Cardiopulmonary Exercise and Lung Function Testing System

Transcription

1 Cardiopulmonary Exercise and Lung Function Testing System INSTRUCTIONS FOR USE CAUTION: Federal Law restricts this device to sale by or on the order of a physician COR-MAN IN (US) Issue E, Rev INNOVISION ApS Skovvænget 2 DK-5620 Glamsbjerg Denmark Tel.: Fax: info@innovision.dk

2 TABLE OF CONTENTS 1. Introduction and Background Information Device Description Inert Gas Rebreathing (Cardiac Output Measurement) Breath-by-Breath Gas Exchange (VO 2 Measurement) Spirometry (Measurement of Lung Volumes and Flows) Multiple-Breath Wash-Out (LCI Measurement) Indications for Use Intended Patient Population Intended Applications Contraindications Adverse Events/Reactions Maintaining Device Effectiveness Patient Counseling Information How Supplied Warnings and Precautions Performance Characteristics (Clinical Studies) Studies with Innocor Studies on Earlier Version of Innocor Others Conclusions from the Clinical Studies Conformance to Standards Physician Labeling Intended Operators Why Use Inert Gas Rebreathing to Measure Cardiac Output? Is Innocor CO Measurement a Validated Technique? Description of Innocor Parameters Cardiac Output (CO) SpO Heart Rate (HR) Stroke Volume (SV) Lung Volume (VL) Cardiac Index (CI) Stroke Index (SI) Blood Pressures (SYS, DIA, MAP) Systemic Vascular Resistance (SVR) Systemic Vascular Resistance Index (SVRI) Oxygen Uptake (VO 2 ) Carbon Dioxide Excretion (VCO 2 ) Expiratory Minute Ventilation (V E ) Oxygen Uptake per kg (VO 2 /kg) Respiratory Exchange Ratio (R) Alveolar Ventilation (V A ) Anatomical Dead Space (Fowler Dead Space) (V D )...20 October 2015 COR-MAN IN (US), E/1 i

3 Tidal Volume (V T ) Respiratory Rate (f R ) End-Tidal Concentration of Oxygen (F ET O 2 ) End-Tidal Concentration of Carbon Dioxide (F ET CO 2 ) Expiratory Quotient/Ventilatory Equivalent for Oxygen (V E /VO 2 ) Expiratory Quotient/Ventilatory Equivalent for Carbon Dioxide (V E /VCO 2 ) Anaerobic Threshold (AT) Respiratory Compensation (RC) Forced expiratory volume in 1 second (FEV 1 ) Forced vital capacity (FVC) FEV 1 /FVC (FEV 1 %) Peak expiratory flow (PEF) Maximal instantaneous forced expiratory flow (MEF 75) Maximal instantaneous forced expiratory flow (MEF 50) Maximal instantaneous forced expiratory flow (MEF 25) Forced expiratory time (FET) Maximum voluntary ventilation (MVV) Functional Residual Capacity (FRC) Lung Clearance Index (LCI) Precision Limitations What if a Patient is on Supplemental O 2? Interpretation of Results Innocor Installation Operating Environment Product Overview and Installation Procedure Instructions for Use Display Symbols / Labels Main Screen (Innocor Program) Measurement Setup Data Management Blood Pressure (Stand-Alone Test) Exit Calibration Ambient data Flowmeter Calibration Flow-gas Delay Calibration Oxygen Calibration Measurement (CO By Rebreathing / CPET Program) Operating Principle Start of Rebreathing / CPET Program Patient Selection Test Preparation Test Execution Option: Breath-by-Breath Rebreathing Test Preparation Rebreathing Test Option: Blood Pressure (BP) Measurement Results...42 October 2015 COR-MAN IN (US), E/1 ii

4 After a Test Setup Data Exchange Blood Pressure Test (Stand-Alone) Recommended Settings Termination of Program Measurement (LCI By Multiple-Breath Wash-Out) Operating Principle Start of LCI Program Patient Selection General Screen Layout Test Preparation Test Execution Results After a Test Setup Data Exchange Recommended Settings Termination of Program RVU Description Operating Principle Valve Insert CO 2 Scrubber Flow Restrictor RVU Test Spirometry Mode Pulse Oximetry Operating Principle Attaching the Sensor Accuracy Precautions for Use Contraindications Blood Pressure (Optional Component) Operating Principle Positioning the Cuff Performance Precautions for Use Cleaning/Maintenance/Calibration Cleaning General Casing LCD / Touch Screen Display Cleaning and Maintenance of RVU Respiratory Parts Gas Analyzer Sampling Tube Pulse Oximetry Sensor NIBP Cuff (Option) External Computer Maintenance/Repair Replacement of Gas Analyzer Filters Replacement of Gas Analyzer Sampling Tube...77 October 2015 COR-MAN IN (US), E/1 iii

5 8.2.3 Replacement of Respiratory Parts Cleaning and Replacement of Dust Filter for Cooling Fan Calibrations Gas Analyzer Oxygen Sensor Airway Pressure Sensor Rebreathing Gas Filling Flow Gas Cylinder Pressure Sensor Pulse Oximeter Non-Invasive Blood Pressure Flowmeter Sensor Calibration Flow-gas Delay Calibration Periodic Checks Inspection Safety Check Performance Check Disassembly and Disposal Disassembly Procedure Disposal of Device and Accessories Specifications Mechanical Electrical Environmental Display Integrated Computer Electrical Interfaces Rebreathing Valve Gas Supply Parameters Gas Analyzer Oxygen Sensor Flowmeter Pulse Oximeter Non-invasive Blood Pressure (NIBP) Parts and Accessories Breathing Assemblies Gases Pulse Oximeter NIBP Cuffs General Spare Parts References/Bibliography Warranty and Liability Warranty Liability / Disclaimer...94 October 2015 COR-MAN IN (US), E/1 iv

6 Annex A: Guidance and manufacturer s declaration...95 Annex B: Information for Patients...99 October 2015 COR-MAN IN (US), E/1 v

7 1. INTRODUCTION AND BACKGROUND INFORMATION 1.1 DEVICE DESCRIPTION Innocor is a non-invasive diagnostic device that measures or calculates a number of hemodynamic and metabolic parameters. Innocor utilizes a non-invasive, inert gas rebreathing technique to measure Cardiac Output Pulmonary Blood Flow Lung volume Innocor incorporates a prefilled breathing bag with an oxygen-enriched mixture containing known quantities of two foreign gases. When a patient breathes the mixture, Innocor s photoacoustic gas analyzer technology measures the relative levels of the foreign gases over about seconds and calculates these three parameters from those measurements. Innocor also measures or calculates other hemodynamic parameters non-invasively based on pulse oximetry. These include: Pulse rate Arterial oxygen saturation Stroke volume With the non-invasive blood pressure (NIBP) Option installed, Innocor also measures or calculates other hemodynamic parameters. These include: Systolic blood pressure Diastolic blood pressure Mean arterial blood pressure Systemic vascular resistance In addition, with certain parameters of the patient manually entered by the operator, Innocor calculates these hemodynamic parameters: Cardiac index Stroke index Systemic vascular resistance index The Breath-by-Breath (BBB) Option for cardiopulmonary exercise testing (CPET) provides measurements of gas exchange parameters including: Oxygen uptake Carbon dioxide excretion Respiratory exchange ratio Ventilation Tidal volume Respiratory rate End-tidal gas concentrations Ventilatory equivalents for O 2 and CO 2 October 2015 COR-MAN IN (US), E/1 1

8 Alveolar ventilation Anatomical deadspace Anaerobic threshold Respiratory compensation point These parameters are determined by simultaneous measurements of the respiratory flow and gas concentrations when breathing ambient air. The respiratory flow is measured by means of a differential pressure type flowmeter (pneumotachometer) placed between the respiratory valve unit and the patient. The gas exchange calculations are carried out online for each breath between the rebreathing tests. This gives the opportunity to perform an incremental exercise test on a bicycle ergometer or treadmill and measure the progress of cardiac function, pulmonary function and gas exchange at the same time. The Spirometry Option provides measurements of the lung function with respect to dynamic lung volumes during forced expiration. This includes the following parameters: Forced expiratory volume in 1 second (FEV 1 ) Forced vital capacity (FVC) FEV 1 /FVC (FEV 1 %) Peak expiratory flow (PEF) Maximal instantaneous forced expiratory flow where 75% of the FVC remains to be expired (MEF 75) Maximal instantaneous forced expiratory flow where 50% of the FVC remains to be expired (MEF 50) Maximal instantaneous forced expiratory flow where 25% of the FVC remains to be expired (MEF 25) Forced expiratory time (FET) Maximum voluntary ventilation (MVV), calculated as 40 FEV 1 These parameters are determined by measurements of the respiratory flow when breathing ambient air during a spirometry maneuver (tidal breathing followed by first a full inspiration then a maximal forced expiration). The respiratory flow is measured by means of a differential pressure type flowmeter (pneumotachometer) placed in a stand-alone position to minimize the flow resistance. This gives the opportunity to determine whether the patient s exercise intolerance is caused by ventilatory limitation or by a limitation in the cardiovascular system. The specific parameters measured by the Innocor LCI Option include: Lung Clearance Index (LCI) Functional Residual Capacity (FRC) These parameters are determined by measurements of the respiratory flow and SF 6 concentration in a combined inert gas rebreathing maneuver for wash-in of tracer gas and determination of FRC and a multiple-breath wash-out test with the patient breathing ambient air. Innocor runs under the Windows XP Embedded operating system on an integrated single-board computer. However, knowledge of Windows is not required to operate the device. The device is operated via a simple touch screen interface. Simply touch/press the buttons on the screen to invoke the desired functions. October 2015 COR-MAN IN (US), E/1 2

9 1.1.1 Inert Gas Rebreathing (Cardiac Output Measurement) Cardiac output (CO) is defined as the volume of blood pumped by the heart per unit of time (blood flow in liters per minute). The measurement with Innocor is non-invasive (i.e., it does not necessitate catheterization or any other penetration through a body orifice or the body surface) because inert gas rebreathing is a pulmonary gas exchange method. The operating principle of Innocor is to let the patient breathe minute quantities of a blood soluble and an insoluble gas in a closed breathing assembly for a short period (approximately 15 seconds). The blood flowing through the lungs (effective pulmonary blood flow, or PBF) absorbs the blood soluble gas; therefore, the disappearance rate is proportional to the blood flow. The blood insoluble gas is also measured to determine the lung volume from which the soluble gas disappears and to account for other factors that affect distribution of the blood soluble gas. A patient able to breathe spontaneously and capable of following directions is told by the person administering the test (Operator) to put on a nose clip and then to breathe into a respiratory valve (using a mouthpiece with a bacterial/viral filter). At the end of an expiration the Operator activates the valve so that the patient will breathe in and out (rebreathe) exclusively from a rubber bag for a period of approximately 15 seconds. The patient is asked to empty the rebreathing bag during each inspiration and breathe with a slightly increased respiration rate. After this period the patient is switched back to ambient air and the test is terminated. The bag is prefilled with an oxygen (O 2 ) enriched mixture containing two foreign gases: typically 0.5% nitrous oxide (N 2 O) and 0.1% sulfur hexafluoride (SF 6 ). These gases and CO 2 are measured continuously and simultaneously at the mouthpiece by a photoacoustic gas analyzer inside Innocor. Oxygen is measured by means of a laser diode absorption spectrometer. N 2 O is soluble in blood and is, therefore, absorbed during the blood s passage of the lungs at a rate that is directly proportional to the blood flow through the lungs. Accordingly, the higher the cardiac output the higher the disappearance rate of N 2 O (slope of measured gas curve). SF 6, on the other hand, is insoluble in blood and, therefore, it stays in the gas phase in the lungs. It is used to determine the lung volume from which the soluble gas is removed by the blood. CAUTION: The Cardiac Output may be subject to error in the presence of a significant pulmonary shunt. Use the pulse oximeter to determine whether there may be the possibility of significant shunting (SpO 2 95 % while breathing room air). The rebreathing test can be performed as a single test at rest or at a given exercise level using e.g. a bicycle ergometer or a treadmill in a stand-alone configuration. Alternatively it can be performed as a part of an exercise protocol where the rebreathing maneuvers are done at pre-programmed intervals/workloads. The pulse oximeter component of Innocor measures heart rate (HR) and arterial oxygen saturation (SpO 2 ) during the test. HR enables a calculation of stroke volume (SV) etc, and SpO 2 indicates whether the patient s oxygenation is normal, or if there is a significant intrapulmonary shunt (SpO 2 < 95%) in which case pulmonary blood flow is not an accurate measure of cardiac output. An oscillometric non-invasive blood pressure (BP) measuring system is also included as an option. It is designed to take blood pressure measurements including systolic (SYS), diastolic (DIA) and mean arterial pressures (MAP). By combining CO and MAP the systemic vascular resistance (SVR) can be determined. October 2015 COR-MAN IN (US), E/1 3

