CONTINUOUS MEASUREMENT OF THE FRACTIONAL OXYGEN EXTRACTION WITH NIRS IN PIGLETS.

CONTINUOUS MEASUREMENT OF THE FRACTIONAL OXYGEN EXTRACTION WITH NIRS IN PIGLETS.

Gunnar Naulaers

, Bart Meyns

, Marc Miserez

, Veerle Leunens

, Sabine Van Huffel

, Paul Casaer

, Michael Weindling

and Hugo Devlieger

1

Department of Paediatrics, University Hospital Leuven, Belgium.

2

Department of Cardiovascular Surgery, University Hospital Leuven, Belgium.

3

ESAT-SCD(SISTA), Dept of Electr Engineering, KU Leuven, Belgium

4

Department of Abdominal Surgery, University Hospital Leuven, Belgium.

5

School of Reproductive and Developmental Medicine, University of Liverpool, Neonatal Unit, Liverpool Women’s Hospital, Liverpool, UK

Mailing correspondence (also for reprint requests):

Gunnar Naulaers

Neonatal Intensive Care Unit Department of Paediatrics University Hospital Leuven Herestraat 49

3000 Leuven Belgium.

Tel: 0032/16343211 Fax: 0032/16343209

E-mail: gunnar.naulaers@uz.kuleuven.ac.be

Support Grants:

Research of GN supported by:

Fund for Scientific Research – Flanders (Belgium): Clinical Doctoral Grant

Steunfonds Margeurite-Marie Delacroix ter bescherming van het kind en van personen met een mentale handicap.

Research of SVH supported by:

Research Council KUL: GOA-Mefisto 666, IDO/99/003 (Predictive Computer models for medical classification problems using patient data and expert knowledge

FWO: PhD/postdoc grants, projects, research communities (ICCoS, ANMMM)

Belgian Federal Government: DWTC (IUAP IV-02 (1996- 2001) and IUAP V-22 (2002-

2006): Dynamical Systems and Control: Computation, Identification and Modelling).

ABSTRACT.

Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI),

measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE).

Methods. Six newborn piglets were measured at 33°C, 35°C, and 37°C and in hypocapnia.

Mean arterial blood pressure (MABP), haemoglobin (Hb), peripheral oxygen saturation (SaO

) and PaCO

were measured at each step. Cerebral blood flow (CBF) was measured by injection of coloured microspheres into the left atrium. Jugular bulb oxygen saturation (JVS), cerebral arterial and venous oxygen content (CaO

and CvO

) and FOE were calculated. TOI of the brain was calculated and FTOE was introduced as (SaO

-TOI)/SaO2. The correlation was calculated with an ANCOVA-test.

Results. There was a positive correlation (R = 0,4 and p = 0,011) between TOI and JVS.

Comparing cerebral TOI with JVS by a Bland-Altman plot, there was agreement to ±10%

between 50% and 60%, but cerebral TOI measurements were consistently lower (bias-13.4%).

No correlation was found with CBF, MABP or Hb. There was a positive correlation between PaCO

and cerebral TOI (R=0,24 and p=0,03).

FTOE correlated well with FOE (R = 0,4 and p = 0,016) and there was a negative correlation between FTOE and PaCO

(R = 0,24, p = 0,03). A Bland-Altman plot showed reasonable agreement between 0,39 and 0,50.

Conclusion. The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE respectively.

Descriptor : Cardiovascular : oxygen consumption and delivery

Keywords : near-infrared spectroscopy, neonates, fractional oxygen extraction, cerebral,

metabolism, oxygenation

1. INTRODUCTION.

Measuring cerebral oxygenation continuously is an important step towards understanding and preventing neurological complications in the course of neonatal intensive care. One approach for the evaluation of oxygenation is to measure the balance between oxygen delivery and oxygen consumption. A useful indicator of this balance is the calculation of the fractional oxygen extraction (FOE). We used spatially resolved near-infrared spectroscopy to measure Tissue Oxygenation Index (TOI) as an index of cerebral oxygenation and a new parameter the fractional tissue oxygen extraction (FTOE) as an index of the cerebral fractional oxygen extraction.

