Preoxygenation, Reoxygenation, and Delayed Sequence

Intubation in the Emergency Department

Scott D. Weingart, MD
Authors and Disclosures
Posted: 07/11/2011; J Emerg Med. 2011;40(6):661-7. © 2011 Elsevier Science, Inc.

 Abstract and Introduction

 Discussion

 Reoxygenation

 Delayed Sequence Intubation

 Conclusion

 References

Abstract and Introduction

Abstract
Background: The goal of preoxygenation is to provide us with a safe buffer of time before desaturation during
Emergency Department intubation. For many intubations, the application of an oxygen mask is sufficient to provide
us with ample time to safely intubate our patients. However, some patients are unable to achieve adequate saturations
by conventional means and are at high risk for immediate desaturation during apnea and laryngoscopy. For these
patients, more advanced methods to achieve preoxygenation and prevent desaturation are vital.
Discussion: We will review the physiology of hypoxemia and the means to correct it before intubation. Next, we will
discuss apneic oxygenation as a means to blunt desaturation and the optimal way to reoxygenate a patient if
desaturation does occur. Last, we will discuss the new concept of delayed sequence intubation, a technique to be used
when the discomfort and delirium of hypoxia and hypercapnia prevents patient tolerance of conventional
preoxygenation.
Conclusions: These new concepts in preoxygenation and reoxygenation may allow safer airway management of the
high-risk patient.

Introduction
Conventional preoxygenation techniques provide safe intubation conditions for a majority of emergency airways.
However, in a subset of patients, these techniques will lead to inadequate preoxygenation and fail to prevent
desaturation. To safely intubate this group, an understanding of the physiology of oxygenation is essential to allow
for optimal intubating conditions. This knowledge can then be applied at the bedside in the care of high-risk patients.
The goal of this work is to translate the tenets of physiology and the most recent literature to allow the safest possible
intubation of critically ill patients.

The Pathophysiology of Hypoxemia

To understand oxygenation, it is essential to understand the causes of hypoxemia. These causes are inadequate
alveolar oxygenation (low environmental oxygen pressure or alveolar hypoventilation), diffusion abnormalities, dead
space (high ventilation, low perfusion [V/Q] mismatch), low V/Q mismatch, shunt, and low venous blood saturation.
In the Emergency Department (ED) patient placed on ≥ 0.4 fraction-inspired oxygen (fiO2), all of these problems
have inconsequential effects on oxygenation except shunt and low venous blood saturation. See Figure 1
for an explanation of these two phenomena.
 Figure 1.

Ventilation/perfusion units. In the normal lung, oxygen enters the alveoli and
raises the saturation from the venous level of 70% to 100% by the time it
reaches the arterial side. In shunt, no oxygen can get in to the alveoli, so the
venous saturation is never increased. In low SvO2 situations, the alveoli are not
able to raise the low venous saturation to the normal arterial level. When these
two problems are both present, the arterial desaturation becomes even worse.

(Enlarge Image)

An anatomical shunt is a direct connection between the arterial and venous blood flow, for example, a septal defect in
the heart. When we speak about shunt as the cause of hypoxemia, we are rarely referring to anatomical shunts.
Physiologic shunt is the major cause of poor oxygenation in ill ED patients already on supplemental oxygen. A
physiologic shunt is caused by areas of alveoli that are blocked from conducting oxygen, but still have intact blood
vessels surrounding them. This perfusion without any ventilation leads to a direct mixing of deoxygenated venous
blood into the arterial blood. Causes of shunt include pneumonia, atelectasis, pulmonary edema, mucus plugging, and
adult respiratory distress syndrome. No matter how high the fiO2, these areas will never have an improved
oxygenation because inhaled gas never reaches the blood. The only way to improve oxygenation in these areas of the
lungs is to fix the shunt.

