HFOV and Inhaled Nitric Oxide

Source: HFOV and Nitric Oxide 24 — 46 slides Author: Sammy Reed Learning levels: Foundation = Band 5 | Intermediate = Band 6 | Advanced = Band 7+

Part A: High-Frequency Oscillatory Ventilation (HFOV)

1. What is HFOV?

Learning level: Foundation

• Ventilation at supra-physiological frequencies (>= 1 Hz; 60+ breaths/min)
• Uses low tidal volumes (lower than dead space: 1-5 mL)
• Does not mimic normal ventilation
• Both inspiration and expiration are active processes (air is pushed in and pulled out)
• Often described as “CPAP with a wobble”
• Based on the open lung concept

2. Why Use HFOV?

Learning level: Foundation

Problems with conventional ventilation that HFOV addresses:

The goal: avoid both overstretching AND cyclic closing/opening of terminal units.

Clinical indications:

• Reduce risk of barotrauma
• Clinically worsening patients on high ventilator pressures
• Poor oxygenation
• Very sick patients (“last attempt” — though this should not be the threshold)

Evidence base:

• None of the paediatric RCTs demonstrated any survival benefit
• However, studies show children treated with HFOV:
  • Demonstrated improvements in oxygenation
  • Were exposed to less oxygen
  • Had less chronic lung disease

3. The Open Lung Concept

Learning level: Intermediate

“A method of ventilation intended to reduce shear forces caused by repeated opening and closing of atelectatic lung. This is done with a recruitment manoeuvre and application of sufficient PEEP to counterbalance retractive forces, and with ventilation at the smallest possible pressure amplitude to prevent lung overdistention.”

• Ventilate between the lower and upper inflection points of the pressure-volume curve

The “Safe Window”:

Cross-reference: The pressure-volume curve and safe window concept is also covered in detail in the 2019 deck (01-fundamentals-of-ventilation.md, Section 10.4).

• Safe window exists between the lower zone of atelectasis and upper zone of overdistension
• Ideally, tidal volumes should fit within this area by setting PEEP above the lower inflection point and reducing pressures to avoid overinflation
• In disordered lung, the safe window may be too small to harbour conventional tidal volumes — this is where HFOV is considered

4. Theory Behind HFOV

Learning level: Intermediate

• Preserves end-expiratory lung volume
• Minimises cyclic stretch
• Avoids parenchymal overdistension by limiting tidal volumes and transpulmonary pressure
• Volume delivered is often less than the patient’s dead space

How it works:

1. Delivers a constant flow of heated, humidified gas
2. Flow produces a continuous MAP (Mean Airway Pressure)
3. MAP is used to inflate the lung continuously — recruiting atelectatic lung units and optimising alveolar surface area for gas exchange
4. Oscillating pump vibrates the gas; forward/backward movements displace flow in and out of the circuit and patient
5. Amplitude (Delta P) controls the distance the oscillating pump travels from its resting position, which controls displaced tidal volume
6. Successful use is dependent upon ventilation with the lung recruited
7. Alveolar recruitment manoeuvres are required on initiation of HFOV and after disconnection/suction

Key parameters (children):

• MAP: 5-10 cmH2O
• Frequency: 3-8 Hz

Since TV is less than dead space, normal bulk flow is inadequate. Gas exchange occurs through several proposed mechanisms (see Section 5 below).

5. Mechanisms of Gas Exchange in HFOV

Learning level: Advanced

Since tidal volumes are smaller than dead space, normal bulk flow cannot explain gas exchange. Five mechanisms are proposed:

5.1 Turbulent Flow and Augmented Diffusion

• Gas moves from high concentration to low concentration
• High MAP opens alveoli and increases surface area for diffusion
• Kinetic energy supplied by the oscillator increases diffusion
• Diffusion is dependent on kinetic energy

5.2 Taylor Dispersion

• Oxygen-rich air from the oscillator flows in laminar flow down the centre of the airway, entraining gas closer to the airway walls
• Fresh gas is streamed into the alveoli
• Gas previously in the alveoli is displaced to the margins of the airways
• Dispersion of molecules beyond the bulk flow front

5.3 Pendelluft (“Swinging Air”)

• Works because of different time constants in the airways
• Time constant = Resistance (RAW) x Compliance
• Determines how quickly air gets in/out
• Patent alveoli = short time constant = fast movement of air in and out
• Atelectatic alveoli = long time constant = longer to open and close
• Some alveoli open while others close, moving air in and out at different times = mixing of gases
• Collateral channels open and close at different times, further mixing gases

