SPAG-2^® User's Guide

Treating Mild RSV at Home
Treating Severe RSV in the Hospital
Virazole as Treatment / Prescribing Information
Patient Support Materials

A. INTRODUCTION

The Small Particle Aerosol Generator Model-2 (SPAG-2) is indicated for administration of Virazole^® (Ribavirin) aerosol only. Virazole^® aerosol is indicated in the treatment of carefully selected hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus (RSV).

B. GENERAL OPERATION OF THE SPAG-2 AEROSOL GENERATOR

The pneumatic flow system of the SPAG-2 is depicted in Figure B-1. The SPAG-2 is driven by a pressurized gas (air or blended oxygen) source, which passes through an external pressure compensated flowmeter before entering the SPAG-2. The incoming gas is regulated to 26 psi (179 kPa), and then is directed, via a manifold and pressure compensated flowmeters, to both the nebulizer and the drying chamber.

The nebulizer generates a fine aerosol of hydrated Virazole, and the drying chamber further dehumidifies the aerosol. The mass median diameter of the aerosol particles is approximately 1.3 microns.

C. EQUIPMENT

1. Each shipping carton contains the following items:

1 -SPAG-2.
2 - 500 ml. reservoirs (polysulfone plastic).
2 - Reservoir caps (polysulfone plastic), with gasket and 0-rings.
2 - Nebulizers.
2 - Drying chambers (polysulfone plastic).
2 - Cleanout wires for nebulizer (0.011" dia., stainless steel).
12 - Lengths nebulizer tubing (silicone).
2 - Extra nebulizer cleanout screws (stainless steel).
2 - Extra nebulizer washers (Teflon).
2 - Operator's manuals.
The spare parts included with the SPAG-2 will allow operation with little or no
downtime.

2. Operation of the SPAG-2 requires that the following equipment and items be provided by the hospital or clinic:

2.1 Compressed gas source, regulated to 40-60 psi (pounds per square inch gauge) (275-413 kPa). Use air which meets specifications for medical breathing use, unless the physician prescribes oxygen which must be blended.

2.2 If greater than 21 % oxygen is to be delivered to the patient, an oxygen blender should be used. Fraction of inspired oxygen (F_iO₂) should be monitored at the point of patient delivery.

CAUTION: Oxygen therapy requires careful monitoring.

2.3 Flowmeter, pressure compensated, capable of measuring 15 liters per minute at 50 psig (344 kPa).

2.4 Hose to supply gas to SPAG-2 (equipped with a standard 9/16-18 hemispherical connector).

2.5 Aerosol conduction tubing, 22 mm diameter.

Further equipment required will depend on the particular mode of aerosol administration. Virazole aerosol may be delivered to a face mask, hood, tent, or mechanical ventilator.

3. Additional equipment that must be provided by the hospital or clinic when operating the SPAG-2 with a ventilator is listed below:

3.1 Bacteria filters
3.2 T adapter
3.3 Coupling connectors
3.4 One-way valve
3.5 Pressure monitor
3.6 Oxygen blender
3.7 Adjustable pressure relief device (Water Column Relief Valve - for volume and pressure cycled ventilators)

IMPORTANT: Internal wire heated ventilator circuits must be used to minimize drug precipitation.

Circuit components described in Sections F, G and H of the manual with the notation or equivalent are generally interchangeable with items available from other manufacturers. It is the responsibility of the user to ensure compatibility of the components and to monitor proper operation of all components in the ventilator circuit. Equipment identification is provided only to assist users. It is not meant as an endorsement of any company or product.

The ICN Pharmaceuticals, Inc. Group makes no warranty for the performance of other manufacturers equipment.

D. ASSEMBLY OF THE SPAG-2 AEROSOL GENERATOR

The following section describes the assembly of the SPAG-2 and connection to a hood, mask, or tent. See Part 2 of this manual for instructions for use in conjunction with mechanical ventilators.

1. Check all 3 nebulizer orifices with the cleanout wire to ensure that they are not occluded. Insert the nebulizer stem into the swage fitting in the center of the reservoir cap. Tighten the swage firmly with the hand tight nut.

