CBTs can be classified into three distinct forms: familial, hyperplastic and sporadic. Familial types have been shown to be associated with germline mutations in three of the four succinate dehydrogenase subunit genes8. Unfortunately, in this study, genetic information of most of our patients was not available. Hyperplastic types are common in patients with chronic continuous hypoxia disease and patients living in plateau regions9. The development of tumors in the carotid body may be stimulated in these cases1. Sex is another risk factor for CBTs. Many other studies1,9−10 have shown that females have a higher incidence of CBTs than males, which is consistent with our data. Some articles have suggested that hormonal changes caused by menstruation and pregnancy and monthly blood loss through menstruation in women might be possible reasons for this difference9. Another hypothesis is that a larger pulmonary capacity and greater enthusiasm for sports and athletic conditioning in men may allow males to escape chronic hypoxia and account for this wide gap between the sexes11.
Regarding the primary outcome of this study, we discovered that the postoperative BP and HR increased to varying degrees in CBT patients compared with control patients. CBT excision, particularly bilateral excision, may be associated with postoperative hemodynamic alterations, which may result in the need for extra antihypertensive agent therapy.
Peripheral chemoreceptors mediate the immediate circulatory and ventilatory response to hypoxemia, and their function is predominantly attributable to the carotid body, which lies in close proximity to the carotid sinus baroreceptors12. The carotid body plays an important role in hemodynamic homeostasis by acting directly through the chemoreflex or indirectly affecting the baroreflex3. Originating from carotid sinus and aortic mechanoreceptors, the baroreflex buffers abrupt transient changes in blood pressure. The baroreflex can be affected by surgical damage directly to the baroreceptor or to the afferent nerve branches of the baroreflex. Iatrogenic injuries to the afferent limb of the baroreflex may result in hypertension and tachycardia13. The surgical excision of CBTs removes the stimulatory effect of the chemoreflex on the sympathetic nervous system; however, it may also produce concomitant baroreflex damage, counteracting the lowering effect that denervation of the chemoreflex might have on BP and HR. Although overt baroreflex failure, characterized as labile hypertension, headache, diaphoresis and emotional instability14, occurs only in a minority of patients, baroreflex sensitivity may decrease in a large proportion of patients treated with CBT excision15. This may offer part of an explanation for the postoperative SBP and HR increases in this study. In recent years, there have also been studies reporting that other carotid interventions, whether endovascular or surgical interventions, especially carotid endarterectomy, correlate with an impairment of baroreceptor functions and therefore influence postinterventional BP behavior in the early postoperative phase16–18. These results provide evidence for our explanation of the hypothesis from another point of view. In this study, 16 out of 116 (13.8%) cases required extra antihypertensive agent therapy after surgery compared with the preoperative medication use, which was significantly more than the number of such patients in the control group. These results indicate the clinical impact of these changes in BP and HR. To summarize, our results suggest that postoperative baroreflex function may be affected in CBT patients. Thus, close monitoring, prompt attention and necessary treatment are essential for CBT patients’ safety.
In addition, our results revealed that compared with controls, postoperative HR alterations in bilateral CBT patients increased more by 5.3 bpm (95% CI 1.0 ~ 9.6, p = 0.016) after adjusting for sex, age and region, while such differences were not observed in unilateral CBT patients. We suppose it may be possible that bilateral CBT excision lead to bilateral damage to the baroreflex and chemoreflex, resulting in attenuated baroreflex sensitivity and increased hemodynamic variability, therefore causing greater HR fluctuations19. Accordingly, close postoperative BP and HR monitoring and attention are especially recommended for patients with bilateral lesions. In this study, no functional CBTs were encountered. To some extent, secreted hormones, such as histamine, serotonin or catecholamine20, were prevented from acting as confounding factors.
Data on the impact of the duration of baroreflex damage are limited and controversial. Previous studies have suggested that after bilateral carotid sinus denervation, BP levels markedly increased but normalized within 14 days in animal experiments; however, BP levels showed a long-term increase in all four patients treated with bilateral CBT excision21. In a retrospective analysis of 20 patients with hypertension, it was reported that unilateral CBT excision was associated with sustained reductions in BP 30 days after surgery22. In addition, alterations in the sensitivity of the baroreflex and chemoreflexes may also affect the variability in BP and HR. For instance, a previous study revealed that patients treated with bilateral CBT resection had a blunted BP response to hypoglycemia23. However, the identification of compensatory effects over the long term and how patients react under conditions of stress need further investigation.
Our secondary findings demonstrated that maximum tumor diameter, intraoperative surgical vascular injury, intraoperative continuous vasoactive agent requirement, total crystalloid/colloidal volume, red blood cell/fresh frozen plasma (RBC/FFP) transfusion volume, blood loss, operative duration, postoperative malignant pathology, ICU/hospital stay, and postoperative overall complications were related to Shamblin type. Some of these results were in accordance with previous studies in the literature24–26. According to the results, advanced Shamblin types necessitated comprehensive preparation. For instance, if required, fluid replacement for resuscitation, adequate blood products and ICU beds should be readily available. Central venous catheterization can be judiciously prepared for intraoperative continuous vasoactive agent infusion before surgery. Preoperative embolization may be considered, although embolization is currently controversial, as some studies have reported that it made no difference in reducing intraoperative blood loss27. Intraoperative autologous blood reinfusion can also be prepared for the reduction of allogeneic products, and leukofiltration can be conditionally considered based on the malignant potential of CBTs28.
Regarding the intraoperative management of patients with CBT, preservation of optimal BP levels, maintenance of cerebral perfusion and optimal operating conditions for the surgeon have always been basic components29. For postoperative complications, associations were not observed between the Shamblin type and specific complications, such as nerve dysfunction, wound hematoma and stroke. This is in line with some studies suggesting that the Shamblin classification has limitations in predicting the occurrence of postoperative complications30–31.
There are several limitations to this study. First, because of the relative rarity of this disease entity, the determined sample size caused some of the analyses to be partly underpowered, especially the results related to DBP and bilateral CBT patients, and therefore increased the likelihood of false-negative results. However, as CBTs do not occur at a high frequency, the inclusion of 108 patients with 116 tumors resulted in a relatively large cohort. In addition, five out of six of the primary statistical conclusions achieved > 70% power. Therefore, we believe this study has sufficient statistical power regarding our main conclusions. Second, as this was a retrospective study, there might be unbalanced potential confounders between the groups, for instance, the complicated perioperative medication interactions, resulting in confounding effects. Third, this study was regarded as an exploratory analysis; therefore, we did not adjust the probability of type I error due to multiple comparisons in the statistical analysis. Finally, all perioperative data were collected during hospitalization, which normally did not exceed three weeks. The long-term compensatory effects on BP and HR after surgery need further observation and summarization. Patients’ recovery from complications after discharge was also not investigated.
Here, we attempted to identify postoperative BP and HR alterations after CBT excision and their clinical impacts in cases compared with controls. Thus, careful assessments, full preparation, gentle operation, close monitoring and continued awareness are essential for the perioperative management of CBT patients.