Many factors affect efficacy and efficiency (Table 3).16 Factors affecting the efficacy of preoxygenation include the FIO2, duration of preoxygenation, and the alveolar ventilation/functional residual capacity ratio. Failure to achieve an FIO2 near 1.0 can be caused by a leak under the face mask,34,35 rebreathing of exhaled gases, and the use of resuscitation bags incapable of delivering high FIO2. 31
Bearded patients, edentulous patients, elderly patients with sunken cheeks, use of the wrong size face mask, improper use of head straps, and the presence of gastric tubes are common factors causing air entrainment and a lower FIO2. The absence of a normal capnographic tracing, and a lower than expected end-tidal carbon dioxide concentration (EtCO2) and EtO2 should alert the anesthesiologist to the presence of leaks in the anesthetic circuit.8 FIO2 can also be influenced by the duration of breathing, technique of breathing, and the level of the fresh gas flow (FGF).36 Adequate time is needed to achieve maximal preoxygenation. With an FIO2 near 1.0, most healthy adults with tidal volume breathing can reach the target level of an EtO2 > 90% within 3 to 5 minutes. The half-time for an exponential change in the fraction of FAO2 following a step change in FIO2 is given by the equation: FAO2 = 0.693 × Volume of gas in the functional residual capacity / alveolar ventilation. With a functional residual capacity of 2.5 L, the half-times are 26 seconds when alveolar ventilation = 4 L/min and 13 seconds when alveolar ventilation = 8 L/min.8 These findings indicate that hyperventilation can reduce the time required to increase the O2 stores in the lungs, which provides the basis for using deep breathing as an alternative to tidal volume breathing.27,37–39 A wide range of preoxygenation techniques have been described (Table 4).16
Increasing the FGF from 5 to 10 L does not increase appreciably the FIO2 during tidal volume breathing, although it does so during deep breathing.36 Because of the breathing characteristics of the circle system, the minute ventilation during deep breathing may exceed the FGF, resulting in rebreathing of N2 in the exhaled gases, consequently decreasing the FIO2. However, during tidal volume breathing, rebreathing of N2 in the exhaled gases is negligible and thus increasing the FGF from 5 to 10 L has minimal effect on FIO2.36 Regardless of the technique used, the goal is to reach the end point of maximal preoxygenation, which can be easily measured with most anesthesia monitors.
All investigations have demonstrated that preoxygenation markedly delays arterial oxyhemoglobin desaturation during apnea.8,21,23,28 The extent of this delay in desaturation depends on the efficacy of preoxygenation, the capacity for O2 loading, and the VO2.33 Patients with a decreased capacity for O2 transport (decreased functional residual capacity, PaO2, arterial O2 content, or cardiac output) or those with an increased VO2 develop oxyhemoglobin desaturation more rapidly during apnea than healthy patients.8,28 Farmery and Roe40 developed and validated a computer model describing the rate of oxyhemoglobin desaturation during apnea. The model is particularly useful for analyzing oxyhemoglobin desaturation values below 90%. These values are dangerous to allow in human subjects, because below 90%, there will be a steep decline of PaO2 because of the sigmoid shape of oxyhemoglobin dissociation curve. In a healthy 70-kg patient, when FAO2 is progressively decreased from 0.87 (FIO2 of 1.0) to 0.13 (air), the apnea time to 60% SaO2 is decreased from 9.9 to 2.8 minutes (Figure 3).28
PREOXYGENATION FOR HIGH-RISK PATIENT POPULATIONS
Rapid sequence induction/intubation is commonly performed in pregnant women who are given general anesthesia and preoxygenation is essential in these patients. Maximal preoxygenation can be achieved more rapidly in pregnant than in nonpregnant women because of a higher alveolar ventilation and a lower functional residual capacity.22,41 However, during apnea, pregnant women tend to develop oxyhemoglobin desaturation more rapidly because of a limited O2 volume in their smaller functional residual capacity combined with an increased VO2. The time required for SaO2 to decrease to 95% during apnea was found to be 173 seconds in pregnant women and 243 seconds in nonpregnant women in the supine position.42 Use of the 45° head-up position results in an increase in desaturation time in nonpregnant women but not in pregnant women. It is possible that the gravid uterus prevents the descent of the diaphragm and does not allow the expected increase in functional residual capacity in the head-up position.42 In pregnant women, the 4 deep breathing technique is inferior to the 3-minute tidal volume breaths technique and should not be used, except in emergencies.43 An increased minute ventilation in pregnant women requires that an O2 flow of 10 L/min be used during preoxygenation.44
Morbidly Obese Patients
Studies have demonstrated that, following preoxygenation with tidal volume breathing for 3 minutes, the time required for SaO2 to fall to 90% during apnea is markedly reduced in morbidly obese patients (BMI > 40 kg/m2) compared with nonobese patients.45,46 During apnea following preoxygenation, the average time to reach an SaO2 of 90% in patients with normal body weight was 6 minutes, whereas that in morbidly obese patients was only 2.7 minutes.47 These findings are particularly concerning because morbid obesity is often complicated by obstructive sleep apnea, which can make mask ventilation and intubation more difficult. Rapid oxyhemoglobin desaturation during apnea in morbidly obese patients was attributed to an increased VO2 and a markedly reduced functional residual capacity. The supine position enhances this decrease in functional residual capacity because of a cephalad displacement of the diaphragm. Placing severely obese patients in the 25° head-up position during preoxygenation has been shown to prolong the time of desaturation by approximately 50 seconds.48
Some anesthesiologists may prefer awake fiberoptic intubation rather than rapid sequence induction/intubation in morbidly and super morbidly obese patients (BMI > 50 kg/m2), especially when they have associated problems.49 An advantage of this approach is the maintenance of airway patency during spontaneous breathing until an “unhurried” tracheal intubation can be accomplished. Face mask preoxygenation should precede intubation attempts and should be continued with the placement of a nasal cannula or an O2 catheter in the oropharynx. O2 flow (up to 5 L/min) through the working channel of the scope has the double advantage of insufflating O2 and enhancing laryngeal visualization by preventing fogging and pushing secretions away. It is important to recognize that airway obstruction can hinder the egress of gases from the fiber-optic scope, which, if prolonged, can result in barotrauma. Thus, caution cannot be overemphasized when this approach is utilized. Techniques to enhance preoxygenation, which are described later, are especially important in morbidly and supermorbidly obese patients.
