INOmax Operation Manual Rev 04

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

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

10003

INOmax® DS part number

©2010 Ikaria Holdings, Inc. INOMAX®, INOmax® DS, 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.

Part No. 20003 Rev - 04

Contents 1. General Information... 1 Introduction to this Manual... 2 Theory of Operation... 10 Environmental Effects... 14 2.

Setup... 15

3.

Pre-Use Checkout... 17

4. Patient Application... 23 Backup NO Delivery... 25 Changing INOMAX® Cylinders and Purging the Regulatory Assembly... 27 Monitoring the Environment... 31 Connection to Various Breathing Systems... 32 5.

Alarms... 55

6.

Troubleshooting... 59

7. Calibration... 63 Low Range Calibration... 64 Oxygen Sensor High Range Calibration... 66 NO Sensor High Range Calibration... 68 NO2 Sensor High Range Calibration... 71 8. Maintenance... 75 Cleaning... 76 Replacing the O2, NO, and NO2 Sensors... 79 Replacing the H2O Separator Cartridge & INOMAX Reg. Tip... 81 Preventative Maintenance... 82 Parts and Accessories... 83 9. Product Specifications... 85 Warranty... 89

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General Information

1/ General Information

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General Information

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1/ General Information • The INOmax® DS (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 DS provides continuous integrated monitoring of inspired O2, NO2 , and NO and a comprehensive alarm system.

WARNING: 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.

Caution: Cautions tell you about a condition that can cause damage to the equipment. Read and obey all warnings and cautions.

• The INOmax DS incorporates a battery that provides up to 6 hours of uninterrupted INOMAX delivery in the absence of an external power source. • The INOmax DS 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.

WARNING: • If an alarm occurs, safeguard the patient first before troubleshooting or repair procedures • Use only pharmaceutical grade NO/N2.

• 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 DS, 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.

• The INOmax DS 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. • The use of devices which radiate high intensity electrical fields may affect the operation of the INOmax DS. Constant surveillance of all monitoring and life support equipment is mandatory whenever interfering devices are in operation on or near a patient. • INO Therapeutics does not recommend that the INOmax DS be utilized with helium/ oxygen mixtures in any situation. The INOmax DS is intended to deliver INOMAX therapy gas only in conjunction with the delivery of air and oxygen.

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.

• Do not connect items, which are not specified as part of the system.

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Introduction to this Manual Definitions and abbreviations

1

% v/v

% volume/volume

Touch screen

A display screen sensitive to touch which selects a function

Control wheel

Rotary control used to change and confirm settings

Display

The electronic information panel on the front of the delivery system

HFOV

High frequency oscillating ventilator

Menu

A list of available choices for an operation

N2

Nitrogen

NO

Nitric oxide for inhalation (INOMAX®)

NO2

Nitrogen dioxide

NO/N2

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

O2

Oxygen

Resolved alarm

An alarm condition that has been corrected

Set NO

The dose of INOMAX set by the user

2

11

10

3

14

13

12

9

8

20

7 1. 2. 3. 4. 5. 6. 7.

6

5

Sample Line Inlet Main Power Indicator Display Screen Backup Switch Control Wheel Injector Module Tubing Outlet Injector Module Cable

19

4

8. Water Trap Bottle 9. Purge Port 10. INOMAX Gas Inlets 11. Blender Gas Outlet 12. Ethernet Port 13. USB Port 14. Water Separator Cartridge

Figure 1-1 INOmax® DS Front View

17

16

15. Water Trap Bottle 16. Sample Gas Outlet Port 17. Power Cord 18. Ground 19. ON/Standby Switch 20. RS232 Port

Figure 1-2 INOmax DS Rear View

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18

15

1

2

3

5

4 6

7

8 9

1. 2. 3. 4. 5. 6. 7. 8. 9.

INOmax® DS Mounting Post INOMAX® Regulator (2) Small Part Bin INOMAX Cylinder Cylinder Holding Bracket Cylinder Mounting Strap Oxygen Cylinder Bracket Caster Lock Lever Caster (4)

Figure 1-3 INOmax® DS and Cart

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Navigating the display screens There are four screens that can be displayed on the INOmax® DS. Note:

The specific level is identified by the highlighted card on the Menu Button. Main Screen (first level)

Alarm History Screen (second level)

Menu Screen (second level)

Calibration Screen (third level)

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1

2

3

5

4

6

7

8

17

18 1. 2. 3. 4. 5. 6.

