INOmax DSIR Operation Manual rev 01

User Responsibility This Product will perform in conformity with the description contained in this operating manual and accompanying labels and/or inserts, when assembled, operated, maintained and repaired in accordance with the instructions provided. This Product must be checked periodically. A defective Product should not be used. Parts that are broken, missing, plainly worn, distorted or contaminated should be replaced immediately. Should such repair or replacement become necessary, INO Therapeutics LLC d/b/a Ikaria recommends that a telephone request for service advice be made to the nearest Field Technical Service Support Center. This Product or any of its parts should not be repaired other than in accordance with written instructions provided by Ikaria. The Product must not be altered without the prior written approval of Ikaria Quality Assurance Department. The user of this Product shall have the sole responsibility for any malfunction which results from improper use, faulty maintenance, improper repair, damage, or alteration by anyone other than Ikaria.

Caution: U. S. Federal and Canadian law restrict this device to sale by or on the order of a licensed medical practitioner. Outside the U. S. A. and Canada, check local laws for any restrictions that may apply. Inhaled Nitric Oxide mixtures must be handled and stored in compliance with federal, state and local regulations. Ikaria products have unit serial numbers with coded logic which indicates the year of manufacture and a sequential unit number for identification. 20051234 10007

The first four digits indicate the year of product manufacture, and the next 4 digits are the sequential unit number produced. INOmax® DSIR part number

© 2010 Ikaria Holdings, Inc. ® ® ® ® ® INOMAX , INOmax DSIR, INOblender , INOcal and INOvent are registered trademarks of INO Therapeutics LLC. No license is conveyed, either expressed or implied, with the purchase hereof under U.S. Patent 5,485,827 and U.S. Patent 5,427,729 and their foreign equivalents. U.S. Patent 5,558,083 and foreign equivalents.

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Contents 1/ General Information ... 3 Introduction to this Manual ... 4 Theory of Operation... 15 Environmental Effects ... 20 2/ Setup ... 21 3/ Pre-Use Checkout ... 23 4/ Patient Application... 30 Backup NO Delivery ... 33 Transport Regulator /Cap Assembly Application ... 34 Changing INOMAX® Cylinders & Purging the Reg. Assembly ... 38 Monitoring the Environment ... 42 Entering Patient Information ... 43 Connection to Various Breathing Systems ... 45 5/ Alarms ... 65 6/ Troubleshooting ... 70 7/ Calibration ... 77 Low Range Calibration ... 78 Oxygen Sensor High Range Calibration ... 80 NO Sensor High Range Calibration ... 82 NO2 Sensor High Range Calibration ... 84 8/ Maintenance ... 86 Cleaning ... 87 Replacing O2, NO and NO2 Sensors ... 91 Replacing the H2O Separator Cartridge & INOMAX Reg. Tip. ... 92 Preventative Maintenance ... 93 Parts and Accessories ... 94 9/ Product Specifications... 95 Warranty ...100

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1/ General Information The INOmax® DSIR (delivery system) delivers INOMAX® (nitric oxide for inhalation) therapy gas into the inspiratory limb of the patient breathing circuit in a way that provides a constant concentration of nitric oxide (NO), as set by the user, to the patient throughout the inspired breath. It uses a specially designed injector module, which enables tracking of the ventilator waveforms and the delivery of a synchronized and proportional dose of NO. It may be used with most ventilators. The INOmax DSIR provides continuous integrated monitoring of inspired O2, NO2, and NO and a comprehensive alarm system. The INOmax DSIR incorporates a battery that provides up to 6 hours of uninterrupted INOMAX delivery in the absence of an external power source. The INOmax DSIR includes a backup NO delivery capability that provides a fixed flow of 250 mL/min of NO which along with user supplied 10 L/min of oxygen provides 20 ppm in the gas flow to a patients breathing circuit. It may also use the INOblender for backup. The target population is controlled by the drug labeling for INOMAX and is currently neonates. The primary targeted clinical setting is the Neonatal Intensive Care Unit (NICU) and secondary targeted clinical setting is the transport of neonates. Important:

Before using the INOmax DSIR, read through this manual. Read through the manuals for the ventilator, humidifier and any other accessory items used. Follow the manual instructions and obey the Warnings and Cautions. Keep this manual readily available to answer questions. Read the User Responsibility statement on the inside front cover of this manual; it describes what the user must do to maintain this product.

