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Phenylephrine versus ephedrine on cerebral perfusion during carotid endarterectomy (PEPPER): study protocol for a randomized controlled trial.

ABSTRACT: Intraoperative arterial hypotension can lead to severe complications in patients undergoing carotid endarterectomy, in particular if cerebral auto-regulation is impaired. Short-acting agents, such as phenylephrine or ephedrine, commonly used to correct intra-operative hypotension, have different hemodynamic effects. Recently, it was reported that, in healthy anesthetized subjects with intact cerebral auto-regulation, frontal lobe cerebral tissue oxygenation declined after phenylephrine bolus administration, while it was preserved after ephedrine use (Br J Anaesth 107:209-217, 2011; Neurocrit Care 12:17-23, 2010). However, the effect of both agents in patients undergoing carotid endarterectomy is unknown. The aim of this study is to assess the effect of two routinely used vasopressors (phenylephrine and ephedrine) on the cerebral hemodynamics during carotid endarterectomy.Patients undergoing carotid endarterectomy will be prospectively included and randomized for correction of intraoperative hypotension with either phenylephrine (50 to 100 ?g) or ephedrine (5 to 10 mg). If hypotension persists for more than five minutes after treatment, the patient will be classified as a non-responder and escape medication as preferred by the anesthesiologist will be administered. Changes in cerebral hemodynamics will be quantified by changes in transcranial Doppler-derived middle cerebral artery blood velocity and near infra-red spectroscopy-derived frontal lobe cerebral tissue oxygenation, when intra-operative hypotension is treated with phenylephrine or ephedrine in patients who undergo carotid endarterectomy with or without an adequate functioning cerebral auto-regulation.To quantify whether the intra-operative cerebral auto-regulation is impaired or not, a decrease in breathing frequency from the normal 12 breaths per minute to 6 breaths per minute for an episode of three minutes will be performed.Phenylephrine and ephedrine are two of the most commonly used short-acting agents to increase blood pressure in clinical anesthesiologic practice. Monitoring of middle cerebral artery blood velocity with transcranial Doppler and frontal lobe cerebral tissue oxygenation with near infra-red spectroscopy are part of the standard of care. Furthermore, there are no reports that the three-minute modification in breathing frequency described in the "intervention"-section is harmful. Therefore, the risks for participating patients are negligible and the burden minimal.Clinical trials.gov: NCT01451294.

SUBMITTER: Pennekamp CW

PROVIDER: S-EPMC3598872 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Phenylephrine versus ephedrine on cerebral perfusion during carotid endarterectomy (PEPPER): study protocol for a randomized controlled trial.

Pennekamp Claire W A CW Immink Rogier V RV Buhre Wolfgang F WF Moll Frans L FL de Borst Gert Jan GJ

Trials 20130214

<h4>Background</h4>Intraoperative arterial hypotension can lead to severe complications in patients undergoing carotid endarterectomy, in particular if cerebral auto-regulation is impaired. Short-acting agents, such as phenylephrine or ephedrine, commonly used to correct intra-operative hypotension, have different hemodynamic effects. Recently, it was reported that, in healthy anesthetized subjects with intact cerebral auto-regulation, frontal lobe cerebral tissue oxygenation declined after phen ...[more]

PMID: 23410186

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Project description:BACKGROUND:Short-acting vasopressor agents like phenylephrine or ephedrine can be used during carotid endarterectomy (CEA) to achieve adequate blood pressure (BP) to prevent periprocedural stroke by preserving the cerebral perfusion. Previous studies in healthy subjects showed that these vasopressors also affected the frontal lobe cerebral tissue oxygenation (rSO2) with a decrease after administration of phenylephrine. This decrease is unwarranted in patients with jeopardized cerebral perfusion, like CEA patients. The study aimed to evaluate the impact of both phenylephrine and ephedrine on the rSO2 during CEA. METHODS:In this double-blinded randomized controlled trial, 29 patients with symptomatic carotid artery stenosis underwent CEA under volatile general anesthesia in a tertiary referral medical center. Patients were preoperative allocated randomly (1:1) for receiving either phenylephrine (50 µg; n?=?14) or ephedrine (5 mg; n?=?15) in case intraoperative hypotension occurred, defined as a decreased mean arterial pressure (MAP)???20% compared to (awake) baseline. Intraoperative MAP was measured by an intra-arterial cannula placed in the radial artery. After administration, the MAP, cardiac output (CO), heart rate (HR), stroke volume, and rSO2 both ipsilateral and contralateral were measured. The timeframe for data analysis was 120 s before, until 600 s after administration. RESULTS:Both phenylephrine (70?±?9 to 101?±?22 mmHg; p?<?0.001; mean?±?SD) and ephedrine (75?±?11 mmHg to 122?±?22 mmHg; p?<?0.001) adequately restored MAP. After administration, HR did not change significantly over time, and CO increased 19% for both phenylephrine and ephedrine. rSO2 ipsilateral and contralateral did not change significantly after administration at 300 and 600 s for either phenylephrine or ephedrine (phenylephrine 73%, 73%, 73% and 73%, 73%, 74%; ephedrine 72%, 73%, 73% and 75%, 74%, 74%). CONCLUSIONS:Within this randomized prospective study, MAP correction by either phenylephrine or ephedrine showed to be equally effective in maintaining rSO2 in patients who underwent CEA. Clinical Trial Registration ClincalTrials.gov, NCT01451294.

