Question 3

College answer

Definition & Equipment:
Variable FiO2 high flow (20L/min or more), humidified and heated to 37oC applied by specific nasal 
cannulae. The cannulae are soft, and have a wide aperture; such that the gas velocity is less for a 
given flow than conventional cannulae; this aids in patient tolerance.

Use:
• Varied and has become common and widespread
• Hypoxaemic respiratory failure of any cause
• Post extubation
• Maintenance of oxygenation during procedures (intubation, bronchoscopy, 
TOE, GI endoscopy)
• Paediatrics
• May be used in hypercapnic respiratory failure as reduces dead space; less 
evidence in this group
• Oxygen therapy in treatment limitation / palliation / not for intubation settings

Rationale & Physiologic Advantages:
• High flow “washes” dead space
• Mechanical splinting of nasopharynx prevents supraglottic collapse
• Small amount of CPAP with effects on work of breathing
• Well tolerated generally, and therefore
• Consistent oxygenation
• Known and titratable FiO2; potentially reduces periods of hypoxia and hyperoxia
• Humidification may be of benefit in reducing epithelial injury in patients with hyperpnoea

Disadvantages:
• PEEP is variable and difficult to measure
• PEEP drops to ~2 cmH2O when mouth open
• More costly and more complex to set up than standard nasal cannulae

Adverse effects:
• Local trauma, discomfort and pressure areas 
• Epistaxis
• Gastric distension
• Secretions block cannulae
• May delay intubation and lead to worse outcomes 
• Excessive PEEP may cause PTX in neonates

Evidence:
• NEJM Study; Frat et al (France) 2015 (DOI: 10.1056/NEJMoa1503326)
o Multicenter
o NIV vs FMO2 vs HFNP
o No change in intubation rates
o Mortality advantage over NIV and face mask O2
o Favourable editorial at the time

• Other studies:
o Some have shown decreased re-intubation rates
o THRIVE as pre-oxygenation may be better than RSI
o Delays intubation (Kang, 2015)
o o THRIVE (Anaesthesia, Pateal, 2015) Mean apnoea time in difficult intubations 14min, 
but PREOXYFLOW (Vour’ch, 2015) lowest SpO2 no better than high flow face mask
o Post extubation HFNP x24h equivalent to NIV (Hernandez, JAMA 2016)

Summary statement and personal practice opinion.

Additional Examiners Comments: 
Many candidates failed to list the indications for this therapy and the knowledge of the evidence and patient groups studied was poor.

Discussion

Question 2 from the first  paper of 2013 asked for indications, contraindications and complications of high flow nasal prong therapy. To cover all bases, the High Flow Nasal Prongs revision chapter was written to answer Question 2 as if it were a "critically evaluate" style SAQ. Then, in this paper, that effort was justified by an actual "critically evaluate" SAQ.

Thus:

Rationale for the use of high flow nasal prongs (HFNP)

• Pharyngeal dead space washout
• Improved oxygenation by PEEP effect (minor though it may be)
• Improved oxygenation by oxygen dilution reduction (at high resp rates)
• Benefits of humidification
• Increased comfort
• HFNP may be appropriate in circumstances where NIV is not (eg. oesophageal surgery)
• HFNP may be used for apnoeic oxygenation as an alternative to the standard mask (eg. PREOXYFLOW and THRIVE trials )

Clinical applications

• As a stand-alone therapy for hypoxic respiratory failure, in which case it could be used in any sort of respiratory failure
• Instead of NIV:
  • When positive pressure is contraindicated, eg. oesophagectomy
  • When the patient is intolerant of NIV (eg. delirium)
  • When clearance of secretions must be maintained, but the patient is too hypoxic for conventional oxygen delivery devices (eg. in pneumonia)
• Instead of intubation:
  • In patients whom it is inappropriate to intubate (i.e. as a palliative measure)
  • In patients for whom intubation is associated with a worse outcome, eg. febrile neutropenic patients and those recovering from bone marrow transplant.
• Prior to intubation, as preoxygenation
  • May significantly improve preoxygenation and reduce episodes of hypoxia (Miguel-Montanes et al, 2015)- but not all trials have been able to confirm this.

Limitations of HFNP and contraindications to their use

• The patient must be able to protect their airway
• The nose must be intact (i.e. its not obstructed, fractured, or
• The base of skull should be intact (in base of skull fracture you might induce a pneumocephalus and god knows what else)
• There should be no epistaxis (or the blood will end up being aspirated)
• If there has been recent nasal surgery, HFNP may do damage the operative site
• If there has been recent oesophageal surgery, use of HFNP must be weighed against the risk of anastomotic breakdown (though it could still be used, and is safer than NIV)
• There is some PEEP, but it is not measured, and is completely unpredictable
• If the patient requires intubation and intubation is delayed because of people wasting time experimenting with HFNP, the outcome may be worse.

