Diagnostic Systems in Medical Technology Course Book PDF

DIAGNOSTIC SYSTEMS IN MEDICAL TECHNOLOGY DLBMETDSM01_E DIAGNOSTIC SYSTEMS IN MEDICAL TECHNOLOGY MASTHEAD Publisher: IU Internationale Hochschule GmbH IU International University of Applied Sciences Juri-Gagarin-Ring 152 D-99084 Erfurt Mailing address: Albert-Proeller-Straße 15-19 D-86675 Buchdorf [email protected] www.iu.de DLBMETDSM01_E Version No.: 001-2024-0328 Prof. Dr.-Ing. Lars Meinecke Cover image: Adobe Stock. © 2024 IU Internationale Hochschule GmbH This course book is protected by copyright. All rights reserved. This course book may not be reproduced and/or electronically edited, duplicated, or dis- tributed in any kind of form without written permission by the IU Internationale Hoch- schule GmbH. The authors/publishers have identified the authors and sources of all graphics to the best of their abilities. However, if any erroneous information has been provided, please notify us accordingly. 2 TABLE OF CONTENTS DIAGNOSTIC SYSTEMS IN MEDICAL TECHNOLOGY Introduction Signposts Throughout the Course Book............................................. 6 Suggested Reading................................................................ 7 Learning Objectives............................................................... 8 Unit 1 Medical Devices in Diagnostics and Reprocessing of Medical Devices 9 1.1 Overview of Medical Devices in Diagnostics..................................... 11 1.2 Regulatory Requirements Related to the Reprocessing of Medical Devices......... 14 1.3 Cleaning, Disinfection, and Sterilization........................................ 17 1.4 Validation of Reprocessing Procedures......................................... 27 Unit 2 Cardiovascular and Neurological Functional Diagnostics 33 2.1 Cardiovascular Functional Diagnostics......................................... 34 2.2 Neurological Functional Diagnostics........................................... 54 Unit 3 Vascular, Neurovascular, and Pneumological Functional Diagnostics 67 3.1 Measuring Principles of Vascular and Neurovascular Functional Diagnostics....... 68 3.2 Pneumological Functional Diagnostics......................................... 76 Unit 4 Biomedical Optics, Ophthalmic Measurement Technology, and Audiometry 87 4.1 Biomedical Optics (Biophotonics)............................................. 88 4.2 Ophthalmic Measurement Technology......................................... 98 4.3 Audiometry................................................................ 100 Unit 5 Medical Imaging Systems 1 111 5.1 Ultrasound Diagnostics (Sonography)......................................... 112 5.2 Conventional X-Ray Diagnostics.............................................. 121 5.3 Computed Tomography..................................................... 126 5.4 Magnetic Resonance Imaging (MRI)........................................... 133 3 Unit 6 Medical Imaging Systems 2 143 6.1 Nuclear Medicine Imaging................................................... 144 6.2 Cone Beam Computed Tomography (CBCT)................................... 155 6.3 Endoscopy................................................................. 157 Appendix List of References............................................................... 166 List of Tables and Figures........................................................ 178 4 INTRODUCTION WELCOME SIGNPOSTS THROUGHOUT THE COURSE BOOK This course book contains the core content for this course. Additional learning materials can be found on the learning platform, but this course book should form the basis for your learning. The content of this course book is divided into units, which are divided further into sec- tions. Each section contains only one new key concept to allow you to quickly and effi- ciently add new learning material to your existing knowledge. At the end of each section of the digital course book, you will find self-check questions. These questions are designed to help you check whether you have understood the con- cepts in each section. For all modules with a final exam, you must complete the knowledge tests on the learning platform. You will pass the knowledge test for each unit when you answer at least 80% of the questions correctly. When you have passed the knowledge tests for all the units, the course is considered fin- ished and you will be able to register for the final assessment. Please ensure that you com- plete the evaluation prior to registering for the assessment. Good luck! 6 SUGGESTED READING Kramme, R., Hoffmann, K.-P., & Pozos, R. S. (Eds.). (2011). Springer handbook of medical technology. Springer. http://search.ebscohost.com.pxz.iubh.de:8080/login.aspx?direct =true&db=cat05114a&AN=ihb.51242&site=eds-live&scope=site Moore, J. E., & Maitland, D. J. (Eds.). (2013). Biomedical technology and devices (2nd ed.). CRC Press. Chan, A. Y. K. (2016). Biomedical device technology: Principles and design (2nd ed.). Charles C. Thomas, publisher, LTD. Christe, B. L. (2009). Introduction to biomedical instrumentation: The technology of patient care. Cambridge University Press. 7 LEARNING OBJECTIVES The course book on Diagnostic Systems in Medical Technology initially examines the diverse reprocessing methods for medical products, subsequently providing an in-depth understanding of medical technology diagnostics. You will acquire the technical and application-specific fundamentals of various medical systems pertinent to diagnostic fields such as cardiovascular, neurological, vascular, neurovascular, and pulmonary func- tional diagnostics, enabling you to comprehend their utilization in medical practice. In subsequent units, you will explore the realms of biomedical optics, ophthalmologic meas- urement technology, and audiometry, as well as the functionality and areas of application for medical imaging techniques, including ultrasound, X-ray, computed tomography, mag- netic resonance imaging, and nuclear medical imaging. 8 UNIT 1 MEDICAL DEVICES IN DIAGNOSTICS AND REPROCESSING OF MEDICAL DEVICES STUDY GOALS On completion of this unit, you will be able to... – classify medical device-based diagnostics in the overall context of medical technology. – identify different application risks of diagnostic systems. – explain the relevance of reprocessing medical devices and the related legal framework. – classify the terms “cleaning,” “disinfection,” and “sterilization,” and explain common sterilization processes. – explain the validation of medical device reprocessing processes. 1. MEDICAL DEVICES IN DIAGNOSTICS AND REPROCESSING OF MEDICAL DEVICES Introduction The development of medical technologies and medical devices has made significant pro- gress in recent years and decades. Whole diagnostic and treatment approaches and even new branches of medicine have been made possible by advances in instrumentation, implant technology, and imaging systems. Today, more and more diseases can be diag- nosed and treated with the help of these and other medical technology systems, and patient outcomes continue to improve at an unprecedented rate. Modern systems and procedures such as sonography, radiological diagnostics, and magnetic resonance imag- ing (MRI) have become indispensable in both clinical and medical practices. There is also a large variety of technically comparatively simple medical products in everyday life. For example, infrared clinical thermometers, blood glucose meters, and patches. In addition, digitization in medical technology in particular is progressing, which benefits doctors and other service providers. For example, a diagnostic support system based on artificial intelligence can assist radiologists in detecting tumors, radiation therapy can be planned very precisely using appropriate software, and 3D images of a patient’s body can help surgeons plan and carry out surgery. Software has long since become an integral part of modern medical technology and is itself becoming a medical product. To be able to produce utilizable statements, however, in many cases, software relies on access to data with adequate quality that first needs to be generated or measured by med- ical technology hardware. In this respect, the hardware represents the basic requirement so that the far-reaching possibilities of medical-technical software may be utilized at all. This course focuses on this medical technology hardware and presents its structure and basic functionality. The next generation of technology, which may enable previously unimaginable treat- ments and make modern medicine more accessible to people around the world, is cur- rently being developed in the field of medical technology in cooperation with physicians, researchers, and engineers. Despite all the enthusiasm for modern (medical) technology, it must be remembered that it is also a challenge to achieve technical-medical break- throughs while avoiding increases in treatment costs and ideally even reducing them. 10 1.1 Overview of Medical Devices in Diagnostics Around the year 1900, after the discovery of X-rays by the German physicist Wilhelm Con- rad Roentgen in 1895, there was a breakthrough in medical technology that revolutionized medical diagnostics. Also in 1895, the Dutchman Willem Einthoven defined the nomencla- ture for the electrocardiogram (ECG), which is still used today. However, the first electro- cardiograph that could be used for clinical applications could not be put into operation until 1903 (Kramme, 2017, p. 3). A completely new era dawned at the beginning of the 1940s, when German engineer Kon- rad Zuse, among others, was able to construct the world’s first functional, program-con- trolled binary calculating machine (Kramme, 2017, p. 3). Based on this, computer science and data processing developed, and with it a technology that – and not just in medical technology – led to a further and even more profound revolution. It surpassed all previous technological developments by far because the step from analog to digital technology opened up completely new possibilities: For example, computed tomography could only be developed with the availability of computers, although the mathematical foundations had already been worked out in 1917. The first commercially available computer tomo- graph for clinical purposes was put into operation in 1972 at London’s Atkinson Morley Hospital (Kalender et al., 1990). The use of computers also enabled the clinical application of MRI. In 1977, it was possible for the first time to image the inside of the body without using X-rays (Kramme, 2017, p. 4). Around the same time, another new imaging system, positron emission tomography (PET), which can be assigned to nuclear medicine, became available. It again significantly expanded the possibilities of medical diagnostics, because PET supplements the diagnostic spectrum with quantitative and location-specific record- ing of physiological and metabolic processes. In recent years, additional hybrid systems such as the combination of PET and computed tomography or MRI and sonography, have been developed. Today, the focus is on evolu- tionary developments of existing technologies with ever shorter product cycles. This trend can be traced back to step innovations (i.e., the continuous development or step-by-step optimization of existing processes, methods, or techniques), which, in contrast with leap innovations (i.e., completely newly developed processes, methods, or techniques that are not based on existing and known ones), are more common today (Kramme et al., 2011). One can also recognize that previously existing boundaries between diagnostics and ther- apy are increasingly disappearing with the use of current technical solutions. This is indi- cated, for example, by relatively young sub-specialties like interventional radiology or interventional endoscopy. In interventional radiology, for example, the focus is not on finding a diagnosis, but on the active execution of minimally invasive therapeutic inter- ventions under radiological image control (e.g., ultrasound, MRI, and computed tomogra- phy; CT) and monitoring. 