10 1.1.2 Breath-by-Breath Gas Exchange (VO 2 Measurement) The Breath-by-Breath (BBB) Option provides measurements of metabolic gas exchange parameters by simultaneous measurements of the respiratory flow and gas concentrations when breathing ambient air. The respiratory flow is measured by means of a differential pressure type flowmeter (pneumotachometer) placed between the respiratory valve unit and the patient. The gas exchange calculations are carried out online for each breath between the rebreathing tests. This gives the opportunity to perform an incremental exercise test on a bicycle ergometer or treadmill and measure the progress of cardiac function, pulmonary function and gas exchange at the same time. The principle in the determination of the oxygen uptake and the carbon dioxide excretion is to estimate the difference between airway influx and efflux of oxygen and carbon dioxide during inspiration and expiration. This is done by integrating the product of oxygen or carbon dioxide concentration and flow in the respiratory gas over an interval, which covers a complete respiratory cycle. The results are corrected partly for changes in oxygen and carbon dioxide contents of the lungs by using equations based on the change in functional residual capacity (FRC) from one breath to the next and by assuming constant end-tidal concentrations of O 2 and CO 2 from breath to breath. The expiratory minute ventilation is estimated by simply integrating the flow over a whole expiration and dividing by the length of the breath. This is also the case for the alveolar ventilation except that the product of anatomical dead space and respiratory rate is subtracted. The anatomical dead space is determined from the capnogram (CO 2 curve) and the flow signal. The respiratory rate, the tidal volume and the time of inspiration are determined from the flow signal alone. The end-tidal concentrations are determined as the minimum/maximum concentrations of oxygen/carbon dioxide at the end of expiration. The respiratory and expiratory quotients are found as the ratio between carbon dioxide excretion and oxygen uptake, and as the ratio between expiratory minute ventilation and oxygen uptake or carbon dioxide excretion, respectively Spirometry (Measurement of Lung Volumes and Flows) The Spirometry Option provides measurements of the lung function in terms of flows and volumes determined during a forced breathing maneuver consisting of tidal breathing followed by a full inspiration and a maximal forced expiration. The respiratory flow is measured by means of a differential pressure type flowmeter (pneumotachometer) placed in a stand-alone position to minimize the flow resistance. The flow signal is integrated to determine volumes. The maneuver and the calculations follow standardized criteria and equations Multiple-Breath Wash-Out (LCI Measurement) The LCI is calculated as the cumulative expired volume (V CE ) required to clear the tracer gas from the lungs during normal breathing, minus the product of the number of wash-out breaths and the external dead space outside the lips, divided by the subject s Functional Residual Capacity (FRC). FRC is the amount of air that stays in the lungs (up to the lips) after a normal expiration. In other words, LCI represents the number of lung volume turnovers (i.e. FRCs) that the subject must breathe to clear the tracer gas from the lungs (by convention, to an end-tidal concentration of 1/40th of the starting concentration over three subsequent breaths). Innocor uses sulfur hexafluoride (SF 6 ) as the tracer gas. SF 6 is an inert, non-toxic gas. The measurement is performed using a sensitive and fast responding photoacoustic infrared gas analyzer and a flowmeter (pneumotachometer) is used to record the inspiratory and expiratory flows at the October 2015 COR-MAN IN (US), E/1 4

11 mouth. The patient is breathing through a mouthpiece or a face mask connected to the flowmeter via a bacterial filter, and a gas sampling tube is connected to the breathing assembly for sidestream gas analysis. Innocor uses a combination of two techniques to determine the LCI, using SF 6 as the inert tracer gas: Inert gas rebreathing (IGR) is used for rapid wash-in of a very small amount of SF 6 until an even concentration is obtained in the lungs before the wash-out can start. During rebreathing the patient inhales an oxygen enriched mixture from a pre-filled rubber bag. This is followed by multiple-breath wash-out (MBW) for determination of the cumulative expired volume (V CE ) required to clear the SF 6 from the lungs. The wash-out phase is initiated by automatically disconnecting from the bag at the end of an inspiration where after the patient breathes room air until the end-tidal SF 6 concentration has fallen below the predetermined fraction of 1/40 th of the starting concentration. When both steps are finished the LCI is calculated as the ratio between V CE and FRC. Guidelines on lung function testing recommend that the MBW test be repeated in order to obtain at least two tests in which the difference between two FRC values is less than 10% when comparing the higher to the lower FRC value. The combination of inert gas rebreathing and multiple breath wash-out the QuickTest Option - offers a number of advantages compared to conventional wash-in/wash-out. Inert gas rebreathing is a more effective manoeuvre to obtain good mixing of the gases compared to multiple breath wash-in. This means significantly shorter test time and significantly reduced consumption of test gas. In combination with Innocor s sensitive SF 6 analyzer and the dilution of the test gas mixture with air this means drastically reduced consumption of SF INDICATIONS FOR USE Innocor is indicated for the determination of a number of hemodynamic parameters. Cardiac Output (CO) is the principal measured parameter. Utilizing inert gas rebreathing, Innocor measures the relative levels of two inhaled gases of differing blood solubility over approximately 3-4 respirations and calculates pulmonary blood flow (PBF). In the absence of a significant intrapulmonary shunt (arterial oxygen saturation 95% as measured by a pulse oximeter incorporated in the Innocor while breathing room air), PBF is equal to CO. As an optional accessory, Innocor includes a noninvasive Blood Pressure (NIBP) monitoring system. This option provides systolic, diastolic and mean arterial pressures. With the NIBP Option, Innocor provides values for the following measured and calculated hemodynamic parameters: October 2015 COR-MAN IN (US), E/1 5

12 Cardiac Output Arterial Oxygen Saturation Heart Rate Stroke Volume Lung Volume Cardiac Index Stroke Index Blood Pressures (Systolic, Diastolic, Mean Arterial) Systemic Vascular Resistance Systemic Vascular Resistance Index A Cardiopulmonary Exercise Testing Option is available for Innocor. This option provides breath-bybreath measurements of flow, oxygen uptake and carbon dioxide production. It is intended to measure oxygen uptake (metabolic rate) and related parameters to objectively and non-invasively assess cardiac and pulmonary function at rest and during exercise. With the Cardiopulmonary Exercise Testing Option, Innocor provides values for: Main metabolic parameters: Oxygen Uptake Carbon Dioxide Excretion Expiratory Minute Ventilation Calculated/derived parameters: Oxygen Uptake per kg Respiratory Exchange Ratio Alveolar Ventilation Anatomical Dead Space (Fowler Dead Space) Tidal Volume Respiratory Rate End-Tidal Concentration of Oxygen End-Tidal Concentration of Carbon Dioxide Expiratory Quotient / Ventilatory Equivalent for Oxygen Expiratory Quotient / Ventilatory Equivalent for Carbon Dioxide And the following calculated parameters after an incremental exercise test: Anaerobic Threshold Respiratory Compensation Rest Values Values at AT Point Values at Max Exercise The Spirometry Option provides measurements of the following parameters: Forced expiratory volume in 1 second (FEV 1 ) Forced vital capacity (FVC) FEV 1 /FVC (FEV 1 %) Peak expiratory flow (PEF) October 2015 COR-MAN IN (US), E/1 6

13 Maximal instantaneous forced expiratory flow where 75% of the FVC remains to be expired (MEF 75) Maximal instantaneous forced expiratory flow where 50% of the FVC remains to be expired (MEF 50) Maximal instantaneous forced expiratory flow where 25% of the FVC remains to be expired (MEF 25) Forced expiratory time (FET) Maximum voluntary ventilation (MVV), calculated as 40 FEV 1 The LCI Option for Innocor is intended to measure the Lung Clearance Index (LCI), which is the cumulative expired volume required to clear an inert gas from the lungs during normal breathing in a multiple-breath washout (MBW) test divided by the Functional Residual Capacity (FRC). The specific parameters measured by the Innocor LCI Option include: Lung Clearance Index (LCI) Functional Residual Capacity (FRC) 1.3 INTENDED PATIENT POPULATION Innocor established that it provided non-invasive cardiac output measurements comparable to those provided by the invasive Fick and thermodilution methods in congestive heart failure patients. However, Innocor is a compact point-of-care device that can be used to provide cardiac output and metabolic gas exchange measurements in any non-comatose patient capable of following the testing protocol. It can be used in patients both in rest and exercise e.g., in patients who have no symptoms in rest or light exercise. The only requirement is that the patient is capable of understanding the instructions from the operator and performing the breathing maneuver well. 1.4 INTENDED APPLICATIONS Innocor can be used in a variety of medical fields where knowledge of a patient s cardiac output, metabolic rate or cardiopulmonary response to exercise is important, e.g., cardiac exercise stress testing, heart failure, cardiac surgery, rehabilitation, hypertension, pulmonary hypertension, hemodialysis and pacemaker programming. 1.5 CONTRAINDICATIONS The Innocor is contraindicated to measure Cardiac Output in patients with a significant pulmonary shunt. A significant shunt may be present if the arterial oxygen saturation, while breathing room air, is low (SpO 2 95% as measured by the Innocor s pulse oximeter), in which case cardiac output is underestimated. 1.6 ADVERSE EVENTS/REACTIONS None known. October 2015 COR-MAN IN (US), E/1 7

14 1.7 MAINTAINING DEVICE EFFECTIVENESS Device effectiveness is ensured by following the recommendations regarding cleaning, general maintenance and replacement of accessories and disposable parts in the sections Cleaning/Maintenance/Calibration and Periodical Checks. It is recommended as a preventative action that the equipment be serviced every 12 months by a service technician authorized by the manufacturer. 1.8 PATIENT COUNSELING INFORMATION Information for patients is provided in Annex B. 1.9 HOW SUPPLIED Innocor is supplied in special packaging consisting of a cardboard box and expanded polystyrene for protection. Accessories are supplied in a cardboard box. Keep the original packaging for use in the event that the equipment needs to be returned for repair or servicing and for transportation/shipping in general. The equipment and its accessories and disposables are supplied non-sterile. October 2015 COR-MAN IN (US), E/1 8

