Carotid artery stenting (CAS) is the treatment of choice in high-risk patients with extracranial carotid occlusive disease.1 Bradycardia and hypotension are well-recognized complications of this procedure and are often transient and self-limiting. This could translate into hemodynamic instability and neurologic sequelae, which occur in 19%-68% of patients and takes a median of 12 H (1-96 H).2 The possible predisposing factors are older age,3 history of coronary artery disease,4 larger balloon diameters,5 contralateral carotid occlusion,6 elevated SBP >180 mm Hg before the procedure,7 lesions involving the carotid bulb or heavy calcification, and ulceration. According to some reports, large fluctuations in SBP after CAS is a predictor of adverse outcomes (stroke and death).3 Some studies showed diabetes as a risk factor but Gupta et al reported that diabetes mellitus and a history of smoking reduce the risk of hemodynamic instability after CAS.2 We had 2 diabetic patients with prolonged hypotension after CAS despite treatment with volumes and vasopressor for 2 days and improved only after tight glycemic control. It seems that acute hyperglycemia may have a role in prolonged hypotension after CAS.
VASCULAR DISEASE MANAGEMENT 2012;9(2):E17–E19
Case Report 1. A 51-year-old female patient with history of diabetes mellitus, hypertension, hyperlipidemia and 3-vessel disease with left ventricular ejection fraction (LVEF) of 55% was a good candidate for coronary artery bypass graft (CABG) due to refractory chest pain. We proceeded with stenting of the right internal carotid because of a calcified plaque with 90% stenosis proximal to the right internal carotid without bulb involvement (Figures 1 and 2). The left internal carotid had a plaque with <50% stenosis. Her blood pressure was 120/80 before the procedure but she had severe prolonged hypotension (70 mmHg/p) after the procedure. By treatment with saline and dopamine, her blood pressure preserved about 120 to 130 mmHg but with a modest decrease in dose of dopamine (decreasing from 15 µg/kg/min to 12 µg/kg/min over 5 days); systolic blood pressure (SBP) dropped to 80 mmHg. This situation took 7 days and improved only after tight control of her blood sugar. Fasting blood sugar (FBS) was 96 mg/dL before and remained high despite divided doses of regular insulin (Table 1).
Case Report 2. A 64-year-old, hypertensive, diabetic female patient presented with 3-vessel disease and LVEF of 50%. This patient was a good candidate for CABG and had previously undergone carotid artery stenting (CAS) on left internal carotid artery for 95% proximal stenosis. The lesion didn't involve the bulb and wasn't calcified. Her right internal carotid artery also had 85% proximal plaque (Figures 3 and 4). After the procedure, treatment began with normal saline and dopamine to keep blood pressure stable. Dopamine titrated to 15 µg/kg/min but she didn`t tolerate tapering and her blood pressure was dependent on inotrope, which persisted for 4 days. The only abnormality in this case was uncontrolled blood glucose after procedure. Her SBP was 130/80 and FBS was 184 before CAS (Table 2).