2. METHODS.

a. Animal preparation.

Newborn piglets were used. The piglet was fully anaesthetised with halothane and ventilated. Ventilation was started with an extra dead space between the endotracheal tube and the ventilator circuit. Peripheral oxygen saturation, ECG and rectal temperature were measured. Denudation of the right inguinal region was performed for cannulation of the femoral artery. A NIRS optode was placed on the left frontoparietal side and fixed with a running suture. Left thoracotomy was done to insert catheters in the left atrium and the pulmonary artery. A left jugular cut down was performed to place a catheter in the jugular bulb.

b. Experimental procedure.

The experiment was performed in four steps. Firstly, the piglet was further cooled to 33° C

and in the second and third step warmed up to 35°C and 37°C. This is the rewarming

procedure. As a fourth step, the extra dead space was removed to achieve hypocapnia without

change in minute ventilation (hypocapnia procedure). At each step, blood samples were taken from the femoral artery, pulmonary artery and jugular vein. Each blood sample was analysed for PCO

, PO

, pH, Hb and HCO

. At each step, polystyrene microspheres of different colours (white, eosin, blue, violet and yellow) were injected. The microspheres were injected into the left atrium in a volume of 3 ml over 30 seconds. Arterial reference blood was withdrawn during 90 seconds from the aorta at a flow rate of 10 ml/min. The experiment was terminated by the injection of potassium chloride. Afterwards, 1 g tissue samples were isolated from the brain.

Derived parameters of oxygenation.

The following were calculated:

CaO

(arterial blood oxygen content) = (Hb x (S

O2/100) x 1,39) + (P

O2 x 0,00003) CvjO

(jugular venous blood oxygen content) = (Hb x (S

O

/100) x 1,39) + (P

O

x 0,00003)

Cerebral blood flow was determined by means of the coloured microspheres content by the methods described Wieland and colleagues (1).

The balance between OD (oxygen delivery) and CMRO

(oxygen consumption) is shown by the fractional oxygen extraction (FOE):

FOE (fractional oxygen extraction) = (C

O

– C

O

)/C

O

Near-infrared spectroscopy.

The cerebral Tissue Oxygenation Index (TOI) was computed using spatially resolved spectroscopy. Spatially resolved spectroscopy (SRS) is a new near-infrared spectroscopy method that measures cerebral haemoglobin oxygen saturation.

The fractional oxygen extraction is calculated by the following equation :

1. FOE = (CaO

– CvjO

)/ CaO

2. CaO

and C

O

are calculated as followed : CaO

= Hb x (SaO

/100) x 1,39 CvO

= Hb x (SvjO

/100) x 1,39 3. This results in the following equation :

(Hb x (SaO

/100) x 1,39) – (Hb x (SvjO

/100) x 1,39) FOE = ---

(Hb x (SaO

/100) x 1,39)

SaO

– SvjO

= --- SaO

4. Since TOI correlates well with SvjO

and can be measured continuously, substitution of SvjO

by TOI yields :

SaO

– TOI ---

SaO

Which is tentatively called here Fractional Tissue Oxygenation Extraction (FTOE).

Other parameters measured.

The data acquisition system Codas (Dataq Instruments, USA) was used to record the analog signals of mean arterial blood pressure (measured in the iliac artery), ECG, pulse rate and peripheral oxygen saturation with a sampling frequency of 100 Hz. Since the near-infrared spectroscopy measurements are digital with a sampling rate of 6 Hz, they were converted to analog signals by a sample-and-hold function before their introduction in the CODAS system.

Statistics

The relationship between variables was assessed using Pearson’s correlation coefficients

(mean, 95% C.I. and p-value). ANCOVA was used to correct for multiple measurements in

different piglets. ANCOVA was also used to describe the effect of temperature on the different parameters (steps 1-3). Paired t-tests were used to describe the effect of hypocapnia on the different parameters. A p-value of less than 0,05 was considered significant.

Ethical Committee

The animal ethical committee of the KU Leuven approved the study.