11 Relevance of Diagnostic Systems A functioning, modern healthcare system as we know it today would be unimaginable without the medical technology currently available. In this way, medical technology has a direct influence on health and, thus, also the population’s quality of life. In addition to other fields of medical technology, diagnostic medical technology plays an important part in the healthcare system. A large number of technological products for medical diagnostics, meanwhile, have become so much a part of the everyday clinical and medical routine that we take them for granted; for example, MRI or, in particular, radiol- ogy. According to BIOPRO Baden-Württemberg GmbH (n.d.): The days when the membrane of a heart-lung machine oxygenator was made from the same material as the skin of a sausage, or a ladies stockings company that also produced non-absorb- able nylon threads used in surgery are long gone. Medical technology has long become an own economic sector that produces technologically advanced products. (para. 1) The increasing speed at which innovations are being made is a major challenge for the medical technology industry today. New products quickly become obsolete; the majority of medical technology manufacturers generate around a third of their turnover with prod- ucts that are less than three years old. Globalization has created international competi- tion, which requires the rapid implementation of ideas into salable products. In this con- text, especially in medical technology, interdisciplinary cooperation between the individual disciplines involved, such as engineering, computer science, and medicine, is of particular importance. In addition, the complex regulatory requirements in medical tech- nology pose an additional challenge for manufacturers. Their influence on the entire life cycle of a medical device is significant and encompasses the innovation and development cycle as well. The European Regulation 2017/745 (Medi- cal Device Regulation; MDR) passed in 2017 led to significantly changed regulatory requirements for European medical device manufacturers compared to the previously valid European Union (EU) Medical Devices Directive. Triggered by the Poly Implant Pros- theses (“PIP”) scandal of 2012, which affected industrial silicone breast implants, the European Parliament felt compelled to accelerate the revision of the Medical Devices Directive and tighten the requirements to increase the safety of medical devices (Pur- nama & Drago, 2019). The transition from an EU directive to an EU regulation led to an EU-wide harmonization of the legal framework and, thus, to a reduction in nationally different legislative frame- works. On the other hand, with the MDR that has now become effective, innovation-inhib- iting amendments that have been accepted in favor of increased patient safety and legal harmonization are likely to prevail. An important factor for the hindrance of innovations is the increased level of detail of the requirements in almost all areas of the MDR. For exam- ple, the requirements for clinical trials and assessments are more extensive and detailed. 12 Although it can be assumed that such regulation will lead to increased product safety, the need for clinical data, as required for the clinical evaluation of a medical device in accord- ance with MDR 2017/745, increases with product safety. In order to obtain this clinical data, an increased number of clinical trials must be carried out (Fennema & Achakri, 2019). However, since the effort involved in organizing and conducting clinical trials is high, they represent a significant obstacle to innovation, especially for small- and medium-sized companies. In addition to the question of innovations in healthcare, another important aspect must be considered: The average age of populations is increasing, and not only in Europe, Japan, and the USA. In Germany, for example, there were around four million people aged 80 and older in 2008, which increased to six million people in 2021 (Statistisches Bunde- samt, 2022b). The reason for this development is not primarily an increase in life expect- ancy, as this only changed insignificantly in the years 2010 to 2020 (Statistisches Bunde- samt, 2022a), but in the increase in population. Such a development and the increasing need for new treatment options pose major challenges for healthcare systems, especially regarding funding. Advances in medical technology should, therefore, be applied effi- ciently. For example, they can be used to optimize both diagnostic and preventive options. In this way, innovative medical technology can provide significant support in reducing the increase in healthcare costs. According to Kramme et al. (2011): In addition to all these aspects, there is also the fundamental question of finding a balance between technical possibilities and clinical requirements. Many medical device manufacturers try to exhaust the technical possibilities to the full in order to be able to offer the best possible and most highly developed products. On the other hand, the result is that [...] the functions of many medical technological products go far beyond the needs and possible uses [in medical rou- tine]. [...] Numerous sophisticated products are perhaps technically perfect but are rarely tail- ored to suit a need. [...] This means that the technical possibilities are frequently beyond the ability of many users to use them. (p. 6). Medical Technology Systems and Their Application Risks The operating complexity and the often insufficient ability of medical users of diagnostic systems are therefore associated with corresponding application risks – in addition to pri- marily technical safety aspects. “Medical electrical (ME) equipment)” is used in particular in medical facilities, such as hospitals, medical practices or rehabilitation centers. There are special regulations and standards for medical electrical equipment which, among other things, stipulate that it may only be operated in special areas or rooms intended for this purpose. The power supply in medical locations must, in turn, meet its own special Medical location requirements, which are specified in IEC 64/2281. This is to ensure the safety of patients “Location intended for purposes of diagnosis, and users as well as the safety and continuity of the power supply for the operation of treatment including cos- medical electrical equipment. The main hazards posed by medical electrical devices and metic treatment, moni- medical electrical systems can be electrical, mechanical, or thermal. There is also a poten- toring and care of patients” (UK Department tial hazard from ionizing radiation, explosion, or fire. Other risks of an infectious nature of Health, 2017, p. 4). that should not be underestimated include hygiene risks from medical devices that are not adequately reprocessed. 13 In the intensive clinical routine, medical products are often used in close succession on different patients. Medical devices must, therefore, be reprocessed after each use on a patient, as otherwise there would be a very high probability of transmission of infectious agents. Medical devices that have cavities and/or maintain a warm, humid environment due to their function can also be regarded as sources of infection. The adequate reproc- essing of medical devices is, therefore, a very important aspect of clinical hygiene. In this context, the term “reprocessing of medical devices” is defined by the MDR as fol- lows: “‘reprocessing’ means a process carried out on a used device in order to allow its safe reuse including cleaning, disinfection, sterilisation and related procedures, as well as testing and restoring the technical and functional safety of the used device” (Regulation (EU) 2017/745, 2017, para. 39). It is mainly the patients who are endangered by contaminated devices or objects. On the other hand, the people who reprocess the medical devices are also exposed to a consider- able risk of infection. These are generally employees of the reprocessing unit for reusable medical devices (RMD). The importance of hygiene, especially in the clinical field, becomes clear when you look at older publications such as Stamm’s from 1978. In it, Nosocomial infection Stamm found that already many years ago around half of all nosocomial infections were This refers to germs that associated with medical interventions or were triggered by these measures (Stamm, trigger an infection and are closely related to an 1978). In this respect, the reprocessing of medical devices or objects that are repeatedly inpatient or outpatient used to care for patients is of particular importance in the prevention of nosocomial infec- medical measure. For this tions. reason, it is sometimes referred to as a “hospital- acquired infection”. 