Redefining endpoints with apnoeic oxygenation in pregnancy – better the devil you know than the devil you don't?

We thank Tanna and Saha 1 for their interest in our study and for raising a thought-provoking discussion about the potential for lowering end-tidal oxygen fraction endpoint in obstetric patients when using high-flow nasal oxygenation. The current recommended pre-oxygenation target of end-tidal oxygen fraction ≥ 0.9 pre-dates the advancement of high-flow nasal oxygenation 2. This specific value originated from the idea that it is desirable to reduce the risk of hypoxia by providing a reservoir of 95% oxygen assuming an obligatory 5% alveolar carbon dioxide, which corresponds to an end-tidal oxygen fraction of 0.9 according to an earlier study by Berry et al. 3. In our study, after 3 min of tidal volume breathing, there were significantly fewer numbers of parturients who were able to achieve the pre-oxygenation target of an end-tidal oxygen fraction ≥ 0.9 in the high-flow nasal oxygenation group compared with the standard flow rate facemask group (47% vs. 85%, respectively). If we had used a lower target of end-tidal oxygen fraction ≥ 0.8 as a primary endpoint, the high-flow nasal oxygenation group would have achieved a substantially greater proportion above the threshold (88% high-flow nasal oxygenation vs. 95% facemask), altering the conclusion of the study 4. Our findings, along with a number of associated studies, have consistently found that not all pregnant women can achieve end-tidal oxygen fraction ≥ 0.9 after 3 min of pre-oxygenation 5, 6. In fact, Chiron et al. reported that even with standard facemask pre-oxygenation, 25% of third trimester healthy pregnant women could not attain the target of end-tidal oxygen fraction ≥ 0.9 following 3 min of tidal volume breathing or eight deep breaths 5. As such, we agree with Tanna and Saha that the threshold of end-tidal oxygen fraction ≥ 0.9 should be re-examined. Indeed, reducing the endpoint of pre-oxygenation would mean a potentially shortened time to delivery of the fetus. Also, using a simple theoretical model, the additional loss in safe apnoea time by lowering the threshold of end-tidal oxygen fraction from 0.9 to 0.8 may not be clinically significant, especially when arterial desaturation rate can be slowed by apnoeic oxygenation (Table 1). However, just as it is difficult to justify the strict need for end-tidal oxygen fraction ≥ 0.9, the paucity of compelling evidence demonstrating reliability of apnoeic oxygenation in obstetric patients makes it just as difficult to challenge the status quo and adopt a lower endpoint. 1. FRC oxygen (ml) a. at FETO2 0.8 = 1536 ml b. at FETO2 0.9 = 1728 ml 2. Rate of oxygen consumption (VO2) at rest = 3.56 ml.kg.min−1 in the thirrd trimester 10 = 284 ml.min−1 Apnoeic time (FRC/VO2) a. at FETO2 80 = 5.4 min b. at FETO2 90 = 6.1 min 3. VO2 in labour in the third trimester = 4.28 ml.kg.min−1 10 = 342 ml.min−1 Apnoeic time (FRC/VO2) a. at FETO2 80 = 4.5 min b. at FETO2 90 = 5.1 min 4. Maximum VO2 in average non-athletic pregnant woman = 27 ml.kg.min−1 11 = 2160 ml.min−1 Apnoeic time (FRC/VO2) a. at FETO2 80 = 42.7 s b. at FETO2 90 = 48 s Using a lower target of end-tidal oxygen fraction may be reasoned if apnoeic oxygenation can consistently maintain the oxygen reservoir following induction of general anaesthesia for obstetric patients; however, the success of this technique relies on a number of ideal conditions to be met. The benefit of apnoeic diffusion oxygenation is highly dependent on airway patency; yet, even with the most careful of pre-assessment, it is impossible to predict which patient may not have the patent airway necessary to support apnoeic diffusion 7. Additionally, an early non-obstetric study by Fraioli et al. 8 demonstrated that apnoeic oxygenation is less effective in patients with a low predicted functional residual capacity to body weight ratio. Although the results are difficult to generalise to obstetric patients, this study highlights the possibility that apnoeic oxygenation may not be as effective in individuals with altered respiratory physiology and thus the need to further affirm its role in pregnancy. We need to better understand how we could identify parturients who would not benefit from apnoeic oxygenation. Studying apnoeic oxygenation in pregnancy is ethically and practically difficult. Most parturients who receive general anaesthesia are higher risk parturients who have lower physiological reserves and are often not included in research studies. However, we believe time should be dedicated to investigate how to conduct apnoeic oxygenation effectively in the parturient and factors associated with its ineffectiveness, as difficult as that may be. Results from ongoing high-flow nasal oxygenation studies may offer further useful insights and information to guide this discussion, but until then, many obstetric anaesthetists would likely practice with the devil they know 9. Much more convincing data would be necessary before advocating the lowering of a safety margin that has persisted for decades.

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