2. Inspect the reservoir cap gasket for cleanliness. Place the cap onto the reservoir containing the Virazole solution (see Section K for instructions describing preparation of Virazole). Twist the cap clockwise to seal the cap onto the reservoir. Make sure that the nebulizer pick-up tubes are not flush against the bottom of the reservoir.

3. Place the cap/reservoir assembly into the housing, and snap it into place in the bracket.

4. Connect the drying air flow (black hose) quick-coupling to the larger fitting on the cap spout. Connect the nebulizer air flow (blue hose) quick-coupling to the smaller fitting on the body of the cap. Press each quick-coupling in with a twisting motion until it snaps in place.

5. Insert the drying chamber through the side hole in the SPAG housing, and push onto the cap spout 0-ring. The flow direction arrow on the chamber must point away from the cap.

6. Connect the aerosol conduction tubing (supplied by the user) to the outlet port of the drying chamber.

NOTE: The length of the aerosol conduction tubing between the SPAG-2 and the mask, hood or tent should be kept as short as conveniently possible to minimize collection of aerosol during operation. The tubing should be changed at the same frequency as the wetted parts (see Section l).

7. For use with a hood, the aerosol delivery tubing from the SPAG-2 should be placed into the inlet port of the hood.

8. For use with a face mask, a standard T piece should be connected to the mask. The aerosol delivery tubing from the SPAG-2 should be connected to one of the open ends of the T. Additional aerosol tubing is attached to the branch of the T for a reservoir. This reservoir tubing is for optimal Virazole delivery. The length of the reservoir tubing will depend on the patient's tidal volume. The practitioner should follow the hospital's procedure for determining the patient's tidal volume. (See Appendix 1.)

9. For use with a tent, the tent must be set up with the customary air flow and cooling systems. The aerosol delivery tubing from the SPAG-2 should be connected to the inlet port of the tent.

E. SPAG-2 OPERATING PROCEDURE

The following section describes the general operating procedures for the SPAG-2. See Part 2 of this manual for instructions for use in conjunction with mechanical ventilators.

NOTE: If greater than 21% oxygen is to be delivered to the patient, an oxygen blender should be used. Fraction of inspired oxygen (F_iO₂) should be monitored at the point of patient delivery.

CAUTION: The gas source must be connected to the SPAG-2 and turned on whenever the SPAG-2 is in use. The source must be regulated in the range 40-60 psi (275-413 kPa). Use air which meets specifications for medical breathing use unless the physician prescribes oxygen which must be blended. Oxygen therapy requires careful monitoring.

 1. Connect the SPAG-2 to the external flowmeter (provided by user). Open the external flowmeter control valve completely. It is important that the external flowmeter does not restrict gas flow to the SPAG-2.

2. Open the nebulizer flowmeter valve completely (approximately six turns counter clockwise from the closed position).

3. Disengage the lock sleeve on the SPAG-2 pressure regulator by pulling the adjustment knob outward. For SPAG-2 devices with a white lock ring on the pressure regulator, disengage the lock ring by pulling the ring outward. Adjust the pressure regulator knob (clockwise to increase) until 26 psi (179 kPa) is indicated on the SPAG-2 pressure gauge.

4. Open the drying air flowmeter valve from the closed position until the external flowmeter indicates the desired total flow through the unit. It is suggested that the external flowmeter should read approximately 15 liters per minute (LPM) when using a hood or a tent, and approximately 12 LPM when using a face mask.

5. Readjust the SPAG-2 pressure regulator to 26 psi (179 kPa).

6. Verify that the external flowmeter reading is correct and, if necessary, adjust again by turning the drying air flowmeter valve.

7. The SPAG-2 is correctly adjusted when the operating parameters stabilize into the following ranges:

7.1 Regulator pressure = 26 ± 2psig (165-193 kPa).
7.2 Nebulizer flowmeter range from 6-10 LPM.
7.3 Drying air flowmeter = range from 2-9 LPM.
Read all rates of flow at the center of the indicator ball.


