I. Subject: Administration of Virazole (Ribavirin) by aerosol.

I. Subject: Administration of Virazole (Ribavirin) by aerosol. II. Policy: Ribavirin therapy will be administered upon the order of a physician by Respiratory Therapy department personnel. Because of the possible teratogenic effects and other hazards associated with exposure to the drug, employees, and visitors who are or may become pregnant during the course of therapy will not be allowed in the patient's room during treatment. Only essential personnel will be allowed in the patient's room during administration. Additionally, a scavenging system will be used during aerosol administration to reduce the escape of aerosolized drug from a tent enclosure. A sign will be placed on the door telling visitors and employees not to enter the room during treatment and to report to the nursing station for instructions. Essential personnel entering the room must be attired in protective gear. III. Indications: Ribavirin 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). Specifically, Ribavirin is indicated in treatment of RSV lower respiratory infections for pediatric patients considered high risk for complications due to pre-existing disease including: 1) Severe cyanotic congenital heart disease 2) Severe bronchopulmonary dysplasia 3) Immunodeficiency 4) Apnea 5) Ventilatory failure 6) Impending ventilatory failure as evidenced by one or more of the following: a. PaCO2 less than 50 mmhg b. Persistent respiratory acidosis c. PaO2 less than 65 mmhg or SaO2 less than 93% 1

7) Infants less than six (6) weeks of age. Additionally, Ribavirin may be used in RSV infection when initiation of mechanical ventilation occurs or appears imminent, and Ribavirin therapy may improve symptomatology. Only severe RSV lower respiratory tract infection is to be treated with Ribavirin aerosol. The vast majority of infants and children with RSV infection have no lower respiratory tract disease or have disease that is mild, self-limited, and does not require hospitalization or antiviral treatment. Many children with mild lower respiratory tract involvement will require shorter hospitalization that would be required for a full course of Ribavirin aerosol (3 to 7 days) and should not be treated with the drug. Thus, the decision to treat with Ribavirin aerosol should be based on the severity of the RSV infection. RSV infection should be documented by a rapid diagnostic method or detection of virus or viral antigens or virus specific nucleic acid sequences in respiratory secretions before or during the first twenty-four hours of treatment. Treatment may be instituted while awaiting rapid diagnostic tests results. However, treatment should not be continued without documentation of RSV infection. IV. Contraindications/Hazards: A. Ribavirin is contraindicated in individuals who have shown hypersensitivity to the drug or its components, and in women who are or may become pregnant during exposure to the drug. B. Deterioration of respiratory function has been associated with Ribavirin use in infants, and in adults with chronic obstructive lung disease or asthma. Respiratory function should be carefully monitored during treatment. If the initiation of Ribavirin aerosol therapy appears to produce sudden deterioration of respiratory function, therapy should be stopped and re-instituted only with extreme caution and continuous monitoring. C. Although Ribavirin is not indicated in adults, the physician should be aware that it is teratogenic. D. Other potential hazards include airway obstruction from the swelling of dried, retained secretions, bronchospasm caused by the inhalation of fine aerosol particles, 2

and fluid overload, especially in infants receiving continuous aerosol therapy. V. Rationale: Ribavirin has antiviral inhibitory activity in vitro against respiratory syncytial virus. When delivered by aerosol, Ribavirin is directly delivered to the site of infection via uniform small size aerosol particles (95% of particles are less than 5 microns). These ultra-fine aerosol particles are carried deep into the lower respiratory tract. Ribavirin has been shown to significantly reduce the duration and amount of viral shedding. Ribavirin is delivered by means of a specialized device known as the SPAG-2 (Small- Particle Aerosol Generator). The SPAG-2 is driven by a pressured gas (air or oxygen) source, which passes through and external pressure compensated flowmeter before entering the SPAG-2. The incoming gas is regulated to 26 psig, and then is directed, via a manifold and pressure-compensated flowmeter, to both the nebulizer and the drying chamber. The nebulizer generates a fine aerosol of hydrated Ribavirin, and the drying chamber further dehumidifies the aerosol. The mass median diameter of the aerosol particles is approximately 1.3 microns. VI. Materials: SPAG-2 unit (Small-Particle Aerosol Generator) Sterile water Aerosol Tubing High pressure hose Oxyhood, tent or aerosol mask Air compression and/or oxygen blender with appropriate flowmeter 1 vial of ribavirin VII. Method: A. Check order. Verify the physician's order as follows: 1) Compare the requisition with the physician's order to ensure that no discrepancies exists. 2) Review the order to ensure that the following are prescribed: a. Type of delivery device b. Frequency of therapy 3

