Efficacy and safety of Clevidipine for blood pressure control after carotid endarterectomy: a prospective cohort study

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Our institution targets a systolic BP (sBP) of 130–145 mmHg post-CEA. This study aimed to compare the efficacy of clevidipine versus standard intravenous antihypertensive treatment (labetalol +/- urapidil) in maintaining this target range. Materials and Methods This single-center, prospective cohort study included consecutive patients (> 18 years) undergoing CEA at Hospital Universitari de Girona Dr J Trueta, Girona, Spain, between August 2018 and October 2021. Patients received either clevidipine or non-clevidipine treatment (labetalol +/- urapidil) based on physician preference. The primary outcome was the Area Under the Curve for sBP outside the target range (AUC-sBP), normalized per hour (mmHg x min/h), during the first six postoperative hours. Data were analyzed using non-parametric tests and adjusted linear regression. Results Data from 97 patients (44 clevidipine, 53 non-clevidipine [38 labetalol only, 15 labetalol + urapidil]) were analyzed. The clevidipine group had higher baseline sBP (144 ± 15 vs 140 ± 7 mmHg, SMD − 0.34) and more comorbidities. Clevidipine use was associated with a significantly lower AUC-sBP compared to the non-clevidipine group (median [IQR]: 120 [92–150] vs 240 [240–300] mmHg x min/h, p < 0.00001). This association remained significant after adjusting for age, sex, and preoperative sBP (coef. -220 mmHg x min/h [95% CI -293 to -146], p = 0.0001). Mean cumulative clevidipine dose was 58 ± 86 mg over 14 ± 10 hours. No significant differences were observed in secondary outcomes or pre-specified adverse events between groups. Conclusion In this cohort, clevidipine treatment was associated with significantly better adherence to the target sBP range during the first six hours post-CEA compared to standard therapy with labetalol +/- urapidil, without an observed increase in adverse effects. Figures Figure 1 Figure 2 Introduction Carotid Endarterectomy (CEA) aims to reduce long-term stroke risk in patients with significant carotid stenosis ( 1 ). However, the procedure itself carries perioperative risks, including stroke and cardiovascular complications, particularly in patients with prevalent comorbidities like hypertension, coronary artery disease, and diabetes ( 2 ). Post-CEA complications include wound hematoma (3–8%), which can cause airway compromise, and intracerebral hemorrhage (< 3%), sometimes associated with cerebral hyperperfusion syndrome (CHS) ( 1 , 2 ). Both hematoma risk and CHS are influenced by postoperative blood pressure (BP) ( 3 , 4 ). Strict BP control is paramount after CEA, yet often challenging. Hemodynamic instability is common due to factors like carotid sinus baroreceptor manipulation during surgery, effects of anesthesia, and underlying patient conditions ( 5 ). Patients with recent transient ischemic attack (TIA) or stroke exhibit altered baroreceptor sensitivity, further increasing instability risk ( 6 ). Maintaining BP within a narrow therapeutic window is crucial: hypotension can precipitate cerebral ischemia, while hypertension increases bleeding risk and may trigger CHS ( 7 ). Traditional intravenous agents like labetalol (alpha-1 and beta-1 antagonist) and urapidil (alpha-1 antagonist and 5-HT1A agonist) are commonly used but can be challenging to titrate precisely, potentially leading to overshoot hypotension ( 8 ). Urapidil, specifically, has been associated with hypotension after prolonged infusion ( 9 ). Clevidipine, a third-generation dihydropyridine calcium channel blocker, offers potential advantages. It is an ultra-short-acting (elimination half-life ~ 1 minute), vascular-selective, arterial-specific vasodilator ( 10 ). This profile enables rapid onset, precise titration, and swift offset of effect, thereby minimizing prolonged hypotension ( 10 , 11 ). Studies in cardiac surgery suggest it maintains cardiac output without significant reflex tachycardia and allows for tight BP control ( 12 – 14 ). Unlike sodium nitroprusside, it lacks associated toxicities, and its metabolism via blood and tissue esterases makes it independent of renal or hepatic function ( 10 ). Despite its theoretical benefits, data comparing clevidipine to standard agents specifically in the post-CEA setting are limited. Therefore, we conducted this prospective cohort study to evaluate the efficacy and safety of clevidipine compared to a non-clevidipine standard treatment regimen (labetalol +/- urapidil) for maintaining postoperative sBP within our institutional target range (130–145 mmHg). We hypothesized that clevidipine would demonstrate superior efficacy in achieving this goal. Materials and Methods Study Design and Population This was an observational, prospective cohort study conducted at Hospital Universitari de Girona Dr J Trueta, Girona, Spain. Data were prospectively collected for consecutive patients aged 18 years or older who underwent CEA between August 2018 and October 2021. The study protocol was approved by the Institutional Ethics Committee at Hospital Trueta de Girona (Cod TEMPO, 7th of March 2018) and complied with the Declaration of Helsinki. Informed consent was obtained from patients or their legal representatives during the perioperative period. Nine patients were excluded due to incomplete data. The flow diagram is detailed in Fig. 1 . Figure 1 . Flow diagram describing enrollment of patients Exposure of Interest The cohort was divided into two groups based on the primary intravenous antihypertensive treatment received during the first six postoperative hours, according to physician preference—namely, those patients who received (n = 44) or had not received clevidipine (n = 53). The group that did not receive clevidipine was treated with intravenous labetalol alone or labetalol plus urapidil. Data Collection Data collected included patient demographics, comorbidities, preoperative sBP, intraoperative details (if relevant), type and dosage of antihypertensive medications used postoperatively, frequent sBP measurements (typically recorded continuously in the initial postoperative period), and clinical outcomes. Outcomes The primary outcome was the Area Under the Curve for systolic Blood Pressure (AUC-sBP) excursions outside the pre-established target range (130–145 mmHg), normalized per hour (mmHg x min/h), calculated during the first six postoperative hours. This metric quantifies both the magnitude and duration of sBP deviations from the target. Figure 1 . Boxplot comparison of AUC-sBP between groups Secondary outcomes included: time to achieve initial sBP control within the target range, need for surgical reintervention for bleeding/hematoma, incidence of hematoma expansion (clinically significant), intensive care unit (ICU) length of stay (LOS), and in-hospital mortality. Safety outcomes included the incidence of predefined adverse events, such as significant hypotension (sBP < 90 mmHg or requiring intervention), significant bradycardia, atrial fibrillation, and other reported drug-related side effects. Statistical Analysis : STATA Version 13.1 (StataCorp LP, College Station, TX) was used. Continuous variables were described using means ± standard deviations (SD) or medians [interquartile ranges (IQR)], based on normality assessed by the Shapiro-Wilk test. Categorical variables were described using counts and frequencies. Baseline characteristics and outcomes between the clevidipine and non-clevidipine groups were compared using the Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables. P-values were calculated for baseline characteristics. To assess the independent association between clevidipine use and the primary outcome (AUC-sBP), a multivariable linear regression analysis was performed, adjusting for potential confounders: age, sex, and preoperative sBP. Results were expressed as regression coefficients (coef.) with 95% confidence intervals (CI). A 2-sided p-value < 0.05 was considered statistically significant. No post-hoc power calculation was performed; instead, 95% CIs were used to interpret the precision of estimates ( 15 ). Results Patient Characteristics A total of 97 consecutive patients undergoing CEA were included (Fig. 1 ). Of these, 44 (45.3%) received clevidipine, and 53 (54.6%) received non-clevidipine treatment (38 [71.6%] labetalol only, 15 [28.4%] labetalol plus urapidil). Baseline characteristics are presented in Table 1 . Patients in the clevidipine group exhibited a higher baseline sBP (mean 144 ± 15 vs 140 ± 7 mmHg; SMD − 0.34) and a higher prevalence of several comorbidities, including previous stroke (54.5% vs 34%), chronic hypertension (95.5% vs 84.9%), contralateral carotid stenosis (25% vs 11.3%), COPD (20.5% vs 7.5%), coronary artery disease (13.6% vs 5.7%), and diabetes (27.3% vs 13.2%). Table 1 Baseline characteristics Clevidipine (n = 44) Non-clevidipine (n = 53) p-value Age (median, IQR) years 67 (64–70) 64 (63–66) 0.01 Sex Females, n (%) Males, n (%) 13 (29.5%) 31 (70.4%) 5 (9.4%) 48 (90.5%) 0.01 Weight (median, IQR) kg 75 (69–80) 77 (75–77) 0.19 Height (median, IQR) cm 166 (160–170) 166 (164–170) 0.97 Body Mass Index (median, IQR) m 2 24 (23–27) 24 (23–25) 0.08 Carotid artery stenosis, (median, IQR) % 80 (70–80) 80 (80–80) 0.02 Previous stroke, n (%) 24 (54.5%) 18 (34%) 0.06 Hypertension, n (%) 42 (95.5%) 45 (84.9%) 0.10 Baseline sBP (median, IQR), mmHg 142 (139–146) 141 (141–142) 0.05 Contralateral carotid stenosis, n (%) 11 (25%) 6 (11.3%) 0.10 COPD, n (%) 9 (20.5%) 4 (7.5%) 0.07 Dyslipidemia, n (%) 36 (81.8%) 23 (43.4%) 0.001 Coronary artery Disease (CAD), n (%) 6 (13.6%) 3 (5.7%) 0.29 Diabetes, n (%) 12 (27.3%) 7 (13.2%) 0.12 Preoperative Hb (median, IQR), mg/dL 13 (12.5–14) 13 ( 12 – 14 ) 0.27 Preoperative creatinine (median, IQR), mg/dL 0.90 (0.84-1) 0.60 (0.60–0.96) 0.001 eGFR, (median, IQR), ml/min 83 (77–87) 92 (87–97) 0.0001 Atrial Fibrilation, n (%) 6 (13.6%) 3 (5.7%) 0.29 Chronic Kidney Disease stage III-V, n (%) 7 (15.9%) 3 (5.7%) 0.17 Aspirin in last 24h, n (%) 37 (84.1%) 50 (94.3%) 0.17 Intraoperative characteristics Clamp time, (median, IQR), min 25 (25–28) 27 (25–27) 0.03 Shunt, n (%) 17 (38.6%) 16 (30.2%) 0.39 sBP pre-clamping, (median, IQR), mmHg 130 (120–130) 130 (130–130) 0.10 Minimum MAP during clamping, (median, IQR), mmHg 74 (70–74) 74 (72–75) 0.39 Maximum sBP post-clamp, (median, IQR), mmHg 166 (150–167) 165 (150–168) 0.32 Minimum sBP post-clamp, (median, IQR), mmHg 110 (89–110) 100 (98–110) 0.04 Abbreviations: COPD: Chronic obstructive pulmonary disease; eGFR – estimated glomerular filtration rate; MAP: Mean arterial pressure; preoperative Hb – preoperative hemoglobin; ICU: Intensive Care Unit; sBP – systolic blood pressure. Table 1 . Baseline characteristics Drug Dosing and Duration In the clevidipine group, the maximum infusion rate was 7 ± 3 mg/h (14 ± 6 ml/h). The mean total cumulative dose of clevidipine was 58 ± 86 mg, administered over a mean duration of 14 ± 10 hours. Primary Outcome : Patients treated with clevidipine demonstrated significantly better adherence to the target sBP range during the first six postoperative hours. The median [IQR] AUC-sBP was significantly lower in the clevidipine group compared to the non-clevidipine group (120 [92–150] mmHg x min/h vs 240 [240–300] mmHg x min/h, respectively; p < 0.00001) (Table 2 ) (Fig. 2 ). After adjusting for age, sex, and preoperative sBP using linear regression, the use of clevidipine remained significantly associated with a lower AUC-sBP (adjusted coefficient: -220 mmHg x min/h; 95% CI -293 to -146; p = 0.0001). Table 2 Primary outcome Clevidipine (n = 44) Non-clevidipine (n = 53) p-value (AUC-sBP) normalized per hour (mmHg x min/h), median [IQR] 120 [92–150] 240 [240–300] p < 0.00001 Table 2 . Primary outcome Figure 2 . Boxplot comparison of AUC-sBP between groups Secondary and Safety Outcomes : There were no statistically significant differences observed between the clevidipine and non-clevidipine groups regarding secondary outcomes, including the time to achieve initial sBP control within the target range (median, IQR: 5 ( 2 – 7 ) vs 4 ( 4 – 4 ) min; p = 0.09), need for reintervention for bleeding, incidence of hematoma expansion (2.2% vs 1.8%, p = 0.20), ICU LOS (median, IQR: 17 ( 16 – 20 ) vs 17 ( 16 – 18 ) hours; p = 0.79), Hospital LOS (median, IQR: 3 ( 2 – 4 ) vs 3 ( 2 – 4 ) hours; p = 0.90), or in-hospital mortality (Table 3 ). Regarding safety, no significant differences were found in the incidence of pre-specified adverse events between the groups (Table 4 ). Specifically, there were