Journal of Clinical Anesthesia 52 (2019) 85–90
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Journal of Clinical Anesthesia journal homepage: www.elsevier.com/locate/jclinane
Preoxygenation during induction of anesthesia in non-critically ill patients: A systematic review
T
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Elena Bignami Full professora, , Francesco Saglietti, MDb, Alessandro Girombelli, MDb, Andrea Briolini, MDa, Tiziana Bove Associate professorc, Luigi Vetrugno, MDc a
Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Viale Gramsci 14, 43126 Parma, Italy University of Milan-Bicocca, School of Medicine and Surgery, Via Cadore 48, 20900 Monza, MB, Italy c Department of Anaesthesia and Intensive Care, University of Udine, Udine, Italy b
A R T I C LE I N FO
A B S T R A C T
Keywords: Preoxygenation Induction General anesthesia Safe apnea time
We conducted a systematic review of the literature to better understand whether preoxygenation in non-critically ill patients (i.e. elective surgery patients) should be recommended, as it lengthens safe apnea time (the time required to reach oxygen saturation < 90% in an apneic patient). Furthermore, we looked for the most efficient technique amongst those currently employed in clinical practice. We searched Scopus, CINAHL, the Cochrane Library, PubMed and MeSH using various combinations of the words “preoxygenation”, “general anesthesia”, “induction”, “operating room” and “oxygen”. RCTs conducted on adult (> 18 years) and non-emergent patients between 2008 and 2017 were deemed eligible. A total of 11 papers were included. Our review suggests that preoxygenation is a safe and efficient technique that allows for longer safe apneic periods in obese (BMI > 30) non-critically ill patients. Non-obese (< 30 BMI) patients do not seem to benefit as much from this procedure. However, there is insufficient evidence in the literature to provide a clear recommendation. For all patients, the procedure was safe and well tolerated with no harm reported. The best technique for preoxygenation appears to be pressure support ventilation plus positive end-expiratory pressure. In conclusion, preoxygenation should be employed during the induction of general anesthesia in obese patients as it allows for a longer safe apnea time and causes no harm. Although data regarding efficacy is limited for the non-obese population, the procedure was still harmless and should continue to be performed pending more robust RCTs. We believe there is sufficient evidence to support a RCT that could offer better evidence for this subset of patients undergoing non-emergent procedures.
1. Introduction Preoxygenation is a widely used technique that improves the safety of endotracheal intubation [1]. The procedure is carried out by supplying 100% oxygen (FiO2 of 1.0) before the induction of general anesthesia until both end-tidal oxygen (EtO2) > 90% and end-tidal N2 (EtN2) < 5% are reached [2]. Both these markers define the efficacy of the procedure. As a result, the lung oxygen content is increased far beyond normal oxygen consumption by saturating the functional residual capacity with 100% oxygen. This allows for a longer safe apnea time (i.e. the time required for oxyhemoglobin saturation to drop below 90%) [3,4]. The rate at which oxyhemoglobin saturation drops during apnea indicates the efficiency of the maneuver [1]. This procedure is strongly recommended for all patients undergoing general anesthesia since it lengthens safe laryngoscopy time and grants a wider timeframe
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to respond to a “cannot intubate/cannot oxygenate” (CICO) scenario, a rare yet life threatening situation. It remains unclear whether this should be considered mandatory for non-critically ill and non-obese patients since their oxygen reserves should suffice for the time required to perform endotracheal intubation or regain spontaneous breathing in the event of a CICO scenario [5–7]. Nonetheless, the guidelines for the management of endotracheal intubation, proposed by the Difficult Airway Society in 2015 UK state how it is pivotal to preoxygenate every patient before attempting to intubate [8]. Several methods of preoxygenation have been validated and compared according to duration of safe apnea time, duration of the procedure, success rate (defined as “avoiding manual re-ventilation”), and patient tolerance [9,10]. The choice between these techniques is based on patient characteristics (age, sex, BMI, ASA score, Cormack-Lehane
Corresponding author. E-mail address:
[email protected] (E. Bignami).
https://doi.org/10.1016/j.jclinane.2018.09.008 Received 29 April 2018; Received in revised form 27 August 2018; Accepted 8 September 2018 0952-8180/ © 2018 Elsevier Inc. All rights reserved.