3) If any part of the order is unfamiliar, question its accuracy. B. Review chart. Use the following procedure to review the patient's condition: 1) On the patient's chart, identify all pertinent data in the following areas: a. History and physical b. Admitting diagnosis c. Progress notes d. Lab data 2) Based on the patient data, identify following: a. Conditions that indicate the need for Ribavirin therapy. b. Potential hazards of aerosol therapy with Ribavirin for the patient. C. Maintain cleanliness. While performing the remainder of this procedure, the technician/therapist is expected to maintain clean conditions. This includes hand washing. D. Drug preparation. Ribavirin (Virazole) is supplied as six (6) grams of lyophilized drug per 100 ml vial. It is prepared for use as follows: 1) By sterile technique, solubilized the drug with 100 ml sterile USP water for injection or inhalation in the 100 ml vial. IMPORTANT: This water should not have had any antimicrobial agent or any other substance added. The solution should be inspected visually for particulate matter and discoloration prior to administration. 2) Transfer to the clean, sterilized 500 ml wide-mouth flask (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. 3) 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. 4) Using the recommended drug concentration of 20 mg/ml Ribavirin as the 4

starting solution in the drug reservoir of the SPAG unit, the average aerosol concentration for a twelve hour period would be 190 micrograms/liter (0.19 mg/l) of air. 5) For further detail regarding Ribavirin, refer to the manufacturer's package insert. E. Obtain equipment. Collect the items listed in Section VI. F. Assemble equipment. Prepare the equipment for use as follows: 1) Check all three (3) nebulizer orifices with the cleaning 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 Ribavirin solution. 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 tube) quick coupling to the larger fitting on the cap spout. Connect the nebulizer air flow (blue tube) quick coupling to the smaller fitting on the body of the cap. Press each quick coupling in with a twisting motion until it snaps into place. 5) Insert the drying chamber through the side hole in the SPAG housing, and push onto the cap spout o-ring. The flow direction arrow on the chamber must point away from the cap. 6) Connect the aerosol tubing to the outlet port of the drying chamber. 7) For use with a hood or a tot-hut, 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 5

one of the open ends of the "T". Additional aerosol tubing is attached to the branch of the "T" to serve as a reservoir. This reservoir tubing is for optimal Ribavirin delivery. The length of the reservoir tubing will depend on the patient's tidal volume. 9) The scavenger evacuation system must be used whenever Ribavirin is administered via a tot-hut, or aerosol mask. This system will reduced exposure to Ribavirin, but does not eliminate exposure, therefore, precautions still exists. Obtain equipment: 1) Straight vacuum connector 2) Suction tubing (10 inch) 3) 15 mm adaptor 4) 2 bacteria filters 5) T-piece 6) 2 large bore corrugated tubings 7) 6" flex tube Assemble equipment: Connect straight vacuum connector to wall suction. Attach 10" section of suction tubing to vacuum connector and 6" flextube. Attach 2 consecutive bacteria filters to 6" flextube and T-piece. Connect the 2 large bore corrugated tubings to the T-piece and run them into the outer tent alongside and in front of the inner tent. This equipment should be checked every 2 hours when the Ribavirin SPAG-2 set-up is being checked. The filters and large bore tubing should be changed out every 24 hours, or when the medication is changed, whichever comes first. G. Confirm patient. Ensure that the procedure is performed with the correct patient as follows: 1) Match the information on the requisition with the following: Patient name and birthdate. 6

2) Place sign for hazardous aerosol on outside of entrance door. 3) Don gloves, mask, eyewear, cap and gown. H. Inform patient. Interact with the patient as follows: 1) Introduce yourself by name and department (if not already acquainted). 2) Tell the patient (or family) what procedure is to be performed. 3) Explain the procedure by describing: a. Why it is to be performed. b. How it will be performed. c. What the patient is expected to do. d. What you will be doing. e. How frequently it will be performed. 4) Explain the fire hazards associated with the use of oxygen and caution the patient's family against smoking. I. Implement procedure. Perform the following tasks: 1) Adjust the external flowmeter to 15 L/min. This initial setting to essentially "wide-open" flow assures that the external flowmeter valve will not restrict air flow to the SPAG-2. 2) Connect the SPAG-2 to the flowmeter. 3) Disengage the lock sleeve on the SPAG-2 pressure regulator knob by pulling firmly outward. From its fully closed position (i.e. counterclockwise to stop) adjust the pressure regulator knob clockwise until 26 psig is indicated on the SPAG-2 pressure gauge. 4) Open the nebulizer flowmeter valve completely (approximately six turns counter clockwise from the closed position). NOTE: On early SPAG-2 units with device serial numbers less than 1798 the valve stem is removable. Do not turn the valve to full open position. 7