no instances of treatment discontinuation due to adverse events attributed solely to clevidipine in this cohort. Table 3 Secondary outcomes Clevidipine (n = 44) Non-clevidipine (n = 53) p-value Time to control SBP within prespecified, minutes (median, IQR) 5 ( 2 – 7 ) 4 ( 4 – 4 ) 0.09 Need for surgical reintervention for bleeding/hematoma, n (%) 0 (0%) 0 (0%) 1 Incidence of clinically significant expansion hematoma, n (%) 1 (2.2%) 1 (1.8%) 0.20 ICU length of stay, h (median, IQR) 17 ( 16 – 20 ) 17 ( 16 – 18 ) 0.79 Hospital length of stay, days (median, IQR) 3 ( 2 – 4 ) 3 ( 2 – 4 ) 0.90 In-hospital mortality, n (%) 0 (0%) 0 (0%) 1 Table 4 Adverse effects Clevidipine (n = 44) Non-clevidipine (n = 53) p-value Significant hypotension (sBP < 90 mmHg), n (%) 0 (0%) 3 (5,3%) 0.06 Significant bradycardia, n (%) 0 (0%) 0 (0%) 1 New atrial fibrillation, n (%) 0 (0%) 0 (0%) 1 Table 3 . Secondary outcomes Table 4 . Adverse effects Discussion This prospective cohort study suggests that the use of clevidipine for postoperative BP management after CEA was associated with significantly tighter control of sBP within the target range of 130–145 mmHg during the critical first six hours, compared to standard treatment with labetalol +/- urapidil. This improved control, quantified by a substantially lower AUC-sBP, was observed despite the clevidipine group having a higher baseline sBP and a greater burden of comorbidities, and the finding remained significant after multivariable adjustment. To our knowledge, this is the first study to specifically use the AUC-sBP metric to compare clevidipine with labetalol/urapidil in the post-CEA setting. The AUC metric provides a robust measure of overall BP control quality, integrating both the magnitude and duration of deviations from the desired range. Our findings align with previous research in other surgical settings demonstrating clevidipine's efficacy in achieving precise BP targets. The ECLIPSE trials in cardiac surgery patients found clevidipine more effective than nitroglycerin or sodium nitroprusside in maintaining BP within pre-specified limits, also using an AUC-based metric ( 12 ). Similarly, a retrospective study by Colomy et al. in cardiac surgery patients reported that clevidipine achieved a higher median percent time within the goal sBP range compared to nicardipine ( 16 ). While some studies in stroke patients found no difference in time to goal BP between clevidipine and nicardipine ( 17 , 18 ), our study focused on the quality of maintenance within a narrow range post-CEA, where clevidipine appeared superior to labetalol/urapidil. The observed efficacy of clevidipine likely stems from its pharmacokinetic properties: rapid onset and offset, and an ultra-short half-life, allowing for precise dose adjustments to match fluctuating patient hemodynamics common after CEA ( 7 , 19 ). This contrasts with the longer half-lives and potentially less predictable dose-response of labetalol and urapidil, which might explain the larger BP excursions observed in the non-clevidipine group. Importantly, the improved BP control with clevidipine did not come at the cost of increased adverse events in our cohort. We observed no significant differences in hypotension, bradycardia, or other safety outcomes compared to the non-clevidipine group. This contrasts slightly with some RCT data in cardiac surgery, where higher incidences of hypotension were reported with calcium channel blockers ( 12 , 20 ), potentially reflecting the ability to rapidly titrate or discontinue clevidipine in a real-world setting upon reaching the lower BP limit, mitigating prolonged hypotension – an advantage less feasible in blinded trials. The favorable safety profile, including independence from renal/hepatic metabolism, supports its use in this often complex patient population ( 10 , 11 ). This study has several limitations. Its observational design is susceptible to selection bias and unmeasured confounding, although we attempted to mitigate this through multivariable adjustment. The baseline differences between groups, particularly the higher cardiovascular risk profile in the clevidipine group, suggest physicians might have preferentially used clevidipine in patients perceived as more challenging to manage; despite this potential bias against clevidipine, it still demonstrated superior control. Being a single-center study, generalizability may be limited. Furthermore, data on the exact doses and duration for labetalol and urapidil were limited to direct dose comparison. We also primarily focused on the first six hours, though mean clevidipine use extended longer. Strengths include the use of prospectively collected data from consecutive patients in a real-world setting, the application of a robust primary outcome measure (AUC-sBP), and the clinical relevance of the research question. In conclusion, our findings suggest that clevidipine is an effective and well-tolerated option for achieving tight postoperative BP control after CEA, demonstrating superior performance in maintaining sBP within a narrow target range compared to standard treatment with labetalol +/- urapidil in this cohort. Tighter BP control may contribute to reducing the risk of neurological and hemorrhagic complications associated with CEA. Prospective, randomized studies are warranted to confirm these findings. Declarations The study protocol was approved by the Institutional Ethics Committee at Hospital Trueta de Girona (Cod TEMPO, 7 th of March 2018) and complied with the Declaration of Helsinki. Informed consent was obtained from patients or their legal representatives during the perioperative period. There was no funding for this study. Clinical trial number: not applicable. Author Contribution M.V and C.S. wrote the main manuscript text and K.R and R.R. prepared tables 1-3. 