15 2. WARNINGS AND PRECAUTIONS Before using Innocor please read this manual thoroughly and pay special attention to WARNING! and CAUTION statements appearing below and throughout the manual and to the ATTENTION symbol. A warning (indicated with the word WARNING!) alerts about a situation which, if not avoided, could result in death or serious injury to the user or the patient. It also describes potential serious adverse reactions and safety hazards. A precaution statement (indicated with the word CAUTION) is used for a hazard alert that warns of a potentially hazardous situation which, if not avoided, may result in minor or moderate injury to the user or patient or damage to the equipment or other property. It is also used to alert against unsafe practices. This includes the special care necessary for the safe and effective use of the device and the care necessary to avoid damage to a device that may occur as a result of use or misuse. WARNING! Explosion hazard: In order to avoid an explosion risk, do not use the system in areas in which flammable anesthetics are applied. WARNING! Never use the device without a new disposable single patient use bacterial/viral filter in the patient connection to minimise the risk of cross-contamination. WARNING! Medical electrical equipment needs special precautions regarding electromagnetic compatibility (EMC) and needs to be installed and put into service according to the EMC information provided in this Instructions for Use (see Guidance and Manufacturer s Declaration in Annex A). Portable and mobile radio frequency (RF) communications equipment can affect medical electrical equipment. WARNING! The use of electrical accessories with Innocor other than those specified may result in increased EMISSION (risk of disturbance of other devices) or decreased IMMUNITY (risk of disturbance of the Innocor). CAUTION: Federal Law restricts this device to sale by or on the order of a physician. CAUTION: The valve insert is not intended to be used sterilized / disinfected. The valve insert is intended to be replaced when changing the Innocor gas cylinder, which corresponds to approx. 75 tests depending on use. CAUTION: Flowmeter must be removed from RVU port to stand-alone position for spirometry test. CAUTION: Long-term exposure to water or to acid may cause damage to the dryer fittings due to swelling of the Nafion (25% when exposed to liquid water). Be careful not to kink or break the Nafion tubing during the cleaning process. October 2015 COR-MAN IN (US), E/1 9

16 CAUTION: Do not autoclave or immerse the sensor in liquid of any kind. Do not sterilise with EtO. Do not use caustic or abrasive cleaning agents on the sensors. CAUTION: The Cardiac Output may be subject to error in the presence of a significant pulmonary shunt. Use the pulse oximeter to determine whether there may be the possibility of significant shunting (SpO 2 95 % while breathing room air). When the ATTENTION symbol is shown on the device, it is accompanied with additional symbols to convey the nature of the WARNING or PRECAUTION: WARNING! Electrical shock hazard. Main power inlet Do not open the cover. Refer servicing to qualified personnel. There are no userserviceable parts inside. The power cord should be connected only to a properly grounded AC electrical outlet. Fuse WARNING! For continued protection against fire hazard, replace only with same type and rating of fuse. Data interfaces Universal serial bus (USB) connections and Network connection WARNING! The electrical interfaces on the data interface panel (USB and Network) shall not be used under normal clinical conditions within the patient zone but only during service and occasionally for data exchange. Peripheral equipment connected to these interfaces must be certified according to the respective European standards (e.g. EN for data processing equipment and EN for medical equipment). October 2015 COR-MAN IN (US), E/1 10

17 Furthermore, all configurations shall comply with the system standard EN Everybody who connects additional equipment to the signal input part configures a medical system, and is therefore responsible that the system complies with the requirements of the system standard EN If using a version with external computer, the computer must be certified according to the European standard EN The computer should only be used on battery power. Otherwise, it is required to use a safety isolating transformer. The computer must be placed outside of the patient zone. Excessive EMI (electromagnetic interference) may to some extent interfere with the measurements. To avoid this interference, it may be necessary to move the interfering equipment or switch to another installation group. Gas outlet / inlet CAUTION. Do not block or connect anything to these connectors. CAUTION. Make sure no protective caps or plugs are fitted before bringing into use. WARNING! Fire hazard. Avoid open flames and smoking in the areas where the device is being used. WARNING! Explosion hazard: Gas cylinder and cylinder connection Improper use, filling, storage or disposal of gas cylinder may result in personal injury, death or property damage. Avoid open flames and smoking in the areas where the device and gas cylinders are being used or stored. Store and use at room temperature (10-40ºC). Make sure that both the male and female gas connections are kept clean and free from oil, grease and hydrocarbons before connecting the cylinder to the Innocor. Use no lubricant. Use only cleaning agents that do not leave organic residues. NOTE: To reduce friction gas cylinders are supplied with a small amount of a special lubricant for oxygen service on the threaded part. Do not remove this lubricant. Aluminium high pressure gas cylinder. October 2015 COR-MAN IN (US), E/1 11

18 WARNING! Do not alter or modify the cylinder or the valve in any way. Do not use any caustic or corrosive paint or cleaners on the gas cylinder. Do not remove the product label from the gas cylinder. Use only gas cylinders provided by the manufacturer or his representative. CAUTION. Make sure the O-ring is in place and not damaged before connecting the cylinder to the device. To avoid damage of the O-ring seal, unscrew the cylinder in the following way: a) Partially unscrew the cylinder slowly 1½ turns counter clockwise. b) Vent the lines in the instrument to eliminate the pressure by following the steps shown on the screen during shut-down of the application program [Exit] (or by disconnecting and eventually reconnecting the rebreathing valve unit quick connector with the application program running). c) Then unscrew the cylinder completely. NOTE: During routine use it is recommended not to unscrew the cylinder completely and vent the gas lines when powering off (e.g., overnight). Just unscrew the cylinder 1½ turns to close the cylinder valve. To reopen the cylinder turn 1½ turns clockwise. Pulse oximeter probe connection WARNING! Use only pulse oximeter sensors specified by the manufacturer (see Accessories). Using other sensors may cause improper performance. CAUTION. Inspect the sensor application site frequently to ensure correct sensor alignment and skin integrity. Patient sensitivity to sensors may vary depending on their medical status or the condition of their skin. CAUTION. Do not use a damaged sensor. If the sensor is damaged in any way, discontinue use immediately and replace the sensor. Non-invasive blood pressure hose connection Ensure that the air hose from Innocor to the cuff is not compressed, crimped or damaged. Ensure that the o-ring is not damaged. October 2015 COR-MAN IN (US), E/1 12

19 To connect, push on the connector until it clicks on. To disconnect, press the metal pushbutton to release the locking mechanism and pull. Gas inlet to gas analyzer CAUTION. Always use a particle filter provided by the manufacturer or his representative between the gas inlet connector (analyser) and the sampling tube. The filter has a male slip luer adapter on the analyser side and a female locking luer connector on the sampling tube side. Make sure the filter (membrane) is not contaminated (grey or black) inside. Use only the Nafion dryer type of sampling tube provided by the manufacturer or his representative. Filter and tubing must be properly screwed together. CAUTION. Make sure not to kink or otherwise damage the sampling tube. Never pull the tube. Ensure that the six O-rings are not damaged. Rebreathing valve unit hose connection To connect, push on the connector until it clicks on (note the position of the key). To disconnect, press the colored pushbutton to release the locking mechanism and pull. CAUTION. Never pull the hose. October 2015 COR-MAN IN (US), E/1 13

20 CO 2 absorber cartridge The Calcium Hydroxide CO 2 absorbent is classified as irritant only and can be handled (and transported by road, air and sea) as non-hazardous material. For use only in Innocor canisters designed for the purpose. Do not use if packaging or product is damaged or has been tampered with. WARNING! Use gloves to handle or touch only plastic covered edges of the CO 2 absorber cartridge. The CO 2 absorbent contains caustic compounds; direct contact with unprotected skin can produce severe burns. In case of contact with skin or eyes, rinse immediately with plenty of fresh water. WARNING! CO 2 absorbent is harmful if swallowed. Keep out of reach of children. Minimize time from opening to use. Do not use after expiration date. Storage temperature: -30 C to +50 C. October 2015 COR-MAN IN (US), E/1 14

21 3. PERFORMANCE CHARACTERISTICS (CLINICAL STUDIES) 3.1 STUDIES WITH INNOCOR Agostoni et al. (2005) measured cardiac output (CO) noninvasively with the Innocor, and invasively by thermodilution (TD) and by the gold standard direct Fick (F). Twenty stable congestive heart failure patients (with Swan-Ganz catheters inserted) were tested from rest to maximum exercise capacity. The correlation between CO measurements by the Innocor and Fick methods (r=0.95) and the Innocor and thermodilution methods (r=0.94) were similar to the correlation between CO measurements by the TD and F methods (r=0.95). The regression lines were: CO,IGR = 0.95xCO,F l/min, CO,IGR = 0.78xCO,TD l/min, and CO,TD = 1.14xCO,F l/min. No significant differences were found between CO measurements with the 3 techniques (95 measurements). The day-to-day repeatability of PBF measurements with the Innocor was assessed with a coefficient of variation of 10.8%. The study demonstrated that CO measurements with Innocor are repeatable and reliable at rest and during exercise in CHF patients. Damgaard et al. (2005) evaluated 10 healthy subjects to determine how changes in ventilatory variables affect the determination of CO with the Innocor. Their aim was to determine which parameters utilizing the Innocor produced the most reliable results. In conclusion, the study recommends that rebreathing procedures at rest should be performed following a normal tidal expiration with a rebreathing bag volume of between 1.5 and 2.5 l and with consecutive procedures separated by at least 3-5 minutes. Varying the rebreathing frequency within the normal physiological range (15-30 breaths/min) did not affect the outcome of the measurements. McEniery et al. (2005) investigated the hemodynamic mechanisms underlying isolated systolic and essential hypertension, respectively, and as part hereof measured cardiac output in 1008 young adults (17-27 yrs) using Innocor. The coefficient of variation of repeated determinations of cardiac output at rest was < 10%. The Breath-by-Breath Option of Innocor has been tested against 1) a metabolic calibrator (VacuMed), and a mixing chamber system (AMIS 2001) (Innovision, June 2007a). The VacuMed calibrator used for the test contains 2 syringes simulating inspiration and expiration. The gas exchange simulation is done by replacing a part of the expiratory volume by a gas mixture from a gas cylinder containing 21% CO 2 in N 2. The AMIS 2001 mixing chamber system measures the inspiratory flow and the concentration of the mixed expiratory gases. With the flowmeter placed at the inspiratory port, the technique is independent of expiratory flow with respect to temperature and humidity. The AMIS 2001 technique has been validated against the Gold Standard Douglas bag technique by Jensen et al. (2002) and shown to be accurate. The accuracy of the Innocor flow measurement is within ±10%, but typically within ±5%, and the accuracy of the gas exchange measurement is within ±12% or 50 ml/min, whichever is greater, when tested against AMIS 2001 and VacuMed. The errors include the errors of the reference systems. The performance of the Innocor with the Breath-by-Breath Option has been evaluated against the statement on cardiopulmonary exercise testing ( CPET ) jointly issued by The American Thoracic Society (ATS) and the American College of Chest Physicians (ACCP), (ATS/ACCP, 2003). An internal Innovision report (Innovision, June 2007b) concludes that the BbB Option conforms in all material respects with the Joint Statement. The performance of the Spirometry Option for Innocor has been evaluated against the Standardisation of Spirometry by Miller et al. (2005). Internal Innovision studies have tested the accuracy of the spirometry system. The flowmeter fulfills the requirements for offset, flow range, October 2015 COR-MAN IN (US), E/1 15

