- Email: [email protected]
Apneic oxygenation during intubation in the emergency department and during retrieval: A systematic review and meta-analysis
Accepted Manuscript Apneic oxygenation during intubation in the emergency department and during retrieval: A systematic review and metaanalysis
Matthew J. Binks, Rhys S. Holyoak, Thomas M. Melhuish, Ruan Vlok, Ellyse Bond, Leigh D. White PII: DOI: Reference:
S0735-6757(17)30497-7 doi: 10.1016/j.ajem.2017.06.046 YAJEM 56774
To appear in: Received date: Revised date: Accepted date:
18 May 2017 23 June 2017 23 June 2017
Please cite this article as: Matthew J. Binks, Rhys S. Holyoak, Thomas M. Melhuish, Ruan Vlok, Ellyse Bond, Leigh D. White , Apneic oxygenation during intubation in the emergency department and during retrieval: A systematic review and meta-analysis, (2017), doi: 10.1016/j.ajem.2017.06.046
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Apneic oxygenation during intubation in the emergency department and during retrieval: A systematic review and meta-analysis. Binks, Matthew J1,2#, Holyoak, Rhys S3, Melhuish, Thomas M1,2, Vlok, Ruan1,4, Bond, Ellyse5 & White, Leigh D 1,3
1. Wagga Wagga Rural Referral Hospital, NSW, Australia. 2. Faculty of Medicine, University of New South Wales, NSW, Australia
T
3. School of Medicine, University of Wollongong, NSW, Australia.
IP
4. University of Notre Dame Australia, School of Medicine Sydney
Corresponding Author: Dr Matthew Binks
US
#
CR
5. Caboolture Hospital, QLD, Australia
AN
Email: [email protected]
M
Address: Wagga Wagga Rural Referral Hospital, Wagga Wagga, NSW, Australia
AC
CE
PT
ED
Word Count (excluding title page, abstract, figures, tables and reference list): 1488
ACCEPTED MANUSCRIPT
Introduction Endotracheal intubation is a life-saving therapy implemented in both the pre-hospital and hospital settings. Though intubation is often considered a routine intervention, it is far from risk-free. Intubation may be particularly troublesome when performed away from the operating room, such as in prehospital or non-critical care based setting, where the support staff may be less experienced, the facilities inadequate and the patient status less stable [1-
T
4].
IP
Apneic oxygenation aims to maintain oxygenation in the absence of patient respiratory effort [2]. The technique was first described in 1959 and uses nasal cannulae to supply high-flow oxygen to the nasopharynx [1, 5]. Given a patent
CR
airway and minimal cardio-pulmonary shunting, the oxygen may then diffuse into the alveoli and sustain blood oxygenation [5, 6].
US
Apneic oxygenation is of particular interest when considering endotracheal intubation. The enforced apnea during the procedure makes hypoxemia a significant risk [2, 7]. Pre-oxygenation - the administration of 100% oxygen for a period prior to intubation – is widely employed to buy time before oxygen desaturation occurs, the so-called safe-
AN
apnea time [2]. Despite this, hypoxemia remains a concern and particularly so in the emergency department and during patient retrieval, where patients may be unstable, preparation or pre-oxygenation time limited and the
M
environment uncontrolled [3, 5, 8-10].
Multiple studies have examined the utility of apneic oxygenation during intubation across an array of clinical
ED
settings. Differing protocols and patient groups make comparing these trials error-prone. In order to generate a clinically meaningful analysis for emergency and retrieval specialists, only trials carried out in these settings were
PT
included in this meta-analysis. Primarily, the aim of this systematic review and meta-analysis was to assess the effect of apneic oxygenation on hypoxemia (lowest SpO2 and incidence of both desaturation and critical desaturation) during intubation undertaken in the ED and during retrieval. The secondary aim was to investigate the apneic
oxygenation
CE
of
AC
impact
on
first
pass
success
rate
of
intubation
in
these
settings.
ACCEPTED MANUSCRIPT Methods: Search Strategy: Two independent reviewers (RH, LW) systematically searched five databases (SCOPUS, Web of Science, CINAHL, Medline and PubMed) for articles up to and including the 19 th November, 2016. Search terms applied were (1) (endotracheal intubation) AND (apneic oxygenation) and (2) (endotracheal intubation) AND (apneic oxygenation).