5.4 Bulk Convection

• Movement of a group of molecules
• As O2 is absorbed, there is continual entrainment of fresh gas into the alveoli
• As O2 is absorbed, this creates more space for fresh O2 to enter

5.5 Cardiogenic Mixing

• Pulsing of the oscillator produces rhythmic mixing of gases
• Agitation of surrounding lung tissue with molecular diffusion
• This aids gas exchange

6. HFOV Settings

Learning level: Intermediate

The four key settings:

7. Adjusting HFOV Settings

Learning level: Intermediate

Gas exchange dependencies:

Adjustment table:

Weaning priority: Reduce FiO2 to < 40% before weaning MAP (except when over-inflation is evident).

CO2 removal — key principle (differs from conventional ventilation):

• A decrease in frequency leads to larger tidal volumes and therefore increased CO2 clearance (opposite direction to conventional ventilation)
• The lower the frequency, the greater the volume displacement (more ventilatory support)
• Increasing the amplitude also increases displacement of the piston, increasing tidal volumes and lowering CO2

Neonatal consideration:

• Cannot decrease frequency in neonates due to risk of BPD/lung injury (bigger pressure differences cause lung trauma)

Oscillation behaviour:

• Works by convective streaming: gases have high turbulence and velocity
• Inward gas travels in the middle of the airway; outward gas travels near the airway walls
• When airway resistance increases, oscillations reduce (e.g. secretion clearance is critical to maintain good VTs)
• Oscillations are damped by increased compliance
• Atelectatic alveoli experience higher oscillatory pressures, which improve recruitment and oxygenation

8. Clinical Uses of HFOV

Learning level: Foundation

Primarily used in neonates — the premature lung is highly susceptible to lung injury.

Contraindications (from 2019 deck):

• Obstructive lung disease (risk of gas trapping and hyperinflation)
• Intolerance to heavy sedation
• TBI/high ICP (CO2 removal may be difficult to monitor/achieve)

9. What the Patient Looks Like on HFOV

Learning level: Foundation

• Visible wobble through abdomen and chest
• Patient is muscle relaxed and sedated
• Potentially proned (to further aid oxygenation) — consider effectiveness of physiotherapy in this position

10. Disadvantages of HFOV

Learning level: Intermediate

• Unable to auscultate — will not hear added sounds (can only compare sides, check if one side quieter, listen for differences in pitch)
• Poor secretion clearance (do not want to disconnect and lose pressures; use inline suction)
• Noisy
• Requires sedation/paralysis
• Derecruitment on disconnection
• No feedback from ventilator regarding lung volumes, compliance, etc.
• Regular CXRs needed to monitor for and avoid hyper-expansion
• Impaired cardiac function: cardiac compression, pulmonary overdistension, compression of pulmonary blood vessels, impeding pulmonary perfusion
• Impedes venous return (constant pleural pressure and minimal lung volume changes = nearly constant intrathoracic pressure)
• May exacerbate gas trapping (if MAP is inappropriately low)

Complications:

• Hypotension
• Gas trapping

11. Important Monitoring Notes

Learning level: Foundation

Due to the way HFOV works, there will be NO respiratory rate, tidal volumes, or ETCO2 displayed. Patients will have more frequent CXRs and blood gases because other objective measures are limited.

Part B: Physiotherapy on HFOV

Learning level: Foundation to Intermediate

12. Indications for Physiotherapy

• Diminished chest wall movement (reduced chest wobble)
• Elevated CO2 and/or worsening oxygenation
• CXR changes
• Secretions suspected

The oscillator can push sputum to the peripheries and reduces clearance as there is no pressure change.

13. Before Treatment

• Time physiotherapy sessions with nursing cares
• Get a THOROUGH handover from the consultant — they need to know if you are going to treat the patient before you do
• Get a THOROUGH nursing handover (e.g. suction history, secretions, stability)

14. Full Assessment on HFOV

Assess:

• I+V (inspection and vital signs)
• OETT details
• HFOV settings: MAP, Delta P, Frequency
• FiO2
• SpO2

Auscultation limitations:

• Compare left and right
• Is one side quieter?
• Differences in pitch
• Unable to hear added sounds

15. Treatment Options

Learning level: Intermediate

Available techniques:

• Manual hyperinflation (MHI) via bag
• Percussions
• Vibrations
• Saline instillation
• Nebulisers (unless otherwise contraindicated)

Key considerations:

• Treating whilst connected to HFOV will not be effective as the machine is already wobbling the patient and there is no RR so cannot time vibrations
• Nebulisers can run through HFOV tubing but long tubing makes this less effective — more effective to bag through with an Aerogen and will likely make the patient more stable
• Keep HFOV tubing straight when turning the patient

16. Disconnection for MHI — Step-by-Step Procedure

Learning level: Intermediate

The goal of HFOV is to keep an open lung concept. Every disconnection causes derecruitment. Patients will have inline suction in the circuit.

