Air removal capacity of two different minimal invasive ECC systems: an in vitro comparison

Abstract

Minimally invasive extracorporeal circulation systems are developed to decrease the deleterious effects of cardiopulmonary bypass. For instance, prime volume and foreign surface area are decreased in these systems. However, because of the lack of a venous reservoir in minimized systems, air handling properties of these minimally invasive extracorporeal circulation systems may be decreased as compared to conventional cardiopulmonary bypass systems. The aim of this in vitro study is to compare the air handling properties of two complete minimized cardiopulmonary bypass systems of two manufacturers, of which one system is provided with the air purge control. In an in vitro study, two minimally invasive extracorporeal circulation systems, Inspire Min.I manufactured by Sorin Group Italia, Mirandola, Italy (LivaNova, London, United Kingdom) and minimized extracorporeal circulation manufactured by Maquet, Rastatt, Germany (Getinge, Germany), were challenged with two types of air challenges; a bolus air challenge and a gaseous microemboli challenge. The air removal characteristics of the venous bubble traps and of the complete minimally invasive extracorporeal circulation systems were assessed by measuring the gaseous microemboli volume and number downstream of the venous bubble traps in the arterial line with a bubble counter. No significant differences were observed in air reduction between the venous bubble traps of Getinge (venous bubble traps) and LivaNova (Inspire venous bubble traps 8 in conjunction with the air purge control). Similarly, no significant differences were observed in volume and number of gaseous microemboli in the arterial line of both complete minimally invasive extracorporeal circulation systems. However, the gaseous microemboli load of the Inspire Min.I system was marginally lower after both the bolus air and the gaseous microemboli challenges. Both minimally invasive extracorporeal circulation systems assessed in this study, the LivaNova Inspire Min.I and the Getinge minimized extracorporeal circulation, showed comparable air removal properties, after both bolus and gaseous microemboli air challenges. Besides, air purge control automatic air removal system provided with the LivaNova Inspire Min.I. system may enhance patient’s safety with the use of a minimally invasive extracorporeal circulation system. We consider both systems equally safe for clinical use.

Keywords

gaseous microemboli air removal MiECT minimized ECC CPB ECC automatic air removal

Introduction

Minimally invasive extracorporeal technology (MiECT) systems are developed to decrease the deleterious effects of cardiopulmonary bypass (CPB) by decreasing prime volume and foreign surface area in contact with blood. To achieve these benefits, a venous and cardiotomy reservoir are omitted from the extracorporeal circuit (ECC) and shed mediastinal blood is processed with an autotransfusion device. Also, low volume cardioplegia, as part of minimally invasive extracorporeal circulation (MiECC), enhances hemodilution reduction. Two meta-analysis studies show that the use of MiECC compared to conventional ECC systems seems to reduce transfusion rates and improve patient outcome on, both morbidity and mortality.^1,2

However, because of the lack of a large venous reservoir in minimized systems, air handling properties of these MiECC systems may be decreased as compared to conventional CPB systems. Air may travel easily through the MiECC system and this may increase the risk of air delivery to the patient.³ Gross air entering patients’ systemic circulation is very rare, but is considered as a major incident since this may lead to cerebral injury and even death.⁴ Air introduction in the venous line will eventually lead to gaseous microemboli (GME) in the arterial line and can be measured with ultrasound Doppler devices.⁵ Introduction of GME into the arterial line of a CPB circuit may lead to cognitive decline and adverse outcome in the cardiac patient.⁶

Minimized circuits of different brands show high variation in air handling⁷ which is probably caused by the different design of the components of these systems. Both the venous bubble trap (VBT)⁸ and the oxygenator with integrated arterial filter (IAF)⁹ are considered as components which play a vital role in protecting the patient against air introduction. Probably, the combination of both the VBT and the oxygenator device is the major contributor to air reduction of the complete MiECC system.

The aim of this in vitro study is to compare the air handling properties of two complete MiECC systems of two manufacturers, of which one system is provided with an automated air purge control (APC) system.