16

15

14

Alarm Silence Button Upper Alarm Limit Button Lower Alarm Limit Button Monitored Value Menu Button Text Message Area

13

12

Main Display Screen • 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), you can access the Menu Screen (see Figure 1-5).

9

11 10

7. Monitor Area 8. Graphical Area 9. Sample Line Icon 10. Water Trap Icon 11. Inspiratory Limb Icon 12. Injector Module Icon

13. Delivery Line Icon 14. Backup Line Icon 15. Backup Switch Icon 16. Delivery Setpoint Display 17. NO Delivery Setpoint Button 18. Cylinder Icon

Figure 1-4 Main Display Screen 1

3

2

4

Menu Screen (second level)

5

• On the Menu Screen the user can change the alarm volume and the display brightness and the user can view, but not change, the software revision. • The Alarm History Screen (second level) will be covered in section 5/ Alarms.

9 1. 2. 3. 4. 5.

8

Software Revision Field Display Brightness Button Alarm Volume Button Return to Previous Level Button Monitor Area

• It also lets the user select different calibration options (third level) which will be covered in section 7/ Calibration.

6

7 6. 7. 8. 9.

NO Calibration Button NO2 Calibration Button Oxygen Calibration Button Room Air Calibration Button

Figure 1-5 Menu Screen (second level)

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Display and user controls The INOmax® DS 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 DS”). 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 a button is de-emphasized (grayed out), it is not accessible.

When a value is being changed, pressing this button during editing will stop the change and return the parameter 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 right.

Dose Setting Range Dose Change Per Click < 1 ppm 0.1 ppm 1 to 40 ppm 1 ppm 40 to 80 ppm 2 ppm

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Setting and making changes on the INOmax® DS. 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 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. 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 the high and low alarm settings to be adjusted. Also, a two minute lockout period will prevent alarms from occurring while measured values stabilize.

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Settings Access the menu screen (second menu level). 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. 4. 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. 4. If you are finished with the Menu Screen, push the return to previous level button on the touch screen.

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Symbols used in this manual or on the system Symbols replace words on the equipment and/or in this manual. These symbols include:

Attention, consult accompanying documents!

Ethernet Port

Equipotential Stud

Type B Electrical Equipment

Water Separator Cartridge

USB Port

Injector Module

Sample Gas Inlet Port

Gas Inlet

Sample Gas Outlet Port

Gas Outlet

Standby

NO Backup OFF

On

NO Backup ON

Ref.

Stock Number

Main Power Connected

SN

Serial Number

Alarm Mute

Purge Location

Fuse Rating

9 Part No. 20003 Rev - 04

Theory of Operation The INOmax® DS provides a constant dose of INOMAX® into the inspiratory limb of the ventilator circuit. The INOmax DS 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. This allows the monitoring system to shutdown INOMAX delivery, if it detects a fault in the delivery system. For example, INOMAX delivery will shut down should the monitored NO concentration become greater than 100 ppm. (See Figure 1-6 for a schematic diagram).

5. A flow sensor inside the INOmax DS also monitors the NO flow out of the machine. A check valve is included prior to the INOmax DS drug outlet to prevent pressure effects from the ventilator breathing circuit interfering with the NO flow sensor reading. 6. Gas Monitoring - The INOmax DS 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, 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.

1. INOMAX drug is stored as a gas mixture of NO/N2 in an aluminum cylinder at a nominal pressure of 2200 psig.

• 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.

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 DS using one of the two NO/N2 quick connect inlets on the back of the machine.

7. Backup Delivery - If the delivery system does go into shut down, the INOmax DS 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.

3. The INOMAX enters the back of the INOmax DS, 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 DS to deliver a constant dose of INOMAX regardless of the ventilator flow pattern or breath rate (see Figure 1-7).