MHI procedure:

1. Clamp ETT with gauze and blue clamp
2. Disconnect HFOV and attach MHI bag
3. Unclamp ETT
4. Begin bagging
5. Add ETCO2 connector into the circuit when disconnecting
6. Consider whether to keep inline suction in for physio or trial open suction

To reconnect — reverse the order:

1. Clamp ETT
2. Disconnect bag
3. Reconnect HFOV
4. Unclamp ETT

17. HFOV Machine Management During MHI

Learning level: Foundation

• HFOV machine will cut out if nothing is attached to it (e.g. when disconnected from ETT)
• A green rubber bung sits on top of the machine — this must go into the end of the HFOV tubing when you change to the bag
• If not done quickly, the machine will cut out
• Reset button needs holding down to turn it back on (not the start/stop button)
• Ensure a nurse is near the machine
• This may also happen when reconnecting the patient — be quick to restart

18. MHI Technique Considerations

Learning level: Intermediate

• Consider rate: HFOV is fast, so the patient may like a high rate (or may not — you will work it out)
• Think about pressures
• Now is the time to auscultate — you will hear normal sounds while the patient is on the bag
• Before reconnecting to HFOV at end of session: give long, slow inspiratory breaths with hold to re-recruit the patient

19. After Reconnecting to HFOV

Learning level: Foundation

• Common that the patient needs to re-recruit
• Increase FiO2 and can increase MAP by 2 cmH2O if required
• Sometimes may need to reconnect to the bag again — be ready

20. MDT Considerations

Learning level: Foundation

• If you are the first one to treat the patient: make sure a doctor is at the bedspace
• You will need lots of hands: nurses will probably complete repositioning with you, which may involve moving the HFOV machine

21. Suction on HFOV

Learning level: Intermediate

• Inline suction is present in the circuit
• You can remove for open suction during physio but weigh the risk of losing all pressure vs secretion clearance
• Open suctioning: every disconnection means MAP is lost; this disrupts MAP and causes derecruitment
• Will need increased FiO2 and possible recruitment manoeuvres (e.g. big inspiratory holds on bag)
• Therefore: yes to inline suction clamp

22. Summary and Key Points

Learning level: Foundation

• Problem-solve using good assessment skills
• Consider treatment options carefully
• Do not treat without talking to a consultant
• Ring your on-call buddy for support
• Ensure there are senior nurses to help

23. Knowledge Check Questions

1. Can we disconnect a patient from HFOV to MHI?
2. What can we consider doing before reconnecting to HFOV?
3. What can we do once we have reconnected them?
4. Is there anything we can do to allow us to suction without losing the MAP significantly?
5. If the child needs more O2, what can we do? What settings can we change?

Part C: Inhaled Nitric Oxide (iNO)

Learning level: Advanced

24. What is iNO?

• Nitric oxide is a potent vasodilator that can be inhaled
• Induces relaxation of vascular and bronchial smooth muscle and vasodilatation of surrounding blood vessels
• iNO reaches the patent alveoli and vasodilates the surrounding capillaries, increasing blood flow to ventilated areas
• Half-life: 3-5 seconds, rapidly inactivated on contact with haemoglobin
• Vasodilatory effect limited to well-ventilated regions of the lung
• This is called selective pulmonary vasodilation

25. Clinical Effects and Indications

Learning level: Advanced

Clinical effects:

• Reduces PVR (Pulmonary Vascular Resistance)
• Reverses V/Q mismatch
• Improves oxygenation
• Reduces baro/volutrauma

Clinical conditions:

• Neonates: Primary Pulmonary Hypertension of the Newborn (PPHN)
• Acute respiratory failure (ARDS)
• Congenital heart disease (CHD)

Considerations/risks:

• Can prolong bleeding
• Can cause surfactant dysfunction
• Oxidant injuries in premature infants
• Expensive: costs GBP 26-90 per hour
• Avoid contact with iNO if pregnant

26. Evidence Base

Learning level: Advanced

Respiratory failure:

• Inconclusive evidence for iNO in treatment of respiratory failure in children; benefits appear to be transient and do not affect long-term outcomes (Dobyns et al 1999; Dobyns 2002; Goldman 1997; Bronicki et al 2015)
• iNO is NOT recommended for routine use in pre-term newborns with respiratory failure (Barrington et al 2017)
• iNO IS recommended for use in term and near-term newborns with respiratory failure (Barrington et al 2017)

Pulmonary hypertension:

• Large body of evidence supports iNO in newborns with PPHN; approved for treatment (NICE 2020)
• CINRGI trial (Clark et al 2000): Low doses of iNO (initiated at 20 ppm, titrated down to 5 ppm) reduced need for ECMO, increased oxygen tension, and reduced chronic lung disease in PPHN
• Bronicki et al (2015): NO associated with significantly reduced time on a ventilator and less need for ECMO (40% less likely), but no significant difference in survival at 28 days

27. iNO Toxicity and Dosing

Learning level: Advanced

• Get off as soon as possible
• Start at 20 ppm and wean quickly (increase O2 at same time)
• Use lowest effective dose: 2-20 ppm

28. iNO Machine Setup

Learning level: Intermediate

Top of the machine:

• Top left number: FiO2 (may differ from what the vent or HFOV reads due to oxygen blending with nitric; the FiO2 on the nitric machine is the accurate reading, not the vent/HFOV number)
• Middle number: Ignore
• Top right number: Amount of nitric oxide in ppm (parts per million); starts at 20, slowly weaned down over a few days

Bottom of the machine (for MHI):

• The bag connects to the iNO machine instead of the oxygen flow meter at the bedspace
• Already set up by nursing staff
• Middle dial: Turn to whatever the nitric is reading (top right number in ppm)
  • Complete this as you are about to disconnect (expensive, do not want it escaping)
  • When reconnecting the patient, turn the dial back to 0
• Right-hand side: Flow meter
  • Turn up to 10 L/min for small bags
  • Turn up to 15 L/min for big bags

29. iNO and Physiotherapy

Learning level: Advanced

CRITICAL SAFETY POINT: Do NOT disconnect iNO to perform MHI. This can cause a sudden rise in pulmonary artery pressure and severe strain on the right side of the heart, as well as potential hypoxaemia. Instead, connect the bag to the iNO machine.

• Physiotherapy can help clear the lungs of sputum and improve airflow for iNO to reach the alveoli
• This aids vasodilation, improving V/Q matching and gas exchange

Part D: References

• Bronicki et al (2015). Multicenter Randomized Controlled Trial of Inhaled Nitric Oxide for Pediatric Acute Respiratory Distress Syndrome. The Journal of Paediatrics, 166(2), 365-369.
• Dobyns EL et al (2002). Interactive effects of high-frequency oscillatory ventilation and inhaled nitric oxide in acute hypoxemic respiratory failure in paediatrics. Critical Care Medicine, 30(11), 2425-2429.
• Goldman AP, Tasker RC, Hosiasson S, Henrichson T, Macrae DJ (1997). Early Response to Inhaled Nitric Oxide and Its Relationship to Outcome in Children With Severe Hypoxemic Respiratory Failure. Chest, 112(3), 752-758.
• Barrington KJ, Finer N, Pennaforte T, Altit G (2017). Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database of Systematic Reviews, 1. DOI: 10.1002/14651858.CD000399.pub3.
• Barrington KJ, Finer N, Pennaforte T (2017). Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database of Systematic Reviews, 1. DOI: 10.1002/14651858.CD000509.pub5.
• Higenbottam TW, Dinh-Xuan AT, Stone D, Wallwork J (1991). Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. The Lancet, 338(8776), 1173-1174.
• Bizzarro M, Gross I, Barbosa FT (2014). Inhaled nitric oxide for the postoperative management of pulmonary hypertension in infants and children with congenital heart disease. The Cochrane Database of Systematic Reviews, 7. DOI: 10.1002/14651858.CD005055.pub3.
• Clark RH et al (2000). Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. N Engl J Med, 342, 469-74.
• Kelly LE, Ohlsson A, Shah PS (2017). [Reference truncated in source]
• NICE (2020). Guidance on iNO in PPHN.
• Paediatric FOAM — HFOV: https://www.paediatricfoam.com/2019/02/hfov/
• LITFL — High Frequency Oscillation Ventilation: https://litfl.com/high-frequency-oscillation-ventilation/
• Auckland DHB HFOV Guidelines: http://www.adhb.govt.nz/newborn/guidelines/respiratory/hfov/hfov.htm