Material and methods

In an in vitro study, two minimized ECC systems, Inspire Min.I from Sorin Group Italia, Mirandola, Italy (part of LivaNova, London, United Kingdom) and Minimized ECC (MECC) from Maquet, Rastatt, Germany (part of Getinge group), were challenged with two types of air challenges; a bolus air challenge and a GME challenge. The air removal characteristics of the complete MiECC systems were assessed by measuring the GME in the arterial line with a BCC200 (GAMPT mbH, Zappendorf, Germany) bubble counter.

In vitro test system

An in vitro test system was set up and connected to a pseudo-patient (Figure 1). The pseudo-patient consisted of an Inspire 6F M oxygenator module and a Phisio Dual chamber hard shell venous reservoir (Sorin Group Italia, Mirandola, Italy) to remove air and GME.

The test circuit consisted of a MiECC system for each brand, namely, the Inspire Min.I system of LivaNova and the MECC system of Getinge. Both systems were constructed consecutively with the following components: VBT, centrifugal pump, oxygenator with IAF. Table 1 presents the details of these components.

Table 1.

Overview of the MiECC systems and the components of both brands.

	LivaNova Inspire Min.I	Getinge MECC
VBT	Inspire VBT 8 with APC	VBT 160
Centrifugal pump	Revolution	Rotaflow RF-32
Oxygenator + IAF	Inspire 6F M	Quadrox-i small adult IAF

MECC: minimized extracorporeal circulation; VBT: venous bubble trap; APC: air purge control; IAF: integrated arterial filter.

The systems were primed with heparinized bovine blood (1,000 IU/L) and the blood was diluted with Ionolyte (Fresenius Kabi, Bad Homburg, Germany) until a hematocrit of approximately 25% was reached. The temperature of the blood-prime was maintained at 32°C with a heater (Julabo, Seelbach, Germany). Hematocrit and blood temperature were measured with an inline blood gas monitor, the blood monitoring unit (BMU) 40 (Getinge). Non-pulsatile perfusion flow was maintained at 4.5 L/minute as measured with the transonic flow probe of the S5 Heart-lung machine (HLM) (LivaNova, London, United Kingdom) and the arterial pressure was set to 200 mmHg with a Hoffman clamp. Active venous drainage between the pseudo-patient reservoir and the venous reservoir was regulated with a Hoffman clamp to a pressure of −40 mmHg. Venous and arterial pressures were measured with a pressure dome.

All oxygenators with IAF purge/recirculation lines were open (thus for the Inspire both pre and post arterial filter and for the Quadrox-i IAF only pre arterial filter), returning the blood to the hard shell reservoir of the pseudo-patient.

The APC of the S5 HLM was enabled during all tests with the Inspire Min.I. to automatically evacuate air from the VBT 8 belonging to the Inspire Min.I. When activated by the bubble sensor (set at medium sensitivity), the APC evacuated air/blood with a flow of 300 mL/minute for 5 second to the hard shell reservoir of the pseudo-patient. Also, the ramp down was activated and the revolutions per minute (RPM), of the Revolution centrifugal pump, was reduced to 1,500 r/minute which resulted in a blood flow of approximately 2 L/minute.

The purge line of the VBT 160 belonging to the MECC system was operated manually. Air was evacuated from the VBT 160 after approximately 10 seconds manually activating a roller pump at a flow of 300 mL/minute and recirculated to the hard shell reservoir of the pseudo-patient.

Each bolus air challenge was repeated five times. The GME challenge was repeated three times. The experiments were repeated with 3 MiECC circuits per manufacturer to exclude discrete differences in the tested devices.

Air challenges

GME challenge

Air was pumped with a roller pump through a luer lock into the venous line of the pseudo-patient (Figure 1: Position A) with 200 mL/minute (¼ inch line) resulting in a constant GME challenge of the test circuit. Measurement probes of the BCC200 were placed 5 cm before and 30 cm after the oxygenator/arterial filter combination of the MiECC circuit. Detailed GME data were collected during 4 minutes. APC was enabled during testing of the LivaNova system.

Bolus challenge

Bolus injection of air was achieved by injecting 5 mL air in 10 second into the venous line of the test circuit (Figure 1: Position B). Measurement probes of the BCC200 were placed 5 cm before and 20 cm after the oxygenator/arterial filter combination of the MiECC circuit. Detailed GME data were collected during 30 second. APC was enabled during testing of the LivaNova system. In the MECC system, air was evacuated from the VBT 160 after approximately 10 second manually activating a roller pump at a flow of 300 mL/minute and recirculated to the hard shell reservoir of the pseudo-patient.