Part No. 20003 Rev - 04

10

Regulator

INOMAX® Cylinder 800 ppm Sample Gas Outlet Port

Sensors O2

F NO Backup ON/OFF

NO

Monitor CPU

Delivery CPU

F

Pressure Switch

NO2

Pressure Shut off valve Restrictor

Sample Flow Sensor

Proportional Valve

Sample Pump

INOMAX Flow Sensor

Zero Valve

Water Trap

Ventilator

Injector Tubing

Sample Line

Injector Module Cable

Patient Expiratory Limb Breathing Circuit Sample Tee

Inspiratory Limb Injector Module

INOMAX Sample Gas

Figure 1-6 Schematic Diagram of INOmax DS ®

Electronic Humidifier

Delivered Nitric Oxide (NO) Concentration using INOmax DS Delivery System Ventilator Flow

Time

Figure 1-7 INOMAX injection method provides a constant NO concentration

11

Part No. 20003 Rev - 04

Effect of the INOmax® DS in a ventilator circuit Minute Volume

There are two main effects of connecting and using the INOmax DS in a ventilator breathing circuit.

When using volume ventilation with the INOmax DS, 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 DS on the delivered minute ventilation can be calculated as follows:

• First, the INOmax DS adds NO/N2 gas to the breathing circuit in proportion to the NO setting and the ventilator flowrate. For example, at an 80 ppm NO setting (the maximum NO setting with an 800 ppm NO cylinder concentration) the INOmax DS adds 10% more gas to that delivered by the ventilator, 5% more for a 40 ppm setting, etc.

If the patient’s minute ventilation is 10 L/min (500 cc X 20 breaths/min)

• Second, the INOmax DS subtracts gas from the breathing circuit via the gas sampling system at a nominal flow rate of 0.23 L/min.

The additional minute volume due to the INOMAX can be calculated as follows:

These two effects of adding and subtracting gas from the ventilator breathing circuit have the following effects: Oxygen Dilution

For a dose of 20 ppm the additional volume would be (20 X 10 / 800 – 20) = 0.25 L/min

The INOmax DS 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 is 50% v/v, then the value after injection, at the 80 ppm setting, should be 45% v/v.

To calculate the net change in minute volume: 0.25 L/min INOMAX added - 0.23 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). Trigger Sensitivity

INOMAX Dose (ppm)

Oxygen Dilution % v/v

80

10

40

5

20

2.5

The addition and subtraction of gases by the INOmax DS 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 DS delivery system.

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Circle Anesthesia Ventilator Systems The effect of the INOmax® DS on circle anesthesia ventilator systems (which use volume ventilation) is to cause small changes in the delivered minute volume as noted previously (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. Recirculation of gases may lead to a rapid increase in INOMAX dose levels creating a shutdown of the INOmax DS. This 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 DS 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 DS is extremely small and the effect on the delivered concentration of NO with respect to the entire range of the breath is small. 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.

1. Maximum deliverable NO concentration (ppm) 2. Constant inspiratory flowrate (L/min)

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Environmental Effects Both these methods show that the exposure levels are significantly less than the levels recommended by NIOSH.

The National Institute for Occupational Safety and Health (NIOSH) have recommended exposure limits as follows (Ref. 1).

NO NO2

If the location for using NO has uncertain ventilation then the location should be evaluated for NO and NO2 build up prior to use.

time-weighted (8 hours) average concentration limit of 25 ppm

References:

ceiling limit of 1 ppm.

(Ref. 1) Centers for Disease Control, Atlanta, GA 30333 USA.

The environmental build up of NO in a well ventilated ICU room can be evaluated using the following calculation.

Room size

(Ref. 2) Hess et al, Use of Inhaled Nitric Oxide in patients with Acute Respiratory Distress Syndrome. Respiratory Care, 1996, vol. 41, No. 5, pg. 424-446.

Room volume of air

10 ft square (approx. 3 meters) 27,000 L

Room ventilation 2,700 L/min at 6 room changes / hour NO flow into the room 14 L/min at 80 ppm Average room 0.4 ppm of NO concentration of NO (80 x 14 / 2,700) This theoretic calculation can be supplemented by measurements as performed by Hess et al (Ref. 2). The NO and NO2 concentrations were measured using a chemiluminescence analyzer when 100 ppm of NO at 8 L/min was delivered into a room with no scavenging being used. The maximum NO and NO2 concentrations measured over a one hour period were 0.12 ppm of NO and 0.03 ppm of NO2.

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NIOSH Recommendations for Occupational Safety and Health Standards 1988. August 26, 1988 / vol. 37 / No. 9.