Predictors of clinically significant postprocedural hypotension after carotid endarterectomy and carotid angioplasty with stenting

Article Outline

• Abstract
• Methods and materials
• Results
• Discussion
• Conclusions
• Author contributions
• References
• Copyright

Objectives

Significant hypotension after carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS) has been correlated with adverse outcomes. The objective of this study was to determine risk factors that predict hypotension after patients undergo CEA and CAS.

Methods

The review included 1474 CEA patients and 157 CAS patients who underwent procedures from 2002 to 2008. Specific patient characteristics, such as comorbid diseases, degree of carotid stenosis, presence of neurologic symptoms, and preprocedure medications, were assessed. Also reviewed were specific postprocedural clinical outcomes, including hypotension requiring pressors, myocardial infarction, stroke, death, and hospital length of stay.

Results

The incidence of clinically significant hypotension was 12.6% in CEA patients and 35% in CAS patients (P < .001). Clinically significant hypotension was correlated with increased postprocedural myocardial infarction (2.1% vs 0.5%, P = .022), increased mortality (2.1% vs 0.1%, P < .001), and length of stay >2 days (46.3% vs 27.4%, P = .01). Hypotension was not associated with increased postprocedural strokes (0.8% vs 0.6%, P = .75) or recurrent neurologic symptoms (0.4% vs 0.3%, P = .55). Preoperative nitrate use predicted a greater incidence of postprocedural hypotension (P = .043). A history of tobacco use was correlated with postprocedure hypotension (P = .033). Preprocedural strokes, the use of calcium channel blockers, β-blockers, angiotensin-converting enzyme inhibitors, prior myocardial infarction, degree of preprocedural carotid stenosis, type of stent, previous ipsilateral and contralateral interventions, and female gender did not correlate with postprocedural hypotension (P >.05).

Conclusions

Postprocedural hypotension occurs more commonly with CAS than CEA and is associated with increased postprocedural myocardial infarction and length of stay, and death. Nitrates and tobacco use predict a higher incidence of postprocedural hypotension. High-risk patients should be aggressively managed to prevent the increased morbidity and mortality due to postprocedural hypotension.

An estimated 750,000 cerebrovascular accidents (strokes) occur annually, leading to >200,000 fatalities.¹ More than two-thirds of stroke survivors are permanently disabled.² Within the last decade, the gold standard of carotid endarterectomy (CEA) for the prevention of strokes in symptomatic³, ⁴ and asymptomatic patients⁵, ⁶ has been challenged by the proliferation of carotid angioplasty with stenting (CAS).⁷, ⁸, ⁹, ¹⁰

A high incidence of hypotension observed after CAS was noted in several large studies.⁷, ¹¹ Several reports have shown a higher incidence of hypotension after CAS than after CEA.¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷ Postprocedural hypotension in this particular patient population has been associated with an increased incidence of complications, poor long-term prognosis, and death.¹⁴, ¹⁷ Many theorize that this complication may occur in part due to excessive stretching of the baroreceptors in the carotid bulb by the angioplasty and stenting procedures.¹³ Supporting this hypothesis is the observation that the incidence of hypotension associated with balloon-expanded stents is 34% vs 14% for self-expanding stents.¹⁶

Although some groups have advocated prophylactic administration of atropine before surgery,¹⁴ or even temporary transvenous pacemakers,¹⁵ no clinical trials have been performed to date to evaluate the efficacy of these modalities. In addition, few studies to date have definitively identified the preoperative risk factors that predict for a higher incidence of hypotension after the CEA or CAS procedure.

The objective of this study was to determine which risk factors predict hypotension in patients after CEA and CAS. For this study, we retrospectively reviewed the medical records of consecutive CEA and CAS patients from three medical institutions. We analyzed these patients to determine the effect of postprocedural hypotension on clinical outcomes. We also analyzed patient characteristics and other aspects of these procedures to determine potential risk factors that predict postprocedural hypotension.

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Methods and materials 

Institutional Review Board approval was obtained from each participating institution for this study. All patients who had undergone CEA or CAS in participating institutions from May 2002 to June 2008 were included in this study. The decision to perform CAS or CEA was made according to patient preference and overall evaluation by the vascular surgeon. There were a few relative exclusion criteria for CEA, including prior neck radiotherapy and high cervical lesions not accessible by CEA. The only exclusion criterion for CAS was complete ipsilateral carotid occlusion or completed, massive hemispheric stroke. This study was not a randomized trial.

Significant postprocedural hypotension was defined as >40 mm Hg drop in systolic blood pressure or a systolic blood pressure <90 mm Hg sustained for >1 hour after carotid intervention, as has been previously described.¹², ¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹ In addition, this hypotension must have occurred ≤1 to 2 hours after CEA or CAS was performed. Hypotensive episodes that occurred after this immediate postprocedural period were not included in this analysis.

These patients required continuous intravenous vasopressor support during their stay in the intensive care unit. The triggers for treating hypotension in these patients were the persistence of hypotension (according to the criteria listed) for >1 hour or the presence of symptoms related to hypotension, such as dizziness, shortness of breath, and signs of orthostasis.