5) Open the drying air flowmeter valve from its fully 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 L/min when using a hood or tent, and approximately 12 L/min when using a face mask. 6) Readjust the SPAG-2 pressure regulator to 26 psig. 7) Verify that the external flowmeter reading is correct and, if necessary, adjust it again by turning the drying air flowmeter valve. 8) The SPAG-2 is correctly adjusted when the operating parameters stabilize into the following pressure ranges: a. Regulator pressure= 26 + or - 2 psig b. Nebulizer flowmeter + 6-10 L/min. (Indicated as 3.5-6 L/min for device serial no.'s less than 1798) c. Drying air flowmeter= range from 2-9 L/min. 9) Monitor the operation of the SPAG-2 for approximately ten minutes and adjust any settings accordingly. 10) Before inactivating the aerosol generator, assure that the patient has been removed from the aerosol and has an alternative source of oxygen air. To inactivate the aerosol generator, turn off the source gas. 11) Turn off gas scavenging suction. Remove patient from Ribavirin therapy inner and outer tents. J. Monitor patient. Determine the patient's response to therapy as follows: 1) Determine the pulse rate. 2) Determine the respiratory rate. 3) Observe respirations to identify any abnormalities in the breathing pattern. 4) Auscultate the patient's chest. 8

K. Record results. Document the therapy as follows: 1) Record the following data on the patient's Respiratory Therapy flowsheet. a. Date and time b. Therapy administered; indicate delivery device and FIO2 c. Pulse rate d. Respiratory rate e. Abnormal patient characteristics f. Therapy-related patient complaints L. Report observations. Report the following information: 1) Report any significant adverse changes in the patient's condition to the nurse or physician whenever observed. 2) Following the procedure, inform the appropriate personnel of: a. Patient requests. b. Patient complaints. c. Unexpressed patient needs. 3) Following the procedure, report to the nurse or physician: a. Any non-critical adverse reactions to the therapy. b. Other pertinent observations of the patient s condition. VIII. Special Considerations: A. The following method is used when the SPAG-2 unit is used in conjunction with a mechanical ventilator: 1) Additional Equipment: 2-Bacteria filters T adaptor One-way valve Oxygen blender 9

Water column relief valve External pressure monitor with high and low alarms. 2) Procedure a. Connect outlet hose of blender to SPAG-2 unit. Adjust FIO2 on blender to equal that of ventilator. b. Turn off the drying air flowmeter on the SPAG-2 unit. c. Adjust the nebulizer flow to 6-10 LPM. d. 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. Check the operation of the one-way valve before installing it is not the circuit. CAUTION: Water/drug precipitation may form in the one-way valve, the ventilator tubing and/or the endotracheal tube. Frequent monitoring of these components for precipitation is required. e. Place two bacteria filters in series in the expiratory line just before the ventilation exhalation valve entrance port. The filter closest to the patient is discarded every two (2) hours and a new filter placed closest to the exhalation valve. CAUTION: Filters should be changed if an increase in peak inspiratory pressure (PIP) or PEEP of 1-2 cmh2o is observed. f. A bacteria filter is placed in the inspiratory line upstream of the humidifier to prevent Ribavirin from entering the ventilator. g. Connection of the SPAG-2 to the ventilator circuit may cause PEEP to increase (1-2 cmh2o). To maintain the desired PEEP, adjust the ventilator PEEP control. h. Connect an external pressure monitor with a high level alarm to detect changes in the PEEP level. Set the high pressure level at 2 cmh2o above the PEEP level. 10

i) Always use a heated wire circuit with temp set at 32 C. CAUTION: Thermometer sensor probes must be checked frequently for evidence of water/drug precipitate which can decrease the accuracy of the sensor. j) Attach a water column pressure relief valve to the SPAG-2 output with a T-connector. The pressure relief valve is needed to vent the continuous flow from the SPAG-2 during the inspiratory phase of the ventilator. Fill to a relieving pressure between 2-5 cm of water greater than the observed PEEP level prevailing in the patient/ventilator circuit. When adjusted properly, the relief valve will bubble during the inspiratory phase and cease during the expiratory phase. If relief valve bubbles continuously, the pressure is set too low. Increase water level in reservoir. If relief valve never bubbles, relief pressure is set too high. Decrease water level in reservoir. k) Change out the entire ventilator circuit after each administration of Ribavirin and at least every 12 hours. IX. Hazards/Complications: COMPLICATIONS: Oxygen induced hypoventilation. Absorption atelectasis Oxygen toxicity Airway obstruction from the swelling of dried, retained secretions. Bronchospasm caused by inhalation of fine aerosol particles. ACTIONS/PRECAUTIONS: Monitor ABG's to avoid hyperoxia. Recommend lowest possible FIO2. Monitor ABG's to avoid hyperoxia. Recommend lowest possible FIO2. Apparently occurs only at an FIO2 greater than 50%. Closely monitor ABGs. Auscultate chest for evidence of increased airway resistance. ET suctioning if unable to clear airway by other means. Discontinue therapy and notify physician. 11

Fluid overload, especially in infants receiving aerosol therapy. Daily weights and chest auscultation to assess volume status. 12