Journal of Clinical Anesthesia 52 (2019) 85–90
E. Bignami et al.
Table 1 Quality of papers. Paper
Consort guidelines
Inclusion/exclusion criteria
Primary endpoint definition
Allocation/ randomization
Blinding
Sample size/power calculation
Statistical plan
N° of items
Hanouz J, 2018 Arab O.A., 2016 Hanouz J, 2015 Melveetil S Sreejit1, 2015 Harbut P, 2014 Kanaya A., 2012 Georgescu M., 2012 Futier E., 2011 Tanoubi I., 2009 Taha S.K., 2009 Sum-Ping S.T., 2008 Delay J.M., 2008
− − − − + − − − − − − −
+ + + + + + + + + + + +
+ + + + + − + + + − + +
+ + + + + + + + + + + +
− − − Double blinded − − Double blinded Single blinded Double blinded − − −
+ + + + + + + + + + − +
+ + + + + + + + + + + +
5/7 5/7 5/7 6/7 6/7 4/7 6/7 6/7 6/7 4/7 4/7 5/7
to 2008, abstracts, animal studies were deemed ineligible. The inclusion criteria were age > 18 years, non-emergent surgery and RCTs. The final list of papers was independently scrutinized by two researchers. If there was disagreement regarding the eligibility of a paper, a third researcher intervened independently to resolve the matter. All of the studies were written in English except for one that was written in French. This was translated into English by one of the authors who is fluent in French. The quality of the papers was evaluated according to the parameters reported in Table 1.
grade and GCS scale), settings (e.g., operating room, ICU, emergency situations), equipment, and anesthesiologist's preferences [11]. The two standard approaches are six deep breaths in 1 min and tidal volume breathing for three to 5 min, both at 100% Inspired oxygen via a face mask [12]. However, several studies have shown how preoxygenation during spontaneous ventilation is often ineffective, with approximately 56% of patients experiencing hypoxemia during induction [6]. Obese, pregnant, elderly, pediatric and ICU/emergency medicine patients are all at greater risk of desaturation and/or hypoxemia. This may be due to several factors, including increased metabolic rate (e.g., fever, epilepsy, pregnancy), blood hemoglobin concentration, general anesthesia, supine position, or any condition leading to a reduction in functional residual capacity (e.g., pulmonary disease). For these patients, applying noninvasive positive airway pressure ventilation (NIPPV), such as pressure support ventilation plus positive end-expiratory pressure (PSV-PEEP) or positive pressure ventilation (PPV) with or without PEEP, may be beneficial [12–14]. Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) provides a novel approach to preoxygenation. The system delivers high flow (> 60 L/min) oxygen through a specially designed nasal cannula while simultaneously providing a small amount of CPAP [15]. THRIVE cannulae also provide apneic oxygenation and limits the rise in CO2 levels during induction and laryngoscopy. This is achieved through the continuous gas mixing and flushing of the dead space that occurs at oxygen flow rates above 60 L/min [16]. The studies that employed the THRIVE system were excluded since preoxygenation with high flow nasal cannula is followed by apneic oxygenation, which is beyond the scope of this systematic review. The main side effect of preoxygenation is absorption atelectasis that occurs when delivering 100% inspired oxygen. This can be avoided using a lower inspired oxygen concentration (90%), positive pressure techniques, and/or recruitment maneuvers post-endotracheal intubation [17]. Due to the short duration of the procedure, the production of reactive oxygen species and cardiovascular responses are minimal and should not prevent routine preoxygenation. This systematic review aims to clarify whether preoxygenation in non-critically ill patients (i.e. elective surgery patients) before the induction of general anesthesia should be recommended. Furthermore, several preoxygenation techniques were analyzed to determine the most efficient in achieving both EtO2 > 90% in the shortest time.