Treatment of hypotension after CEA or CAS consisted of a routine protocol of 500 mL of intravenous fluid boluses, followed by the addition of intravenous vasopressor medications such as dopamine or vasopressin if the hypotension was sustained. Intravenous pressor agents were titrated to the minimum dose required to maintain a systolic blood pressure >90 mm Hg.

The study included 1631 patients, consisting of 157 CAS and 1474 CEA procedures. We retrospectively analyzed data for four groups of patients: for CAS, 102 patients without significant hypotension (nonhypotensive CAS) and 55 patients with significant hypotension (hypotensive CAS); for CEA, 1288 patients without significant hypotension (nonhypotensive CEA) and 186 patients with significant hypotension (hypotensive CEA).

The anatomic criteria by which patients had been accepted for CAS were identical to the criteria used for CEA. These were an internal carotid artery stenosis of >80% stenosis (defined as a peak systolic duplex velocity of >125 cm/s), and an end diastolic internal carotid velocity of >125 cm/s corresponding to 80% to 89% stenosis for asymptomatic patients. For symptomatic patients, we used a definition of >50% stenosis (defined as a peak systolic duplex velocity >125 cm/s, and an end diastolic velocity <125 cm/s).

Carotid duplex ultrasound (DUS) imaging was performed preoperatively and for surveillance in the noninvasive vascular laboratories of participating institutions. Ultrasound technicians experienced in carotid imaging (Intersocietal Commission for the Accreditation of Vascular Laboratories or American College of Radiology certified) performed these studies. Interpretation of the results was performed by both a radiologist and vascular surgeon.

CAS had been performed according to a standard protocol. All patients were pretreated with acetylsalicylic acid (81 mg per day, aspirin) and clopidogrel (75 mg per day, Plavix; Sanofi-Aventis, Bridgewater, NJ) for 5 days before the procedure. CAS was performed under conscious sedation in the Special Procedures Section of the Radiology Department. Carotid stenting was performed using Smart Precise (Cordis Inc, Miami Lakes, Fla), Acculink (Guidant Corp, Indianapolis, Ind), and Exact (Abbott Vascular Inc, Abbott Park, Ill) stents. All procedures used the Filter Wire (Boston Scientific Inc, Natick, Mass), Accunet (Guidant Inc), or Emboshield (Abbott Vascular Inc) cerebral protection devices. After placement of the cerebral protection device, most patients underwent predilatation of the carotid stenosis with a 3.5-mm balloon. All patients underwent postdilatation after stent placement with a 5- to 5.5-mm balloon. All patients received 0.5 mg of atropine before balloon angioplasty to minimize bradycardia and an additional 0.5 mg of atropine before final stent dilatation.

After the procedure, patients were maintained on clopidogrel for 8 to 12 weeks, with aspirin therapy indefinitely. These procedures were performed exclusively by vascular surgeons. Routine arch angiograms were not performed because this may increase the risk of stroke.¹⁸

Magnetic resonance arteriography was obtained to examine the arch before the procedure unless the patients had renal insufficiency. Under the latter circumstances, the carotid DUS imaging remained the sole imaging modality.

CEA was performed in the operating room under primarily general or local anesthesia. Shunts were placed intraoperatively to minimize cerebral ischemic time based on the preference of the vascular surgeon. All CEAs were closed using a Dacron (DuPont, Wilmington, DE) or a bovine pericardium patch. Patients received heparin (100 U/kg) immediately before shunt placement. Prophylactic atropine dosing was not performed during CEA in contrast to CAS procedures. CEA patients continued aspirin therapy indefinitely after surgery.

To determine the effect of possible risk factors on clinically significant hypotension after carotid reconstruction, we retrospectively collected data on baseline patient characteristics, clinical outcomes, and other potential risk factors as described below. We assessed baseline characteristics such as gender, average age, degree of ipsilateral carotid stenosis, degree of contralateral carotid stenosis, prior strokes, prior transient ischemic attacks (TIA), atrial fibrillation, diabetes, previous myocardial infarction (MI), coronary artery disease (CAD), prior coronary artery bypass grafting (CABG), chronic obstructive pulmonary disease (COPD), hypertension, and a history of tobacco use (either recent intake of tobacco products or a history of tobacco use) to determine if significant differences existed in our four patient subgroups that represented potential confounding factors to influence our analyses.

To normalize the variability in carotid DUS results from the participating institutions in this study, velocity data corresponding to <50% stenosis was given a grade of class I stenosis, 50% to 79% stenosis was class II, 80% to 99% was class III, and total occlusion was class IV. We then assessed the incidence of postprocedural MI (confirmed by electrocardiograms and cardiac enzymes), TIA, strokes (neurologic deficits lasting longer >1 hour with changes noted on CT scans or magnetic resonance imaging of the brain), death, and average length of stay to determine the effect that postprocedural hypotension had on these measures of general clinical outcomes.

Baseline patient characteristics and potentially modifiable risk factors, such as preoperative medications, general vs local anesthesia, the use of prosthetic patch materials, the use of carotid shunts, and the type of carotid stent device were further analyzed to determine which risk factors predicted a greater incidence of postprocedural hypotension.