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Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis. PLoS One 2016; 11(3):e0150625. doi: 10.1371/journal.pone.0150625 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 09 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviews received at journal 26 Nov, 2025 Reviewers agreed at journal 26 Nov, 2025 Reviewers invited by journal 28 Oct, 2025 Editor assigned by journal 28 Oct, 2025 Submission checks completed at journal 28 Oct, 2025 First submitted to journal 19 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7899586","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":536159679,"identity":"a9895068-eda0-43dc-9d02-88e69ebbbc51","order_by":0,"name":"Marc Vives","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApElEQVRIiWNgGAWjYFACxgYgYUO6ljTSrTpMglrdGcltEh/+nE/czn7GgOHDHyK0mN1IbJOc2XY7cWdPjgHjzDZitJw52GzM23A7ccOBtARm3gZitfz5cy5xw/lnCcx/iHLY8cbGxwxsBxI33Eg+wMzARqSWh71tycYbbjw+cLCXKL8cZn9w4McfO9kN5xMbH/wgxmEo4ACpGkbBKBgFo2AU4AAAW78+62cO/5QAAAAASUVORK5CYII=","orcid":"","institution":"Clínica Universidad de Navarra. 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05:24:06","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":86542,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7899586/v1/2793d5b08b7034f2fe787f25.html"},{"id":95501003,"identity":"b952dee9-a0f3-4354-8a56-5a3eeec7b014","added_by":"auto","created_at":"2025-11-10 05:24:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":38768,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram describing enrollment of patients\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7899586/v1/fb6edac0f61d6193315f35ce.jpg"},{"id":95501001,"identity":"fa438ef0-a130-4d47-95e4-ba090f10d044","added_by":"auto","created_at":"2025-11-10 05:24:06","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":49722,"visible":true,"origin":"","legend":"\u003cp\u003eBoxplot comparison of AUC-sBP between groups\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7899586/v1/21223f136721297366dcfc8d.jpg"},{"id":95531732,"identity":"e90eed9f-94ce-4b8d-aab0-3d36f12edcd0","added_by":"auto","created_at":"2025-11-10 10:24:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":713126,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7899586/v1/75ad84f8-11bc-4ea1-8a2d-5c6c8d1badd2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and safety of Clevidipine for blood pressure control after carotid endarterectomy: a prospective cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCarotid Endarterectomy (CEA) aims to reduce long-term stroke risk in patients with significant carotid stenosis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, the procedure itself carries perioperative risks, including stroke and cardiovascular complications, particularly in patients with prevalent comorbidities like hypertension, coronary artery disease, and diabetes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Post-CEA complications include wound hematoma (3\u0026ndash;8%), which can cause airway compromise, and intracerebral hemorrhage (\u0026lt;\u0026thinsp;3%), sometimes associated with cerebral hyperperfusion syndrome (CHS) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Both hematoma risk and CHS are influenced by postoperative blood pressure (BP) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Strict BP control is paramount after CEA, yet often challenging. Hemodynamic instability is common due to factors like carotid sinus baroreceptor manipulation during surgery, effects of anesthesia, and underlying patient conditions (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Patients with recent transient ischemic attack (TIA) or stroke exhibit altered baroreceptor sensitivity, further increasing instability risk (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Maintaining BP within a narrow therapeutic window is crucial: hypotension can precipitate cerebral ischemia, while hypertension increases bleeding risk and may trigger CHS (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTraditional intravenous agents like labetalol (alpha-1 and beta-1 antagonist) and urapidil (alpha-1 antagonist and 5-HT1A agonist) are commonly used but can be challenging to titrate precisely, potentially leading to overshoot hypotension (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Urapidil, specifically, has been associated with hypotension after prolonged infusion (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Clevidipine, a third-generation dihydropyridine calcium channel blocker, offers potential advantages. It is an ultra-short-acting (elimination half-life\u0026thinsp;~\u0026thinsp;1 minute), vascular-selective, arterial-specific vasodilator (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This profile enables rapid onset, precise titration, and swift offset of effect, thereby minimizing prolonged hypotension (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Studies in cardiac surgery suggest it maintains cardiac output without significant reflex tachycardia and allows for tight BP control (\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Unlike sodium nitroprusside, it lacks associated toxicities, and its metabolism via blood and tissue esterases makes it independent of renal or hepatic function (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDespite its theoretical benefits, data comparing clevidipine to standard agents specifically in the post-CEA setting are limited. Therefore, we conducted this prospective cohort study to evaluate the efficacy and safety of clevidipine compared to a non-clevidipine standard treatment regimen (labetalol +/- urapidil) for maintaining postoperative sBP within our institutional target range (130\u0026ndash;145 mmHg). We hypothesized that clevidipine would demonstrate superior efficacy in achieving this goal.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Population\u003c/strong\u003e\u003cp\u003eThis was an observational, prospective cohort study conducted at Hospital Universitari de Girona Dr J Trueta, Girona, Spain. Data were prospectively collected for consecutive patients aged 18 years or older who underwent CEA between August 2018 and October 2021. The study protocol was approved by the Institutional Ethics Committee at Hospital Trueta de Girona (Cod TEMPO, 7th of March 2018) and complied with the Declaration of Helsinki. Informed consent was obtained from patients or their legal representatives during the perioperative period. Nine patients were excluded due to incomplete data. The flow diagram is detailed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eFlow diagram describing enrollment of patients\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eExposure of Interest\u003c/strong\u003e\u003cp\u003eThe cohort was divided into two groups based on the primary intravenous antihypertensive treatment received during the first six postoperative hours, according to physician preference\u0026mdash;namely, those patients who received (n\u0026thinsp;=\u0026thinsp;44) or had not received clevidipine (n\u0026thinsp;=\u0026thinsp;53). The group that did not receive clevidipine was treated with intravenous labetalol alone or labetalol plus urapidil.