Low venous oxygen saturation is also an important cause of hypoxemia in the ED. Venous blood is never fully
desaturated when it reaches the lungs. In normal patients, the hemoglobin reaching the lungs has a saturation of ~ 65–
70%, therefore, only a small amount of exposure to oxygen can rapidly bring the saturation to 100%. In shock states,
the venous blood will arrive at the lungs with lower saturations due to greater tissue extraction. This venous blood
will require more exposure to oxygen to reach a saturation of 100%; in injured lungs this may not occur. This
problem becomes much more deleterious when combined with physiologic shunt. In this combination, the already
abnormally low saturation venous blood mixes directly into the arterial supply.

This should impel the practitioner to always consider the circulatory system when evaluating the patient's respiratory
status. If the patient about to be intubated is in shock, attempts to improve and prevent the reduction of cardiac output
become methods to improve oxygenation. Tailoring sedative medications to the patient's cardiac status and blood
volume is critical.[1,2] If time allows, these patients will also benefit from aggressive preintubation normalization of
preload, afterload, and inotropy.[3,4]

Standard ED Preoxygenation
The standard recommended technique for ED preoxygenation is tidal volume breathing of oxygen from a high fiO 2
source for at least 3 min or eight vital capacity breaths.[5] When possible, a maximal exhalation preceding the tidal
volume breathing improves preoxygenation.[6,7] The non-rebreather mask (NRB), though the routine oxygen source,
provides only 65–80% of fiO2.[8] In a healthy non-obese adult patient, these standard techniques have been shown to
provide a buffer as long as 8 min before the saturation drops below the critical 90% threshold.[9] In the ill patient with
injured lungs, abnormal body habitus, or upregulated metabolism, this time is significantly shortened. [9] In some cases
it is impossible to obtain a saturation > 90% before the intubation attempt, regardless of the duration of standard
preoxygenation.

A patient with a saturation < 95% on a nasal cannula set to 6 L/min of oxygen is exhibiting at least some degree of
shunting, as this setting will provide ~ 0.4 fiO2.[8] If the saturation is < 95% on a NRB, the patient is exhibiting signs
of moderate to severe shunting. These latter patients are at risk for a precipitous and dramatic decline in oxygen
saturation during the intubation procedure.

We have seen many situations in which a patient preintubation is saturating < 90% even with a NRB; the providers
become frustrated, abandon further attempts at preoxygenation, and proceed to the immediate intubation of the
patient to improve the saturation. However, if the patient is saturating < 90% before rapid
sequence intubation (RSI), they may have an immediate and profound desaturation almost
immediately after the RSI drugs are administered. Figure 2 shows the oxygen-hemoglobin
dissociation (saturation) curve. The patient in this circumstance is already on the steep portion
of this curve and will shortly be at critically low pressures of oxygen.
 Figure 2.

Oxyhemoglobin dissociation curve. The shape of the curve demonstrates that

at 90% saturation, the patient is at risk of critically low oxygen levels (< 40 mm
Hg PaO2) if even a brief period of time elapses without reoxygenation. Patients
will take a much longer time to desaturate from 100% to 90% than to go from
90% to 70%.

(Enlarge Image)

This abandonment of preoxygenation and rush to premature intubation may be predicated on the fallacy that
saturation declines in a linear fashion over time. The shape of the curve in Figure 2 demonstrates that the time to go
from 100% to 90% is dramatically longer than the time it takes to go from 90% to injuriously low levels of oxygen
pressure resulting in dysrhythmia, seizure, and cardiac arrest.

In this circumstance of low saturation before RSI, many airway experts recommend preoxygenation with a
bag/valve/mask device (BVM). When the BVM is manufactured with an appropriate exhalation port and a tight mask
seal is obtained, it can deliver > 0.9 fiO2 both when the patient spontaneously breathes and with assisted ventilations.
[10]
However, this increase from a fiO2 of ~ 0.7 (NRB) to ~ 0.9 (BVM) will do nothing to ameliorate shunt and little to
correct low V/Q mismatched alveoli. In addition, it requires a practitioner to maintain an ideal mask seal during the
stressful moments of preparing for RSI. If the mask seal is inadequate, room air will be entrained.