The data for CAS and CEA patients were analyzed and compared using analysis of variance (ANOVA) for interval data and a χ² test for proportions. Variables with a value of P ≤ .05 were considered statistically different. The P values from the ANOVA and χ² tests are reported in the data tables. Variables that were statistically different between treatment groups underwent further post hoc testing with a Student-Newman-Keuls test for further analysis with subdivided contingency tables, as appropriate. The P values from these post hoc tests are reported separately in the Results.

Potential risk factors for hypotension underwent further logistic regression univariate and subsequent multivariate analysis to determine which factors independently predicted a greater risk of significant postprocedural hypotension. Additional subanalyses were performed for clinical outcomes comparing only CAS or CEA patients, and similarly for potential risk factors for hypotension. These analyses were performed using the t test or χ² tests where appropriate. Data processing and statistical analyses were performed using SAS 9.1 software (SAS Institute Inc, Cary, NC).

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Results 

The preoperative patient characteristics in the 102 nonhypotensive CAS patients, 55 hypotensive CAS patients, 1288 nonhypotensive CEA patients, and 186 hypotensive CEA patients were generally similar. The mean age was 70.4 in the nonhypotensive CAS group, 71.9 in the hypotensive CAS group, 71.4 in the nonhypotensive CEA group, and 70.6 the hypotensive CEA group (P = 1.0). There was also a predominance of men in all subgroups. The degree of ipsilateral internal carotid stenosis was quite severe in all groups, with an average grade of 2.67 to 2.78 corresponding to >70% stenosis to complete occlusion.

There were 11 patients (20%) with prior neurologic symptoms in the hypotensive CAS cohort, 20 symptomatic patients (20%) in the nonhypotensive CAS cohort, 40 patients (21%) with neurologic symptoms in the hypotensive CEA cohort, and 307 symptomatic patients (24%) in the nonhypotensive CEA cohort. These neurologic symptoms were either previous TIAs or strokes. Most patients were asymptomatic before CEA and CAS. The nonhypotensive CAS cohort had more patients with comorbid COPD compared with the other subgroups (P < .001). In addition, tobacco use was also more prevalent in the hypotensive CEA groups compared with the other cohorts (P < .01). These patients were similar with regards to the other patient characteristics listed in Table I.

Table I. Patient characteristics

Variable	CAS cohort		CEA cohort		P
No. (%) or mean	Hypotensive	Nonhypotensive	Hypotensive	Nonhypotensive
Total patients	55	102	186	1288
Male gender	33(60)	62(61)	120(65)	799(62)	1.0
Age, mean y	71.9	70.4	70.6	71.4	.51
Pre-op stenosis, grade
Ipsilateral	2.74	2.69	2.67	2.78	.41
Contralateral	1.87	1.92	2.01	2.06	.54
Prior stroke	5(9)	10(10)	15(8)	129(10)	1.0
Prior TIA	6(11)	10(10)	25(13)	178(14)	.94
Atrial fibrillation	1(2)	7(7)	9(5)	86(7)	.35
Diabetes mellitus	12(22)	37(36)	47(25)	394(21)	.15
Prior MI	8(15)	21(21)	32(17)	223(17)	1.0
CAD	29(54)	46(46)	81(44)	600(47)	.84
Prior CABG	17(31)	19(19)	48(26)	362(28)	.18
COPD	7(13)	33(33)	30(16)	199(15)	<.001
Hypertension	50(91)	92(90)	165(89)	1142(89)	.34
Tobacco use	29(57)	63(63)	138(74)	810(63)	<.01

CABG, Coronary artery bypass grafting; CAD, coronary artery disease; CAS, coronary angioplasty and stenting; CEA, carotid endarterectomy; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; TIA, transient ischemic attack; NS, not significant.

Overall clinical postprocedural outcomes were excellent for both CEA and CAS patients. For all CEA patients, the incidence of MI infarction was 0.7%, the incidence of strokes was 0.6%, and mortality was 0.5%. For all CAS patients, the incidence of MI was 1.3%, the incidence of strokes was 1.3%, and mortality was 0%.

Clinical outcomes were assessed for the four subgroups of patients. Overall, the incidence of clinically significant hypotension was 12.6% in CEA patients and 35% in CAS patients (P < .001). No CAS patients died. Two patients (0.2%) died in the nonhypotensive CEA group, and five (3%) in the hypotensive CEA group. Clinically significant hypotension predicted greater mortality after CEA compared with all other subgroups (P < .001).

Postprocedural MI occurred in 2% of hypotensive CEA and 2% of hypotensive CAS patients compared with 0.5% of nonhypotensive CEA and 1% of nonhypotensive CAS patients (P = .022). Length of stay was an average of 2.49 days in the hypotensive CEA group compared with 1.97 in the nonhypotensive CEA group, 2.06 in the hypotensive CAS group, and 1.9 in the nonhypotensive CAS group (P = .01). Postprocedural strokes and TIA were not significantly different, and these results are listed in Table II. A subanalysis of clinical outcomes for CAS patients is presented in Table II, A. No significant differences were noted for the variables assessed between hypotensive and nonhypotensive CAS patients. In addition, another subanalysis of clinical outcomes demonstrated a significant increase in the rate of postoperative myocardial infarctions, death, and length of stay for hypotensive CEA patients compared with nonhypotensive CEA patients (Table II, B).

