Apnoeic oxygenation

OVERVIEW

Apnoeic oxygenation is used to extend the ‘safe apnoea time’ beyond that which can be achieved by preoxygenation alone

• Apnoeic oxygenation is merely an adjunct, it is not a substitute for effective preoxygenation
• Apnoeic oxygenation is most commonly provided using nasal cannulae in addition to a face mask

SAFE APNOEA TIME

Safe apnoea time is the duration of time until critical arterial desaturation (SaO2 88%-90%) occurs following cessation of breathing/ventilation

• an alternative term in use is duration of apnoea without desaturation (DAWD)
• SaO2 88%-90% marks the upper inflection point on the oxygen-haemoglobin dissociation curve beyond which further decreases in PaO2 leads to a rapid decline in SaO2 (~ 30% every minute)
• In a healthy preoxygenated patient the safe apnea time can be up to 8 or 9 minutes, compared to ~1 min if they were breathing room air
• In critically ill patients critical desaturation can occur almost immediately despite optimal attempts at preoxygenation

Factors that decrease safe apnoea time include:

• inadequate preoxygenation
• airway occlusion (see below)
• pulmonary shunt
• increased oxygen consumption (VO2) (e.g. high metabolic rate, fasciculations from suxamethonium)
• critical illness
• obesity
• pregnancy
• small children

In patients who develop airway occlusion, desaturation will occur more rapidly due to loss of functional residual capacity (FRC)

• FRC usually decreases by 200-250 mL during the first minute after airway occlusion in a healthy adult patient
• This occurs due to resorption atelectasis as oxygen transfers from the lungs into the pulmonary circulation
• Pulmonary shunting (blood flow to the non-oxygenated, collapsed lung units) can now occur resulting in much more rapid desaturation than otherwise predicted — even when effective preoxygenation is performed

PHYSIOLOGY OF APNOEIC OXYGENATION

Alveoli will continue to take up oxygen even without diaphragmatic movements or lung expansion

• In a healthy apnoeic patient, ~200-250 mL/min oxygen will move from the alveoli into the bloodstream
• Only ~8-20 mL/min of carbon dioxide moves into the alveoli during apnea, with the remainder being buffered in the bloodstream given the high water solubility of CO2
• This causes the net pressure in the alveoli to become subatmospheric, generating a mass flow of gas from pharynx to alveoli

In healthy people under ideal circumstances, PaO₂ can be maintained at >100 mm Hg for up to 100 minutes without a single breath, although the lack of ventilation will eventually cause marked hypercapnia and significant acidosis

• this assumes effective preoxygenation, ongoing provision of high flow oxygen and maintenance of a patent airway

Nasal cannulae can be used for apnoeic oxygenation because the pharynx fills with high FiO2 gas and functions as an oxygen reservoir, even when the mouth is open (a patent airway must be maintained!)

PROCEDURE

• ensure patient is preoxygenated with nasal cannula in situ (15 L/min oxygen flow rate) (see Preoxygenation)
• administer induction agent
• maintain the nasal cannula flow rate at 15 L/min and adminster oxygen via bag-valve-mask (BVM) as well
• If SpO2 <95% consider apneic oxygenation with positive pressure
  • CPAP or with BVM with PEEP valve with coexistent administration of oxygen at 15 L/min via nasal cannulae
  • alternatively, abandon apnoeic oxygenation and provide 6 gentle ventilations/minute (<15cmH20) if the risk:benefit of apnoea is unfavourable)
• maintain a patent airway until the time of intubation using:
  • Two-handed face-mask technique with jaw thrust
  • nasopharnygeal airway(s)
  • oropharyngeal airway
• remove the mask at the time of intubation, but continue to oxygenate via the nasal cannulae
  • this has been termed “NO DESAT” (nasal oxygen during efforts securing a tube) by Rich Levitan

EVIDENCE

Tracheal oxygenation

• Half a dozen observational studies with small numbers of patients showing that safe apnoea times can be prolonged up to 55 minutes with apnoeic oxygenation provided by tracheal catheters or equivalent devices
• This technique is widely used in ICU patients during the apnea test for brain death
• More recently Rudlof and Hohenhorst (2013) found that apnoeic oxygenation via a tracheal catheter was well tolerated during ENT procedures for up to 45 minutes in over 40 patients. Exceptions were 2 patients where the technique was not performed correctly and 1 obese patient who could not be adequately oxygenated

Additional studies of apnoeic oxygenation using nasal cannulae are described below.