Preoxygenation in High-risk Patients

Non-invasive ventilation (NIV) has become a mainstay in the management of respiratory emergencies in most EDs.
NIV is also the optimal technique for preoxygenation of high-risk patients. With a properly fitted, full-face NIV
mask, fiO2 of ~ 1.0 is assured, and because these masks strap around the patient's head, no practitioner is needed to
maintain the mask seal. With a setting of continuous positive airway pressure (CPAP) at 0 cm H 2O, this NIV set-up
will simply provide a source of nearly 100% oxygen. With increased CPAP settings, shunt can actually be treated and
the patient's oxygenation significantly improved.[11-15]

Starting with a CPAP setting of 5 and titrating up to a maximum of 15 cm H2O, 100% saturation can be achieved in
patients in whom NRB or BVM preoxygenation did not result in adequate saturations. This strategy requires the NIV
machine or, preferably, a standard ventilator standing by in the ED. Unless the ED is consistently staffed with an in-
department respiratory therapist, it is also necessary for the clinicians to know how to immediately set up and apply
NIV themselves.

In EDs where neither a ventilator nor a NIV machine is available, the patient can be preoxygenated by spontaneously
breathing through a BVM with a positive end-expiratory pressure (PEEP) valve attached. This is suboptimal, as a
provider must hold the mask tightly over the patient's face and even a slight break in the mask seal eliminates the
PEEP. PEEP valves will be discussed in more detail below.

Oxygenation During the Apneic Period

In standard RSI, the oxygen mask is left on the patient's face until the time of intubation. However, nothing is done to
maintain a patent connection between the mouth and the glottis. As the sedative and paralytic drugs take effect, the
tongue and the posterior pharyngeal tissues can occlude the passageway of oxygen to the glottis. Although this seems
irrelevant as the patient is no longer breathing, it ignores the benefits of apneic oxygenation.

Apneic Oxygenation
In an experiment by Frumin et al., patients were preoxygenated, intubated, paralyzed, and placed on an anesthesia
machine that provided 1.0 fiO2 and no ventilations.[16] These patients were maintained in this apneic state for between
18 and 55 min. None of these patients desaturated below 98%, despite being paralyzed and receiving no breaths.
Although their CO2 levels rose, their oxygenation was maintained due to apneic oxygenation. Oxygen was absorbed
from the patients' alveoli by pulmonary blood flow; this established a gradient for the continued pull of oxygen from
the endotracheal tube and anesthesia circuit. In another study, Teller et al. showed that pharyngeal insufflation with
oxygen significantly extended the time to desaturation during apnea.[17] Numerous studies on apneic oxygenation
during brain death testing confirm that even without any respiratory effort, oxygen saturation can be maintained. [18-20]

If a continuous path of oxygen is maintained from the pharynx to the glottis during the apneic period of RSI, the
patient will continue to oxygenate. This has led us to perform a jaw thrust in all high-risk patients during their apneic
period. In some cases, we also place nasopharyngeal airways to augment the passage of oxygen. These techniques,
combined with high-flow O2 from a NRB mask, NIV mask, or the facemask of a BVM, will allow continued apneic
oxygenation.

Another problem during the apneic period is absorption atelectasis due to alveoli filled with near 100% oxygen. The
nitrogen in normally ventilated alveoli serves to maintain their patency. When we preoxygenate with high fiO 2, our
 goal is to completely wash out this nitrogen. This can lead to alveolar collapse as the oxygen is taken up by
pulmonary blood; further shunt is the result.[21] The use of NIV ventilation with CPAP can maintain these alveoli in an
open state during the apneic period. When NIV is combined with a jaw thrust and patent oro/nasopharyngeal passage
of air, the potential benefits of apneic oxygenation can be fully realized

Reoxygenation

If the first pass at intubation fails and the patient's oxygen saturation drops below 90–95%, reoxygenation is required
before any further intubation attempts. The standard method for reoxygenation is to ventilate the patient with a BVM
apparatus attached to high-flow O2. Skilled practitioners will also place an oropharyngeal airway and, if there is any
difficulty, nasopharyngeal airways as well. Even in skilled hands, this method can be problematic; when performed
by a novice, it can be deadly.