Table II. Clinical outcomes

Post-op outcome	CAS cohort		CEA cohort		P
	Hypotensive	Nonhypotensive	Hypotensive	Nonhypotensive
	(n = 55)	(n = 102)	(n = 186)	(n = 1288)
MI, No. (%)	1(2)	1(1)	4(2)	6(0.5)	.022
TIA, No. (%)	0(0)	2(2)	1(1)	2(0.2)	.1
Stroke, No. (%)	1(2)	1(1)	1(1)	8(1)	.9
Death	0(0)	0(0)	5(3)	2(0.2)	<.001
Average LOS, d	1.9(1-11)	2.06(1-22)	2.49(1-22)	1.97(1-34)	.01

CAS, Coronary angioplasty and stenting; CEA, carotid endarterectomy; LOS, length of stay; MI, myocardial infarction; TIA, transient ischemic attack.

Table II, A. Clinical outcomes after carotid angioplasty and stenting^a

Outcome	Hypotensive	Nonhypotensive	P
	(n = 55)	(n =102)
MI, No. (%)	1(2)	1(1)	.77
TIA, No. (%)	0(0)	2(2)	.76
Stroke, No. (%)	1(2)	1(1)	.77
Death, No. (%)	0(0)	0(0)	.85
Average LOS, d	1.9(1-11)	2.06(1-22)	.77

LOS, Length of stay; MI, myocardial infarction; TIA, transient ischemic attack.

Table II, B. Clinical outcomes after carotid endarterectomy^a

Post-op outcome	Hypotensive	Nonhypotensive	P
	(n = 186)	(n = 1288)
MI, No. (%)	4(2)	6(0.5)	.03
TIA, No. (%)	1(1)	2(0.2)	.83
Stroke, No. (%)	1(1)	8(1)	.71
Death, No. (%)	5(3)	2(0.2)	<.001
Average LOS, d	2.49(1-22)	1.97(1-34)	.017

LOS, Length of stay; MI, myocardial infarction; TIA, transient ischemic attack.

This analysis of the potential risk factors for clinically significant hypotension after CEA and CAS produced the following results. All potential risk factors underwent univariate analysis. Those factors that were potentially significant then underwent multivariate analysis to determine which were independently associated with a higher risk of postprocedural hypotension. Preprocedural nitrate use (isosorbide mononitrate, nitroglycerin [oral and transdermal], and isosorbide dinitrate) was present in 8% of hypotensive CAS patients and 7% of hypotensive CEA patients compared with 2% of nonhypotensive CAS patients and 4% of nonhypotensive CEA patients (P = .043). Tobacco use also was more prevalent in CAS and CEA patients who developed hypotension and was identified as an independent risk factor for hypotension (P = .033).

Baseline patient characteristics such as age, gender, degree of preoperative ipsilateral stenosis, preoperative contralateral stenosis, atrial fibrillation, prior ipsilateral procedure, prior contralateral procedure, diabetes, prior MI, coronary artery disease, prior CABG, COPD, and hypertension were not independent risk factors for postprocedural hypotension (P > .05). Preoperative medications such as statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors), antiplatelet agents (aspirin and clopidogrel), Coumadin (Bristol-Myers Squibb, Princeton, NJ), calcium channel blockers, diuretics (hydrochlorothiazide and furosemide), oral diabetic agents (metformin and glyburide), β-blockers, and angiotensin-converting enzyme (ACE) inhibitors were also not significantly associated with postprocedural hypotension.

Specific procedural factors such as local vs general anesthesia, bulb block technique, patch angioplasty after CEA, and placement of carotid shunts were not protective or harmful in terms of significant hypotension. These data are summarized in Table III. A separate analysis was performed to determine if specific stent devices were more frequently associated with hypotension after CAS. No correlation was observed between stent type and a greater incidence of hypotension (Table IV).