WARNINGS tell you about dangerous conditions that can cause injury to the operator or the patient if you do not obey all of the instructions in this manual. CAUTIONS tell you about a condition that can cause damage to the equipment. Read and obey all warnings and cautions. WARNING:

If an alarm occurs, safeguard the patient first before troubleshooting or repair procedures. Use only pharmaceutical grade NO/N2. WARNING: The INOmax DSIR must only be used in accordance with the indications, usage, contraindications, warnings and precautions described in the INOMAX (nitric oxide) drug package inserts and labeling. Refer to this material prior to use. WARNING: The use of devices which radiate high-intensity electrical fields may affect the operation of the INOmax DSIR. Constant surveillance of all monitoring and life support equipment is mandatory whenever interfering devices are in operation on or near a patient. WARNING: INO Therapeutics does not recommend that the INOmax DSIR be utilized with helium/oxygen mixtures in any situation. The INOmax DSIR is intended to deliver INOMAX therapy gas only in conjunction with the delivery of air and oxygen. WARNING: Do not connect items which are not specified as part of the system.

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Introduction to this manual Definitions and abbreviations % v/v

% volume/volume

ARDS

Acute Respiratory Distress Syndrome

CDH

Congenital Diaphragmatic Hernia

Control wheel

Rotary control used to change and confirm settings

CV

Cardiovascular

Display

The electronic information panel on the front of the delivery system

HFOV

High frequency oscillating ventilator

HRF

Hypoxemic Respiratory Failure

Menu

A list of available choices for an operation

N2

Nitrogen

NICU

Neonatal Intensive Care Unit

NO

Nitric oxide for inhalation (INOMAX®)

NO2

Nitrogen dioxide

NO/N2

Nitric oxide (NO) and nitrogen (N2) gas mixture

O2

Oxygen

PICU

Pediatric Intensive Care Unit

Resolved alarm

An alarm condition that has been corrected

Set NO

The dose of INOMAX set by the user

Touch screen

A display screen sensitive to touch used to select a function Water Separator

Sample Line

Main Power Indicator

Inlet

Light

Blender Gas Outlet

Cartridge

INOMAX Gas Inlets Ethernet Port

Display Screen

Infrared Connector Water Trap

USB Port Purge Port

Bottle

Control Wheel

Backup Switch

RS 232 Port

Injector Module

Injector Module

ON/Standby

Cable

Tubing Outlet

Switch

Power Cord

Sample Gas Outlet Port

Figure 1-1 INOmax® DSIR Front View

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Water Trap Bottle

Ground

Figure 1-2 INOmax DSIR Rear View 4

INOmax DSIRIR and Cart

1 2 3

4

5 6

7

8 9

1. INOmax® DSIR Mounting Post 2. INOMAX® Regulator (2) 3. Small Part Bin 4. INOMAX Cylinder 5. Cylinder Holding Bracket 6. Cylinder Mounting Strap 7. Oxygen Cylinder Bracket 8. Caster Lock Lever 9. Caster (4)

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Navigating the display screens There are four screens that can be displayed on the INOmax® DSIR. Note: The specific level is identified by the highlighted card on the Menu Button. The red arrows indicate going back to a previous screen.

Main Screen (first level)

Alarm History Screen (second level)

Patient Information Screens

Menu Screen (second level)

Calibration Screen (third level)

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On the Main Screen the user can view alarm messages, monitored values and graphical information. By pressing the “Menu Button” on the touch screen (top right hand corner), the user can access the Menu Screen (see figure 1-4).

Figure 1-3 Main Display Screen

On the Menu Screen the user can change the alarm volume and the display brightness and view, the software version.

Calibration due dates

Figure 1-4 Menu Screen (second level)

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To review the Alarm History Screen (second level), refer to Section 5/ Alarms. It also lets the user select different calibration options (third level) which will be covered in Section 7/ Calibration.