1.2 Regulatory Requirements Related to the Reprocessing of Medical Devices Medical device reprocessing and related areas as a whole are regulated by a variety of legal regimes, each of different legal significance. These include: laws and regulations: Regulations are rules that determine how certain laws are to be carried out. They are also called “ordinances”. Laws determine what should happen whereas regulations determine how laws should be implemented. international and national standards: Standards are regulatory frameworks. They are developed by consensus by technical specialists and represent the state of the art and knowledge. Most standards are revised regularly and therefore have a year and month in their name. directives: In the EU, a directive is a legal act of the EU that has to be transposed into national law by all EU member states within a certain period of time. The objective specified in the directive (e.g., a limit value for an environmentally harmful production) is binding. However, the choice of means of achieving the goal (prohibition or tax incen- tive) is left to the member states. guidelines: Guidelines, which are often also referred to as recommendations, represent instructions for the practical implementation of standards or legal acts. The guidelines are usually drawn up by experts in the relevant specialist societies. 14 Legal Acts in the European Union Since May 26, 2021, the MDR (EU 2017/745) has been the most binding regulation within the EU for all aspects mentioned therein that are related to medical devices. With regard to the processing of medical devices, for example, it obliges the manufacturer to provide the following information in the instructions for the use of the medical device (Regulation (EU) 2017/745, 2017): If the device is reusable, information on the appropriate processes for allowing reuse, including cleaning, disinfection, packaging and, where appropriate, the validated method of re-sterilisa- tion appropriate to the Member State or Member States in which the device has been placed on the market. Information shall be provided to identify when the device should no longer be reused, e.g., signs of material degradation or the maximum number of allowable reuses. (Annex I, Chapter III, 23.4 n) The quoted section shows that the MDR does not specify any precise requirements for the reprocessing of medical devices, but rather gives the member states a certain degree of leeway for national legislation. In Germany, as an example, Section 8 of the Medical Devi- ces Operator Regulation (Medizinprodukte-Betreiberverordnung, 2021) regulates the proc- essing of medical devices. However, there are still no direct concrete requirements in the MPBetreibV. Section 8.1 only states that the processing must be carried out using suitable, validated methods, taking into account the information provided by the manufacturer, in such a way that the success of these methods is comprehensibly guaranteed. The situation in other EU member states and even on a global scale is very similar to that in Germany: For more specific information on the concrete requirements for the reproc- essing of medical devices, reference is made to the respective recommendations of the relevant professional societies. In Germany, for example, there is the recommendation of the Commission on Hospital Hygiene and Infection Protection at the Robert Koch Institute (RKI) and the Federal Institute for Drugs and Medical Devices (BfArM) on Hygiene Require- ments for the Reprocessing of Medical Devices (Kommission für Krankenhaushygiene und Infektionsprävention & Bundesinstitut für Arzneimittel und Medizinprodukte, 2012). Such recommendations, which can also be understood as guidelines in the sense of the defini- tion of the term above, are then often published in specialist journals. If the recommenda- tions are observed and implemented, the authorities generally assume that the medical device has been properly reprocessed. In the USA similar guidelines entitled Guideline for Disinfection and Sterilization in Healthcare Facilities are published by the Centers for Dis- ease Control and Prevention (CDC; Rutala et al., 2019). Decontamination and reprocessing of medical devices for healthcare facilities is yet another such recommendation. This document is issued by the WHO; addresses an even more global audience; and is available in English, Russian, and Chinese (World Health Organization, 2016). Risk Assessment and Classification of Medical Devices Prior to Their Processing All of the recommendations mentioned in the previous section require a risk assessment and classification as a first step before the reprocessing of medical devices. As stated in Spaulding (1970), this step is essential to apply“risk assessment to determine the level of 15 decontamination [...]. This is known as the ‘Spaulding classification’. This system should be applied to categorize a reused medical device (RMD) according to its intended use and the subsequent level of reprocessing required to render the RMD safe for reuse.” (World Health Organization, 2016, p. 22). There are two reasons for this requirement: 1. On the one hand, for the large number of different medical devices used in everyday treatment, the risk associated with their intended use (i.e., with the type of applica- tion), is to be classified. 2. On the other hand, there should be a classification with regard to reprocessing requirements, which, in turn, result from the aforementioned application risk. The application risk is decisive for the effort and “cleaning goal” with which the reprocess- ing of the respective medical product has to take place. For example, the reprocessing requirements for an ultrasound probe that only comes into contact with intact skin in a non-invasive manner are less stringent than those for the reprocessing of a scalpel, because the risk of infection during use is naturally much higher in the latter case. The risk classification according to the application risk (“Spaulding classification”) includes three groups: Table 1: Risk Classification According to the Application Risk Risk category Level of decontami- Examples of medical devices nation High (critical items), i.e., “items that Cleaning and steriliza- Scalpels, cannulas, surgical instru- are involved with a break in the skin or tion ments, intravascular catheters, uri- mucous membrane or entering a ster- nary catheters, implants ile body cavity” (WHO, 2016, p. 22) Intermediate (semi-critical items), i.e., Cleaning and disinfec- Ventilation and anesthetic accesso- “items in contact with mucous mem- tion ries, flexible endoscopes (gastro- branes or body fluids” (WHO, 2016, scopes), clamps or forceps p. 22) Low (non-critical items), i.e., “items in Cleaning Blood pressure cuffs, ECG electrodes, contact with intact skin” (WHO, 2016, ultrasound probes, stethoscopes, p. 22) bandage scissors, bed frames, furni- ture, sinks, walls, floors Source: Lars Meinecke (2023), based on WHO (2016, p. 22). The classification with regard to the reprocessing requirements in some regions (e.g., the EU) is also divided into three groups, as shown in the following table. Table 2: Classification With Regard to Reprocessing Requirements Reprocessing Reprocessing requirements Examples category A No special requirements Laryngoscope blade 16 B With stricter requirements Medical products with sensitive surfaces that are sensitive to buckling, flexible endoscopes. C With particularly high requirements; Thermolabile instruments such as reprocessing may only be carried out probes for transesophageal echocar- automated; certification of the quality diography (TEE probes), vaginal or rectal management system; International ultrasound probes, rhinoscopes, ERCP Organization for Standardization (ISO) catheters Standard 13485:2016 required Source: Lars Meinecke (2023). When classifying according to the reprocessing requirements, those factors that may influ- ence the effectiveness or the suitability of the reprocessing process must also be taken into account for each medical device. These factors include the properties of the medical device (i.e., its construction, the material it is made of, and its functional properties), the manufacturer’s specifications on reprocessing as indicated in ISO 17664-1:2021 and ISO 17664-2:2021 (International Organization for Standardization, 2021), and the type of the previous and subsequent use of the medical device. Due to the complexity of carrying out the risk classification, different assessment aids are often available, including flow charts and even complete commercial IT solutions. 1.3 Cleaning, Disinfection, and Sterilization Cleaning, disinfection, and sterilization are procedures for decontamination that differ (in ascending order) in the degree of microbial “cleanliness” they can achieve. Since infec- tious agents such as viruses, bacteria, and fungi consist mainly of water, proteins, and nucleic acids, cell structure-destroying procedures are used during disinfection and sterili- zation. However, success is largely independent of the chosen approach. Instead, it pri- marily depends on the following factors: the number of pathogens present (initial germ count) the impact intensity of the chosen method (e.g., chemical or physical) the impact duration Since the effectiveness of disinfection and sterilization depends on the initial germ count in particular, prior cleaning of the object to be disinfected or sterilized is of crucial impor- tance. In addition, even minor residual contamination can result in the selected disinfec- tion or sterilization method or the medium used in this process not being able to fully advance to the microbes protected by dirt particles. Thorough cleaning is, therefore, the most important condition for effective disinfection or sterilization. 