Table III. Potential risk factors^a

Variable	CAS cohort		CEA cohort		OR	P
	Hypotensive	Nonhypotensive	Hypotensive	Nonhypotensive
No. (%) or mean	(n = 55)	(n =102)	(n =186)	(n =1,288)
Age, y	71.9	70.4	70.6	71.4	1.12	.87
Male gender	33(60)	62(61)	120(65)	799(62)	.98	.67
Pre-op stenosis
Ipsilateral	2.74	2.69	2.67	2.78	1.05	1.0
Contralateral	1.87	1.92	2.01	2.06	1.12	1.0
Symptomatic lesions	13(25)	25(25)	46(25)	370(29)	1.1	.22
Atrial fibrillation	1(2)	7(7)	9(5)	86(7)	1.08	.81
Prior procedure
Ipsilateral	10(18)	23(23)	5(3)	33(3)	1.22	.12
Contralateral	12(22)	24(24)	17(9)	147(11)	1.27	1.0
Diabetes mellitus	12(22)	37(36)	47(25)	394(31)	1.15	.47
Statins	46(84)	74(73)	135(73)	953(75)	1.09	.81
Antiplatelet agents	50(91)	90(89)	148(80)	1,037(81)	.76	.86
Coumadin	5(9)	11(11)	26(14)	123(10)	1.01	.13
Calcium channel blockers	21(38)	36(36)	40(22)	366(29)	1.36	.25
Diuretics	21(38)	42(42)	60(33)	470(37)	.95	.32
Oral diabetic drugs	10(18)	33(33)	40(22)	338(27)	.91	.55
β-Blockers	33(60)	51(50)	92(50)	719(57)	.96	.29
ACE inhibitors	22(40)	44(44)	86(47)	502(39)	.87	.12
Nitrates	4(8)	2(2)	13(7)	52(4)	1.92	.043
Prior MI	8(15)	21(21)	32(17)	223(17)	1.28	.78
Coronary artery disease	29(54)	46(46)	81(44)	600(47)	1.24	.82
Prior CABG	17(31)	19(19)	48(26)	362(28)	1.31	.94
COPD	7(13)	33(33)	30(16)	199(15)	1.15	.64
Hypertension	50(91)	92(90)	165(89)	1142(89)	1.2	.94
Tobacco use	29(57)	44(43)	138(74)	810(63)	2.17	.033
Anesthesia
Local	54(98)	101(99)	1(1)	12(1)	1.02	1.0
General	1(2)	1(1)	185(99)	1272(99)	.95	1.0
Bulb block	NA	NA	7(4)	34(3)	.84	.66
Patch Angioplasty	NA	NA	182(98.4)	1,234(96)	.99	1.0
Shunt	NA	NA	145(80)	983(76)	1.12	.78

ACE, Angiotensin converting enzyme inhibitors; CABG, coronary artery bypass grafting; CAS, coronary angioplasty and stenting; CEA, carotid endarterectomy; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; transient ischemic attack; NS, not significant; OR, odds ratio.

An additional analysis of potential risk factors for hypotension comparing only hypotensive CAS patients with nonhypotensive CAS patients was also performed (Table III, A). Of note, COPD was more common in nonhypotensive CAS patients (33%) than in hypotensive CAS patients (13%; P = .01). In contrast to the findings from our combined analysis of all CEA and CAS patients, nitrate use and tobacco use were not significantly different between hypotensive CAS and nonhypotensive CAS patients. Similarly, an additional analysis of potential risk factors for hypotension comparing only hypotensive CEA with nonhypotensive CEA patients (Table III, B) found that tobacco use was more common in hypotensive CEA patients (P = .003); however, nitrate use failed to reach significance (P = .1).

Table III, A. Potential risk factors—carotid angioplasty and stenting^a

Variable	Hypotensive (n = 55)	Nonhypotensive (n = 102)	P
No. (%) or mean
Age, y	71.9(42-91)	70.4(46-92)	.38
Male gender	33(60)	62(61)	.94
Pre-op stenosis, grade
Ipsilateral	2.74(2-4)	2.69(2-4)	.62
Contralateral	1.87(1-4)	1.92(1-4)	.80
Symptomatic lesions	13(25)	25(25)	.94
Atrial fibrillation	1(2)	7(7)	.32
Prior procedure
Ipsilateral	10(18)	23(23)	.66
Contralateral	12(22)	24(24)	.97
Diabetes mellitus	12(22)	37(36)	.09
Statins	46(84)	74(73)	.17
Antiplatelet agents	50(91)	90(89)	.81
Coumadin	5(9)	11(11)	.95
Calcium channel blockers	21(38)	36(36)	.85
Diuretics	21(38)	42(42)	.85
Oral diabetic drugs	10(18)	33(33)	.09
β-Blockers	33(60)	51(50)	.30
ACE inhibitors	22(40)	44(44)	.83
Nitrates	4(8)	2(2)	.22
Prior MI	8(15)	21(21)	.47
Coronary artery disease	29(54)	46(46)	.46
Prior CABG	17(31)	19(19)	.12
COPD	7(13)	33(33)	.01
Hypertension	50(91)	92(90)	.89
Tobacco use	29(57)	44(43)	.33
Anesthesia
Local	54(98)	101(99)	.77
General	1(2)	1(1)	.77