GME detection

GME were detected with the bubble counter BCC 200 (GAMPT). The measurements were conducted with two non-invasive sensor probes clamped on the 3/8 inch tubing. The probes were clamped on the inflow and outflow lines of the oxygenator of the test circuit.

The measurement is based on a self-calibrating ultrasonic Doppler device. The BCC 200 device measures accurately the number and the size of GME, with a diameter ranging from 20 to 500 μm. The device specifies the bubbles with a diameter of more than 500 μm as “over range.” Particulate emboli do not influence the count results.

Statistics

Quantitative variables are presented as mean ± standard deviation (SD), when appropriate unless stated otherwise. The mean of five bolus injections or three (4 minute) GME challenges were calculated and collected for three MiECC systems for every brand. Subsequently, this n = 3, was used for statistical analysis. Continuous variables were compared by means of the Student’s t-test. A p-value of < 0.05 is considered significant.

Reduction is calculated by the formula, % Reduction = [1 – GME_out/GME_in]*100.

Results

Baseline conditions for the in vitro experiments are presented in Table 2.

Table 2.

Baseline conditions.

	Mean
Volume pseudo-patient (mL)	2,900
Blood flow^a (L/minute )	4.50
Ht (%)	24
Blood temperature	32.8
P art (mmHg)	200
P ven (mmHg)	−43

As measured with the flow probe of the S5 heart-lung machine (in both groups).

GME challenge

All obtained data of the 4-minute GME challenge are shown in Table 3. Both volume and number of GME, measured distal of the VBTs showed no significant differences between both brands. Also, the GME (volume and number) measured in the arterial line showed no significant difference (Figure 2).

Table 3.

Overview of volume and number of GME measurements distal of VBT and in the arterial line after a GME challenge.

	Distal of VBT		Arterial
	Volume (µL)	Number (n)	Volume (µL)	Number (n)
Inspire Min.I	23.69 ± 19.45	25,429 ± 6,639	1.24 ± 0.74	15,583 ± 6,368
MECC	30.89 ± 39.27	23,582 ± 5,896	2.98 ± 2.79	15,058 ± 5,002
p-value	0.79	0.74	0.36	0.92

GME: gaseous microemboli; VBT: venous bubble trap; MECC: minimized extracorporeal circulation.

Bolus challenge

In Table 4, the results of the bolus challenge are presented. No significant differences were observed. After an injection of 5 mL bolus air, in the MECC system a mean volume of GME of 0.96 ± 0.53 µL and in the Inspire Min.I circuit 0.52 ± 0.28 µL was observed distal of the VBT. This means that the VBTs reduced, respectively, 99.98% and 99.99% of the 5 mL bolus injection. In the arterial line, the air was reduced even more to 0.022 ± 0.005 µL and 0.023 ± 0.004 µL for the MECC and the Inspire Min.I circuits (Figure 3), respectively, and a reduction of 99.9996% was reached in both systems.

Table 4.

Overview of volume and number of GME measurements distal of VBT and in the arterial line after a bolus challenge.

	Distal of VBT		Arterial
	Volume (µL)	Number (n)	Volume (µL)	Number (n)
Inspire Min.I	0.52 ± 0.28	988 ± 192	0.023 ± 0.004	307 ± 119
MECC	0.96 ± 0.53	895 ± 221	0.022 ± 0.005	376 ± 30
p-value	0.27	0.61	0.69	0.39

GME: gaseous microemboli; VBT: venous bubble trap; MECC: minimized extracorporeal circulation.

Discussion

After a challenge of both micro (GME) or bolus air in the venous line in an in vitro setup, no significant differences were observed in air reduction between the VBTs of Getinge (VBT) and LivaNova (Inspire VBT 8 in conjunction with the APC). More importantly, no significant differences were observed in volume and number of GME in the arterial line of both complete MiECC systems, the MECC (Getinge) and the Inspire Min.I (LivaNova).