3. Results The search yielded 429 results, of which 397 met the exclusion criteria based on the title alone. Another 13 were excluded after reading the abstracts. Deeper reading of the papers led to the exclusion of nine articles. At the end of the process, 10 studies were included for systematic analysis [18–27], as summarized in Table 2. Table 3 shows the PRISMA flowchart [28]. Two article were added after the review of the paper [29,30]. Seven items were considered when analyzing the quality of the papers: the statement about following CONSORT guidelines, clear inclusion/exclusion criteria, definition of a primary end point, presence of an allocation/randomization strategy, blinding of the study, sample size/power calculation, and the presence of a statistical plan. Only one paper stated CONSORT guidelines [20]. All studies stated their inclusion and exclusion criteria, although two did not define a clear primary endpoint [21,25]. Allocation to the experimental arms was described in all papers, but only three were blinded studies [22–24]. A statistical plan was present for all the studies, although one did not describe its sample size calculation [26]. All papers concluded that preoxygenation lengthened safe apnea time compared to no preoxygenation. A total of seven papers demonstrated that the use of PSV allowed for more efficient preoxygenation, with Georgescu M. et al. reporting an 80% success rate compared to a 60% without PSV. Tanoubi I. et al. showed a 100% efficacy in the PSV group as opposed to a 60% in spontaneously breathing patients [22,24]. Arab O.A. et al. and Delay J.M. et al. both proved that PSV considerably shortens the time to EtO2 > 90%, with the former also reporting a longer safe apnea time in all patients [18,27]. Hanouz J. et al., on the other hand, reported a longer safe apnea time for obese patients only, with no difference in non-obese patients [19]. All studies showed that preoxygenation is a safe and well-tolerated procedure. PSV was slightly more uncomfortable for patients, but never to a degree that required to cease the maneuver. Table 4 resumes preoxygenation techniques used in those papers.
2. Materials and methods In accordance with PRISMA guidelines, the authors conducted a systematic search of Scopus, CINAHL, the Cochrane Library, PubMed and MeSH string comprised of various combinations of the following keywords: “preoxygenation”, “general anesthesia”, “induction”, “operating room” and “oxygen”. Only RCTs from 2008 to 2018 were considered. Papers concerning children (age < 18 years), published prior
4. Discussion Preoxygenation was not associated with any major side effect (i.e. life threatening or that required the cessation of the maneuver) and was 86
87
2009
Taha S.K.
2012
Kanaya A.
2009
2014
Harbut P.
Tanoubi I.
2015
Melveetil S Sreejit
2011
2015
Hanouz J.
Futier E.
2016
Arab O.A.
2012
2018
Hanouz J
Georgescu M.
Year
First author
J Clin Anesth
Ann Fr Anesth Reanim
Anesthesiology
Ann Fr Anesth Reanim
J Anesth
Acta Anaesthesiol Scand
Indian Journal of Anaesthesia
Eur J Anaesthesiol
Eur J Anaesthesiol
Br J Anaesth
Journal
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Randomized
10
20
66
30
20
44
40
146
50
20
No. adult patients
Healthy volunteers (no anesthesia)
Healthy volunteers (no anesthesia)
Obesea (bariatric surg.)
Obesea (elective surg.)
Elective surg.
Obesea (bariatric surg.)
Elective surg.
Elective surg.