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eData Collection\u003c/strong\u003e\u003cp\u003eData collected included patient demographics, comorbidities, preoperative sBP, intraoperative details (if relevant), type and dosage of antihypertensive medications used postoperatively, frequent sBP measurements (typically recorded continuously in the initial postoperative period), and clinical outcomes.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003cp\u003eThe \u003cb\u003eprimary outcome\u003c/b\u003e was the Area Under the Curve for systolic Blood Pressure (AUC-sBP) excursions outside the pre-established target range (130\u0026ndash;145 mmHg), normalized per hour (mmHg x min/h), calculated during the first six postoperative hours. This metric quantifies both the magnitude and duration of sBP deviations from the target.\u003c/p\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBoxplot comparison of AUC-sBP between groups\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary outcomes\u003c/b\u003e included: time to achieve initial sBP control within the target range, need for surgical reintervention for bleeding/hematoma, incidence of hematoma expansion (clinically significant), intensive care unit (ICU) length of stay (LOS), and in-hospital mortality. \u003cb\u003eSafety outcomes\u003c/b\u003e included the incidence of predefined adverse events, such as significant hypotension (sBP\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg or requiring intervention), significant bradycardia, atrial fibrillation, and other reported drug-related side effects.\u003c/p\u003e\u003cp\u003e\u003cem\u003eStatistical Analysis\u003c/em\u003e: STATA Version 13.1 (StataCorp LP, College Station, TX) was used. Continuous variables were described using means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations (SD) or medians [interquartile ranges (IQR)], based on normality assessed by the Shapiro-Wilk test. Categorical variables were described using counts and frequencies. Baseline characteristics and outcomes between the clevidipine and non-clevidipine groups were compared using the Wilcoxon rank-sum test for continuous variables and Fisher\u0026rsquo;s exact test for categorical variables. P-values were calculated for baseline characteristics. To assess the independent association between clevidipine use and the primary outcome (AUC-sBP), a multivariable linear regression analysis was performed, adjusting for potential confounders: age, sex, and preoperative sBP. Results were expressed as regression coefficients (coef.) with 95% confidence intervals (CI). A 2-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. No post-hoc power calculation was performed; instead, 95% CIs were used to interpret the precision of estimates (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003ePatient Characteristics\u003c/strong\u003e\u003cp\u003eA total of 97 consecutive patients undergoing CEA were included (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Of these, 44 (45.3%) received clevidipine, and 53 (54.6%) received non-clevidipine treatment (38 [71.6%] labetalol only, 15 [28.4%] labetalol plus urapidil). Baseline characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients in the clevidipine group exhibited a higher baseline sBP (mean 144\u0026thinsp;\u0026plusmn;\u0026thinsp;15 vs 140\u0026thinsp;\u0026plusmn;\u0026thinsp;7 mmHg; SMD \u0026minus;\u0026thinsp;0.34) and a higher prevalence of several comorbidities, including previous stroke (54.5% vs 34%), chronic hypertension (95.5% vs 84.9%), contralateral carotid stenosis (25% vs 11.3%), COPD (20.5% vs 7.5%), coronary artery disease (13.6% vs 5.7%), and diabetes (27.3% vs 13.2%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eClevidipine (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-clevidipine (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (median, IQR) years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67 (64\u0026ndash;70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64 (63\u0026ndash;66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003cp\u003eFemales, n (%)\u003c/p\u003e\u003cp\u003eMales, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (29.5%)\u003c/p\u003e\u003cp\u003e31 (70.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (9.4%)\u003c/p\u003e\u003cp\u003e48 (90.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight (median, IQR) kg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75 (69\u0026ndash;80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77 (75\u0026ndash;77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight (median, IQR) cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e166 (160\u0026ndash;170)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e166 (164\u0026ndash;170)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.97\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBody Mass Index (median, IQR) m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (23\u0026ndash;27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (23\u0026ndash;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCarotid artery stenosis, (median, IQR) %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80 (70\u0026ndash;80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80 (80\u0026ndash;80)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious stroke, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (54.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (34%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e42 (95.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45 (84.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline sBP (median, IQR), mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e142 (139\u0026ndash;146)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e141 (141\u0026ndash;142)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eContralateral carotid stenosis, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (11.