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Three Part Question

In [patients requing endotracheal intubation], does [nasal oxygen administration during the apneic period] following induction increase the time to desaturation]?

Clinical Scenario

A patient in your ED requires endotracheal
intubation due to respiratory failure, refractory to non-invasive ventilation. The patient is preoxygenated with non-invasive ventilation on 100% oxygen prior to anaesthetic induction and until apnoea. During the intubation attempt,
the oxygen saturation falls significantly. This leads you to consider if additional strategies alongside optimised preoxygenation may have provided more time before desaturation during apnoea. You decide to search and appraise the currently available literature to see if the use of the so-called apnoeic oxygenation would delay critical desaturation.

Search Strategy

Ovid journals and full texts from 1985 to March 2016

Embase from 1974 to March 2016

AMED from 1985 to March 2016

HMIC from 1979 to March 2016
{(apnoeic oxygenation.mp) OR (apnoeic oxygen$.mp) OR (apneic oxygenation.mp)} OR {[(exp Oxygen Inhalation Therapy/) OR (oxygen inhalation.mp)] OR [(exp Oxygen Inhalation Therapy/) AND (exp Insufflation/)] OR [(exp Oxygen/) AND (exp Insufflation/)] AND [(exp Nasal Absorption/) OR (nasal.mp)]} AND {[(exp Intubation, Intratracheal/) OR (rapid sequence intubation.mp) OR (rapid sequence induction.mp) OR (RSI.mp)]}

ClinicalTrials.gov site for ongoing trials using the term ‘apnoeic oxygenation’.

Search Outcome

One hundred and sixty-seven papers were found using the above-described search strategy. Eight articles seemed to address our specific question. Of these one was retracted after publication and three were audit/abstract only papers. The only ongoing trial, now completed (but not published) yielded on the ClinicalTrials.gov site could not be retrieved.

The remaining four papers are tabulated

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Miguel-Montanes et al, 2015 France	Rapid sequence induction on critical care 9 months control period of preoxygenation with non-rebreathing mask and apnoeic oxygenation at 6 L/min (N=50) 10 months intervention period of pre-oxygenation with high flow nasal cannula 60 L/min maintained throughout intubation (N=51) Patients excluded: O2Sats <95% despite 15 L/min O2, patients already receiving NIV/HFNC, those not having standard RSI (awake fibre-optic intubation, intubation for cardiac arrest)	Prospective before and after study	Primary outcome measured was lowest SpO2 in each patient. Desaturation to <80% was expressed as a percentage of occurrence Multivariate analysis was performed and results expressed as OR and 95% CI	In nasal high flow group 2% of patients desaturated to <80% compared with 14% desaturating to <80% in the control group (p=0.03) HFNC was found to be independent protective factor against severe hypoxia OR 0.14, 95%CI 0.01 to 09, (p=0.037) Median SpO2 after pre-oxygenation with NRBM was 100% (IQR 98–100%) vs 100% (IQR 100–100%) in HFNC group p=0.01 Median lowest SpO2 in the NRBM group was 94% (IQR 83–98%) vs 100% (IQR 95–100%) in HFNC group p≤0.000	Biases of a before and after study Higher Cormac Lehane score and lower junior resident success rate in the NRBM group may have confounded the results Potential for recall bias as data collected by procedural operator
Semler et al, 2016 USA	Rapid sequence induction on critical care, over a 12-month period. Patients were randomised in a 1:1 ratio to receive apnoeic oxygenation via high flow nasal cannula at 15 L/min 100% O2 (N=77) vs standard care, pre-oxygenation with non-rebreathe mask but no apnoeic oxygenation (N=73) Data collected by independent observers Patients were also randomised to receive video or direct laryngoscopy Excluded were patients requiring intubation for cardiorespiratory arrest, fibre-optic intubation	Single centre, randomised, open-label, parallel group, pragmatic trial	Primary outcome measured was lowest SpO2 measured between induction and 2 min after successful ET tube placement Secondary outcome of incidence of hypoxaemia <80%. Results as median saturations or IQR	Median lowest SpO2 in standard care was 92 (IQR 84–99%) vs 90% (IQR 80–96%) apnoeic oxygenation group (p=0.16) Incidence of severe hypoxia (SpO2 <80%) standard care was 25% vs 15.8% in apnoeic oxygenation group (p=0.22)	Position of the patient for intubation was variable Different intubation techniques were used which may have influenced the results 50% of patients were ventilated through the apnoeic period with either BVM or BIPAP Only 56 patients in total were not ventilated through apnoea although there was an equal distribution and manual ventilation between groups Some of the crucial confounders in this study are only mentioned in the online supplemental data
Wimalasena, Burns, Reid et al, 2015 Australia	Intubations performed by Australian Helicopter Service Electronic registry data collected from a 22-month period pre and post the introduction of apnoeic oxygenation to the standard operating procedure for RSI Pre-apnoeic oxygenation group, N=310 Receiving apnoeic oxygenation, N=418	Observational Trial	Oxygen saturation below 93% at any point during induction and intubation. ORs with 95% CIs	In the pre-apnoeic oxygenation period 22% desaturated below 93% vs 16% in the apnoeic oxygenation period. 6% absolute reduction in desaturation (95% CI 0.2 to 11) OR for desaturation 0.68 (95% CI 0.47 to 0.98)	Convenience sample No propensity matching Larger post-apnoeic oxygenation population may have skewed results Potential improvements in practice over the time course of the study No description of the RSI process Very broad CI Data collected by procedural operator so recall bias is potentially introduced No documentation of compliance to SOP, or if apnoeic oxygenation received
Sakles Mosier et al, 2014 USA	N=127 adults with intracranial haemorrhage requiring ED intubations split into two groups N=72 in apnoeic oxygenation group N=55, no apnoeic oxygenation group	Single centre, non-randomised observational study	Primary outcome episodes of hypoxaemia defined as SpO2 <90% during intubation	29% (16/55) of patients in the standard care group desaturated to <90% compared with 7% (5/72) of the apnoeic oxygenation group OR 0.13 (95% CI 0.03 to 0.53)	Non-randomised, trial (intervention decided by the operator) Data collected by the operator Variable flow rates in the apnoeic oxygenation group First-pass success was higher in the apnoeic oxygenation group Different intubation techniques used