Table III, B. Potential risk factors—carotid endarterectomy^a

Variable	Hypotensive (n = 186)	Nonhypotensive (n = 1288)	P
No. (%) or mean
Age, y	70.6(49-90)	71.4(38-92)	.27
Male gender	120(65)	799(62)	.83
Pre-op stenosis
Ipsilateral	2.67(2-4)	2.78(2-4)	.29
Contralateral	2.01(1-4)	2.06(1-4)	.25
Symptomatic lesions	46(25)	370(29)	.24
Atrial fibrillation	9(5)	86(7)	.43
Prior procedure
Ipsilateral	5(3)	33(3)	.88
Contralateral	17(9)	147(11)	.43
Diabetes mellitus	47(25)	394(31)	.16
Statins	135(73)	953(75)	.28
Antiplatelet agents	148(80)	1,037(81)	.84
Coumadin	26(14)	123(10)	.08
Calcium channel blockers	40(22)	366(29)	.06
Diuretics	60(33)	470(37)	.18
Oral diabetic drugs	40(22)	338(27)	.20
β-Blockers	92(50)	719(57)	.12
ACE inhibitors	86(47)	502(39)	.07
Nitrates	13(7)	52(4)	.10
Prior MI	32(17)	223(17)	.95
Coronary artery disease	81(44)	600(47)	.49
Prior CABG	48(26)	362(28)	.57
COPD	30(16)	199(15)	.93
Hypertension	165(89)	1,142(89)	.92
Tobacco use	138(74)	810(63)	.003
Anesthesia
Local	1(1)	12(1)	.91
General	185(99)	1,272(99)	.64
Bulb block	7(4)	34(3)	.53
Patch angioplasty	182(98.4)	1,234(96)	.26
Shunt	145(80)	983(76)	.82

ACE, Angiotensin converting enzyme inhibitors; CABG, coronary artery bypass grafting; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; NS, not significant.

Table IV. Stent type and hypotension^a

CAS patients	No.	Acculink	Smart precise	Exact
Hypotensive, No. (%)	55	28(51)	11(20)	16(29)
Nonhypotensive, No. (%)	102	66(64)	18(18)	18(18)

CAS, Carotid angioplasty and stenting.

Some interesting findings trending toward significance indicated that use of calcium channel blockers and β-blockers was more common among nonhypotensive CEA patients. In contrast, use of Coumadin and ACE inhibitors was more common among hypotensive CEA patients. These associations failed to meet significance, however, and further details are presented in Table III, B.

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Discussion 

This study reports a combined analysis of CEA and CAS to determine risk factors for clinically significant postprocedural hypotension. We determined that hypotension was more common with CAS than CEA. Clinically significant hypotension was also associated with a greater incidence of postprocedural MI and an increased length of stay and mortality rate. Preoperative use of nitrates and a history of tobacco use were the only independent risk factors that we identified for a greater incidence of hypotension.

Previous studies have attempted to identify some potential risk factors that place patients undergoing CEA and CAS at greater risk for clinically significant hypotension and adverse clinical outcomes. A study by Qureshi et al¹⁹ in 51 patients undergoing CAS identified previous MI and age as independent predictors for hypotension after the procedure. However, neither of these risk factors was significantly correlated with hypotension in CEA or CAS patients in our larger study.

Another study identified tobacco abuse, diabetes, and β-blocker use as protective against hypotension after CAS.¹² These results were inconsistent with our findings, and that study did not include patients undergoing CEA. In addition, it is difficult to reconcile the known adverse effects on vasomotor tone and endothelial dysfunction, which are inherent to patients with a history of tobacco abuse and diabetes, with these findings. Prior MI, age >80 years, and female gender were identified in another study²⁰ as associated with increased hypotension after 143 CAS procedures. That study also did not include CEA procedures, and the authors also concluded that these episodes of hypotension were not associated with adverse cardiac events.

Finally, one of the few large studies to address hypotension after CEA indicated no demographic or procedural factors that predicted a greater incidence of hypotension.²¹ That study also concluded that hypotension after CEA was transient and not associated with adverse clinical outcomes.

The findings of these studies are inconsistent with our results: We have determined that clinically significant hypotension is correlated with adverse clinical outcomes after CEA and CAS. We also have evidence that only preoperative nitrate use and tobacco use indicate those at higher risk for these complications. The other potential risk factors identified by previous studies were not correlated with a greater incidence of hypotension in our investigation.

This study has some advantages compared with other previous attempts to identify potential risk factors for clinically significant hypotension after CEA and CAS. First, to our knowledge this study is the largest to date to address this specific issue. Our study included 1631 patients who underwent 157 CAS and 1474 CEA procedures. In addition, this study directly addressed hypotension for both CEA and CAS patients together and allowed for a direct comparison of the effect of sustained hypotension on clinical outcomes after CEA and CAS. Potential risk factors for hypotension were also evaluated and compared for both types of carotid reconstructions.

This study has some inherent limitations. The first is that these data were retrospectively collected. Many inherent biases are prevalent in this type of study, regardless of the careful analysis by the investigators. The ability to standardize the compliance of patients with preoperative medications or the management of significant comorbid diseases is not possible with this type of study. However, the potential risk factors that we analyzed were documented with good reliability and are generally not subject to recall biases. In addition, this study evaluated a number of potential risk factors for postprocedural hypotension for patients undergoing CEA or CAS. Because CAS is being performed with an increased frequency throughout this country, this investigation may provide insights that prevent adverse outcomes in a growing number of patients.