Systematic reviews and meta-analyses

• Oliveira J E Silva et al (2017) conducted a meta-analysis of 8 studies (1,837 patients) and found that apneic oxygenation during emergency intubation. was associated with increased peri-intubation oxygen saturation, decreased rates of hypoxemia, and increased first-pass intubation success.
• Binks et al (2017) performed a systematic review and meta-analysis of six studies (518 patients) of Apnoeic oxygenation during intubation in the ICU. Apnoeic oxygenation reduces patient hypoxaemia during intubation performed in the ICU. This meta-analysis found evidence that apnoeic oxygenation may significantly reduce the incidence of critical desaturation and significantly raises the minimum recorded SpO2 in this setting.
• White et al (2017) performed a meta-analysis of 11 studies and found strong evidence for benefit of apnoeic oxygenation in terms of improved SpO₂ in elective surgical patients, obese patients and those undergoing emergency intubation without respiratory failure, but not in patients with respiratory failure.

FELLOW trial, 2015

• Single-centre, randomised controlled trial
  • Allocation concealment, treating clinicians non-blinded
  • Data collection was by independent observers unaware of the study design
  • intention to treat analysis
• Population
  • n=150 Medical ICU patients at Vanderbilt 18+ years old intubated by a pulmonary and critical care medicine fellow
  • Additional 46 were excluded
    • 23 required intubation too urgently, 18 were felt to require video or fiberoptic intubation, 1 was felt to require direct laryngoscopy, 1 was felt to require apneic oxygenation, 3 excluded for unknown reasons.
• Intervention/ Comparison
  • apneic oxygenation (n=73)
  • usual care (n=73)
  • patients were also randomised to video laryngoscopy or directed laryngoscopy
• Outcomes (apox vs usual care)
  • No statistically significant difference in:
    • Median lowest arterial oxygen saturation: 92% vs 90% (95% CI 1.6 – 7.5%; p = 0.16)
    • Incidence of oxygen saturation <90%: 44.7% vs 47.2% (p = 0.87)
    • Incidence of oxygen saturation <80%: 15.8% vs 25.0% (p = 0.22)
    • Incidence of decrease in oxygen saturation >3%: 53.9% vs 55.6% (p = 0.87)
    • duration of mechanical ventilation, ICU length of stay, and in-hospital mortality
• Commentary and criticisms:
  • Study design
    • Pragmatic design with other treatments left to treating physicians
    • had 80% power to detect a mean lowest arterial oxygen saturation difference of 4.6%
    • Lack of blinding (could not be avoided)
  • High likelihood of selection bias due to difficult airways/ sicker patients being excluded from the trial:
    • patients deemed to benefit from a particular strategy (e.g. suspected difficult airways or prolonged intubation times – the precise patients expected to benefit from apnoeic oxygenation)
    • true emergencies and could not be randomised were excluded
    • 75% of intubations were rated “easy” – these patients are unlikely to benefit from apnoeic oxygenation
  • Lack of external validity
    • Most patients in both arms were not truly apnoeic prior to laryngoscopy
      • 73% of patients received either BVM or NIV up until laryngoscopy
      • this is a critical flaw – these patients clearly will not benefit ‘apnoeic oxygenation’ as they are being ventilated!
    • Airway patency must be strictly maintained during apnoeic oxygenation for it to work, specific measures on how to achieve this was not part of the protocol and data on airway patency is not provided for the ~2/3 patients who were not receiving NIV
    • May not be generalisable outside of PulmCCM Fellow led medical ICUs (patient and skill mix)
    • A study powered to detect differences in reaching critical desaturation, rather than absolute difference on SpO2, may be more clinically relevant
• Conclusion
  • This study found no benefit or harm with using nasal cannulae for apnoeic oxygenation in medical ICU patients requiring intubation. Apnoeic oxygenation is only likely to benefit patients with difficult airways and prolonged intubation times who are truly apnoeic prior to intubation. These patients were under-represented in this study which greatly limits it’s external validity.

