JECT. 2015;47:174–179 The Journal of ExtraCorporeal Technology
Should Air Bubble Detectors Be Used to Quantify Microbubble Activity during Cardiopulmonary Bypass? Richard F. Newland, BSc, Dip Perf, CCP (Aust);*† Robert A. Baker, PhD, Dip Perf, CCP (Aust);*† Annette L. Mazzone, BSc(Hons), Dip Perf, CCP (Aust);* Vijaykumar N. Valiyapurayil, MSc, CCP (Ind)* *Cardiac Surgery Research and Perfusion, Flinders Medical Centre and †Flinders University, Bedford Park, South Australia
Presented at the 29th ANZCP Annual Scientific Meeting, 2012, Uluru, Australia; the 33rd Annual Cardiothoracic Surgery Symposium, 2013, San Diego, California; and the 50th AmSECT International Meeting, 2013, Las Vegas, Nevada.
Abstract: Air bubble detectors (ABDs) are utilized during cardiopulmonary bypass (CPB) to protect against massive air embolism. Stockert (Munich, Germany) ABD quantify microbubbles >300 mm; however, their reliability has not been reported. The aim of this study was to assess the reliability of the microbubble data from the ABD with the SIII and S5 heart–lung machines. Microbubble counts from the ABD with the SIII (SIII ABD) and S5 (S5 ABD) were measured simultaneously with the emboli detection and classification (EDAC) quantifier in 12 CPB procedures using two EDAC detectors and two ABDs in series in the arterial line. Reliability was assessed by the Spearman correlation co-efficient (r) between measurements for each detector type, and between each ABD and EDAC detector for counts >300 mm. No correlation was found between the SIII ABD (r = .008, p = .793). A weak negative correlation was found with the S5 ABD (r = –.16, p < .001). A strong correlation was found between the EDAC
detectors (SIII; r = .958, p < .001), (S5; r = .908, p < .001). With counts >300 mm, the SIII ABDs showed a correlation of small– medium effect size between EDAC detectors and ABD1 (r = .286, p < .001 [EDAC1], r = .347, p < .001 [EDAC2]). There was no correlation found between ABD2 and either EDAC detector (r = .003, p = .925 (EDAC1), r = .003, p = .929 [EDAC2]). A correlation between EDAC and the S5 ABD, was not able to be determined due to the low bubble count detected by the EDAC >300 mm. Both SIII ABD and S5 ABD were found to be unreliable for quantification of microbubble activity during CPB in comparison with the EDAC. These results highlight the importance of ensuring that data included in the CPB report is accurate and clinically relevant, and suggests that microbubble counts from devices such as the SIII ABD and S5 ABD should not be reported. Keywords: cardiopulmonary bypass (CPB), equipment, microemboli, embolism. JECT. 2015;47:174–179
Air bubble detectors (ABDs) are used during cardiopulmonary bypass (CPB) to alert perfusionists to the presence of air in the arterial line and help protect against massive air embolism. Contemporary equipment, technology, and perfusion techniques have reduced the potential for massive air embolism; however, arterial gaseous microemboli (GME) still remain a concern during CPB in the context of postoperative neurological dysfunction (1). GME may arise from a number of sources during cardiac surgery including manipulation of the aorta, cannulation, and cross clamping, and via entrainment of air into
the CPB venous line (2–4) or during drug injection into the sampling manifold (3). In addition, the design of the venous reservoir (5), the use of vacuum-assisted venous drainage (4), high blood flow rates (5), and high temperature gradients may also contribute to GME formation (3). Cognitive decline is a common complication after cardiac surgery, and has been variably reported to occur in up to 50% of patients at discharge, 36% at 6 weeks, 26–33% at 1 year, and 42% at 5 years, postoperatively (6). Although there has been some controversy as to the size and number of GME that are associated with cognitive decline, there is some evidence linking embolization to clinical outcome (2,6,7). Doganci et al. (7) demonstrated significantly greater cognitive decline in patients exposed to >500 GME during CPB compared with those that were exposed to 36 C with a maximum arterial outlet temperature of 37 C and rewarming rate 70 g/L; none of the patients required red blood cell transfusion either in the priming solution or during CPB. Data Analysis Reliability was assessed by the Spearman correlation co-efficient (r) between simultaneous measurements for each detector type. As the manufacturer reports that the ABD detect microbubbles >300 mm, we evaluated correlation in simultaneous measurements between each ABD and EDAC detector for microbubbles >300 mm using SPSS V20.0 (IBM Corporation, New York, NY). Reliability: Correlation of Simultaneous Air Bubble Detector Microbubble Counts Total Microbubble Counts: A total of 4592 measurements at 20-second intervals were obtained for the SIII JECT. 2015;47:174–179
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ABD in six procedures, and 5924 measurements using the S5 ABD. Microbubble counts for each detector are reported in Table 1 for each procedure, and summarized in Figures 2 and 3. No correlation was found between microbubble counts recorded using the two SIII ABD’s as shown in Figure 4 (r = .008, p = .793). A weak negative correlation was found with between the two S5 ABD (r = –.16, p < .001) (Figure 5). A strong correlation was found between microbubble counts recorded using the EDAC detectors in the procedures using the SIII or S5 heart–lung machine (r = .958, p < .001; r = .908, p < .001, respectively).
