clin. phys. Physiol. Meas., 1987, Vol. 8, NO. 3, 249-259. Printed in Great Britain

Clinical comparison of one in nitro and three in-line blood gas Po, Sensors during cardiopulmonary bypass

S J Poslad, D T Pearson and A Murray Regional Medical Physics Department and Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NE7 7DN, England

Received 4 December 1986, in final form 15 April 1987

Abstract. During 17 cardiopulmonary bypass (CPB) operations, arterial PO, measurements were taken at 5 min intervals using four different types of PO, sensor; three in-line (CardioMet-1000, Polytrode, and Gas-Stat) and one blood gas analyser (IL-I 302). Comparisons between sensors were made relative to the CardioMet-1000. The three in-line sensors showed close agreement. The mean and standard deviation of the difference between the Gas-Stat and the CardioMet-1000 was 0.7 t 4.7 kPa, and between the Polytrode and the CardioMet-1000 was - 1.4 4.0 kPa. Agreement between the IL-1302 blood gas analyser and CardioMet-1000 was not as good, the difference being - 7.0 8.6 kPa

1. Introduction

Monitoring of the PO, of arterial blood (P,,o,) is routine during cardiopulmonary bypass (CPB) surgery, providing essential information on the adequacy of oxygen transfer provided by the oxygenator (gas transfer device). Sensors available to measure P,,O, may be divided into two types depending on whether the sensor is situated in vivo (in the cardiopulmonary bypass circuit) or situated in vitro (blood gas analyser). In the latter case, measurement of PO, involves analysis of blood samples withdrawn from the oxygenator circuit. A review of blood gas analysis is given by Hahn (1987).

Although irz vitro Po, analysis is the standard technique used to monitor the arterial Po2 during CPB (Reeder and Hood 1983, Claremont et a1 1984), the intermittent data provided does not allow for adequate control of oxygenation (Pearson et a1 1984). In an attempt to overcome this problem, in-line PO, sensors have recently become available. These sensors are based either on the standard electrochemical cell used in in vitro sensors (Parker eta1 1983), or on an optochemical technique (Lubbers and Opitz 1983). The early studies of P,,o, sensors were inevitably laboratory based (Parker et a1 1983, Reeder and Hood 1983, Claremont et a1 1984) and although such studies were useful, they did not give a full appreciation of how well the sensors would work in clinical practice. More recently comparisons between a single make of in-line sensor and an in citro blood gas analyser have been published (Hill et a1 1984, Claremont and Pagdin 1985, Janssenwillen et a/ 1985). One study compares two i n 4 n e Sensors (Hill et a/ 1985), but an average of only four arterial blood samples were taken during each clinical case.

We report the comparative PO, data from three commercially available makes of in-line Sensor and one in vitro blood gas analyser during 17 CPB operations, with comparative Pa ,o , data recorded every five minutes. The study was specifically designed as a comparative study, and no attempt has been made to determine the absolute accuracy of any device.

249

250

2. Methods

S J Poslad et a f

2.1. Po2 sensors

The three in-line sensors investigated were the CardioMet-1000 (BioMedical Sensors Ltd, High Wycombe, UK), Gas-Stat (Cardiovascular Devices Inc, Irvine, USA) and the Polytrode (Polystan A/S, Copenhagen, Denmark). The in vitro sensor formed part of the IL- 1302 (Instrument Laboratories, Milan, Italy) blood gas analysis (BGA) system.

The sensors in the CardioMet-1000 (CM), Polytrode (PO) and IL-1302 (IL) systems are based on the standard Clark electrochemical cell (Clark 1956). These typically consist of a silver anode and a platinum cathode surrounded by an electrolyte solution and separated from the blood by a gas permeable membrane. This type of sensor operates according to the principle of polarography. When a specific polarising voltage is applied to the cathode with respect to the anode (the reference electrode), O2 molecules are reduced at the cathode. As a result, electrons are supplied by reactions at the anode and a current is generated which is proportional to the rate at which the O2 molecules are reduced. Because the Po, of the blood is proportional to the number of O2 molecules dissolved (Henry’s law), the sensor produces a signal proportional to the PO, of the blood.