Studies have demonstrated that maximal preoxygenation (EtO2 = 90%) can be accomplished in children faster than in adults.50,51 With tidal volume breathing, an EtO2 of 90% can be reached within 100 seconds in almost all children, whereas with deep breathing, it can be reached in 30 seconds.50,51 Nevertheless, because children have a smaller functional residual capacity and a higher VO2 than adults, they are at a greater risk for developing hypoxemia, when there is interruption in O2 delivery, such as during apnea or airway obstruction.52–54 In a comparison of 3 groups of children who breathed O2 (Flo2 = 1.0) with tidal volume breathing for 1, 2, and 3 minutes before apnea, the time needed for SaO2 to decrease from 100% to 95% and then to 90% during apnea was least in those who breathed O2 for 1 minute and there was no difference between those who breathed O2 for 2 and 3 minutes.55 Based on these findings, 2 minutes of preoxygenation with tidal volume breathing seems sufficient for a maximum benefit and to allow a safe period of apnea.55 The benefit of preoxygenation is greater in an older child than that in an infant. For example, in an 8-year-old child, the duration of safe period of apnea can be extended from 0.47 minute without preoxygenation to 5 minutes or longer with preoxygenation.56 The younger the child, the faster the onset of desaturation.53,54,57 Most infants reach a SaO2 of 90% in 70 to 90 seconds after the onset of apnea (in spite of preoxygenation),58 and this period can be even shorter in the presence of upper respiratory tract infection.59 Pediatric anesthesiologists have expressed concerns about the use of the “adult” version of the rapid sequence induction/intubation technique in children.60 The concerns include the safe duration of apnea and the potential for cricoid pressure-induced airway obstruction. A modified version of the rapid sequence induction/intubation technique, with emphasis on complete muscular relaxation, gentle manual ventilation using high O2 concentration without cricoid pressure and sufficient anesthetic depth before intubation would seem more appropriate in children.61
Aging is associated with significant structural and physiologic changes in the respiratory system.62,63 The changes include weakened respiratory muscles and parenchymal alterations within the lungs accompanied by a decrease in the elastic recoil. Lung volumes are decreased with increased closing volume, resulting in ventilation—perfusion mismatch, a reduced pulmonary reserve, and an impaired O2 uptake at the lung. Even though basal VO2 decreases with aging, the impaired O2 uptake produces a more rapid desaturation during apnea under anesthesia.63 In elderly patients, tidal volume breathing for 3 minutes or longer has been shown to be more effective than the 4 deep breathing technique.64,65
Patients With Pulmonary Disease
Both efficacy and efficiency can be adversely affected by pulmonary disease. Significant pulmonary disease is associated with a decreased functional residual capacity, appreciable ventilation—perfusion mismatch, and an increased VO2, which can reduce the margin of safety. Anesthesia has been shown to cause further impairment to gas exchange in patients with chronic obstructive pulmonary disease.66 Even brief interruption of ventilation, such as during suctioning can result in significant desaturation. However, atelectasis is not a consequence, possibly because chronic hyperinflation of the lungs resists volume decrease and collapse.67 Maximal preoxygenation, which is essential in these patients, may require as much as 5 minutes or longer with tidal volume breathing.68
Patients at High Altitude
High altitude does not alter the concentration of inspired O2 (21%), but the reduced barometric pressure produces a decrease in the partial pressure of alveolar and arterial PO2.69 For example, in Flagstaff, AZ, with an altitude of 2100 m (approximately 7000 feet above sea level), PaO2 is reduced from the normal value of 100 mm Hg to approximately 74 mm Hg.69 As altitude increases, PaO2 decreases exponentially. No studies, to our knowledge, have been performed to assess the effect of high altitude on preoxygenation. This is difficult to predict because of the multiple determinants of preoxygenation and the potential influence of compensatory mechanisms, especially in acclimatized individuals. It is possible that patients at high altitude will require a longer duration of preoxygenation to achieve an acceptable degree of protection, but this remains to be confirmed experimentally.
TECHNIQUE OF PREOXYGENATION
To provide effective preoxygenation, a methodical approach is necessary. The importance of preoxygenation with a tight-fitting mask should be explained to the patient beforehand. Once preoxygenation is initiated, EtO2 and FIO2 values should be monitored closely. If the EtO2 value does not increase as expected, the anesthesia provider may have to hold the mask with both hands and/or replace the mask with a better-fitting one. Whenever possible, the induction should not start until the EtO2 value approximates or exceeds 90%.