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (20.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (7.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDyslipidemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36 (81.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (43.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoronary artery Disease (CAD), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (13.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (5.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (27.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (13.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative Hb (median, IQR), mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (12.5\u0026ndash;14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative creatinine (median, IQR), mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.90 (0.84-1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.60 (0.60\u0026ndash;0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR, (median, IQR), ml/min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83 (77\u0026ndash;87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e92 (87\u0026ndash;97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.0001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAtrial Fibrilation, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (13.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (5.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic Kidney Disease stage III-V, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (15.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (5.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAspirin in last 24h, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e37 (84.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (94.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eIntraoperative characteristics\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClamp time, (median, IQR), min\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (25\u0026ndash;28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (25\u0026ndash;27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eShunt, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (38.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (30.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esBP pre-clamping, (median, IQR), mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e130 (120\u0026ndash;130)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130 (130\u0026ndash;130)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMinimum MAP during clamping, (median, IQR), mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (70\u0026ndash;74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74 (72\u0026ndash;75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMaximum sBP post-clamp, (median, IQR), mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e166 (150\u0026ndash;167)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e165 (150\u0026ndash;168)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMinimum sBP post-clamp, (median, IQR), mmHg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110 (89\u0026ndash;110)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100 (98\u0026ndash;110)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: COPD: Chronic obstructive pulmonary disease; eGFR \u0026ndash; estimated glomerular filtration rate; MAP: Mean arterial pressure; preoperative Hb \u0026ndash; preoperative hemoglobin; ICU: Intensive Care Unit; sBP \u0026ndash; systolic blood pressure.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBaseline characteristics\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDrug Dosing and Duration\u003c/strong\u003e\u003cp\u003eIn the clevidipine group, the maximum infusion rate was 7\u0026thinsp;\u0026plusmn;\u0026thinsp;3 mg/h (14\u0026thinsp;\u0026plusmn;\u0026thinsp;6 ml/h). The mean total cumulative dose of clevidipine was 58\u0026thinsp;\u0026plusmn;\u0026thinsp;86 mg, administered over a mean duration of 14\u0026thinsp;\u0026plusmn;\u0026thinsp;10 hours.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ePrimary Outcome\u003c/em\u003e: Patients treated with clevidipine demonstrated significantly better adherence to the target sBP range during the first six postoperative hours. The median [IQR] AUC-sBP was significantly lower in the clevidipine group compared to the non-clevidipine group (120 [92\u0026ndash;150] mmHg x min/h vs 240 [240\u0026ndash;300] mmHg x min/h, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). After adjusting for age, sex, and preoperative sBP using linear regression, the use of clevidipine remained significantly associated with a lower AUC-sBP (adjusted coefficient: -220 mmHg x min/h; 95% CI -293 to -146; p\u0026thinsp;=\u0026thinsp;0.0001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePrimary outcome\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eClevidipine (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-clevidipine (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e(AUC-sBP) normalized per hour (mmHg x min/h), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e120 [92\u0026ndash;150]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e240 [240\u0026ndash;300]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.00001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePrimary outcome\u003c/span\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eBoxplot comparison of AUC-sBP between groups\u003c/span\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003eSecondary and Safety Outcomes\u003c/em\u003e: There were no statistically significant differences observed between the clevidipine and non-clevidipine groups regarding secondary outcomes, including the time to achieve initial sBP control within the target range (median, IQR: 5 (\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) vs 4 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) min; p\u0026thinsp;=\u0026thinsp;0.09), need for reintervention for bleeding, incidence of hematoma expansion (2.2% vs 1.8%, p\u0026thinsp;=\u0026thinsp;0.20), ICU LOS (median, IQR: 17 (\u003cspan additionalcitationids=\"CR17 CR18 CR19\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) vs 17 (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) hours; p\u0026thinsp;=\u0026thinsp;0.79), Hospital LOS (median, IQR: 3 (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) vs 3 (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) hours; p\u0026thinsp;=\u0026thinsp;0.90), or in-hospital mortality (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Regarding safety, no significant differences were found in the incidence of pre-specified adverse events between the groups (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Specifically, there were no instances of treatment discontinuation due to adverse events attributed solely to clevidipine in this cohort.