ISO/TR 19024:2016

TECHNICAL ISO/TR
REPORT 19024
First edition
2016-09-01
Evaluation of CPB devices relative
to their capabilities of reducing the
transmission of gaseous microemboli
(GME) to a patient during
cardiopulmonary bypass
Évaluation des dispositifs PCP relative à leurs capacités de réduire la
transmission des micro-embolies gazeuses (MEG) à un patient durant
un pontage cardiopulmonaire
Reference number
ISO/TR 19024:2016(E)
©
ISO 2016

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ISO/TR 19024:2016(E)

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ISO/TR 19024:2016(E)

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviated terms . 2
5 Recommendations . 2
5.1 General . 2
5.2 Materials and methods . 2
5.3 Results and verification of test . 3
5.4 Components . 3
Annex A (informative) Rationale for the recommendations of this document .5
Bibliography . 6
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ISO/TR 19024:2016(E)

Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www.iso.org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www.iso.org/patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation on the meaning of ISO specific terms and expressions related to conformity assessment,
as well as information about ISO’s adherence to the World Trade Organization (WTO) principles in the
Technical Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.
The committee responsible for this document is ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
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ISO/TR 19024:2016(E)

Introduction
Present-generation extracorporeal circuit devices are not designed to generate gas bubbles, as was
the case with bubble oxygenators, as a function of their mechanism to achieve gas transfer. Gaseous
microemboli (GME), while significantly reduced in current extracorporeal circuits, are still detectable.
The presence of GME in blood is not a normal condition and can trigger potentially adverse conditions
as both a foreign surface and as a particle or embolus. Adverse systemic sequelae from GME may include
activation of blood cells, immune responses, and blockage of blood vessels.
While attributing a causal relationship between GME and significant adverse clinical sequelae is not
clear, laboratory equipment and methodology for testing extracorporeal devices on the bench top and
are clinically available for use.
This document will review the current scientific literature on GME detection methodologies and their
clinical relevance.
GME testing is currently being performed by companies and research groups. Both users and
manufacturers will benefit from the creation of standardized terminology for use in this work.
Development of a consensus position on the clinical implications of GME and the capabilities and
limitations of currently utilized monitoring equipment will also serve both users and manufacturers.
The currently available monitoring equipment will have a cost impact on all manufacturers and may
burden small enterprises more so than existing larger companies. The equipment cost, however, is less
expensive than equipment currently required to evaluate many of the extracorporeal devices such as
blood gas analysers, cell counters or spectrometers. Independent investigators with such equipment
and expertise are also an option.
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TECHNICAL REPORT ISO/TR 19024:2016(E)
Evaluation of CPB devices relative to their capabilities of
reducing the transmission of gaseous microemboli (GME)
to a patient during cardiopulmonary bypass
1 Scope
This document recommends acceptable methodology for conducting gaseous microemboli (GME)
testing and discusses limitations of current test methods. Tests described in this document are limited
to those conducted using an in vitro circulatory system.
This document is applicable to all devices intended for extracorporeal circulatory support during
cardiopulmonary bypass (CPB). It outlines approaches currently used to assess the ability of CPB
devices to handle GME.
2 Normative references
There are no normative references in this document.
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
• ISO Online browsing platform: available at http://www.iso.org/obp
• IEC Electropedia: available at http://www.electropedia.org/
3.1
cardiopulmonary bypass
extracorporeal circuit used to support a subject’s circulatory and gas exchange requirements when the
heart and lungs are temporarily functionally excluded from normal circulation during cardiac surgery
3.2
gaseous microemboli
air bubbles present in circulating blood that are in the range 10 µm to 500 µm diameter
3.3
ultrasonic detector
device based on Doppler phenomenon (pulsed or continuous wave) that emits sound signals from a
piezoelectric crystal that are reflected from moving blood
EXAMPLE 1 Transcranial Doppler, transesophageal echocardiography, or clamp-on sensors for extracorporeal
tubing with the latter used for bench top in vitro testing.
EXAMPLE 2 Ultrasonic detectors are able to discriminate circulating particles from background blood flow,
and detected reflections (or signals) can be analysed in real time to produce a display of approximate quantities
and sizes during the sampling time frame.
3.4
whole blood
fluid used for bench-top studies involving gaseous microbubbles is anticoagulated whole blood
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ISO/TR 19024:2016(E)