Elective ENT panendoscopy
Healthy volunteers
Patient population
Preox 100% O2, 3 groups: - SB via FM - NPPV - NPPV + RM (post-endotracheal intubation) Preox 100% O2, 3 groups: - SV - PS-PEEP 4 cm H2O - PS 6 cm H2O-PEEP 4 cm H2O Preox 100% O2, 8 dB/60 (5 & 10 L/ min), 3 groups (crossover): - Mapleson A - Circle system - Mapleson D
Preox and apneic ox, 2 groups: - Inspired oxygen 40% - Inspired oxygen 100% Post-endotracheal intubation patients received Inspired oxygen 40% Preox 100% O2, 2 groups (crossover): - TVB - NIPPV
Preox, 3 groups: - SB - PPV - PPV + PEEP Preox 2 groups: - With CPAP of 5 cm H2O - without CPAP Preox, 2 groups: - CPAP-PSV (interventional) - Neutral pressure (control)
Preox, 3 groups: - SB - SB with calibrated leak - PPV Preox 100% O2, 2 groups: - PSV (interventional) - Neutral pressure (control)
Arms
Preox duration Preox failure (EtO2 < 90%) Apnoea duration (SpO2 93%)
None
NHA duration (SpO2 90%)
Preox duration (FeO2 90%)
Safe duration of apnoea
Tolerance of preox technique
FeO2 after 3 min
Preox FetO2
Post-preox PaO2 Post-endotracheal intubation PaO2 and EELV
Patients reaching FeO2 ≥ 90% TV RR PaO2 5 min after ventilation onset
Effects preox and apneic ox Inspired oxygenelevation: - FRC - PaO2/FiO2 FeO2 after 3 min
PaO2, PaCO2 and SpO2: - Pre/post-preox - At ventilation start/ exsufflation - 30 min after PACU admission
FeO2 measured at 3 min
Proportion of FeO2 > 90% at 3 min
Post-endotracheal intubation PaO2
Secondary outcomes
Primary outcome
(continued on next page)
PS methods > mean FeO2 at 3 min than SV. FeO2 reached > 90% in: 60% SV, 90% PSPEEP 4 cm H2O, 100% PS 6 cm H2O-PEEP 4 cm H2O 10 L/min O2: no difference between FetO2. 5 L/min O2: no difference between FetO2 but significantly lower than 10 L/min (suboptimal)
No difference between FeO2 after 3 min FeO2 ≥ 90% reached in 80% NIPPV & 60% TVB TV > in TVB No difference in RR NPPV increase PaO2 post-preox and postendotracheal intubation RM post-endotracheal intubation improve PaO2 and EELV
Inspired oxygen-elevation no influences FRC and PaO2/FiO2
Low pressure CPAP-PSV group: < PaCO2 post-preox > PaO2 post-endotracheal intubation higher median nadir SpO2
Preox with CPAP prologues safe apnea time
PSV group: > NHA duration < preox duration No preox failure (20% in control group) Preox duration: PPV + PEEP < PPV < SB No significant difference in NHA duration (but difference between obese/non obese)
PPV more efficient to provide adequate preoxygenation, followed by SB without leak
Results
Table 2 Table of major randomized studies analyzed. Main points of the 12 randomized studies selected from scientific literature (2008–2018 period, 429 articles) for this systematic review about preoxygenation.
E. Bignami et al.
Journal of Clinical Anesthesia 52 (2019) 85–90
Journal of Clinical Anesthesia 52 (2019) 85–90
CPAP, continuous positive airway pressure; DB, deep breathing/breaths; EELV, end-expiratory lung volume; endotracheal intubation, endotracheal intubation; FM, facial mask; FRC, functional residual capacity; HFFM, high-flow facial mask; HFNC, high-flow nasal cannula; IS, incentive spirometry; MV, minute ventilation; NHA, non-hypoxaemic apnea; NIPPV/NPPV, non-invasive positive pressure ventilation; PACU, post-anesthesia care unit; PEEP, positive end-expiratory pressure; PLMA, ProSeal LMA; PPV, positive inspiratory pressure ventilation; PSV, pressure support ventilation; RM, recruitment maneuver; RR, respiratory rate; SB, spontaneous breathing; SV, spontaneous ventilation; TVB, tidal volume breathing. a Obesity defined as body mass index (BMI) greater or equal to 30 kg/m2.
Preox 100% O2, 2 groups: - NPPV (interventional) - SV (control) 2008 Delay J.M.
Anesth Analg
Yes
28
Obesea (elective surg.)
