USER MANUAL . INTEGRATED PLATFORM. FOR PRECLINICAL. PULMONARY RESEARCH. WELCOME TO THE FLEXIVENT FX Congratulations, and thank you for selecting the flexiVent! The flexiVent FX combines the most accurate, detailed and reproducible measurements of respiratory mechanics with flexible and efficient experimentation management. The flexiVent FX operates with flexiWare software in a system designed for mechanical ventilation and life support execution of measurement manoeuvres including the Forced Oscillation Technique (FOT) management and storage of acquired raw data data analysis & model fitting visualization, storage and export of results, and maintenance of experimental records in electronic format. This user manual contains important information and should be studied in detail before operating the flexiVent FX. However, this manual is not intended to be a complete guide of the flexiWare software. For detailed information about using and configuring the flexiWare software, please refer to the flexiWare user manual. The information contained in this manual is believed to be accurate at the time of print. However, SCIREQ Scientific Respiratory Equipment Inc. does not offer any warranties, express or implied, for the content of the manual and the use of all related products. The license and operating conditions apply. SCIREQ Scientific Respiratory Equipment Inc. 6600 rue St-Urbain, Suite 300 Montreal, Quebec, Canada H2S 3G8 P. 514-286-1429 P. 877-5-SCIREQ (toll-free in Canada and USA; 877-572-4737) F. 514-286-1627 www.scireq.com flexiVent User Manual version 6.2. (Document No: FV-FXUM) Revised July 31, 2014 © SCIREQ Scientific Respiratory Equipment Inc., 1997–2014. All rights reserved. This manual may not be reproduced or duplicated in print or any other media, including electronic storage and transmission, without prior written permission from SCIREQ Scientific Respiratory Equipment, Inc. Aerogen and Aeroneb are registered trademarks of Aerogen, Inc., Galway, Ireland. iv SAFETY CONSIDERATIONS WARNINGS The flexiVent is not intended for use with human subjects. If you use anaesthetic gas and/or aerosols, take precautions to ensure that the expired gas/aerosol does not escape into the room air. Ensure proper evacuation and control of potentially harmful substances being introduced into the system to protect the user(s). Disengage the motor lock before connecting a power source. Do not attempt to open the base unit cover while the instrument is running; there is a danger of moving parts. When carrying or moving the flexiVent, always ensure that the device is kept horizontal and supported by two hands underneath the unit. The power cord used should comply with local standards. Use only the power supply provided by SCIREQ with the flexiVent system. v Only gases may be introduced through the air intake (e.g. room air, non-flammable mixed gas, inhaled anesthesia). Introduction of other substances through the air/gas intake, e.g. particulates or aerosol, may damage the module’s piston. Always unscrew the piston rod before attempting to remove the module from the base unit. Handle the module carefully. Avoid straining or bending the piston rod. Clean the expiratory valve only. Do not attempt to clean the refill or inspiratory valves. Do not attempt to clean or dry the expiratory line while an FX adapter is in place in the module. Also, do not attempt to clean or dry the expiratory line while outside of an experimentation session. Attempting to clean or dry the expiratory line with the valve close will damage the module. Do not use abrasive or corrosive detergents or mechanical cleaning aids. Do not dismantle the module or base unit to attempt to clean it. Do not use abrasive or sharp tools to clean the nebulizer unit. Do not autoclave the Aeroneb controller or cables. Do not immerse the Aeroneb controller or cables in water. vi Avoid removing the nebulizer from the mount while a subject is attached. If it is necessary (e.g. for cleaning), do so quickly and immediately replace the nebulizer or use a cap to close the ventilator circuit. When you are using and handling the flexiVent, always observe all of the cautionary notes included in this manual. SCIREQ is not liable for damage or injury resulting from misuse of this product. LIST OF SYMBOLS The following table describes the electrical and safety symbols that may be displayed on the flexiVent FX. The safety symbols may also appear throughout this manual and other product support documents. SYMBOL DESCRIPTION Direct current Alternating current Caution, risk of electric shock Caution; closely observe all cautionary statements to prevent equipment damage and ensure operator safety Power button Ethernet network cable connection port vii SYMBOL DESCRIPTION Auxiliary channels Synchronization port (in) Synchronization port (out) Power supply connection Intake/Inspiratory line Exhaust/Expiratory line Inappropriate for disposal in general waste Aluminum components; please recycle as appropriate Internal magnet viii TABLE OF CONTENTS 1 Introduction ....................................................................................................................................................................11 1.1 Intended Use ........................................................................................................................................................... 11 1.2 UnitWise Platform & flexiWare.................................................................................................................... 12 1.3 flexiVent FX System Overview ..................................................................................................................... 16 1.4 Theory of Operation ............................................................................................................................................ 17 2 Set up & Installation ................................................................................................................................................. 25 2.1 Selecting a Location ...........................................................................................................................................25 2.2 Preparing for Installation ...........................................................................................................................25 2.3 Placing the System ....................................................................................................................................... 28 2.4 Connecting the Components ................................................................................................................... 28 2.5 Opening the flexiVent protective cover .............................................................................................33 2.6 Working with an Alternate Module....................................................................................................... 34 2.7 Configuring flexiWare................................................................................................................................. 38 3 Getting Started ......................................................................................................................................................... 39 4 Accessories ................................................................................................................................................................. 50 4.1 UNIT Transducers ............................................................................................................................................... 50 ix 4.2 Nebulizer............................................................................................................................................................ 54 4.3 Calibration Accessories ..............................................................................................................................57 4.4 Hardware Extension for Negative Pressure Forced Expirations (NPFE).......................... 58 4.5 Multi-subject Extension (MSX) ..............................................................................................................60 5 Cleaning, Decontamination and Maintenance ............................................................................................. 61 5.1 Cylinder ..................................................................................................................................................................... 61 5.2 Cleaning flow pathways and Valves ..................................................................................................... 62 5.3 FX Adapter and Y-tubing ...........................................................................................................................66 5.4 External Surfaces ..........................................................................................................................................66 5.5 Aeroneb Nebulizer ........................................................................................................................................ 67 5.6 Annual Cleaning and Maintenance ........................................................................................................68 5.7 Repackaging, Transport and Storage..................................................................................................69 5.8 Replacement Components ....................................................................................................................... 74 Appendix A: Technical Specifications .........................................................................................................................76 x 11 1 INTRODUCTION The flexiVent FX is a UnitWise instrument most often used for assessment of respiratory mechanics in pre-clinical research. Your system is customized to your research application and may be enhanced as new products are released. 1.1 INTENDED USE At its core, the flexiVent is a computer-controlled piston ventilator that allows you control over ventilation parameters. To perform an assessment of respiratory mechanics, ventilation is momentarily suspended and a pre-defined volume waveform is applied by the piston. The data collected during the manoeuvre are analyzed by the software, which reports measurements of mechanics. The computer control of the piston and precision with which data are collected generates accurate, reproducible measurements of respiratory mechanics. The flexiVent FX is designed for full mechanics assessments in subjects weighing approximately 8 g to 1 kg. It may be used for ventilation and mechanics measurements from small amplitude manoeuvres in subjects weighing approximately 8 g to 5 kg. Additional details are available in Table A-2. If you intend to use the flexiVent outside typical operating conditions explained in this user manual, please contact SCIREQ Technical Support for additional instructions and documentation. The flexiVent is not intended for use with human subjects. 