4 Abbreviated terms
CPB cardiopulmonary bypass
GME gaseous microemboli
5 Recommendations
5.1 General
This document addresses current state-of-the-art bench-top testing and is intended to provide guidance
to those performing such tests so that reproducible results may be obtained to compare devices. Use of
anticoagulated whole blood is noted to provide more relevant results when performing bench-top GME
studies. This clause provides testing recommendations.
5.2 Materials and methods
5.2.1 The bench-top circuit should be described in sufficient detail so that an identical circuit can be
assembled for additional testing by other parties.
5.2.2 The description of the circuit should include the following:
— physical components, including:
— tubing dimensions (material, internal diameter, wall thickness, length);
— types and dimensions of tubing connectors used;
— manufacturer and model of detector;
— number, specific location, and method of attachment of detector sensors in the test circuit;
— other circuit components such as the device being evaluated;
— type of pump used to circulate blood;
— presence of a debubbling chamber (if used);
— conditions of the test, including temperature of test fluid, fluid flow rate, establishment of baseline
conditions, site of injection of bubbles;
— hematocrit (should be specified);
— isotonic solution (shall be used for dilution);
— anticoagulant used (should be specified);
— evidence of calibration of the bubble detector;
— method of introduction of bubbles into the test circuit (e.g. continuous injection vs. bolus injection),
total volume over time of bubbles introduced and means of introduction (e.g. calibrated pump vs.
hand injection);
— gas composition (should be room atmosphere only);
— reservoir level when using a hard shell (should be specified);
— volume of blood and the presence (when a soft bag venous reservoir is being tested) and the position
of volume regulation mechanism (should be described).
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ISO/TR 19024:2016(E)

5.2.3 The duration of the test, sampling schedule, and number of tests should be described.
5.3 Results and verification of test
5.3.1 Bubble counts according to the location of the detector sensors should be quantified in terms of
sizes and numbers.
5.3.2 The total volume of gas may be reported based on calculations of sizes and numbers.
5.3.3 Results may be reported in numerical or graphical form.
5.3.4 As noted in 5.2.3 above, the number of tests performed under a given set of conditions must be
reported with the results, and if the results represent mean values of several tests, this should be noted.
5.4 Components
Components that may be tested include, but are not limited to, one or a combination of the following:
5.4.1 Combination cardiotomy/venous reservoir
This component consists of a hard shell reservoir with multiple inlet connectors and internal chambers
used to process either cardiotomy-suctioned blood or venous blood.
These components may contain gross filters and defoamers for removal of large bubbles and blood
debris such as large clots or fat particles.
After processing both types of blood, a settling chamber collects the blood for removal by a pump and
transmission through the gas exchange section of the oxygenator.
5.4.2 Standalone cardiotomy reservoir
This component is used for processing either cardiotomy-suctioned blood or vent blood.
After processing, blood typically drains by gravity into a larger reservoir and becomes part of the
circulating blood.
Processed blood may be sequestered in the reservoir for additional processing by a cell
salvage/wash unit.
5.4.3 Standalone venous reservoir, either hard shell or flexible bag type
These components only collect blood from the CPB venous drainage tubing.
5.4.4 Oxygenator with or without integral arterial filter
This component consists of multiple fine strands of hollow fibres containing flowing gas arranged in a
configuration to promote mixing of venous blood near the fibre surfaces for gas exchange to take place.
A heat exchanger for circulation of temperature-controlled water most often is integral to the
oxygenator.
An integral arterial filter may or may not be part of the oxygenator.
5.4.5 Standalone arterial filter
This component consists of a fine screen mesh fan-folded to provide sufficient surface area for flows
used during CPB with an acceptable pressure drop.
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ISO/TR 19024:2016(E)

5.4.6 Venous bubble trap
This component consists of a chamber intended to trap and remove air bubbles that may be present in
the CPB venous tubing.
5.4.7 Blood pump
Either a roller pump or a centrifugal pump may be used in the test circuit.
When using a roller pump, the specifications (e.g. dimensions of pump, tubing
...