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSecondary outcomes\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eClevidipine (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-clevidipine (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime to control SBP within prespecified, minutes (median, IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeed for surgical reintervention for bleeding/hematoma, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIncidence of clinically significant expansion hematoma, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (2.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICU length of stay, h (median, IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (\u003cspan additionalcitationids=\"CR17 CR18 CR19\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.79\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital length of stay, days (median, IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.90\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIn-hospital mortality, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAdverse effects\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eClevidipine (n\u0026thinsp;=\u0026thinsp;44)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-clevidipine (n\u0026thinsp;=\u0026thinsp;53)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSignificant hypotension (sBP\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (5,3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSignificant bradycardia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNew atrial fibrillation, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSecondary outcomes\u003c/span\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAdverse effects\u003c/span\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective cohort study suggests that the use of clevidipine for postoperative BP management after CEA was associated with significantly tighter control of sBP within the target range of 130\u0026ndash;145 mmHg during the critical first six hours, compared to standard treatment with labetalol +/- urapidil. This improved control, quantified by a substantially lower AUC-sBP, was observed despite the clevidipine group having a higher baseline sBP and a greater burden of comorbidities, and the finding remained significant after multivariable adjustment.\u003c/p\u003e\u003cp\u003eTo our knowledge, this is the first study to specifically use the AUC-sBP metric to compare clevidipine with labetalol/urapidil in the post-CEA setting. The AUC metric provides a robust measure of overall BP control quality, integrating both the magnitude and duration of deviations from the desired range. Our findings align with previous research in other surgical settings demonstrating clevidipine's efficacy in achieving precise BP targets. The ECLIPSE trials in cardiac surgery patients found clevidipine more effective than nitroglycerin or sodium nitroprusside in maintaining BP within pre-specified limits, also using an AUC-based metric (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Similarly, a retrospective study by Colomy et al. in cardiac surgery patients reported that clevidipine achieved a higher median percent time within the goal sBP range compared to nicardipine (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWhile some studies in stroke patients found no difference in \u003cem\u003etime to goal BP\u003c/em\u003e between clevidipine and nicardipine (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), our study focused on the \u003cem\u003equality of maintenance\u003c/em\u003e within a narrow range post-CEA, where clevidipine appeared superior to labetalol/urapidil.\u003c/p\u003e\u003cp\u003eThe observed efficacy of clevidipine likely stems from its pharmacokinetic properties: rapid onset and offset, and an ultra-short half-life, allowing for precise dose adjustments to match fluctuating patient hemodynamics common after CEA (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). This contrasts with the longer half-lives and potentially less predictable dose-response of labetalol and urapidil, which might explain the larger BP excursions observed in the non-clevidipine group.\u003c/p\u003e\u003cp\u003eImportantly, the improved BP control with clevidipine did not come at the cost of increased adverse events in our cohort. We observed no significant differences in hypotension, bradycardia, or other safety outcomes compared to the non-clevidipine group. This contrasts slightly with some RCT data in cardiac surgery, where higher incidences of hypotension were reported with calcium channel blockers (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), potentially reflecting the ability to rapidly titrate or discontinue clevidipine in a real-world setting upon reaching the lower BP limit, mitigating prolonged hypotension \u0026ndash; an advantage less feasible in blinded trials. The favorable safety profile, including independence from renal/hepatic metabolism, supports its use in this often complex patient population (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThis study has several limitations. Its observational design is susceptible to selection bias and unmeasured confounding, although we attempted to mitigate this through multivariable adjustment. The baseline differences between groups, particularly the higher cardiovascular risk profile in the clevidipine group, suggest physicians might have preferentially used clevidipine in patients perceived as more challenging to manage; despite this potential bias \u003cem\u003eagainst\u003c/em\u003e clevidipine, it still demonstrated superior control. Being a single-center study, generalizability may be limited. Furthermore, data on the exact doses and duration for labetalol and urapidil were limited to direct dose comparison. We also primarily focused on the first six hours, though mean clevidipine use extended longer.