12 1.2 UNITWISE PLATFORM & FLEXIWARE The flexiVent FX is built on the second generation UnitWise platform, a fully digital, data acquisition and control architecture designed to be operated by flexiWare software. For additional details on flexiWare refer to the flexiWare user manual. FIGURE 1-1: UNITWISE PLATFORM The flexiWare/UnitWise platform consists of a variety of different components that are optimized for their individual tasks and communicate digitally with each other, as illustrated in Figure 1-1. This section provides an overview of the different platform components to permit users a better understanding of the interplay between the different system components. 13 1.2.1 WORKSTATIONS The UnitWise platform uses standard Ethernet connectivity as the backbone to connect the high-level components of a UnitWise data acquisition and experimentation environment. The list of high-level components includes the individual UnitWise instruments (see section 1.2.2), experimentation and review workstations (both running flexiWare), and the database server on which data may be stored in a central location. In the simplest scenario, a single stand-alone computer can serve as experimentation workstation, review workstation and database server. On the other hand, the UnitWise/flexiWare architecture permits distributed multi-client environments where data may be simultaneously collected from several parallel workstations into a central database, allowing study directors to observe the evolution of the experiment in real time from the comfort of their office. 1.2.2 INSTRUMENTS & SYSTEMS In UnitWise terminology, “instruments” are compact laboratory instrumentation devices that possess both an Ethernet connection and several ports for Universal Intelligent Transducers (UNITs). Recent UnitWise instruments also feature a display and local user interface on the device. Instruments serve as the central building blocks of UnitWise data acquisition systems and perform the large majority of all real-time data acquisition, control and automation functions. In UnitWise terminology, “systems” comprise one or more instruments as well as a variety of UNITs selected according to the application at hand, connected together in such a way that the specific data acquisition and control needs of this application are met. Every UnitWise system must contain one primary instrument, and may contain one or more secondary instruments. The secondary instruments are controlled by the primary instrument, permitting phase-locked data acquisition systems with a virtually unlimited number of channels. 14 FIGURE 1-2: UNIVERSAL INTELLIGENT TRANSDUCER (UNIT) ARCHITECTURE 1.2.3 PORTS, UNITS & CHANNELS UnitWise instruments typically possess eight ports, each of which may be occupied by one Universal Intelligent Transducer (UNIT) without further adapters, amplifiers or pods, so that any UNIT can fit into and be recognized by any instrument port (see Figure 1-2). Every UNIT contains between one and four sensor elements or other input/output channels, each permitting the measurement or modification of a physical property. To optimize the signalto-noise ratios, all input signals are digitized right in the UNIT. A small micro-controller (μC) 15 contained in every UNIT scales and linearizes the signals and performs self-tests and local control functions. The controller also retains calibration and identification details that are communicated digitally to the instrument and the host software to log the system configuration and assert its integrity. A common example for a simple UNIT is shown in UNIT A in Figure 1-2. This UNIT has a single analog input channel to measure a signal from a single sensing element and communicate it to the instrument and the software. A precision differential pressure transducer such as model UT-DPD-02 is an example of this type of UNIT. UNIT B in Figure 1-2 provides an example of local low-level servo control. This UNIT combines an analog input channel with an embedded actuator that has the ability to manipulate the attribute being measured in order to simultaneously collect the actual measurement and push it towards a desired value as provided by the instrument and/or the software. An example for this type of UNIT would be a temperature-controlled water bath. UNIT C in Figure 1-2 provides a further example of the platform’s flexibility as it shows 3 analog input channels communicating measurements to the software while a fourth digital output channel is used to allow the software to switch or send synchronization signals to outside instruments. 1.2.4 INTEGRATED SYSTEMS In UnitWise terminology, some SCIREQ products are referred to as “integrated systems” since they contain both an instrument and one or more UNITs in a common package. For example, a flexiVent FX has all features of a UnitWise instrument (Ethernet, ports and embedded display) but also possesses several internal ports to measure and control volume displacement, pressures and valve states. Integrated systems such as the flexiVent typically feature a limited number of external (auxiliary) ports for accessories, and their port count can be further extended by adding a secondary instrument (see section 1.2.2). Some integrated systems offer functionality that goes above and beyond the capabilities of a standard UnitWise data acquisition system (e.g. mechanical ventilation for the flexiVent, pump profiles for the inExpose). When working with an integrated system such as the inExpose or the 16 flexiVent, menus and commands are automatically configured in the software such that you have complete access to your instrument’s functionality. The instrument-specific configuration is controlled by flexiWare licensing, SDMs and template mechanisms. It does not require any additional steps or configuration settings during operation. All commands necessary for your application are available for your use, following setup and installation. 1.3 FLEXIVENT FX SYSTEM OVERVIEW The flexiVent FX is composed of two main parts: the base unit and a module. The base unit includes the following: a computer-controlled linear actuator; an optical position sensor; a processing platform (controller); a base plate with a protective enclosure ; a module connection platform; and an embedded user interface. A module is comprised of the following: a precision piston-cylinder set; three computer-controlled valves; pressure transducers; a micro-processor; and air flow pathways and connections. For additional details, see section 1.2. 17 1.4 THEORY OF OPERATION As is mentioned in section 1.1, the flexiVent is a computer controlled piston ventilator. The computer control afforded by flexiWare software makes the flexiVent versatile because you control the parameters of the ventilation and measurement manoeuvres that it executes. Its design adds to its versatility in part because it may be used with a range of subject sizes, but also because it allows for the integration of a variety of accessories and hardware extensions, which includes both SCIREQ products and third-party products. 1.4.1 RESPIRATORY MECHANICS Generally speaking, mechanics is the relationship of objects and the forces that act upon them. Respiratory mechanics is a way to quantify the airway constriction and stiffness of the lungs through relationships between pressure, volume and flow using mathematical models. 1.4.2 FORCED OSCILLATION TECHNIQUE Measurement manoeuvres executed by the flexiVent are referred to as perturbations. During a perturbation, an iso-volume ventilator compartment is established when the valves within the module close to the outside environment. The ventilator compartment consists of the subjects respiratory system, the cylinder, pathways outside the module (e.g. Y-tubing) and pathways within the module (e.g. from the cylinder to the Y-tubing). Once the valves are closed, the perturbation, or Forced Oscillation, is applied to the ventilator compartment through movement of the piston (see Figure 1-3). The signals generated during the perturbation are used to calculate parameters of respiratory mechanics that help to quantify acute and/or chronic disease-related changes to the lungs. 18 FIGURE 1-3: VALVE CONFIGURATION DURING A PERTURBATION There are six families of perturbations. A description of each follows. The properties (e.g. duration, maximum pressure) for the perturbations are established in the flexiWare software. For detailed information about perturbation properties, refer to the flexiWare user manual. TABLE 1-1: STANDARD FLEXIVENT PERTURBATIONS NAME DESCRIPTION Deep Inflation Deep inflation of the subject's lungs to a pressure of 30 cmH20 (or other user-specified value) followed by a breath hold of typically a few seconds. SAMPLE 19 NAME DESCRIPTION SnapShot Single frequency, sinusoidal forced oscillation waveform. The oscillation frequency is typically matched to the subject's respiratory rate (e.g. "SnapShot150" for mice breathing at 150 br/min). Broadband (multi-frequency) forced oscillation waveforms, Primewave typically denoted by duration (e.g. "Prime-8" lasts 8 seconds). PV Loop Slow stepwise or continuous (ramp) inflation to TLC (or other user-specified value) and deflation back to FRC, controlling either volume or pressure. SAMPLE 20 NAME DESCRIPTION NPFE Deep inflation followed by rapid switch to negative pressure reservoir (hardware extension required). Imaging Pressure-controlled breath-hold, with or without a preceding deep inflation with synchronized trigger signals for imaging modalities such as Micro-CT or microscopes (imaging system not supplied by SCIREQ, auxiliary hardware required). 