T
A manual check of reference lists to detect additional studies followed this.
IP
Inclusion Criteria:
Articles were included if they assessed the performance of apneic oxygenation during intubation with that of a
CR
control group in the pre-hospital or emergency department setting. Two reviewers (RH, LW) independently assessed the papers against these criteria. There were no restrictions on study design.
US
Data extraction:
Indication for intubation, apneic oxygenation intervention and patient outcomes were extracted. The collected data
AN
was then assessed for heterogeneity. Outcome measures:
M
The pooled data was analysed for desaturation, incidence of critical desaturation and first-pass successful intubation.
ED
Definition(s):
Apneic Oxygenation: administration of oxygen via nasal cannulae at flow rates of 5-60 litres per minute during
PT
intubation.
Low Flow Apneic Oxygenation: administration of oxygen via nasal cannulae at flow rates of 15 litres per minute or
CE
less during intubation.
High Flow Apneic Oxygenation: administration of oxygen via nasal cannulae at flow rates of 50-60 litres per minute
AC
during intubation.
Desaturation: reduction in oxygen saturations (SpO2) to less than 93-95% during intubation. Critical Desaturation: reduction in oxygen saturations (SpO2) to less than 80% during intubation [13]. Statistical Analyses The combined data was examined using the RevMan 5.3 software (The Nordic Cochrane Centre, Copenhagen, Denmark). Dichotomous outcomes were assessed for relative risk (RR) with 95% confidence interval (CI). The Mantel-Haenszel (M-H) fixed effects model was used. Heterogeneity was assessed by use of I2 and chi squared statistics. Heterogeneity was deemed significant if I2 >50%. A P value of <0.05 indicated statistical significance when calculating RR, WMD or I2.
ACCEPTED MANUSCRIPT Results The initial systematic literature review identified 2011 citations (Figure 1). This total was filtered by duplicate exclusion and abstract review, yielding 30 trials. Specific Inclusion criteria eliminated a further 24 papers during full-text review, leaving 6 articles and a total 1822 cases for analysis [3, 7, 10-13]. There was one high quality level one randomized controlled trial [11], three low quality level 2 prospective comparative trials [3, 10, 12], one level 3 retrospective comparative trial [13] and one level 3
T
retrospective observational trial [7] (Table 1, Figure 2). The six papers measured three outcomes in total
IP
(Table 1).
CR
Figure 1: Systematic database search strategy.
Study
Study Type
Number
Patient Group
Nasal Prong
of
Oxygen
Patients
Intervention
[3]
Comparative
Sakles et al.
Prospective
(2016b) [10]
Comparative
635
ED Patients
0 L/min (255)
127
Observationa
728
l Randomised
[11]
Controlled Trial Prospective
[12]
Comparative
Evidence*
2
Desaturation
Haemorrhage
5-15 L/min (72)
2)
First Pass Success
3)
Incidence of Critical Desaturation (SpO2 <80%)
Helicopter
0 L/min (310)
1)
Desaturation
Emergency
15 L/min (418)
2)
First Pass Success
0 L/min (50)
1)
Desaturation
Intervention rate
2)
Incidence of Critical Desaturation (SpO2 <80%)
2
3
Medical Service 100
139
AC
Dyett et al. (2015)
First Pass Success
1)
ED Patients
CE
Caputo et.al. (2016)
Level of
Lowest SpO2
3)
0 L/min (55)
PT
Retrospective
(2015) [7]
Desaturation
ED Intracranial
Patients Wimalasena et al.