.

8. TROUBLESHOOTING

8.1 INCORRECT AIR FLOW READING: Ensure that the SPAG-2 flows have stabilized before deciding that they are out of tolerance.

a. Nebulizer air flow: If the indicated nebulizer air flow is greater than the specification in 7.2 above, check for leaks in the connections delivering air to the nebulizer. Ensure that the clean out screw in the nebulizer is not leaking. If the flow is less than the specification in 7.2, clean the nebulizer and check for occlusions in the orifices. If these measures do not bring the flow into the correct range, change the nebulizer.

b. Drying chamber air flow: Ensure that the flow to the nebulizer is within the specified range before troubleshooting the drying chamber air flow. If the flow to the drying chamber cannot be adjusted within the specified range, check for leaks or occlusions in the plumbing connections.

8.2 NEBULlZER FUNCTION

Check that all three (3) orifices of the nebulizer are spraying correctly by looking for three approximately one-half inch diameter spray spots on the wall of the flask. If any problem is detected, clean or change the nebulizer.

The SPAG-2 should nebulize the drug solution from the reservoir at a rate of 12.5-15.0 ml/hour. If the nebulization rate is slow, ensure that the external flowmeter (provided by the user) is completely opened, and that the nebulizer orifices are not clogged. Change the silicone tubing or the nebulizer tubing assembly after ensuring that other operating parameters are correct. If the nebulization rate appears to be fast, check for excessive leaks at the cap gasket.

9. Monitor the operation of the SPAG-2 for approximately ten minutes and adjust any settings accordingly.

CAUTION: During operation, water/drug collection may form in the reservoir cap spout, inside the drying chamber, at the outlet port of the drying chamber and in the 22 mm aerosol conduction tubing. Monitor these components hourly. Collection may increase after 10 hours of operation. If excessive collection is seen, these components should be cleaned or replaced.

10. Before inactivating the aerosol generator, assure that the patient has been removed from the aerosol and has an alternative source of oxygen or air. To inactivate the aerosol generator, turn off the gas source.

INSTRUCTIONS FOR USE OF THE SPAG-2 IN CONJUNCTION WITH MECHANICAL VENTILATORS

F. OPERATION OF THE SPAG-2 WITH A VENTILATOR-GENERAL INSTRUCTIONS:

The following instructions apply to use of the SPAG-2 with either pressure cycled or volume cycled ventilators and must be read before continuing.

Also see additional specific instructions for volume cycled ventilators (Section G), or pressure cycled ventilators (Section H).

1. Use an oxygen blender as the gas source if greater than 21 % oxygen is to be delivered to the patient. Fraction of inspired oxygen (F_iO₂) should be monitored at the point of patient delivery.

2. Turn off the drying air flowmeter on the SPAG-2 unit.

3. Adjust the nebulizer flow to 6-10 LPM.

4. Connect the SPAG-2 delivery tube into the inspiratory line of the patient breathing circuit immediately downstream from the heated humidifier. Place a one-way valve in the SPAG-2 tubing at the junction with the ventilator circuit. (See Figure F-1). Check the operation of the one-way valve before installing it into the circuit. 

Figure Fl. Junction of SPAG-2 with ventilator circuit, and location of bacteria filters

CAUTION: Water/drug precipitate may form in the one way valve, the ventilation tubing and/or the endotracheal tube; frequent (hourly) monitoring of these components for precipitate is required. If the valve and/or tubing collect precipitate, they must be cleaned or replaced.

IMPORTANT: If airway pressures increase, the endotracheal tube should be checked, and the patient suctioned, to minimize precipitate build-up. Airway pressure increases can also be caused by clogged bacteria filters (see Item 5 of this section).

5. Bacteria filter(s) (Pall BB-50T, Marquest' #MQ-303-01, or equivalent) are mandatory in the expiratory line just before the ventilator exhalation valve entrance port (see Figure F-1). Filters should be changed every 2-4 hours, or more frequently as needed.