The measurement technique used by the remaining PO, system, the Gas-Stat (GS), is based on optical fluorescence. The sensor consists of a fluorescent material deposited on a support. The sensor is surrounded on one side by a contact solution which separates the optical sensor from a gas permeable membrane in an in-line connector in the CPB loop. On the other side the optical sensor is coupled via a fibre optical cable to the main display and processing module. O2 molecules from blood in the loop diffuse across the gas permeable membrane and dissolve in the contact solution in proportion to the Po, of the blood. When light generated in the main display and processing module is conducted to the fluorescent material, molecular excitation occurs and light of a different colour is emitted. The intensity of the emitted light is related to the concentration of dissolved 0,. The emitted light is transported via separate optical fibres back to the main module where its intensity is converted into a digital read-out of P,,o,.

The different in-line devices have different output time constants (table 1). No attempt was made to modify the outputs, this study being concerned with the measurements displayed on the devices during clinical use.

Table 1. Descriptions of the sensors studied

Sensor Sensor name type

CM Electro-

PO Electro-

GS Opto-

IL Electro-

chemical

chemical

chemical

chemical

In-line/ Sensor Connection Calibration Time in vitro position to CPB loop points (kPa) constants

in-line Arterial line, Detachable 0, 21 150 s 90%

in-line Arterial line, Integral 21 60 s 95%

in-line Arterial line Integral IO, 30 3-7 min

post-pump

post-pump

post-pump

arterial sample port

in vino Oxygenator External 0, 12 -

Clinical comparison ojblood gas Po, sensors 25 1 2.2. Measurement and calibration technique

In-line sensors were connected into the CPB loop distal to the arterial blood pump (figure 1). Blood samples for in vitro analysis were taken from the arterial sample port of the oxygenator and from the arterial line (figure 1). Calibration of each sensor was carried out according to the manufacturers' instructions. The calibration data and loop connections for each sensor are summarised in table 1. Calibration of the CM and PO sensors used air (21 kPa Pa,02). The CM also required N z (0 kPa Pa,0,) . Calibration of the GS sensor used special calibration gas mixtures, and these were contained in small gas cylinders within the calibration unit of the instrument. Controls on the CM, PO and GS instruments allowed the output of each device to be set at the calibration PO, value. The CM sensor, unlike the GS or PO sensors, could be removed from the loop to check its calibration without compromising the sterility of the loop or the integrity of the sensor. The IL sensor was calibrated automatically, after every sample at a single point, and every 2 h at 0 and 12 kPa. In addition, once each day a quality control check was performed at 7, 14 and 19 kPa.

The Po2 values measured by the CM, PO and GS were those measured at blood temperature. The IL measured the PO, at 37 "C and corrected the values to blood temperature.

Venous blood

Blood gas analysers

Figure 1. Block diagram showing where the measurements are made.

2.3. Perfitsion technique

The in-line sensors were situated in a standard cardiopulmonary bypass circuit containing a bubble oxygenator, cardiotomy reservoir and roller-type blood pumps.

The perfusion technique involved cooling the blood to between 24 and 28 "C (cooling phase), maintaining the blood at this temperature (hypothermic phase) and rewarming to 37 "C towards the end of CPB (normothermic phase). The blood flow rate was maintained constant at 2.4 I min-' for each m7 of body surface area through the period of CPB. The perfusionist attempted to control manually the arterial PO? and Pco2 to within the physiological limits corresponding to 37 "C (10-14 kPa and 4-6 kPa respectively) according to the technique described by Pearson et al (1986).

252

2.4. Patient groups

Sensors were studied during 17 CPB operations in adult patients having operations for ischaemic or acquired valvular heart disease. Because all sensors were not available simultaneously, patients were divided into two study groups (group A and group B) depending on the sensor comparisons being made. There were I O patients in group A and 9 in group B ; 2 patients being common to both groups.

