Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 1  |  Page : 77-81

Alpha blocker – A better antihypertensive option for postendarterectomy hypertension


1 Department of Cardiovascular and Thoracic Surgery, Division of Vascular Surgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
2 Department of General Surgery, Division of Vascular Surgery, Government of Medical College, Thiruvananthapuram, Kerala, India
3 Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India

Date of Submission11-Nov-2020
Date of Acceptance07-Dec-2020
Date of Web Publication20-Feb-2021

Correspondence Address:
Shivanesan Pitchai
Department of Cardiovascular and Thoracic Surgery, Division of Vascular Surgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_155_20

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  Abstract 


Introduction: The immediate postoperative hemodynamic alterations occurring after carotid endarterectomy (CEA) is called postendarterectomy hypertension (PEH). PEH results in prolonged hospital admission, increased peri-operative morbidity, and mortality. The exact causes of the PEH whether it is due to carotid sinus denervation or due to the increased norepinephrine production in cerebral and peripheral circulation remain unclear. Materials and Methods: A prospective analysis of 62 patients who underwent CEA from 2018 to 2019 were carried out by dividing into two groups based on the technique of surgery (conventional CEA [c-CEA], n = 31; eversion CEA [e-CEA], n = 31), and the effect of four class of drugs mainly beta blockers (βBs), calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), and alpha blockers (αBs) were studied for the prevention of PEH. Results: 72.6% of patients developed PEH irrespective of the technique of surgery (e-CEA n = 25 c-CEA n = 20; P = 0.15). The mean postoperative dose of antihypertensive drugs (Mpostoperative) were found significantly increased compared to mean preoperative dose (Mpreoperative) in all PEH patients among βB? group (Mpreoperative 18.95 mg vs. Mpostoperative 45.76 mg; P = 0.00); CCB group (preoperative Mpreoperative 6.21 mg vs. Mpostoperative 9.79 mg; P = 0.01); ARB group (Mpreoperative 14.03 mg vs. Mpostoperative 38.23 mg; P = 0.01); but those patients with preoperative αBs have well controlled BP in the postoperative period without significant change in mean dosage; αB (Mpreoperative 0.16 mg vs. Mpostoperative 3.74 mg: P = 0.27). Conclusions: This study indirectly showed that fluctuations of sympathetic system are happening in both e- and c-CEA irrespective of the technique of surgery. These fluctuations were better controlled in patients who had adequate sympathetic blockade preoperatively. In other words, αB can be considered a drug of choice for PEH.

Keywords: Conventional carotid endarterectomy, eversion carotid endarterectomy, postendarterectomy hypertension, treatment of postendarterectomy hypertension


How to cite this article:
Kumar V, Ramachandran S, Sylaja P N, Pitchai S. Alpha blocker – A better antihypertensive option for postendarterectomy hypertension. Indian J Vasc Endovasc Surg 2021;8:77-81

How to cite this URL:
Kumar V, Ramachandran S, Sylaja P N, Pitchai S. Alpha blocker – A better antihypertensive option for postendarterectomy hypertension. Indian J Vasc Endovasc Surg [serial online] 2021 [cited 2021 Feb 25];8:77-81. Available from: https://www.indjvascsurg.org/text.asp?2021/8/1/77/309703




  Introduction Top


The immediate postoperative hemodynamic alterations occurring after carotid endarterectomy (CEA) is called postendarterectomy hypertension (PEH). PEH was associated with a 3.3-fold higher risk of early major cardiovascular complications and an eightfold elevated risk of cardiovascular mortality in the first 5 postoperative years.[1] PEH prolongs hospital admission and in severe form may lead to cerebral hyper perfusion syndrome.[2] Several reports showed that injury of baroreceptors (BRSs) during CEA results in PEH.[3] This phenomenon is more evident in eversion CEA (e-CEA) as internal carotid artery (ICA) is divided at bifurcation, which involves BRS damage. In this study, we have evaluated the effectiveness of various anti-hypertensive agents for the prevention of PEH in e-CEA and conventional CEA (c-CEA).


  Materials and Methods Top


A total of 62 patients who underwent CEA (c-CEA, n = 31; e-CEA, n = 31) in Division of Vascular Surgery, between January 2018 and December 2019 with hypertension as major comorbidity and having symptomatic ipsilateral ICA stenosis ≥50% on computed tomography angiogram were included in our study. Those symptomatic patients with ICA stenosis not taking any antihypertensive medication preoperatively were excluded from the study. The choice of e- or c-CEA was decided based on the discretion of surgeon who performed the procedure, and the preoperative evaluation was same for both. Baseline blood pressure (BP) values were obtained on the day of admission, and BP was always measured on both arms, and the higher pressure was taken into consideration.