size with both EDAC detectors for microbubble counts >300 mm with ABD1 (r = .286, p < .001 [EDAC1], r = .347, p < .001 [EDAC2]). However, the second detector, SIII ABD2, showed no correlation with either EDAC detector for microbubble counts >300 mm (r = .003, p = .925 [EDAC1], r = .003, p = .929 [EDAC2]). A correlation between EDAC and the S5 ABD was not able to be determined because of the low bubble count detected by the EDAC >300 mm.
Microbubble Counts >300 mm: The SIII ABD, demonstrated a weak correlation with small–medium effect
This study demonstrated that there was no correlation of microbubble data obtained with simultaneous measurements
DISCUSSION
Table 1. Emboli counts during CPB for each detector and heart–lung machine. Emboli counts were recorded in counts/20-second interval. SIII Procedure 1
2
3
4
5
6
Overall
Device ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC2 EDAC1 > 300 EDAC2 > 300
Median 0 0 107 0 191 0 0 0 1 0 0 0 0 0 300 0 317 0 0 0 0 0 3.5 0 0 0 0 0 0 0 0 110 0 0 1 0 0 0 2 4 0 0
S5 Minimum
Maximum
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
10 54 3074 11 5378 31 0 9 838 0 778 0 0 0 2158 0 2257 0 0 0 10 0 365 0 0 0 11 0 45 0 0 340 262 0 1236 0 10 340 3074 5378 11 31
Procedure 1
2
3
4
5
6
Overall
Device ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC2 EDAC1 > 300 EDAC2 > 300
ABDs, air bubble detectors; CPB, cardiopulmonary bypass; EDAC, emboli detection and classification.
JECT. 2015;47:174–179
Median 249 0 0 0 0 0 260 0 1 0 1 0 54 225 19 0 14 0 0 312 14 0 31 0 15 53 27 0 10.5 0 47 286 3 0 8 0 58 200 4 6 0 0
Minimum
Maximum
48 0 0 0 0 0 73 0 0 0 0 0 0 0 0 0 0 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
723 446 50 0 58 0 1022 807 147 0 211 0 697 978 190 0 316 0 1148 1054 1844 0 1638 0 456 522 6703 0 3014 1 496 1207 2175 0 3849 0 1148 1207 6703 3849 0 1
AIR BUBBLE DETECTOR USAGE TO QUANTIFY MICROBUBBLE ACTIVITY DURING CPB
Figure 2. Boxplot of microbubble counts for the air bubble detectors and for microbubbles >300 mm detected by the EDAC transducers, recorded using the SIII heart–lung machine. *Values >3 times the interquartile range. EDAC, emboli detection and classification.
using the ABDs on either the SIII or S5 heart–lung machines. A strong correlation was observed with simultaneous measurements using the EDAC detectors. In addition, the greater number of microbubbles were detected using the S5 ABD than with the SIII ABD, in contrast to the number of emboli >300 mm detected by the EDAC quantifiers. Furthermore, only one of the ABDs showed a correlation to the EDAC (emboli >300 mm), with a small–medium effect size, these results are consistent with our clinical observations that the ABD microbubble data
Figure 3. Boxplot of microbubble counts for the air bubble detectors and for microbubbles >300 mm detected by the EDAC transducers, recorded using the S5 heart–lung machine. O, values between 1.5 and 3 times the interquartile range. EDAC, emboli detection and classification.