1)
5-15 L/min (380) 2)
M
Prospective
ED
Sakles et al. (2016a)
Primary Outcome(s)
AN
(no of pts)
US
Table 1: Study characteristics
ED Patients-
Subgroups of Respiratory
1
not specified (50) 0 L/min (92) 15
1) Desaturation
2
3
/min (47)
Failure and NonRespiratory Failure
Riyapan et al. 2016 Retrospective [13]
93
Comparative
Retrieval
0 L/min (39)
1)
First Pass Success
Respiratory
15L/min (14)
2)
Incidence of Critical Desaturation (SpO2 <80%)
Failure *Level of Evidence evaluated with the Centre for Evidence Based Medicine (CEBM): Levels of Evidence Introduction Document [14]. Figure 2: Risk of bias summary
ACCEPTED MANUSCRIPT
All but one [13] of the included studies examined the incidence of desaturation when apneic oxygenation was and was not utilized [3, 7, 10-12]. This outcome showed a significant relative risk reduction (RR= 0.76, 95%CI= 0.60 to 0.90, p= 0.002) with significant heterogeneity (I2= 80%, p= 0.0005)(Figure 3). Figure 3: Incidence of desaturation with (n=967) and without (n=762) apneic oxygenation during intubation.
T
A group of three studies investigated the incidence of critical desaturation during intubation [10, 11, 13].
IP
Regarding this outcome, there was a significant reduction in relative risk ratio (RR= 0.51, 95%CI= 0.30
CR
to 0.87, p= 0.01) without significant heterogeneity (I2= 43%, p= 0.17)(Figure 4).
Figure 4: Incidence of critical desaturation (SpO2<80%) with (n=151) and without (n=169) apneic oxygenation during intubation.
Three studies evaluated the first pass success rate of intubation [3, 10, 13]. In this there was a significant
US
increase in successful first pass intubation (RR= 1.09, 95%CI= 1.03 to 1.16, p= 0.004) with no heterogeneity (I2= 0%, p= 0.87) (Figure 5).
AC
CE
PT
ED
M
AN
Figure 5: First pass success rate with (n=481) and without (n=374) apneic oxygenation during intubation.
ACCEPTED MANUSCRIPT Discussion This is the first systematic review and meta-analysis to investigate the use of apneic oxygenation during intubation in emergency department and retrieval patients. The review was tailored to the emergency and retrieval cohort to offer results of clinical relevance to emergency and retrieval specialists. A total of 6 studies were included in this analysis, offering a pool of 1822 patients. Five papers used low flow oxygen
T
at 15L/min and the sixth did not offer flow rate information [11].
IP
The primary outcome of this systematic review and meta-analysis was the relationship between blood oxygen levels during intubation and the use of apneic oxygenation. Firstly, across the five studies that
CR
measured the incidence of desaturation (Sp02<93-95%) during intubation, there was a significant improvement in hypoxemia of 3.04% [3, 7, 10-12]. This result is striking when one considers the sigmoid
US
relationship between blood oxygen levels and haemoglobin saturation. However, the result came with significant heterogeneity between the studies. This was primarily due to the result delivered by Caputo et al (2016), which showed a significantly increased rate of hypoxemia. Unfortunately, these were interim
AN
results from a published abstract, making comparison of the methodology and analysis with other studies difficult. The other measure of hypoxemia in this analysis, the rate of critical desaturation, was studied by
M
three trials [10, 11, 13]. According to these findings, the risk of critical desaturation was halved (RR =
ED
0.51, p= 0.01) in these trials when apneic oxygenation was employed [3, 7, 10, 11]. It may be hypothesized that the additional clutter of high flow nasal cannulae would complicate the process of intubation. Three studies evaluated the first-pass intubation success rate in patients with and
PT
without apneic oxygenation [3, 10, 13]. The meta-analysis revealed a significant increase in first pass success rate (RR= 1.09, p= 0.004) with no heterogeneity. This result potentially reflects the prolonged
CE
safe apnea time offered by apneic oxygenation and the additional time allowed to locate the epiglottis and laryngeal vestibule. Knowledge of this supplementary time may also help to reassure and steady a
Limitations
AC
practitioner faced with an emergent intubation.
This study is limited by a relatively small patient pool (n= 1822) that was spread across patient outcomes that were inconsistently assessed. The included studies included a single randomized controlled trial (abstract only) and were predominantly level 2 prospective cohort studies, limiting their internal validity. The necessary brevity of Caputo et al (2016)’s abstract and its subsequent lack of details regarding study design make it difficult to analyse. This is poignant given it was the sole outlier in the analysis of incidence of desaturation.