TECHNIQUES TO ENHANCE PREOXYGENATION
Apneic Diffusion Oxygenation
Preoxygenation followed by “apneic diffusion oxygenation” is an effective maneuver for prolonging the safe duration of apnea.16,70–73 The physiologic basis of this maneuver is as follows. During apnea in adults, VO2 averages 230 mL/min, whereas CO2 delivery to the alveoli is only 21 mL/min.16 The remaining 90% (or more) of CO2 is buffered within body tissues. The result is that lung volume decreases initially by 209 mL/min, which creates a pressure gradient between the upper airway and the alveoli, and provided that the airway is not obstructed, O2 enters the lung via diffusion. Because CO2 cannot be exhaled, PaCO2 rises from 8 to 16 mm Hg in the first minute of apnea, followed by a linear rise of approximately 3 mm Hg/min.74
The benefit of apneic diffusion oxygenation is dependent on achieving maximal preoxygenation before apnea, maintaining airway patency, and the existence of a high functional residual capacity to body weight ratio. Fraioli et al75 demonstrated that patients with a low predicted functional residual capacity/body weight ratio (37 ± 9 mL/kg) could not tolerate apneic oxygenation for more than 5 minutes, whereas patients with a high predicted functional residual capacity/body weight ratio (53 ± 8 mL/kg) could tolerate apneic oxygenation for at least 15 minutes. Although PaO2 falls in direct relation to PAO2, SaO2 remains greater than 90% as long as the hemoglobin can be reoxygenated in the lungs.32,71,75 SaO2 starts to decrease only after the O2 stores in the lungs are depleted, and PaO2 falls below 60 mm Hg. When SaO2 is <80%, the rate of decrease in saturation is approximately 30%/min. In the presence of an airway obstruction, gas volume in the lungs decreases rapidly, and intrathoracic pressure decreases at a rate dependent on lung compliance and VO2. When the airway obstruction is relieved, a rapid flow of O2 into the lungs resumes, and with high FIO2, preoxygenation is restored.32 Some studies have demonstrated that, with a patent airway, apneic diffusion oxygenation can maintain SaO2 above 90% for up to 100 minutes.71 When FIO2 is at a high level, a small increment can produce a profoundly disproportionate delay in hemoglobin desaturation; the delay in hemoglobin desaturation achieved by increasing FIO2 from 0.9 to 1.0 was greater than that achieved by increasing FIO2 from 0.21 to 0.9 (Figure 4).76
Apneic diffusion oxygenation can be achieved by maximal face mask preoxygenation followed by O2 insufflation up to 15 L/min through a nasopharyngeal or an oropharyngeal cannula or through a needle inserted in the cricothyroid membrane. In healthy patients with an unobstructed airway, this technique can provide at least 10 minutes of adequate oxygenation. The clinical applications include patients who are difficult to intubate or ventilate and patients with limited oxygen reserves. The technique can also be used during bronchoscopy and can provide adequate time for short glottic surgical procedures unimpeded by the presence of a tracheal tube or the patient’s respiratory excursions. Although oxygenation can be maintained for longer periods, a limiting factor of apneic oxygenation is the progressive rise of PaCO2 during apnea.74
Continuous Positive Airway Pressure and Positive End-Expiratory Pressure
Use of continuous positive airway pressure (CPAP) during preoxygenation of obese patients did not delay the onset of desaturation, because the functional residual capacity returned to the pre-CPAP level when the patient was induced and the mask was removed.78 However, the use of CPAP during preoxygenation followed by mechanical ventilation using positive end-expiratory pressure (PEEP) for 5 minutes before removing the mask and securing the airway, delayed the desaturation time.78,79
Noninvasive Bilevel Positive Airway Pressure
BiPAP (bilevel positive airway pressure; inspiratory positive airway pressure and expiratory positive airway pressure) combines the benefits of pressure support ventilation and CPAP and keeps the lungs open during the entire respiratory cycle. BiPAP has been used during preoxygenation to decrease intrapulmonary shunting and to increase the margin of safety during apnea in morbidly obese patients.80 The technique has also been used to reduce postoperative pulmonary dysfunction and to treat patients with respiratory failure from various etiologies.81
Transnasal Humidified Rapid Insufflation Ventilatory Exchange
Transnasal humidified rapid insufflation ventilatory exchange (THRIVE) is a new technique that is available for use in critically ill patients and in patients with difficult airways. The technique combines the benefits of apneic oxygenation and CPAP with a reduction in CO2 levels through gaseous mixing and flushing of the dead space (Figure 5).82 THRIVE is administered through a standard, commercially available, nasal, high-flow oxygen delivery system. Insufflation of O2 up to 70 L/min via a purpose-made nasal cannula is used initially to provide preoxygenation, which can be continued during intravenous induction and neuromuscular blockade until a definitive airway is secured. CPAP of approximately 7 cm H2O splints the upper airways and reduces shunting.84 The THRIVE technique has been demonstrated to appreciably prolong the safe duration of apnea while avoiding increase in CO2.83
POTENTIAL RISKS OF PREOXYGENATION
Delayed Diagnosis of Esophageal Intubation
Although an unrecognized esophageal intubation ultimately results in severe hypoxemia, minutes may elapse before this occurs. Preoxygenation extends the time period before hypoxemia ensues and, thus, delays the detection of a misplaced endotracheal tube when SpO2 is being used as an indicator. Cases attributing a delayed diagnosis of esophageal intubation to preoxygenation85,86 prompted some clinicians to suggest abandoning the maneuver.84 However, this would seem to be an extreme reaction when the practice has proven benefits. Furthermore, it should be emphasized (1) that normal pulse oximetry readings after intubation should not be regarded as evidence of proper endotracheal tube placement and (2) that a severe fall in SpO2 is a relatively late manifestation of an esophageal intubation. In spite of occasional false-positive and false-negative results, identification of CO2 in the exhaled gas (end-tidal CO2), which is readily available on all anesthesia monitors, is a well-accepted and routinely used indicator of proper endotracheal tube placement. The reader is referred to airway management texts and review articles discussing the methods of verification of endotracheal tube placement.87
Atelectasis occurs in 75% to 90% of healthy individuals undergoing general anesthesia,87,88 and absorption atelectasis is the most common side effect of preoxygenation. It is initiated by 2 mechanisms during anesthesia.89–92 One mechanism is the decrease in the functional residual capacity. Both the supine position and induction of anesthesia reduce lung volume, so that it approximates the residual volume. The end-expiratory volume may be lower than the closing capacity leading to airway closure and collapse of the dependent areas of the lung. The second mechanism is compression atelectasis. This is because of changes in the shape of the chest wall, spine, and diaphragm, which cause an increase in intraabdominal pressure leading to compression of the thoracic cavity and airway closure. Normally, O2 shares alveolar space with other gases, principally N2 which is poorly soluble in plasma and therefore remains in high concentration in alveolar gas. In the presence of a partial or complete airway closure, the gases gradually diffuse out of the alveoli and are not replaced. During air breathing, emptying of the lung is limited by the sluggish diffusion of N2. However, during preoxygenation, the rapid replacement of N2 with O2 promotes loss of gas from the lung to the blood stream resulting in alveolar collapse, that is, absorption atelectasis. Absorption of gas does not in itself cause atelectasis, but in effect accelerates collapse should airway closure occur from either of the above 2 mechanisms.91,92
Techniques that have been proposed to decrease the extent of absorption atelectasis following preoxygenation are (1) decreasing the concentration of FIO2 and (2) various recruitment maneuvers. Studies using computer modeling, as well as those involving actual measurements in patients using computerized tomography (CT), have demonstrated that decreasing the value of FIO2 can have a profound effect on the extent of atelectasis.93–96 Computer model of absorption atelectasis predicted that preoxygenation with an FIO2 of 1.0 would accelerate the collapse of the lung.93 A CT study found that atelectasis was less when patients were ventilated with 30% O2 during induction of anesthesia than when 100% O2 was used.94 Another CT study evaluated the effect of stepwise variations in inspired O2 on the extent of atelectasis and the time to arterial desaturation (Table 5).95 The investigators found (1) that atelectasis was significant in patients receiving 100% O2, but that it was small and virtually absent in patients receiving 80% and 60% O2, respectively and (2) that the time to desaturation fell with decreasing O2 concentration. Studies have also shown that administering 100% O2 during emergence from anesthesia can increase atelectasis. Benoit et al96 found a 6.8% atelectasis in patients awakened on an FIO2 of 1.0 compared with 2.6% in those awakened on an FIO2 of 0.4.
