed. Blinding would not be useful unless normative data is obtained. Unblinded studies would allow interventions based on NIRS measurements and observe possible benefits. An anecdotal example was a rotated ECMO cannula that led to a steep decrease in cerebral r-SO2 with all other vital signs remaining unchanged. The caregivers responded immediately avoiding adverse consequences. Greisen in a paper from November 2011 estimates one needs to study 4000 infants with cerebral oximetry to have the power to detect the reduction of a clinically relevant endpoint, such as death or

In the meantime, NIRS monitors could be further improved to make interpretation of data

While the information gained is tempting, interpretation of data takes experience. NIRS does not stand alone. It needs to be viewed in context of other occurring physiologic changes. Recently data collection and interpretation has been made easier and more precise by the increasing ability to synchronize collection of different data points and thus link NIRS observations, possibly from multiple channels, with vital signs, EEG, interventions, medications, stimulation and care giving events. At this point this technology is not

Eventually more channels to measure greater than 3 sites, allowing for more than one

Once norms are established for cerebral, renal and splanchnic sites, normal limits at each site for different gestational and postnatal ages could be indicated on the monitor. Alarms could signal when a patient's rSO2-c is outside the normal range. Variability could be reported both by percent change and change over time, also possibly in reference to gestational age for the observed organ. Incorporation of the ability for the monitor to calculate physiologic equations like FTOE or cerebral blood flow could give more value to NIRS monitoring.

Will those changes improve life and care in the NICU for patients and staff? Perhaps. Possibly clinicians find themselves confronted by unexpected physiology and new problems

own control, using the NIRS monitor as a trend monitor. (van Bel et al., 2008).

neurodevelopmental handicap, by 20%. (Greisen et al., 2011)

cerebral site plus somatic sites, may be needed.

Kangaroo care (Begum et al., 2008)

Endotracheal tube suctioning (Kohlhauser et al., 2000)

CPAP (Dani et al., 2007; van den Berg et al.,2009, 2010; Zaramella et al., 2006)

Blood draws from umbilical artery catheters (Bray et al., 2003; Hüning et al., 2007; Roll et al., 2006; Schulz et al., 2003) \*\*

Stimuli, Pain (Bartocci et al., 2001, 2006; Holsti et al., 2011; Liao et al., 2010; Ozawa et al., 2010, 2011; Slater et al., 2007)

Posture/Position (Ancora et al., 2009, 2010; Pichler et al., 2001)

NIRS/EEG (van den Berg et al., 2009, 2010)

#### **5.3 Medications**

Caffeine (Tracy et al., 2010)

Dopamine (Wong et al., 2009)

Epinephrine (Pellicer et al., 2005)

Ibuprofen (Bray et al. 2003; Naulaers et al., 2005)

Indomethacin (Dave et al., 2008, 2009; Keating et al., 2010)

Morphine/Midozalam (van Alfen-van der Velden et al., 2006)

Propofol (Vanderhaegen et al.,2009, 2010)

Surfactant (Fahnenstich et al., 1991; van den Berg et al., 2009, 2010)

**\*Blood transfusions** too are a routine part of NICU care. 3 studies found increases in rSO2-c following transfusion, in addition 2 of the authors reported increase in splanchnic oxygenation and lastly one of the studies found increased renal rSO2 as well. These findings are overall encouraging. Dani however questions whether the increases in rSO2 are reflecting benefits or administration of a pro-oxidant. Another author is attempting to identify the need for transfusion by calculating splanchnic-cerebral oxygen ratios. Infants with low ratios pre-transfusion are more likely to improve post-transfusion. (Bailey et al., 2010 ; Dani et al., 2010; Hess, 2010; van Hoften et al., 2010)

**\*\*Blood draws from umbilical artery catheters** decrease rSO2-c. Two reports conflict on whether volume or a rapid draw causes the decrease in rSO2. (Roll et al., 2006; Schulz et al., 2003)

#### **6. Conclusions**

NIRS is a fascinating technology with impressive potential. The opportunities to learn more about physiology and effects of therapy through monitoring with NIRS are limitless.

The literature reporting about NIRS in the clinical setting of the NICU is abundant. However published supporting scientific evidence for the use of NIRS in neonatology has limitations. There are no large multi-center collaborative studies. The advent of NIRS has

Blood draws from umbilical artery catheters (Bray et al., 2003; Hüning et al., 2007; Roll

Stimuli, Pain (Bartocci et al., 2001, 2006; Holsti et al., 2011; Liao et al., 2010; Ozawa et al.,

CPAP (Dani et al., 2007; van den Berg et al.,2009, 2010; Zaramella et al., 2006)

Kangaroo care (Begum et al., 2008)

et al., 2006; Schulz et al., 2003) \*\*

NIRS/EEG (van den Berg et al., 2009, 2010)

Ibuprofen (Bray et al. 2003; Naulaers et al., 2005)

2010 ; Dani et al., 2010; Hess, 2010; van Hoften et al., 2010)

Propofol (Vanderhaegen et al.,2009, 2010)

Indomethacin (Dave et al., 2008, 2009; Keating et al., 2010)

Morphine/Midozalam (van Alfen-van der Velden et al., 2006)

Surfactant (Fahnenstich et al., 1991; van den Berg et al., 2009, 2010)