CAUTION: Filters should be changed if an increase in peak inspiratory pressure (PIP) or positive end expiratory pressure (PEEP) of 1-2 centimeters of water is observed. Because these pressure increases may occur, airway and ventilator circuits should include CONTINUOUS MONITORING as described in item 8 of this section.

NOTE: Two filters may be placed in series. When changing filters, discard the upstream filter. Place a fresh filter downstream of the remaining filter.

6. A bacteria filter may be placed in the inspiratory line upstream of the humidifier to prevent Virazole from entering the ventilator, should a reversal of flow occur during operation.

7. Connection of the SPAG-2 to the ventilator circuit may cause the end expiratory pressure to increase (1-2 cm H₂O). To maintain the desired positive end expiratory pressure (PEEP) level, adjust the ventilator PEEP control.

8. Use of a pressure monitor with both high and low PEEP alarms is essential to assist the user in detecting changes in the PEEP level (e.g. Novametrix pneumogard #1250, Bunnell #00120, or equivalent).

9. Water condensation (rainout) associated with the use of conventional tubing may require frequent (hourly) removal of the condensate. To minimize rainout, internal wire-heated tubing must be used.

10. Maintain the temperature in the circuit at 33-37°C. It may be necessary to set the heated humidifier at a higher temperature. BEFORE DlSCONNECTlNG THE SPAG-2 FROM THE VENTILATOR CIRCUIT, THE TEMPERATURE AT THE HEATED HUMIDIFIER MUST BE ADJUSTED APPROPRIATELY.

CAUTION: Both the heater/humidifier and the internal wire heater sensors must be checked hourly for evidence of water/drug precipitate which can decrease the accuracy of the sensor. When internal wire heated circuits are used, precipitate may also form at the loop of the wire.

10.1 When using conventional tubing, place the heated humidifier temperature sensor at the patient wye.



10.2 When using internal wire heated tubing, place the heated humidifier temperature sensor immediately downstream from the junction of the SPAG-2 tubing and the inspiration line of the ventilator. Place the internal wire heater temperature sensor at the patient wye. Set the internal wire heater to 37°C, and the heated humidifier slightly less (approximately 33°C) to maximize prevention of rainout.



11. Both the SPAG-2 tubing and the conventional ventilator circuits should be changed daily. It is recommended that internal wire heated circuits be changed every 8-10 hours.

G. OPERATION OF THE SPAG-2 WITH A VENTILATOR - ADDITIONAL INSTRUCTIONS FOR VOLUME CYCLED VENTILATORS

1. Read Section F before continuing with this section.

2. Figure G-1 is a schematic drawing of the ventilator tubing circuit used with the SPAG-2 in conjunction with a volume cycled ventilator. Pediatric clinical experience with the Siemens Servo 900C suggests that any equivalent volume cycled ventilator may be used with the SPAG-2.

Figure G-1.Schematic of ventilator and SPAG-2 system used with a volume cycled machine.

(A): Silicone rubber coupling (Puritan-Bennett #3443, or equivalent).
(B): Disposable aerosol T adapter (Hudson #1077, or equivalent).
(C): Bacteria filters (Marquest #MQ-303-01, Pall #BB-50T, or equivalent).
(D): One-way valve (Inspiron #001671, or equivalent).
(E): ICN Water Column Relief Valve (ICN #6003, see replacement parts section of this manual).

3. The calculated volume of the tubing between the one-way valve and the patient wye must be at least one tidal volume for correct aerosol delivery. Figure G-2 below indicates the section of tubing of concern. See Appendix 1 as an aid to estimate tidal volume and tubing volume.

Figure G-2. Section of ventilator circuit tubing where one patient tidal volume is required.

4. Exhaled volumes displayed on the ventilator will read falsely high due to the additional volume (flow) supplied by the SPAG-2.

5. Use of a low-pressure monitor (e.g. Ventronics^® Model 5522 or equivalent) will assist the user in detecting potentially dangerous low pressure situations.

CAUTION: Certain alarm settings, such as the low minute volume alarm on the Siemens Servo 900C, will read falsely high and thus rendered unreliable when the SPAG-2 is connected to the ventilator.