Display and user controls The INOmax® DSIR has a color touch screen display and a control wheel for adjusting and entering user settings. The buttons on the touch screen and the control wheel perform a variety of functions using a three step procedure (see “Setting and making changes on the INOmax DSIR”). Note: If a button has been selected and no activity has been sensed within 20 seconds, the display will return to its previous condition. If on a specific screen a button is de-emphasized (grayed out), it is not accessible.

When a value is being changed, pressing the “Cancel Active Status” button during editing will stop the change and return the value to its original value (similar to the escape key on a computer).

Dose Settings Displayed dose settings are 1, 5, 10, 20, 40, 60 and 80 ppm. Each click on the control knob corresponds to a known change in dose. The incremental dose per click corresponds to a value dependent upon the dose range in which the change is made, as illustrated in the table at the right. Dose Setting Range < 1 ppm 1 to 40 ppm 40 to 80 ppm

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Dose Change Per Click 0.1 ppm 1 ppm 2 ppm

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Setting and making changes on the INOmax® DSIR. The touch screen buttons and control wheel are used to: Set the concentration of delivered NO Adjust alarm limits Silence alarms Calibrate the sensors Review alarm history Define setup options Enter patient data Note: After confirming a desired dose, the NO alarm setting (high and low) will automatically be set for the first setting only. Any other changes will require changing the high and low alarm setting. Also, a two minute lockout period will prevent alarms from occurring while measured values stabilize.

1. SELECT (press) a button on the touch screen associated with the desired function. (an audible beep will sound when a button is selected, and the button will be displayed in inverse video)

2. ROTATE the control wheel to adjust the value.

3. CONFIRM the selection by pressing the control wheel or the button associated with the desired function again.

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Alarm Loudness setting 1. Push the alarm loudness button on the touch screen. 2. Turn the control wheel to indicate the loudness level you want. Choices range from 1 (softest) to 5 (loudest). 3. Push the control wheel to confirm your selection. Note: If you are finished with the Menu Screen, push the return to previous level button on the touch screen.

Display Brightness setting 1. Push the display brightness button on the touch screen. 2. Turn the control wheel to indicate the display brightness level you want. Choices range from 1 (darkest) to 10 (brightest). 3. Push the control wheel to confirm your selection. Note: If you are finished with the Menu Screen, push the return to previous level button on the touch screen.

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Infrared Communication between the INOMAX® Cylinders and the INOmax® DS The INOmax DSIR has an interface using infrared technology which will allow the INOmax DSIR to communicate with the INOmeter which is mounted to each INOMAX cylinder. The INOmax DSIR cart (PN 10018) has a cover () with an infrared transceiver mounted directly above each INOMAX cylinder. When INOMAX cylinders are loaded, communication will take place between the INOmax DSIR and the INOmeter () after the boot up phase of the INOmax DSIR is complete. A cylinder icon will be displayed on the main screen when an INOMAX cylinder is recognized by the INOmax DSIR (see “Loading INOMAX Cylinders onto the INOmax DSIR Cart”, page 12).

 

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Loading INOMAX® Cylinders onto the INOmax® DSIR Cart Note: Check the INOMAX gas cylinders for the correct product identity labels, cylinder concentration and expiration date. Ensure at least one INOMAX gas cylinder (with more than 200 psi), is available. Refer to Section 3 / Pre-Use Checkout prior to use.



 



Loading the first INOMAX cylinder on the cart  will result in a cylinder icon displayed on the screen .

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Loading a second INOMAX cylinder onto the cart  will result in a second cylinder icon displayed on the screen .

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Symbols used in this manual or on the system Other symbols replace words on the equipment or in this manual. These symbols include: Attention, consult accompanying documents! Equipotential Stud

Water Separator Cartridge

Injector Module

Gas Inlet

Gas Outlet NO Backup OFF NO Backup ON Main Power Connected Purge Location Fuse Rating

Ethernet Port

Type B Electrical Equipment USB Port Sample gas Inlet Port Sample Gas Outlet Port

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Standby On Ref.