Every BVM breath during reoxygenation potentially puts the patient at risk for gastric insufflation and aspiration.
Ideally, the patient would receive the minimum number of ventilations to achieve reoxygenation and these breaths
would be delivered in a slow, gentle manner to avoid overcoming the lower esophageal sphincter opening pressure of
~20–25 cm H2O.[22] However, studies show the difficulty of maintaining these goals during the stressful environment
of an emergency resuscitation.[23,24]

In addition to changes in time perception when stressed, another possible explanation for this is a misunderstanding
of the effects of increased ventilations on oxygen saturation. Ventilating the patient at increased respiratory rates will
not raise the oxygen saturation any faster than at a controlled rate. In Figure 3, the effects of alveolar ventilation on
oxygenation can be appreciated. At a fiO2 of 0.5, only ~ 500 mL/min of ventilation must reach the alveoli to generate
a high PaO2. At a fiO2 of 1.0, even less alveolar ventilation must occur to yield a PaO2 > 500 mm Hg. Even assuming
a high fraction of dead space in a patient undergoing resuscitation, this means that to achieve reoxygenation with the
buffer of a high PaO2, only 3–4 breaths/min are needed. Given this information, the rate of 10
breaths/min recommended by most resuscitation guidelines seems reasonable and safe,
offering at least double the required number of breaths. Ten slow (1.5–2 s per breath), low
tidal volume breaths per minute would seem the optimum rate for reoxygenation. Yet, when
the patient has desaturated, we often witness rates as high as 60–120 breaths/min.

Figure 3.

Alveolar ventilation vs. alveolar oxygenation. When breathing room air,

approximately 3 L must reach the alveoli to maintain a PaO2 > 100 mm Hg. If
the fiO2 is increased to 0.5, only 1 L/min is needed to generate a PaO2 > 500
mm Hg. If the fiO2 is increased beyond 0.5, even less alveolar ventilation is
needed.

(Enlarge Image)

Beyond ensuring the proper rate and timing of ventilations, ideal mask seal is also imperative or the ventilations will
not reach the alveoli. During our training, we are still taught how to correctly hold the mask of the BVM with one
hand, but this is an inferior method that often does not achieve an adequate seal. Two providers are needed for
reliably effective BVM ventilation: one to hold the mask with two hands and a second person to squeeze the bag.

Standard BVMs cannot provide PEEP, which, as we have previously discussed, is the only effective means to treat
shunt during emergent intubation. In patients who required CPAP for preoxygenation, to attempt to reoxygenate with
zero PEEP is illogical and often unsuccessful. PEEP valves are available that fit on the exhalation port of most BVM
devices. These strain valves allow the generation of some PEEP by occluding the exhalation port to a selectable
extent, but the PEEP disappears with continued gas absorption or with any loss of mask seal. Despite these
disadvantages, when no other options exist, PEEP valves can have dramatic effects on reoxygenation.

There is, however, another commonly available solution to the problems of BVM reoxygenation: the standard ED
mechanical ventilator as a reoxygenation device. This same ventilator can be used for the non-invasive
preoxygenation as mentioned above and therefore it is advantageous to have at the bedside a standard ventilator
rather than a non-invasive ventilation machine for the intubation of a high-risk patient.

The ventilator provides guaranteed slow, low tidal volume breaths. PEEP can be added and titrated to the patient's
requirements. A single provider can hold the two-hand mask seal while the ventilator delivers the respirations, freeing
up a practitioner. Ventilator settings for reoxygenation are shown in Figure 4. Two studies have compared handheld
ventilators to BVMs for non-intubated ventilations; these studies have shown the handheld ventilator to be safe and
that it may be associated with fewer complications.[25,26] The improved valve structure and more precise
settings of a standard rather than handheld ventilator make it even more desirable. For this
 strategy to be successful, the clinicians must be able to set up the ventilator themselves
without having to wait for a therapist to be paged down to the ED.