N. patients EtO2 > 95% after 5 min (preox end)
Time to reach maximal EtO2 EtO2 at preox end
MV, FCR, age are significant factors for deN2 rate. High-flow rate appears critical for achieving rapid preox NPPV group: > patients with EtO2 > 95% < time to reach max EtO2 > mean EtO2 at preox end Modest but significant gastric distension Reach of FeN2 5% Denitrogenation (circle system) at 5 & 10 L/min, ambient-air or 100% O2 (crossover) Healthy volunteers (no anesthesia) 14 Yes 2008 Sum-Ping S.T.
J Clin Anesth
Year First author
Table 2 (continued)
Journal
Randomized
No. adult patients
Patient population
Arms
Primary outcome
Secondary outcomes
Results
E. Bignami et al.
well tolerated. Only one paper reported the minor side effect of a modest gastric distension when PSV + PEEP was administered [27]. The procedure was faster and more efficient for all patients and healthy volunteers when employing PSV, with PSV + PEEP being the fastest and most efficient strategy amongst those considered in this paper [18,19,22–24,27]. The choice of equipment may be irrelevant, as long as high flow 100% oxygen is administered in conjunction with PSV. Studies on healthy volunteers support these claims [24–26]. Obese patients appear to benefit the most from preoxygenation, as their safe apnea time is greatly extended and EtO2 significantly improved with this maneuver, both before and after intubation [20,22,23,27]. Performing recruitment maneuvers post-endotracheal tube placement may further improve oxygenation in this population. While preoxygenation caused no harm in non-obese, non-critically ill elective surgery patients, it did not significantly extend the safe apnea time compared to no preoxygenation [18,19,21]. Doubt remains as to whether this procedure is beneficial and should be routinely performed in this subset of patients. During elective surgery, Arab O.A. et al. reported longer safe apnea time, faster preoxygenation and no failures (i.e., unable to achieve EtO2 > 90%) with PSV [18]. Hanouz J. et al. showed that preoxygenation is faster with any PSV technique compared to spontaneous breathing, with positive pressure plus PEEP being the fastest [19]. However, safe apnea time was significantly longer only in obese patients. Melveetil S Sreejit et al. compared 5 minute preoxygenation with CPAP with preoxygenation without CPAP. The results showed a longer safe apnea time (peripheral oxygen saturation above 93%) with the use of CPAP [29]. Regarding obese patients undergoing bariatric surgery, Harbut P. et al. proved that low pressure continuous positive airway pressure (CPAP)-PSV preoxygenation yields higher post-intubation PaO2 levels and higher median nadir for SpO2 compared to neutral pressure preoxygenation [20]. Georgescu M. et al. compared PSV and total lung volume breathing without pressure support, reporting higher success rates with the former technique (fraction of inspired oxygen > 90% in 80% of patients) [22]. Futier E. et al. observed higher post-preoxygenation and post-intubation PaO2 in the PSV group compared to the spontaneous ventilation (SV) group [23]. Furthermore, the study had a third group in which PSV preoxygenation and recruitment maneuvers after intubation were performed, yielding higher post-intubation PaO2 and end-expiratory lung volumes. The results of Delay J.M. et al. are in line with those of previous papers, demonstrating higher success rates, higher EtO2 levels after the maneuver, and a shorter preoxygenation time when employing PSV [27]. A modest yet significant gastric distension was reported in the PSV group. Amongst healthy volunteers, Tanoubi I. et al. showed how, at the three-minute mark, PSV methods are superior in obtaining a higher fraction of expired O2 (FeO2) compared to SV [24]. The success rate (i.e., FeO2 > 90%) was also higher in this group, with PSV + PEEP reaching 100% compared to 90% in CPAP and 60% in SV. Hanouz J. (Hanouz J 2018) compared positive pressure ventilation with spontaneous breathing without mask leaks in healthy volunteers. At the three minute mark, the former technique achieved a 100% success rate, while the latter reached only 95%. Furthermore, spontaneous breathing with mask leaks was completely ineffective [30]. Taha S.K. compared the Mapelson A, Mapelson D and Circle breathing systems with 5 L/min and 10 L/min oxygen in healthy volunteers. EtO2 levels were higher with 10 L/min of oxygen, regardless of the equipment [25]. Sum-Ping S.T. et al. analyzed denitrogenation with end-tidal N2 (EtN2) < 5% using the Circle system and either 10 L/min or 5 L/min flow rates at ambient air or at 100% inspired oxygen. They concluded that high-flow rates are crucial for a rapid preoxygenation [26]. The potential risks of preoxygenation are absorption atelectasis, delayed recognition of esophageal intubation, and production of reactive oxygen species. The most common side effect of preoxygenation is absorption atelectasis secondary to the administration of 100% inspired oxygen. This occurs in up to 90% of healthy patients undergoing 88
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Table 3 PRISMA flowchart.