Carotid angioplasty and stenting (CAS) is important in the treatment of high-risk patients with extracranial carotid atery occlusive disease (CAD).1 The incidence of stroke, death, and myocardial infarction (MI) is lower with CAS compared with CEA in high-risk patients.8,9
Hemodynamic alterations such as bradycardia or hypotension are well-recognized physiologic responses during catheter-based carotid artery intervention, but most of these events are transient and self-limiting in nature.3,10
The adventitial baroreceptors located in the carotid sinus plays a critical role in hemodynamic alterations during and after CAS. Impulses originating in the carotid sinus reach the medullary vasomotor nuclei by way of the carotid sinus nerve and the glossopharyngeal nerve. Distension of the carotid bulb by means of balloon angioplasty or stent placement leads to baroreceptor stimulation that not only triggers a reflex inhibition of adrenergic output, which reduces peripheral sympathetic tones, but also increases parasympathetic activity and ultimately leads to hypotension and bradycardia.1
The incidence of hypotension during CAS ranges widely, from 14% to 28%, based on available reports.1 Gupta et al reported that hypotension occurred in 27%; 59% of all hypotension patients developed during the procedure and 41% after the procedure. Vasopressor treatment (one-time bolus or continuous infusion) was required in 18%, atropine in 18%, and the combination of atropine and vasopressor in 7%. Persistent hemodynamic depression (HD), defined as SBP <90 mmHg or patients with heart rate <60 who required continuous vasopressor infusion after the procedure, developed in 17% of all interventions but 40% of all HD patients. Patients who developed persistent HD were more likely to have had intraprocedural HD. Patients received intravenous vasopressors for a mean time of 15.9-16.4 H (median: 12 H; range: 1 to 96 H).2 Taha et al reported hypotension in 32.6% and prolonged hypotension in 19.7% of their patients. The mean period of blood pressure instability, defined as latest reading of less than 90 mmHg with intermittent higher readings, was 7.8 H (range: 10 min to 72 H).6
Interestingly Gupta et al reported that diabetes mellitus and history of smoking predicts lower risk of hemodynamic instability after CAS.2 They found that long-term smoking impairs the carotid baroreceptor response and augments the sympathetic tone, which raises the blood pressure and heart rate.2,11,12 Similarly, diabetes mellitus is known to impair cardiovascular autonomic response by attenuating parasympathetic nerve function, which may attenuate the carotid baroreceptor stimulation triggered by carotid intervention.13,14
Both our patients were diabetic and had persistent hypotension after the procedure. There was serious dependency on high doses of vasopressor therapy. During this period, we found elevated blood sugar that showed severe fluctuation during follow-up. After median 6 days and only after tight control of blood sugar by continuous insulin infusion, it was possible to discontinue vasopressor therapy.
Marfella et al found the effects of acute hyperglycemia on autonomic function in 12 healthy male volunteers showed a reduced baroreflex activation.15 Other observations show that cardiovascular autonomic function inversely relates to blood glucose (BG) levels in nondiabetic patients.16-19 Baroreflex sensitivity (BRS) was negatively associated with HbA1c levels in a population with a normal glucose tolerance.16 The corrected QT (QTc) duration, a measure of cardiac autonomic function, was related to high fasting blood glucose (BG) levels in a population-based study of 6543 healthy subjects17 and Marfella et al showed an increase in QTc duration in response to hyperglycemia in healthy subjects.18 Lefrandt et al observed a negative relationship between BRS and glucose levels that was independent from other risk factors20 in contrast to the study by Watkins et al19 in which the relationship was explained by the association with age, BP, and BMI. They proposed that a parasympatholytic effect of insulin was involved, because BRS was related to fasting insulin levels.19 In the study by Marfella et al, the effect of acute hyperglycemia on QTc was still evident during inhibition of insulin secretion by octreotide, suggesting that mechanisms other than insulin might be involved, or even that BG directly affects autonomic function.18 Watkins19 found that fasting glucose and fasting insulin were each related to BRS in univariate models, but only fasting insulin was significantly related in a multivariate model adjusted for significant covariates in 162 young nondiabetic volunteers.21
In an animal model, acute hyperglycemia significantly attenuated motor nerve conduction velocity and nerve blood flow.21 Finally, the relation between hyperglycemia and diminished autonomic function has been well demonstrated in both controlled clinical studies18 and large population studies.17
Although published data are in favor of reduced BRS and therefore, lesser probability of hypotension after CAS in diabetic patients, we observed severe persistent hypotension that resolved only after tight glycemic control in 2 diabetic cases. We still need to explore the question, “is there any cause and effect relationship between hypotension and hyperglycemia or insulin level?”
- Lin PH, Zhou W, Kougias P, El Sayed HF, Barshes NR, Huynh TT. Factors associated with hypotension and bradycardia after carotid angioplasty and stenting. J Vasc Surg. 2007 Nov;46(5):846-854.
- Gupta R, Abou-Chebl A, Bajzer CT, Schumacher HC, Yadav JS. Rate, predictors, and consequences of hemodynamic depression after carotid artery stenting. J Am Coll Cardiol. 2006 Apr;47(8):1538-1543.
- Mlekusch W, Schillinger M, Sabeti S, et al. Hypotension and bradycardia after elective carotid stenting: frequency and risk factors. J Endovasc Ther. 2003 Oct;10(5):851-859.