Figure 4.

The steps of non-invasive ventilation for preoxygenation, using the ventilator

for reoxygenation, and delayed sequence intubation (DSI).

(Enlarge Image)

Delayed Sequence Intubation

In some circumstances, the patients who most desperately require preoxygenation impede its provision. Hypoxia and
hypercapnia can lead to delirium, causing these patients to rip off their non-rebreather or NIV masks. This delirium,
combined with the oxygen desaturation on the monitor, often leads to precipitous attempts at intubation without
adequate preoxygenation. Thanks to the availability of novel pharmacologic agents, another pathway exists to
manage these patients.

Standard RSI consists of the simultaneous administration of a sedative and a paralytic agent and the provision of no
ventilations until after endotracheal intubation.[27] This sequence can be broken to allow for adequate preoxygenation
without risking gastric insufflation or aspiration; we call this method "delayed sequence intubation" (DSI). DSI
consists of the administration of specific sedative agents, which do not blunt spontaneous ventilations or airway
reflexes; followed by a period of preoxygenation before the administration of a paralytic agent.

Another way to think about DSI is as a procedural sedation, the procedure in this case being effective
preoxygenation. After the completion of this procedure, the patient can be paralyzed and intubated. Just like in a
procedural sedation, we want the patient to be comfortable, but still spontaneously breathing and protecting their
airway.

The ideal agent for this use is ketamine. This medication will not blunt patient respirations or airway reflexes and
provides a dissociative state, allowing the application of a NRB or, preferably, NIV.[28] A dose of 1–1.5 mg/kg by
slow intravenous push will produce a calmed patient within ~ 45 s. Preoxygenation can then proceed in a safe
controlled fashion. After a saturation of 100% is achieved, the patient is allowed to breathe the high fiO 2 oxygen for
an additional 2–3 min to achieve adequate denitrogenation of the alveoli. A paralytic is then administered and after
the 45–60-s apneic period, the patient can be intubated.

In patients with high blood pressure or tachycardia, the sympathomimetic effects of ketamine may be undesirable.
These effects can be ameliorated with small doses of benzodiazepine and labetalol.[28] In a slowly growing number of
EDs, a preferable sedation agent is available for hypertensive or tachycardic patients. Dexmedetomidine is an alpha-2
agonist, which provides sedation with no blunting of respiratory drive or airway reflexes.[29] It also will slightly lower
heart rate and blood pressure.[29] Acceptable conditions can be obtained with a bolus of 1 μg/kg over 10 min; if
continued sedation is necessary, a drip can be started at 0.5 μg/kg/h.[30-33] In many U.S. hospitals, this agent has not yet
moved from the operating room and intensive care unit to the ED, mainly due to cost.

Another advantage of DSI is that frequently, after the sedative agent is administered and the patient is placed on non-
invasive ventilation, the respiratory parameters improve so dramatically that intubation can be avoided. We then
allow the sedative to wear off and reassess the patient's mental status and work of breathing. If we deem that
intubation is still necessary at this point, we can proceed with standard RSI as the patient has already been
appropriately preoxygenated.

A video demonstrating the above concepts is available online at: http://blog.emcrit.org/misc/preox/

Conclusion

Conventional preoxygenation techniques provide safe intubation conditions for a majority of emergency airways.
However, in a subset of high-risk patients, these techniques will lead to inadequate preoxygenation and fail to prevent
desaturation. To safely intubate this group, meticulous attention must be paid to optimizing preoxygenation,
preventing deoxygenation and, if necessary, providing reoxygenation in a controlled manner. Future research is
needed to delineate optimal timing, dosing, and methods to achieve these goals.

New techniques such as NIV as a preoxygenation technique, the ventilator as a better BVM, and breaking the
sequence of RSI using the concepts of delayed sequence intubation may make the peri-intubation period safer
 References
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