Operative procedure details of conventional carotid endarterectomy

All c-CEA were performed under general anesthesia. Longitudinal incision along the anterior border of sternocleidomastoid muscles was made; carotid sheath was opened; common carotid artery (CCA), ICA and external carotid artery (ECA) was looped. Neuroprotective medications such as methyl prednisolone (30 mg/kg) and thiopentone (1 mg/kg) were administered, and systemic heparinization was done. First ICA, then CCA, followed by ECA was clamped. Longitudinal arteriotomy was made from ICA extending to CCA. Pruitt Inahara shunt (Le Maitre® Vascular, USA) was inserted. The plaque was removed ensuring proper distal feathering [Figure 1]a and [Figure 1]b. The arteriotomy was closed using supra malleolar great saphenous vein patch. If vein not available, then bovine pericardial patch using continuous 6-0 Proline suture [Figure 1]c. After proper de-airing, the clamps are released sequentially ECA and CCA first followed by ICA.
Figure 1: Carotid endarterectomy specimen showing (a) smooth plaque with feathering (black arrow) (b) ulcerated plaque with feathering (yellow arrow) (c) bovine pericardial patch closure in conventional carotid endarterectomy

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Operative procedure details eversion carotid endarterectomy

All e-CEAs were also performed under general anesthesia. A transverse skin crease incision is made over the carotid bifurcation. Dissection and order of clamping same as in c-CEA. ICA is then disconnected from the carotid bulb by an oblique incision. Then assistant evert the ICA and endarterectomy is completed followed by distal CCA and ECA endarterectomy. ICA was then re-anastomosed to the side of CCA bulb in an end-to-side fashion using continuous 6-0 Proline suture.

Statistical analysis

Student t-test was used to compare the group's baseline characteristics and continuous measures. The Chi-square statistical analysis was used to compare the groups with discontinuous variables. All statistical tests were 2-tailed, and P < 0.05 was considered to represent statistical significance. Karl–Pearson correlation coefficient was used for comparing the mean values of systolic BP (SBP), diastolic BP (DBP), and mean BP (MBP) preoperatively and PEH. All data analysis was done using the? Windows Excel 2010 (Microsoft Corporation, USA) and SPSS statistical analysis software (SPSS Inc, Illinois, USA).


  Results Top


Demographic profile

The study population were divided into eversion (n = 31) and conventional (n = 31) groups. The age, sex, and distribution of risk factors such as smoking, dyslipidemia, coronary artery disease, diabetes, hypertension both controlled and uncontrolled, COPD, CKD, thyroid dysfunction, Peripheral arterial occlusive disease (POAD), unilateral and bilateral ICA disease, severity of stroke assessed by NIHSS and mRS score were uniformly distributed between the two study groups (P > 0.05). 58% in e-CEA group and 58% within c-CEA group had stroke prior to CEA (P = 1). 41.9% in e-CEA and 43.3% in c-CEA group had prior TIA (P = 0.912) [Table 1].
Table 1: Demographic profile

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Carotid endarterectomy in bilateral carotid disease

The patients with asymptomatic contra lateral carotid stenosis were 19.35% in e-CEA and 29.03% in c-CEA. There was one patient in e-CEA and two patients in c-CEA with C/L ICA occlusion. There was no significant difference in the number of patients with bilateral carotid stenosis in both CEA groups (P = 0.263). The right and left sided CEA were also matched in both e- and c-CEA (P = 0.793) [Table 2].
Table 2: Carotid endarterectomy in bilateral carotid disease

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Postendarterectomy hypertension and technique of surgery

In our study, 87.1% of patients after e-CEA and 74.2% of patients after c-CEA developed PEH. There was no difference in the incidence of PEH between two study groups (P = 0.199); thus, the technique of surgery had no impact on the development of PEH [Table 3].
Table 3: Postendarterectomy hypertension and technique of surgery

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Preoperative uncontrolled hypertension and postendarterectomy hypertension

All the patients included in our study were hypertensives on treatment. Preoperatively, around 61.3% patients in e-CEA and 41.9% patients in c-CEA had uncontrolled BP (>140/90 mm of Hg), and there was no statistical difference in the distribution of the same [Table 4]a.
Table 4:

