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Nitric Oxide

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Introduction

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.

It is a potent vasodilator. 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.

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 echocardiography/ultrasound; OR
  • Severe respiratory failure (i.e. oxygenation index>25, PaO2 <60 mmHg despite 100% FiO2)

Prescribing of 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) including all changes in concentration.

Dose and administration

See Nitric Oxide Drug Protocol

Administration via Drager Babylog (in all modes) or SensorMedics

The following equipment is required:

Nitric Oxide Accessory Pack for Drager VN500 or Sensormedics

  • Neonatal Nitric Accessory Kit for VN500
  • Scavenging set for the sensormedics is placed on circuit at time of set up
  • Two Elbow connectors (Sensormedics)
  • Two Nitric Oxide tank extension sets (anaesthesia gas sampling line) and one three way tap (to connect b)
  • Printer Nitric Oxide connector
  • Metal Neopuff Nitric Oxide connector (not disposable)

Assemble Circuit

  • Add the required equipment from Nitric Oxide Accessory Pack
 Set Up for Nitric Oxide via Drager Ventilators using Printer NOx
 New setup                  Setup using Printer
New setup shown above left
Nitric Oxide Administration
Insert Nitric T piece into humidifier dry side
• Attach gas sample line from Nitric cylinder
• Insert monitoring line as usual on inspiratory limb at manifold
  (closest to infant)
• Turn on Nitric flow until desired ppm achieved
• (This will reduce the rainout from the unheated extension of tubing)
 Administration
NO via SensorMedics HFOV showing Connections Needed
Sensor medics Sensormedics1
Sensormedics 2 Sensor medics 3
Sensor medics 4


Scavenging system for SensorMedics
Scavenging sensor 1 Scavneging sensor 2 Scavenging 3  
Nitric on Hudson CPAP

Sampling line

See photo above of CPAP prongs and attachments showing where to put in the sampling line for the Printer NOX
Neopuff attachment

Neopuff 1   Neopuff 2

See photos above of 3 way tap with 2 sampling lines - one to vent circuit and one to neopuff attachment. When neopuffing turn 3 way tap on to neopuff.

Nitric Oxide set up for HFOV

Photo displaying circuit set up for Nitric Oxide (NO) administration via SensorMedics Oscillator

HFOV

Process to commence administration of Nitric Oxide

  1. Ensure circuit is set up correctly as per appropriate diagram:
    3 way tap attached to flow meter on the cylinder.
    Attach a sampling line to each port. One sampling line is attached to the nitric T piece which is fitted to the humidifier dry side as per picture.
    Printer NOx plus sampling line attached to nitric adaptor on the inspiratory limb at the manifold, close to the infant.
  2. Doctor/NS-ANP prescribes the required nitric oxide flow rate in ventilation settings prescription on the infants observation chart.
    Doctor/NS-ANP is to be present when NO flow is turned on:
    1. On cylinder: either one knob or two knobs - middle knob first (different cylinder heads in service)
    2. Flow meter: 0.2 litres (200mls) per min with a gas flow of 10 litres per minute gives around 17ppm (check approximate concentration using the nitric oxide calculator)
    3. 2 nurses check that the prescribed flow rate is set.
      Monitor nitric oxide and nitric dioxide levels in the circuit continuously and record hourly on the infants observation chart.

Please note: The circuit should not be routinely changed while the infant is on Nitric Oxide.
The NO cylinder is checked for leaks using a "snoop liquid leak detection" (instructions on bottle):

  • when regulator is attached to a new cylinder
  • if leak suspected

Contraindications and precautions

See Nitric Oxide Drug Protocol

Possible adverse effects

See  Nitric Oxide Drug Protocol

Monitoring

Printer NOx

The printer NOx is a combined Nitric Oxide (NO)/Nitrogen Dioxide (NO2) monitor based on electrochemical fuel cells. It pumps a constant gas flow of 250ml/min through to obtain a measurement.

Printer Nox

Process

Follow the steps below when preparing Printer NOx for use

  1. When not in use and for long term monitoring, keep printer NOx plugged into mains power. Printer NOx has batteries with a life of 3 hours.
  2. Connect the water trap and sampling line (single patient use) into machine (see diagram).
  3. Switch on Printer NOx (switch is at rear of machine). An introduction screen and printing occurs at this point.
  4. Calibration status then shows on screen. Calibration will be performed monthly by Anaesthetics. If calibration is due to be performed and machine is in use it can be overridden by pressing enter and sampling will continue. Send Printer NOx for calibration when free.
  5. Press enter. This displays the 'select option' menu. To acquire:
    - Measurement - press 1
    - Set alarms - press 3
    - To return to menu - press 4
  6. To set alarms:
    Press enter to bring up menu.
    Press 3 to bring up alarm options.
    - Set NO alarm at 5 above and 3 below prescribed amount of NO.
    - Set NO2 at 1.
    Press 4 to return to previous select option menu.