22 response time and volume accuracy, and the system fulfills the requirements for accuracy when validated against standard test waveforms (c.f. internal Innovision study, November 2007). Except for the way the indicator gas is washed in and the way FRC is determined, the LCI Option for Innocor has been developed in accordance with the Official ATS/ERS Statement: Pulmonary Function Testing in Preschool Children, Section 7: The Multiple-Breath Inert Gas Washout Technique (Gustafsson et al., 2007). An internal Innovision study (Innovision, 2010) has tested the accuracy of the LCI Option. The FRC measurement is within ±0.2 liters or ±6% relative when validated using a calibration syringe and the accuracy of the LCI measurement is within ±0.2 or ±4% relative when comparing with data from a simulation. 3.2 STUDIES ON EARLIER VERSION OF INNOCOR Gabrielsen et al. (2002) have shown that using an infrared photoacoustic gas analyzer for measurement of cardiac output by inert gas rebreathing (IGR) provides at least as reliable an estimate of cardiac output as does thermodilution. The study compared IGR with thermodilution (TD) and direct Fick (F) in 11 patients with heart failure or pulmonary hypertension. The mean difference (bias) and limits of agreement (± 2 SD) were 0.1 ± 0.9 l/min when comparing CO,F and CO,IGR, and 0.8 ± 1.3 l/min when comparing CO,F and CO,TD. The correlation between CO,IGR and CO,F was CO,IGR = 0.94xCO,F l/min, r=0.94. The equipment used was a prototype of Innocor using an earlier type of photoacoustic gas analyzer measuring the same inert gases and applying the same algorithms as Innocor. Clemensen et al. (1994) showed that an infrared (IR) gas analyzer (similar to the photoacoustic gas analyzer used in Innocor and using the same algorithms) can replace a medical mass spectrometer in inert gas rebreathing measurements of cardiac output and FRC. Ten healthy young adults participated in the study. The results also showed the expected relationship between cardiac output, oxygen consumption and workload during exercise using the IR gas analyzer and demonstrated a good reproducibility. Horsley et al. (2008) showed that lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. They concluded that Innocor can be adapted to measure LCI and affords a simpler alternative to a mass spectrometer. The adaptation was implemented due to the fact that conventional multiple-breath wash-in/wash-out was used. 3.3 OTHERS Liu et al. (1997) showed that the cardiac output determined by acetylene rebreathing with a medical mass spectrometer using the same algorithms as Innocor is valid and nearly identical to that measured by the direct Fick technique not only at rest but also during high-intensity exercise (up to 90% of VO2max). When appropriately performed the measurement is not influenced by recirculation of acetylene. Nine subjects participated, and there was no significant difference in cardiac output measured by each method at rest as well as at each work rate. Hoeper et al. (1999), using a medical mass spectrometer and the same algorithms as Innocor, reported that the inert gas rebreathing method gives a reliable assessment of cardiac output in patients with pulmonary hypertension. They simultaneously compared 105 cardiac output measurements by the Fick method, thermodilution and acetylene rebreathing technique in 35 patients with pulmonary hypertension. They concluded that acetylene rebreathing is a useful tool for October 2015 COR-MAN IN (US), E/1 16

23 assessing cardiac output in patients with pulmonary hypertension, even in the presence of low cardiac output or severe tricuspid regurgitation. A huge number of papers have been written over the last 4-5 decades reporting results of experimental studies, theoretical studies and simulations with the inert gas rebreathing method in healthy volunteers and patients with various lung and cardiac diseases (Barazanji et al.,1996; Cander and Forster, 1959; Friedman et al., 1984; Hsia et al., 1995; Hunt et al., 1997, Kallay et al., 1987; Petrini et al., 1978; Reinhart et al., 1979; Rosenthal et al., 1997; Sackner et al., 1975; Sackner, M., 1987). Several of these studies have compared the non-invasive rebreathing method with invasive reference techniques such as thermodilution, dye dilution and the gold standard; direct Fick. Generally, the studies conclude that inert gas rebreathing is a reliable, accurate and reproducible method of determining cardiac output, FRC and derived parameters in healthy and diseased subjects (Sackner M, 1987). 3.4 CONCLUSIONS FROM THE CLINICAL STUDIES The inert gas rebreathing method implemented in the Innocor system is shown to be reliable and sufficiently accurate and reproducible for clinical applications. The reproducibility of the method is comparable with that of invasive techniques. The method can be used equally well at rest and in exercising subjects. The inert gas rebreathing method is a quick, safe and easy technique to apply for measurements of cardiac output, whereas the thermodilution or direct Fick method requires cardiac catheterisation which is associated with potential risk of adverse events. There are no risks or discomfort combined with the maneuver, and the low concentrations of foreign gases are not harmful. This conclusion is based on both clinical trials using Innocor versus invasive reference techniques, comparative studies using similar infrared photoacoustic gas analyzers, clinical studies using mass spectrometer systems developed by the Innocor manufacturer, and a scientific literature review. The comprehensive amount of literature on inert gas rebreathing underlines the robustness, efficacy and safety of using this technique. The accuracy of the Breath-by-Breath Metabolic Measurement Option is verified against a Vacumed calibrator/simulator and an AMIS 2001 mixing chamber system. The accuracy of the flow measurement is within ±10%, but typically within ±5%, and that of the gas exchange measurements is within ±12% or 50 ml/min, whichever is greater. The errors include the errors of the reference systems. The Spirometry Option for Innocor fulfills the requirements for accuracy when validated against standard test waveforms from ATS. For the LCI Option the FRC measurement is within ±0.2 liters or ±6% relative when validated using a calibration syringe and the accuracy of the LCI measurement is within ±0.2 or ±4% relative when comparing with data from a simulation. 4. CONFORMANCE TO STANDARDS The Innocor device is classified as CLASS I Type BF equipment according to the type and degree of protection against electrical shock in accordance with EN October 2015 COR-MAN IN (US), E/1 17

24 Certification / Safety standards 93/42/EEC EN EN EN EN ISO 9919 EN Medical Device Directive General Requirements for Safety Safety Requirements for Medical Electrical Systems Electromagnetic compatibility Pulse oximeters - Particular requirements Non-invasive sphygmomanometers - Part 3: Supplementary requirements for electromechanical blood pressure measuring systems 5. PHYSICIAN LABELING 5.1 INTENDED OPERATORS The Innocor should be used only by professional health care providers who have received training in the use of the equipment. Equipment specific training is required for the primary operating functions of Innocor. Two to four hours of on-site training is typically offered by the manufacturer or its representative during installation. 5.2 WHY USE INERT GAS REBREATHING TO MEASURE CARDIAC OUTPUT? The major advantage of the Innocor is that it is non-invasive and its determination of CO using inert gas rebreathing is purely analytical. Non-invasiveness is a key advantage of the device, because other widely used and relied upon products/techniques for the measurement of CO require an indwelling venous catheter to be in place or to be placed in the patient. This makes the measurement of CO problematic in terms of risk in all but very ill patients. As opposed to many other non-invasive techniques Innocor can be used equally well in patients at rest and during exercise e.g., in patients who have no symptoms in rest or light exercise. The only requirement is that the patient is capable of understanding the instructions from the operator and performing the breathing maneuver well. A CO measurement with the inert gas rebreathing technique requires about 15 seconds, or 5 breaths. Inert gas rebreathing relies on a simple principle that the rate of disappearance from the gas phase in the lungs of a moderately blood soluble gas N 2 O is proportional to the flow of blood perfusing the lungs (equal to cardiac output in the absence of intrapulmonary shunt). The measurement is easy to carry out, and it involves no risk or pain to the patient. There are no calibrations, significant warm-up time or other mandatory procedures required during daily use of Innocor. October 2015 COR-MAN IN (US), E/1 18

25 5.3 IS INNOCOR CO MEASUREMENT A VALIDATED TECHNIQUE? Innocor utilizes a long (>50 years) validated inert gas rebreathing technology that used full sized mass spectroscopy units at its inception, but which has evolved in the Innocor to photoacoustic spectroscopy that enables the technique to be performed by and housed in the Innocor. The inert gas rebreathing method implemented in the Innocor system has been shown to be reliable and sufficiently accurate and reproducible for clinical applications. The measurements agree well with invasive techniques, and the reproducibility of the method is comparable with that of invasive techniques. This has been shown in comparative clinical trials using Innocor versus invasive reference techniques. 5.4 DESCRIPTION OF INNOCOR PARAMETERS Cardiac Output (CO) The amount of blood ejected from the left ventricle into the aorta (systemic circulation) per unit time [l/min]. CO is equal to pulmonary blood flow in the absence of intrapulmonary shunts SpO2 The oxygen saturation of hemoglobin in arterial blood as determined by pulse oximetry Heart Rate (HR) The number of heart beats per unit time Stroke Volume (SV) The amount of blood ejected from the left ventricle in a single heart beat Lung Volume (VL) The volume of the lungs at the end of the last expiration prior to rebreathing, including deadspace. After a normal non-forced expiration VL is equal to the Functional Residual Capacity (FRC) Cardiac Index (CI) The amount of blood ejected from the left ventricle into the aorta (systemic circulation) per unit time seen in proportion to body size (surface area) Stroke Index (SI) The stroke volume seen in proportion to the body size (surface area). October 2015 COR-MAN IN (US), E/1 19

26 5.4.8 Blood Pressures (SYS, DIA, MAP) Systolic Pressure (SYS): The maximum blood pressure during the systole (heart contraction period). Diastolic Pressure (DIA): The lowest blood pressure during the diastole (heart filling period). Mean Arterial Pressure (MAP): The mean arterial blood pressure Systemic Vascular Resistance (SVR) The resistance to blood flow in the systemic blood circulation, i.e. the average resistance that the left ventricle works against when delivering the stroke volume into the aorta Systemic Vascular Resistance Index (SVRI) The resistance to blood flow in the systemic blood circulation seen in proportion to body size (surface area) Oxygen Uptake (VO 2 ) The amount of oxygen extracted from the inspired gas in a given time Carbon Dioxide Excretion (VCO 2 ) The amount of carbon dioxide exhaled from the body into the atmosphere in a given time Expiratory Minute Ventilation (V E ) The volume of air exhaled from the body in one minute Oxygen Uptake per kg (VO 2 /kg) The amount of oxygen extracted from the inspired gas in a given time per kg body weight Respiratory Exchange Ratio (R) The ratio of the carbon dioxide excretion to the oxygen uptake Alveolar Ventilation (V A ) The volume of air exhaled from the alveoli per minute Anatomical Dead Space (Fowler Dead Space) (V D ) The volume of the upper airways, trachea and bronchi Tidal Volume (V T ) The volume of expired air during a breath Respiratory Rate (f R ) The breathing frequency (number of breaths per minute). October 2015 COR-MAN IN (US), E/1 20

27 End-Tidal Concentration of Oxygen (F ET O 2 ) The oxygen concentration in the expired gas at the end of the exhalation End-Tidal Concentration of Carbon Dioxide (F ET CO 2 ) The carbon dioxide concentration in the expired gas at the end of the exhalation Expiratory Quotient/Ventilatory Equivalent for Oxygen (V E /VO 2 ) The ratio of ventilation to oxygen uptake Expiratory Quotient/Ventilatory Equivalent for Carbon Dioxide (V E /VCO 2 ) The ratio of ventilation to carbon dioxide excretion Anaerobic Threshold (AT) The exercise VO 2 above which anaerobic production supplements aerobic production. Exercise above AT is reflected by an increase in lactate concentration. The AT is measured by the V-slope method on the plot of VCO 2 against VO Respiratory Compensation (RC) The exercise VO 2 above which the ventilation starts to increase more than the VCO 2 in order to compensate for the lactic acidosis. The RC is measured by the V-slope method on the plot of V E against VCO Forced expiratory volume in 1 second (FEV 1 ) The maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration, expressed in liters at BTPS Forced vital capacity (FVC) The maximal volume of air exhaled with maximally forced effort from a maximal inspiration, i.e. vital capacity performed with a maximally forced expiratory effort, expressed in liters at body temperature and ambient pressure saturated with water vapor (BTPS) FEV 1 /FVC (FEV 1 %) The ratio of the FEV 1 to the FVC. Identifies the percentage of total FVC exhaled during the first second of the test. It is sometimes called the FEV 1 Ratio or the FEV 1 /FVC% when shown as a percentage of the FVC Peak expiratory flow (PEF) The maximum expiratory flow achieved from a maximum forced expiration, starting without hesitation from the point of maximal lung inflation, expressed in liters per second. October 2015 COR-MAN IN (US), E/1 21