Recruitment maneuvers are commonly performed in patients under general anesthesia, but they have particular value in conjunction with preoxygenation. These maneuvers include CPAP, PEEP, and/or reexpansion maneuver. A CT study found that the combined use of CPAP (6 cm H2O) during 5 minutes of preoxygenation with face mask while breathing spontaneously, and PEEP (6 cm H2O) during mask ventilation for additional 5 minutes during induction of anesthesia, prevented the marked increase in atelectasis that was evident in a control group.77 A reexpansion maneuver is a vital capacity maneuver. Rothen et al97 evaluated the dynamics of reexpansion of atelectasis with a vital capacity maneuver during general anesthesia. They found that reopening of the alveoli occurred mainly during the first 7 to 8 seconds of application of an airway pressure of 40 cm H2O. Typically, this maneuver is used soon after tracheal intubation and before tracheal extubation.
Production of Reactive Oxygen Species
Oxygen is a paramagnetic atom containing 2 unpaired electrons in its outer shell that usually exists in the form of dioxygen (O2). In biological tissues, the dioxygen molecule can be accidentally or deliberately split, producing reactive oxygen species, which include superoxide anion, hydroxyl radical, and hydrogen peroxide.98–100 Reactive oxygen species can react with critical molecular components, such as lipids, DNA, and proteins, causing significant cellular damage.101,102 Although endogenous antioxidant mechanisms are normally sufficient to prevent high tissue concentrations of reactive oxygen species, these mechanisms can become overwhelmed resulting in oxidative stress.102,103 It is known that prolonged use of FIO2 = 1.0 can cause production of reactive oxygen species. Clinical manifestations are pulmonary edema, acute respiratory distress syndrome, retinal detachment, retinopathy of prematurity, and seizures.104 The signs of early lung injury begin to appear after 12 hours of high concentrations of O2 breathing.105 Thus, because of its short duration, cellular injury due to reactive oxygen species would not be applicable to preoxygenation.
The cardiovascular responses during preoxygenation have received limited attention and have not been well characterized. But there have been many studies, both in humans and animal models, assessing the steady state cardiovascular responses during high O2 breathing, which may provide insight into the hemodynamic changes during preoxygenation. However, the changes in PaO2 during preoxygenation are dynamic and brief, and, furthermore, they have been demonstrated to vary in different patient populations. Thus, caution should be exercised in extrapolating the experimental findings described below to a given patient undergoing preoxygenation.
Several studies in normal male subjects have demonstrated that breathing 100% O2 causes a modest decrease in heart rate accompanied by a parallel decrease in cardiac output. Systemic vascular resistance and arterial blood pressure increase.106–108 These changes are attributable to a reflex loop, either chemoreceptor or baroreceptor in origin. Since atropine abolishes the reduction in heart rate, this response is mediated by the vagus nerves.107
A number of physiologic studies have assessed the effect of inhalation of 100% O2 in the human coronary circulation.109–113 Hyperoxia consistently caused a marked decrease in coronary blood flow (reflecting coronary vasoconstriction) accompanied by a decrease in myocardial oxygen consumption. The direct coronary vasoconstrictor effect of hyperoxia is due to the oxidative inactivation of nitric oxide110,112 and other vasodilators released from the vascular endothelium and to closure of the ATP-sensitive K+ channels.113,114 Investigations in patients with normal coronary arteries have indicated that, despite the decrease in coronary blood flow, oxygenation at the level of the myocytes remains adequate, as indicated by continued myocardial lactate extraction rather than conversion to production.108,109 This is likely explained by the ability of the increase in arterial O2 content to blunt the reduction in coronary O2 supply caused by the reduced coronary blood flow combined with a reduction in myocardial O2 demand, secondary to the hyperoxia-induced bradycardia. Metabolic findings in patients with severe coronary artery disease have been inconsistent. Some studies have found that O2 breathing by these patients converts myocardial lactate production to extraction, suggesting a beneficial effect,108 whereas others have found that O2 breathing precipitates or accentuates myocardial lactate production, implying ischemic changes.110
It is well established that inhalation of high O2 can also reduce cerebral blood flow because of vasoconstriction.115–118 It has been proposed that this effect may be because, at least in part, of the associated decrease in PaCO2 that accompanies high O2 breathing rather than to a direct effect of O2.116 The mechanism for the decrease in PACO2 is as follows. When PaO2 is increased by inhalation of 100% O2, the CO2 dissociation curve for blood is altered (the Christiansen-Douglas-Haldane effect), such that there is a reduction in the affinity of blood for CO2. This produces an increase in cerebral tissue PCO2 and hydrogen ion concentration, which stimulates respiration with a result that PaCO2 decreases causing cerebral vasoconstriction.117,118 Investigators have also assessed the effect of hyperoxia on cerebral O2 consumption, using a functional magnetic resonance technique.117 They found that hyperoxia causes an approximate 20% decrease in cerebral O2 consumption, reflecting reduced neural activity.117 It was speculated that the decrease in cerebral O2 consumption was because of the ability of reactive oxygen species to damage lipids and proteins, and, in turn, decrease the enzyme activity in oxidative metabolic pathways.
