Avoiding desaturation during endotracheal intubation: is high-flow nasal cannula the answer?

Tracheal intubation in critically ill patients is a common procedure in the intensive care unit (ICU), and often is realized in an emergency scenario. Hypoxemia, hypotension, arrhythmia and cardiac arrest are described as severe adverse events related to the procedure, with an incidence around 28% (1,2). Among these intubation-related adverse events, life-threatening hypoxemia and profound desaturation (SpO₂ below 80%) are the most frequent ones (3).

For several years, desaturation during intubation and the consequent need of preoxygenation has been discussed (4). Preoxygenation before intubation is used as standard of care in the majority of the ICUs, and the goal is to prolong the time until desaturation during apnea, earning time to safely perform the procedure, and avoiding hypoxemia. In healthy patients, preoxygenation can result in several minutes of apnea without desaturation, however, critically ill patients frequently have a decreased functional residual capacity (FRC), low hemoglobin levels, and decreased alveolar ventilation and cardiac output, leading to faster desaturation during apnea (3).

The effectiveness of preoxygenation can be defined by its efficacy and efficiency. The efficiency is the rate of decrease in oxyhemoglobin desaturation during apnea, while efficacy is the capacity of increase the alveolar fraction of oxygen and decrease the alveolar fraction of nitrogen (5,6). The rate of oxyhemoglobin desaturation is highly sensitive to the initial alveolar fraction oxygen and, therefore, adequate efficacy is better assessed measuring end-tidal oxygen concentration (EtO₂) (7,8).

Peripheral oxygen saturation (SpO₂) can be a misleading guide for preoxygenation, since a SpO₂ of 100% can occur before the lungs are properly denitrogenated. Also, SpO₂ starts to decrease only after the oxygen reserve is already depleted, thus, EtO₂ monitoring during intubation is considered standard of care in the operating room (6,9). Nevertheless, measurements of the EtO₂ must be performed with a sealed system and non-occlusive devices, such as high-flow nasal cannula (HFNC), are not adequate for it (10).

To improve safety during intubation, current guidelines suggest preoxygenation using oxygen through facemask, continuous positive airway pressure (CPAP), noninvasive ventilation (NIV) or nasal catheters with 10 to 15 liters of oxygen per min (L/min). In addition, the concentration of oxygen should be 100% for 3 minutes before laryngoscopy, aiming at an EtO₂ higher than 90%. The best choice between the devices is not clear, but it is suggested that CPAP should be selected when oxygenation is impaired, and that HFNC or NIV should be kept during the procedure when already in use before it (2). Moreover, a systematic review of clinical trials suggests a possible benefit of pre-oxygenation with NIV and/or HFNC over oxygen alone in ICU patients (11).

HFNC is a popular device due its worldwide use in neonatal setting and is a relatively new method for respiratory support in adult patients. The device gained popularity in the ICU due to its ability to improve oxygenation, increase FRC, and offer a high inspiratory flow with higher and accurate measurement of the inspired fraction of oxygen (FiO₂). In addition, HFNC induces a modest positive end-expiratory pressure effect when the mouth is closed, and is well tolerated by the patients, resulting in good comfort even with flows up to 60 L/min (12,13).

During intubation, HFNC may improve safety because it can offer not only adequate preoxygenation, but also apneic oxygenation during the procedure. Nasal prongs can be left in place during the entire intubation, offering oxygen at the pharyngeal level, while standard bag-valve mask (SMO) must be removed during laryngoscopy (3). In previous studies, apneic oxygenation was associated with increased peri-intubation SpO₂, decreased rates of hypoxemia, and increased first-pass intubation (14-16).

In this context, Guitton et al., designed a randomized clinical trial to evaluate the benefits of HFNC in the preoxygenation of non-severely hypoxemic patients undergoing endotracheal intubation. The study, known as the PROTRACH trial, was a multicenter, randomized and open-label clinical trial. In the intervention arm, HFNC was maintained throughout the whole intubation procedure, while in the control group SMO was used during the preoxygenation but removed during laryngoscopy, as usual. The primary outcome was the lowest SpO₂ during the procedure. Secondary outcomes were the incidence of desaturation (defined according to different cut-offs of SpO₂), rate of difficult intubation, intubation difficulty scale score, need to proceed to face mask ventilation to correct desaturation, intubation-related adverse events [classified as severe (death, cardiac arrest, SpO₂ <80% and/or severe hypotension)] or moderate [arrhythmia requiring intervention, esophageal intubation, aspiration of gastric content and/or dental injury)], organ failure during the first 5 days, time on ventilator, ICU length of stay, occurrence of ventilator-associated pneumonia, and 28-day mortality (17).

