Nitric Oxide
Nitric oxide is a colourless, odourless toxic and non-inflammable gas that can be administered via the ventilator circuit as an additional therapy in Newborn Services.
- Introduction
- Dose and administration
- Prescribing inhaled Nitric Oxide
- Weaning iNO and FiO2
- Indications
- Contraindications and precautions
- Clinical pharmacology
- Possible adverse effects
- Administration via Drager Babylog (in all modes) or Senso...
- Safety and emergency precautions
- Signs of toxicity NO and NO₂
- Emergency management of suspected minor gas leak
- Emergency management of a major leak
- Storage
- References
- Document Control
Introduction
Inhaled Nitric Oxide (iNO) is a potent vasodilator used to treat pulmonary hypertension in the newborn. When given into the ventilator circuit, it dilates the pulmonary vasculature. It is inactivated instantly in blood, by reacting with haemoglobin. Therefore it has no action on the systemic vasculature and therefore (theoretically) on systemic blood pressure.
Dose and administration
Start on 20 ppm. Doses above 20 ppm are not indicated as there would be little if any additional benefit and risk of toxicity.
For very preterm infants starting at 10 ppm might be sufficient.
Evaluate for response to treatment in 30 - 60 minutes. Examples of complete (and partial) responses to iNO include:
Increase in PaO2 > 20 mmHg (or 10 - 20)
Increase in saturations > 10% (or 5 - 10%)
Ability to wean FiO2 by 0.2 (or 0.05 - 0.2)
Prescribing inhaled Nitric Oxide
Treatment initiated only on Consultant's orders.
Charted and signed by Registrar/Nurse Specialist - Advanced Neonatal Practice (NS-ANP) on Level 3 Nursing Chart in parts per million (ppm).
Changes in flow are signed by registrar/NS-ANP.
Weaning iNO and FiO2
There is little evidence to guide the best method of weaning iNO. If a positive response is seen after iNO initiation, then iNO dose should continue at 20 ppm while the bedside nurse weans FiO2.
Goal saturations are ≥95%. (In Congenital Diaphragmatic Hernia the target saturations may be lower when initiating weaning of iNO.)
Weaning FiO2 should be gradual with a maximum wean rate of ~0.10 FiO2 per hour.
Weaning iNO occurs step-wise every 1-2 hours.
If, after 4-6 hours of iNO, the FiO2 is down to 0.60, then begin to wean iNO.
If no response to iNO is found after 60 minutes, then the iNO may be discontinued with caution - see weaning flow diagram.
"Rebound" pulmonary hypertension occurs when FiO2 must be increased by 0.20 or more to maintain saturations>95%, following an iNO wean. If this occurs, halt weaning or return to the previous therapeutic iNO dose.
Indications
Nitric oxide is used to treat:
Persistent pulmonary hypertension of the newborn (PPHN) (proven clinically (i.e. 20% differential in pre-postductal saturations) or by point of care ultrasound or echocardiography; OR
Severe respiratory failure (i.e. oxygenation index >25, PaO₂ < 60 mmHg despite 100% FiO₂)
Contraindications and precautions
Cyanotic congenital heart disease, i.e. systemic perfusion dependent on right-to-left shunting. An echocardiogram is not always needed before starting iNO but in many cases congenital heart disease needs to be eliminated soon after. Total or Partial Anomalous Pulmonary Venous Drainage is difficult to diagnose and should be considered in pure Right to Left shunting at the Ductus and PFO. It is also wise to check for coarctation and abnormal heart structure.
Caution in preterm infants. Benefit has not been proven by randomised studies but may be indicated in case-by-case basis.
Caution if known or suspected major haemorrhage (ICH, GI, pulmonary), for risk of platelet dysfunction secondary to iNO.
Caution in Congenital Diaphragmatic Hernia as there is limited evidence to support use. It should not be started routinely however, should be tried if there is difficulty maintaining pre-ductal saturations > 85%, an Oxygen Index > 20 or pre-post ductal saturation difference > 10%.
Clinical pharmacology
Nitric oxide is endothelial derived relaxing factor (EDRF). It is produced in the endothelium of blood vessels and diffuses out of the cells. It then enters vascular smooth muscle cells and activates guanalate cyclase which forms cyclic guanosine monophosphate (cGMP). This is a smooth muscle relaxer. cGMP is inactivated by cGMP phosphodiesterase. The half-life of iNO is 3 - 6 seconds.
iNO is bound to haemoglobin and inactivated to nitosylhaemoglobins and methaemoglobin.