177
Figure 4. Microbubble counts from each of the SIII ABD plotted at simultaneous time points during cardiopulmonary bypass (n = 4592, Spearman’s correlation coefficient, r = .008).
are inconsistent in comparison to each other, and to the EDAC quantifier. These results highlight that the data currently being recorded and reported in CPB reports generated using data from the SIII ABD or the S5 ABD is not accurate when compared with either a second ABD in series or when compared with an in-series EDAC quantifier. De Somer et al. (9) reported a comparison of commercially available microbubble detection devices used during CPB including the EDAC and Gampt BC200 (GAMPT mbH, Zappendorf, Germany) against industrial standards
Figure 5. Microbubble counts from each of the S5 ABD plotted at simultaneous time points during cardiopulmonary bypass (n = 5924, Spearman’s correlation coefficient, r = –.16).
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of microbubble detection (optical counting using monochromatic laser and backlight shadowgraph technique). Each device uses different algorithms to quantify emboli. The EDAC transducer emits ultrasonic pulses every 1 ms that are reflected by emboli in the blood as they pass through the EDAC connector. The amplitude of the reflected signals is then analyzed to determine bubble size, count, and calculated volume (total embolic load). The manufacturer states that the device is capable of counting emboli with diameters from 10 mm up to the diameter of the connector at a rate of up to 1000 emboli per second, at flow rates between .2 and 6 l per minute (9). The BC200 uses a pulsed ultrasonic Doppler system to generate an amplitude-modulated low-frequency signal depending on the size of the bubble and the time that the bubble is present in the detection signal. Signal transformations allow calculation of the bubble size from the maximum amplitude of the corrected signal. The manufacturer states that the device is capable of counting emboli with diameters between 5 mm and 500 mm at a rate of up to 1000 emboli per second, at flow rates between .5 and 8 L/min(9). Even using commercially available devices designed specifically to quantify microbubbles during CPB, there are some limitations. De Somer et al.’s study reported that both devices underestimate the number of microbubbles; at 3 L/min the EDAC counts 38%, the Gampt 18% of total counts and at 6 L/min, both the EDAC and Gampt only count 3% of total counts. The authors concluded that both the EDAC and Gampt can be used in a clinical setting for monitoring basal GME production; however, both devices have limitations when used for studying “worst case” scenarios. These findings highlight the limitations associated with microbubble measurement. In contrast, ABDs do not provide detail of bubble sizes; therefore, it is impossible to quantify bubble volume to define total embolic load. In our study, we observed a significant correlation between the two EDAC detectors for simultaneous measurements (SIII measurements [r = .958, p < .001], S5 measurements [r = .908, p < .001]) demonstrating reliability, in contrast to the SIII and S5 ABDs. The Sorin Group ABDs transmit an ultrasonic pulse through the circuit tubing that is received by a piezo-element detector, which is able to detect changes in signal amplitude resulting from the difference in speed that sound travels in fluid relative to air. The presence of air bubbles in the blood will result in a drop in the signal amplitude that is received by the detector as the blood travels past the detector. The manufacturer’s instructions for operation of the SIII heart–lung machine state that the smallest single microbubble that the sensor can detect is 300 mm in diameter. This is not specifically stated in the operating manual for the S5; however, we confirmed with the manufacturer that the same thresholds apply for the S5 (personal communication with JECT. 2015;47:174–179
Sorin Group). The sensor can detect conglomerates of much smaller microbubbles if the drop in signal amplitude is equal to or greater than that of a 300-mm diameter single microbubble. Since the system detects a total drop in received signal amplitude, the fidelity of the device to count individual microbubbles is limited as is its ability to determine how large the individual bubbles are. Given these limitations, the ABDs should not be used to quantify microbubbles. This is supported by the results of our study in which we not only observed differences in measurements among ABDs on the same heart–lung machine, but also among heart–lung machines. Although ABDs are interchangeable between Sorin SIII and S5 heart–lung machines, the modules used to process the signals from the detectors are not, which may account