Comment(s)

For any patient requiring emergency intubation and ventilation it is crucial to optimise chances of maintaining oxygen saturations during intubation attempts.5 This involves optimal patient positioning, oxygenation techniques and optimal intubation conditions. Waiting for paralysis prevents initiation of a gag reflex upon laryngoscopy and allows maximal laryngeal exposure, increasing chances of first-pass success.5 Apnoeic oxygenation allows oxygenation and ventilation of patients during the onset phase of muscle relaxation.5 During apnoea gas exchange between the alveoli and the bloodstream still occurs.5 It is estimated that 250 mL/min of oxygen diffuse into the blood stream compared with 20 mL/min of carbon dioxide moving into the alveoli from the blood stream.5 This means pressure in the alveoli reduces creating a gradient for gas transfer from the pharynx into the alveoli.5 The majority of the retrieved and analysed papers seem to suggest that the use of apnoeic oxygenation reduces the incidence of desaturation during intubation. These studies are however very heterogeneous in terms of methodology, outcomes and most importantly populations studied so it is somewhat difficult to draw conclusions for everyday emergency medicine practice.

Clinical Bottom Line

Apnoeic oxygenation is a harmless procedure and there is emerging evidence that its use does help prevent oxygen desaturations during emergency intubation attempts. Further well-constructed and ED-based studies are however needed to explore its benefits in the ED.

References

1. Miguel-Montanes R, Hajage D, Messika J, 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. Crit Care Med 2015;43:574–83.
2. Semler MW, Janz DR, Lentz RJ, et al. Randomized trial of apneic oxygenation during endotracheal intubation of the critically ill. Am J Respir Crit Care Med 2016;193:273–80.
3. Wimalasena Y, Burns B, Reid C, et al. Apneic oxygenation was associated with decreased desaturation rates during rapid sequence intubation by an Australian helicopter emergency medicine service.. Ann Emerg Med 2015;65:371–6.
4. Sakles JC, Mosier JM, Patanwala AE, et al. Apneic oxygenation is associated with a reduction in the incidence of hypoxemia during the RSI of patients with intracranial hemorrhage in the emergency department. Intern Emerg Med 2016 11(7):983-92.
5. Weingart S, Levitan R. Preoxygenation and prevention of desaturation during emergency airway management. Ann Emerg Med 2012;59:165–75.