28 Maximal instantaneous forced expiratory flow (MEF 75) Maximal instantaneous forced expiratory flow where 75% of the FVC remains to be expired Maximal instantaneous forced expiratory flow (MEF 50) Maximal instantaneous forced expiratory flow where 50% of the FVC remains to be expired Maximal instantaneous forced expiratory flow (MEF 25) Maximal instantaneous forced expiratory flow where 25% of the FVC remains to be expired Forced expiratory time (FET) The total time of exhalation expressed in seconds Maximum voluntary ventilation (MVV) The maximum volume of air a subject can breathe over a specified period of time (12 s for normal subjects). It is expressed in liters per minute at BTPS. In Innocor, MVV is calculated as 40 times FEV Functional Residual Capacity (FRC) The lung volume, including deadspace, after a normal non-forced expiration Lung Clearance Index (LCI) The cumulative expired volume required to clear an inert gas from the lungs during normal breathing divided by the Functional Residual Capacity (FRC). LCI represents the number of lung volume turnovers (i.e. FRCs) that the subject must breathe to clear the inert tracer gas from the lungs (by convention, to an end-tidal concentration of 1/40 th of the starting concentration. 5.5 PRECISION Accuracy (bias ± 2 SD) of CO determinations by Innocor has been demonstrated by comparison with the gold standard direct Fick invasive technique. Bias was close to 0 l/min, and limits of agreement (bias±2sd) were approximately 2 l/min on each side of the bias. Precision (coefficient of variation of repeated measurements) has been shown to be around 10% or better. 5.6 LIMITATIONS Pulmonary blood flow (measured by Innocor) equals CO except in patients with large diffusion limitations, as reflected in low oxygen saturations ( 95%) as measured by Innocor's built-in pulse oximeter while breathing room air. Repeated cardiac output tests on the same patient should be separated by an adequate period of time in order to allow sufficient time for washout of inert gases between tests. A period of 5 minutes in rest and 2 minutes during exercise is recommended. October 2015 COR-MAN IN (US), E/1 22

29 The number of tests conducted per patient per day should be limited to 20 in order to prevent the daily exposure to the inert gases from exceeding established limits according to occupational safety and health/hygiene standards. 5.7 WHAT IF A PATIENT IS ON SUPPLEMENTAL O 2? The rebreathing mixture is oxygen enriched (as opposed to ambient air). However, the physician must decide whether the use of Innocor would be safe for testing patients on supplemental oxygen. 5.8 INTERPRETATION OF RESULTS No interpretation of results is provided by Innocor as the interpretation depends on the setting in which the device is used. CO measured during exercise as a complement to a standard exercise test may be used for prognostic evaluation of CHF patients, to distinguish between different causes of exercise limitation, and to monitor the recovery of CHF patients and the progress of cardiovascular function in rehabilitation programs. 6. INNOCOR INSTALLATION Do not connect anything or turn anything on before you have become fully familiar with the contents of this chapter on installation. 6.1 OPERATING ENVIRONMENT Safe ambient operating temperatures range from C. Humidity should not exceed 90% RH non-condensing at 30 C. If the device has been exposed to temperatures significantly below the operating environment temperature, an acclimatisation period is necessary. Avoid excessive heat, dust and direct sunlight. For optimum performance the device must be used in a reasonably vibration-free environment because of the photoacoustic gas measurement principle. Place on a flat, horizontal and solid surface. WARNING! Fire hazard: Avoid open flames and smoking in the areas where the device is being used. WARNING! Explosion hazard: In order to avoid an explosion risk, do not use the equipment in areas in which flammable anesthetics are applied. October 2015 COR-MAN IN (US), E/1 23

30 6.2 PRODUCT OVERVIEW AND INSTALLATION PROCEDURE Innocor is shown in figure 1a and 1b. Depending on the configuration of the device it may look different from what is shown in this and the following figures ) Colour LCD / Touch Screen* 2) Patient Interface Panel 3) Cooling Air Inlet * For devices with external computer, see figure 1b. 1) Lifting Slot 2) Cooling Air Outlet 3) Gas Cylinder Connection 4) Power Interface Panel 5) Data Interface Panel FIGURE 1a. Left) Right side view, Right) Rear view. The rear panel to the left is the power interface panel (figure 2) for the mains AC power input. October 2015 COR-MAN IN (US), E/1 24

31 FIGURE 1b. Innocor version with external computer (tablet). FIGURE 2. Power interface panel for the mains AC power input. Connect an earthed main power cord to the 230 V / 110 V input. The rear panel to the right is the data interface panel (figure 3). October 2015 COR-MAN IN (US), E/1 25

32 FIGURE 3. Data interface panel. Upper: Innocor version with integrated computer and network connection. Lower: Innocor version with external computer (tablet) equipped with a USB type B connector and earth terminal screw (with cable connected to the right). For versions using an external computer, connect the computer using the USB type B connector to the right on the Data interface panel. Also, connect the earth wire to the earth terminal and tighten using a tool. Connect the USB type A end of the cable to the computer. WARNING! If using a version with external computer, the computer must be certified according to the European standard EN The computer should only be used on battery power. Otherwise, it is required to use a safety isolating transformer. The computer must be placed outside of the patient zone. Make sure not to block the gas outlet/inlet connector when installing the device. Remove protective plugs from the gas outlet/inlet connectors if mounted. Before connecting the gas cylinder to the fitting in the lower middle of the rear part (figure 1a), ensure that an intact O-ring is in place (figure 4). Connect the gas cylinder to the fitting (figure 5) by hand tightening. NOTE: When the valve opens automatically extra torque is required to screw the cylinder onto the device (an additional approx. 2 turns). October 2015 COR-MAN IN (US), E/1 26

33 FIGURE 4. Gas cylinder connection, position (left) and cross sectional view (right). Note correct positioning of O-ring seal (right). FIGURE 5. Innocor with gas cylinder mounted and RVU in storage position. October 2015 COR-MAN IN (US), E/1 27

34 FIGURE 6. Patient interface panel. Left) Shown without connections, Right) Shown with connections. Connect the six-tube quick connector to the rebreathing valve unit hose connection on the side panel (it clicks on) see figure 6. Connect the gas analyzer sampling tube to the gas inlet connection. Make sure to use a particle filter between the gas inlet connection (analyzer) and the sampling tube. The filter has a male Luer-Slip adapter on the analyzer side and a female Luer-Lock connector on the sampling tube side. Make sure the filter (membrane) is not contaminated (grey or black) inside. Guide the gas analyzer sampling tube along the flexible tubing to the rebreathing valve unit, making sure not to kink or damage the sampling tube. Connect the pulse oximeter finger probe to the D-sub connector marked SpO2 on the side panel. Connect the NIBP arm cuff to the NIBP quick connector on the side panel using the air hose (optional). The rebreathing valve unit is shown with connections in figure 7a and 7b. October 2015 COR-MAN IN (US), E/1 28

35 Innovision FIGURE 7a. Rebreathing valve unit with connections (upper: standard RVU, lower: RVU with BBB/LCI Option). 1) Gas sampling tube, 2) flowmeter, 3) respiratory bacterial/viral filter, 4) mouthpiece, 5) rebreathing bag, 6) BBB port, 7) RB port. October 2015 COR-MAN IN (US), E/1 29

36 Connect the gas sampling tube to the Luer-Lock connector on the rebreathing valve unit. Make sure a small tube is connected to the insert at the RB port. Connect a rebreathing bag to the rebreathing valve unit s RB port. Standard Innocor Connect a respiratory bacterial/viral filter with mouthpiece to the mouthpiece port of the rebreathing valve unit. Innocor with BBB Option Connect the flowmeter to the mouthpiece port of the rebreathing valve unit. Connect a respiratory bacterial/viral filter with mouthpiece to the flowmeter. Connect a flow resistor on the BBB port if the patient is unable to trigger / start a rebreathing test (only for measurements at rest). Innocor with LCI Option Connect an optional CO 2 scrubber (absorber) to the rebreathing port of the rebreathing valve unit before connecting the rebreathing bag. Make sure a small tube is connected to the insert at the RB port and guided through the centre hole of the scrubber material. See figure 7b Figure 7b. Rebreathing valve unit with connections (RVU with LCI option). 1) gas sampling tube, 2) flowmeter, 3) respiratory bacterial/viral filter, 4) mouthpiece, 5) rebreathing bag, 6) BbB port, 7) RB port, 8) CO 2 scrubber (absorber). October 2015 COR-MAN IN (US), E/1 30

37 7. INSTRUCTIONS FOR USE 7.1 DISPLAY SYMBOLS / LABELS The following symbols are used on the equipment, accessories and packaging: Symbol Description CAUTION Caution, consult accompanying documents Attention, see instructions for use i Consult instructions for use On (power) Off (power) Mains power inlet; Input voltage ranges and fuse rating ~ Alternating current Fuse October 2015 COR-MAN IN (US), E/1 31

38 Symbol Description Universal serial bus (USB) connections Network connection Gas outlet / inlet Gas inlet to gas analyzer Rebreathing valve unit hose connection Non-invasive blood pressure hose connection Pulse oximeter probe connection Type BF Applied Part (EN ) (protection against electrical shock) Do not use oil or grease October 2015 COR-MAN IN (US), E/1 32

39 Symbol Description CE Marking indicating conformance to EC Directive No. 93/42/EEC concerning medical devices, with identification number of notified body LOT Lot number (batch code) SN Serial number REF Catalogue/Reference number Date of manufacture (yyyy-mm / yyyy-mm-dd) Manufacturer Use by (yyyy-mm/yyyy-mm-dd) Temperature limitation Keep dry 180 October 2015 COR-MAN IN (US), E/1 33

40 Symbol Description Dangerous goods label. CLASS 2 HAZARD - Gases (No. 2.2) Non-flammable, non-toxic gas. Black or white on green background. Dangerous goods label. Class 5.1 HAZARD - Oxidizing substances (No. 5.1) Black on yellow background. COMPRESSED GAS OXIDIZING, N.O.S. (OXYGEN MIXTURE) UN 3156, 5.1 Dangerous goods label. Irritant. October 2015 COR-MAN IN (US), E/1 34

41 7.2 MAIN SCREEN (INNOCOR PROGRAM) When all electrical and pneumatic connections are made you can switch the power on ( I ). The device is ready after a couple of minutes after being powered up. The Innocor application program's main screen appears (figure 8): FIGURE 8. Innocor main screen Measurement Select Measurement to perform rebreathing tests or to examine data from previous tests Setup Select Setup to change test, calculation or graphic settings and to perform service and calibration procedures Data Management Select Data Management for data exchange functions Blood Pressure (Stand-Alone Test) Option: Select Blood Pressure to make a stand-alone blood pressure measurement without rebreathing. Set the initial pressure and press start to initiate the measurement. See also section Blood Pressure below. October 2015 COR-MAN IN (US), E/1 35

42 7.2.5 Exit Select Exit to terminate the program and switch Innocor off. 7.3 CALIBRATION It is recommended to perform all calibrations below once a day before starting the tests. It is also recommended to make a new flow-gas delay calibration every time the gas sample line or the flowmeter screen is replaced. Select Configuration Press Measurement on Screen. Select the configuration: E.g. StdRVU_Ser_Scr (adults,+25kg). Press Prepare to calibrate Innocor (only once a day). FIGURE 9. Selection of configuration (example). FIGURE 10. Calibration status menu. October 2015 COR-MAN IN (US), E/1 36