for the differences in measurements between the SIII and the S5. In our study, ABDs on the S5 routinely detected higher counts of microbubbles than the SIII, by orders of magnitude, which were not demonstrated with the EDAC detectors. From a safety perspective, ABDs have an important role. In a recent U.S. survey (10), 96.8% of respondents routinely used an ABD during CPB, a figure comparable to the 2006 Australian and New Zealand survey that reported 100% use (11), in contrast to the 32% of respondents in the 2006 French survey (12). The reported incidence of air embolism during CPB is relatively infrequent; the French 2006 survey, reported a rate of 1:3757 procedures, and 1:13,426 in an American survey in 2000 (13). It is unclear as to the number of procedures in which the ABD has resulted in the avoidance of air embolus being delivered to the patient although the 2010 Dutch incident survey indicated 13% of respondents had experienced air embolus after the venous reservoir (14). Our study was not designed to assess the use of ABDs as a safety device. Sorin Group ABD’s alarm threshold is a bubble detected with a diameter of 5.5 mm or greater in 3/800 tubing with the SIII (8) and greater than 4 mm with the S5 (15); therefore, the issues with regard to microbubble quantification are in the context of clinical informatics and medicolegal concerns in the reporting of the microbubble data rather than gross air. Our study did not assess the alarm threshold of the ABD devices as reported by the manufacturer. The limitations of our study include that our data were not limited to open-chamber procedures; hence, we may not have had the opportunity to measure as many emboli as possible. We compared the ABDs against the EDAC rather than an industrial reference; therefore, our comparison of accuracy is limited by the underestimation of microbubble activity as reported by De Somer for the EDAC (9). The correlation between the EDAC and the ABD for emboli >300 mm was limited by the low numbers of emboli detected by the EDAC; however, the data clearly indicate inconsistency in the comparison of each
AIR BUBBLE DETECTOR USAGE TO QUANTIFY MICROBUBBLE ACTIVITY DURING CPB ABD against the EDAC, in particular, the large order of magnitude of emboli detected by the ABD using the S5. We performed Bland–Altman analysis between the EDAC and ABD measurements; however, due to the unreliability in measurements from the ABD and the limited number of emboli >300 mm, we found that this analysis was not meaningful. An additional potential limitation was the age of the ABDs, with the S5 ABDs both
Should Air Bubble Detectors Be Used to Quantify Microbubble Activity during Cardiopulmonary Bypass? Richard F. Newland, BSc, Dip Perf, CCP (Aust);*† Robert A. Baker, PhD, Dip Perf, CCP (Aust);*† Annette L. Mazzone, BSc(Hons), Dip Perf, CCP (Aust);* Vijaykumar N. Valiyapurayil, MSc, CCP (Ind)* *Cardiac Surgery Research and Perfusion, Flinders Medical Centre and †Flinders University, Bedford Park, South Australia
Presented at the 29th ANZCP Annual Scientific Meeting, 2012, Uluru, Australia; the 33rd Annual Cardiothoracic Surgery Symposium, 2013, San Diego, California; and the 50th AmSECT International Meeting, 2013, Las Vegas, Nevada.
Abstract: Air bubble detectors (ABDs) are utilized during cardiopulmonary bypass (CPB) to protect against massive air embolism. Stockert (Munich, Germany) ABD quantify microbubbles >300 mm; however, their reliability has not been reported. The aim of this study was to assess the reliability of the microbubble data from the ABD with the SIII and S5 heart–lung machines. Microbubble counts from the ABD with the SIII (SIII ABD) and S5 (S5 ABD) were measured simultaneously with the emboli detection and classification (EDAC) quantifier in 12 CPB procedures using two EDAC detectors and two ABDs in series in the arterial line. Reliability was assessed by the Spearman correlation co-efficient (r) between measurements for each detector type, and between each ABD and EDAC detector for counts >300 mm. No correlation was found between the SIII ABD (r = .008, p = .793). A weak negative correlation was found with the S5 ABD (r = –.16, p < .001). A strong correlation was found between the EDAC
detectors (SIII; r = .958, p < .001), (S5; r = .908, p < .001). With counts >300 mm, the SIII ABDs showed a correlation of small– medium effect size between EDAC detectors and ABD1 (r = .286, p < .001 [EDAC1], r = .347, p < .001 [EDAC2]). There was no correlation found between ABD2 and either EDAC detector (r = .003, p = .925 (EDAC1), r = .003, p = .929 [EDAC2]). A correlation between EDAC and the S5 ABD, was not able to be determined due to the low bubble count detected by the EDAC >300 mm. Both SIII ABD and S5 ABD were found to be unreliable for quantification of microbubble activity during CPB in comparison with the EDAC. These results highlight the importance of ensuring that data included in the CPB report is accurate and clinically relevant, and suggests that microbubble counts from devices such as the SIII ABD and S5 ABD should not be reported. Keywords: cardiopulmonary bypass (CPB), equipment, microemboli, embolism. JECT. 2015;47:174–179