17 All three procedures for reprocessing, cleaning, disinfection, and sterilization aim to mini- mize the risk of infection by removing, killing, or inactivating pathogens. The following table distinguishes between the three terms. Table 3: Definition of Terms: “Cleaning,” “Disinfection,” and “Sterilization” Cleaning Definition: Cleaning means removing visible contamination (e.g., dirt, dust, and organic material). At the same time, a large proportion of microorganisms is elimi- nated. Objective: Mechanically removing microorganisms, but the microbes are not kil- led/inactivated. Germ reduction: 50 to 80%. The surface is freed from visible dirt. Cleaning must be carried out prior to disin- fection or sterilization. Disinfection Definition: Disinfection is the extensive or complete elimination of potentially pathogenic microorganisms; bacterial spores are excluded. Objective: Killing germs and inactivating pathogens on surfaces and objects to minimize the risk of infection. Germ reduction: 80 to 99.9%. Sterilization Definition: The complete elimination of all microbial states including bacterial spores (i.e., both potentially pathogenic microorganisms and non-pathogenic germs). Objective: Total absence of germs (i.e., the killing of all microorganisms) and/or the inactivation of all viruses in all stages of development. Germ reduction: 100%. Sterilization allows complete sterility by killing all microorganisms, inactivating all viruses, and killing stubborn spores. Source: Lars Meinecke (2024). The selection of the reprocessing process(es) suitable for a product initially depends on the manufacturer’s specifications. The user is obliged to obtain this information from the manufacturer and to include it in the risk assessment, the design of the reprocessing proc- ess, and its documentation. This inclusion ensures that the manufacturer- and product- specific recommendations for reprocessing are taken into account. According to the EU MDR under “reusable devices requiring cleaning, disinfection, sterili- sation or refurbishing between uses” (EU Regulation 2017/745, Annex VI Section 6.2), it can be assumed that the manufacturer will be able to provide the most appropriate rec- ommendations for the reprocessing of their own product. All medical device manufactur- ers are, therefore, obliged under the EU MDR to provide users with such reprocessing rec- ommendations (Regulation 2017/745, Annex I, 23.4., Paras. i and n). The previously- mentioned ISO 17664-1 and ISO 17664-2 standards specify which information is to be provided in which form. The reprocessing process of a medical device in a typical reprocessing unit for medical devices (called a “Central Decontamination Unit”; CDU), such as in a hospital, includes mechanical cleaning and disinfection in a “washer-disinfector” and subsequent steam sterilization. This reprocessing process is normally suitable for all medical devices with an application risk category up to “High (critical items)” and a reprocessing category up to Group B (also called “critical-B” or “high-B”). For all medical devices that cannot go 18 through this typical reprocessing process (“critical-C”), careful examination, justification, and documentation are imperative to determine whether the “standard process” remains applicable. In general, critical-C medical devices are thermolabile and must not be exposed to high temperatures, such as 134 °C during steam sterilization. In the following sections, the most widespread sterilization processes are presented. As already mentioned, the principle applies to every sterilization process that the items to be sterilized must be thoroughly cleaned before sterilization, since protein residues or salt crystals, for example, can serve as a protective cover for microorganisms and pose an impediment to killing them. In addition, the materials to be sterilized must be dry. Steam Sterilization Steam sterilization is a sterilization process based on the use of water vapor. Because of its ease of use, it is the most important and, at the same time, the safest sterilization process for medical devices. The mode of action is based on the transfer of thermal energy to the contaminated surfa- ces. This happens through the condensation of saturated, pressurized water vapor (satu- Pressurized steam rated steam) on these surfaces. The energy released during the condensation process on This is water vapor above the barometric pressure. the item to be sterilized kills or inactivates the microorganisms. Since the condensation of This pressure is reached the steam is a phase transition (change of state), the thermal energy of the heated steam is automatically as soon as transferred to the surface of the items to be sterilized. The temperature during this (and water is heated above 100 °C and the water any other) phase transition is constant and does not change. vapor cannot escape (i.e., in a closed container, comparable with a pres- Vapor pressure and vapor temperature are interdependent and clearly correlate in a sys- sure cooker). The higher tem where liquid water and a pure, 100% water vapor atmosphere are present. Both water the steam temperature, and vapor are present exactly at their boiling points and the amount of evaporating water the higher the pressure. and condensing vapor is identical. There is a stable equilibrium. The state of the vapor is called “saturated steam.” A 100% saturated steam atmosphere ensures the presence of moisture and a uniform temperature distribution since the pressure determines the tem- perature. This effect can be observed in everyday life when boiling water: The normal ambient pressure of 1013 mbar determines the boiling temperature of water at 100 °C. In the high mountains, where the ambient pressure can be much lower, the boiling tempera- ture is also much lower than 100 °C. In a pressure cooker, it is the other way around. Here, the ambient pressure (in the pot) is higher, and thus, the boiling temperature of the water is also above 100 °C. In practical use, two standard conditions are used in steam sterilization: 121 °C at a pressure of 2 bar and at least 15 minutes residence time 134 °C at a pressure of 3.2 bar and at least 3 minutes residence time Due to the relatively high temperatures, the sterilization method is only suitable for ade- quately heat-resistant goods. 19 Steam sterilization exploits the distinct correlation of boiling temperature and boiling pressure in a 100% water vapor atmosphere by first completely removing the air from the sterilization chamber and replacing it with saturated steam. This process is necessary because the steam can only exert its effect on the items to be sterilized if (residual) air has first been completely removed from the sterilization chamber and the (potentially wrap- ped) items to be sterilized. The surface of an object exposed to ambient air is studded with air constituents (oxygen, nitrogen, etc.). In steam sterilization, these air molecules are first replaced by water molecules in a steam atmosphere (Meurer, 2011). Since evacuation sig- nificantly accelerates this process, this step is preceding the actual sterilization process and is referred to as “fractionated vacuum process.” The fractionated vacuum process represents the state of the art in steam sterilizers for medical devices and has been used for several decades. During the process, which is repeated several times, steam is injected into the sterilization chamber after evacuation (steam surge) and the resulting mixture of steam and residual air is directly removed again by means of another evacuation (Wintermantel & Ha, 2009). The number of evacuation repetitions plays an important role in the degree of residual air removal. These are repeated until the required residual air percentage is reached or undercut. In the following figure, the air content in the chamber after repeated evacuation is indicated by different blackening of the fields. Figure 1: Air Thinning During the Fractionated Vacuum Process Source: Meurer et al. (2011, p. 66). 20 It must be ensured that no air pockets remain (e.g., in porous materials), otherwise suc- cessful sterilization cannot be guaranteed. This is because, at any point where there is a pocket of air, it displaces the steam. At such a spot, moisture (condensate) evaporates until the air is saturated. Heat is consumed in the process and the temperature drops locally, which jeopardizes the sterilization success and may lead to incorrect sterilizations. The individual process steps of a sterilization cycle in a steam sterilizer are shown sche- matically in the following figure. Figure 2: Process Steps in Steam Sterilization Source: Lars Meinecke (2024), based on Popp (2017). Accordingly, steam sterilization can be divided into the following phases: venting phase: This includes the fractionated vacuum process to achieve uniform steam permeation. heat-up time and compensation time: The heat-up time is the time required to reach the sterilization temperature in the chamber. Since the temperature in the material to be sterilized lags behind the chamber temperature, the compensation time is the time that elapses after the heat-up time until the sterilization temperature is reached in the sterilization material. In the fractionated vacuum process, this time usually amounts to a few seconds. plateau period: Also called the “hold period,” the plateau period (formerly called the “sterilization time”) is the sum of compensation time, the exposure or inactivation time, and the safety margins added in practice: plateau period = compensation time + exposure or inactivation time + safety margin drying period: The sterilization chamber is again vacuumed to dry the sterilized load. This is because water (in this case the water vapor condensed on the items that have been sterilized) boils when the pressure is reduced below the boiling pressure corre- sponding to the water temperature. In this way, the condensate evaporates more quickly. The lower the vacuum, the better the drying. Proper drying generally requires a drying vacuum between 20 and 40 mbar, which corresponds to evaporation tempera- 21 tures between 18 and 29 °C (Meurer, 2011, p. 69). The amount of condensate produced is proportional to the amount of heat quantity required to heat the sterilizer load. Inci- dentally, it differs considerably at the same temperature and weight: Plastics, such as polypropylene, for example, have a much higher condensate quantity compared to metals due to the high specific heat capacity of plastics. In practice, the drying phase lasts less than 10 minutes and ends once the pressure has been equalized. The following figures show an example of a large steam sterilizer used in the central ster- sterile ile supply department (CSSD) of a hospital and its loading with containers or soft packs. An object may be descri- bed as sterile if the statis- tical probability of viable Figure 3: Large Steam Sterilizer: Loading With Containers residual germs on the object is less than 1:1,000,000. For example, if a million scalpels were to be sterilized, a viable microorganism should only be found on one of the scalpels. Source: Meurer et al. (2011). 22 Figure 4: Large Steam Sterilizer: Loading With Soft Packs Source: Meurer et al. (2011). 