43 7.3.1 Ambient data Press Change ambient data and enter actual values Flowmeter Calibration If the Innocor contains the Breath-by-Breath or LCI Option, it is recommended to perform a gain calibration of the flowmeter once a day. It is also recommended to make a new calibration every time the flowmeter screen is replaced. NOTE: Press Calibrate flowmeter. Connect a 1 liter or 3 liter calibrated syringe to the RVU, and set the S/W switch accordingly. Empty the syringe Press Calibrate Fill the syringe at a relatively low rate without bumping at the end. When the S/W is ready empty the syringe again at a low rate. Repeat the filling and emptying until 2x5 strokes have been applied, and the OK button is highlighted. Increase the flow rate at each of the 2x5 strokes in order to try to cover the physiological test range. Press OK if the new gain values are in the range 0.9 to 1.1, otherwise replace the flowmeter screen and repeat the calibration. The flowmeter is automatically offset adjusted prior to each stroke. A gas cylinder must be connected in order to close the RB port of the RB valve during the flow calibration Flow-gas Delay Calibration If the Innocor contains the Breath-by-Breath or LCI Option, it is recommended to perform a calibration of the flow-gas delay once a day. It is also recommended to make a new calibration every time the gas sample line is replaced. If only the Spirometry Option is used the flow-gas delay calibration can be skipped. NOTE: Press Calibrate flow-gas delay. Wait 1 minute for warming up. The operator (not the subject) starts breathing in and out of the RVU. When ready the Calibration button is pressed. Then the operator must make some slow expirations followed by very fast inspirations until the OK button is highlighted. The inspirations have to be fast in order to get a precise determination of the flow-gas delay. If one or two breaths fail the software will automatically filter these results. The delays should not vary more than ms from day to day if the same gas sample inlet is used. A gas cylinder must be connected in order to close the RB valve during the delay calibration The BBB port on the RVU must not be connected to other devices during the delay calibration October 2015 COR-MAN IN (US), E/1 37

44 The calibration of the flow-gas delay is critical an error of 25 ms can give a 5% error on the Vo 2, Vco 2, FRC and LCI results! Oxygen Calibration If an oxygen sensor is included in the system it is recommended to perform a calibration of the baseline of the oxygen sensor once a day. Press Calibrate Oxygen. Expose gas sample line to air by removing it from breathing assembly. Press Start to perform a one point calibration of the Oxygen. Press OK (to Exit Prepare). Press OK (to select configuration). 7.4 MEASUREMENT (CO BY REBREATHING / CPET PROGRAM) Operating Principle The operating principle of Inert Gas Rebreathing by Innocor is to let the patient breathe minute quantities of a blood soluble and an insoluble gas in a closed breathing assembly for a short period. The blood flowing through the lungs (effective pulmonary blood flow, PBF) absorbs the blood soluble gas. Therefore, its disappearance rate is proportional to the blood flow. Other factors affecting the distribution of the blood soluble gas are accounted for by measuring the levels of the blood insoluble gas Start of Rebreathing / CPET Program The procedure described in the following sections will under normal conditions be adequate to perform a rebreathing measurement or cardiopulmonary exercise test: Start the program from the Innocor menu by selecting Measurement. The screen layout is as shown in figure 11. October 2015 COR-MAN IN (US), E/1 38

45 FIGURE 11. General screen layout. 1) Patient identification field, 2) date and time field, 3) push button panel, 4) status bar and numerical display*, 5) data field for numerical results, graphics and database information etc. * Abnormal operation of pulse oximeter or probe faults is indicated by --- in the HR and SpO2 fields Patient Selection Choose Patient to enter the patient database section of the program. Press New Pt. to enter data for a new patient. Enter relevant data for the patient or test subject by pointing at the appropriate entry field and using the alphanumeric keyboard shown on the screen. Select Male or Female from the selection list or type M or F on the keyboard to select the patient s sex. Press Clear to clear all fields. Instead of entering new data it is also possible to search a patient already appearing in the database. Use the Search button for this feature. Enter one or more search criteria and press Filter to start the search process. Press All to disable all search criteria and display all patients. October 2015 COR-MAN IN (US), E/1 39

46 Press Edit to change patient data if necessary. After having entered or chosen the patient data, press the Select button. Results from the latest previous test are shown on the screen if available Test Preparation Check that the bottle pressure displayed in the status bar at the bottom of the screen is adequate (i.e. > 10 bar). Attach the articulated pulse oximeter (SpO 2 ) finger clip sensor. See also section Pulse Oximetry. Option: Attach the BP cuff. Avoid using the same arm for BP and SpO 2 measurements. See also section Blood Pressure. Connect to the mouthpiece and attach a nose clip, or use a face mask. WARNING! Never use the device without a new disposable single patient use bacterial/viral filter in the patient connection to minimise the risk of crosscontamination Test Execution Press Test to prepare a new measurement. Enter or verify the height and weight of the patient and enter the hemoglobin (Hb) concentration to allow calculation of derived parameters (optional). Option: If the Innocor software is an exercise or Breath-by-Breath version, the user can select an exercise protocol, which controls the progress of the exercise level and controls a series of predefined rebreathing tests in respect to bag volume and bolus concentration. Option: If the Innocor software contains the Spirometry version, the user can select a Spirometry test, where the user performs up to 8 forced expiration maneuvers in order to determine the basic spirometry parameters of the subject. If the Innocor software is a standard version without exercise or Breath-by-Breath, the Test button will start a Rebreathing test immediately. OPTION: Spirometry Press Test and select Spirometry. The spirometry maneuver starts with normal tidal breathing followed by a rapid and complete inspiration. Then immediately after the subject makes a maximal forced expiration until no more air can be expelled. Finally the subject performs a fast inspiration. It is recommended to make more than one spirometry maneuver in order to be sure that the measurement is representative for the subject. ATS requires at least 3 well performed spirometry maneuvers. The best performed maneuver is automatically selected and saved together with the other Innocor results. October 2015 COR-MAN IN (US), E/1 40

47 7.4.6 Option: Breath-by-Breath The breath-by-breath calculation of gas exchange parameters starts when the exercise protocol is selected and continues until the protocol is finished - only interrupted by the rebreathings. The results of the breath-by-breath calculation are displayed on-line in a table to the left and as graphics to the right. The content of the table can be modified using the Table Setup, and similar with the graphics, which can be configured in 1, 2 or 3 plots using the Graph Setup. The default display is the breath-by-breath display, but the user can select other displays using the Show results button. The Show protocol displays the progress of the exercise test, and gives the possibility to change settings of the next steps to come if necessary. The Show results displays the results of the previous rebreathing test, and the Show online data displays the raw flow and gas data. A protocol can be temporary interrupted using the Hold protocol / Stop protocol. The Innocor switches to 5 minutes cool down period, when the protocol finishes, or when the protocol is manually terminated using the Stop protocol Rebreathing Test Preparation The device automatically prepares the rebreathing bag by emptying (using automatic detection of when the bag is empty) and filling it with the desired volume of gas. A mixture of ambient air and gas from the cylinder is filled into the bag. When the bag is ready the screen shows end-tidal gas concentrations, gas curves and the airway pressure curve. Option: The BP measurement can be stopped / aborted (the Stop NIBP button) and restarted again during the test. Only the last measured values are saved in the database. Option: When the BP measurement is finished the resulting Systolic / Diastolic pressures are shown for 20 s in the status bar. Attach the articulated pulse oximeter (SpO 2 ) finger clip sensor. Avoid using the same arm for BP and SpO 2 measurements. See also section Pulse Oximetry. Connect to the mouthpiece and attach a nose clip. WARNING! Never use the device without a new disposable single patient use bacterial/viral filter in the patient connection to minimise the risk of crosscontamination. October 2015 COR-MAN IN (US), E/1 41

48 7.4.8 Rebreathing Test Press Start to start the rebreathing test. Start can be pressed during any phase of the breathing cycle. The device will open to the rebreathing bag at the end of the actual expiration or at the end of the subsequent expiration following the actual inspiration. When the valve shifts the patient should hold the breath until the valve has switched completely (approx. half a second). When breathing, try to follow the speed indicator. Breathe faster if the indicator is to the right of OK ( Faster ). Breathe slower if the indicator is to the left of OK ( Slower ). It is essential that the rebreathing bag is being emptied completely during the first and the subsequent inspirations. The test stops automatically with empty bag when an adequate number of breaths are acquired typical 4 or 5 breaths Option: Blood Pressure (BP) Measurement It is a good idea to start a BP measurement during the bag filling (the Start NIBP button). See also section Blood Pressure. The current cuff pressure is shown in the status bar in the lower right corner of the main test window. The BP measurement can be stopped / aborted (the Stop NIBP button) and restarted again during the test. Only the last measured values are saved in the database. When the BP measurement is finished the resulting Systolic / Diastolic pressures are shown for 20 s in the status bar. If the BP measurement has not finished when the rebreathing test is finished, you get a message to wait for the BP measurement. If the BP measurement is stopped the rebreathing test results will still be saved in the patient database Results Data is being saved automatically and results are shown immediately on the screen. The display of results is organized in the following views: Tab \ Focus Exercise test Single rebreathing test Results Main results of the rebreathing: Selected parameters at rest, AT and max. exercise. Details Graphs Data Table Data View 1-4 Data View 5-8 Table display of BBB parameters versus time. Graphic display of BBB parameters in up to 3x3 plots. Main results of a rebreathing: CO, CI, Vo 2 /kg, SV, A-V O 2 diff Detailed results of a rebreathing Rebreathing curves for evaluation of the quality of the test Main results of a spirometry test: FVC, FEV 1, FEV 1 %, PEF, MEF 75, MEF 50, MEF 25, FET & MVV Detailed results of the spirometry maneuvers Graphic display of the best performed spirometry maneuver Table display of rebreathing and BBB results for one or more rebreathing/exercise tests Graphic display of rebreathing and BBB results for one or more rebreathing/exercise tests October 2015 COR-MAN IN (US), E/1 42

49 The results are displayed in different ways depending on where the focus is set in the Date/Time list (figure 12): A complete exercise test, a spirometry test or a single rebreathing test. The focus is set on an exercise test by selecting a line in bold with name Ex.n. or BBB.n, see below. Selecting a line named n:1, n:2 etc. will set the focus on a single rebreathing test. A spirometry test is selected by selecting a line named Spi. FIGURE 12. Test selection panel. The rebreathing Results window is shown in figure 13. FIGURE 13. Main rebreathing results. Press the Details tab to display detailed results (including derived variables, figure 14). October 2015 COR-MAN IN (US), E/1 43

50 FIGURE 14. Detailed rebreathing results. Press the Graphs tab to display rebreathing curves for evaluation of the quality of the test. Pointing inside a rebreathing plot can expand each of the four plots. See the examples below in figure 15. FIGURE 15a. Rebreathing curves. October 2015 COR-MAN IN (US), E/1 44

51 FIGURE 15b. Normalized soluble gas (N 2 O). FIGURE 15c. Insoluble gas (SF 6 ). FIGURE 15d. Normalized oxygen. October 2015 COR-MAN IN (US), E/1 45

52 FIGURE 15e. Soluble (N 2 O) and insoluble gas (SF 6 ). See note (*). FIGURE 15f. Carbon dioxide (CO 2 ). See note (*). * The plot in the upper left corner of figure 15a can be configured to show one or more curves on a common y-axis. Curves are set on/off using the Graph Setup button. Breath-by-Breath results: With focus on an exercise test and the Results tab activated will display selected BBB parameters at Rest, AT (Anaerobic Threshold) and at Max exercise level: October 2015 COR-MAN IN (US), E/1 46