- Mendelsohn FO, Weissman NJ, Lederman RJ, et al. Acute hemodynamic changes during carotid artery stenting. Am J Cardiol. 1998 Nov;82(9):1077-1081.
- Dangas G, Laird JR Jr., Satler LF, et al. Postprocedural hypotension after carotid artery stent placement: predictors and short- and long-term clinical outcomes. Radiology. 2000 Jun;215(3):677-683.
- Taha MM, Toma N, Sakaida H, et al. Periprocedural hemodynamic instability with carotid angioplasty and stenting. Surg Neurol. 2008 Sep;70(3):279-285.
- Howell M, Krajcer Z, Dougherty K, et al. Correlation of periprocedural systolic blood pressure changes with neurological events in high-risk carotid stent patients. J Endovasc Ther. 2002 Dec;9(6):810-816.
- Yadav JS. Carotid stenting in high-risk patients: design and rationale of the SAPPHIRE trial. Cleve Clin J Med. 2004 Jan;71(suppl 1):S45-46.
- Yadav JS, Wholey MH, Kuntz RE, et al; for the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy Investigators. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med. 2004 Oct;351(15):1493-1501.
- McKevitt FM, Sivaguru A, Venables GS, et al. Effect of treatment of carotid artery stenosis on blood pressure: a comparison of hemodynamic disturbances after carotid endarterectomy and endovascular treatment. Stroke. 2003 Nov;34(11):2576-2581.
- Grassi G, Seravalle G, Calhoun DA, Bolla G, Mancia G. Cigarette smoking and the adrenergic nervous system. Clin Exp Hypertens A. 1992;14(1-2):251-260.
- Grassi G, Seravalle G, Calhoun DA, et al. Mechanisms responsible for sympathetic activation by cigarette smoking in humans. Circulation. 1994 Jul;90(1):248-253.
- Pfeifer MA, Weinberg CR, Cook DL, et al. Autonomic neural dysfunction in recently diagnosed diabetic subjects. Diabetes Care. 1984 Sep-Oct;7(5):447-453.
- Watkins PJ, Edmonds ME. Sympathetic nerve failure in diabetes. Diabetologia. 1983 Aug;25(2):73-77.
- Marfella R, Verrazzo G, Acampora R, et al. Glutathione reverses systemic hemodynamic changes induced by acute hyperglycemia in health subjects. Am J Physiol. 1995 Jun;268: E1167-E1173.
- Gerritsen J, Dekker JM, TenVoorde BJ, et al. Glucose tolerance and other determinants of cardiovascular autonomic function: the Hoorn study. Diabetologia. 2000 May:43(5):561-570.
- Lefrandt JD, Diercks GF, van Boven AJ, Crijns HJ, van Gilst WH, Gans RO. High fasting glucose and QTc duration in a large healthy population. Diabetologia. 2000 Oct;43(10):1332-1333.
- Marfella R, Nappo F, De Angelis L, Siniscalchi M, Rossi F, Giugliano D. The effect of acute hyperglycaemia on QTc duration in healthy man. Diabetologia. 2000 May;43(5):571-575.
- Watkins LL, Surwit RS, Grossman P, Sherwood A. Is there are a glycemic threshold for impaired autonomic control? Diabetes Care. 2000 Jun;23(6):826-830.
- Lefrandt JD, Mulder MC, Bosma E, Smit AJ, Hoogenberg K. Inverse relationship between blood glucose and autonomic function in healthy subjects. Diabetes Care. 2000 Dec;23(12):1862-1864.
- Saini AK, Arun KH, Kaul CL, Sharma SS. Acute hyperglycemia attenuates nerve conduction velocity and nerve blood flow in male Sprague-Dawley rats: reversal by adenosine. Pharmacol Res. 2004 Dec;50(6):593-599.
From the Guilan University of Medical Science, Dr. Heshmat Heart Hospital, Rasht, Iran.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted August 23, 2011, final version accepted September 1, 2011.
Address for correspondence: Dr. Samira Arami, Resident of Cardiology, Gilan University, Heshmat Hospital, Shahid Beheshti, Heshmat Square, Rasht, Gilan, 4193955588, Iran. Email: email@example.com