NB: The Printer NOx will default to measuring after 45 seconds.

Emptying Water Trap for Printer NOx

Water trap

  1. Take extreme care with water trap. Empty when near full or when instructed by the machine 'empty water trap.
  2. Unscrew the two retaining screws and remove the water trap from the Printer NOx.
  3. Disconnect the NO sampling line from surfactant connector and occlude the hole with a luer plug.
  4. Connect syringe adapter to water trap (filter end).
  5. Connect 20ml syringe to adapter.
  6. Use specimen pot to collect water from sampling line.
  7. Flush with air through the water trap and NO sampling line to empty water trap.
  8. Reconnect water trap to the Printer NOx and secure with the two retaining screws.
  9. Reconnect NO sampling line to surfactant connector.
  10. Press 1 for measuring to continue.

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.

  1. Concentration of Nitric Oxide is adjusted and documented by Doctor/NS-ANP on ventilator chart in ppm.
  2. Nursing staff:  An experienced Level 3 Nurse or Level 4 Nurse who has completed the NO/HFV workbook, cares for baby
  3. Ensure at the beginning of each shift the concentration of NO prescribed on ventilation chart is consistent with the level showing on the Printer NOx and signed as correct by the nurse handing over and nurse taking over the care of the infant.
  4. 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.
  5. If NO readout levels rise rapidly, check that there is not a leak or loose fitting in ventilator circuit. If ventilator alarms indicating no gas flow from ventilator, bag baby turning the 3 way tap to the NO sampling line to the Nitric adapter delivery line of Neopuff (otherwise baby receives 800ppm NO).
  6. If NO2 levels >1ppm notify Doctor/NS-ANP. NO2 levels should not exceed 3 ppm.
  7. Methaemoglobin levels should not exceed 3% (measured with each arterial blood gas). Inform medical staff if levels are rising.
  8. Observe water trap in Printer NOx sampling line and empty PRN. If this over fills, water will run back to baby.
  9. Monitor Blood Pressure continuously and document hourly.
  10. 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).
  11. During a circuit change hand bag baby until NO and NO2 monitoring is stable (Doctor/NS-ANP present).
  12. 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.
  13. Observe and monitor baby closely for signs of deterioration during any trial off NO. (Consultant orders this to determine need for continuing NO administration)
  14. Replace cylinder if less than 300 pounds per square inch (psi). (If baby is on i.e. 20ppm of NO and a ventilator flow of 10, the cylinder only drops one little line over 24 hour period.). CCN to order new cylinder.

Weaning iNO and FiO2

See Nitric Oxide Drug Protocol

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 800ppm NO. A full cylinder completely emptying into a room would give 80ppm.
  • Air conditioning clearance in NICU is 15-20mins. Air is cleaned to outside the building, i.e., is not recycled to other areas of the Hospital.
  • Recommended maximum environmental exposure is 5ppm 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.

  1. Check the cylinder pressure.
  2. Check the cylinder connections. Use "snoop liquid leak detector".
  3. Note the symptoms and conditions and exposure of any staff (see previous page re signs of Toxicity NO and NO2).
  4. Notify Clinical Nurse Manager who will contact the Occupational Physician on call for appropriate assistance.
  5. Change the cylinder and connections, if available. (Call shift engineer to do this).
  6. 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).
  7. Rotate the staff to a non contaminated pod.
  8. 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.
  9. Repeat these observations hourly for a total of 6 hours or more frequently if indicated. (Occupational Health will advise where monitoring to occur).
  10.  Refer the staff member for assessment if concerned.
  11.  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.
  12.  An on-line Datix form should be completed.

Emergency management of a major leak

A major leak is sudden decompression of the cylinder.

  1. Close the regulator tap.
  2. 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.
  3. Inform medical staff immediately.
  4. 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).
  5. All parents and staff to leave the pod, closing doors.
  6. Non-ventilated babies on heat tables or in cots should be removed from the pod.
  7. Non ventilated babies in incubators should have air directed into their incubator from wall outlet.
  8. Occupational Health Physician must be notified immediately (day or night, via the Clinical Nurse Manager) and will come in and assess the situation.
  9. 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).
  10. An on-line Datix form should be completed.

References

  1. Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD000509. DOI: 10.1002/14651858.CD000509.pub5 
  2. Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD000399. DOI: 10.1002/14651858.CD000399.pub3 
  3. Baczynski M, Ginty S, Weisz DE, et al. Short-term and long-term outcomes of preterm neonates with acute severe pulmonary hypertension following rescue treatment with inhaled nitric oxide. Arch Dis Child Fetal Neonatal Ed 2017;102:F508-F514. Doi:10.1136/ archdischild-2016-312409.

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Document Control

  • Date last published: 03 October 2018
  • Document type: Clinical Guideline
  • Services responsible: Neonatology
  • Owner: Newborn Services Clinical Practice Committee
  • Editor: Sarah Bellhouse
  • Review frequency: 2 years