23 The commercial range of steam sterilizers covers varying sizes for different areas of appli- cation. A basic distinction is made between batch sterilization and continuous steriliza- tion. In the healthcare sector, only batch sterilizers are used. Batch refers to the material to be sterilized that is grouped together in a load. The capacity of a sterilizer is specified in sterilization units (StU). An StU has the nominal dimensions (height x width x depth) 300mm x 300mm x 600mm. Thus, one StU has a volume of 54 liters (Miorini, 2008). Steriliz- ers are classified on the basis of their capacity: If the capacity is greater than or equal to one StU, they are referred to as large sterilizers. If the capacity is smaller, they are small sterilizers. In the EU, the following standards specify the essential performance requirements for ster- ilizers used predominantly in healthcare for the sterilization of medical devices and their accessories, including the corresponding test methods: EN 285:2021-12: Sterilization - Steam Sterilizers - Large Sterilizers (Deutsches Institut für Normung, 2021) EN 13060:2019-02: Small Steam Sterilizers (Deutsches Institut für Normung, 2019) Dry Heat Sterilization Dry heat sterilization is another thermal sterilization process. Unlike steam sterilization, however, dry heat sterilization works with hot air. However, its applicability is limited. The reason for this is the higher resistance of microorganisms to lower relative humidity and the lower thermal conductivity of air, characterized by its heat transfer coefficient, as shown in the following table. Therefore, hot air sterilization must be performed at much higher temperatures and with a prolonged plateau period to ensure safe sterilization. To clarify: Compared to steam sterilization with an exposure time of 3 minutes at a tempera- ture of 134 °C, the exposure time of hot air sterilization at a roughly comparable tempera- ture of 160 °C is a full 120 minutes. Table 4: Comparison of the Heat Transfer Capability of Air and Condensing steam Heat transfer coefficient W/ m2 · K Condensing steam 5000–12000 Air 10–30 Source: Lars Meinecke (2024), based on Wintermantel and Ha (2009). These factors mean that hot air sterilization is mainly used for very temperature-resistant and mostly unwrapped items or materials. It must be ensured that the hot air can flow freely around the items to be sterilized and that large items do not generate a slipstream, for example, depending on the direction of flow. In this respect, a block arrangement of the items must be avoided. According to Kramme et al. (2011), “because of their unreliable operation, hot air sterilizers should only be used to a very limited degree. Their ﬁelds of use are glass (laboratory), metal, porcelain [and] packaging materials [like] metal cases, glass bowls [and] aluminium foil” (p. 22). 24 Low-Temperature Chemical Gas sterilization With Ethylene Oxide or Steam Formaldehyde Chemical gas sterilization processes operate at comparatively low temperatures. Their active principle is, therefore, not based on thermal factors but on the germicidal effect of gases. Direct contact of the gas used with the microorganisms is necessary for the effec- tiveness of such processes. Whether a sterilizing gas is suitable, therefore, depends on two factors: (1) on the penetration behavior of the gas into the item to be sterilized and (2) on the surface properties of the item. In practice, the sterilizing gases ethylene oxide (EO) or steam formaldehyde (FO) are used. Both gases are toxic. For this reason, gas sterilization processes should only be used if the material properties of the items to be sterilized do not permit sterilization with other processes (e.g., for thermolabile products classified as critical-C). Both sterilization gases have specific advantages and disadvantages: While in the case of EO sterilization, particular attention must be paid to the hazardous nature of handling and the long desorption times, the main disadvantage of FO is its insufficient depth penetration. Ethylene oxide sterilization EO sterilization is a low-temperature process that can kill microorganisms from as low as 10 °C. However, the sterilization time depends on the temperature: The higher the sterili- zation temperature, the shorter the sterilization time. For this reason, a temperature range of 37 to 55 °C is often used. EO has the greatest sterilization capacity and is also absorbed by most polymeric materials and can penetrate their material walls without having to be transported to difficult-to-reach areas of the items to be sterilized by complex procedures. During the sterilization phase, this is an extremely advantageous property. However, it often leads to long venting times in the desorption phase following sterilization (where the sterilizing gas is removed from the sterilized goods). EO can be used in an underpressure process, but special attention must be paid to the highly explosive properties of pure ethylene oxide. If, on the other hand, it is used by means of a positive pressure process with CO2 as the carrier gas, the sterilization system must be elaborately sealed and checked very regularly. This is because the odor threshold of the EO, which is classified as carcinogenic, in combination with the carrier gas, is around 700 times higher than the permissible workplace limit. The disposal of the EO fol- lowing the actual sterilization is also complex and cost-intensive: For example, its conver- sion into ethylene glycol, its incineration, or the use of catalysts. For this reason, the EO process is practically no longer used in hospitals; instead, it is mainly found in industrial facilities. Formaldehyde steam sterilization The potential endangerment to users posed by FO is lower than that posed by EO. The working temperature of the low-temperature steam-and-EO sterilization process is 55 to 75 °C, which is higher than that of the ethylene oxide process. Although this limits the applicability of the process for thermally sensitive items, FO steam sterilization is never- theless an alternative to the EO process. This is because FO is non-explosive and non- flammable. In addition, sorption in the items to be sterilized is considerably lower, which 25 Sorption means that FO can be removed from the sterilized items immediately after the sterilization This refers to the accumu- process without subsequent venting. This means that the goods can be used again imme- lation or uptake of a gas or dissolved substance on diately. On the other hand, this advantage also represents a disadvantage, because the or by a porous solid mate- penetrating power into the items to be sterilized is lower than with EO. rial. Depending on the sorption mechanism, a distinction is mainly The FO process uses a combination of FO gas and water vapor to kill germs. Only the com- made between adsorp- bination of these two substances can achieve the effectiveness required for sterilization. tion and absorption. Steam or dry FO gas alone, on the other hand, would not be sufficient at the prevailing Adsorption is the accu- mulation or binding of process temperature. The FO process uses underpressure because the vapor pressure of gases, vapors, or dis- the gas combination at the prevailing process temperature is below atmospheric pressure. solved substances on the surface of solid, especially After the plateau period, the gas is removed from the chamber and sterilized items by porous bodies. Absorp- steam washing using the fractionated vacuum process. Finally, flushing with air is carried tion, on the other hand, out. The exposure time of the steam-FO mixture is about 60 minutes at a temperature of refers to their diffusion into the body. 60 °C. The entire process, including desorption and drying, takes about 3 hours. Low temperature plasma sterilization Plasma The process is based on the generation of a plasma from a gas. The plasma is generated in As the temperature rises, a deep vacuum using a high-frequency alternating electric field. In this way, free gas radi- there is a sequential tran- sition of all substances cals are generated which are highly reactive and have a very high sterilization capacity. from a solid to a liquid The gas used is usually highly diluted hydrogen peroxide (H2O2) in vapor form. In princi- and, subsequently, to a ple, other gases could also be used, but the advantage of hydrogen peroxide is its microbi- gaseous state. Upon fur- ther increase in tempera- cidal effect, as no plasma can be generated in the cavities of the items to be sterilized. ture, the formation of a When a microbicidal gas is used, a sterilization effect can still be achieved inside the plasma occurs. Therefore, plasma is commonly goods: The plasma acts on their outer surfaces, while H2O2 acts mainly on the inside. referred to as the “fourth phase of matter,” as it Low-temperature plasma sterilization requires comparatively high investments and also involves the dissociation of gas atoms into their has high operating costs and only a limited range of applications. For these reasons, it is constituent parts, namely often used only as a supplement to other sterilization processes, in particular, when rapid electrons and nuclei reusability of certain (e.g., thermolabile) and geometrically less complex medical devices (Günter, n.d.). is required. Sterilization with Ionizing Radiation Sterilization by ionizing radiation is a low-temperature sterilization process used for a number of medical products. A distinction is made between particle radiation (beta or electron radiation) and electromagnetic waves (gamma radiation). The principle is based on the radical generation, ionization, and excitation of atoms or molecules by ionizing radiation. The resulting ionized or excited atoms and radicals are highly reactive, which leads to the killing of microorganisms in the sterilized material. Both electron beams with low penetration depth and gamma beams with particularly high penetration depth are 60 used for sterilization. Primarily, cobalt-60 ( Co) is used as a readily available and reliable gamma ray source. Its high penetration depth results in very efficient sterilization. How- ever, for certain materials, gamma irradiation may cause chemical or physical changes. For example, oxidation in polyethylene and delamination and cracking in polyethylene knee bearings used in prosthetics (Williams et al., 1998). Another disadvantage is the high cost of the process. Due to the investment costs for such facilities, which are expensive and subject to approval, sterilization with ionizing radiation is only used in the industrial 26 sector with a correspondingly high throughput. The main area of application is the sterili- zation of disposable medical products, pharmaceutical products, and the treatment of medical transplants. 