Potential adverse events associated with HFNP

• Overdistension of the alveoli, and barotrauma
  • In fact, in neonates this may lead to pneumothorax - and it is slightly thrilling that the college mention this (it was a part of the old Deranged Physiology HFNP article; did an examiner read it, or did we all arrive at the same answers simultaneously? Either way, it leads to mildly raised neck-hairs).
• Nasal mucosal damage due to high flow
• Pressure areas due to the device
• Aspiration of food
• Patient discomfort, including irritation by the annoying hissing sound

Evidence in the literature:

Parke et al (2011):  one of the first studies comparing HFNP and standard high-flow face mask

• 60 patients randomised to either normal mask or HFNP
• Main outcome measure was having to resort to NIV
• HFNP group did much better (10% rate of NIV vs. 30% for the standard mask)

FLORALI trial (2015): multicenter open-label trial, 310 patients

• Only hypoxic patients were selected (P/F ratio <300) - hypercapnea was excluded
• Primary outcome was intubation rate, secondary outcome was mortality
• HNFP was compared to standard oxygen and NIV
• There was no difference in intubation rate, but somehow there was a improvement in 90 day mortality associated with the use of high-flow oxygen.
• The NIV group had 9ml/kg tidal volumes, which may have influenced their mortality by exacerbating their lung injury
• Of the intubated and NIV patients, more died of shock rather than respiratory failure.

PREOXYFLOW (2015): multicenter open-label trial,124 patients

• Randomised to either high flow oxygen mask (removed at the end of intubation) or high flow nasal prongs (kept on during the whole process).
• The main point was to see whether an apnoeic patient would benefit from high flow oxygen blowing into their airway; theoretically they should desaturate more slowly during the intubation attempt because pure oxygen from the HFNP-irrigated upper airways will be entrained into the lung by mass transfer.
• No such effect was seen (a statistically insignificant difference of 1% SpO2 was found).

THRIVE (2014): observational case series of 25 patients with difficult airways

• HFNP was commenced prior to the induction of anaesthesia
• While maintaining jaw thrust, HFNP delivered oxygen to the apnoeic patient (apnoea time was counted from the administration of muscle relaxant)
• Median apnoea time was 14 minutes (ranging from 9 to 19 minutes) and the patients did not desaturate beyond 90%.
• Given that half of these patients were obese and a third had stridor, this is an outstanding result. Amazed authors concluded that this technique "has the potential to transform the practice of anaesthesia".

S68 Hi-Flo study (2014): Randomised controlled trial of 72 babies under 18 months of age

• Bronchiolitis was the specific pathology under investigation
• Comparison of 2L vs 8L O₂
• There was a minor improvement of clinical parameters (a modified Tal score), but no real difference otherwise

BiPOP (2015): Multicenter, randomized trial in 830 post-op cardiothoracic patients

• Inclusion criteria were respiratory failure after surgery, or those who were "deemed at risk" of this following extubation
• The patients were then randomised to either HFNP or NIV
• HFNP was non-inferior: the rate of reintubation was the same in both groups
• There was also no difference in ICU mortality.
• NIV produced more skin pressure areas, but was otherwise equivalent.

Groves, Nicole, and Antony Tobin. "High flow nasal oxygen generates positive airway pressure in adult volunteers." Australian Critical Care 20.4 (2007): 126-131.

Ricard, J. D. "High flow nasal oxygen in acute respiratory failure." Minerva Anestesiol 78.7 (2012): 836-841.

Locke, Robert G., et al. "Inadvertent administration of positive end-distending pressure during nasal cannula flow." Pediatrics 91.1 (1993): 135-138.

O’Brien, Bj, J. V. Rosenfeld, and J. E. Elder. "Tension pneumo‐orbitus and pneumocephalus induced by a nasal oxygen cannula: Report on two paediatric cases." Journal of paediatrics and child health 36.5 (2000): 511-514.

Corley, Amanda, et al. "Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients." British journal of anaesthesia (2011): aer265.

Boyer, Alexandre, et al. "Prognostic impact of high-flow nasal cannula oxygen supply in an ICU patient with pulmonary fibrosis complicated by acute respiratory failure." Intensive care medicine 37.3 (2011): 558-559.

Stéphan, François, et al. "High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial." JAMA (2015).

Miguel-Montanes, Romain, et al. "Use of high-flow nasal cannula oxygen therapy to prevent desaturation during tracheal intubation of intensive care patients with mild-to-moderate hypoxemia*." Critical care medicine 43.3 (2015): 574-583.

Kang, Byung Ju, et al. "Failure of high-flow nasal cannula therapy may delay intubation and increase mortality." Intensive care medicine 41.4 (2015): 623-632.

Frat, Jean-Pierre, et al. "High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure." New England Journal of Medicine (2015).

Vourc’h, Mickaël, et al. "High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial." Intensive care medicine (2015): 1-11.

Patel, A., and S. A. R. Nouraei. "Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways." Anaesthesia 70.3 (2015): 323-329.

Hathorn, C., et al. "S68 The Hi-flo Study: A Prospective Open Randomised Controlled Trial Of High Flow Nasal Cannula Oxygen Therapy Against Standard Care In Bronchiolitis." Thorax 69.Suppl 2 (2014): A38-A38.

Parke, Rachael L., Shay P. McGuinness, and Michelle L. Eccleston. "A preliminary randomized controlled trial to assess effectiveness of nasal high-flow oxygen in intensive care patients." Respiratory Care 56.3 (2011): 265-270.

Vourc’h, Mickaël, et al. "High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial." Intensive care medicine 41.9 (2015): 1538-1548.