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Introduction
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Last summer I wrote a postabout preoxygenation and apneic oxygenation using high-flow nasal cannula (HFNC). At that point there was no evidence supporting it, so the post was based primarily on the physiology of HFNC. Recently two papers were published supporting the use of HFNC for preoxygenation and apneic oxygenation (Patel 2015, Miguel-Montanes 2015). The surprising part is that Patel et al additionally found that high-flow nasal cannula provided apneic ventilation.
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Patel A et al. Transnasal humidified rapid-insufflation ventilator exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia 2015; 70:323.
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This is a case series of 25 patients undergoing hypopharyngeal or laryngotracheal surgery judged to be at high risk of peri-intubation desaturation based on both a predicted difficult airway plus obesity or underlying cardiorespiratory disease. Preoxygenation and apneic oxygenation was performed using HFNC at 70 liters/minute. The median apnea time was 14 minutes with an inter-quartile range between 9-19 minutes. No patient desaturated below 90% nor had an apnea time under five minutes.
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These apnea times likely under-estimate the maximal apnea time that might be expected for most patients. The study investigated a highly selected group of patients at high risk for desaturation. Furthermore, apnea was usually terminated when the airway was secured, preventing us from knowing how much longer the patient might have gone before desaturating.
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The most significant part of this paper may be that HFNC reduced the rise of carbon dioxide over time by a factor of three compared to prior studies:
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Classical apneic oxygenation with low-flow oxygen improves oxygenation without affecting ventilation. Without ventilation, PaCO2 increases about 8-16 mm in the first minute of apnea and then at a rate of about 3 mm/hg/min (Weingart and Levitan 2012). Thus, as a rough estimate, a patient with a bicarbonate of 24 can remain apneic for about 17 minutes before their PaCO2 reaches 100mm and their pH falls to 7.0. In contrast, Patel et al found some patients who were able to remain apneic for over 30 minutes with PaCO2<100 mm (figure below). In one case, a patient was left apneic for 65 minutes and the entire surgical procedure was performed during the apnea time.
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Low-flow apneic oxygenation provides no ventilation
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Low-flow apneic oxygenation works via aventilatory mass flow. The rate of oxygen removal in the alveoli exceeds the rate of carbon dioxide entering the alveoli, generating negative pressure. This causes a slow, likely laminar flow of oxygen gas from the nasal cannula into the oropharynx and trachea and finally into the alveoli (figure below). This slow, steady inward flow of gas provides oxygenation without any ventilation.
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The physiology of apneic ventilation
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In order to provide apneic ventilation, HFNC must be operating in a fundamentally different way. The ability to perform apneic ventilation with low-flow oxygen insufflated into the trachea has been known for decades. In 1985, Slutskydemonstrated that in paralyzed dogs, a mere 2 liter/minute of oxygen continuously insufflated into the trachea was sufficient to maintain oxygenation and ventilation indefinitely:
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The physiology underlying this is complicated. Within some of the larger airways, turbulent flow could generate a cascade of turbulent vortex flows extending into smaller airways (figure below). Each vortex could communicate with the vortex above and below it, like a series of interlocking gears.
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Beyond these airways, there are smaller airways with little flow where gas transport may occur by molecular diffusion. Ventilation through these smaller airways may also be enhanced by cardiac pulsation of the lung (Slutsky 1985). There is probably more to it than this, but suffice it to say that it has been validated in several experiments and somehow it works.
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HFNC could take advantage of this mechanism if even a very small fraction of the flow was transmitted from the nose to the trachea (figure below). For example, Rudolf 2013 found that insufflating only 0.5 liters/minute into the trachea of patients undergoing endoscopy reduced the rate of CO2 rise by ~50% to 1.8 mm/min. Thus, if HFNC could achieve a flow of just 1 liter/minute in the trachea this might be sufficient to achieve significant ventilation:
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Oxyventilation: Apneic ventilation improves apneic oxygenation
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In general, it is useful to think about a patient's oxygenation and ventilation status separately. However, ventilating the lungs with pure oxygen will improve oxygenation as well. Rather than ventilating the lungs with air (in which case removed carbon dioxide is largely replaced by nitrogen), ventilation with oxygen should remove carbon dioxide and replace it with oxygen. As such, it is difficult to tease these two processes apart and it may be best to conceptualize them as a single process: oxyventilation.
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The marriage between ventilation and oxygenation derives from Dalton's Law of Partial Pressures, which states that the sum of all partial pressures in the alveolus must equal atmospheric pressure (equation below). If the alveolus is ventilated with oxygen, then any decrease in the PCO2 due to ventilation will force the PO2 to increase:
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For example, after 10 minute of apnea, HFNC will lead to an alveolar PaCO2 which is about 20mm lower than it would be using low-flow apneic oxygenation (based on data from Patel et al). This 20mm of pressure, rather than being occupied with carbon dioxide, will be replaced with oxygen, thereby increasing the PaO2 by 20mm.
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Directions for future research
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The ability of HFNC to provide oxyventilation, if confirmed, would be profound and extremely important. This could certainly improve the safety of endotracheal intubation. It could also have many other implications, for example regarding procedural sedation. Imagine being able to safely render a patient apneic for a couple of minutes to allow for cardioversion or joint manipulation.
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It might be useful to combine high-flow nasal cannula with a nasopharyngeal airway in order to maintain upper airway patency and deliver high-flow oxygen more deeply into the airway (figure below). A nasopharyngeal airway could avoid irritating the more delicate tissues of the nose, which might allow delivering gas at a higher flow rate. A nasopharyngeal airway would also direct the flow exactly where it needs to go – right into the larynx and trachea. If a combination of HFNC and a nasopharyngeal airway could achieve a tracheal flow of several liters/minute, it might be capable of maintaining oxygenation and ventilation indefinitely.
