Oxygenation pattern and compensatory responses to hypoxia and hypercapnia following bilateral carotid body resection in humans

Abstract

Key points Five years after bilateral carotid body resection (bCBR) performed in four patients, the absence of the hypoxic ventilatory response persisted, suggesting no compensatory regrowth. Breathing hypoxic gas mixtures (15% and 12%) results in a lower (by ∼10%) minimal blood oxygen saturation (SnormalpO2) in bCBR patients compared to heart failure subjects (CHF) with intact peripheral chemoreceptors. After bCBR, patients were characterized by a greater short‐term variability in SnormalpO2 during mild hypoxia in comparison to the CHF group. The ventilatory response to hypercapnia was preserved following bCBR and was sufficient to maintain minimal SnormalpO2 at levels comparable to controls when combined with hypoxia. Bilateral CBR – a novel treatment modality for sympathetically mediated diseases – should be used with caution due to the risk of significant desaturation even during mild hypoxia equivalent to that experienced during long‐haul air travel and high altitude. Abstract Carotid body resection has been proposed as a novel treatment for sympathetically mediated diseases but the safety of bilateral carotid body resection (bCBR) for blood oxygenation during hypoxic stress (long‐haul flights or high altitude) remains uncertain. Also unknown is whether central ventilatory drive is sufficient to maintain adequate oxygen saturation when exposed to hypercapnia with concomitant hypoxia. Thus, we administered: 15% O2, 12% O2, 5% CO2/12% O2 and 5% CO2/95% O2 to a group of four patients with congestive heart failure (65 ± 2.9 years) in whom bCBR was performed 5 years earlier. Ventilatory, haemodynamic and blood oxygen saturation (SnormalpO2) responses were recorded non‐invasively and compared to control groups with intact peripheral chemoreceptors (both healthy and heart failure patients). First, we confirmed that the ventilatory response to hypoxia was eliminated in patients with bCBR, although the increase in cardiac output was preserved. Second, administration of hypoxic gas mixtures resulted in a larger decrease in SnormalpO2 and greater short‐term variability of the SnormalpO2 leading to a lower minimal SnormalpO2 for both hypoxia levels in the bCBR group compared to heart failure controls (82.5 ± 1.2% vs. 91.6 ± 2.3% for 15% O2 and 73.8 ± 4.0% vs. 83.7 ± 3.1% for 12% O2). Third, in bCBR patients the ventilatory response to hypercapnia was present and sufficient to maintain a minimal SnormalpO2 at a level comparable to heart failure controls following administration of 5% CO2/12% O2 (88.7 ± 4.2% vs. 91.1 ± 2.8%). We conclude that bCBR carries a risk of significant oxygen desaturation even during mild hypoxia. Despite preservation of central chemosensitivity, future studies should focus on unilateral CBR or on pharmacological modulation of peripheral chemosensitivity.

Worth the risk? Effects of prolonged hypoxia and hypercapnia on ventilatory responses in patients with bilateral resection of the carotid bodies

“…Considering that attenuating peripheral chemoreceptor afferent discharge may be a useful intervention for CHF patients, understanding the consequences of bCBR surgeries on patients is of clinical significance. The present study showed that when exposed to prolonged mild hypoxia, bCBR patients had a 10% lower minimal value of S pO 2 when compared to CHF subjects with intact CB (Niewinski et al 2021). They also stated that mild hypoxia (15% O 2 ) is comparable to travelling 2700 m above sea level, equivalent to a transatlantic flight.…”

“…Since previous studies have conceptualized the therapeutic benefits of reducing afferent signals from the CB in CHF patients (Niewinski et al 2017), continuing to measure oxygenation patterns using short-term variability analysis seems both logical and necessary in the future. The study of Niewinski et al (2021) is not without its limitations, but it is clear that the authors are aware of its pitfalls. As the authors discussed, the use of a small sample size (i.e.…”

“…Therefore, it should be noted that the parameters seen in the paper reflect a practical setting and not an experimental one. The study of Niewinski et al (2021) opens the door for future studies to incorporate cardiovascular measures such as baroreflex sensitivity (BRS) and MSNA into their model, both of which this group has had experience investigating in the past. In previous studies, Niewinski et al (2013) studied a single 56-year-old male patient with CHF who underwent uCBR by measuring the parameters BRS via sequence methods and MSNA via microneurography.…”

Cerebral blood flow, cerebrovascular reactivity and their influence on ventilatory sensitivity

“…Since peripheral chemoreceptors sample arterial blood directly, changes in the P aCO 2 and P aO 2 contribute more rapidly to changes inV E than do the changes in CSF and ISF pH at the central chemoreceptors. Nevertheless, brainstem chemoreceptor neurons contribute to roughly two-thirds of the effect of P aCO 2 /[H + ] on steady-state ventilation (Forster et al, 2008), as indicated by carotid body denervation and resection studies (Bellville et al, 1979;Klein et al, 1982;Niewinski et al, 2021 (Guyenet, 2014;Klein et al, 1982;Smith et al, 2006). This combination of peripheral and central chemoreceptors creates a system such that the brain and the whole body are protected from extremes of acidosis or alkalosis.…”

Bilateral carotid body resection – a challenge for blood oxygen homeostasis

“…Alternatively, it may help identify patients whose phenotype might warrant carotid body resection as a therapeutic strategy. The novelty in the work by Niewinski et al (2021) is in the assessment of blood oxygen saturation during exposure to mild (15% O 2 , ∼2700 m) and moderate hypoxia (12% O 2 , ∼4500 m). Minimum blood oxygen saturation was generally 10% lower in congestive heart failure patients and the variability of blood oxygen saturation was much greater following bilateral carotid body resection compared with both carotid body intact and healthy controls.…”