**\*Blood transfusions** too are a routine part of NICU care. 3 studies found increases in rSO2-c following transfusion, in addition 2 of the authors reported increase in splanchnic oxygenation and lastly one of the studies found increased renal rSO2 as well. These findings are overall encouraging. Dani however questions whether the increases in rSO2 are reflecting benefits or administration of a pro-oxidant. Another author is attempting to identify the need for transfusion by calculating splanchnic-cerebral oxygen ratios. Infants with low ratios pre-transfusion are more likely to improve post-transfusion. (Bailey et al.,

**\*\*Blood draws from umbilical artery catheters** decrease rSO2-c. Two reports conflict on whether volume or a rapid draw causes the decrease in rSO2. (Roll et al., 2006; Schulz et al.,

NIRS is a fascinating technology with impressive potential. The opportunities to learn more

The literature reporting about NIRS in the clinical setting of the NICU is abundant. However published supporting scientific evidence for the use of NIRS in neonatology has limitations. There are no large multi-center collaborative studies. The advent of NIRS has

about physiology and effects of therapy through monitoring with NIRS are limitless.

2010, 2011; Slater et al., 2007)

Caffeine (Tracy et al., 2010) Dopamine (Wong et al., 2009) Epinephrine (Pellicer et al., 2005)

**5.3 Medications** 

2003)

**6. Conclusions** 

Endotracheal tube suctioning (Kohlhauser et al., 2000)

Posture/Position (Ancora et al., 2009, 2010; Pichler et al., 2001)

been affected by coinciding with the era of limited research funding for large clinical studies.

Studies are largely observational either observing a group of patients over time or following changes caused by therapeutic interventions (ECMO, heart surgery, transfusion, medications). Studies for the most part are small in patient numbers and short in time of observation. Study protocols observing the same phenomenon are often distinctly different from each other. Devices used may differ from trial to trial as well. All this can contribute to differences in study results. Due to the differences in study design meta-analysis, as an opportunity to obtain more robust results from a large number of trials and patients, may not be an option. Cerebral NIRS measurements are the most researched and incorporated into daily care. There is some consensus regarding critical lower limits of cerebral oxygenation (Wolf & Greisen, 2009; Wider, 2009). In addition the patient is accepted as his own control, using the NIRS monitor as a trend monitor. (van Bel et al., 2008).

For the future of NIRS monitoring in the NICU, it may be necessary for another NIH panel to be called to review the existing evidence obtained since the initial group met in 1999 and devise a hopefully low budget strategy to validate NIRS in the NICU further. Larger, randomized trials will be needed. Blinding would not be useful unless normative data is obtained. Unblinded studies would allow interventions based on NIRS measurements and observe possible benefits. An anecdotal example was a rotated ECMO cannula that led to a steep decrease in cerebral r-SO2 with all other vital signs remaining unchanged. The caregivers responded immediately avoiding adverse consequences. Greisen in a paper from November 2011 estimates one needs to study 4000 infants with cerebral oximetry to have the power to detect the reduction of a clinically relevant endpoint, such as death or neurodevelopmental handicap, by 20%. (Greisen et al., 2011)

In the meantime, NIRS monitors could be further improved to make interpretation of data easier:

While the information gained is tempting, interpretation of data takes experience. NIRS does not stand alone. It needs to be viewed in context of other occurring physiologic changes. Recently data collection and interpretation has been made easier and more precise by the increasing ability to synchronize collection of different data points and thus link NIRS observations, possibly from multiple channels, with vital signs, EEG, interventions, medications, stimulation and care giving events. At this point this technology is not generally available.

Eventually more channels to measure greater than 3 sites, allowing for more than one cerebral site plus somatic sites, may be needed.

Once norms are established for cerebral, renal and splanchnic sites, normal limits at each site for different gestational and postnatal ages could be indicated on the monitor. Alarms could signal when a patient's rSO2-c is outside the normal range. Variability could be reported both by percent change and change over time, also possibly in reference to gestational age for the observed organ. Incorporation of the ability for the monitor to calculate physiologic equations like FTOE or cerebral blood flow could give more value to NIRS monitoring.

Will those changes improve life and care in the NICU for patients and staff? Perhaps. Possibly clinicians find themselves confronted by unexpected physiology and new problems to solve. Now it is time to prove benefits of using the NIRS technology by decreasing adverse events in day-to-day patient care and improving outcome.

Greisen summarized the current situation in an article published recently:

*"On the one hand, cerebral oximetry can potentially become inexpensive as it is based on technology that can be mass produced. Also, the probe may be miniaturized and integrated with the electronics into a soft 'plaster' that may stick to the skin of the head of tiny infants and need little attention. Solid evidence of benefit to patients will create a large market. Evidence of benefit of an instrument using public domain technology can serve as a platform for healthy competition on user-friendliness and price. On the other hand, what will happen if the clinical use of cerebral oximetry is not developed in a rational, evidence-based format? Then it may become another randomly applied expensive technology. Cerebral oximetry will be supported by anecdotal evidence, expert opinion, active branding and marketing. The consequences include unnecessary disturbances and risks to a very vulnerable group of patients and depletion of scarce healthcare resources".* 

(Greisen et al., 2011)

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In closing, this chapter is not a manual for patient management. It demonstrated the implementation of a new tool as well as the temptations and hurdles faced by investigators and clinicians using a new promising device, which the author herself understands from both observation and personal experience.

## **7. Acknowledgment**

We would like to thank Michelle Carretero for her help with the preparation of this chapter.