Records idenfied through database searching (n = 429)
Addional records idenfied through other sources (n = 2)
Records aer duplicates removed (n = 431)
Records screened (n = 431)
Full-text arcles assessed for eligibility (n = 21)
Studies included in qualitave synthesis (n = 12)
Records excluded with tle alone (n = 397) Records excluded aer reading abstract (n = 13)
Full-text arcles excluded, aer reading full text (n=9)
Table 4 Preoxygenation methods. Method
Pros
Cons
Spontaneous breathing Tidal volume breathing
- Comfort
- Longer time to reach preoxygenation - Higher incidence of preox failure - 5 L/min less effective than 10 L/min
Deep breathing Non-invasive positive pressure ventilation Continuous positive pressure ventilation Pressure support ventilation
- Comfort - Requires less time - Faster pre-oxygenation - Faster pre-oxygenation - Greater improvement in post-preox PaO2
- Greater complexity than spontaneous breathing techniques - Possible discomfort - Greater complexity than spontaneous breathing techniques
oxygen saturation value that defined safe apnea time differed amongst the studies, limiting the extent to which they can be compared. Lastly, papers that employed the THRIVE system were excluded since high flow nasal cannula provide both preoxygenation and apneic oxygenation, while our study focused solely on preoxygenation.
general anesthesia. Another concurrent cause of atelectasis is the induction of general anesthesia itself, since the functional residual capacity diminishes in the supine, paralyzed and mechanically ventilated patient [31,32]. This issue can be easily addressed by employing either CPAP or PS (pressure support) + PEEP during preoxygenation or performing recruitment maneuvers as soon as the endotracheal tube is placed [33]. Preoxygenation extends the time to critical hypoxemia that would indicate esophageal intubation [34]. Verifying correct endotracheal tube placement via SpO2 is not considered the best indicator of a successful intubation, since it requires quite some time to drop if the tube is misplaced. EtCO2 is the current best practice for confirming endotracheal tube placement. This marker is not influenced by preoxygenation [35]. Reactive oxygen species do not pose any serious threat during preoxygenation. The entire procedure only lasts 3 min and the serious harm caused by reactive oxygen species seems to occur after 12 h of breathing high levels of inspired oxygen [1,36]. Finally, it would be interesting to evaluate the effectiveness of preoxygenation in non-critically ill patients with new methods, such as the oxygen reserve index [37]. The limitations of our review were the substantial lack of studies involving non-critically ill and non-ICU patients. Furthermore, the
5. Conclusion Preoxygenation is a safe and well tolerated procedure that lessens the harm of induction of general anesthesia in obese patients and should thus be employed. The use of PSV + PEEP allows for the fastest and most efficient rise in EtO2, with longer safe apnea time. For nonobese elective surgery patients, preoxygenation lengthened safe apnea time and caused no harm. However, the benefit of the procedure (i.e. less adverse events) is open to debate and requires further examination, possibly with a RCT. It must be noted that the authors were unable to perform a metanalysis since the pooled population of all the papers was to scarce and the definition of the basic parameters (e.g. peripheral oxyhemoglobin saturation level that defined a successful preoxygenation maneuver) varied considerably between the RCTs. 89
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Disclosures This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
[20]
[21]
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