Air bubble detectors (ABDs) are used during cardiopulmonary bypass (CPB) to alert perfusionists to the presence of air in the arterial line and help protect against massive air embolism. Contemporary equipment, technology, and perfusion techniques have reduced the potential for massive air embolism; however, arterial gaseous microemboli (GME) still remain a concern during CPB in the context of postoperative neurological dysfunction (1). GME may arise from a number of sources during cardiac surgery including manipulation of the aorta, cannulation, and cross clamping, and via entrainment of air into
the CPB venous line (2–4) or during drug injection into the sampling manifold (3). In addition, the design of the venous reservoir (5), the use of vacuum-assisted venous drainage (4), high blood flow rates (5), and high temperature gradients may also contribute to GME formation (3). Cognitive decline is a common complication after cardiac surgery, and has been variably reported to occur in up to 50% of patients at discharge, 36% at 6 weeks, 26–33% at 1 year, and 42% at 5 years, postoperatively (6). Although there has been some controversy as to the size and number of GME that are associated with cognitive decline, there is some evidence linking embolization to clinical outcome (2,6,7). Doganci et al. (7) demonstrated significantly greater cognitive decline in patients exposed to >500 GME during CPB compared with those that were exposed to 36 C with a maximum arterial outlet temperature of 37 C and rewarming rate 70 g/L; none of the patients required red blood cell transfusion either in the priming solution or during CPB. Data Analysis Reliability was assessed by the Spearman correlation co-efficient (r) between simultaneous measurements for each detector type. As the manufacturer reports that the ABD detect microbubbles >300 mm, we evaluated correlation in simultaneous measurements between each ABD and EDAC detector for microbubbles >300 mm using SPSS V20.0 (IBM Corporation, New York, NY). Reliability: Correlation of Simultaneous Air Bubble Detector Microbubble Counts Total Microbubble Counts: A total of 4592 measurements at 20-second intervals were obtained for the SIII JECT. 2015;47:174–179
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ABD in six procedures, and 5924 measurements using the S5 ABD. Microbubble counts for each detector are reported in Table 1 for each procedure, and summarized in Figures 2 and 3. No correlation was found between microbubble counts recorded using the two SIII ABD’s as shown in Figure 4 (r = .008, p = .793). A weak negative correlation was found with between the two S5 ABD (r = –.16, p < .001) (Figure 5). A strong correlation was found between microbubble counts recorded using the EDAC detectors in the procedures using the SIII or S5 heart–lung machine (r = .958, p < .001; r = .908, p < .001, respectively).
size with both EDAC detectors for microbubble counts >300 mm with ABD1 (r = .286, p < .001 [EDAC1], r = .347, p < .001 [EDAC2]). However, the second detector, SIII ABD2, showed no correlation with either EDAC detector for microbubble counts >300 mm (r = .003, p = .925 [EDAC1], r = .003, p = .929 [EDAC2]). A correlation between EDAC and the S5 ABD was not able to be determined because of the low bubble count detected by the EDAC >300 mm.
Microbubble Counts >300 mm: The SIII ABD, demonstrated a weak correlation with small–medium effect
This study demonstrated that there was no correlation of microbubble data obtained with simultaneous measurements
DISCUSSION
Table 1. Emboli counts during CPB for each detector and heart–lung machine. Emboli counts were recorded in counts/20-second interval. SIII Procedure 1
2
3
4
5
6
Overall
Device ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC2 EDAC1 > 300 EDAC2 > 300
Median 0 0 107 0 191 0 0 0 1 0 0 0 0 0 300 0 317 0 0 0 0 0 3.5 0 0 0 0 0 0 0 0 110 0 0 1 0 0 0 2 4 0 0
S5 Minimum
Maximum
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
10 54 3074 11 5378 31 0 9 838 0 778 0 0 0 2158 0 2257 0 0 0 10 0 365 0 0 0 11 0 45 0 0 340 262 0 1236 0 10 340 3074 5378 11 31
Procedure 1
2
3
4
5
6
Overall
Device ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC1 > 300 EDAC2 EDAC2 > 300 ABD1 ABD2 EDAC1 EDAC2 EDAC1 > 300 EDAC2 > 300
ABDs, air bubble detectors; CPB, cardiopulmonary bypass; EDAC, emboli detection and classification.