1.4.3 SAMPLE INDIRECT MEASUREMENT The flexiVent uses the indirect measurement technique to assess respiratory mechanics. In animal subjects, especially those that do not generate large tidal flows, precise flow measurement can be quite difficult. Flow measurement difficulty is compounded by signal losses due to gas compression, so use of flow measurements to calculate mechanics is technically challenging. The flexiVent uses measurements of position and pressure, both which can be measured with great precision and consistency, to calculate mechanics outcomes. The indirect measurement technique also helps address the technical challenge introduced by the signal effects of gas compression and cannula resistance. During the inspiratory portion of ventilation the pressure in the cylinder is slightly higher than that at the airway opening, and the airway opening pressure is slightly higher than that within the subject’s trachea. Similarly, the 21 volume of air displaced by the piston is slightly higher than the volume delivered to the subject. Before any perturbations are run with the subject attached, the ventilator compartment is characterized for each perturbation. When the subject is attached and a perturbation subsequently run, the contribution of the subject may be isolated by subtracting that of the ventilator compartment. 1.4.4 SERVO-CONTROLLED PISTON The module of the flexiVent FX contains the piston/cylinder set. Movement of the piston is servo-controlled through a closed feedback-control loop as in Figure 1-2. The piston is driven by the linear actuator in the base unit and its position is measured by an optical sensor. The differential pressures in the cylinder and ventilator compartment are measured by transducers within the module. When the piston moves, it causes a change in the pressures measured by the transducers. These pressures are measured for the purpose of calculating respiratory mechanics, but also to provide feedback so the piston’s movement may be adjusted as needed (e.g. it will move less to generate a given pressure following administration of a bronchoconstrictor). 1.4.5 CONTROLLING EXPERIMENTAL CONDITIONS Section 1.4.3 discusses a technical challenge in pre-clinical respiratory mechanics. An additional physiological challenge is addressed by controlling experimental conditions. Mechanics assessments using other methods may be based on measurements taken breath-by-breath in spontaneously breathing subjects. As breathing frequency increases, resistance decreases. Respiratory mechanics also vary with tidal volume. If breath-by-breath measurements are taken following any variation in the experimental conditions, it is not possible to distinguish mechanics changes caused by that variation from mechanics changes that may be introduced due to an increase or decrease in breathing frequency, for example. As discussed in section 1.4.2 the flexiVent takes measurements during perturbations. Perturbation properties are set in the software, so little to no variation exists between subjects. 22 1.4.5.1 STANDARDIZING VOLUME HISTORY A subject’s volume history affects mechanics measurements. Ventilation parameters (e.g. tidal volume, I/E ratio) are set in the software to ensure that all subjects in a study are ventilated in a similar manner. In addition, the Deep Inflation perturbation is commonly used to re-set or standardize volume history. This is especially true in dose response studies (in which the Deep Inflation may be used to help subjects return to baseline before subsequent doses are administered) and imaging studies (in which the Deep Inflation is used to ensure consistent inflation prior to image acquisition). 1.4.6 INTERCHANGEABLE MODULES As mentioned in section 1.3, the flexiVent FX piston/cylinder set and valves that create the ventilator compartment are mounted on the portion of the system called the module. There are five modules currently available. Each module is designed to minimize its inherent resistance which permits the highest precision mechanics measurements. The piston/cylinder set size determines whether or not the system is appropriate for work with a given subject, so the system can be easily adapted for a wide range of subject sizes. Furthermore, one base unit may be used with a variety of subjects by incorporating additional modules. Refer to Table A-2 for module specifications, including estimates for subject weight ranges. 1.4.7 INTEGRATING A NEBULIZER The Aerogen Aeroneb ultrasonic nebulizer can be integrated with the flexiVent FX in order to deliver aerosols to the subject. The parameters of aerosol production are set in the software, which allows for precise control of the aerosol delivery. Specially designed adapters allow tight integration of the nebulizer to minimize aerosol rainout. The flow pathways within the adapters are also designed to minimize the addition of volume to the ventilator compartment for nebulizer integration. Refer to section 4.2 for additional details about the nebulizer. Refer to the flexiWare user manual for additional details on software settings to control the nebulizer as well as nebulizer output rate and rainout characterization. 23 1.4.8 APPLYING PEEP Positive end expiratory pressure, or PEEP, is applied to subjects being mechanically ventilated to prevent airway closure. One method for applying PEEP is to submerge expiratory tubing into a column or beaker of water; this method is used in earlier generation flexiVent instruments. To adjust the PEEP applied using a water column, the level to which the tubing is submerged is adjusted. In the flexiVent FX, the valves within the module are specifically selected to allow for computer-controlled PEEP, thereby eliminating the need to use the historical water column method. The level of PEEP applied may be adjusted in the ventilation pattern dialogue in the software and may be easily adjusted. 1.4.9 INTEGRATING OTHER ACCESSORIES The flexiVent FX is highly configurable and may be integrated with other devices, including UNIT transducers, SCIREQ product extensions geared toward particular measurements (e.g. SCIREQ NPFE hardware extension), and third party devices (e.g. Micro-CT scanner for gated image acquisition). The integration may require customized adapters and/or data files for full functionality. For questions regarding integration with a particular accessory, contact SCIREQ Technical Support or refer to user instructions provided with your additional hardware. Please note that only accessories approved and recommended by SCIREQ Technical support should be used in conjunction with the flexiVent FX. 24 25 2 SET UP & INSTALLATION The installation sequence described in this section applies to the hardware portion of configuring a flexiVent FX instrument for use in a UnitWise system. Customized installation procedures may be required for some application-specific configurations. Please read the set up and installation instructions for all of your system components before proceeding. When carrying or moving the flexiVent, always ensure that the device is kept horizontal and supported by two hands underneath the unit. 2.1 SELECTING A LOCATION The flexiVent FX requires approximately 2’ x 2’ (60 x 60 cm) of level workspace near the data acquisition workstation. The flexiVent needs to connect to at least one power outlet (more may be necessary if your instrument includes certain hardware extensions). Your workstation likely requires two outlets, one for the monitor and one for the CPU. With these electricity requirements in mind, select a location for your workstation and flexiVent FX that has at least three outlets, adequate workspace and that allows all users to easily access all connections present on the flexiVent FX. 2.2 PREPARING FOR INSTALLATION When the shipment arrives, carefully remove the flexiVent FX from the boxes and packaging. These should be kept, if possible, as they may be used for future transportation of the system (e.g. routine maintenance) or to prevent any damages to the instrument when it is not used for 26 an extended period of time (see section 2.6.1). The flexiVent base unit is shipped with a module attached. If your instrument includes additional modules, they are shipped in separate boxes. The following components are part of every flexiVent FX system: a flexiVent FX base unit; one or more flexiVent FX modules; a power supply; an Ethernet cable; THE FLEXIVENT AT A GLANCE (OPPOSITE PAGE) one or more FX adapters; 1 BASE UNIT one or more Y-tubing kits; 2 EMBEDDED DISPLAY one flexiWare installation DVD; and 3 CONTROLLER flexiWare and flexiVent FX user manuals. 4 MODULE 5 PISTON/CYLINDER SET 6 FX ADAPTER (PICTURED WITH NEBULIZER AND Y-TUBING ATTACHED) an Aeroneb controller, 7 AIR/GAS INTAKE an Aeroneb nebulizer, 8 AIR/GAS EXHAUST an FX adapter with nebulizer mount, and 9 AUXILIARY PORTS (4) a rainout characterization kit including a drying tube; 10 SYNC PORT (IN) The system may also contain the following optional components: Nebulizer setup, which includes a pressure manometer; 11 SYNC PORT (OUT) one or more UNIT transducers 12 ETHERNET PORT appropriate Allen keys and screwdriver; and 13 POWER CONNECTOR other product extensions or accessories. 27 1 2 3 7 10 8 11 4 5 12 9 6 FIGURE 2-1: THE FLEXIVENT FX 13 28 2.3 PLACING THE SYSTEM The flexiVent and all extensions require a dry, flat, stable workspace of 2’ x 2’ x 2’ (60 x 60 x 60 cm). Ensure that the system is stable on the workbench. If the surface is not quite level, use the adjustable foot located under the front corner below the module to help level it and prevent unwanted vibrations. Once the flexiVent is in place, you may disengage the motor lock. To disengage the lock (refer to Figure 2-2), remove the thumb screw (A) then rotate the motor lock to open position (B). After disengaging the lock, reattach the thumb screw to the FX base unit (C). FIGURE 2-2: DISENGAGING THE MOTOR LOCK 2.4 CONNECTING THE COMPONENTS Please refer to Figure 2-1 for each of the connection locations. Plug in and unplug accessories only when the base unit is off. 29 2.4.1 POWER Disengage the motor lock before connecting a power source. Refer to section 2.3 for details. The power cord used should comply with local standards. Use only the power supply provided by SCIREQ with the flexiVent system. Ensure that the motor lock is disengaged. Connect the power supply to the appropriate location on the controller module. Plug the power supply into a standard wall outlet using the appropriate cord. 2.4.2 WORKSTATION OR NETWORK Connect an Ethernet cable to the Ethernet port on the controller module. Connect the other end of the cable to a server, data acquisition workstation or network port. The appropriate connection for the Ethernet cable varies with the complexity of your UnitWise system. 