ACCEPTED MANUSCRIPT Study protocols differed in their methods of pre-oxygenation, with some employing positive pressure ventilation. Accordingly, baseline alveolar recruitment will have varied. The lack of analysis of all-cause 30-day mortality in the included studies is an important oversight, but an understandable one given patient flow from the emergency department and retrieval.
IP
T
Conclusions:
This study found a significant improvement in blood oxygenation during intubation in the emergency
CR
department and during retrieval when apneic oxygenation is used. Employing the technique may reduce the incidences of both desaturation and critical desaturation. The meta-analysis also found a significant
US
improvement in successful first-pass intubation when using apneic oxygenation. Despite these promising results, apneic oxygenation in the ED and retrieval scenarios is in need of further investigation. Future high quality randomized controlled trials using standardized outcomes will help to bolster the results of
M
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this study.
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Conflicts of Interest: On behalf of all authors, the corresponding author states that there is no conflict of interest.
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Funding source: no funding was provided for this research
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Ethics: no ethics approval required
ACCEPTED MANUSCRIPT References
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4.
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3.
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2.
Frumin, M.J., R.M. Epstein, and G. Cohen, Apneic oxygenation in man. The Journal of the American Society of Anesthesiologists, 1959. 20(6): p. 789-798. Weingart, S.D. and R.M. Levitan, Preoxygenation and prevention of desaturation during emergency airway management. Annals of emergency medicine, 2012. 59(3): p. 165-175. e1. Sakles, J.C., et al., First Pass Success Without Hypoxemia Is Increased With the Use of Apneic Oxygenation During Rapid Sequence Intubation in the Emergency Department. Academic Emergency Medicine, 2016. 23(6): p. 703-710. Schwartz, D.E., M.A. Matthay, and N.H. Cohen, Death and Other Complications of Emergency Airway Management in Critically Ill Adults A Prospective Investigation of 297 Tracheal Intubations. The Journal of the American Society of Anesthesiologists, 1995. 82(2): p. 367-376. De Jong, A. and S. Jaber, Apneic Oxygenation for Intubation in the Critically Ill. Let's Not Give Up! American journal of respiratory and critical care medicine, 2016. 193(3): p. 230-232. Ramachandran, S.K., et al., Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. Journal of clinical anesthesia, 2010. 22(3): p. 164-168. Wimalasena, Y., et al., Apneic oxygenation was associated with decreased desaturation rates during rapid sequence intubation by an Australian helicopter emergency medicine service. Annals of emergency medicine, 2015. 65(4): p. 371-376. Besnier, E., et al., Pre-oxygenation with high-flow nasal cannula oxygen therapy and noninvasive ventilation for intubation in the intensive care unit. Intensive care medicine, 2016. Miguel-Montanes, R., 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, 2015. 43(3): p. 574-583. Sakles, J.C., 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. Internal and emergency medicine, 2016: p. 1-10. Caputo, N., et al., 9 The Use of Emergency Department Diffuse Apneic Oxygenation Versus Usual Care During Rapid Sequence Intubation of Emergency Department Patients: A Randomized Controlled Trial (Preliminary Results of the ENDAO Study). Annals of Emergency Medicine, 2016. 68(4): p. S4. Dyett, J., M. Moser, and A. Tobin, Prospective observational study of emergency airway management in the critical care environment of a tertiary hospital in Melbourne. Anaesthesia & Intensive Care, 2015. 43(5). Riyapan, S. and J. Lubin, Apneic Oxygenation May Not Prevent Severe Hypoxemia During Rapid Sequence Intubation: A Retrospective Helicopter Emergency Medical Service Study. Air Medical Journal, 2016. 35(6): p. 365-368. Howick, J., et al., The 2011 Oxford CEBM levels of evidence (introductory document). Oxford Centre for Evidence-Based Medicine. Retrieved January, 2011. 20: p. 2011.
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Figure 1: Systematic database search strategy.
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Figure 2: Risk of bias summary
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Figure 3: Incidence of desaturation with (n=967) and without (n=762) apnoeic oxygenation during intubation.
ACCEPTED MANUSCRIPT
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Figure 4: Incidence of critical desaturation (SpO2<80%) with (n=151) and without (n=169) apnoeic oxygenation during intubation.