Possible adverse effects
Methaemoglobinaemia when nitric combines with haemoglobin to form methaemoglobin. At clinically used doses (i.e. 20 ppm or less) high methaemoglobin levels have not been reported. In overdose, it may be fatal. If methaemoglobinaemia (>5%) occurs, check the ventilator circuit, particularly the delivery and measuring points of iNO.
iNO is a free radical and causes tissue damage. iNO is used by macrophages to kill bacteria. It can theoretically damage the lung through lipid peroxidation. The precise importance of this has not been elucidated. Biproducts called peroxynitrates can be toxic to tissue.
iNO converts to nitrogen dioxide NO2 spontaneously when mixed with oxygen. High concentration of iNO in O2 lasts 6 seconds. At clinical doses (<20 ppm), the half-life is much longer. NO2 is toxic.
iNO is an inhibitor of platelet function. Caution when there is thrombocytopenia or bleeding.
Administration via Drager Babylog (in all modes) or SensorMedics
Safety Considerations:
Do NOT operate the AeroNOx on battery for longer than 5 hours.
No Nitrix Oxide can be delivered if the device is off.
Do NOT use the AeroNOx without the ventilator running simultaneously.
Do NOT calibrate while giving treatment unless necessary during troubleshooting, Nitric Oxide cannot be delivered during the calibration process.
Always check that the NO flow meter to the Neopuff is CLOSED at the start of each shift (if used for bagging baby, please ensure it is closed after use)
Always have a test lung available.
See Aeronox operational guideline for set up and usage instructions. (Under Newborn Nursing Resources on Hippo).
Monitoring and documentation
Follow the steps below while administering Nitric Oxide to ensure appropriate monitoring is in place to maintain safety for the baby and documentation is complete.
Concentration of Nitric Oxide is adjusted and documented by Doctor/NS-ANP on ventilator chart in ppm.
Nursing staff: An experienced Level 3 Nurse or Level 4 Nurse with a Neonatal IV Drug Certification and who has completed the NO/HFV workbook, cares for baby.
Ensure at the beginning of each shift the concentration of NO prescribed on ventilation chart is consistent with the level showing on the Aeronox and signed as correct by the nurse handing over and nurse taking over the care of the infant.
NO and NO₂ levels are monitored continuously and checked and documented on the ventilation chart, in ppm hourly. Upper safety level of NO determined by Medical Staff for each individual baby. NO alarms usually at 5 above and 3 below prescribed amount of NO. NO2 alarm set at 1.
If NO readout levels rise, check that there is not a leak or loose fitting in ventilator circuit. Ventilator pressures will be reduced and because there is less flow the NO levels rise. If ventilator alarms indicating no gas flow from ventilator, bag baby turning up the flow meter on nitric tank.
If NO₂ levels >1 ppm notify Doctor/NS-ANP. NO₂ levels should not exceed 3 ppm.
Methaemoglobin levels should not exceed 3% (measured with each arterial blood gas). If these exceed this, check the amount of iNO being delivered, and check that the sample tubing is connected in the correct place. Inform medical staff if levels are rising.
Ensure sampling line is oriented upwards of the ventilator tubing (otherwise water will run back to the filter).
Monitor Blood Pressure continuously and document hourly.
Circuits are not changed routinely without discussion with Doctor/NS-ANP as baby may deteriorate rapidly if NO is discontinued (due to very short half-life of NO).
During a circuit change hand bag baby until NO and NO2 monitoring is stable (Doctor/NS-ANP present).
When baby is reintubated or hand bagged cap the ventilator end. DO NOT TURN VENTILATOR OFF AS THE NO AND NO2 LEVELS RISE IN THE TUBING.
Observe and monitor baby closely for signs of deterioration during any trial off NO. (Consultant orders this to determine need for continuing NO administration)
The NO gauge is checked each shift for the amount left in the cylinder. When half empty inform CCN and a replacement cylinder is ordered.