2.4.3 TRANSDUCERS & ACCESSORIES Connect transducers and accessories (e.g. UNIT Aeroneb adapter cable) to the auxiliary ports found on the controller module. Selection of the appropriate port is determined by the template selected for experimentation, and a prompt will appear during the start-up sequence of experimentation denoting the appropriate configuration. A selection of configurations is provided in Table 2-1; for configurations including hardware extensions or custom applications, refer to documentation that accompanies the hardware or information supplied by SCIREQ Technical Support. 30 TABLE 2-1: SELECTION OF AUXILIARY PORT CONFIGURATIONS AUX PORT AEROSOL AEROSOL AND EKG AEROSOL AND ALL VITAL SIGNS DEFAULT 1 none UNIT Aeroneb adapter cable UNIT Aeroneb adapter cable UNIT Aeroneb adapter cable 2 none none UNIT EKG transducer UNIT EKG transducer 3 none none none UNIT Temperature transducer 4 none none none UNIT blood pressure transducer Once the transducer or accessory hardware is connected, its cable may be threaded underneath the center of the base unit if needed for ease of subject access. 2.4.4 AIR INTAKE & EXHAUST The intake and exhaust connections are at the rear side of the module. These connections exist in order to introduce an external gas source (e.g. filtered air or air with specific gas concentration) or to manage the exhaled gases (e.g. for collection or evacuation). 2.4.4.1 ALTERNATE INTAKE SOURCE Alternate air sources or inhaled anaesthesia may be used with the flexiVent. It is extremely important that the intake is not pressurized. In order to install an alternate external air source, use one of two methods to ensure that no pressure is applied: 1) Use a very compliant bag and fill it with the desired gas mixture or the anaesthesia gas. Attach it directly to the intake port using a Quick-Connect fitting. Every time the piston 31 pulls back, it will draw in some of the gas mixture and then deliver it to the subject. Since the bag is very compliant, it will not pressurize the system. 2) Use a flow-past circuit, which involves putting a T-piece on the intake (refill) port as shown in Figure 2-3. You will have to supply your own T-piece as every gas anaesthesia machine has different sized tubing. The T-piece’s single port will be attached to the intake valve tubing. The anaesthetic gas mixture will then be flowing past the intake valve, and not directly pressurizing the port. Every time the piston pulls back, it will draw in some of the gas mixture and then deliver it to the subject. Extra gas can be re-circulated to the anaesthesia machine or sent to exhaust (e.g. fume hood). FIGURE 2-3: GAS ANAESTHESIA INTEGRATION Do not pressurize the air/gas intake or exhaust. 32 Only gases may be introduced through the air intake (e.g. room air, non-flammable mixed gas, inhaled anesthesia). Introduction of other substances through the air/gas intake, e.g. particulates or aerosol, may damage the module’s piston. If you use anaesthetic gas and/or aerosols, take precautions to ensure that the expired gas/aerosol does not escape into the room air as this can be hazardous for the operator. 2.4.5 SUBJECTS Before attaching a subject to the flexiVent, proceed through the start-up sequence described in section 1. Failure to initiate the start-up sequence in advance of connecting the subject may result in loss of the subject. Connect subjects to the flexiVent using a cannula or endotracheal tube that is attached to the Ytubing at the front of the module. The Y-tubing must be connected to an FX adapter (with or without a nebulizer mount, refer to Figure 2-4) which is inserted into the opening on the front of the module. You will hear a click when the adapter is securely in place. 33 FIGURE 2-4: FX ADAPTER SHOWN WITH NEBULIZER MOUNT AND WITHOUT NEBULIZER MOUNT; SUBJECTS ARE ATTACHED AT THE END OF THE Y-TUBING. 2.5 OPENING THE FLEXIVENT PROTECTIVE COVER The flexiVent cover is locked in order to ensure protection from moving parts. Unlocking the cover should only be necessary in order to replace the module or for maintenance purposes. Please carefully read all relevant documentation before opening the flexiVent FX cover. 1) Power off the flexiVent and disconnect it from its power supply. 2) Introduce a pen or other such tool into the small opening as shown in Figure 2-5 34 FIGURE 2-5: COVER LOCK MECHANISM 3) Press gently to unlock the cover. 4) While pressing gently lift the cover to open it. 2.6 WORKING WITH AN ALTERNATE MODULE As mentioned in section 2.2, the instrument ships with a module attached. If you have ordered an instrument that contains multiple modules, they will ship in separate packages. If you would like to work with a module that shipped separately, you must assemble the alternate module, remove the one that is attached to the base unit, and then install the alternate module on the base unit. 2.6.1 ASSEMBLING A SEPARATELY SHIPPED MODULE To assemble the alternate module, follow the module-specific instructions below or refer to the instruction card that is included within the module’s packaging. 35 2.6.1.1 FX MODULES 1, 2 AND 3 FIGURE 2-6: ASSEMBLY STEPS, FX MODULES 1, 2 AND 3 5) Align the O-ring and the piston/cylinder assembly with the module per Figure 2-6. 6) Insert screws to hold the piston/cylinder in place This step requires a 7/64” hex/allen wrench. Screws should be secure, but do not over-tighten them, as this may cause damage. 36 2.6.1.2 FX MODULES 4 AND 5 FIGURE 2-7: ASSEMBLY STEPS, FX MODULES 4 AND 5 1) Align the O-ring and the piston/cylinder assembly with the module per Figure 2-7. 2) Rotate the piston/cylinder clockwise until it is secure, but do not over-tighten as this may cause damage. 2.6.2 1) REMOVING A MODULE FROM THE FX BASE UNIT Power off the flexiVent and disconnect it from its power supply. 2) Open the base unit protective cover. 37 3) Unscrew the piston rod from the motor arm per Figure 2-8. FIGURE 2-8: PISTON ROD UNSCREWED FROM THE MOTOR ARM (LEFT) 4) Loosen the module securing screw. FIGURE 2-9: MODULE SECURING SCREW 5) Lift module upwards. Be sure to unscrew the piston before attempting to remove the module. Handle the module carefully. Take extra precautions to protect piston rod because minor bending could cause it to break or cease to function properly. 2.6.3 1) INSTALLING AN ALTERNATE MODULE Be sure to complete the steps detailed in sections 2.6.1 and 2.6.2 before proceeding. 38 2) Power off the flexiVent and disconnect it from the power supply. 3) Open the base unit protective cover. 4) Lower the module onto the base unit. The module snaps into place once it is positioned correctly 5) Tighten the module securing screw (see Figure 2-9). 6) Attach the piston rod to the motor arm per Figure 2-10. FIGURE 2-10: PISTON ROD CONNECTED TO THE MOTOR ARM (RIGHT) 2.7 CONFIGURING FLEXIWARE The flexiVent FX is operated by flexiWare software. To complete the instrument installation, please refer to the flexiWare user manual, section 2 (Set Up & Installation). These sections guide you through the steps necessary to connect the flexiVent to the workstation(s), server or network desired. 39 3 GETTING STARTED When you are using and handling the flexiVent FX, always observe all of the cautionary safety notes included in this manual. SCIREQ is not liable for damage or injury resulting from misuse of the product. The following section is designed as a quick guide to using the flexiVent FX, and it notes only those features in the experimentation session module of flexiWare software that are required for hardware operation. To make the most of the software functionality (e.g. study definition and planning and data review and reporting modules), refer to the flexiWare user manual. STEP-BY-STEP INSTRUCTIONS An existing connection between the flexiVent FX and flexiWare software is required to proceed through the following step-by-step guide. If you have not completed the steps detailed in section 2, go back and review them. 1) Power on the flexiVent by pressing the power button next to the embedded user interface, on the front of the instrument. When the flexiVent is on, its cylinder and embedded display are illuminated. Do not open the base unit cover while the instrument is running. 2) Start flexiWare by double-clicking the icon on the desktop. If an icon does not exist, go to the start menu and select All Programs SCIREQ flexiWare flexiWare 7. Once the software is launched, the Welcome dialogue is displayed. 40 FIGURE 3-1: FLEXIWARE WELCOME DIALOGUE 3) Start an experimentation session by selecting the Experimentation Session button on the Welcome dialogue, as highlighted in Figure 3-1. 4) Select Default Study in the Study Selection dialogue. The default study contains two subject groups, Control and Experimental. Should you prefer to use a study that is customized to your research, refer to the flexiWare user manual for guidance using the Study Definition & Planning module of the software. 5) Enter the operator name or initials, experimentation session title and pertinent comments about the session in the Session Properties dialogue. 6) Select a template from the list of those available. The template you select must match the hardware configuration you are using. For more information on templates, including the 41 naming convention and a guide for choosing the appropriate template, refer to the flexiVent-Specific Features section of the flexiWare user manual. 7) Confirm the module that is attached to the flexiVent. 8) Click Subject Management to define one or more subjects that will be used in the current experimentation session. To define a subject, assign it a unique identifier and define its weight as shown in Figure 3-2. Other fields (e.g. strain, gender) are optional. FIGURE 3-2: SUBJECT PROPERTIES DETAILED IN SUBJECT MANAGEMENT 9) Click Group Membership, and then select the group to which the subject should be added using the drop-down menu, per Figure 3-3. 42 FIGURE 3-3: GROUP MEMBERSHIP SELECTION OF SUBJECT DETAILS 10) Click Ok to exit subject management. 11) Drag and drop the subject onto the measurement site. FIGURE 3-4: ASSIGNING A SUBJECT TO THE MEASUREMENT SITE 12) If you have selected a template that includes aerosol delivery (e.g. a default template with ‘AN’ in its name), you will be prompted to prime the nebulizer. The settings for this are preconfigured in the software. Simply ensure that the nebulizer reservoir contains 1-2 mL of fluid (e.g. saline), remove the nebulizer from its mount on the FX adapter and then click OK. 43 The nebulizer will generate aerosol for a few seconds. Once this is complete place it securely on the mount of the FX adapter. 