ACCEPTED MANUSCRIPT
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Figure 5: First pass success rate with (n=481) and without (n=374) apnoeic oxygenation during intubation.
Matthew J. Binks, Rhys S. Holyoak, Thomas M. Melhuish, Ruan Vlok, Ellyse Bond, Leigh D. White PII: DOI: Reference:
S0735-6757(17)30497-7 doi: 10.1016/j.ajem.2017.06.046 YAJEM 56774
To appear in: Received date: Revised date: Accepted date:
18 May 2017 23 June 2017 23 June 2017
Please cite this article as: Matthew J. Binks, Rhys S. Holyoak, Thomas M. Melhuish, Ruan Vlok, Ellyse Bond, Leigh D. White , Apneic oxygenation during intubation in the emergency department and during retrieval: A systematic review and meta-analysis, (2017), doi: 10.1016/j.ajem.2017.06.046
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Apneic oxygenation during intubation in the emergency department and during retrieval: A systematic review and meta-analysis. Binks, Matthew J1,2#, Holyoak, Rhys S3, Melhuish, Thomas M1,2, Vlok, Ruan1,4, Bond, Ellyse5 & White, Leigh D 1,3
1. Wagga Wagga Rural Referral Hospital, NSW, Australia. 2. Faculty of Medicine, University of New South Wales, NSW, Australia
T
3. School of Medicine, University of Wollongong, NSW, Australia.
IP
4. University of Notre Dame Australia, School of Medicine Sydney
Corresponding Author: Dr Matthew Binks
US
#
CR
5. Caboolture Hospital, QLD, Australia
AN
Email: [email protected]
M
Address: Wagga Wagga Rural Referral Hospital, Wagga Wagga, NSW, Australia
AC
CE
PT
ED
Word Count (excluding title page, abstract, figures, tables and reference list): 1488
ACCEPTED MANUSCRIPT
Introduction Endotracheal intubation is a life-saving therapy implemented in both the pre-hospital and hospital settings. Though intubation is often considered a routine intervention, it is far from risk-free. Intubation may be particularly troublesome when performed away from the operating room, such as in prehospital or non-critical care based setting, where the support staff may be less experienced, the facilities inadequate and the patient status less stable [1-
T
4].
IP
Apneic oxygenation aims to maintain oxygenation in the absence of patient respiratory effort [2]. The technique was first described in 1959 and uses nasal cannulae to supply high-flow oxygen to the nasopharynx [1, 5]. Given a patent
CR
airway and minimal cardio-pulmonary shunting, the oxygen may then diffuse into the alveoli and sustain blood oxygenation [5, 6].
US
Apneic oxygenation is of particular interest when considering endotracheal intubation. The enforced apnea during the procedure makes hypoxemia a significant risk [2, 7]. Pre-oxygenation - the administration of 100% oxygen for a period prior to intubation – is widely employed to buy time before oxygen desaturation occurs, the so-called safe-
AN
apnea time [2]. Despite this, hypoxemia remains a concern and particularly so in the emergency department and during patient retrieval, where patients may be unstable, preparation or pre-oxygenation time limited and the
M
environment uncontrolled [3, 5, 8-10].
Multiple studies have examined the utility of apneic oxygenation during intubation across an array of clinical
ED
settings. Differing protocols and patient groups make comparing these trials error-prone. In order to generate a clinically meaningful analysis for emergency and retrieval specialists, only trials carried out in these settings were
PT
included in this meta-analysis. Primarily, the aim of this systematic review and meta-analysis was to assess the effect of apneic oxygenation on hypoxemia (lowest SpO2 and incidence of both desaturation and critical desaturation) during intubation undertaken in the ED and during retrieval. The secondary aim was to investigate the apneic
oxygenation
CE
of
AC
impact
on
first
pass
success
rate
of
intubation
in
these
settings.
ACCEPTED MANUSCRIPT Methods: Search Strategy: Two independent reviewers (RH, LW) systematically searched five databases (SCOPUS, Web of Science, CINAHL, Medline and PubMed) for articles up to and including the 19 th November, 2016. Search terms applied were (1) (endotracheal intubation) AND (apneic oxygenation) and (2) (endotracheal intubation) AND (apneic oxygenation).
