Preoxygenation is a widely used technique where a high fraction of inspired oxygen (FIO2) is delivered to a patient. This increases oxygen stored in the lungs which provides the blood an increased reservoir in which to draw oxygen from during a period of apnea which then delays arterial oxyhemoglobin desaturation. Most commonly, preoxygenation is done prior to endotracheal intubation in order to provide enough oxygen during the period of apnea starting from inducing paralysis of the patient until the start of invasive mechanical ventilation. It can also be done prior to other situations where apnea is expected such as airway surgeries where mechanical ventilation must be stopped (tracheobronchial suctioning) or prior to extubation if there are concerns about the reversal of neuromuscular blockade or delayed emergence from anesthesia. Preoxygenation is most helpful in situations in which accessing the airway of a patient for intubation may be difficult such as patients with obesity or anatomical abnormalities, or when a patient has limited oxygen reserves such as patients with pulmonary disease.


Oxygen follows a well-defined pathway that begins with the atmosphere and ends with delivery to the mitochondria to be used for aerobic respiration. From the atmosphere, oxygen is stored in the alveoli in our lungs which then diffuses into blood. Oxygen is stored as oxyhemoglobin in red blood cells from which oxygen dissociates during tissue perfusion. It is then stored into tissues and used for aerobic respiration.1 (Figure 1).

Functional residual capacity (FRC) is the primary reservoir by which our lungs store oxygen. While breathing ambient air, about 13% of the FRC is oxygen, with an absolute volume of about 270mL in a healthy adult weighing 70kg1. By increasing the fraction of oxygen in inspired air, other gases present in FRC can be displaced by oxygen instead, increasing the absolute volume of oxygen present in the alveoli in FRC. Preoxygenation is referred to as denitrogenation, as nitrogen is the gas present at the highest concentrations in FRC during normal breathing. The displacement of nitrogen with oxygen is a process occurring in an exponential fashion, where the amount of oxygen present in FRC increases more and more slowly up to a certain limit.2 (Figure 2). This exponential relationship makes it so that after a certain point, delivery of oxygen at inspired concentrations of 100% (FIO2 = 1.0) has a minimal effect at increasing the alveolar concentration of oxygen. The end point that is commonly used is achieving an end-tidal O2 (EtO2) concentration of approximately 90% and an end tidal N2 concentration of about 5%.3 EtO2 = 90% means that 90% of expired gas consists of oxygen, thus closely approximating that gas left in the lungs after expiration is about 90% oxygen. EtO2 is a value that is readily seen and measured on an anesthesia machine during the process of preoxygenation, thus providing real-time feedback for physicians to know when they can safely proceed with apnea. With an FIO2 near 1.0, most healthy adults can reach the target EtO2 > 90% in about 3-5 minutes of breathing at tidal volumes.4 EtO2 concentration > 90% correlates with an absolute volume of oxygen greater than 2000mL in the lungs in a healthy 70kg adult.5 EtO2 values greater than 94% are difficult to achieve due to the inevitable presence of some residual CO2 and water vapor in alveolar gas.

The increase in oxygen stored in the lungs provides the blood an increased reservoir in which to draw oxygen from during a period of apnea. Values of O2 saturation (SaO2) should be greater than 90% because further desaturation below that point causes rapid desaturation of oxygen. This is due to the sigmoidal shape of the oxyhemoglobin dissociation curve, shaped in this way due to the property of cooperativity that oxygen exhibits when binding to hemoglobin.6 Essentially, when hemoglobin is more saturated, it is easier for hemoglobin to bind to oxygen and vice versa. In a healthy adult weighing 70kg, models have shown that the time during apnea until SaO2 falls below 90% is about 1 minute and a few seconds.7 By increasing the oxygen stored in the lungs to 87%, the time to 60% SaO2 is increased to about 9.9 minutes.5 (Figure 3) This time will be shorter in patients with a decreased ability to store oxygen in the lungs (pulmonary disease, obesity), and patients with a greater VO2 (pregnant, children).


Preoxygenation is most commonly done by mask ventilation prior to intubation. Typically, a patient will be asked to breathe deeply while wearing a mask that is providing a high concentration of oxygen. Induction of anesthesia will proceed with both sedation and paralysis. Once end expired oxygen concentration (EtO2) is greater than 90%, preoxygenation is complete. Intubation can proceed once there is sufficient paralysis of the patient.

Effective preoxygenation requires three factors: increasing FRC, maximizing FIO2, and then giving time.1 All three factors should be optimized in order to achieve effective preoxygenation.

Increasing FRC

Maximizing FRC gives oxygen the largest possible basin in which to be stored during preoxygenation. Many factors can contribute to the reduction of FRC from irreversible factors such as interstitial lung disease and anatomical chest wall deficiencies to reversible factors such as position dependent compression atelectasis. Specific ways to increase FRC in high-risk patients are discussed below and generally involve strategies that help offset the effect of gravity in compressing the lungs.

Maximizing FIO2

Preoxygenation should try and maximize the concentration of oxygen as much as possible with a high FIO2. The major reason for failure is a leak in the circuit that causes inspiration of room air.8 The most common place for a circuit leak is in the interface between the patient and the mask. Bearded patients, patients with facial anomalies, burns, edentulous patients, the presence of an NG tube, or ineffective technique are all factors that can make a leak more likely. The absence of normal capnographic tracing and lower end-tidal carbon dioxide concentration should alert the anesthesiologist to the presence of leaks in the circuit. Masking of the patient can be improved by extending the neck of the patient, a jaw thrust maneuver, the use of an oropharyngeal or nasopharyngeal airway, or utilizing two-handed mask ventilation.