13) Proceed to channel calibration Calibrate the cylinder pressure channel. Most templates require a two point calibration in which the first point is 0 mmH2O (open to atmosphere) and the second point is approximately 300 mmH2O (applied using a manometer) to cover the range of expected pressures. The square to the right of the bar will turn green when a pressure adequate for calibration is reached. During Step 4 of the calibration, enter the exact pressure value applied by the using manometer. For example, if the pressure actually applied was 295 mmH2O, enter 295 mmH2O; do not retain the default value of 300 mmH2O that is initially displayed. FIGURE 3-5: STEP 4 OF CHANNEL CALIBRATION, CYLINDER PRESSURE Verify the calibration results when they are displayed (see Figure 3-6). Cylinder pressure channel calibration values should fall within the following ranges: Max. value: 80.0 cmH2O ± 5 cmH2O Min. value: -80.0 cmH2O ± 5 cmH2O 44 FIGURE 3-6: RESULTS OF CALIBRATING THE CYLINDER PRESSURE CHANNEL If your values are not within the expected range, the pressure applied with the manometer may not have matched the value entered in the calibration dialogue. Note that if you are using a U-shaped manometer, the amount of pressure applied is equal to double the change in height on one of the columns. If you used a SCIREQ manometer, the amount of pressure applied is equal to the level of fluid in the single column. Please refer to the instructions provided with the SCIREQ manometer for further details. If you have questions concerning the use of the SCIREQ manometer, contact Technical Support. Calibrate the airway opening pressure channel. Again, most templates require a two point calibration in which the first point is 0 mmH2O (open to atmosphere) and the second point is approximately 300 mmH2O (applied using a manometer) to cover the range of expected pressures. Be sure to enter the actual pressure applied in Step 8 (see Figure 3-7). 45 FIGURE 3-7: STEP 8 OF CHANNEL CALIBRATION FOR CYLINDER PRESSURE Verify the calibration results when they are displayed (see Figure 3-8). Airway opening pressure channel calibration values should fall within the following ranges: Max. value: 80.0 cmH2O ± 5 cmH2O Min. value: -80.0 cmH2O ± 5 cmH2O FIGURE 3-8: RESULTS OF CALIBRATING THE AIRWAY OPENING PRESSURE CHANNEL If your values are not within the expected range, please see the note above regarding proper use of a manometer. Should you have questions, contact SCIREQ Technical Support. Characterize your Aeroneb nebulizer to obtain its output rate as well as the delivery ratio of your configuration. To perform this characterization, an accurate mass balance 46 (0.001g) and Rainout characterization kit will be required. Refer to the Advanced features section in the flexiWare user manual for further information. Verify the results when they are displayed. The nebulizer output rate should be greater than the values listed below for each nebulizer type. Fine mist (ANP-1100): 0.1 ml/min Standard mist (ANP-1000):0.3 ml/min Additional channels may require calibration depending on the template selected. Please refer to application specific documentation for further instructions. 14) Proceed to dynamic tube calibration . This calibration must be performed with a cannula attached to the end of the Y-tubing. Use the exact cannula that will be used for the experimentation. The Dynamic Tube Calibration Wizard provides detailed steps for this process. In short, there are 7 steps in tube calibration as follows: Welcome Simply click Next to begin tube calibration. Perturbation Selection Each perturbation loaded into the template that you have selected is displayed. All perturbations that are used during the experimentation session that follows should be calibrated; they are not available for use otherwise. The Deep Inflation and SnapShot perturbations must be calibrated in order to perform the quality control check of your setup and ventilator circuit as described further. Ensure that each perturbation is preceeded by a checkmark as in Figure 3-9 and click Next. 47 FIGURE 3-9: SELECTION OF PERTURBATIONS TO BE CALIBRATED Closed Preparation Be sure to block the end of the cannula tightly, and then click Next. If the cannula is not completely blocked, the calibration may need to be repeated. Closed Calibration While the cannula is blocked, the flexiVent executes each perturbation that you selected. Do not unblock the cannula until all perturbations are complete. Open Preparation Unblock the cannula and click Next. Open Calibration While the cannula is open to atmosphere, the flexiVent executes each perturbation again. Do not reposition or remove the cannula until all perturbations are complete. Calibration Results The tube calibration results contain important information that can help you validate your setup. Verify that the Rl (leak resistance) value associated with your Deep Inflation perturbation is within acceptable range using the results as shown in Figure 3-10 and the calibration guide in Table 3-1. In addition, examine the Rt (tube resistance) value associated with the SnapShot perturbation. This value reflects the resistance of your tracheal cannula or intubation tube and as such, it should be lower than a typical baseline resistance for the species you are studying. 48 FIGURE 3-10: TUBE CALIBRATION RESULTS TABLE 3-1: TUBE CALIBRATION GUIDE Deep Inflation Rl value (cmH2O.s/mL) should exceed FX1 FX2 MODULE FX3 2000 1125 600 FX4 FX5 370 260 If your values are not acceptable, confirm that all tubing connections are tight and re-perform the calibration making sure the cannula is tightly blocked during the closed calibration. If you continue to get values that are not within acceptable range, please contact SCIREQ Technical Support. The importance of proper calibration cannot be overstated. Any errors or inaccuracies introduced during calibration become part of the data until the next calibration is performed. 15) The software prompts you to start default ventilation. If you plan to connect a subject right away, select Yes. Please refer to the flexiVent-Specific Features section of the flexiWare User Manual for information on customizing ventilation patterns. 49 16) When the software prompts you to start recording data, select Yes if you want to record data streams for all input channels (e.g. cylinder pressure). Select No if you prefer not to record data streams (i.e. if your primary interest is dataset outcomes). 17) Connect a subject to the Y-tubing with the same cannula that was used during calibration. 18) Execute perturbation(s) to generate datasets, either by double-clicking the perturbation name in the perturbation docker or by typing the hotkey for the perturbation. Refer to the flexiVent-Specific Features section of the flexiWare user manual for perturbation settings and outcomes. To automate the execution of perturbations, use a script. There may be scripts preloaded into the template you have selected. 19) After you have completed your experiment involving the current subject, stop ventilation ; if you have been recording data streams, stop recording . Once ventilation is stopped, understand that your subject is no longer receiving air. Data from the present experimentation session may be reviewed immediately. To review all data contained within the study, you must use the Review & Reporting module of flexiWare software. 20) Remove the subject. 21) Proceed to either adding another subject to the experimentation session or cleaning the expiratory line, after which you may end the experimentation session. To add another subject to the experimentation session, click Edit Site Assignment from the Edit menu. You may need to define another subject to proceed (per Steps 8 through 11), then you will be prompted to repeat steps 13 through 20 as many times as needed until you are finished with the experimentation session. To clean the expiratory line and then exit the experimentation session, follow the steps detailed in section 5.2.2. To end the experimentation session, go to the File Menu and select Close Session. 50 4 ACCESSORIES The flexiVent FX system may be customized for a variety of applications through the incorporation of one or more accessories. To ensure proper function, the experimentation template you select must correlate to the accessories in your configuration. For details regarding template selection, naming convention and customization, refer to the flexiWare user manual. 4.1 UNIT TRANSDUCERS Per section 1.2.3, a UNIT contains between one and four sensor elements or other input/output channels, each permitting the measurement or modification of a physical property. In the case of UNIT transducers, the sensing elements are intended to monitor and record vital signs (e.g. body temperature) and other parameters (e.g. pressure). UNIT transducer cables plug into the auxiliary ports at the rear of the flexiVent FX (see section 2.2). 4.1.1 USING UNIT TRANSDUCERS UNIT transducers are designed for immediate use without the need for calibrations, amplifiers or additional signal conditioning. Transducer identification and calibrations are stored within the UNIT to eliminate uncertainty during experimentation or data review. If you prefer to manually calibrate a UNIT transducer before each experimentation session, contact SCIREQ Technical Support and request a custom SDM. 51 4.1.2 EKG The UNIT transducer for monitoring heart rate is comprised of three leads with alligator clips. To properly use the transducer, first select a lead configuration from the options listed on the transducer box. Then, wrap a length of copper braid around the appropriate location on the subject (e.g. left front limb). Attach the lead to the copper braid using the alligator clip. If necessary, apply conductive gel or saline to the limb and copper braid contact point. However, ensure that liquid does not reach the alligator clips; the clips are intended for use in dry conditions only. The EKG trace is displayed in real-time and may be recorded in the database. If you wish, you may use the flexiWare heart rate analyzer to calculate a heart rate from the EKG trace. 4.1.3 BODY TEMPERATURE The UNIT transducer for monitoring body temperature is a rectal thermometer. Temperature readings are displayed in real-time and may be recorded in the database. 