JECT. 2015;47:174–179
Median 249 0 0 0 0 0 260 0 1 0 1 0 54 225 19 0 14 0 0 312 14 0 31 0 15 53 27 0 10.5 0 47 286 3 0 8 0 58 200 4 6 0 0
Minimum
Maximum
48 0 0 0 0 0 73 0 0 0 0 0 0 0 0 0 0 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
723 446 50 0 58 0 1022 807 147 0 211 0 697 978 190 0 316 0 1148 1054 1844 0 1638 0 456 522 6703 0 3014 1 496 1207 2175 0 3849 0 1148 1207 6703 3849 0 1
AIR BUBBLE DETECTOR USAGE TO QUANTIFY MICROBUBBLE ACTIVITY DURING CPB
Figure 2. Boxplot of microbubble counts for the air bubble detectors and for microbubbles >300 mm detected by the EDAC transducers, recorded using the SIII heart–lung machine. *Values >3 times the interquartile range. EDAC, emboli detection and classification.
using the ABDs on either the SIII or S5 heart–lung machines. A strong correlation was observed with simultaneous measurements using the EDAC detectors. In addition, the greater number of microbubbles were detected using the S5 ABD than with the SIII ABD, in contrast to the number of emboli >300 mm detected by the EDAC quantifiers. Furthermore, only one of the ABDs showed a correlation to the EDAC (emboli >300 mm), with a small–medium effect size, these results are consistent with our clinical observations that the ABD microbubble data
Figure 3. Boxplot of microbubble counts for the air bubble detectors and for microbubbles >300 mm detected by the EDAC transducers, recorded using the S5 heart–lung machine. O, values between 1.5 and 3 times the interquartile range. EDAC, emboli detection and classification.
177
Figure 4. Microbubble counts from each of the SIII ABD plotted at simultaneous time points during cardiopulmonary bypass (n = 4592, Spearman’s correlation coefficient, r = .008).
are inconsistent in comparison to each other, and to the EDAC quantifier. These results highlight that the data currently being recorded and reported in CPB reports generated using data from the SIII ABD or the S5 ABD is not accurate when compared with either a second ABD in series or when compared with an in-series EDAC quantifier. De Somer et al. (9) reported a comparison of commercially available microbubble detection devices used during CPB including the EDAC and Gampt BC200 (GAMPT mbH, Zappendorf, Germany) against industrial standards
Figure 5. Microbubble counts from each of the S5 ABD plotted at simultaneous time points during cardiopulmonary bypass (n = 5924, Spearman’s correlation coefficient, r = –.16).