Dyett et al, 2015

• prospective observational study of intubations outside of the operating theatre
• no episodes of hypoxaemia in the 31 patients that used apnoeic oxygenation with nasal prongs, whereas 10 of 60 patients that did not have apnoeic oxygenation developed hypoxaemia
• The calculated NNT for apnoeic oxygenation is 6
• There may be important confounders, given the observational design of this study

Wimalesena et al, 2015

• Retrospective analysis of 9,901 NSW HEMS missions
• 728 rapid sequence intubations (310 pre- and 418 post apnoeic oxygenation)
• introduction of apneic oxygenation (with nasal prongs) was followed by a decrease in desaturation rates from 22.6% to 16.5% (ARR=6.1%; 95% CI 0.2% to 11.2%)
• Subject to multiple confounders due to retrospective study design

THRIVE, 2014

• 25 patients who underwent general anaesthesia for hypopharyngeal or laryngotracheal surgery; included 12 obese patients and 9 patients were stridulous
• patients had “Transnasal Humidified Rapid-Insufflation Ventilatory Exchange”: continuous delivery of transnasal high-flow humidified oxygen, initially to provide pre-oxygenation, and continuing as post-oxygenation during IV induction of anaesthesia and neuromuscular blockade until a definitive airway was secured. Airway was kept open with jaw thrust
• The median apnoea time was 14 (5-65) min, no patient experienced arterial desaturation < 90%

Ramachandran et al, 2010

• RCT of obese operative patients, n=30
• Nasal cannula attached to 5 L/min 100% FiO₂ versus room air
• Apnoeic oxygenation group had significant prolongation of SpO₂ ≥95% time (5.29 versus 3.49 min), a significant increase in patients with SpO₂≥95% at the 6-min mark (8 patients versus 1 patient), and significantly higher minimum SpO₂ (94.3% versus 87.7%)
• not blinded

Taha et al, 2006

• RCT, n=30
• Nasal catheters attached to 5L/min of 100% FiO₂ versus room air
• No desaturation during the course of the 6-min predetermined stopping point in patients receiving apnoeic oxygenation, whereas the control group desaturated to the study cutoff of 95% in an average of 3.65 min
• not blinded

Teller et al, 1988

• RCT, blinded, crossover trial, n=12
• Nasopharyngeal catheters attached to 100% FiO₂ at 3 L/min versus room air
• None of the patients in the insufflation arm desaturated below 98% during the 10 min

Evidence for apnoeic oxygenation in humans prior to 2012 is summarised here (from Levitan and Weingart, 2012)

OTHER INFORMATION

In addition to intubation, apnoeic oxygenation is also used in other circumstances:

• during brain death studies
• during bronchoscopy
• at the end of elective anaesthesia cases when allowing CO2 to build up and stimulate spontaneous breathing

Nasal cannula

• Nasal cannulae at 15 L/min has no significant adverse effects in the sedated patient with short-term use, and is even well tolerated in awake patients (Brainard et al, 2015). The desiccating effect is uncomfortable in the longer term in awake patients
• Can be used with non-rebreather masks as well as BVM, however a BVM will provide better preoxygenation that a NRB mask and allows for rescue ventilation
• Although flow meters for wall oxygen have 15 L/min as the maximum setting (gives FiO2 0.6 via NRB) if over-dialed up to 30-60 L/min flow can be achieved (gives FiO2 0.8-0.9 via non-rebreather mask). The flow rates achieved by over-dialing may vary between centers and countries.
• If nasal cannulae compromise the seal of the face mask, they can be placed above the face mask until just prior to attempting laryngoscopy, at which point they are placed in the nares
• High flow nasal cannulae have been used for apnoeic oxygenation (e.g. THRIVE study) however they are more likely to impair face mask seal during preoxygenation and some devices do not generate high enough FiO2

Bag-Valve-Mask (BVM) with PEEP valve for apnoeic oxygenation

• A bag-valve mask (BVM) with a one-way valve or PEEP valve has been demonstrated to provide oxygen concentrations close to that of an anaesthesia circuit, but its effectiveness is drastically reduced if a proper mask seal is not maintained during the entire pre-oxygenation period (Hayes-Bradley et al, 2016)
• A BVM with a PEEP valve will only provide PEEP when the patient expires, so positive pressure is not provided in non-ventilated apnoeic patients
• However, continuous positive airways pressure (CPAP) (approx 6 cmH2O) is generated when 15L/min O2 via nasal cannulae are applied to an apnoeic patient in addition to a BVM with a PEEP valve set at 10 cm H20. This is shown below:

Apnoeic oxygenation can also be performed on children

• using high flow nasal cannula alone PEEP of 4 cmH20 can be achieved (8-12 L/min flow in infants, 20-30 L/min in children <12y)