Safety and emergency precautions
Hospital Transport and Storage | Cylinders will be stored upright and chained onto specially provided trolleys. Cylinders are stored in a designated storage area. Cylinders are to be transported only on the specially provided trolleys. |
Transport Between Hospitals | Should be kept to a minimum to prevent accidents. CCNs will arrange as per current policy. |
Cylinder Regulator | To be changed only by: Medical Electronics Personnel Precision Engineering Personnel CCNs |
Leakage Testing | This will be carried out at any time there is a suspicion of a leak. The test will be carried out using "SNOOP" Liquid Leak Detector |
Recommended Extra Precautions | SCAVENGING: Where possible Nitric Oxide is scavenged from the ventilator system (now only Sensormedics). TAMPER-PROOFING: The flow-meter is modified to prevent accidental adjustments to flow rates. |
Signs of toxicity NO and NO₂
A large cylinder of nitric oxide contains 800 ppm NO. A full cylinder completely emptying into a room would give 80 ppm.
Air conditioning clearance in NICU is 15-20 mins. Air is cleaned to outside the building, i.e., is not recycled to other areas of the Hospital.
Recommended maximum environmental exposure is 5 ppm for 8 hours.
Early Signs
Respiratory discomfort.
Headache.
Dizziness.
Lassitude.
Nausea and vomiting.
Signs After 5-8 hours
Cyanosis.
Increased difficulty in breathing (choking).
Dizziness.
Chest tightness.
Palpitations.
Physical examination shows signs of pulmonary oedema.
Emergency management of suspected minor gas leak
A minor leak is usually due to a leak in the regulator as evidenced by staff developing early symptoms of a nitric oxide exposure as above or become aware of a leak that is not major, by a distinctive smell or detection using the SNOOP liquid detector.
The Nurse in charge will assess the nature and extent of the leak and do the following.
Check the cylinder pressure.
Check the cylinder connections. Use "snoop liquid leak detector".
Note the symptoms and conditions and exposure of any staff (see previous page re signs of Toxicity NO and NO2).
Notify Clinical Nurse Manager who will contact the Occupational Physician on call for appropriate assistance.
Change the cylinder and connections, if available. (Call shift engineer to do this).
All non essential people (staff and infants) to leave the pod for at least 15 minutes. (Air conditioning clearance in NICU is 15-20 min).
Rotate the staff to a non contaminated pod.
Take baseline observations of affected staff including pulse rate, respiratory rate and blood pressure. Adult cuff kept in the emergency trolley, use the M540 on the stand in the equipment room.
Repeat these observations hourly for a total of 6 hours or more frequently if indicated. (Occupational Health will advise where monitoring to occur).
Refer the staff member for assessment if concerned.
Provided the leak is assessed as minor and the staff exposed to the suspected leak are well, they should continue working provided the environment has been corrected.
An on-line Datix form should be completed.
Emergency management of a major leak
A major leak is sudden decompression of the cylinder.
Close the regulator tap.
Dial 777 state 'Hazmat Alert'. State Fire Service required, but fire alarm activation not required. Use the Emergency Response Flip Chart and follow the Hazardous materials flow chart. For more detailed information go to the Emergency Preparedness and Response Manual (EPARM) Hazardous Materials Incident file. The Occupational Health physician should be notified by the Clinical Nurse Manager. The NICU Clinical Director and the Nurse Unit Manager will need to be contacted.
Inform medical staff immediately.
Contain gas by closing all nursery doors. The air-conditioning is to remain on. (In NICU this ensures a complete change of air every 15 minutes).
All parents and staff to leave the pod, closing doors.
Non-ventilated babies on heat tables or in cots should be removed from the pod.
Non ventilated babies in incubators should have air directed into their incubator from wall outlet.
Occupational Health Physician must be notified immediately (day or night, via the Clinical Nurse Manager) and will come in and assess the situation.
All staff/parents who have been exposed to Nitric Oxide must go to Auckland City Hospital Emergency Department to be examined and monitored as per advice from Occupational Health Physician. (Signs of toxicity may be delayed).
An on-line Datix form should be completed.
Storage
Store at room temperature. Is guaranteed for 1 year by NZIG Special Gases.
Cylinders must always be stored chained onto provided NO trolley.
Check for leakage from cylinders using snoop liquid leak detector: when regulators are attached to a new cylinder and anytime cylinders are moved.
A new cylinder should be ordered by NICU Nurse Manager when the cylinder is 1/2 empty. Full = 2000 psi