4.1.4 BLOOD PRESSURE There are two UNIT transducers available to obtain invasive blood pressure measurements. Both consist of a digital liquid pressure transducer and a chamber for the blood/liquid interface. Use of the transducers requires arterial access to the subject in which measurements are taken. It also requires physiological saline and two three-way stopcocks, not supplied by SCIREQ. Selection of the appropriate transducer is based on the range of pressures to be measured. The range for each transducer is available in Table 4-1. 52 TABLE 4-1: RANGE FOR BLOOD PRESSURE TRANSDUCERS PRODUCT CODE DESCRIPTION PRESSURE RANGE UT-DPL-100 Digital blood/liquid pressure transducer -10 – 10 kPa (-75 – 75 mmHg) UT-DPL-400 Digital blood/liquid pressure transducer -40 – 40 kPa (-300 – 300 mmHg) To confirm whether or not a transducer is appropriate for a certain application, please contact SCIREQ Technical Support. To use the transducer, proceed as follows: 1) Attach a saline-filled syringe to the transducer via the three-way stopcock that is nearest to the black box of the transducer. 2) Orient the valve of the stopcock to isolate the transducer from the liquid. 3) Fill the transducer chamber with physiological saline from the syringe, and ensure that there are no air bubbles in the circuit. 4) Orient the valve of the stopcock to isolate the syringe from the circuit. 5) Connect an arterial line to the other end of the circuit via the three-way stopcock furthest from the black box of the transducer, and then open it to the transducer chamber. Keep the entire transducer in a horizontal position near the subject while taking measurements. Pressure measurements are displayed in real-time and may be recorded in the database. 4.1.5 AUXILIARY PRESSURE SCIREQ offers a wide array of pressure sensors that are optimized to offer the highest sensitivity for a given pressure range. Each sensor comprises a pressure sensing element that is further linearized by a microprocessor. Use of auxiliary pressure transducers may be necessary if you wish to record pressure in a location outside the module. Applications that use auxiliary pressure transducer include use of negative pressure forced expirations and imaging, though monitoring auxiliary pressure in the latter case is not required. 53 Selection of the appropriate transducer is based on the range of pressures to be measured. The range for each transducer is available in Table 4-2. TABLE 4-2: RANGE FOR DIGITAL PRESSURE TRANSDUCERS PRODUCT CODE DESCRIPTION PRESSURE RANGE UT-DPD-02 Digital precision differential pressure transducer, 0.2 kPa nominal -0.2 – 0.2 kPa (-2.0 – 2.0 cmH2O) UT-DPD-05 Digital precision differential pressure transducer, 0.5 kPa nominal -0.5 – 0.5 kPa (-5.0 – 5 .0 cmH2O) UT-DPD-25 Digital precision differential pressure transducer, 2.5 kPa nominal -2.5 – 2.5 kPa (-25.5 – 25.5 cmH2O) UT-DPD-50 Digital precision differential pressure transducer, 5.0 kPa nominal -5.0 – 5.0 kPa (-51.0 – 51.0 cmH2O) UT-DPD-75 Digital precision differential pressure transducer, 7.5 kPa nominal -7.5 – 7.5 kPa (-76.5 – 76.5 cmH2O) UT-DPD-100 Digital precision differential pressure transducer, 10.0 kPa nominal -10.0 – 10.0 kPa (-102 – 102 cmH2O) UT-DPD-300 Digital precision differential pressure transducer, 30.0 kPa nominal -30.0 – 30.0 kPa (-305.9 – 305.9 cmH2O) To confirm whether or not a transducer is appropriate for a certain application, please contact SCIREQ Technical Support. 54 4.2 NEBULIZER The nebulizer available for tight integration with flexiVent is the Aeroneb Lab nebulizer, which is manufactured by Aerogen (Galway, Ireland). The Aeroneb uses ultrasonic vibrating plate technology to generate consistently-sized droplets without heat, shear force or propelled air, making it ideal for biological substances. There are two stock models available, see section 4.2.1 for details. Use of the Aeroneb nebulizer requires that you have the nebulizer, its controller module and a module-appropriate FX adapter with nebulizer mount. To pre-dry the air entering the flexiVent FX (i.e. in an effort to minimize aerosol rainout), you will also need a drying tube, plus a quick-connect and length of tubing with which to connect it. During aerosol production, rain-out will occur and may accumulate in the FX adapter and/or Y-tubing. The rain-out must be removed frequently to prevent airflow obstruction as excessive rain-out may compromise mechanical ventilation of the subject and measurement accuracy. When using the FX adapter with nebulizer mount, removal of the nebulizer opens the ventilator circuit and reduces the volume of air delivered to the subject. If possible, avoid removing the nebulizer from the mount while a subject is attached. If it is necessary to remove the nebulizer (e.g. for cleaning), do so quickly and immediately replace the nebulizer or use a cap to close the ventilator circuit. To use the Aeroneb nebulizer, proceed as follows: 1) Connect the beige cable from the controller to the nebulizer. 2) Plug the 7-pin connector of the nebulizer controller into the auxiliary port on the back of the flexiVent. 3) Add a set of Y-tubing to the FX adapter with the nebulizer mount. 4) Insert the FX adapter into the module. 55 5) Once you initiate the software you must select a template that is configured to include the Aeroneb nebulizer; templates automatically included with the flexiWare software include ‘AN’ in their filename if they are configured for nebulizer use. Before you proceed through calibration steps, the nebulizer is primed (run continuously) per the settings in the template to create a seal through which air will not escape. As such, be sure you have placed liquid in the nebulizer before proceeding through this step. 6) Place the nebulizer on the mount of the FX adapter and push down until it is flush with the adapter base to ensure it is securely fastened. 7) Proceed through the next steps of the start-up sequence (e.g. channel calibration). Templates configured to include the Aeroneb often come pre-loaded with a script for an inhaled dose response. If you opt to use this script (or a variation thereof), the triggering of the Aeroneb is automated. You simply need to load it with the substance as needed during the script execution. To remove excess fluid from the Aeroneb reservoir, gently wick it up with a tissue. Take care that no sharp tools come into contact with the nebulizer screen as this may damage the Aeroneb. 56 4.2.1 AERONEB SPECIFICATIONS FINE MIST STANDARD MIST ANP-1100 ANP-1000 3.5 μm 5 μm > 0.1 mL/min > 0.2 mL/min Residual Volume < 0.2 mL < 0.2 mL Mass Median Aerodynamic Diameter (MMAD) ~ 1.8 μm 2.5-3.0 μm 2.0 μm 2.0 μm Particle Size (VMD – Volume Median Diameter) Nominal Nebulization Output Rate Geometric Standard Deviation (GSD) STANDARDIZING MULTIPLE NEBULIZERS Adjusting the nebulizer settings can allow two or more similar nebulizers to operate at approximately the same output rate. For example: If nebulizer A has a slightly higher output than nebulizer B when run at default duty cycle (50%), you can adjust the settings to effectively obtain similar outputs from both. To standardize multiple nebulizers, use the following procedure: 1) Determine the actual aerosol output rate for each nebulizer by characterizing the nebulizers in flexiWare. 2) Use the following to determine the new nebulization rate (rNeb) at which one nebulizer will be operated to match the other one: rNeb A rNeb B rao B rao A 57 Example: Aeroneb A has an output of 0.25 mL/min and Aeroneb B has an output of 0.20 mL/min when both are run at a 50% duty cycle. The aerosol output of Aeroneb A can be reduced by modifying its nebulization settings so that both nebulizers produce equal amounts of aerosol. rNeb A 0.5 0.20 0.25 mL min mL 0.4 min 3) Select the Tools menu → Options and then select Aeroneb from the left column. 4) Modify the Nebulization duty cycle to the calculated percentage (e.g. 40% in above example). 4.3 CALIBRATION ACCESSORIES The importance of proper calibration cannot be overstated. SCIREQ has a number of accessories used only during calibration steps that may be integrated into your system. 4.3.1 PRESSURE MANOMETER The SCIREQ pressure manometer is a J-column pressure manometer with a range of 0-300 mmH2O. The fluid used with the manometer must have specific gravity = 0.87. The ruler on the front of the manometer may be adjusted by loosening the silver screws on the ruler and moving the ruler to the appropriate location. The 0 mmH2O mark must correspond with the bottom of the fluid meniscus when no pressure is applied. Additional fluid may be ordered if needed; refer to section 1.2. 58 4.3.2 RAINOUT CHARACTERIZATION KIT The SCIREQ rain-out characterization kit includes a drying tube and connective tubing as well as an instruction card. The rainout characterization kit is required when characterizing the nebulizer in the flexiWare software. To ensure accuracy during the nebulizer characterization, it is important to replace the drying tube once it has turned pink. 4.3.3 TEST LOAD KITS The SCIREQ Test Load Kit includes two custom-machined test loads to ensure consistency in outcomes measured by the flexiVent. One test load will produce respiratory system resistance (Rrs) outcomes similar to a healthy subject while the other test load produces outcomes similar to a constricted lung. 4.4 HARDWARE EXTENSION FOR NEGATIVE PRESSURE FORCED EXPIRATIONS (NPFE) The SCIREQ hardware extension for negative pressure forced expirations consists of a negative pressure reservoir and valves that integrate into the configuration of the flexiVent FX. Use of the extension allows you to measure flows (e.g. peak expiratory flow) and volumes (e.g. forced expired volume at a specific time point, forced vital capacity) generated during a forced expiration. The computer-controlled NPFE perturbation may be interspersed with other flexiVent measurements, which allows for the most comprehensive mechanics assessment available in a single experiment with a single subject. 59 SCIREQ currently offers the negative pressure forced expiration extension for mice and rats only. Clients should use an FX module 1 with the mouse extension and an FX4 for the rat extension. For details on the hardware set up and use of the hardware extension with the flexiVent, consult the SCIREQ TechNote 036 and other documentation that accompanies the hardware. 