Patients in group A were studied before those in group B. As these studies were Carried out during an oxygenator evaluation programme, it was not possible to use the same oxygenator throughout both study groups. In group A ten Bentley Bio-10 oxygenators (Bentley Labs, California, USA) were used, while in group B seven Polystan (Polystan A/S, Copenhagen, Denmark) and two Bentley Bio-10 oxygenators were used. The perfusion data from groups A and B are compared in table 2. Both groups had similar patient and perfusion characteristics apart from the P,,o, (determined by the C M sensor). The P a , 0 , was lower for group B than for group A because in group B the bubble oxygenators used enabled the perfusionist to regulate the Pa ,0 , closer to the target levels (Pearson et a1 1986).

S J Poslarl et a1

Table 2. Similarity of groups A and B.

Group A ( N = IO) Group B ( N = 9) Factor Mean +_ SD Mean i SD

Patient surface area (m') 1.77 f 0.78 1.82 k 0.23 Hypothermic temperature ("C) 24 i 2 24 f 1 Blood flow rate ( I min- ') 3.7 k 0.6 Bypass time (min) 101 f 24 100 f 23

Pa.0, CM (kPa) 38 f 15 22 k 16

~

4.0 f 0.5

Arterial pH 7.33 k 0.05 7.35 f 0.03

2.5. Description of'stttrlies

In group A, data from the CardioMet-1000, Gas-Stat, and IL-1302 were compared. For the ten studies, arterial blood gas samples were taken from the arterial sample port of the bubble oxygenator. Blood samples were analysed within 5 min of sampling or held in ice (up to an hour) before the analysis was performed. The measurement process using the in oitro BGA involved temperature correction of the Pa,0, data by the standard formula (NCCLS 1979). In group B, data from the CardioMet-1000 and the Polytrode were compared.

In both groups, all measurements were compared with those from the CardioMet-1000 sensor as this was the sensor in routine use during oxygenator research at Freeman Hospital.

In the two patients who were common to both groups, blood samples were also drawn from the arterial line close to the in-line sensors. Data from these samples were compared with data from the samples obtained from the oxygenator arterial port. This was performed to assess any measurement errors due to streaming of oxygenated blood with inadequate mixing at the arterial sample port (Rithalia et ul 1979).

2.6. Data collection urd analrsis

For those PO, devices which had electrical outputs (CardioMet-0000 and Polytrode), samples of their outputs were automatically collected by computer using a sample interval of 5 s. For the other two types of PO, monitor (Gas-Stat and IL-1302) which had no electrical output, the data were collected manually a t 2.5 min and 5 min intervals respectively. Each alternate

Clinical comparison of blood gas Po2 sensors 253 Gas-Stat measurement was taken simultaneously with a blood sample for IL-1302 measurement.

For quantitative sensor comparisons, only the data taken synchronously with the 5 min blood samples were used.

40-

3. Results

Hypothermia

3.1. Qua1itatii.e comparison of' sensors

In figure 2(a), all the Pa,o, data collected for a typical study in group A are shown. Overall, the two in-line sensors produced a similar trend in Pa,0,. Although the data from the IL-1302 (IL) trended similarly to the two in-line techniques, the Poz obtained from the IL was in general considerably lower than the Po1 obtained from the two in-line monitors, CardioMet- 1000 (CM) and Gas-Stat (GS), throughout CPB.

40. - m 4 a" IL--' '

V .

0

20.

0 4

60 120 Time (min)

Figure 2. Measurements made from two typical patients.

254

In figure 2(b), all the Pa,0, data collected for a typical study in group B are shown. There was generally very good agreement in this group between the two in-line sensors, CM and PO (Polytrode). The faster time response of the PO sensor compared with the CM sensor can be seen. There was a small relatively constant offset between the two sensors which increased at high P,,o, (towards the end of bypass). Similar observations were made in other group B studies.

S J Poslad et al

3.2. Ouerall quantifatiae comparisons

In figure 3(a-c), all the individual paired P,,O, measurements (5 min data) in all the studies are plotted for different sensor comparisons. The IL-CM data showed a greater scatter than either the GS-CM or the PO-CM data.

In figure 3(d-f), the differences between individual data pairs in each CPB are plotted against the individual CM data points. The mean and standard deviation of all the individual differences are given in table 3, and show that the differences between the in-line techniques (figure 3(d,f)) are smaller than with the in a i m technique (figure 3(e)).