3. RESULTS

The full procedure was performed in six piglets. The results of cerebral TOI, cerebral blood flow and cerebral fractional oxygen extraction measurements during temperature rise are presented in table 1.

When temperature rose, there was a decrease in cerebral blood flow and FOE and an increase in jugular venous saturation, although these changes were not significant. There was a significant increase in heart rate.

Jugular venous saturation could only be measured in three of the six piglets during the hypocapnia procedure. There were non-significant decreases in jugular venous saturation, cerebral blood flow and cerebral TOI during hypocapnia.

ANCOVA was used to calculate the correlation and significance because four different

measurements were performed in six different piglets. The results are shown in table 2. There

was a positive correlation between jugular venous saturation and cerebral TOI (R = 0,4 and

p=0,011). This is shown for the different subjects in figure 1. The correlation between

cerebral TOI and mixed venous saturation was also significant (R = 0,27 and p=0,026). There

was no correlation between cerebral TOI and arterial oxygen saturation, cerebral blood flow,

mean arterial blood pressure, haemoglobin or temperature. There was a positive correlation between PaCO

and cerebral TOI (R = 0,24 and p=0,03).

A positive correlation was found between FOE and FTOE (R =0,4 and p = 0,016).

A negative correlation was found between FOE and PaCO

during the rewarming procedure (R = -0,23 and p=0,04). No significant correlation was found between FOE and mean arterial blood pressure, haemoglobin or temperature.

DISCUSSION.

By using spatially resolved spectroscopy with NIRO 300 in this study, we observed a close correlation between cerebral TOI and jugular bulb oxygen saturation in both the rewarming and hypocapnia procedures. Several studies have been performed in humans. Quaresima et al (2) compared TOI with the cerebral venous oxygen saturation, measured by near-infrared spectroscopy (NIRO 300, Hamamatsu), and concluded that TOI reflected mainly the saturation of the intracranial venous compartment of circulation. Different studies with different NIRS instruments also found a good correlation between TOI and jugular bulb oximetry (3-5), although this was not confirmed by others (6-8). One possible explanation for the variation in these findings could be the ratio between the arterial and venous distributions of cerebral blood (9).

We used two models to test the effect of changing cerebral blood flow on TOI. In the

rewarming procedure, normal neurovascular coupling was expected with no change in TOI,

while in the hypocapnia procedure a decrease in TOI was expected.. In our study, a decrease

in cerebral blood flow was noted during rewarming. Skin blood flow was not measured when

a re-warming lamp was used because this method of warming resulted in very hot, even

hyperaemic, skin in the region under the lamp. It is therefore likely that there was a redistribution of blood to this area. This was described by Doering et al who found a decrease in cerebral blood flow after applications of hot packs to both thighs for ten minutes (10).

In this study there was a strongly positive correlation between PaCO

and TOI during both the rewarming and the hypocapnia experiments. This would appear to confirm the importance of taking careful account of PaCO

during ventilation.

Using TOI as a measure of venous oxygen saturation, it is possible to measure the fractional extraction of oxygen continuously. Indeed, by monitoring simultaneously SaO

and TOI, an equivalent measure of FOE, tentatively called here FTOE, can be calculated. This is likely to yield important information about the oxygenation status of the brain because it reflects the balance between oxygen delivery and oxygen consumption. The cerebral fractional tissue oxygen extraction (FTOE) showed a good correlation with FOE. Therefore we can conclude that FTOE can be seen as a trend parameter for FOE. There was a negative correlation between cerebral FOE and PaCO

and this fits well with the observations of other authors describing the negative correlation between PaCO

and FOE (11, 12).

The studies described in this paper have shown that continuous measurement of TOI and

FTOE by near-infrared spectroscopy is possible using spatially resolved spectroscopy and that

measuring FTOE can therefore be used to measure an equivalent of FOE continuously and

non-invasively.. It must be stressed that these can only be used as trends and not as absolute

values of venous oxygen saturation and FOE. Further studies are needed to validate these

findings and to investigate the size of change in these indices that might indicate cerebral

hypoxic damage.

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