Studies in animal models have demonstrated that hyperoxia causes vasoconstriction and a decrease in blood flow in peripheral vascular beds, including the kidney, gastrointestinal tract, and hindlimb.115,119,120 Whether this vasoconstriction is because of a direct effect of O2 on vascular smooth muscle or reflex-mediated via an arterial chemoreceptor/autonomic nerve remains unclear. Regardless, it is doubtful that changes in the peripheral vascular beds would have any important clinical effect during preoxygenation. The cardiovascular findings to date provide no justification for limiting the use of preoxygenation.
The literature provides overwhelming evidence that preoxygenation, whether instituted before induction or to emergence from anesthesia, delays the onset of hypoxemia during apnea. On that basis, preoxygenation should be performed in all patients given general anesthesia. Preoxygenation should also be performed whenever there is an anticipated interruption of O2 delivery, such as during open tracheobronchial suctioning, and before and during awake fiber-optic intubation, especially in high-risk patients, such as the supermorbidly obese. The technique should be performed correctly, with monitoring of EtO2. Because the advantage of preoxygenation may be blunted in high-risk patients, various maneuvers are available to prolong its effectiveness. The clinician should be familiar with these maneuvers. Absorption atelectasis during preoxygenation can be readily minimized, and thus it should not be a deterrent to the routine use of the technique.
Name: Usharani Nimmagadda, MD.
Contribution: This author helped write the manuscript.
Name: M. Ramez Salem, MD.
Contribution: This author helped write the manuscript.
Name: George J. Crystal, PhD.
Contribution: This author helped write the manuscript.
This manuscript was handled by: Richard C. Prielipp, MD, MBA, FCCM.
1. Dillon JB, Darsi ML. Oxygen for acute respiratory depression due to administration of thiopental sodium. JAMA. 1955;159:1114–1116.
2. Hamilton WK, Eastwood DW. A study of denitrogenation with some inhalation anesthetic systems. Anesthesiology. 1955;16:861–867.
3. Heller ML, Watson TR Jr. Polarographic study of arterial oxygenation during apnea in man. N Engl J Med. 1961;264:326–330.
4. Snow RG, Nunn JF. Induction of anaesthesia in the foot-down position for patients with a full stomach. Br J Anaesth. 1959;31:493–497.
5. Sellick BA. Cricoid pressure to control regurgitation of stomach contents during induction of anaesthesia. Lancet. 1961;2:404–406.
6. Wylie WD. The use of muscle relaxants at the induction of anaesthesia of patients with a full stomach. Br J Anaesth. 1963;35:168–173.
7. Salem MR, Wong AY, Collins VJ. The pediatric patient with a full stomach. Anesthesiology. 1973;39:435–440.
8. Benumof JL. Preoxygenation: best method for both efficacy and efficiency. Anesthesiology. 1999;91:603–605.
9. Kung MC, Hung CT, Ng KP, Au TK, Lo R, Lam A. Arterial desaturation during induction in healthy adults: should preoxygenation be a routine? Anaesth Intensive Care. 1991;19:192–196.
10. American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Practice guidelines for the management of the difficult airway. Anesthesiology. 2003;98:1269–1277.
11. Lake A. A response to ‘Avoiding adverse outcomes when faced with “difficulty with ventilation”’, Bell D, Anaesthesia 2003; 58: 945-948. Anaesthesia. 2004;59:202–203.
12. Frerk C, Mitchell VS, McNarry AF, et al. Difficult airway society 2015 guidelines for management of unanticipated difficult intubation in adults. Br J Anaesth. 2015;115:827–848.
13. Ericson LI. The effects of residual neuromuscular blockade and volatile anesthetics on the control of ventilation. Anesth Analg. 1999;89:243–251.
14. Eriksson LI, Sundman E, Olsson R, et al. Functional assessment of the pharynx at rest and during swallowing in partially paralyzed humans: simultaneous videomanometry and mechanomyography of awake human volunteers. Anesthesiology. 1997;87:1035–1043.
15. Baraka A. Safe reversal. 1. Atropine followed by neostigmine. An electrocardiographic study. Br J Anaesth. 1968;40:27–29.
16. Baraka AS, Salem MR. Hagberg CA. Preoxygenation. Benumof and Hagberg’s Airway Management, 2012:3rd ed. Philadelphia, PA: Mosby Elsevier; 657–682.
17. Popat M, Mitchell R, Dravid R, Patel A, Swampillai C, Higgs A. Difficult airway society guidelines for the management of tracheal extubation. Anaesthesia. 2012;67:318–340.
18. Nunn JF. Nunn JF. Oxygen. Nunn’s Applied Respiratory Physiology, 1993;4th ed. Philadelphia, PA: Butterworth-Heinemann; 247–305.
19. Campbell IT, Beatty PC. Monitoring preoxygenation. Br J Anaesth. 1994;72:3–4.
20. Berry CB, Myles PS. Preoxygenation in healthy volunteers: a graph of oxygen “washin” using end-tidal oxygraphy. Br J Anaesth. 1994;72:116–118.
21. Bhatia PK, Bhandari SC, Tulsiani KL, Kumar Y. End-tidal oxygraphy and safe duration of apnoea in young adults and elderly patients. Anaesthesia. 1997;52:175–178.
22. Russell GN, Smith CL, Snowdon SL, Bryson TH. Pre-oxygenation and the parturient patient. Anaesthesia. 1987;42:346–351.
23. Carmichael FJ, Cruise CJ, Crago RR, Paluck S. Preoxygenation: a study of denitrogenation. Anesth Analg. 1989;68:406–409.