Stock Number

SN

Serial Number Alarm Mute

Low Cal

Low Range Calibration Infrared Input/Output

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Theory Of Operation The INOmax® DSIR provides a constant dose of INOMAX® into the inspiratory limb of the ventilator circuit. The INOmax DSIR uses a "dual-channel" design to ensure the safe delivery of INOMAX. The first channel has the delivery CPU, the flow controller and the injector module to ensure the accurate delivery of NO. The second channel is the monitoring system, which includes a separate monitor CPU, the gas sensors (NO, NO2, and O2 sensors) and the user interface, including the display and alarms. The dual-channel approach to delivery and monitoring permits INOMAX delivery independent of monitoring, but also allows the monitoring system to shutdown INOMAX delivery, if it detects a fault in the delivery system, such that the NO concentration could become greater than 100 ppm (see figure 1-5 for a schematic diagram). 1. INOMAX drug is stored as a gas mixture of NO/N2 in an aluminum cylinder (800 ppm) at a nominal pressure of 2200 psig. 2. The cylinder is attached to a high pressure regulator, which incorporates a pressure gauge that indicates cylinder pressure when the cylinder valve is open. The cylinder regulator is attached via tubing to the INOmax DSIR using one of the two NO/N2 quick connect inlets on the back of the machine. 3. The INOMAX enters the back of the INOmax DSIR, passes through a filter, then a safety shutoff valve, which is open under normal operation. 4. An injector module is placed in the ventilator gas flow between the ventilator inspiratory outlet and the humidifier. Based on the ventilator flow, the INOMAX cylinder concentration and set INOMAX dose, the proportional solenoid valve delivers INOMAX into the ventilator circuit via the injector module. This allows the INOmax DSIR to deliver a constant dose of INOMAX regardless of the ventilator flow pattern or breath rate (see figure 1-6). 5. A flow sensor inside the INOmax DSIR also monitors the NO flow out of the machine. A check valve is included prior to the INOmax DSIR drug outlet to prevent pressure effects from the ventilator breathing circuit interfering with the NO flow sensor reading. 6. Gas Monitoring The INOmax DSIR gas monitoring system provides monitored values for inspired NO, NO2, and O2. The sample gas is withdrawn from the breathing circuit and goes through a water trap to remove excess water, a zero valve, a sample pump and finally a sample flow sensor to the gas monitoring sensors. The zero valve allows the gas sensors to be zeroed (during low calibration) without having to disconnect the sample line from the breathing circuit. The pump and sample flow sensor ensure a sample gas flow rate is maintained to the monitoring sensors. The gas monitoring sensors are electrochemical; they are specific to each gas and provide an electronic signal which is proportional to the concentration of the gas present. 7. Backup Delivery If the delivery system does go into shut down, the INOmax DSIR has an integrated backup function which provides a fixed flow of INOMAX (250 mL/min) into the injector module using a pneumatic on/off switch and a restrictor built into the delivery side of the system. This fixed flow of INOMAX will provide 20 ppm of NO when the continuous ventilator gas flow is 10 L/min. The backup is only for short term use until a replacement delivery system can be obtained. An alarm will warn the user if the backup system is turned on while the main delivery system is in use for INOMAX delivery. The INOblender can also be used as a backup.

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INOmax Sample Gas Electronic

Figure 1-5 Schematic diagram of INOmax® DSIR

Ventilator Flow

Figure 1-6 INOMAX® injection method provides a constant NO concentration

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Effect of the INOmax® DSIR in a ventilator circuit There are two main effects of connecting and using the INOmax DSIR in a ventilator breathing circuit. First, the INOmax DSIR adds NO/N2 gas to the breathing circuit in proportion to the NO setting and the ventilator flowrate. For example, at a 80 ppm NO setting (the maximum NO setting with a 800 ppm NO cylinder concentration) the INOmax DSIR adds 10% more gas to that delivered by the ventilator, 5% more for a 40 ppm setting, etc. Second, the INOmax DSIR subtracts gas from the breathing circuit via the gas sampling system at a nominal flow rate of 0.23 L/min. These two effects of adding and subtracting gas from the ventilator breathing circuit have the following effects: Oxygen Dilution The INOmax DSIR adds gas to the breathing circuit in proportion to the NO setting as described above. The NO/N2 mixture added to the ventilator gas dilutes the oxygen in proportion to the set INOMAX® dose. At an INOMAX dose setting of 80 ppm with a cylinder concentration of 800 ppm NO, the added gas is 10%. Thus, the O2 concentration is reduced by 10% of its original value. For example, if the original O2 concentration was 50% v/v, then the value after injection, at the 80 ppm setting, is 45% v/v.