1.4 Validation of Reprocessing Procedures To “validate” means to determine the importance, validity, or value of something. In terms of the reprocessing of medical devices, it refers to the reliability of the reprocessing proc- ess. Operators of medical institutions must be able to prove that, depending on the type of reprocessing, the reprocessing method used either ensures low-germ or sterile goods, and can thus achieve the required safety for patients and users. Validation aims to obtain safe, reproducible, and traceable reprocessing processes for reusable medical devices. The relevant standard defines the term validation as follows: Validation is a “documented procedure for obtaining, recording and interpreting the results required to establish that a process will consistently yield [products] complying with predetermined specifications” (ISO, 2021, Section 3.20). If this definition is transfer- red to the situation of reprocessing medical devices, the validation of the reprocessing process represents the proof that the process reproducibly achieves the intended effect under the operating conditions at the installation site and for each of the defined goods, packaging types, and loading arrangements (i.e., that it produces clean, disinfected, or sterile products). In this context, the validation of reprocessing procedures needs to be separated from the testing of devices for the reprocessing of medical devices, such as sterilizers. This is because a differentiation has to be made between devices that are tested and procedures or processes that are validated. Likewise, different standards are relevant for the two activities. First, washer disinfectors (WDs) and sterilizers must be checked by the manufac- turer after they have been installed. The manufacturer must provide evidence that the respective device meets the requirements specified by the relevant standard at the final installation site. If the manufacturer obtains a positive result after completion of the test, it has fulfilled its responsibility. On the other hand, validation of the procedures used for sterilization, cleaning, and disin- fection falls under the responsibility of the operator. By means of validation, the operator determines whether the equipment is capable of achieving the required effect (i.e., clean- ing, disinfection, or sterilization), namely for the items to be sterilized that are used at the installation site, with the operating resources available at the site of operation (e.g., with regard to the quality of water, steam, cleaning agents, etc.), and with regard to the loading method and type of packaging (e.g., unpacked, container- ized, or soft-packed). 27 Since validation itself is a complex process that differs not insignificantly for the various reprocessing methods, recommendations for the validation and routine monitoring of sterilization processes have been developed by professional societies in and for most of the legally independent regions of the world and, in fact, sometimes even individually for each of the various reprocessing methods. The following are just a few examples: Recommendation for the Validation and Routine Monitoring of Sterilization Processes With Saturated Steam for Medical Devices (German Society for Hospital Hygiene; DGKH, n.d.) Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling (U.S. Food & Drug Administration, n.d.) Testing, Validation and Routine Control of Decontamination Processes for Medical Devices (World Federation for Hospital Sterilization Sciences; WFHSS, n.d.) Alongside the actual sterilization as a part of the overall reprocessing process, the upstream automated cleaning and disinfection process in the WD also needs to be vali- dated. The workflow of this validation and its scope are often described in guidelines spe- cific to each global region. One example is the Guideline Compiled by DGKH, DGSV and AKI for the Validation and Routine Monitoring of Automated Cleaning and Therman Disinfection Processes for Medical Devices (DGKH et al., 2017, p. 1). Sometimes guidelines are not only specific to a region but also for a certain medical device or family of devices, such as the ESGE-ESGENA Guideline for Cleaning and Disinfection in Gastrointestinal Endoscopy (Bei- lenhoff et al., 2008, p. 939). Validation involves several steps and is usually divided into the following three subsec- tions: 1. Installation qualification (IQ) is a one-off check to ensure that the work area and equipment are suitable and correctly installed for the intended use. For example, it is checked whether the installation room is suitable for the WD and whether the unit itself is suitable and correctly connected. 2. Operational qualification (OQ) aims to ensure the functionality of all the devices, work equipment, and accessories used. For example, it is checked whether the WD is functioning properly from a technical point of view, whether suitable sterilization load carts are available, whether the operating supplies such as water correspond to the manufacturer’s speciﬁcation, and whether suitable test equipment is used. 3. Performance qualification (PQ) involves checking predefined cleaning and disinfec- tion programs for typical operational loads (or “reference loads”) and documenting the results. This is to ensure that reproducible results are achieved at all times when these pre-determined parameters are adhered to. PQ is the process commonly refer- red to as validation. PQ, or revalidation, is repeated periodically (usually annually). A test report has to be prepared on the qualiﬁcations carried out, which must meet cer- tain minimum standards. It is required that the entire reprocessing process be validated as a basic principle. Proc- esses that take place within the WDs and sterilizers are often reviewed by external valida- tion service providers. The often manual sub-steps that follow these device processes are usually specified and checked by CDU management or in-house quality management. For this purpose, each sub-step must be defined in a “standard operating procedure” (SOP). 28 Furthermore, testing procedures and their acceptance criteria, as well as any necessary corrective actions, need to be defined. The result of a validation has to be documented and acknowledged by the responsible persons according to the ISO 15883 series of stand- ards for WD and DIN EN ISO 17665:2022-11 (Deutsches Institüt für Normung, 2022). Example: Validation of a Steam Sterilization Process in the EU The validation of a steam sterilization process starts with the IQ. Here, the device itself (i.e., the steam sterilizer) as well as the installation, equipment, and operating conditions, are first inspected. Subsequently, the sterilization processes intended for the device are tested in the OQ during several test cycles. The test is performed both with and without loading of the sterilizer. Finally, the PQ has to prove that sterile medical devices are obtained after the application of the specified sterilization process. This proof must be provided on a regular basis. Before validation, the items to be sterilized (i.e., which medical devices are to be sterilized in which loading configuration) must be defined. The validator and the CDU manager should concentrate on the most unfavorable or most difficult loading scenario for the vali- dation and determine this scenario together. The report associated with the validation also needs to include the steps preceding the actual sterilization; for example, regarding the packaging type chosen for the medical devices. Furthermore, routine tests and their intervals of execution must be defined, which have to take place between the regular PQs. During such a routine test, for example, it is tested whether the sterilization chamber is completely emptied of residual air, whether there are no leaks, and whether undesirable non-condensable gases (NCG) can be detected. Non-condensable gases Examples of these include air and carbon dioxide For a large steam sterilizer, a steam penetration test such as the Bowie-Dick test should, (CO2). They prevent the therefore, be performed on a daily basis. The Bowie-Dick test is carried out (in contrast to formation of a 100% satu- validation with the standard test package) with chemical or electronic tests that are easier rated steam atmosphere in the sterilization cham- to perform. The Bowie-Dick test is not feasible for small steam sterilizers due to space limi- ber, potentially compro- tations, but it is also not required by the corresponding standard, DIN EN 13060:2019-02. mising heat transfer and ultimately sterilization In addition, a vacuum test should be performed monthly. quality. Therefore, they are largely removed prior The personnel appointed to carry out the validation or corresponding service companies to the sterilization proc- ess using the fractional must prove that they have sufficient qualifications. The institution responsible for valida- vacuum procedure. tion, such as an external service provider or the operator himself, must demonstrate a quality management system and knowledge of the relevant laws, standards, directives, and guidelines with regard to OQ. HINT The validation of reprocessing methods can be outlined as follows: Reprocessing processes for medical devices must comply with existing rec- ommendations, guidelines, and standards for their validation. 