60 4.5 MULTI-SUBJECT EXTENSION (MSX) The SCIREQ multi-subject extension consists of a multi-subject flow controller and four plethysmograph chambers. Use of the extension allows you to gather mechanics data in up to four anesthetized subject in parallel, thereby accelerating data collection and allowing you to expediently carry out time-sensitive studies, for example when respiratory mechanics measurements must be obtained within a limited time after birth or an intervention. SCIREQ currently offers the multiple subject extension for mice only. Clients should be utilizing an FX module 2 with this extension. For details on the hardware set up and use of the hardware extension with the flexiVent, consult SCIREQ Technical Support and the MSX user manual. 61 5 CLEANING, DECONTAMINATION AND MAINTENANCE Routine cleaning and maintenance of the flexiVent FX system are essential to ensure it continues to operate properly. 5.1 CYLINDER The precision ground glass cylinder and graphite piston assembly is the most sensitive part of the flexiVent. Please note the following to ensure a long lifespan of this component. The cylinder does not require lubrication and should not be lubricated in any way for any reason. The cylinder must not be exposed to particulate matter or aerosols, as this may cause permanent damage. If particles, aerosol or other substance accidentally enters the cylinder, stop operation immediately. The module must be thoroughly cleaned by an authorized representative or the SCIREQ service team before operation resumes. Contact SCIREQ Customer Support for additional details. 62 5.2 CLEANING FLOW PATHWAYS AND VALVES 5.2.1 INSPIRATORY PATHWAYS & VALVES Under normal operating conditions, the refill and inspiratory valves of the flexiVent FX contact gas only. As such, these valves do not require routine cleaning. 5.2.2 EXPIRATORY PATHWAYS AND VALVE The expiratory valve of the flexiVent FX is subjected to a number of pollutants, including humidity, mucus and aerosol particles in the expired air. This valve must be cleaned regularly to ensure proper performance. We recommend that the expiratory pathway (in which the expiratory valve is housed) is cleaned at the end of every experiment day. Additional items required for the cleaning procedure include the following: a module cleaning kit (product code FV-FXQCS or FV-FXQCL); a syringe (60 mL or larger); a beaker or similar container (100 mL or larger); at least 60 mL soapy water or isopropyl alcohol; and compressed air (optional). To clean the expiratory line of an FX module, proceed as follows: 1) Power on the flexiVent. 2) Launch flexiWare and proceed through start-up for a normal experimentation session. You may cancel out of the Dynamic Tube Calibration dialogue if you only intend to clean the expiratory line. Do not start recording data. Do not start ventilation. 63 3) Remove the FX adapter. Do not run fluids through the FX adapter when it is attached to the flexiVent. 4) Connect the quick-connects from the cleaning kit to the expiratory port on the front of the module (A) and the air/gas exhaust port on the back of the module (B) per Figure 5-1. FIGURE 5-1: QUICK-CONNECT ATTACHMENT FOR CLEANING 5) Add a length of tubing (C) to each quick-connect per Figure 5-2. 64 FIGURE 5-2: TUBING ATTACHMENT FOR CLEANING 6) Place the beaker at the end of the tubing connected to the air/gas exhaust port per Figure FIGURE 5-3: FULL CLEANING CONFIGURATION 5-3. 65 7) Fill the syringe with soapy water or isopropyl alcohol and attach it to the tubing per Figure 5-3. Flush the alcohol through the tubing and expiratory line then collect it in the beaker. Larger modules may require a larger volume of soapy water or isopropyl alcohol to thoroughly clean the line. As such, use a syringe with greater capacity or repeat Step 7 as needed. If the instrument has been used heavily or aerosol was delivered during recent experimentation sessions, repeat Step 7 as needed. 8) Flush out any liquid remaining in the lines by blowing compressed air through the tubing attached to the front of the module (A). 9) Remove both quick-connects. 10) Replace the FX adapter. 11) Attach a test load (e.g. syringe) to the Y-tubing. 12) Start default ventilation and let it run for approximately 15 minutes to ensure that the expiratory line is completely dry. Clean the expiratory valve only. Do not attempt to clean the refill or inspiratory valves. Do not attempt to clean or dry the expiratory line before completing steps 1-3. The software must be in a particular stage of an experimentation session, otherwise the expiratory valve is closed. Attempting to clean or dry the expiratory line with the valve close will damage the module. Do not use abrasive or corrosive detergents or mechanical cleaning aids. Do not dismantle the module or base unit to attempt to clean it. 66 5.3 FX ADAPTER AND Y-TUBING The FX adapter and Y-tubing come into contact with aerosol particles, mucus and humidity. Routine cleaning of both is necessary to prevent particle accumulation on the interior surfaces. To clean the FX adapter and Y-tubing, proceed as follows: Prepare a solution of mild liquid dish soap and water. Detach the adapter from the module. Submerge the adapter in the solution and agitate to ensure that the solution enters all three flow pathways. Soak if necessary. Remove the adapter from the soapy solution and rinse thoroughly with clean water. Use dry compressed air to thoroughly dry the three adapter flow pathways. Be sure no droplets remain in the small, middle pathway to the module as this can result in damage to the module when the adapter is subsequently used for an experimentation session. The Y-tubing that connects subjects to the FX adapter is a consumable item that must be replaced periodically. The initial instrument purchase includes appropriate tubing for each module that is ordered. Additional Y-tubing kits may be ordered when the initial supply is depleted. 5.4 EXTERNAL SURFACES To clean the external surfaces of the flexiVent FX, simply run a damp, non-abrasive cloth across the surface, using a mild solution of water and liquid dish soap if necessary. When cleaning the clear panel that covers the piston (Lexan material), use only a clean, nonabrasive cloth. Do not use Windex, Pledge, Isopropyl Alcohol or any alcohol-based cleaning products. Similarly, do not use harsh soaps. 67 Do not use paper or paper towels on the Lexan panel, as these materials are abrasive and may damage the surface. 5.5 AERONEB NEBULIZER The domed aperture plate within the nebulizer pump unit is extremely sensitive and should be treated with extreme care. Do not apply undue pressure to this mesh plate or use a syringe with a needle to add the liquid. The instructions that follow are taken directly from Aerogen’s Aeroneb nebulizer information sheet. Steps 1 through 4 may suffice for everyday use, but continue through step 7 should you wish to sterilize your nebulizer between subjects, between experiments or following long periods during which the nebulizer was not used. 5.5.1 1) NEBULIZER UNIT (INCLUDING FILLER CAP) Disconnect the control module and cable from the nebulizer unit. 2) Remove the filler cap from the nebulizer unit. 3) Clean parts with warm water and mild liquid detergent. Rinse thoroughly and air dry. Do not use abrasive or sharp tools to clean the nebulizer unit. 4) Check for cracks or damage, and replace the unit if any defects are visible. 5) Place the disassembled components into appropriate sterilization wrapping. The Aeroneb can be autoclaved (details provided by manufacturer Aerogen), however this may shorten its lifespan. Do not reassemble parts prior to autoclaving. 6) To sterilize, autoclave wrapped parts using steam sterilization pre-vacuum cycle, 132 -135°C (270 - 275°F) for 3 - 4 minutes with drying cycle. Refer to the autoclave manufacturer’s instructions if necessary. Please contact SCIREQ Technical Support for additional information. 68 Prior to the next use, check for cracks or damage, and replace the unit if any defects are visible. 5.5.2 1) AERONEB CONTROLLER Wipe clean with a damp cloth. 2) Check for exposed wiring, damaged connectors, or other defects and replace if any are visible. Do not autoclave the Aeroneb controller. Do not immerse it in water. 5.6 ANNUAL CLEANING AND MAINTENANCE The flexiVent modules have been designed to be field serviceable. With an inspiratory and expiratory cartridge, the module was designed to minimize the downtime required for annual cleaning and maintenance by allowing users to simply replace a cartridge in the comfort of their own lab in a matter of minutes. We recommend that the expiratory cartridge be replaced once a year or as needed based on usage. Please contact SCIREQ Customer Support to purchase spare cartridges. Note that we also offer a service plan that includes pre-paid cartridges along with an extended warranty and software subscription. Please contact SCIREQ Customer Support for details. 69 5.7 REPACKAGING, TRANSPORT AND STORAGE If the instrument is not in use for an extended period of time, it is important to protect it from damage, at a minimum by covering it, but ideally by repacking it in the shipping materials originally used to ship it to your location. Once packed, the boxes should be stored in a dry, temperature-controlled location (see Table A-1). Also, if the instrument or its components need to be moved from one location to another or shipped, it is important to pack it correctly to avoid damage during transportation. To pack the instrument, follow the instructions below as appropriate. 5.7.1 PACKING THE BASE UNIT WITH A MODULE ATTACHED As noted in section 2.2, the base unit is initially shipped with a module attached. This is a configuration appropriate for storage and transportation. To proceed with packing the base unit with a module attached, proceed as follows: 1) Be sure the flexiVent is off (embedded display is dark, piston is not backlit). If it is on, press the power button to turn it off. 2) Disconnect all transducers, extensions and auxiliary equipment. 3) Disconnect the Ethernet cable. 4) Disconnect the power supply. 5) Open the base unit’s protective cover and ensure that the module securing screw is not loose. 6) Move the motor arm (to which the piston is connected) to its left-most position. 7) Unscrew the motor lock thumb screw. 8) Rotate the motor lock counter-clockwise. 9) Insert the motor lock thumb screw to engage the motor lock. When the motor is locked, the motor arm will not move back and forth. 70 10) Close the base unit cover and secure with a piece of tape or a large rubber band. 11) Place the instrument in a vinyl or cloth bag to prevent scratches to the surface. 12) Place the custom-cut foam pieces over the instrument. 13) Gently lower the instrument into its box. 14) Place foam pieces as needed to pad the bottom of the instrument. 