Another limitation is that we did not analyze the anatomic characteristics of the carotid lesions, such as plaque proximity to the carotid bifurcation, degree of calcification, and length of lesion, that other investigators have indicated may predict for higher incidences of hypotension.¹², ¹⁶, ¹⁸ Although these characteristics might indicate which patients are at greater risk for postprocedural hypotension, risk factors such as age and gender cannot be modified before procedure. In addition, one of these previous studies that identified anatomic risk factors for a greater risk of hypotension found no effect on clinical outcomes such as stroke or MI associated with episodes of hypotension.²¹ We chose to focus more of our investigation on risk factors that can be modified before carotid reconstruction, including preoperative medications, anesthesia type, and stent type. We attempted to determine how modification of these risk factors might affect the incidence of clinically significant postprocedure hypotension.

Hypotension can be associated with an increased risk of untoward cardiac events, especially in patients with prior myocardial ischemia and in patients with carotid occlusive disease. The increase rate of MI that we noted after CEA and CAS may in be partly attributed to the effect of hypotension on diseased myocardium. However, the increase in the rate of MI was far less than what we would expect with an incidence of hypotension in 12.6% of CEA and 35% of CAS patients. These complications are interrelated, but the direct effect of hypotension on myocardial ischemia could not be fully assessed in this investigation.

The identification of predictors of clinically significant hypotension after CEA and CAS seems to be an elusive task. Previous investigators have failed to clearly identify any specific patients at risk for these adverse outcomes after CEA and CAS.²¹, ²² In addition, other investigators have shown that common prophylactic measures to prevent hypotension, such as the intraprocedural administration of intravenous atropine, are ineffective.²², ²³ A recent, small trial comparing intravenous dopamine with oral midodrine (an α-1 adrenergic receptor agonist) in patients undergoing CAS showed promising results in clinical outcomes and costs associated with these admissions.²⁴ However, that was a very limited study of only 4 patients receiving midodrine, and its findings require further evaluation by larger, prospective, randomized investigations.

The only finding that seems to have a widespread effect on practice patterns is that balloon-expandable stents are associated with a greater incidence of hypotension and adverse outcomes compared with newer self-expanding stents.¹⁷, ²⁵ Our study only identified the potentially modifiable factors of preoperative nitrate use and tobacco use. However, the design of our study did not allow us to determine what affect that modification of these risk factors would have on subsequent rates of clinically significant hypotension after CEA and CAS.

A limitation inherent to any retrospective study is the inability to fully determine medication compliance and timing of dosing before procedures. Similarly, the timing and magnitude of tobacco use cannot be fully characterized. The clinically relevant findings of our study are that prolonged hypotension occurs after both CEA and CAS, although with greater frequency after endovascular treatment. These hypotensive episodes are also related to increased MI, death, and longer hospital admissions. However, it is not possible to ascertain whether the hypotension itself, or the vasopressor medications and additional intravenous fluids used to manage these hemodynamic disturbances, are the cause for these adverse outcomes.

There are several theories about the cause of sustained hypotension after CEA and CAS. The most commonly cited mechanism involves stretch or distortion of the baroreceptors in the carotid bulb that triggers the glossopharyngeal nerve to send impulses to the caudal medulla. This results in decreased sympathetic activity and vasomotor tone.²⁰, ²², ²⁶ Other investigators have suggested that CEA and CAS modify the distensibility of the carotid arteries, thus altering the shear stress present within these vessels. This may necessitate a reset mechanism that adjusts how pressure gradients are detected by the carotid sinus. Temporarily, this may translate into transient hypotension or hypotension.²², ²⁶ A final possible mechanism involves a potential feedback mechanism of the chronically ischemic brain attempting to protect itself from a perceived overperfusion after CEA or CAS.²¹ To date, none of these theories have been fully substantiated through basic science or clinical studies.

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Conclusions 

This study has demonstrated that clinically significant hypotension is a more common occurrence after CAS compared with CEA. Our findings show that these episodes of sustained hypotension are related to increased adverse clinical outcomes, including increased rates of MI and death. An analysis of many potential risk factors for hypotension found nitrate use and tobacco use were significantly correlated with an increased risk for hypotension; however, no definitive recommendations against the use of nitrates can be made from our results. What is clear from this investigation is that sustained hypotension after CEA and CAS remains a significant problem for all patients undergoing these carotid reconstructions. Further efforts are mandated to identify those patients at increased risk for hypotension after CEA and CAS to prevent adverse clinical outcomes.