53 FIGURE 16. Main exercise results (example of setup). Pressing the Details tab will display selected BBB parameters in a table. The time step can be configured to 30, 60, 90, 120 seconds or every breath. FIGURE 17. Detailed exercise results (example of setup). Pointing on the Breath-by-Breath plots (Graphs) will expand the plots. A second press on a plot will expand the actual plot. October 2015 COR-MAN IN (US), E/1 47

54 FIGURE 18. 3x3 plots of Breath-by-Breath results. Spirometry results: Focus on a spirometry test and the Results tab activated gives a numerical display of the spirometry results: FIGURE 19. Spirometry main results. October 2015 COR-MAN IN (US), E/1 48

55 Pressing the Details tab gives a display of the results of the individual spirometry maneuvers. FIGURE 20. Spirometry detailed results. Pressing the Graphs tab gives a display of the graphic result of the best performed spirometry maneuver. FIGURE 21. Spirometry graphic results. By pointing on the spirometry plots (Graphs) the detailed display of the individual spirometry maneuvers is entered. Common results: Press the Data Table Tab to display the results in a tabular form for the selected tests. The Table Setup can be used to configure the contents of the table. The table can be printed directly using the Print Table. October 2015 COR-MAN IN (US), E/1 49

56 FIGURE 22. Data Table. Pressing the Data View Tabs will display the results in XY plots for the selected tests. The data view can be configured via the Dataview Setup. Both the X-axis and the Y-axis can be defined with respect to what to display, grid and min/max on axes. Up to 5 parameters can be selected on the y-axis. Each parameter can be assigned to the left or right y-axis, and a 1st or 2nd order regression line can be fitted to the data. FIGURE 23. Data View After a Test Press one of the following buttons: October 2015 COR-MAN IN (US), E/1 50

57 Test to repeat a test on the same patient (allow sufficient time for washout of inert gases). Print Prev. to preview and print results. Patient to enter the patient database for entering or searching patient data. Pt. Data to change patient data (Hb, Height, Weight). Test Param. to change settings for the rebreathing maneuver. Demo to perform a trial rebreathing test using air (dry run). Exit Meas. to exit to the Innocor main screen (menu) Setup From the Innocor main screen (menu), use the Setup button to change test settings (or press the Test Param. button from a test result screen). Change settings for the rebreathing test from the main Setup screen. It is recommended to use the factory default settings. As a guideline use a Bolus fraction of 10%. Choose Ambient from the Setup screen to change ambient data (pressure, temperature and humidity). Press Misc to change system settings. Choose Gas Cylinder to enter the Gas Cylinder identification menu. Use this menu to mount a new gas cylinder to the Innocor, or when changing gas cylinders. Choose User Params to define up to 5 user defined parameters (numbers). The name of the user parameters are limited to standard characters [a..z, A..Z, 0..9, _]. A user parameter is deleted by deleting the name of the parameter. User parameters are manual entered before or after a test. Choose Date to set date and time and to change formats. Choose Language to select the language. Choose Unit to change the units of weights and heights. Option: Choose Protocol Setup to define one or more protocols. A protocol is defined as a series of rebreathing tests at different exercise levels on a bicycle ergometer or a treadmill. For each step the exercise level, time interval, bag volume, bolus and breathing frequency shall be defined as a fixed or auto value. An auto value calculates automatically the value during the execution of the protocol. Calibration: Choose Adjust O2 from the Setup screen for calibration of the oxygen sensor (option). Follow the instructions on the screen. It is recommended to perform a one-point calibration using air (20.95% O 2 ) once every month. Option: Choose Adjust Flowmeter for a calibration of the flowmeter. It is recommended to perform the calibration every day. Option: Choose Calculate gas delay for a calibration of the delay between the gas signal and the flow signal. It is recommended to perform the calibration every day. October 2015 COR-MAN IN (US), E/1 51

58 Gas calibration will normally not be necessary because of the stability of the analyzer and the fact that only relative changes are determined in the rebreathing method. Press Close from the Setup screen to go back to the Innocor main screen (menu) Data Exchange For data exchange, press the Data management button in the Innocor main menu Blood Pressure Test (Stand-Alone) Option: For access to a stand-alone blood pressure program press Blood Pressure. Set the initial pressure and press start to initiate the measurement. See also section Blood Pressure Recommended Settings At rest it is recommended to use a rebreathing frequency of /min. During exercise it is recommended to use a larger rebreathing bag volume of liters and a rebreathing frequency of 30 /min, resulting in a ventilation of at least 60 l/min. Allow sufficient time for washout of inert gases between repeated tests on the same patient. At rest 5 minutes is generally adequate. During exercise 2 minutes is recommended. Select a bolus fraction of e.g. 10 % of the bag volume (can be set to % of the bag volume). However, ensure that the bolus volume is big enough to prevent a situation with deficiency of oxygen in the inspired air, in particular when testing during exercise Termination of Program Remember to unscrew the gas cylinder (as a minimum 1½ turns) before you exit the Innocor application. When turning the gas cylinder 1½ turns counter-clockwise the main valve of the gas cylinder is closed. 7.5 MEASUREMENT (LCI BY MULTIPLE-BREATH WASH-OUT) Operating Principle Innocor uses a combination of two techniques to determine the LCI, using SF 6 as the inert tracer gas: Inert gas rebreathing (IGR) is used for rapid wash-in of a very small amount of SF 6 until an even concentration is obtained in the lungs before the wash-out can start. During rebreathing the patient inhales an oxygen enriched mixture from a pre-filled rubber bag. This is followed by multiple-breath wash-out (MBW) for determination of the cumulative expired volume (V CE ) required to clear the SF 6 from the lungs. The wash-out phase is initiated by automatically disconnecting from the bag at the end of an inspiration where after the patient breathes October 2015 COR-MAN IN (US), E/1 52

59 room air until the end-tidal SF 6 concentration has fallen below the predetermined fraction of 1/40 th of the starting concentration. Normal values for LCI are 6-8 in healthy young people and can increase to in sick people. See figure SF6 conc. (%) 0.05 Quick equilibration and reliable FRC determination Washout to 1/40 of starting concentration Time (s) Figure 24. The SF 6 concentration measured during wash-in by rebreathing followed by wash-out in open-circuit breath-by-breath mode Start of LCI Program After a successful calibration the following procedure (7.5.3 to ) will under normal conditions be adequate to perform a measurement: Start a test from the Innocor menu by selecting Measurement Patient Selection Select a patient in the patient database or press New Pt. to enter data for a new patient. Enter relevant data for the patient or test subject by pointing at the appropriate entry field and using the alphanumeric keyboard shown on the screen. Select Male or Female from the selection list or type M or F on the keyboard to select the patient s sex. Press Clear to clear all fields. It is possible to search a patient already appearing in the database. Use the Search button for this purpose. October 2015 COR-MAN IN (US), E/1 53

60 Enter one or more search criteria and press Search to start the search process. Press Show All to disable all search criteria and display all patients. Press Edit to change patient data if necessary. After having entered or chosen the patient data, press the Select button General Screen Layout The general screen layout is shown in figure FIGURE 25. General screen layout. 1) Patient identification field, 2) data field for numerical results, 3) date and time field, 4) list of performed tests, 5) push button panel, 6) data field for graphic results, 7) status field for Gas bottle pressure, heart rate and oxygen saturation*, and 8) test comments field. * Abnormal operation of pulse oximeter or probe faults is indicated by --- in the HR and SpO2 fields. Results from the most recent test are shown on the screen if available. October 2015 COR-MAN IN (US), E/1 54

61 7.5.5 Test Preparation Check that the bottle pressure displayed in the status bar at the bottom of the screen is adequate (i.e. > 10 bar). Attach the articulated pulse oximeter (SpO 2 ) finger clip sensor. See also section Pulse Oximetry. Connect to the mouthpiece or face mask and attach a nose clip. WARNING! Never use the device without a new disposable single patient use bacterial/viral filter in the patient connection to minimise the risk of crosscontamination. Press Test Param. to edit the setup. FIGURE 26. Setup menu. It is recommended to use the factory default settings. October 2015 COR-MAN IN (US), E/1 55

62 Parameter Default Comments O 2 limit 13% The wash-in is stopped if the O 2 gets lower than the O 2 limit. CO 2 limit 10% The wash-in is stopped if the CO 2 gets higher than the CO 2 limit. Bolus fraction 20% Fraction of the bag volume coming from the gas bottle. A higher bolus fraction gives a higher O 2 concentration in the bag. FRC mixing threshold 15% Threshold to find the location of the breaths used for the FRC calculation. LCI mixing threshold 2% Threshold to determine the stop of the wash-in. Bag volume VT ratio 1.5 Ratio to determine the bag volume based on the VT. FRC breaths after mixing 3 Number of breaths used to calculate the FRC. Trigger signal O 2 Trigger signal to find the expirations (O 2 or CO 2 ). FRC calculation on soluble Average Method to fit the FRC line. Reg. line or Average. Bag dead space 13 ml Dead space of the bag when empty. Valve dead space 103 ml Dead space of valve in rebreathing / wash-in mode. FRC skip at start exp. 30% Part of expiration not used in the calculations at the start. FRC skip at end exp. 15% Part of expiration not used in the calculations at the end Test Execution The LCI test contains 3 phases: Preparation, where the subject s resting tidal breathing is measured and used to prepare the correct amount of rebreathing volume. Wash-in, where the subject is rebreathing in the bag until the insoluble tracer gas is mixed with the lungs. Washout, where the subject is breathing in normal air until the insoluble tracer gas is washed out of the lungs. Preparation: Press Test to prepare a new measurement. The subject shall breathe quietly. The CO 2 scrubber cartridge is designed for approx. 20 tests and should be replaced when either the inspired or expired CO 2 concentration exceeds certain limits, e.g. F I CO 2 > 2.5 % or F ET CO 2 > 6.5 % (see section and 8.2.3). The material is non-indicating. The device detects the subject breathing and when stable the Prepare Bag is highlighted. With the subject breathing quietly the operator can press the Prepare Bag. The device automatically prepares the rebreathing bag by emptying (and automatically detecting when the bag is empty) and filling it with the desired volume of gas. A mixture of ambient air and gas from the cylinder is filled into the bag. October 2015 COR-MAN IN (US), E/1 56

63 Volume versus time with averaged VT VT and Freq versus time Numerical display Configuration of numerical display Configuration of grapical display FIGURE 27. LCI preparation. October 2015 COR-MAN IN (US), E/1 57

64 Wash-in: When the bag is ready the Start Wash-in button is highlighted. If the subject is still breathing quietly the operator presses the Start Wash-in. Start Wash-in can be pressed during any phase of the breathing cycle. The device will open to the rebreathing bag at the end of the actual expiration or at the end of the subsequent expiration following the actual inspiration. The subject is guided to breathe quietly but emptying the bag, and when the insoluble gas is mixed well between the bag and the lungs, the device will close to the rebreathing bag at the end of the next expiration, and the washout period is started. At this time the subject is guided to breathe quietly again. The wash-in takes typically one minute for a subject with healthy lungs. Insoluble gas during wash-in Wash-in mixing status FIGURE 28. Wash-in. If down going spikes are detected on the insoluble curve during wash-in a leak is present and has to be located and corrected before the start of washout. A leak will not destroy the wash-in, but will affect the washout and thereby the results (FRC and LCI). Note: It is difficult to see a leak during washout. October 2015 COR-MAN IN (US), E/1 58