29 Bowie-Dick test The requirements for personnel qualification for validations are high. The This examines the process approval after validation is associated with a high level of responsibil- removal of residual air in medical large steam steri- ity. lizers according to Following the initial validation, a PQ of the individual process parts must be EN 285:2021-12 and carried out on a regular basis. DIN EN ISO 11140-3:2007. It simulates steam pene- Thorough cleaning and disinfection is a basic requirement for successful steri- tration through a package lization. The processes involved with this must also be validated. of textiles and demon- strates the success of the test through uniform steam penetration. Fail- ure of the test can be caused by ineffective venting, leakage, or non- condensable gases (EN 285:2021-12, 2021). SUMMARY Over the past century, medical technology has undergone remarkable advancements, from the discovery of X-rays and the development of compact cardiac pacemakers to Konrad Zuse’s pioneering computer, enabling the growth of computer science in medicine. Presently, indis- pensable medical devices, such as MRI and ultrasound, are essential in the healthcare systems of developed countries. The industry’s innovation pace has accelerated, presenting challenges to global companies. Given globalization and international competition, the rapid translation of ideas into marketable products is crucial. Regu- latory frameworks like the European MDR impose safety requirements influencing the commercial readiness of products. Operational complex- ity, user comprehension, and compliance with regulations regarding the power supply of electric devices are vital for risk minimization. Primary infectious risks are associated with the reprocessing of reusable medical devices. Inadequate reprocessing can lead to nosocomial infec- tions endangering patient well-being, making the reprocessing process essential in preventing such infections. Regulatory frameworks encom- passing laws, regulations, standards, guidelines, and directives govern this reprocessing, which classifies devices into non-critical, semi-critical, and critical, based on their risk levels and individual reprocessing requirements. Reprocessing involves cleaning, disinfection, and sterilization. Steriliza- tion is the most effective, with steam sterilization and dry heat steriliza- tion being most prevalent. For thermolabile products, low-temperature sterilization techniques are used. Medical facility operators need to vali- date that their reprocessing methods consistently produce low-germ or sterile medical devices, necessitating a comprehensive validation proc- ess that includes IQ, OQ, and PQ. Various professional societies globally 30 have formulated guidelines for the validation and routine monitoring of reprocessing methods to ensure the safety and quality of medical devi- ces. 31 UNIT 2 CARDIOVASCULAR AND NEUROLOGICAL FUNCTIONAL DIAGNOSTICS STUDY GOALS On completion of this unit, you will be able to... – explain the physiological and technical principles and medical indications of electro- cardiography. – explain the physiological and technical principles and medical indications of blood pressure measurement. – explain the physiological and technical principles and medical indications of electroen- cephalography. – explain the physiological and technical principles and medical indications of electro- myography. – explain the physiological and technical principles and medical indications of electro- neurography. 2. CARDIOVASCULAR AND NEUROLOGICAL FUNCTIONAL DIAGNOSTICS Introduction “Functional diagnostics” is a term that refers to diagnostic procedures in a variety of medi- cal specialties in which the specific performances (functions) of an organ or organ system are tested under conditions that are as standardized as possible. Medical functional diag- nostics makes use of clinical, chemical clinical laboratory, electrophysiological, and imag- ing techniques, among others. The parameters can be determined while the subject is at rest or under stress. The range of services covers almost all medical specialties. The term “clinical functional diagnostics” refers to situations in which the physician requires no or only a few technical aids for a functional test. One example of clinical func- tional diagnostics would be the testing of joint mobility by an orthopedist. In addition, clinical laboratory functional diagnostics play a major role in modern medicine as a whole. They are used, for example, to determine red and white blood cells, liver values, or cholesterol by means of laboratory analyses. Functional diagnostics are frequently performed with the aid of modern imaging diagnos- tic methods. For example, ultrasound examinations can be used to assess the function of the liver, bile ducts, and kidneys, as well as the heart valves and the heart muscles. As many processes in the human body are also based on electrical voltages and/or currents, these can be recorded by means of electrophysiological procedures. Among the most important and best-known electrophysiological procedures are electrocardiography and electroencephalography. In the human body, both nerves and muscle cells have the ability to actively shift intra- and extracellular ion concentrations and, thus, influence the electrical potential distribu- tion in their environment. Via different synchronization processes, macroscopic cell clus- ters are additionally able to change their electric fields in a coordinated manner and, therefore, also generate significant electrical signals that can be measured at the body surface. 2.1 Cardiovascular Functional Diagnostics Electrocardiography Before delving into the detailed examination of electrocardiography, it is essential to first become acquainted with the electrophysiological fundamentals that form the foundation for understanding and analyzing electrocardiography. 34 Electrophysiological fundamentals One of the most important muscle cell clusters in the human body for life is the myocar- dium (i.e., the cell cluster of the heart muscle tissue). If we first consider just a single car- diac muscle cell, we find that it can be stimulated to contract mechanically by an external electrical impulse. This is also true for other muscle cells, such as those of the skeletal muscles, but by what processes is this contraction triggered? Like other cells, the cardiac muscle cell consists of an intracellular (i.e., inside the cell) and an extracellular (i.e., outside the cell) area. These two areas are separated by the cell mem- brane. However, the cell membrane does not hermetically seal the cell interior but con- tains a multitude of tiny ion channels. The permeability of these ion channels can be changed by electric fields or voltages. The ion channels can, thus, be practically opened or closed in this way. This occurs selectively for individual ion types such as sodium (Na+) or potassium (K+) ions. The “transmembrane voltage,” therefore, has a decisive influence on the state of the voltage-dependent ion channels. This voltage is present across the cell membrane and arises from the difference between the intracellular and the extracellular electrical potential: U membrane = φinside − φoutside. In the resting state of the cell, the ion channels are primarily permeable to K+ ions, but predominantly not to Na+ ions. The muscle cell then possesses an intracellular potential of about -85 mV, while the potential in the extracellular region is 0 mV. Thus, the mem- brane voltage is about -85 mV. The cell interior is, therefore, negatively charged. If an electrical stimulus causes the transmembrane voltage to rise above the value of the “threshold voltage” (as illustrated in the figure below) to a positive value, the permeability properties of the cell membrane change. There is an increase in membrane permeability for Na+ ions and thus an increased influx of Na+ into the previously negatively charged intracellular space. The cell is, thus, further depolarized, and there is an additional increase in the resting potential. As a consequence of the membrane voltage being changed in this way (toward positive values), the permeability is increased even more, and more Na+ can flow in. As a result, the intracellular potential skyrockets to a positive value above 0 mV, and the muscle cell contracts mechanically. Subsequently, the spatially- developing electric field also depolarizes the previously unexcited neighboring areas of the cell membrane, and the excitation propagates in a directed manner due to the abso- lute refractory period. In the further course of the excitation process, an increased out- flow of K+ ions from the cell takes place, resulting in the restoration of the resting voltage across the cell membrane. This process, which always occurs in the same way, is called the intracellular “action potential” of excitation. In muscle cells, the action potential is the trigger for mechanical contraction. This process is referred to as “electromechanical cou- pling.” The action potential follows the “all-or-nothing” principle: If an initial increase in transmembrane voltage remains below the threshold voltage, no action potential is gener- ated and the cell repolarizes again. However, if the threshold voltage is exceeded, a full action potential is triggered. In this respect, the action potential could be described as a “digital process.” 35 Refractory period The following figure shows the course of the transmembrane voltage of a cardiac muscle This is the time during cell during an action potential. The cycle is also identical in principle for other muscle and which no new action potential can be triggered nerve cells and consists of the following three sections: in an excitable cell, such as the muscle cell, after 1. depolarization phase its depolarization. A dis- tinction is made between 2. plateau phase absolute and relative 3. repolarization phase refractory periods: During the absolute refractory period, no new action Figure 5: Course of the Transmembrane Voltage of a Cardiac Muscle Cell During an potential can be trig- Action Potential gered, even with very strong stimulation. Dur- ing the relative refractory period following the absolute refractory period, the cell is basi- cally excitable, but the stimulus threshold (threshold voltage) for triggering new action potentials is increased. The stimuli must, there- fore, be significantly stronger than outside the refractory period. Source: Lars Meinecke (2024), based on Wintermantel and Ha (2009, p. 1325). The action potential of cardiac muscle cells is characterized by a relatively long duration of about 300 ms, whereas this duration is only about 10 ms in skeletal muscle cells and about 1 ms in nerve cells. Most of the increased duration of the action potential of cardiac muscle cells is explained by the absolute refractory period of 250 ms, during which no new action potential and, thus, no new contraction can be triggered, even in the case of very strong stimulation. The absolute refractory period of the cardiac muscle cell is evolutionarily adapted to the hemodynamically-required times and is one of the control mechanisms of the cardiac cycle; the refractory period is sufficient for the chambers of the heart to fill with blood. Subsequently, the blood is ejected again by the contraction of the heart muscle. The abso- lute refractory period thus also mathematically limits the maximum frequency of action potentials to a value of 1/250 ms (i.e., four beats per second, or 240 beats per minute). The heart is, thus, protected by the relatively long refractory period from a too-rapid sequence of uncoordinated contractions. In ventricular fibrillation, a life-threatening cardiac arrhythmia, local disturbances in the propagation of excitation or over the course of excitation cause circular waves of excita- tion. The heart muscle then no longer pumps in a coordinated fashion; it contracts only in sections and