6. Attach a water column pressure relief valve to the SPAG-2 output with a T connector (see Figure G-1). The pressure relief valve is needed to vent the continuous flow from the SPAG-2 during the inspiratory phase of a volume cycled ventilator.

An ICN Water Column Relief Valve is available with mounting brackets for the SPAG-2 (ICN #6003, see replacement parts section of this manual). A user supplied water column relief valve may also be used.

Adjust the relieving pressure between 2-5 cm of water greater than the observed end expiratory pressure (EEP) prevailing in the patient/ventilator circuit. When adjusted properly the relief valve will bubble during the inspiratory phase of the ventilator and cease bubbling during the expiratory phase. When using the ICN Water Column Relief Valve, thoroughly read the instructions for use provided with the valve.

CAUTION: Monitor the relief valve hourly to ensure proper operation. Adjust the water level in the relief valve according to any changes made in the EEP during the course of therapy. Maintain the water level in the relief valve at 2-5 cm H₂O greater than the prevailing EEP. Clean or replace the valve as necessary.

7. TROUBLESHOOTlNG RELIEF VALVE OPERATION:

7.1 Relief valve bubbles continuously:

a. Relief valve pressure is set too low. Increase water level in reservoir to 2-5 cm H₂O greater than the prevailing EEP level.

b. One-way valve is stuck closed or clogged. Clean or replace the< one-way valve.

7.2 Relief valve never bubbles:

a. Relief valve pressure is set too high. Decrease water level in reservoir to 2-5 cm H₂O greater than the prevailing EEP level.

b. One-way valve is stuck open. Clean or replace the one-way valve.

H. OPERATION OF THE SPAG-2 WITH A VENTILATOR ADDITIONAL INSTRUCTIONS FOR PRESSURE CYCLED VENTILATORS

1.Read Section F before continuing with this section. in treating very small infants with a pressure cycled ventilator, the flow rate may be considerably less than 6 LPM which makes it impossible to employ the method of Virazole administration described in this section. A Water-Column Relief Valve can be inserted in the SPAG circuit, just as would be done with a volume cycled machine (see Section G). This modification is advantageous because the controls of the pressure cycled ventilator need not be altered. In addition, ventilator adjustments need not be made during periods when SPAG flow must be discontinued (such as in preparation for suctioning the patient).

2.Figure H-1 is a schematic drawing of the ventilator tubing circuit used with the SPAG-2 in conjunction with a pressure cycled ventilator. Any of various ventilators, such as the Bear® BP-200, Healthdyne®- 105, Sechrist® Model lV-100B, or equivalent, can be used in assisted ventilation, controlled ventilation, intermittent mandatory ventilation (IMV), or continuous positive airway pressure (CPAP) mode.

Figure H-I. Schematic of ventilator and system used with a pressure cycled machine.

(A): Silicone rubber coupling (Puritan-Bennett® #3443, or equivalent).
(B): Disposable aerosol "T" adapter (Hudson® #1077, or equivalent).
(C): Bacteria filters (Marquest® #MQ-303-01, Pall® #BB-50T, or equivalent).
(D): One-way valve (lnspiron® #0016671, or equivalent).
(E):ION Water Column Relief Valve (lCN #6003, see replacement parts section of this manual).

3.Adjust the ventilator flow setting so that the peak inspiratory pressure (PIP) observed is the same as before the SPAG-2 was connected to the circuit.

GENERAL INFORMATION

I.STERILIZATION OF SPAG-2 WETTED COMPONENTS

All parts of the SPAG-2 are clean as delivered. It is the responsibility of the user to sterilize all wetted parts before beginning each course of therapy. At a minimum, sterilization of all wetted parts should be done daily.

Sterilize, by autoclaving, the following parts:

1. Drying chamber (polysulfone plastic).

2. Reservoir (polysulfone plastic).

3. Reservoir cap (polysulfone plastic) with gasket and 0-rings.

4. Nebulizer assembly with tubing.

5. ICN Water Column Relief Valve, with plug, if used.

Autoclave these items by standard procedures.