65 Washout: The subject breathes quietly, and when the insoluble gas is washed out of the lungs, the test is completed. The wash-out takes typically 2 minutes for a subject with healthy lungs. When 2 or more LCI manoeuvres have FRC s within 10% they are marked online with a. The operator can stop the LCI test when 2 or more manoeuvres are marked with a - otherwise continue up to max 5 manoeuvres. Accepted tests: FRC within 10% Online predicted FRC and LCI Washout status Insoluble gas during washout Washout time and no. of breaths FIGURE 29. Washout. If the patient coughs during the washout the maneuver can not be used and an extra maneuver must be collected. After the test the operator must manually change the mode to not be used see below. October 2015 COR-MAN IN (US), E/1 59

66 7.5.7 Results Data is being saved automatically and results are shown immediately on the screen. The display of Multiple Breath Washout (MBW) results are organised in the following views: Tab \ Focus Results Details Graphs Data Table Data View 1-4 Data View 5-8 Display Main results of the MBW: Averaged LCI & FRC. Main results of the MBW: Averaged LCI & FRC, as well as detailed LCI & FRC for each maneuver. N/A Table display of LCI & FRC results for one or more MBW tests Graphic display of LCI & FRC results for one or more MBW tests The Results are displayed for the test in focus in the Date/Time list (see figure 30). Date & time of LCI tests Numerical results Washout of insoluble gas versus FRC turnovers FIGURE 30. LCI results. Pointing inside a plot gives an expanded view of each of the plots. October 2015 COR-MAN IN (US), E/1 60

67 Main LCI results Status of each wash-in Manoeuvres used in main results? FIGURE 31. Detailed results (expanded view). Innocor selects as default the best LCI maneuvers by looking at the maneuvers with FRC s within 10%. It first takes the maneuvers with accepted status, i.e. the maneuvers where the wash-in mixing is below 2%. If no one is accepted, it takes the maneuvers with FRC s within 10% of all maneuvers. The main LCI results are the average of the used LCI s and FRC s. If the patient coughs during the washout the maneuver shall not be used and the operator shall remove the under used see below. Pressing the tab 1, 2, 3 will bring up detailed graphs for the individual maneuvers see figure 32. The displays can be user configured to show: - raw curves, - wash-in of insoluble gas, - washout of insoluble gas and - turnover plot. Iwi displayed in the upper left windows is the wash-in index at the end. To be accepted the number must be below 2%. October 2015 COR-MAN IN (US), E/1 61

68 FIGURE 32. Results for a single maneuver. Pressing Setup will bring up the menu for configuration of the graphic. FIGURE 33. Setup menu for graphs. October 2015 COR-MAN IN (US), E/1 62

69 Pressing the Details tab on the measurement screen see figure 34 will bring up numerical results of each maneuver behind the test as well as the averaged result. FIGURE 34. LCI numerical results. Press the Data Table tab to display the results in a tabular form for the selected tests, and thereby compare results of different days. The Table Setup can be used to configure the contents of the table. The table can be printed directly using the Report. Pressing the Data View tabs will display the results in XY plots for the selected tests. The data view can be configured via the Dataview Setup. Both the X-axis and the Y-axis can be defined with respect to what to display, grid and min/max on axes. Up to 5 parameters can be selected on the y- axis. Each parameter can be assigned to the left or right y-axis, and a 1st or 2nd order regression line can be fitted to the data After a Test Press one of the following buttons: Test to repeat a test on the same patient. A new test can be started immediately after the previous also if the previous has been interrupted. Report to print results. Delete to delete a test. Exit Meas. to exit to the Innocor main screen (menu) Setup From the Innocor main screen (menu), use the Setup button to change test settings. Choose Ambient from the Setup screen to change ambient data (pressure, temperature and humidity). October 2015 COR-MAN IN (US), E/1 63

70 Press Misc to change system settings. Choose Gas Cylinder from the Setup screen to enter the Gas Cylinder identification menu. Use this menu to mount a new gas cylinder to the Innocor, or when changing gas cylinders. Choose User Params to define up to 5 user defined parameters (numbers). The name of the user parameters are limited to standard characters [a..z,a..z,0..9,_]. A user parameter is deleted by deleting the name of the parameter. User parameters are manual entered before or after a test. Choose Date to set date and time and to change formats. Choose Language from the Setup screen to select the language. Choose Unit to change the units of weights and heights. Calibration Choose Calibrate - Adjust O2 for calibration of the oxygen sensor. Follow the instructions on the screen. It is recommended to perform a one-point calibration using air (20.95% O 2 ) once every day. Choose Calibrate - Adjust Flowmeter for calibration of the flowmeter. It is recommended to perform the calibration every day. Choose Calibrate - Calculate gas delay for a calibration of the delay between the gas signal and the flow signal. This is not necessary for the LCI measurement, but it can be a good check of the Innocor device with respect to gas sample flow. The flow-gas delays are typically between 1,200 and 1,400 ms. Gas calibration will normally not be necessary because of the stability of the analyzer and the fact that only relative changes are determined in the LCI method. Press Exit Setup from the Setup screen to go back to the Innocor main screen (menu) Data Exchange For data exchange, press the Data management button in the Innocor main menu. Insert an empty USB memory stick in the Innocor see figure 3. Press Script found Find and select the script: Copy Data to USB.idm Press Perform Move the USB memory stick to a standard computer. Locate the actual test files in the folder USB:\LCI named as LCIEnnnnmmm-ddmmyyyy-hhmm.LCI Where Ennnnmmm is the patient ID ddmmyyyy is the date of the test hhmm is the time of the test October 2015 COR-MAN IN (US), E/1 64

71 Recommended Settings The setup menu is shown in figure 35. FIGURE 35. Setup menu. It is recommended to use the factory default settings. Parameter Default Comments Bag volume VT ratio 1.5 Ratio to determine the bag volume based on the VT. Bolus fraction 20% Fraction of the bag volume coming from the gas bottle. A higher bolus fraction gives a higher O 2 concentration in the bag. O 2 limit 10% The wash-in is stopped if the O 2 gets lower than the O 2 limit. CO 2 limit 10% The wash-in is stopped if the CO 2 gets higher than the CO 2 limit. Scrubber type Serial Termination of Program Remember to unscrew the gas cylinder (as a minimum 1½ turns) before you exit the Innocor application. When turning the gas cylinder 1½ turns counter-clockwise the main valve of the gas cylinder is closed. October 2015 COR-MAN IN (US), E/1 65

72 7.6 RVU DESCRIPTION Operating Principle The Innocor RVU is a low resistance respiratory valve unit with a high level of hygiene due to a disposable valve insert. The RVU controls the breathing path of the subject to either breathing air or gas from the rebreathing bag. The subject is connected to the RVU via a bacterial filter to avoid contamination of the valve insert. The RVU is connected to the Innocor via a 6-tube containing tubes for controlling the pneumatic valves, bag filling and evacuation, and a tube for measuring the mouthpiece pressure. A rebreathing bag is connected to the lower port of the RVU at the back. If the subject has very low ventilation and is not able to trigger a start of a rebreathing test a flow restrictor can be inserted at the lower port of the RVU at the front. Ambient air port with flow restrictor Respiratory Valve Unit Rebreathing bag port Bacterial filter Mouthpiece Connection to Innocor 6-tube Rebreathing bag FIGURE 36. Respiratory Valve Unit (RVU) with rebreathing bag, bacterial filter and mouthpiece Valve Insert CAUTION: The valve insert is not intended to be used sterilized / disinfected. The valve insert is intended to be replaced when changing the Innocor gas bottle, which corresponds to approx. 75 tests depending on use. The disposable valve insert is made of silicone, and is placed inside a plastic housing, which is easy to dissemble and assemble (figure 37). Remember to power off the Innocor or enter the main menu of the Innocor software before changing the valve insert otherwise the gas cylinder will be emptied. October 2015 COR-MAN IN (US), E/1 66

73 When done rotate the knob with the Innovision logo clockwise and the plastic housing becomes loose and can be taken apart. The old valve insert is removed and a new valve insert is fitted on the metal plate inside the plastic housing. Put the other part of the plastic housing on top and press the two parts gently together until a click is heard. The RVU is now ready to use. Plastic housing Valve insert Plastic housing Bacterial filter port Knob Rebreathing bag port 6-tube Ambient air port with flow restrictor FIGURE 37. Assembly of RVU. The valve insert is mounted with a small fitting and a short tube to the bag filling / evacuation port inside the rebreathing bag port (figure 38). This must not be removed; otherwise the mixing of the bolus and air gas will not be adequate. October 2015 COR-MAN IN (US), E/1 67

74 Bag filling / evacuation port Fitting Ambient air port Rebreathing bag port Tube Rebreathing bag connector FIGURE 38. Valve insert CO 2 Scrubber For LCI testing a CO 2 scrubber (absorber) is mounted in the rebreathing port (see figure 7b) to avoid build-up of CO 2 during the rebreathing period where the inert tracer gas is washed in. The absorber material is a Calcium Hydroxide mixture with the trade name ExtendAir CO 2 Absorbent. The absorbent material, which uses the same chemistry as a granular sodalime absorbent, is a microporous polyethylene sheet coiled to form a cartridge. The molded ribs in the material create channels through which the breathing gases flow (see figure 39). One of the unique features of an ExtendAir cartridge is that the breathing resistance of the absorbent is precisely controlled by the constant rib height and spacing, resulting in a uniform reaction zone within the absorbent. Also, dusting is avoided. Figure 39. CO 2 scrubber (cartridge and canister parts). October 2015 COR-MAN IN (US), E/1 68

75 7.6.4 Flow Restrictor The flow restrictor, which can be used if the ventilation is too low to trigger the start of a rebreathing, contains 4 small membrane flaps (figure 40). Flow restrictor FIGURE 40. Flow restrictor RVU Test The RVU operates via pneumatic gas and is designed to open to either the rebreathing bag port at the back or to the ambient air port at the front. The RVU valve can be tested using the service part of the Innocor software: Disconnect the rebreathing bag and flow restrictor Enter Setup Enter Service Press the Misc TAB Press the Valve TAB Press the Pneu 1 button, and check that the rebreathing bag port is closed Press the Pneu 2 button, and check that the ambient air port is closed Spirometry Mode Option: When running a spirometry test the flowmeter must be set in stand alone mode, where the inspiration / expiration flow only enters the flowmeter and bacterial filter in order to minimize the flow resistance. The flowmeter and holder are disconnected from the RVU, moved upwards and reconnected using the knob on the lower part of the holder. October 2015 COR-MAN IN (US), E/1 69

76 FIGURE 41. Flowmeter in spirometry mode CAUTION: Flowmeter must be removed from RVU port to stand-alone position for spirometry test. 7.7 PULSE OXIMETRY Operating Principle Oxygen saturation SpO 2, expressed as a percentage, defines the amount of oxygen carried compared to total capacity. It is measured by a two-wavelength pulse oximeter incorporated in the Innocor. The SpO 2 value is measured by a light absorption technique: Red and infrared light (660 nm and 910 nm) is emitted from the emitter side of the sensor. The light is partly absorbed when it passes through the monitored tissue. The amount of transmitted light is detected in the detector side of the sensor. When the pulsative part of the light signal is examined, the amount of light absorbed by arterial hemoglobins is discovered and the saturation level can be calculated. The pulse oximeter equipment is calibrated to display functional oxygen saturation. No SpO2 Alarms Attaching the Sensor Connect the sensor to the SpO 2 connection on the Innocor patient interface (right side) panel. Remove finger nail polish, artificial nails etc. from the finger that will serve as the measuring site. October 2015 COR-MAN IN (US), E/1 70