-201

m a. Y

=' d s" v

4 x I

( f ) 20- - (d

60-

L - m - .

x E . 9 " ; X. " X I x

~ "I... " .:", o . -+ ! Jm&- . " f x

* x " I

-20-

0 30 60 0 30 CO

Pao, (CM) (kPd pao2 (CM) (kPa)

Fipre3. Comparison of all Pa,O, measurements of the CardioMet-1000 with those from the Gas-Stat (a), IL-1302 (b ) and Polytrode (c). The differences are given in (d:fl. The line of identity is indicated in (a-c).

Clinical comparison of blood gas PO, sensors

Table 3. Difference between sensor measurements.

255

Total Hypothermic Normothermic Lower Pa.o, bypass phase phase (CM e 30 kPa)

Comparison (kPa) &Pa) ( k W (kPa)

GS-CM 0.7 k 4.7 (188) 2.3 k 3.1 (90) - 1.6 rt 4.6 (79) 1.1 k 4.8 (55) IL-CM -7.0 rt 8.6 (192) -8.3 k 7.3 (88) -9.1 i 7.3 (77) -0.9 k 8.2 (60) PO-CM -1.4 k 4.0 (168) -2.2 i 4.8 (56) -0.9 & 3.7 (75) -0.6 t 1.9 (134)

The values are the mean pairs available for analysis.

SD of the difference between pairs of measurements, with the number of

3.3. Variation of results from operation to operation

Figure 4(a-c) shows the variations of the difference between sensors from one CPB operation to another. For perfect agreement between sensors all the points should lie along the central line. For the comparison of the GS with the CM, the points were scattered near to the central line, indicating that the mean difference between sensors was never greater than 5 kPa. For the comparison of the PO with the CM, agreement was good at low Pa,02 but there was a large deviation for the two studies which had a relatively high mean Pa,oZ. For the comparison of the IL with the CM, the data are spread further from the line, with a mean difference up to as much as 17 kPa.

3.4. Other relationships

3.4.1. Temperature. Some of the differences between the GS and CM appeared to depend on temperature. For example, the hypothermic phase can be seen in figure 2(a) from 30 to 70min, and during this phase the CM read lower than the GS. The data were therefore divided into groups to separate out the hypothermic and the normothermic phases. For the GS-CM comparison (figure 5) the differences tended to be positive during hypothermia (2.3 +- 3.1 kPa), and negative during normothermia (- 1.6 f 4.6 kPa).

A smaller temperature related effect was detected in the PO-CM difference, and none in the IL-CM difference (table 3).

3.4.2. P,,02 /ess than 30 kPa. All the comparisons were reanalysed (table 3) for lower Pa,q (CM Paso, < 30 kPa). The results indicated that there was better agreement between some sensors at lower Pa,0, values. For the IL-CM comparison there was better agreement (-0.9 f 8.2 kPa) than for the complete range, although the random variation was just as great. For the GS-CM comparison there was no improvement at lower P,,o,. However for the PO-CM comparison the difference was reduced to a low value of -0.6 f 1.9 kPa.

3.4.3. Percentage error. Because some of the differences appeared to the dependent on the absolute value ofPa,o,, the percentage error was also calculated for each comparison. These results are shown in table 4. It can be seen that the difference between the PO and the CM is in fact dependent on the absolute value; the SD of the difference being 12% throughout the whole range in comparison with a similar value of 11% when the Pa,o, is less than 30 kPa. Although i t is the absolute difference which is generally of relevance, it is of interest to note that these errors can be related to the level of Pa.o,.

256 S J Poslad et a1

! I

-20 i

10 30 50 M e a n (CM) (kPa)

Figure 4. Mean and SD for the differences in Pa.q for each patient analysed

3.4.4. Blood snmpliiig point. The difference between IL measurements of blood samples from the arterial port and from the arterial line (1.9 f 5.0 kPa) was much less than the difference between the IL and CM sensors. The choice of blood sample point had therefore little influence on the results obtained.

Clinical rontparison of blood gas PO, sensors

Hypothermia Hypothermia 20 -

m . X - 8

5 . z 2 30.

a"

I " a .* XII '*~***,"&%* - ."