INOMAX Dose (ppm) 80 40 20

Oxygen Dilution % v/v 10 5 2.5

Minute Volume When using volume ventilation with the INOmax DSIR, the measured tidal volume delivered to the patient shows small changes depending on the NO setting being used due to the addition and subtraction of gases by the delivery system. Some minor ventilator adjustments to the minute volume may be required. The net result of the INOmax DSIR on the delivered minute ventilation can be calculated as follows. If the patient’s minute ventilation is 10 L/min (500 cc X 20 breaths/min) The additional minute volume due to the INOMAX can be calculated as follows: INOMAX dose X Minute Volume

= Additional INOMAX volume added per minute Cylinder Concentration – INOMAX dose For a dose of 20 ppm the additional volume would be (20 X 10 / 800 – 20) = 0.25 L/min To calculate the net change in minute volume: 0.25 L/min INOMAX added - 0.230 L/min removed (sample system) = 0.02 L/min. (net change) This formula may be used when calculating the changes to continuous flow on continuous flow ventilators as well (using the continuous flow in place of minute ventilation).

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Trigger Sensitivity The addition and subtraction of gases by the INOmax® DSIR may affect the trigger sensitivity of the ventilator when using synchronized modes of ventilation. This may cause the ventilator to autotrigger in ventilators which have flow trigger modes, especially where the trigger flow is set to less than 1 L/min. The trigger sensitivity of the ventilator should be checked after connecting the INOmax DSIR. Circle Anesthesia Ventilator Systems The effect of the INOmax DSIR on circle anesthesia ventilator systems (which use volume ventilation) is to cause small changes in the delivered minute volume as noted above (see Minute Volume). Recirculation of INOMAX® in circle breathing systems should be avoided. The gas in the ventilator bellows may also contain undesirable levels of NO2 which may not be removed by the CO2 absorbent. This may lead to a rapid increase in INOMAX dose levels creating a shutdown of the INOmax DSIR. Recirculation of gases can be avoided by using a fresh gas flow rate equal to or above that of the patient’s minute volume. This will ensure that there is sufficient fresh gas in the absorber such that no accumulated gas from the ventilator bellows reaches the inspiratory limb of the breathing circuit and hence the patient. Maximum NO Delivery The INOmax DSIR is limited to a maximum NO flow of 6.35 L/min. This means the maximum deliverable NO concentration will vary based on the ventilator flow rate. The maximum deliverable NO concentration will vary from approximately 80 ppm at a constant flow of 60 L/min to approximately 40 ppm at constant flow 120 L/min.

When intermittent inspiratory flow rates are used, peak ventilator flows may be achieved which will exceed 120 L/min. Peak inspiratory flow rates are transient and extremely short in duration. As a result, the portion of the breath which is not matched by the INOmax DSIR is extremely small and the effect on the delivered concentration of NO with respect to the entire range of the breath is small.

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Does acid form in the humidifier or breathing circuit when delivering INOMAX®? A long term test was performed at Datex-Ohmeda to determine if acid would build up in a breathing circuit over time when delivering inhaled Nitric Oxide. The test equipment was a Sechrist IV-100B neonatal ventilator and a Fisher Paykel MR500 humidifier. The ventilator settings were Rate 40 breaths per minute, Flow 6 L/min and Oxygen 100% v/v and the humidifier was set to 36 degree’s C. The pH level was measured at the humidifier (the water in the humidifier chamber), at the patient Y (the condensate in the breathing circuit) and at the exhalation valve back at the ventilator (the condensate in the breathing circuit). Distilled water was used for the test which had an initial pH of 5.75 and the pH was measured with Hydrion Paper (4.5 to 7.5). A control test without NO being delivered was run initially to see if the pH would change over time due to the slightly acidic nature of distilled water. The control test was run for 6 days with no change in the pH at any of the test points. The test was then repeated with 80 ppm of NO being delivered continuously for 9 days with the pH being tested daily at each of the test points. There was no change of pH at any of the test points for any of the daily tests.

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