A meta-analysis has shown that non-invasive mask ventilation (NIV) is superior to high-flow nasal cannula (HFNC) or conventional oxygen therapy (COT) in achieving effective preoxygenation.9 However, using adjunct techniques such as a combination strategy of both NIV and HFNC after mask ventilation during a period of apnea could extend the period of period before critical desaturation of the lungs and should be explored for further study.9

Give time

For most patients, the goal is to make the end tidal O2 to be above 90% which can be done with 3 minutes of tidal volume breathing or by increasing ventilation for a shorter time (8 vital capacity in 60 seconds).

However, emergency situations where there is insufficient time to achieve 3 minutes of tidal volume breathing, patients can instead be asked to perform eight vital capacity breathes over the course of sixty seconds.10 In these cases, the oxygen flow rate should be at least 10L/min. In situations where this is not possible due to acuity or mental status, even a few breaths of inspired high concentration FIO2 can provide some additional time until desaturation due to the exponential relationship of oxygenation.

At Risk Populations

Patients with Obesity

Patients with obesity are at greater risk for desaturation due to both having a lower FRC and an increased VO2 compared to patients without obesity. FRC is lower due to the compression of the chest wall by an increased mass of adipose tissue and VO2 is increased due to having a greater mass of tissue to perfuse. Additionally, patients with obesity tend to also have obstructive sleep apnea as a common comorbidity, thus making mask ventilation and intubation more difficult and increasing the apnea time required to complete the procedure. Studies have shown that the average time period for SaO2 to reach 90% was 2.7 minutes in patients with obesity while patients with normal body weight.12

Strategies to improve preoxygenation in obese patients include putting the bed in a head up position. This has the dual effect of reducing the compression of the lungs by the chest wall while also pulling down the diaphragm, both of which helps to increase FRC. Putting the head of the bed up 25 degrees prolongs desaturation time by 50 seconds.13

Pregnant Patients

Pregnant patients also have a lower FRC due and an increased VO2 compared to nonpregnant patients. FRC is lower due to compression of the diaphragm by the gravid uterus. Progesterone also causes pregnant patients to breathe with higher tidal volumes and be in a state of chronic respiratory alkalosis due to the increased amount of CO2 that they produce that needs to be exhaled. VO2 is increased due to increased metabolic demands caused by the fetus. The time to decrease to SaO2 = 95% during apnea was 173 seconds in pregnant patients and 243 patients in nonpregnant patients in supine position after preoxygenation4.

Improving preoxygenation can utilize putting the bed in head up position. Additionally, using higher O2 flow (10L/min) was shown to help due to the increased minute ventilation of pregnant patients.14


Elderly patients have weaker respiratory muscles and parenchymal changes in the lungs related to elastic recoil. Even though oxygen use (VO2) is decreased in elderly patients, O2 intake is disordered which results in faster desaturation during apnea.8


Pediatric patients are at greater risk of desaturation due to having smaller FRC and higher VO2 relative to body mass compared with adult patients. They only require 2 minutes of preoxygenation due to their smaller lung volumes.15 The younger the child, the faster the desaturation time.

Pulmonary Disease

Patients with pulmonary disease tend to have decreased FRC, V/Q mismatch, and increased VO2 relative to healthy patients. Even in patients with technically increased FRC from chronic obstructive pulmonary disease, the shunting caused by poor ventilation due to air trapping causes their oxygen reserves to be lower than healthy patients.4 They require 5 or more minutes of tidal volume breathing in order to reach sufficient EtO2 levels for preoxygenation.16

Side Effects

Delayed Diagnosis of Esophageal Intubation

Preoxygenation can potentially lead to the delayed recognition of esophageal intubation due to extending the time before hypoxemia occurs due to the increased oxygen reserve. This is especially true if SpO2 is used as the metric of successful intubation. However, there are many other ways to confirm a successful intubation, including the presence of an end-tidal CO2 concentration, visualization of chest-rise with ventilation, and auscultation of breath sounds.17 Due to the benefits of preoxygenation, this is not a reason to abandon the procedure and metrics other than SpO2 should be used to confirm successful intubation.

Absorption Atelectasis

Absorption atelectasis is the most common side effect of patients undergoing general anesthesia, present in 75 to 90% of patients to some degree.18 Absorption atelectasis occurs gas is absorbed into pulmonary capillaries causing the lungs to collapse when there is no additional ventilation. Nitrogen gas is poorly soluble in plasma, thus replacing it with the much more soluble oxygen gas in preoxygenation makes the overall volume of gas in the alveoli more absorbable, making the alveoli more likely to collapse.4 This can be prevented with the use of continuous positive airway pressure (CPAP) (6cm H2O) during preoxygenation or the use or positive end expiratory pressure (PEEP) during mask ventilation.19 Recruitment measures such as using an airway pressure of 40cm H2O for 4-9 seconds can be used to reopen closed off alveoli.20 This can be done after intubation or before extubation in situations where absorption atelectasis is suspected.

Generation of Reactive Oxygen Species

High concentrations of oxygen can cause oxygen toxicity through the generation of reactive oxygen species. When a dioxygen molecule is split inadvertently, it can create superoxide anions, hydroxyl radicals, and hydrogen peroxide, all of which are molecules that can react with biological components such as lipids, DNA, and proteins and damage them.21 This can lead to clinical manifestations of pulmonary edema, acute respiratory distress syndrome, retinal detachment, retinopathy of prematurity, and seizures.22 However, studies have shown that the symptoms of oxygen related injury manifest after 12 hours of breathing oxygen at high concentrations, thus the relatively short period of time required for preoxygenation is unlikely to result in the production of sufficient reactive oxygen species needed to cause injury.23


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