References and Links

LITFL

• Own the Oxygen!
• CCC — Preoxygenation
• CCC — High flow nasal cannula

Journal articles and textbooks

• Binks MJ, Holyoak RS, Melhuish TM. Apnoeic oxygenation during intubation in the intensive care unit: A systematic review and meta-analysis. Heart & lung : the journal of critical care; 46(6):452-457. [pubmed]
• Brainard A, Chuang D, Zeng I, Larkin GL. A Randomized Trial on Subject Tolerance and the Adverse Effects Associated With Higher- versus Lower-Flow Oxygen Through a Standard Nasal Cannula. Ann Emerg Med. 2015 Apr;65(4):356-61. PMID: 25458980.
• Dyett JF, Moser MS, Tobin AE. Prospective observational study of emergency airway management in the critical care environment of a tertiary hospital in Melbourne. Anaesthesia and intensive care. 43(5):577-86. 2015. [pubmed]
• Frumin MJ, Epstein RM, Cohen G. Apneic oxygenation in man. Anesthesiology. 1959 Nov-Dec;20:789-98. PMID: 13825447.
• Hayes-Bradley C, Lewis A, Burns B, Miller M. Efficacy of Nasal Cannula Oxygen as a Preoxygenation Adjunct in Emergency Airway Management. Annals of emergency medicine. 68(2):174-80. 2016. [pubmed]
• Levitan R. NO DESAT! EP Monthly Dec 9, 2010. [Free Full Text]
• Moran C, Karalapillai D, Darvall J, Nanuan A. Is it time for apnoeic oxygenation during endotracheal intubation in critically ill patients? Critical care and resuscitation. 16(3):233-5. 2014. [pubmed] [free full text]
• Oliveira J E Silva L, Cabrera D, Barrionuevo P. Effectiveness of Apneic Oxygenation During Intubation: A Systematic Review and Meta-Analysis. Annals of emergency medicine. 2017; 70(4):483-494.e11. [pubmed]
• Patel A, Nouraei SA. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015 Mar;70(3):323-9. doi: 10.1111/anae.12923. Epub 2014 Nov 10. PubMed PMID: 25388828.
• Ramachandran SK, Cosnowski A, Shanks A, Turner CR. Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. Journal of clinical anesthesia. 22(3):164-8. 2010. [pubmed]
• Roppolo LP, Wigginton JG. Preventing severe hypoxia during emergent intubation: is nasopharyngeal oxygenation the answer? Crit Care. 2010;14(6):1005. PMC3220012.
• Rudlof B, Hohenhorst W. Use of apneic oxygenation for the performance of pan-endoscopy. Otolaryngol Head Neck Surg. 2013 Aug;149(2):235-9. doi: 10.1177/0194599813486248. Epub 2013 Apr 12. PMID: 23585155.
• Semler MW, Janz DR, Lentz RJ. Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill. American journal of respiratory and critical care medicine. 2015. [pubmed]
• Taha SK, Siddik-Sayyid SM, El-Khatib MF, Dagher CM, Hakki MA, Baraka AS. Nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique. Anaesthesia. 61(5):427-30. 2006. [pubmed]
• Teller LE, Alexander CM, Frumin MJ, Gross JB. Pharyngeal insufflation of oxygen prevents arterial desaturation during apnea. Anesthesiology. 1988; 69(6):980-2. [pubmed]
• Weingart SD. Preoxygenation, reoxygenation, and delayed sequence intubation in the emergency department. J Emerg Med. 2011 Jun;40(6):661-7. Epub 2010 Apr 8 PMID: 20378297. [Free Full Text]
• Weingart SD, Levitan RM. Preoxygenation and prevention of desaturation during emergency airway management. Ann Emerg Med. 2012 Mar;59(3):165-75.e1. Epub 2011 Nov 3. Review. PubMed PMID: 22050948. [Free Full Text]
• White LD, Melhuish TM, White LK, Wallace LA. Apnoeic oxygenation during intubation: a systematic review and meta-analysis. Anaesthesia and intensive care. 2017; 45(1):21-27. [pubmed]
• Wimalasena Y, Burns B, Reid C, Ware S, Habig K. Apneic oxygenation was associated with decreased desaturation rates during rapid sequence intubation by an Australian helicopter emergency medicine service. Ann Emerg Med. 2015 Apr;65(4):371-6. doi: 10.1016/j.annemergmed.2014.11.014. PMID: 25536868.

FOAM and web resources

• Auckland HEMS — DSI, apnoeic ventilation and preoxygenation
• EMCRIT — Preoxygenation, Reoxygenation and Deoxygenation
• EMCRIT — Podcast 158 – The FELLOW Trial on Apneic Oxygenation (2015)
• Resus.ME — Don’t just pre-oxygenate: have an Oxygenation Strategy (2015)
• The Bottom Line — FELLOW trial: Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill (2015)