T
A manual check of reference lists to detect additional studies followed this.
IP
Inclusion Criteria:
Articles were included if they assessed the performance of apneic oxygenation during intubation with that of a
CR
control group in the pre-hospital or emergency department setting. Two reviewers (RH, LW) independently assessed the papers against these criteria. There were no restrictions on study design.
US
Data extraction:
Indication for intubation, apneic oxygenation intervention and patient outcomes were extracted. The collected data
AN
was then assessed for heterogeneity. Outcome measures:
M
The pooled data was analysed for desaturation, incidence of critical desaturation and first-pass successful intubation.
ED
Definition(s):
Apneic Oxygenation: administration of oxygen via nasal cannulae at flow rates of 5-60 litres per minute during
PT
intubation.
Low Flow Apneic Oxygenation: administration of oxygen via nasal cannulae at flow rates of 15 litres per minute or
CE
less during intubation.
High Flow Apneic Oxygenation: administration of oxygen via nasal cannulae at flow rates of 50-60 litres per minute
AC
during intubation.
Desaturation: reduction in oxygen saturations (SpO2) to less than 93-95% during intubation. Critical Desaturation: reduction in oxygen saturations (SpO2) to less than 80% during intubation [13]. Statistical Analyses The combined data was examined using the RevMan 5.3 software (The Nordic Cochrane Centre, Copenhagen, Denmark). Dichotomous outcomes were assessed for relative risk (RR) with 95% confidence interval (CI). The Mantel-Haenszel (M-H) fixed effects model was used. Heterogeneity was assessed by use of I2 and chi squared statistics. Heterogeneity was deemed significant if I2 >50%. A P value of <0.05 indicated statistical significance when calculating RR, WMD or I2.
ACCEPTED MANUSCRIPT Results The initial systematic literature review identified 2011 citations (Figure 1). This total was filtered by duplicate exclusion and abstract review, yielding 30 trials. Specific Inclusion criteria eliminated a further 24 papers during full-text review, leaving 6 articles and a total 1822 cases for analysis [3, 7, 10-13]. There was one high quality level one randomized controlled trial [11], three low quality level 2 prospective comparative trials [3, 10, 12], one level 3 retrospective comparative trial [13] and one level 3
T
retrospective observational trial [7] (Table 1, Figure 2). The six papers measured three outcomes in total
IP
(Table 1).
CR
Figure 1: Systematic database search strategy.
Study
Study Type
Number
Patient Group
Nasal Prong
of
Oxygen
Patients
Intervention
[3]
Comparative
Sakles et al.
Prospective
(2016b) [10]
Comparative
635
ED Patients
0 L/min (255)
127
Observationa
728
l Randomised
[11]
Controlled Trial Prospective
[12]
Comparative
Evidence*
2
Desaturation
Haemorrhage
5-15 L/min (72)
2)
First Pass Success
3)
Incidence of Critical Desaturation (SpO2 <80%)
Helicopter
0 L/min (310)
1)
Desaturation
Emergency
15 L/min (418)
2)
First Pass Success
0 L/min (50)
1)
Desaturation
Intervention rate
2)
Incidence of Critical Desaturation (SpO2 <80%)
2
3
Medical Service 100
139
AC
Dyett et al. (2015)
First Pass Success
1)
ED Patients
CE
Caputo et.al. (2016)
Level of
Lowest SpO2
3)
0 L/min (55)
PT
Retrospective
(2015) [7]
Desaturation
ED Intracranial
Patients Wimalasena et al.