in an uncoordinated way at a high frequency of up to 800 per minute. It fibril- lates. Functional pumping is no longer present, a pulse can no longer be detected, and 36 circulatory arrest occurs, leading to death without immediate medical intervention. In terms of diagnostic value, it is, therefore, important to be aware of the difference between electrical excitation on the one hand, and the actual pumping capacity of the heart on the other. The electrocardiogram Before we go into the electrocardiogram (ECG; or “electrocardiography”) let us review the basics of cardiology – more specifically, electrophysiology – for a better understanding. The following figure shows the schematic of a human heart. Figure 6: Schematic of a Human Heart Source: Lars Meinecke (2024), based on Jakov (2008). The heart is a hollow muscle containing two “pumps,” the left and right halves of the heart. Both halves have an atrium and a ventricle. In addition, four heart valves ensure the correct direction of blood flow. The sinoatrial node in the upper, rear right atrium (shown schematically in yellow in the figure above) is of crucial importance for the pumping func- 37 tion of the heart. The cells in the sinoatrial node provide the electrical impulse for each heartbeat. As an excitation generation system, the sinoatrial node represents the natural pacemaker of the heart and periodically generates action potentials. These action potentials are transmitted via the conductive system of the heart to the vari- ous myocardial areas. There, they lead to a uniform electrical excitation of large areas according to the aforementioned “all-or-nothing” principle, the result of which the individ- ual action potentials add up in their electrical effect, leading to a coordinated contraction of the two ventricles of the heart. By summing up the multitude of action potentials, the resulting signal can be derived comparatively easily at the body’s surface. The superposi- tion of the temporal and spatial courses of the individual electrical excitation processes in the heart thereby leads to the specific potential distribution on the body’s surface, which can be measured as the familiar ECG signal. In the following section, we will look at how the ECG can be technically measured and evaluated. First of all, such measurement requires an electrical coupling between the measuring device and the patient. This “coupling device” is necessary because the electri- cal processes in the measuring device and in the human body are based on different mechanisms: In metals, it is the principle of electron conduction, while in the human body, ionic conduction is the basis of charge transport. Since both types of charge trans- port are incompatible, electrodes are used to enable a transition between the two types of charge transport. The electrodes are commercially available in disposable or reusable form. Disposable electrodes are mostly made of silver (Ag) coated with a silver chloride layer (AgCl). This actual metal electrode is often embedded in a plastic housing and surrounded by a milli- meter-thick electrolyte layer, known as the wet contact gel. The purpose of the contact gel is, on the one hand, to reduce the transfer impedance between the body and the measur- ing device, and on the other hand, it also dampens movements between the electrode and the skin. On the electrode housing itself, there is usually a self-adhesive ring to attach the electrode to the body. The following figures show the front and back of a classic disposa- ble ECG electrode and its attachment to the body. 38 Figure 7: Disposable ECG Electrode Source: c (n. d.). Figure 8: Application of Disposable ECG Electrodes Source: Ilyaska (n. d.). 39 Reusable ECG electrodes are typically available as silver sintered electrodes. They are air- permeable and, after moistening, are held on the body’s surface by means of a vacuum. Compared to disposable electrodes, reusable electrodes represent a significant reduction in ongoing costs. The following two illustrations show an ECG vacuum system and the accompanying reusable silver sintered electrodes in use. 40 Figure 9: ECG Vacuum System for Reusable ECG Electrodes Source: Strässle & Co. Medizintechnik GmbH (n. d.) 41 Figure 10: Reusable Silver Sintered ECG Electrodes in Application Source: Strässle & Co. Medizintechnik GmbH (n. d.) The correct positioning of the lead electrodes on the body plays an important role in the recording of an ECG. A basic distinction is made between three types of lead configura- tions, as illustrated in the following table. Table 5: Three Types of Lead Configurations Goldberger’s unipolar Wilson’s unipolar Einthoven’s Bipolar limb leads (aug- chest leads (precor- limb leads mented limb leads) dial leads) ECG lead notation I, II, III aVR, aVL, aVF V1, V2, V3, V4, V5, and V6 (alternatively, C is used instead of V) Measurement setup Measurement of the Determination of the Determination of the potential difference potential difference potential difference between each two between one limb between one precor- limb lead electrodes: electrode each and a dial lead each and a I = yellow–red reference potential. reference potential. II = green–red Electrical reference The electrical refer- potential is the middle ence potential (also III = green–yellow potential between the called the “central ter- two other limb poten- minal”) is formed by tials. The abbreviation the parallel connection “aV” stands for “aug- of the three limb leads mented voltage.” according to Eint- hoven, each via a 5 kΩ resistor. Source: Lars Meinecke (2024). 42 The positioning of the individual electrodes is standardized by a special color and label- ling scheme. DIGRESSION Willem Einthoven was a Dutch physician who invented the first practical electro- cardiogram and was awarded the Nobel Prize in Physiology or Medicine in 1924 for his work. Emanuel Goldberger and Frank Norman Wilson were American car- diologists, with Goldberger known for adding three augmented leads to the ECG and Wilson for introducing precordial chest leads, both augmenting the diag- nostic capabilities of cardiac electrophysiology. The following figure shows an overview of all lead electrode locations of the three men- tioned lead configurations. Figure 11: Lead Electrode Locations for the Electrocardiogram Source: Lars Meinecke (2024), based on TomCatX (2011). The three ECG lead configurations are to be considered as different projections of the elec- tric field of the heart, which leads to the potential distribution on the body surface. Resting 12-lead ECG Thus, for a comprehensive ECG, multiple synchronous lead configurations are required for the different projection screens. For this reason, a standard clinical recording is performed as a 12-lead ECG at rest. It includes the three lead configurations according to Einthoven, 43 Goldberger, and Wilson, and uses a total of 10 lead electrodes to record the twelve ECG channels. Following the lead configurations mentioned above, the individual channels of the 12-lead ECG are labeled I, II, III, aVR, aVL, aVF, V1, V2, V3, V4, V5, and V6. An example of a resting 12-lead ECG from Klinge (2015, pp. 96-97) is shown below. Figure 12: Normal Diagnostic Findings in Resting 12-Lead ECG Source: Lars Meinecke (2024), based on Klinge (2015). The following figure, whose vertical circle is referred to as the “Cabrera” presentation sys- tem, facilitates the spatial assignment of the individual leads or projections to the corre- sponding cardiac sections in the vertical and horizontal planes. 44 Figure 13: Spatial Assignment of the Individual Leads of a 12-lead ECG Source: Lars Meinecke (2024), based on TomCatX (2011) and Klinge (2015, p. 54). In addition to the 12-lead ECG, a number of other ECG procedures are used for different purposes. These include the stress ECG and the 24-hour ECG, both of which are performed with a reduced number and/or deviating positioning of the surface leads. In addition, inva- sive intracardiac electrograms are also obtained but are not within the scope of this unit. From the point of view of diagnostic value, a distinction must be made between the infor- mation that an ECG can provide and aspects about which the ECG cannot provide any information. The ECG can provide information on the origin of excitation, excitation rhythm, repolarization, cardiac position/axis, heart rate, impulse propagation, and possi- ble disturbances. However, the ECG does not provide information on the mechanical func- tion of the heart (i.e., contraction and pumping capacity). Furthermore, the value of the information depends on the knowledge and experience of the assessor. For this reason, disturbances during the ECG recording also pose the risk of an often-sub- tle, but substantial, alteration of the recording. The following table gives a brief overview of common sources of artifacts and their causes, as well as possible misinterpretations of the ECG. 45 Table 6: Overview of Common Sources of Artifacts and Their Causes, as well as Possible Misinterpretations of the ECG Causes Interpretation Operator-related artifacts Incorrect/swapped electrode Inversion of one or more ECG position traces and/or increased levels of Poor electrode-skin contact artifact due to insufficient sig- due to insufficient moistening nal-to-noise ratio Electrodes that are too old or have been improperly stored Device-related artifacts Alternating current coupling Pacemaker spikes could be mis- Potentials appearing as interpreted as QRS spikes. spikes (e.g., due to pacemak- ers) Patient-related artifacts Motion or respiration artifacts Muscular artifacts from muscles leading to baseline variations close to the heart may be super- Muscular artifacts imposed on the actual ECG and lead to misinterpretation due to their similarity. Source: Lars Meinecke (2024). 24-hour ECG The 24-hour electrocardiography (also known as “the Holter monitor,” after its inventor) is a non-invasive routine ECG procedure of crucial importance in the primary diagnosis and therapy control of cardiac arrhythmias, in which the ECG is recorded and analyzed over a longer period (usually 24 hours but at least 18 hours) under everyday stress. It, thus, ena- bles the recording and analysis of the various stresses (physical and emotional) of a patient over at least one day-night cycle. Depending on the device and indication, the recording period can also be several days or weeks. The placement of the lead electrodes is subject to the following special considerations in 24-hour ECG: Muscle artifact

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