24. Berthoud M, Read DH, Norman J. Pre-oxygenation—how long? Anaesthesia. 1983;38:96–102.
25. Archer GW Jr, Marx GF. Arterial oxygen tension during apnoea in parturient women. Br J Anaesth. 1974;46:358–360.
26. Gold MI, Duarte I, Muravchick S. Arterial oxygenation in conscious patients after 5 minutes and after 30 seconds of oxygen breathing. Anesth Analg. 1981;60:313–315.
27. Baraka AS, Taha SK, Aouad MT, El-Khatib MF, Kawkabani NI. Preoxygenation: comparison of maximal breathing and tidal volume breathing techniques. Anesthesiology. 1999;91:612–616.
28. Benumof JL, Dagg R, Benumof R. Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine. Anesthesiology. 1997;87:979–982.
29. Hayes AH, Breslin DS, Mirakhur RK, Reid JE, O’Hare RA. Frequency of haemoglobin desaturation with the use of succinylcholine during rapid sequence induction of anaesthesia. Acta Anaesthesiol Scand. 2001;45:746–749.
30. Heier T, Feiner JR, Lin J, Brown R, Caldwell JE. Hemoglobin desaturation after succinylcholine-induced apnea: a study of the recovery of spontaneous ventilation in healthy volunteers. Anesthesiology. 2001;94:754–759.
31. Nimmagadda U, Salem MR, Joseph NJ, et al. Efficacy of preoxygenation with tidal volume breathing. Comparison of breathing systems. Anesthesiology. 2000;93:693–698.
32. Sirian R, Wills J. Physiology of apnoea and the benefits of preoxygenation. Contin Educ Crit Care Pain. 2009;9:105–108.
33. Baraka AS, Salem MR. Hagberg C. Preoxygenation. Benumof and Hagberg’s Airway Management, 2007:2nd ed. Philadelphia, PA: Mosby Elsevier; 306.
34. McGowan P, Skinner A. Preoxygenation—the importance of a good face mask seal. Br J Anaesth. 1995;75:777–778.
35. Schlack W, Heck Z, Lorenz C. Mask tolerance and preoxygenation: a problem for anesthesiologists but not for patients. Anesthesiology. 2001;94:546.
36. Nimmagadda U, Chiravuri SD, Salem MR, et al. Preoxygenation with tidal volume and deep breathing techniques: the impact of duration of breathing and fresh gas flow. Anesth Analg. 2001;92:1337–1341.
37. Gold MI, Duarte I, Muravchick S. Arterial oxygenation in conscious patients after 5 minutes and after 30 seconds of oxygen breathing. Anesth Analg. 1981;60:313–315.
38. Gambee AM, Hertzka RE, Fisher DM. Preoxygenation techniques: comparison of three minutes and four breaths. Anesth Analg. 1987;66:468–470.
39. Pandit JJ, Duncan T, Robbins PA. Total oxygen uptake with two maximal breathing techniques and the tidal volume breathing technique: a physiologic study of preoxygenation. Anesthesiology. 2003;99:841–846.
40. Farmery AD, Roe PG. A model to describe the rate of oxyhaemoglobin desaturation during apnoea. Br J Anaesth. 1996;76:284–291.
41. Byrne F, Oduro-Dominah A, Kipling R. The effect of pregnancy on pulmonary nitrogen washout. A study of pre-oxygenation. Anaesthesia. 1987;42:148–150.
42. Baraka AS, Hanna MT, Jabbour SI, et al. Preoxygenation of pregnant and non-pregnant women in head-up versus supine position. Anesth Analg. 1991;46:824–827.
43. Norris MC, Dewan DM. Preoxygenation for cesarean section: a comparison of two techniques. Anesthesiology. 1985;62:827–829.
44. Russel EC, Wrench J, Feast M, Mohammed F. Preoxygenation in pregnancy: the effect of fresh gas flow rates within a circle breathing system. Anaesthesia. 2008;63:833–836.
45. Berthoud MC, Peacock JE, Reilly CS. Effectiveness of preoxygenation in morbidly obese patients. Br J Anaesth. 1991;67:464–466.
46. Baraka AS, Taha SK, Siddik-Sayyid SM, et al. Supplementation of pre-oxygenation in morbidly obese patients using nasopharyngeal oxygen insufflation. Anaesthesia. 2007;62:769–773.
47. Jense HG, Dubin SA, Silverstein PI, O’Leary-Escolas U. Effect of obesity on safe duration of apnea in anesthetized humans. Anesth Analg. 1991;72:89–93.
48. Dixon BJ, Dixon JB, Carden JR, et al. Preoxygenation is more effective in the 25 degrees head-up position than in the supine position in severely obese patients: a randomized controlled study. Anesthesiology. 2005;102:1110–1115.
49. Gil KSL, Diemunsch PA. Hagberg CA. Fiberoptic and flexible endoscopic aided techniques. Benumof’s and Hagberg’s Airway Management, 2013:3rd ed. Philadelphia, PA: Elsevier Saunders; 184–198.
50. Butler PJ, Munro HM, Kenny MB. Preoxygenation in children using expired oxygraphy. Br J Anaesth. 1996;77:333–334.
51. Morrison JE Jr, Collier E, Friesen RH, Logan L. Preoxygenation before laryngoscopy in children: how long is enough? Paediatr Anaesth. 1998;8:293–298.
52. Kinouchi K, Fukumitsu K, Tashiro C, Takauchi Y, Ohashi Y, Nishida T. Duration of apnoea in anaesthetized children required for desaturation of haemoglobin to 95%: comparison of three different breathing gases. Paediatr Anaesth. 1995;5:115–119.
53. Laycock GJ, McNicol LR. Hypoxaemia during induction of anaesthesia—an audit of children who underwent general anaesthesia for routine elective surgery. Anaesthesia. 1988;43:981–984.
54. Patel R, Lenczyck M, Hannallah RS, Mcgill WA. Age and onset of desaturation in apneic children. Can J Anaesth. 1994;41:771–774.
55. Xue FS, Tong SY, Wang XL, Deng XM, An G. Study of the optimal duration of preoxygenation in children. J Clin Anesth. 1995;7:93–96.