15) The power supply, small accessories and cables may be contained within a small box and packed with the flexiVent as long as there is adequate padding between it and the flexiVent. 5.7.2 PACKING A MODULE SEPARATELY If your instrument includes multiple modules, or if a module must be shipped separately (e.g. for module maintenance service), it may be necessary to pack a module on its own. To pack a module separately, proceed as follows: 1) Remove the module from the base unit per the instructions in section 2.6.2. 2) Carefully disconnect the piston/cylinder set from the module. Not all modules attach to the piston/cylinder the same way. Refer to the module-appropriate instructions below to complete this step. 71 FX Module 1, 2 and 3: 3) Remove the screws above and below the cylinder while supporting the cylinder and piston rod per Figure 5-4. This step requires a 7/64” hex/allen wrench. 4) Gently pull the cylinder back from the module. 5) Locate the O-ring that is seated between the cylinder and module. Place the O-ring and screws from the assembly into a container (e.g. envelope or small plastic bag). FIGURE 5-4: MODULE 1, 2 OR 3 DISASSEMBLY 72 6) Wrap bubble wrap or foam around the piston per Figure 5-5. FIGURE 5-5: PISTON OF MODULE 1, 2 OR 3 WRAPPED 7) Wrap the entire assembly with hard plastic or pliable metal per Figure 5-6. FIGURE 5-6: CYLINDER ASSEMBLY OF MODULE 1, 2 OR 3 WRAPPED 8) Secure the cylinder and the wrapped piston to the plastic with tape or rubber bands. The piston should not move within the cylinder if this is done properly. 9) Secure the wrapped assembly to a piece of rigid plastic or cardboard similar to that shown in Figure 5-7. FIGURE 5-7: WRAPPED ASSEMBLY SECURED TO RIGID BOARD 10) Tape the container with the O-ring and screws to the back of the rigid board. 73 11) Place the module in an appropriately sized box with 4-6” of padding on all sides. 12) Place the cylinder in the box such that it is padded on all sides and does not move about. FX Modules 4 and 5: 3) Gently rotate the cylinder counter-clockwise per Figure 5-8. 4) Gently pull the cylinder back from the module. 5) Locate the O-ring that is seated between the cylinder and module. Place the O-ring into a container (e.g. envelope or small plastic bag). FIGURE 5-8: MODULE 4 OR 5 DISASSEMBLY 6) Wrap bubble wrap or foam around the piston per Figure 5-4. 7) Wrap entire assembly with hard plastic or pliable metal per Figure 5-6. 74 8) Secure the cylinder and the wrapped piston to the plastic with tape or rubber bands. The piston should not move within the cylinder if this is done properly. 9) Secure the wrapped assembly to a piece of rigid plastic or cardboard similar to that shown in Figure 5-7. 10) Tape the container with the O-ring and screws to the back of the rigid board. 11) Place the module in an appropriately sized box with 4-6” of padding on all sides. 12) Place the cylinder in the box such that it is padded on all sides and does not move about. 5.8 REPLACEMENT COMPONENTS A selection of components used with the flexiVent FX need to be replaced periodically. To order replacements, contact SCIREQ Customer Relations. The following table includes a listing of frequently replaced products: TABLE 5-1: LISTING OF REPLACEMENT PRODUCTS PRODUCT CODE DESCRIPTION ANP-1000 standard particle size Aeroneb nebulizer ANP-1100 small particle size Aeroneb nebulizer FV-FEV1-FT tubing kit for integration of rotameter into NPFE extension FV-FEV1-YFX Y-tubing kit for NPFE extension FV-FXA-SK123 service kit for FX adapter, Modules 1, 2 and 3 FV-FXA-SK123N service kit for FX adapter with nebulizer mount, Modules 1, 2 and 3 FV-FXA-SK456 service kit for FX adapter, Modules 4 and 5 FV-FXA-SK456N service kit for FX adapter with nebulizer mount, Modules 4 and 5 FV-FXM[1-5]-I flexiVent FX Module [1-5] inspiratory cartridge 75 PRODUCT CODE DESCRIPTION FV-FXM[1-5]-E flexiVent FX Module [1-5] expiratory cartridge FV-FXQCL cleaning kit for FX Modules 4 and 5 FV-FXQCS cleaning kit for FX Modules 1, 2 and 3 FV-FXY-1L Y-tubing kit for FX Module 1, Luer end (qty 6) FV-FXY-23L Y-tubing kit for FX Modules 2 and 3, Luer end (qty 6) FV-FXY-456B Y-tubing kit for FX Modules 4 and 5, barbed end (qty 3) FV-FXY-456L Y-tubing kit for FX Modules 4 and5, Luer end (qty 3) UT-EKG-SK EKG transducer service kit XS-DRY replacement drying tube XS-PM-SK manometer oil APPENDIX A:TECHNICAL SPECIFICATIONS TABLE A-1: SPECIFICATIONS FOR THE FLEXIVENT FX SPECIFICATION CONDITIONS MIN TYP MAX UNITS NOTES Dimensions Depth 22 (8 ¾) cm (in) Height 14.5 (5 ¾) cm (in) FX Base Unit + Module 41 (16 ¼) cm (in) FX Base Unit 6.6 (14.5) kg (lbs) 3 FX Base Unit Power Supply 1.1 (2.5) kg (lbs) 3 FX Modules 1 – 3 2.7 (6) kg (lbs) 3 FX Modules 4 – 5 4.1 (9) kg (lbs) 3 Resolution 320 x 240 Pixels Width Weight Display Size 9 (3 ½) Available volume Modules FX1 – FX5 1.56 cm (in) Ventilation Module Stroke Volume 51.7 mL 1 SPECIFICATION CONDITIONS MIN TYP MAX UNITS Used volume Modules FX1 – FX5 1.5 Ventilation frequency Based on 1:1 I:E (max varies with subject weight) 6 Ventilation tidal volume Modules FX1 - FX5 Subject size Modules FX1 - FX5 Control modes Software controlled mechanical and pressure controlled ventilation Gas supply Room air or non-flammable mixed gas 51 600 10 8 I:E ratio 1:10 Number of subjects measured simultaneously 1 PEEP 0 Pressure range mL 3 6 mL/kg 5 g 1 2:1 6 4 2 20 cmH2O 8 -80 80 cmH2O 7 DC 50 Hz 10 mL/kg 1 mL/kg Respiratory Mechanics Oscillation frequency Oscillation amplitude Up to 20% full stroke 3-20Hz up to 50 Hz 1 br/min 5,100 2:3 NOTES SPECIFICATION CONDITIONS MIN TYP MAX UNITS NOTES Environment Operating temperature Operating and storage humidity 21 non-condensing Storage and transport temperature 40 °C 90% -20 Altitude 70 2000 (6560) °C m (ft) Electronics Power supply output voltage 24 V DC Power supply output current 9.2 A Power supply input range 110 Power Power supply frequency Sampling frequency For 4 channels of data, which is typical of an FX flexiVent 240 V AC 221 W 50/60 Hz 256 Hz 9 SPECIFICATION CONDITIONS MIN Inspiratory and Expiratory ports (FX adapter/Y-tubing) 1/8 Air/gas intake and exhaust 1/8 TYP MAX UNITS NOTES 3/8 in dia. 1 3/8 in dia. 1 Connections Gas port size Auxiliary ports (Available UnitWise transducer power entry & data I/O) Power - Voltage 12 V Power - Current 0.25 mA Data - Voltage 5 V Data - Current 0.032 mA Lemo, DC Power & I/O, 7-pin snap & lock connectors, compatible with UNIT transducers 4 Channels per Auxiliary 1 port Sync ports (Multi-Instrument synchronization) Ethernet port SMA connectors, 3.3 V, 0.024A 10/100 Ethernet network cable, +/-2.5V qty 4 1 input 1 output qty 1 qty SPECIFICATION Power supply (Main flexiVent FX power entry) CONDITIONS MIN TYP MAX UNITS Kycon, DC Power connector, 4 pin DIN R7B female, Snap & Lock on flexiVent 1 qty IEC320C14 male on power supply 1 qty NOTES 4 Notes: 1 See Table A-2. 2 4 subjects can be studied with the extension for multiple subjects. 3 The FX base unit ships with one module attached; additional modules ship separately. 4 Appropriate AC power cord typically provided only to direct SCIREQ clients in North America. Clients served by a distribution partner may receive cords through their distributor. Direct clients outside of North America will need to obtain an appropriate cord. 5 Ventilation tidal volume is configurable in the software. Tidal volume is limited by the stroke volume of the module in use, so refer to Table A-2 for details. 6 The I:E ratio in the software is expressed as a percentage of the exhalation time that the inhalation time lasts, e.g. the default 2:3 I:E ratio is expressed as 67%, a 1:1 ratio is expressed as 100%. 7 Linearity of the transducers is only guaranteed up to ± 76.2 cmH2O 8 The lower limit for computer-controlled PEEP is on the order of 0.25-0.5 cmH2O and may vary slightly from one configuration to the next. The minimum of 0 cmH2O reflected in the table is achievable if the option for PEEP control is set to ‘External’ in the ventilation pattern definition dialogue. 9 Alternate sampling frequencies are available and included in some pre-configured templates (e.g. those for use with the negative pressure forced expiration hardware). Use of alternate sampling frequencies may require increased computer RAM and/or modifications to the real time data view. Please contact Technical Support for more details. TABLE A-2: MODULE SELECTION TABLE ACCORDING TO STROKE VOLUME AND APPROXIMATE SUBJECT WEIGHT MAXIMUM1 MAXIMUM WEIGHT (g) FOR WEIGHT (g) VENTILATION INTAKE AND 1 STROKE MINIMUM FOR LARGE AND SMALL Y-TUBING EXHAUST VOLUME WEIGHT AMPLITUDE2 AMPLITUDE3 PORT SIZE PORT SIZE 4 MODULE (mL) (g) MANOEUVRES MANOEUVRES (in) (in) 1 FX1 1.53 8 30 150 1/8 1/8 (barbed) FX2 4.22 20 85 420 3/16 1/8 (barbed) FX3 12.4 60 240 1,230 3/16 1/8 (barbed) FX4 28.2 150 560 2,810 3/8 1/4 (barbed) FX5 51.7 260 1,000 5,100 3/8 1/4 (barbed) Note: 1 Minimum and maximum weight ranges are subject to change with further development and are listed for healthy subjects. 2 Estimated using 50 mL/kg ratio. 3 Estimated using 10 mL/kg ratio. 4 Intake and exhaust ports use Colder PMC/PLC connectors. FX Modules are shipped with mating fittings for easy connection to standard tubing size Our Customer Service and Technical Support departments are happy to assist you during business days from 9 am to 5 pm Eastern Standard Time. Most inquiries are addressed within one business day if not immediately. TELEPHONE/FAX: For all inquiries, dial 514.286.1429 and we will direct your call. To contact us by fax, please dial 514.286.1627 EMAIL: To reach us by email, please use the following addresses: For Customer Service: info@scireq.com For Technical Support: TechSupport@scireq.com INTERNET: A large amount of product and support information is available at any time via our website: www.scireq.com. Log in to the Downloads section for specific product support information and to download software updates and other useful files. SCIREQ Scientific Respiratory Equipment Inc. 6600 rue St-Urbain, Suite 300 Montreal, Quebec, Canada H2S 3G8 T. 514.286.1429 F. 514.286.1627 www.scireq.com This manual, as all SCIREQ documentation, is believed to be accurate and free of errors at the time of print. However, all product specifications and other information are subject to change without notice. Some product features are projected and may not be available immediately. Expected release dates, where provided, are estimates that are subject to change without notice. © SCIREQ Scientific Respiratory Equipment Inc. 2014