\u003c/p\u003e\u003cp\u003eStrengths include the use of prospectively collected data from consecutive patients in a real-world setting, the application of a robust primary outcome measure (AUC-sBP), and the clinical relevance of the research question.\u003c/p\u003e\u003cp\u003eIn conclusion, our findings suggest that clevidipine is an effective and well-tolerated option for achieving tight postoperative BP control after CEA, demonstrating superior performance in maintaining sBP within a narrow target range compared to standard treatment with labetalol +/- urapidil in this cohort. Tighter BP control may contribute to reducing the risk of neurological and hemorrhagic complications associated with CEA. Prospective, randomized studies are warranted to confirm these findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe study protocol was approved by the Institutional Ethics Committee at Hospital Trueta de Girona (Cod TEMPO, 7\u003csup\u003eth\u003c/sup\u003e of March 2018) and complied with the Declaration of Helsinki. Informed consent was obtained from patients or their legal representatives during the perioperative period.\u003c/p\u003e\n\u003cp\u003eThere was no funding for this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.V and C.S. wrote the main manuscript text and K.R and R.R. prepared tables 1-3. AC and B.LL prepared figures 1-2. All authors reviewed the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFerguson GG, Eliasziw M, Barr HW, et al. 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J Vasc Surg 2022;75(2):592\u0026ndash;598.e1. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jvs.2021.08.070\u003c/span\u003e\u003cspan address=\"10.1016/j.jvs.2021.08.070\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEspinosa A, Ripoll\u0026eacute;s-Melchor J, Casans-Franc\u0026eacute;s R, et al. Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis. PLoS One 2016; 11(3):e0150625. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0150625\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0150625\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7899586/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7899586/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eStrict postoperative blood pressure (BP) control within a narrow range is crucial after Carotid Endarterectomy (CEA) to minimize risks like stroke and hyperperfusion syndrome. Our institution targets a systolic BP (sBP) of 130\u0026ndash;145 mmHg post-CEA. This study aimed to compare the efficacy of clevidipine versus standard intravenous antihypertensive treatment (labetalol +/- urapidil) in maintaining this target range.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e\u003cp\u003eThis single-center, prospective cohort study included consecutive patients (\u0026gt;\u0026thinsp;18 years) undergoing CEA at Hospital Universitari de Girona Dr J Trueta, Girona, Spain, between August 2018 and October 2021. Patients received either clevidipine or non-clevidipine treatment (labetalol +/- urapidil) based on physician preference. The primary outcome was the Area Under the Curve for sBP outside the target range (AUC-sBP), normalized per hour (mmHg x min/h), during the first six postoperative hours. Data were analyzed using non-parametric tests and adjusted linear regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eData from 97 patients (44 clevidipine, 53 non-clevidipine [38 labetalol only, 15 labetalol\u0026thinsp;+\u0026thinsp;urapidil]) were analyzed. The clevidipine group had higher baseline sBP (144\u0026thinsp;\u0026plusmn;\u0026thinsp;15 vs 140\u0026thinsp;\u0026plusmn;\u0026thinsp;7 mmHg, SMD \u0026minus;\u0026thinsp;0.34) and more comorbidities. Clevidipine use was associated with a significantly lower AUC-sBP compared to the non-clevidipine group (median [IQR]: 120 [92\u0026ndash;150] vs 240 [240\u0026ndash;300] mmHg x min/h, p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001). This association remained significant after adjusting for age, sex, and preoperative sBP (coef. -220 mmHg x min/h [95% CI -293 to -146], p\u0026thinsp;=\u0026thinsp;0.0001). Mean cumulative clevidipine dose was 58\u0026thinsp;\u0026plusmn;\u0026thinsp;86 mg over 14\u0026thinsp;\u0026plusmn;\u0026thinsp;10 hours. No significant differences were observed in secondary outcomes or pre-specified adverse events between groups.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn this cohort, clevidipine treatment was associated with significantly better adherence to the target sBP range during the first six hours post-CEA compared to standard therapy with labetalol +/- urapidil, without an observed increase in adverse effects.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of Clevidipine for blood pressure control after carotid endarterectomy: a prospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 05:24:01","doi":"10.21203/rs.3.rs-7899586/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-12-09T23:56:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"59511015614099978157281022682285048206","date":"2025-12-01T15:23:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-26T16:34:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"339334827065438434004634230976350932241","date":"2025-11-26T13:51:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-28T09:39:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-28T08:02:15+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-28T08:01:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Anesthesia, Analgesia and Critical Care","date":"2025-10-19T15:26:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c64e4cca-431e-4311-8d80-412dfb83ed99","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T12:39:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-10 05:24:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7899586","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7899586","identity":"rs-7899586","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}