60. - 2 v 0- E= *. .;- -. - -

0' c7

a

v)

d 4"

-20- 0 1 ' '

251

Figure 5. Separation of the hypothermic phase and the normothermic phase for the Gas-Stat and CardioMet-1000 comparison. The line of identity is indicated.

Table 4. Difference between sensor measurements.

All Lower Pa,o, bypass (CM < 30 kPa)

Comparison (:<) (%)

GS-CM 3 + 1 7 9 + 2 6 IL-CM -12 41 60 i: 66 PO-CM -5i: 12 - 4 k I I

The values given are the mean 2 SD of the difference between pairs of' measurements.

4. Discussion

4.1. Agreement bericwn in-line sensors

The agreement between the in-line sensors was much better than the agreement with the in virro technique. Hill el a/ (1985) noted similar results. There are many possible reasons for the differences experienced.

For the GS versus CM, the GS generally read higher than the CM during hypothermia, but generally lower than the CM during normothermia, indicating a temperature dependence of the GS-CM difference. In addition, it was apparent in all bypasses in group A that the pa,o? was also higher during the hypothermic phase. Hence, the difference may be a systematic error dependent on the level in one or both of the in-line sensors. Some of the differences between PO and CM sensors may arise from calibration inaccuracies which become magnified at high P,,o? values.

258 S J Poslad et a1

The differences in time constants of the different devices must also have played some part in the differences observed. However since most of the fast Pa,O, changes were fairly small in amplitude (see for example figure 2(a)), the overall effect of different time constants is small in comparison with the major differences observed.

Because of the much lower Pa,0, in group B compared with group A, the comparison of the in-line techniques is difficult. However, in two studies in group B, the data were comparable with studies in group A with a high mean Pa,ol. These two studies show that at higher Pa,0, the agreement between the PO and CM was not as good, and comparable with the differences observed between the GS and CM. Therefore we are unable to conclude that the differences between the PO and CM are smaller than those with the GS simply because of the PO’s similar performance a t low Pa,0,. Nevertheless the clinically normal physiological range of Pa,ol does fall within the lower end of the Pa,0, range.

4.2 . Agreement between in citro and in-line sensors

The agreement between in citro and in-line sensors was poorer. Generally, the IL tended to underestimate the in-line PO,. This is in agreement with other workers (Claremont and Pagdin 1985, Janssenwillen et a1 1985, Hill et al 1984, 1985). Claremont and Pagdin (1985) observed a difference of similar magnitude (7 kPa) between the CM and Corning-175. Some of the spread of differences between individual data pairs may arise due to slight differences in sample times between automatic and manually sampled data (Janssenwillen et a1 1985). The differences between the IL and CM was less apparent at a lower Pa,0,. Unlike other workers (Hill e ta / 1984, 1985) the differences we observed between IL and CM did not tend to increase with decreasing temperature during CPB. In addition, the differences between in uitro and in-line measurements was not principally due to performing in citro measurements at a different point in the CPB loop compared with in-line measurements.

5. Conclusions

The in citro blood gas analyser tended to underestimate the P,,Q in comparison with the in- line techniques. The underestimation tended to increase with increasing Pa,0,.

The agreement between in-line sensors was good, especially at lower Pa,0, (< 30 kPa) which contains the normal physiological range of Pa,0,.

Acknowledgments

We acknowledge the support of the DHSS for funding the oxygenator evaluation programme, which included the research presented here. We thank the Perfusion Technicians for their help in taking the in zYrro blood gas measurements.

Resume Comparaison clinique d’un capteur in uirro et de trois capteurs en ligne pour la mesure de la Po1 du sang au cours de shunts cardiopulmonaires.