Hospital personnel should follow their established procedures for monitoring bacterial contamination of respiratory equipment for the care of the SPAG-2.

J. CLEANING OF COMPONENTS

1. Any Virazole solution remaining in the reservoir flask after treatment should be discarded.

2. Virazole is a very water soluble material. The components (reservoir, cap, nebulizer, drying chamber, and water column relief valve) can be effectively cleaned with warm tap water and mild detergent. After cleaning, rinse with warm tap water followed with distilled or deionized water.

3. Extra attention should be given to cleaning the nebulizer. Do not disassemble unless an occlusion is suspected. Probe the orifices of the nebulizer with the 0.011" cleanout wire to dislodge any material. Ensure that the wire is inserted completely into each of the three small inner holes on the side of the nebulizer tip. After cleaning and rinsing the nebulizer, shake it to remove water from the small passageways.


4. If disassembly of the nebulizer becomes necessary, remove the small cleanout screw (with washer) and the silicone tubing. Probe all orifices with the cleanout wire. Soak all nebulizer parts in warm to hot water containing detergent, rinse thoroughly, then blow dry with compressed air. Reassemble the nebulizer.

5. The reservoir, cap, nebulizer, drying chamber, and water column relief valve should be sterilized by autoclaving. (See Section I.)

6. The housing can be cleaned with any disinfectant currently used by the hospital for cleaning the exterior of similar respiratory therapy equipment (e.g., ventilators, IPPB devices). For example, Sanamaster III (quaternary compound), 1 oz/gallon.

K. PREPARATION OF VlRAZOLE^® FOR USE IN THE SPAG-2

Virazole is supplied as 6 grams of lyophilized drug per 100 ml vial for aerosol administration only. By sterile technique, dissolve the drug with sterile USP water for injection or inhalation in the 100 ml vial. Transfer to the clean, sterilized 500 ml SPAG-2 reservoir and further dilute to a final volume of 300 ml with sterile USP water for injection or inhalation. The final concentration should be 20 mg/ml.

Important: This water should not have had any antimicrobial agent or other substance added. The solution should be inspected visually for particulate matter and discoloration prior to administration. Solutions that have been placed in the SPAG-2 unit should be discarded at least every 24 hours and when the liquid level is low before adding newly reconstituted solution.

Using the recommended drug concentration of 20 mg/ml Virazole as the starting solution in the drug reservoir of the SPAG-2 unit, the average aerosol concentrations for a 12 hour period would be 190 micrograms/liter (0.19 mg/l) of air.

Vials containing the lyophilized drug powder should be stored in a dry place at 15- 25°C (59-78°F). Reconstituted solutions may be stored, under sterile conditions, at room temperature (20-30°C, 68-86°F) for 24 hours. Solutions which have been placed in the SPAG-2 unit should be discarded at least every 24 hours.

NOTE: Levels of Virazole in the environment are expected to be very low during proper administration of the drug. To help minimize incidental exposure, Virazole should be administered in a well-ventilated hospital setting. Hospital staff responsible for aerosol delivery should consider using a protective face cover (nose and mouth) to reduce incidental exposure. Common surgical masks do not provide a significant amount of protection. The 3M Model 9970 personal mask has been identified as one which supplies significant protection when properly fitted. NIOSH has recommended: Training programs should be developed; scavenging systems should be used, where possible, to reduce environmental exposure; treatment should be administered in rooms with at least six air changes per hour; treatment rooms should be under negative pressure; where possible, turn off the SPAG-2 five minutes before each health care worker enters the room; avoid dermal, oral, or ocular contact with airborne Virazole; respirators may be used to further reduce Virazole exposure; American Academy of Pediatrics recommendation for patient selection should be considered.

L. SELECTED REPLACEMENT PARTS FOR THE SPAG-2

Replacement parts and technical assistance for the SPAG-2 6000 Series may be obtained by contacting your local representative or the ICN office listed below. When ordering, please specify the SPAG-2 device serial number, as well as the part number and description of the item desired.