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of microbubble detection (optical counting using monochromatic laser and backlight shadowgraph technique). Each device uses different algorithms to quantify emboli. The EDAC transducer emits ultrasonic pulses every 1 ms that are reflected by emboli in the blood as they pass through the EDAC connector. The amplitude of the reflected signals is then analyzed to determine bubble size, count, and calculated volume (total embolic load). The manufacturer states that the device is capable of counting emboli with diameters from 10 mm up to the diameter of the connector at a rate of up to 1000 emboli per second, at flow rates between .2 and 6 l per minute (9). The BC200 uses a pulsed ultrasonic Doppler system to generate an amplitude-modulated low-frequency signal depending on the size of the bubble and the time that the bubble is present in the detection signal. Signal transformations allow calculation of the bubble size from the maximum amplitude of the corrected signal. The manufacturer states that the device is capable of counting emboli with diameters between 5 mm and 500 mm at a rate of up to 1000 emboli per second, at flow rates between .5 and 8 L/min(9). Even using commercially available devices designed specifically to quantify microbubbles during CPB, there are some limitations. De Somer et al.’s study reported that both devices underestimate the number of microbubbles; at 3 L/min the EDAC counts 38%, the Gampt 18% of total counts and at 6 L/min, both the EDAC and Gampt only count 3% of total counts. The authors concluded that both the EDAC and Gampt can be used in a clinical setting for monitoring basal GME production; however, both devices have limitations when used for studying “worst case” scenarios. These findings highlight the limitations associated with microbubble measurement. In contrast, ABDs do not provide detail of bubble sizes; therefore, it is impossible to quantify bubble volume to define total embolic load. In our study, we observed a significant correlation between the two EDAC detectors for simultaneous measurements (SIII measurements [r = .958, p < .001], S5 measurements [r = .908, p < .001]) demonstrating reliability, in contrast to the SIII and S5 ABDs. The Sorin Group ABDs transmit an ultrasonic pulse through the circuit tubing that is received by a piezo-element detector, which is able to detect changes in signal amplitude resulting from the difference in speed that sound travels in fluid relative to air. The presence of air bubbles in the blood will result in a drop in the signal amplitude that is received by the detector as the blood travels past the detector. The manufacturer’s instructions for operation of the SIII heart–lung machine state that the smallest single microbubble that the sensor can detect is 300 mm in diameter. This is not specifically stated in the operating manual for the S5; however, we confirmed with the manufacturer that the same thresholds apply for the S5 (personal communication with JECT. 2015;47:174–179
Sorin Group). The sensor can detect conglomerates of much smaller microbubbles if the drop in signal amplitude is equal to or greater than that of a 300-mm diameter single microbubble. Since the system detects a total drop in received signal amplitude, the fidelity of the device to count individual microbubbles is limited as is its ability to determine how large the individual bubbles are. Given these limitations, the ABDs should not be used to quantify microbubbles. This is supported by the results of our study in which we not only observed differences in measurements among ABDs on the same heart–lung machine, but also among heart–lung machines. Although ABDs are interchangeable between Sorin SIII and S5 heart–lung machines, the modules used to process the signals from the detectors are not, which may account for the differences in measurements between the SIII and the S5. In our study, ABDs on the S5 routinely detected higher counts of microbubbles than the SIII, by orders of magnitude, which were not demonstrated with the EDAC detectors. From a safety perspective, ABDs have an important role. In a recent U.S. survey (10), 96.8% of respondents routinely used an ABD during CPB, a figure comparable to the 2006 Australian and New Zealand survey that reported 100% use (11), in contrast to the 32% of respondents in the 2006 French survey (12). The reported incidence of air embolism during CPB is relatively infrequent; the French 2006 survey, reported a rate of 1:3757 procedures, and 1:13,426 in an American survey in 2000 (13). It is unclear as to the number of procedures in which the ABD has resulted in the avoidance of air embolus being delivered to the patient although the 2010 Dutch incident survey indicated 13% of respondents had experienced air embolus after the venous reservoir (14). Our study was not designed to assess the use of ABDs as a safety device. Sorin Group ABD’s alarm threshold is a bubble detected with a diameter of 5.5 mm or greater in 3/800 tubing with the SIII (8) and greater than 4 mm with the S5 (15); therefore, the issues with regard to microbubble quantification are in the context of clinical informatics and medicolegal concerns in the reporting of the microbubble data rather than gross air. Our study did not assess the alarm threshold of the ABD devices as reported by the manufacturer. The limitations of our study include that our data were not limited to open-chamber procedures; hence, we may not have had the opportunity to measure as many emboli as possible. We compared the ABDs against the EDAC rather than an industrial reference; therefore, our comparison of accuracy is limited by the underestimation of microbubble activity as reported by De Somer for the EDAC (9). The correlation between the EDAC and the ABD for emboli >300 mm was limited by the low numbers of emboli detected by the EDAC; however, the data clearly indicate inconsistency in the comparison of each
AIR BUBBLE DETECTOR USAGE TO QUANTIFY MICROBUBBLE ACTIVITY DURING CPB ABD against the EDAC, in particular, the large order of magnitude of emboli detected by the ABD using the S5. We performed Bland–Altman analysis between the EDAC and ABD measurements; however, due to the unreliability in measurements from the ABD and the limited number of emboli >300 mm, we found that this analysis was not meaningful. An additional potential limitation was the age of the ABDs, with the S5 ABDs both