Patients were randomized from April 2016 to June 2017 in 7 French ICUs and followed for 28 days after randomization. Non-severe hypoxemia, defined as a PaO₂/FiO₂ <200 up to 4 hours before inclusion in the study was used as a key inclusion criterion, and the patients randomized were mainly in comatose state and intubated because of neurologic reasons. In the intention-to-treat analysis, the median lowest SpO₂ was similar in both groups (100% in the HFNC vs. 99% in the SMO group; P=0.300), while mild desaturation (SpO₂ <95%) was less frequent in the HFNC group [12% vs. 23%; relative risk (RR) 0.51, 95% confidence interval (CI): 0.26–0.99; P=0.045]. During intubation, the incidence of at least one intubation-related adverse event was lower in the HFNC group (6% vs. 19%; RR 0.31, 95% CI: 0.13–0.76; P=0.007), as was the incidence of severe complications (6% vs. 16%; RR 0.38, 95% CI: 0.15–0.95; P=0.030). Multivariable analysis showed that HFNC was associated with less desaturation, less intubation-related adverse events, and there was a trend towards reduced incidence of a SpO₂ <80%. The authors concluded that during intubation of non-severely hypoxemic patients in the ICU, HFNC did not improved the median lowest SpO₂ compared to SMO, however, HFNC was as associated with increased safety, leading to a reduction in intubation-related adverse events (17).

In line with these findings, Miguel-Montanes et al., conducted a single center before-after study, including non-hypoxemic patients mainly requiring intubation because of shock or coma, and found that HFNC significantly improved preoxygenation and reduced the prevalence of severe hypoxemia compared with SMO (18). In hypoxemic patients, Baillard et al., found that preoxygenation using NIV is more effective at decreasing the incidence of desaturation than SMO and, since then, NIV has been considered a useful approach for intubation of hypoxemic patients in the ICU (11). In 2015, the PREOXYFLOW trial evaluated the impact of HFNC compared to SMO for preoxygenation in severely hypoxemic patients (median PaO₂/FiO₂ of 120 mmHg), and no significant differences between the devices were found (19). Moreover, in 2016, the OPTINIV study showed that in severely hypoxemic patients, the preoxygenation with NIV combined with HFNC increased the lowest SpO₂ during intubation compared to NIV alone (20). Finally, recently the FLORALI-2 study compared the use of NIV versus HFNC for the preoxygenation of patients with acute hypoxemic respiratory failure and found no difference between the devices in the risk of severe hypoxemia. However, in patients with PaO₂/FiO₂ ≤200, severe hypoxemia occurred in 24% of the patients in the NIV group and 35% of the patients in the HFNC group (absolute difference estimate −11.3%, 95% CI: −22.3 to 0.3; P=0.055), suggesting a possible benefit of NIV among this group of patients (21).

It is important to emphasize that these studies evaluated different populations. As shown in Table 1, the studies comparing HFNC to SMO in non-hypoxemic patients found better results in patients undergoing HFNC, while the trials evaluating severely hypoxemic patients did not find this association (17-19). Furthermore, for hypoxemic patients, the OPTINIV and the FLORALI-2 trials found better results for preoxygenation with NIV or combining NIV and HFNC compared to the devices alone. Hence, it is possible to infer from the data that HFNC provides better oxygenation during intubation of non-hypoxemic patients but, in severely hypoxemic patients, it might not be enough to prevent desaturation. This hypothesis can be supported by the physiological fact that hypoxemic patients usually have a higher amount of alveoli collapsed, and HFNC may not provide sufficient pressure to recruit these alveoli and prevent further collapse.

Table 1 Characteristics of six studies on preoxygenation techniques in patients with acute respiratory failure and requiring endotracheal intubation in ICU
Full table

A recent trial comparing preoxygenation with HFNC vs. SMO in patients undergoing general anesthesia for surgery, found that HFNC is not a reliable method of preoxygenation before the induction of anesthesia. In this study, only 4% of the patients in the HFNC group achieved an EtO₂ equal or greater than 90% after 3 minutes, while 54% of the patients in the face mask group reached the expected EtO₂. The measurements of EtO₂ were performed by exchanging the HFNC for a face mask while the subject held their breath at end inspiration and the EtO₂ was assessed after a deep expiration and, due to the possibility of leaks during this exchange, the values of EtO₂ could have been inaccurate. According to the authors, the reasons for the difference in oxygenation among the devices are the occurrence of air leaks through the mouth and a high inter-individual variability in the EtO₂ values measured in the HFNC group (22).

The PROTRACH study has some limitations. First, the preoxygenation device was unblinded what may have interfered in the findings. Although difficult to be performed in a large sample of patients, the blinding is feasible and has been done previously (20). Second, the study did not compare HFNC to NIV, and NIV may have beneficial effects even in non-hypoxemic patients, although the risk of gastric aspiration and the significant number of patients with contraindications to NIV, such as those with neurological impairment should be considered. Third, the outcomes were based on the SpO₂ and it may not reflect effectiveness of preoxygenation as discussed previously. Nevertheless, measuring EtO₂ is not easy in patients undergoing HFNC and exchanging devices is not feasible in an emergency intubation.

In conclusion, the PROTRACH trial provides the best evidence until the moment comparing SMO and HFNC for preoxygenation of non-severely hypoxemic patients. Despite neutral for its primary outcome, the study demonstrated a potential benefit with the use of HFNC regarding the prevention of intubation-related adverse events. Given the small number of adverse events, these findings must be confirmed in well powered studies. Meanwhile, HFNC can be considered instead of SMO for the preoxygenation of non-severely hypoxemic patients, especially in intubations performed due to neurologic impairment, when NIV is commonly contraindicated.

Acknowledgments

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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