1)
5-15 L/min (380) 2)
M
Prospective
ED
Sakles et al. (2016a)
Primary Outcome(s)
AN
(no of pts)
US
Table 1: Study characteristics
ED Patients-
Subgroups of Respiratory
1
not specified (50) 0 L/min (92) 15
1) Desaturation
2
3
/min (47)
Failure and NonRespiratory Failure
Riyapan et al. 2016 Retrospective [13]
93
Comparative
Retrieval
0 L/min (39)
1)
First Pass Success
Respiratory
15L/min (14)
2)
Incidence of Critical Desaturation (SpO2 <80%)
Failure *Level of Evidence evaluated with the Centre for Evidence Based Medicine (CEBM): Levels of Evidence Introduction Document [14]. Figure 2: Risk of bias summary
ACCEPTED MANUSCRIPT
All but one [13] of the included studies examined the incidence of desaturation when apneic oxygenation was and was not utilized [3, 7, 10-12]. This outcome showed a significant relative risk reduction (RR= 0.76, 95%CI= 0.60 to 0.90, p= 0.002) with significant heterogeneity (I2= 80%, p= 0.0005)(Figure 3). Figure 3: Incidence of desaturation with (n=967) and without (n=762) apneic oxygenation during intubation.
T
A group of three studies investigated the incidence of critical desaturation during intubation [10, 11, 13].
IP
Regarding this outcome, there was a significant reduction in relative risk ratio (RR= 0.51, 95%CI= 0.30
CR
to 0.87, p= 0.01) without significant heterogeneity (I2= 43%, p= 0.17)(Figure 4).
Figure 4: Incidence of critical desaturation (SpO2<80%) with (n=151) and without (n=169) apneic oxygenation during intubation.
Three studies evaluated the first pass success rate of intubation [3, 10, 13]. In this there was a significant
US
increase in successful first pass intubation (RR= 1.09, 95%CI= 1.03 to 1.16, p= 0.004) with no heterogeneity (I2= 0%, p= 0.87) (Figure 5).
AC
CE
PT
ED
M
AN
Figure 5: First pass success rate with (n=481) and without (n=374) apneic oxygenation during intubation.
ACCEPTED MANUSCRIPT Discussion This is the first systematic review and meta-analysis to investigate the use of apneic oxygenation during intubation in emergency department and retrieval patients. The review was tailored to the emergency and retrieval cohort to offer results of clinical relevance to emergency and retrieval specialists. A total of 6 studies were included in this analysis, offering a pool of 1822 patients. Five papers used low flow oxygen
T
at 15L/min and the sixth did not offer flow rate information [11].
IP
The primary outcome of this systematic review and meta-analysis was the relationship between blood oxygen levels during intubation and the use of apneic oxygenation. Firstly, across the five studies that
CR
measured the incidence of desaturation (Sp02<93-95%) during intubation, there was a significant improvement in hypoxemia of 3.04% [3, 7, 10-12]. This result is striking when one considers the sigmoid
US
relationship between blood oxygen levels and haemoglobin saturation. However, the result came with significant heterogeneity between the studies. This was primarily due to the result delivered by Caputo et al (2016), which showed a significantly increased rate of hypoxemia. Unfortunately, these were interim
AN
results from a published abstract, making comparison of the methodology and analysis with other studies difficult. The other measure of hypoxemia in this analysis, the rate of critical desaturation, was studied by
M
three trials [10, 11, 13]. According to these findings, the risk of critical desaturation was halved (RR =
ED
0.51, p= 0.01) in these trials when apneic oxygenation was employed [3, 7, 10, 11]. It may be hypothesized that the additional clutter of high flow nasal cannulae would complicate the process of intubation. Three studies evaluated the first-pass intubation success rate in patients with and
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without apneic oxygenation [3, 10, 13]. The meta-analysis revealed a significant increase in first pass success rate (RR= 1.09, p= 0.004) with no heterogeneity. This result potentially reflects the prolonged
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safe apnea time offered by apneic oxygenation and the additional time allowed to locate the epiglottis and laryngeal vestibule. Knowledge of this supplementary time may also help to reassure and steady a
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practitioner faced with an emergent intubation.
This study is limited by a relatively small patient pool (n= 1822) that was spread across patient outcomes that were inconsistently assessed. The included studies included a single randomized controlled trial (abstract only) and were predominantly level 2 prospective cohort studies, limiting their internal validity. The necessary brevity of Caputo et al (2016)’s abstract and its subsequent lack of details regarding study design make it difficult to analyse. This is poignant given it was the sole outlier in the analysis of incidence of desaturation.