56. Hardman JG, Wills JS. The development of hypoxaemia during apnoea in children: a computational modelling investigation. Br J Anaesth. 2006;97:564–570.
57. Patel R, Lenczyk M, Hannallah RS, McGill WA. Age and the onset of desaturation in apnoeic children. Can J Anaesth. 1994;41:771–774.
58. Dupeyrat A, Dubreuil M, Ecoffey C. Preoxygenation in children. Anesth Analg. 1994;79:1027.
59. Kinouchi K, Tanigami H, Tashiro C, Nishimura M, Fukumitsu K, Takauchi Y. Duration of apnea in anesthetized infants and children required for desaturation of hemoglobin to 95%: the influence of upper respiratory infection. Anesthesiology. 1992;77:1105–1107.
60. Weiss M, Gerber AC. Rapid sequence induction in children—it’s not a matter of time! Paediatr Anaesth. 2008;18:97–99.
61. Priebe HJ. Cricoid force in children. Br J Anaesth. 2010;104:511.
62. Davies GA, Bolton CE. Fillit HM, Rockwood K, Woodhouse KW. Age related changes in respiratory system. Brockhurst’s Text Book of Geriatric Medicine and Gerontology, 2010:7th ed. Philadelphia, PA: Saunders Elsevier. 97–100.
63. Wahba WM. Influence of aging on lung function—clinical significance of changes from age twenty. Anesth Analg. 1983;62:764–776.
64. McCarthy G, Elliott P, Mirakhur RK, McLoughlin C. A comparison of different pre-oxygenation techniques in the elderly. Anaesthesia. 1991;46:824–827.
65. Valentine SJ, Marjot R, Monk CR. Preoxygenation in the elderly: a comparison of the four-maximal-breath and three-minute techniques. Anesth Analg. 1990;71:516–519.
66. Tarhan S, Moffit EA, Sessler A, Douglas WW, Taylor WF. Risk of anesthesia and surgery in patients with chronic bronchitis and chronic obstructive pulmonary disease. Br J Anaesth. 1973;74:720–726.
67. Gunnarsson L, Tokics L, Lundquist H, et al. Chronic obstructive pulmonary disease and anaesthesia: formation of atelectasis and gas exchange impairment. Eur Respir J. 1991;4:1106–1116.
68. Samain E, Biard M, Farah E, Holtzer S, Delefosse D, Marty J. Monitoring expired oxygen fraction in preoxygenation of patients with chronic obstructive pulmonary disease. Ann Fr Anesth Reanim. 2002;21:14–19.
69. Leissner KB, Mahmood FU. Physiology and pathophysiology at high altitude: considerations for the anesthesiologist. J Anesth. 2009;23:543–553.
70. Baraka A, Salem MR, Joseph NJ. Critical hemoglobin desaturation can be delayed by apneic diffusion oxygenation. Anesthesiology. 1999;90:332–333.
71. Frumin MJ, Epstein RM, Cohen G. Apneic oxygenation in man. Anesthesiology. 1959;20:789–798.
72. Ramachandran SK, Cosnowski A, Shanks A, Turner CR. Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration. J Clin Anesth. 2010;22:164–168.
73. Teller LE, Alexander CM, Frumin MJ, Gross JB. Pharyngeal insufflation of oxygen prevents arterial desaturation during apnea. Anesthesiology. 1988;69:980–982.
74. Eger EI, Severinghaus JW. The rate of rise of PaCO2
in the apneic anesthetized patient. Anesthesiology. 1961;22:419–425.
75. Fraioli RL, Sheffer LA, Steffenson JL. Pulmonary and cardiovascular effects of apneic oxygenation in man. Anesthesiology. 1973;39:588–596.
76. McNamara MJ, Hardman JG. Hypoxaemia during open-airway apnoea: a computational modelling analysis. Anaesthesia. 2005;60:741–746.
77. Cressey DM, Berthoud MC, Reilly CS. Effectiveness of continuous positive airway pressure to enhance pre-oxygenation in morbidly obese women. Anaesthesia. 2001;56:680–684.
78. Rusca M, Proietti S, Schnyder P, et al. Prevention of atelectasis formation during induction of general anesthesia. Anesth Analg. 2003;97:1835–1839.
79. Herriger A, Frascarolo P, Spahn DR, Magnusson L. The effect of positive airway pressure during pre-oxygenation and induction of anaesthesia upon duration of non-hypoxic apnoea. Anaesthesia. 2004;59:243–247.
80. El-Khatib MF, Kanazi G, Baraka AS. Noninvasive bilevel positive airway pressure for preoxygenation of the critically ill morbidly obese patient. Can J Anaesth. 2007;54:744–747.
81. Joris JL, Sottiaux TM, Chiche JD, Desaive CJ, Lamy ML. Effect of bi-level positive airway pressure (BiPAP) nasal ventilation on the postoperative pulmonary restrictive syndrome in obese patients undergoing gastroplasty. Chest. 1997;111:665–670.
82. 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;70:323–329.
83. Ritchie JE, Williams AB, Gerard C, Hockey H. Evaluation of a humidified nasal high-flow oxygen system, using oxygraphy, capnography and measurement of upper airway pressures. Anaesth Intensive Care. 2011;39:1103–1110.
84. Howells TH, Riethmuller RJ. Signs of endotracheal intubation. Anaesthesia. 1980;35:984–986.
85. McShane AJ, Martin JL. Preoxygenation and pulse oximetry may delay detection of esophageal intubation. J Natl Med Assoc. 1987;79:987–992991–992.
86. Salem MR, Baraka A. Hagberg CA. Confirmation of tracheal intubation. Benumof and Hagberg’s Airway Management. 2007;2nd ed. Philadelphia, PA: Mosby Elsevier. 697–216.
87. Gunnarsson L, Tokics L, Gustavsson H, Hedenstierna G. Influence of age on atelectasis formation and gas exchange impairment during general anaesthesia. Br J Anaesth. 1991;66:423–432.