Au cours de dix-sept operations necessitant un shunt cardiopulmonaire (CPB), des mesures de Po. arterielle ont kt6 effectuees a 5 minutes d’intervalle en utilisant quatre types diffbrents de capteurs de Po: : trois en ligne (CardioMet- 1000, Polytrode et Gas-Stat) et un analyseur de gaz du sang (IL-I 302). Les comparaisons entre capteurs ont Ctt faites par rapport au CardioMet-1000. Les trois capteurs en ligne ont fourni des resultats tres proches. La moyenne et I’ecart-type de la difference entre le Gas-Stat et le CardioMet-1000 etaient de 0,7 4,7 kPa, et entre le Polytrode et le

Clinical comparison of’ blood gas PO, sensors 259 ,-ardioMet-lOOO de - I ,4 k 4,O kPa. L’accord entre I’analyseur des gaz du IL-1302 et le CardioMet-1000 n’etait pas

le difference etant de -7,O 8,6 kPa.

Zusamnenfassung

pass-Operationen.

Wghrend 17 kardiopulmonaler By-Pass-Operationen (CPB) wurden arterielle Po,-Messungen in 5 min Intervallen mit Hilfe vier verschiedener Arten von Po,-Sensoren durchgefiihrt : drei in-line-Sensoren (CardioMet-1000, Polytrode und Gas-Stat) und einem Blutgasanalysator (IL-I 302). Vergleiche zwischen den Sensoren wurden in Bezug auf den CardioMet-1 000-Sensor durchgefuhrt. Die drei in-line-Sensoren zeigen eine gute Ubereinstimmung. Der Mittelwert und die Standardabweichung zwischen Gas-Stat und CardioMet-1000 war 0.7 i 4.7 kPa und zwischen Polytrode und CardioMet- 1000 - I .4 i 4.0 kPa. Die Ubereinstimmung zwischen dem IL-1302-Blutgasanalysator und dem Cardioldet- 1000-Sensor war nicht so gut: - 7.0 k 8.6 kPa.

Klinischer Vergleich zwischen einem in cirro- und drei in-line-Blutgas-Po,-Sensoren wtihrend kardiopulmonaler By-

References Claremont D J , Pagdin T M and Walton N 1984 Continuous monitoring of blood PO, in extracorporeal systems

Claremont D J and Pagdin T M 1985 Evaluation of a new re-usable electrode for continuous monitoring of blood PO,

Clark L C 1956 Monitor and control of blood and tissue oxygen tensions Trans. Am. Soc. Art. Int. Organs 2 41-8 Hahn C E W 1987 Blood gas measurement Clin. Phj . Phvsiol. Meas. 8 3-38 Hill A G, Vinansky R P, Todd R W, Groom R C and Lefrak E A 1984 Continuous measurement ofO, tension during

cardiopulmonary bypass Proc. Am. Acad. Cardiocasc. Perfusion 5 39-42 Hill A G, Groom R C, Vinansky R P and Lefrak E A 1985 On-line or off-line blood gas analysis: cost vs time vs

accuracy Proc. Am. Acad. Cardiatasc. Perfirsion 6 148-54 Janssenwillen E, Steenmans M, Rucquoi M , Cham Band Welch W 1985 Importance of precise sample handling when

comparative studies are made between in-line and intermittent pH and blood gas monitoring Cercle dEtude de la Circulation E.rtra-corporelle (Paris)

Lubbers D W and Optitz N (1983 Optical fluorescence sensors for continuous measurement of chemical concentrations in biological systems Sensors and Actuators 4 641-54

NCCLS 1979 Tentative standards for definitions of quantities and conventions related to blood pH and gas analysis National Coniniittee .for Clinical Laboratory Srandords 2 335-56

Parker D, Delpy D T and Halsall D N 1983 A new approach to inline gas monitoring: development of an oxygen sensor Med. B i d Eng. Coniput. 21 134-7

Pearson D T , Holden M P, Poslad S J , Murray A and Waterhouse P S 1986 A clinical evaluation of the performance characteristics of one membrane and five bubble oxygenators: gas transfer and gaseous microemboli production Perfusioti 1 15-26

Reeder G D and Hood A G 1983 Accuracy of oxygen partial pressure measurements: an in-vitro study J . E.utra- Corporeal Technol. 15 89-95

Rithalia S V S, Bennett P J , Sturridge M F and Tinker J 1979 Need for caution in interpreting blood-gas results in extracorporeal oxygenators Lancet 2 465-6

Anaesthesia 39 362-9

during open-heart surgery J . Med. Eng. Technol. 9 174-9