ACCEPTED MANUSCRIPT Study protocols differed in their methods of pre-oxygenation, with some employing positive pressure ventilation. Accordingly, baseline alveolar recruitment will have varied. The lack of analysis of all-cause 30-day mortality in the included studies is an important oversight, but an understandable one given patient flow from the emergency department and retrieval.
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Conclusions:
This study found a significant improvement in blood oxygenation during intubation in the emergency
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department and during retrieval when apneic oxygenation is used. Employing the technique may reduce the incidences of both desaturation and critical desaturation. The meta-analysis also found a significant
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improvement in successful first-pass intubation when using apneic oxygenation. Despite these promising results, apneic oxygenation in the ED and retrieval scenarios is in need of further investigation. Future high quality randomized controlled trials using standardized outcomes will help to bolster the results of
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Conflicts of Interest: On behalf of all authors, the corresponding author states that there is no conflict of interest.
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Funding source: no funding was provided for this research
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Ethics: no ethics approval required
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Frumin, M.J., R.M. Epstein, and G. Cohen, Apneic oxygenation in man. The Journal of the American Society of Anesthesiologists, 1959. 20(6): p. 789-798. Weingart, S.D. and R.M. Levitan, Preoxygenation and prevention of desaturation during emergency airway management. Annals of emergency medicine, 2012. 59(3): p. 165-175. e1. Sakles, J.C., et al., First Pass Success Without Hypoxemia Is Increased With the Use of Apneic Oxygenation During Rapid Sequence Intubation in the Emergency Department. Academic Emergency Medicine, 2016. 23(6): p. 703-710. Schwartz, D.E., M.A. Matthay, and N.H. Cohen, Death and Other Complications of Emergency Airway Management in Critically Ill Adults A Prospective Investigation of 297 Tracheal Intubations. The Journal of the American Society of Anesthesiologists, 1995. 82(2): p. 367-376. De Jong, A. and S. Jaber, Apneic Oxygenation for Intubation in the Critically Ill. Let's Not Give Up! American journal of respiratory and critical care medicine, 2016. 193(3): p. 230-232. Ramachandran, S.K., et al., Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. Journal of clinical anesthesia, 2010. 22(3): p. 164-168. Wimalasena, Y., et al., Apneic oxygenation was associated with decreased desaturation rates during rapid sequence intubation by an Australian helicopter emergency medicine service. Annals of emergency medicine, 2015. 65(4): p. 371-376. Besnier, E., et al., Pre-oxygenation with high-flow nasal cannula oxygen therapy and noninvasive ventilation for intubation in the intensive care unit. Intensive care medicine, 2016. Miguel-Montanes, R., 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, 2015. 43(3): p. 574-583. Sakles, J.C., 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. Internal and emergency medicine, 2016: p. 1-10. Caputo, N., et al., 9 The Use of Emergency Department Diffuse Apneic Oxygenation Versus Usual Care During Rapid Sequence Intubation of Emergency Department Patients: A Randomized Controlled Trial (Preliminary Results of the ENDAO Study). Annals of Emergency Medicine, 2016. 68(4): p. S4. Dyett, J., M. Moser, and A. Tobin, Prospective observational study of emergency airway management in the critical care environment of a tertiary hospital in Melbourne. Anaesthesia & Intensive Care, 2015. 43(5). Riyapan, S. and J. Lubin, Apneic Oxygenation May Not Prevent Severe Hypoxemia During Rapid Sequence Intubation: A Retrospective Helicopter Emergency Medical Service Study. Air Medical Journal, 2016. 35(6): p. 365-368. Howick, J., et al., The 2011 Oxford CEBM levels of evidence (introductory document). Oxford Centre for Evidence-Based Medicine. Retrieved January, 2011. 20: p. 2011.
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Figure 1: Systematic database search strategy.
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Figure 2: Risk of bias summary
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Figure 3: Incidence of desaturation with (n=967) and without (n=762) apnoeic oxygenation during intubation.
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Figure 4: Incidence of critical desaturation (SpO2<80%) with (n=151) and without (n=169) apnoeic oxygenation during intubation.
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Figure 5: First pass success rate with (n=481) and without (n=374) apnoeic oxygenation during intubation.