88. Lundquist H, Hedenstierna G, Strandberg A, Tokics L, Brismar B. CT-assessment of dependent lung densities in man during general anaesthesia. Acta Radiol. 1995;36:626–632.
89. Joyce CJ, Baker AB. What is the role of absorption atelectasis in the genesis of perioperative pulmonary collapse? Anaesth Intensive Care. 1995;23:691–696.
90. Nunn JF, Williams IP, Jones JG, Hewlett AM, Hulands GH, Minty BD. Detection and reversal of pulmonary absorption collapse. Br J Anaesth. 1978;50:91–100.
91. Lumb AB, Pearl RG. Lumb AB. Anaesthesia. Nunn’s Applied Respiratory Physiology, 2010;7th ed. Philadelphia, PA: Churchill Livingstone Elsevier. 327–354.
92. Hedenstierna G, Edmark L. Mechanisms of atelectasis in the perioperative period. Best Pract Res Clin Anaesthesiol. 2010;24:157–169.
93. Joyce CJ, Williams AB. Kinetics of absorption atelectasis during anesthesia: a mathematical model. J Appl Physiol (1985). 1999;86:1116–1125.
94. Rothen HU, Sporre B, Engberg G, Wegenius G, Reber A, Hedenstierna G. Prevention of atelectasis during general anaesthesia. Lancet. 1995;345:1387–1391.
95. Edmark L, Kostova-Aherdan K, Enlund M, Hedenstierna G. Optimal oxygen concentration during induction of general anesthesia. Anesthesiology. 2003;98:28–33.
96. Benoît Z, Wicky S, Fischer JF, et al. The effect of increased FIO(2) before tracheal extubation on postoperative atelectasis. Anesth Analg. 2002;95:1777–1781.
97. Rothen HU, Neumann P, Berglund JE, Valtysson J, Magnusson A, Hedenstierna G. Dynamics of re-expansion of atelectasis during general anaesthesia. Br J Anaesth. 1999;82:551–556.
98. Jamieson D, Chance B, Cadenas E, Boveris A. The relation of free radical production to hyperoxia. Annu Rev Physiol. 1986;48:703–719.
99. Turrens JF, Freeman BA, Levitt JG, Crapo JD. The effect of hyperoxia on superoxide production by lung submitochondrial particles. Arch Biochem Biophys. 1982;217:401–410.
100. Turrens JF, Freeman BA, Crapo JD. Hyperoxia increases H2
release by lung mitochondria and microsomes. Arch Biochem Biophys. 1982;217:411–421.
101. Chandel NS, Budinger GR. The cellular basis for diverse responses to oxygen. Free Radic Biol Med. 2007;42:165–174.
102. Crystal GJ, Malik G, Yoon SH, Kim SJ. Isoflurane late preconditioning against myocardial stunning is associated with enhanced antioxidant defenses. Acta Anaesthesiol Scand. 2012;56:39–47.
103. Jenkinson SG. Oxygen toxicity. New Horiz. 1993;1:504–511.
104. Lumb AB, Walton LJ. Perioperative oxygen toxicity. Anesthesiol Clin. 2012;30:591–605.
105. Lumb AB. Just a little oxygen to breathe as you go off to sleep...is it always a good idea? Br J Anaesth. 2007;99:769–771.
106. Eggers J, Paley HW, Leonard JJ, Warren JV. Hemodynamic responses to oxygen breathing in man. J Appl Physiol. 1962;17:75–79.
107. Daly WJ, Bondurant S. Effects of oxygen breathing on the heart rate, blood pressure, and cardiac index of normal men—resting, with reactive hyperemia, and after atropine. J Clin Invest. 1962;41:126–132.
108. Ganz W, Donoso R, Marcus H, Swan HJ. Coronary hemodynamics and myocardial oxygen metabolism during oxygen breathing in patients with and without coronary artery disease. Circulation. 1972;45:763–768.
109. Neill WA. Effects of arterial hypoxemia and hyperoxia on oxygen availability for myocardial metabolism. Patients with and without coronary heart disease. Am J Cardiol. 1969;24:166–171.
110. Bourassa MG, Campeau L, Bois MA, Rico O. The effects of inhalation of 100 percent oxygen on myocardial lactate metabolism in coronary heart disease. Am J Cardiol. 1969;24:172–177.
111. McNulty PH, King N, Scott S, et al. Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheterization. Am J Physiol Heart Circ Physiol. 2005;288:H1057–H1062.
112. Farquhar H, Weatherall M, Wijesinghe M, et al. Systematic review of studies of the effect of hyperoxia on coronary blood flow. Am Heart J. 2009;158:371–377.
113. Rubanyi GM, Vanhoutte PM. Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol. 1986;250:H822–H827.
114. Mouren S, Souktani R, Beaussier M, et al. Mechanisms of coronary vasoconstriction induced by high arterial oxygen tension. Am J Physiol. 1997;272:H67–H75.
115. Bergofsky EH, Bertun P. Response of regional circulations to hyperoxia. J Appl Physiol. 1966;21:567–572.
116. Purves MJ. Regulation of cerebral vessels by oxygen. The Physiology of the Cerebral Circulation. 1972:Cambridge, UK: Cambridge University Press; 232–252.
117. Xu F, Liu P, Pascual JM, Xiao G, Lu H. Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism. J Cereb Blood Flow Metab. 2012;32:1909–1918.
118. Lambertsen CJ, Dough RH, Cooper DY, Emmel GL, Loeschcke HH, Schmidt CF. Oxygen toxicity; effects in man of oxygen inhalation at 1 and 3.5 atmospheres upon blood gas transport, cerebral circulation and cerebral metabolism.J Appl Physiol. 1953;5:471–486.
119. Kainuma M, Kimura N, Shimada Y. Effect of acute changes in renal arterial blood flow on urine oxygen tension in dogs. Crit Care Med. 1990;18:309–312.
© 2017 International Anesthesia Research Society
120. Flemming B, Seeliger E, Wronski T, Steer K, Arenz N, Persson PB. Oxygen and renal hemodynamics in the conscious rat. J Am Soc Nephrol. 2000;11:18–24.