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Is HFNC preoxygenation ready for prime time?
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Unfortunately, the new evidence on HFNC for apneic oxygenation doesn't reveal much about its exact power at maintaining oxygenation. Miguel-Montanes 2015 demonstrated that HFNC appeared more effective than a non-rebreather mask at 15 liters/minute. However, since non-rebreather masks generally provide at most ~70% FiO2, the superiority of HFNC to this approach was entirely predictable.
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Although Patel et al requires validation, it is quite compelling. They selected a very challenging group of patients (BMI up to 52) and had excellent outcomes with them. The ability to maintain over an hour of apnea time without life-threatening hypercapnia is an impressive feat which would probably be impossible with traditional apneic oxygenation. Although indirect evidence, this success with ventilation implies improved power to oxygenate as well. It must be noted that Patel et al involved patients undergoing elective anesthesia, so these findings may not apply to patients with active lung disease such as pneumonia, with obstructing mucus and secretions.
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Thus it remains unclear to what extent HFNC should be used for preoxygenation. Overall I agree with Scott Weingart's recent podcast on preoxygenation. We have been using the Weingart/Levitan approach of combining a non-rebreather facemask at 15 liters/minute plus nasal cannula at 15 liters/minute at Genius General Hospital for a while now, with excellent results. HFNC takes some effort and cost setting up, so it may not be worthwhile using it routinely just for the purpose of preoxygenation.
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There may be selected cases, however, where HFNC could be worth utilizing for preoxygenation and apneic oxyventilation. One example of this might be a patient with normal lungs and an anticipated anatomically challenging airway (e.g., prior neck radiation). Of course, for very high-risk cases awake intubation may be safer. Exactly where HFNC might be integrated into clinical practice remains to be defined.
Unfortunately, the new evidence on HFNC for apneic oxygenation doesn't reveal much about its exact power at maintaining oxygenation. Miguel-Montanes 2015 demonstrated that HFNC appeared more effective than a non-rebreather mask at 15 liters/minute. However, since non-rebreather masks generally provide at most ~70% FiO2, the superiority of HFNC to this approach was entirely predictable.
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Although Patel et al requires validation, it is quite compelling. They selected a very challenging group of patients (BMI up to 52) and had excellent outcomes with them. The ability to maintain over an hour of apnea time without life-threatening hypercapnia is an impressive feat which would probably be impossible with traditional apneic oxygenation. Although indirect evidence, this success with ventilation implies improved power to oxygenate as well. It must be noted that Patel et al involved patients undergoing elective anesthesia, so these findings may not apply to patients with active lung disease such as pneumonia, with obstructing mucus and secretions.
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Thus it remains unclear to what extent HFNC should be used for preoxygenation. Overall I agree with Scott Weingart's recent podcast on preoxygenation. We have been using the Weingart/Levitan approach of combining a non-rebreather facemask at 15 liters/minute plus nasal cannula at 15 liters/minute at Genius General Hospital for a while now, with excellent results. HFNC takes some effort and cost setting up, so it may not be worthwhile using it routinely just for the purpose of preoxygenation.
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There may be selected cases, however, where HFNC could be worth utilizing for preoxygenation and apneic oxyventilation. One example of this might be a patient with normal lungs and an anticipated anatomically challenging airway (e.g., prior neck radiation). Of course, for very high-risk cases awake intubation may be safer. Exactly where HFNC might be integrated into clinical practice remains to be defined.
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Conclusions
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The expanding use of noninvasive ventilation and HFNC may be the most important new development in the management of respiratory failure over the last several years. We are only beginning to appreciate exactly how these devices work, and how best to use them.
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Patel's study suggests that HFNC provides apneic oxyventilation (ventilation with oxygen, simultaneously supporting oxygenation and ventilation). This implies that high-flow apneic oxygenation operates in a fundamentally different mechanism than low-flow apneic oxygenation. The physiology by which delivery of low amounts of oxygen to the trachea may support oxygenation and ventilation has already been described, suggesting that HFNC may be taking advantage of this mechanism. If this finding is confirmed, it would have broad implications for the use and development of high-flow oxygen devices in the future.
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Currently the role of HFNC for preoxygenation remains unclear. Further studies are needed, ideally including direct comparison with a preoxygenation method that provides close to 100% FiO2 (e.g., noninvasive ventilation or a combination of non-rebreather at 15 liters/minute plus nasal cannula at 15 liters/minute).
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Patel's study suggests that HFNC provides apneic oxyventilation (ventilation with oxygen, simultaneously supporting oxygenation and ventilation). This implies that high-flow apneic oxygenation operates in a fundamentally different mechanism than low-flow apneic oxygenation. The physiology by which delivery of low amounts of oxygen to the trachea may support oxygenation and ventilation has already been described, suggesting that HFNC may be taking advantage of this mechanism. If this finding is confirmed, it would have broad implications for the use and development of high-flow oxygen devices in the future.
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Currently the role of HFNC for preoxygenation remains unclear. Further studies are needed, ideally including direct comparison with a preoxygenation method that provides close to 100% FiO2 (e.g., noninvasive ventilation or a combination of non-rebreather at 15 liters/minute plus nasal cannula at 15 liters/minute).
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Does it have the same benefits if you use a normal nasal canula set at 15lpm?
I would think you’d have to have a cannula and hose that can allow 15L through. Some you cannot use. I didn’t know it until one of my recent stays in the hospital, but some are regulated to only allow so much through.
Excellent point. Will have another post about this within the next few months – stay tuned.
I have used nasal bipap with VL with antidotal success – no desat or complications thus far. Since my pts are generally on nippv prior to ett it logistically works in the normal workflow.