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After surgery, those patients with BP >140/90 mm Hg in the preoperative period and those patients developed PEH are almost similar (Karl–Pearson correlation coefficient with all r > 0) [Table 4]b and [Figure 2].
Figure 2: Karl–Pearson correlation of preoperative uncontrolled hypertension and postendarterectomy hypertension

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Antihypertensive medications and postendarterectomy hypertension

The mean postoperative dose of four classes of antihypertensives mainly beta blockers (βB), calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), and alpha blockers (αBs) were compared with? preoperative dose. In βB group, the mean postoperative dose (Mpost-operative = 45.766 ± 35.85) were significantly increased compared to? preoperative dose (Mpreoperative = 18.95 ± 26.66 mg). Similar analysis was done with CCB and ARB also. It was found that the mean postoperative dose (Mpostoperative) of above antihypertensives were found significantly increased compared to mean preoperative dose (Mpreoperative); (CCB group [preoperative Mpreoperative 6.21 mg vs. Mpostoperative 9.79 mg; P = 0.01]; ARB group [Mpreoperative 14.03 mg vs. Mpostoperative 38.23 mg; P = 0.01]). This indirectly indicates that all these patients developed significant hemodynamic instability (PEH), i.e., PEH after CEA. In case of αB, there was no change in the mean postoperative dose (Mpreoperative 0.16 mg vs. Mpostoperative 3.74 mg: P = 0.27) compared to its preoperative value. In other words, patients on preoperative αBs did not developed PEH [Table 5].
Table 5: Antihypertensive medications and postendarterectomy hypertension

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  Discussion Top


BRS lies in the tunica media and adventitia of ICA where it joins the carotid bulb. When BRS are stretched by increased BP, they send signals through the nerve of Herring, which is a branch of glossopharyngeal nerve to the corresponding brain centres. As a result, the sympathetic outflow is decreased and parasympathetic outflow is increased, resulting in bradycardia, decreased cardiac contractility, and peripheral vascular resistance and an overall decrease in BP.

In CEA, this BRS circuit is disturbed by the dissection or transection in c- or e-CEA, respectively. The exact mechanism of PEH remains unclear. Two theories have been postulated (1) BRS denervation during carotid dissection-(local mechanism) (2) increased norepinephrine production in cerebral and peripheral level (sympathetic mechanism) in which the former one is widely accepted.[4] Since e-CEA involves oblique transection of ICA from carotid bulb, the chance of BRS denervation and subsequent development of PEH is high compared to c-CEA which involves only dissection of ICA-carotid bulb.

It was Mehta et al. in 2001 who first showed that e-CEA had higher incidence of PEH.[5] The main limitation of this study was the absence of BP determinations beyond the first 24 postoperative hours. A 2017 meta-analysis of PEH by Demirel et al. concluded that e-CEA increases the risk for post-CEA hypertension with postoperative BP recording from 1 to 6 days.[6] In all the above studies, the confounding variables such as stenosis severity and bilaterality of the ICA disease were well balanced, none of the studies included in the above meta-analysis incorporated the influence of preoperative uncontrolled BP on PEH. In the present study, also there was no significant difference in the number of patients with bilateral carotid disease in both e- and c-CEA (P = 0.263).

In our study, 87.1% of patients after e-CEA and 74.2% of patients after c-CEA developed PEH, which was very high compared to previous studies which were in the range of 11%–56%,[7] even though there was no statistical significant difference in PEH between the two study groups.(P = 0.199). The probable reason for the above is all patients included in our study were hypertensives on treatment, i.e., 61.3% of patients in e-CEA group and 41.9% of patients in c-CEA had uncontrolled Hypertension (HTN) before surgery. Moreover, those patients developing PEH and having high SBP, DBP, and MBP before surgery had significant statistical correlation (Karl-Pearson-coefficient R-value for SBP = 0.38, DBP = 0.38, MAP = 0.402). Newman et al. showed a similar finding that those patients who developed PEH were significantly less likely to be taking antihypertensive medications or to have a previous diagnosis of hypertension before admission.[8] There was also a strong association between PEH and patient age, being more common in younger patients. No other preoperative patient demographics or clinical variables were significantly associated with PEH, including the degree and severity of ICA stenosis (as well as severe bilateral disease) or any preoperative cerebral hemodynamic measurements.