Venous filtration may be considered as the most important safety net against air introduction into the ECC system and consequently avoiding air to be fractionated by the various components of the CPB circuit resulting in GME entering the cardiac patient. Numerous studies show that air is always introduced into the venous site of the ECC system by perfusionist interventions such as blood sampling, transfusing volume or injecting drugs^10–13 and eventually lead to increased GME activity in the arterial line. Also air, when directly introduced into the venous line of the CPB circuit through residual air in the venous cannula after connecting or caused by excessive negative pressure, leads to increased embolization of the patient.^14,15 Since MiECC systems seems more vulnerable to air,¹⁶ air is transported more easily through small systems, by which the role of the VBTs may be even more important than in conventional ECC systems.

Both VBTs assessed in this study reduced similarly the two air challenges, GME and bolus. The VBTs of both brands were able to scavenge > 99.9% of the injected 5 mL air bolus, which is similar to the results we previously obtained with a neonatal venous hard shell reservoir in a comparable in vitro setting.⁵ Interestingly, the Inspire VBT 8 has a slightly smaller mesh size of 120 µm compared to the 160 µm mesh size of the VBT of Getinge. Although no significant difference could be detected, the smaller mesh size might be the cause of the slightly lower volume of GME distal of the VBT 8 after both the GME and the bolus challenges.

Although the VBT plays an important role in the first defense against air introduction, the final GME load in the arterial line is the most important factor contributing to the adverse outcome of the patient. Both complete MiECC systems reduced the bolus and GME challenges similarly and no significant differences were reported in number and volume of GME in the arterial line. This could have been anticipated since both oxygenators with IAF, as used in the MiECC systems, showed very excellent and comparable air removal characteristics, as reported in a clinical study.⁹ Together with the similar air removal properties of both VBTs as assessed in our study, an equal GME load in the arterial line is expected. Interestingly, the marginally, but not significant, lower GME load in the arterial line of the Inspire Mini.I system may be caused by the slightly better air removal of the Inspire VBT 8. The two complete systems were able to reduce the bolus challenge volume of 5 mL even more and a total reduction of 99.999% was reached.

Since the Inspire Min.I system of LivaNova shows almost the same GME removal characteristics as the MECC of Getinge, we may expect that the use of the Inspire Min.I will result in comparable clinical GME data. Our group showed that the MECC system resulted in a mean GME load of 3.1 ± 3.0 µL, which was considered safe.⁵ From our current in vitro results, we may expect comparable results with the Inspire Min.I system in a clinical setting.

Although the use of the APC system with the Inspire VBT 8 of the Inspire Min.I did not result in significant improved air removal compared to the MECC with VBT 160, the APC seems to contribute to safety. Namely, the number of actions required by the perfusionist was reduced, as the incoming air was scavenged automatically from the Inspire VBT 8, and the arterial pump was ramped down by the APC system. This actively contributes to simplifying the air management ability of the MiECC system which contributes to increased safety, as supported by two other studies with this system assessed in the clinical setting.^17,18 Inspire VBT 8 (LivaNova) priming volume is 128 mL, which is smaller than the Getinge VBT (160 mL). It has to be noted that, in the field of MiECC systems, the smaller prime volume is considered an important factor for avoiding transfusions. In fact, it has been shown that, even small differences in prime volume of only 120 mL influence the rate of red blood cell transfusions in heart surgery.¹⁹

This study has some limitations. The study was conducted with air challenges in an in vitro setup. In the clinical setting, different air and GME properties may play a role. In this test, one bubble counter was used. Two previous studies^20,21 showed that bubble counters are very difficult to validate and different bubble counters may provide different measurements of the absolute numbers and volume of GME. Importantly, the results obtained with bubble counters can be used as relative values. Besides, this study was performed with the exact bubble counter which was used in all our previous studies^5,8,9 and this bubble counter was also validated.²²

Conclusion

Both MiECC systems assessed in this study, the LivaNova Inspire Min.I and the MECC of Getinge, have comparable air removal properties, after both bolus and GME air challenges in an in vitro setup. Although the difference was not significant, the Inspire Min.I systems showed a slightly lower GME load in the arterial line after both the bolus and the GME challenges. Besides, APC system automatic air removal, as applied in the Inspire VBT 8 of the LivaNova system, may enhance patient’s safety with the use of a MiECC system since air management is simplified. We consider both systems equally safe for clinical use.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: LivaNova.

ORCID iD

Marco C Stehouwer

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