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Author contributions 

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References 

1. In:  Welch KMA,  Caplan LR,  Reis DJ editor. Primer on Cerebrovascular Diseases. Academic Press; 1997;
   • View In Article
2. American Heart Association Web site. http://circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.108.191261Accessed: June 13, 2009
   • View In Article
3. Barnett HJM, Taylor WD, Eliasziw M, Fox A, Ferguson G, Haynes BR, et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med. 1998;339:1415–1425
   • View In Article
   • MEDLINE
   • CrossRef
4. European Carotid Surgery Trialists' Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998;351:1379–1387
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (109 KB)
   • CrossRef
5. Roubin GS, New G, Iyer SS, Vitek J, Al-Mubarak N, Liu M, et al. Endarterectomy for asymptomatic carotid artery stenosis. JAMA. 1995;273:1421–1428
   • View In Article
   • MEDLINE
6. Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, et al. MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet. 2004;363:1491–1502
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (163 KB)
   • CrossRef
7. Yadav JS, Wholey MH, Kuntz RE, Fayad P, Katzen BT, Mishkel GJ, et al. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med. 2004;351:1493–1501
   • View In Article
   • CrossRef
8. McCabe DH, Pereira AC, Clifton A, Bland JM, Brown MM CAVATAS Investigators. Restenosis after carotid angioplasty, stenting, or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). Stroke. 2005;36:281–286
   • View In Article
   • CrossRef
9. Gray WA, Hopkins LN, Yadav S, Davis T, Wholey M, Atkinson A, et al. Protected carotid stenting in high-surgical-risk patients: The ARCHeR Results. J Vasc Surg. 2006;44:258–268
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (158 KB)
   • CrossRef
10. The SPACE Collaborative Group. 30 day results from the SPACE trial of sten-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomized non-inferiority trial. Lancet. 2006;368:1239–1247
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (107 KB)
    • CrossRef
11. Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. New Engl J Med. 2006;355:1660–1671
    • View In Article
12. Gupta R, Abou-Chebl A, Bajzer C, Schumacher HC, Yadav JS. Rate, predictors, and consequences of hemodynamic depression after carotid artery stenting. J Am Coll Cardiol. 2006;47:1538–1543
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (99 KB)
    • CrossRef
13. Gupta R, Horowitz M, Jovin T. Hemodynamic instability after carotid artery and stent placement: a review of the literature. Neurosurg Focus. 2005;18:1–4
    • View In Article
    • MEDLINE
    • CrossRef
14. Lin PH, Zhou W, Kougias , El Sayed HF, Barshes NR, Huynh TT. Factors associated with hypotension and bradycardia after carotid angioplasty and stenting. J Vasc Surg. 2007;46:846–854
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (110 KB)
    • CrossRef
15. Harrop J, Sharan A, Benitez R, Armonda R, Thomas J, Rosenwaser R. Prevention of Carotid Angioplasty-induced Bradycardia and Hypotension with Temporary Venous Pacemakers. Neurosurgery. 2001;49:814–822
    • View In Article
    • MEDLINE
    • CrossRef
16. Leisch F, Kerschner K, Hofmann R, Steinwender C, Grund M, Bibl D, et al. Carotid sinus reactions during carotid artery stenting: predictors, incidence, and influence on outcome. Catheter Cardiovasc Interv. 2003;58:516–523
    • View In Article
    • MEDLINE
    • CrossRef
17. Dangas G, Laird JR, Satler LF, Mehran R, Mintz GS, Larrain G, et al. Postprocedural hypotension after carotid artery stent placement: predictors of short and long-term clinical outcomes. Radiology. 2000;215:677–683
    • View In Article
    • MEDLINE
18. Tedesco MM, Dalman RL, Zhou W, Coogan SM. Reduction of postprocedure microemboli following retrospective quality assessment and practice improvement measures for carotid angioplasty and stenting. J Vasc Surg. 2009;49:607–613
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (179 KB)
    • CrossRef
19. Qureshi AI, Luft AR, Sharma M, Janardhan V, Lopes DK, Khan J, et al. Frequency and determinants of postprocedural hemodynamic instability after carotid angioplasty and stenting. Stroke. 1999;30:2086–2093
    • View In Article
    • MEDLINE
    • CrossRef
20. Trocciola SM, Chaer RA, Lin SC, Ryer EJ, De Rubertis B, Morisssey NJ, et al. Analysis of parameters associated with hypotension requiring vasopressor support after carotid angioplasty with stenting. J Vasc Surg. 2006;43:714–720
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (95 KB)
    • CrossRef
21. Gibbs B. Temporary hypotension following endarterectomy for severe carotid stenosis: should we treat it?. Vasc Endovasc Surg. 2003;37:33–38
    • View In Article
22. Cayne NS, Faries PL, Trocciola SM, Saltzberg SS, Dayal RD, Clair D, et al. Carotid angioplasty and stent-induced bradycardia and hypotension: impact of prophylactic atropine administration and prior carotid endarterectomy. J Vasc Surg. 2005;41:956–961
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (83 KB)
    • CrossRef
23. Shawl FA. Carotid artery stenting: acute and long-term results. Curr Opin Cardiol. 2002;17:671–676
    • View In Article
    • MEDLINE
    • CrossRef
24. Sharma S, Lardizabal JA, Bhambi B. Oral midodrine is effective for the treatment of hypotension associated with carotid artery stenting. J Cardiovasc Pharmacol Therapeut. 2008;13:94–97
    • View In Article
25. McKevitt FM, Sivaguru A, Venables GS, Cleveland TJ, Gaines PA, Beard JD, 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;34:2576–2582
    • View In Article
    • CrossRef
26. Nonaka T, Oka S, Miyata K, Mikami T, Koyanagi I, Houkin K, et al. Prediction of prolonged postprocedural hypotension after carotid artery stenting. Neurosurgery. 2005;57:472–477
    • View In Article
    • CrossRef