If preoperative HTN is an important factor in determining the development of PEH, then we proceeded further to see the effect of antihypertensive drugs on PEH?. Four class of drugs routinely used in clinical practice was studied, mainly βB, CCBs, ARBs, and αBs. The dose of each anti-hypertensive drug was noted in mg preoperatively. When a patient develops HTN in the peri-operative period, the same class of antihypertensive is started in postoperative. For the study purpose, any increase in the dose of same antihypertensive as well addition of new class of antihypertensive for high BP >140/90 mm Hg in the postoperative period is considered as PEH.

To answer this question, we analyzed the dose of each class of antihypertensive and compared the preoperative and postoperative dose. For the simplicity of analysis, when a patient develops PEH, the same class of antihypertensive is started in postoperative. Any increase in dose of same antihypertensive or addition of new class of antihypertensive is considered as PEH. It was found that mean postoperative dose of all the above antihypertensive drugs (Mpostoperative) were significantly increased, compared to mean preoperative dose (Mpreoperative) except αBs. Those patients on preoperative αB did not developed PEH and maintained almost a similar preoperative dose at the time of discharge.

Theoretically, BRS function should improve after CEA, because a previously nondistensible BRS are brought back into neuronal circuit by the removal of the atherosclerotic carotid intima and media during CEA.[9] This improvement should be more evident in c-CEA as it does not involve sinus nerve transection as well. Hence, this improvement in BRS function should be reflected in the dose of antihypertensive, i.e., it should come down, especially after c-CEA, but in our study, none of the anti-hypertensive medications dose were found decreased after surgery.

The fluctuations in sympathetic system during CEA can be better controlled in patients who are started on sympathetic blocker preoperatively. In other words, whether αB can be considered as a novel therapeutic option for PEH. To the best of our knowledge, this is the first study to evaluate the role of medication in controlling PEH, but the main limitations are being a nonrandomized one, and the sample size was small.


  Conclusions Top


Our study showed sympathetic mechanism rather than local BRS breakdown as a cause of PEH, as both groups are developed PEH irrespective of the technique of surgery. The most important factor determining the development of PEH in our study is preoperative uncontrolled hypertension. One of the reasons for uncontrolled HTN in patients with ICA stenosis may be due to an overactive sympathetic system. If we were able to control this sympathetic overactivity preoperatively by an anti-hypertensive medication like αB, then we can prevent the development of PEH.

Financial support and sonsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hirschl M, Kundi M, Blazek G. Five-year follow-up of patients after thromboendarterectomy of the internal carotid artery: Relevance of baroreceptor sensitivity. Stroke 1996;27:1167-72.  Back to cited text no. 1
    
2.
Lin YH, Liu HM. Update on cerebral hyperperfusion syndrome. J Neurointerv Surg 2020;12:788-93.  Back to cited text no. 2
    
3.
Demirel S, Attigah N, Bruijnen H, Macek L, Hakimi M, Able T, et al. Changes in baroreceptor sensitivity after eversion carotid endarterectomy. J Vasc Surg 2012;55:1322-8.  Back to cited text no. 3
    
4.
Skydell JL, Machleder HI, Baker JD, Busuttil RW, Moore WS. Incidence and mechanism of post – Carotid endarterectomy hypertension. Arch Surg 1987;122:1153-5.  Back to cited text no. 4
    
5.
Mehta M, Rahmani O, Dietzek AM, Mecenas J, Scher LA, Friedman SG, et al. Eversion technique increases the risk for post – Carotid endarterectomy hypertension. J Vasc Surg 2001;34:839-45.  Back to cited text no. 5
    
6.
Demirel S, Goossen K, Bruijnen H, Probst P, Böckler D. Systematic review and meta-analysis of postcarotid endarterectomy hypertension after eversion versus conventional carotid endarterectomy. J Vasc Surg. 2017;65:868-82.  Back to cited text no. 6
    
7.
Deser SB, Demirag MK, Kolbakir F. Does surgical technique influence the postoperative hemodynamic disturbances and neurological outcomes in carotid endarterectomy? Acta Chir Belg 2019;119:78-82.  Back to cited text no. 7
    
8.
Newman JE, Bown MJ, Sayers RD, Thompson JP, Robinson TG, Williams B, et al. Post-carotid endarterectomy hypertension. Part 1: Association with pre-operative clinical, imaging, an?d physiological parameters. Eur J Vasc Endovasc Surg 2017;54:551-63.  Back to cited text no. 8
    
9.
Angell-James JE, Lumley JS. The effects of carotid endarterectomy on the mechanical properties of the carotid sinus and carotid sinus nerve activity in atherosclerotic patients. Br J Surg 1974;61:805-10.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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