Project description:INTRODUCTION:During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy. We hypothesised that phenylephrine is associated with an increase in capillary transit-time heterogeneity and a reduction in cerebral metabolic rate of oxygen compared with ephedrine. Using MRI and positron emission tomography (PET) as measurements in anaesthetised patients with brain tumours, this study will examine whether phenylephrine administration elevates capillary transit-time heterogeneity more than ephedrine, thereby reducing brain oxygenation. METHODS AND ANALYSIS:This is a double-blind, randomised clinical trial including 48 patients scheduled for surgical brain tumour removal. Prior to imaging and surgery, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60?mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood flow, capillary transit-time heterogeneity, cerebral blood volume, blood mean transit time, and calculated oxygen extraction fraction and cerebral metabolic rate of oxygen for negligible tissue oxygen extraction. PET measurements include cerebral metabolic rate of oxygen, cerebral blood flow and oxygen extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured. ETHICS AND DISSEMINATION:This study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBER:NCT02713087; Pre-results. 2015-001359-60; Pre-results.

Project description:ObjectivesThe purpose of this study was to compare health-related quality of life (HRQOL) outcomes in patients treated with carotid artery stenting (CAS) versus carotid endarterectomy (CEA).BackgroundIn CREST (Carotid Revascularization Endarterectomy versus Stenting Trial), the largest randomized trial of carotid revascularization to date, there was no significant difference in the primary composite endpoint, but rates of stroke and myocardial infarction (MI) differed between CAS and CEA. To help guide individualized clinical decision making, we compared HRQOL among patients enrolled in the CREST study. We also performed exploratory analyses to evaluate the association between periprocedural complications and HRQOL.MethodsWe measured HRQOL at baseline, and after 2 weeks, 1 month, and 1 year among 2,502 patients randomly assigned to either CAS or CEA in the CREST study. The HRQOL was assessed using the Medical Outcomes Study Short-Form 36 (SF-36) and 6 disease-specific scales designed to study HRQOL in patients undergoing carotid revascularization.ResultsAt both 2 weeks and 1 month, CAS patients had better outcomes for multiple components of the SF-36, with large differences for role physical function, pain, and the physical component summary scale (all p < 0.01). On the disease-specific scales, CAS patients reported less difficulty with driving, eating/swallowing, neck pain, and headaches but more difficulty with walking and leg pain (all p < 0.05). However, by 1 year, there were no differences in any HRQOL measure between CAS and CEA. In the exploratory analyses, periprocedural stroke was associated with poorer 1-year HRQOL across all SF-36 domains, but periprocedural MI or cranial nerve palsy were not.ConclusionsAmong patients undergoing carotid revascularization, CAS is associated with better HRQOL during the early recovery period as compared with CEA-particularly with regard to physical limitations and pain-but these differences diminish over time and are not evident after 1 year. Although CAS and CEA are associated with similar overall HRQOL at 1 year, event-specific analyses confirm that stroke has a greater and more sustained impact on HRQOL than MI. (Carotid Revascularization Endarterectomy versus Stenting Trial [CREST]; NCT00004732)

Project description:BackgroundThe Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) found a higher risk of stroke after carotid artery stenting and a higher risk of myocardial infarction (MI) after carotid endarterectomy.Methods and resultsCardiac biomarkers and ECGs were performed before and 6 to 8 hours after either procedure and if there was clinical evidence of ischemia. In CREST, MI was defined as biomarker elevation plus either chest pain or ECG evidence of ischemia. An additional category of biomarker elevation with neither chest pain nor ECG abnormality was prespecified (biomarker+ only). Crude mortality and risk-adjusted mortality for MI and biomarker+ only were assessed during follow-up. Among 2502 patients, 14 MIs occurred in carotid artery stenting and 28 MIs in carotid endarterectomy (hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.032) with a median biomarker ratio of 40 times the upper limit of normal. An additional 8 carotid artery stenting and 12 carotid endarterectomy patients had biomarker+ only (hazard ratio, 0.66; 95% confidence interval, 0.27 to 1.61; P=0.36), and their median biomarker ratio was 14 times the upper limit of normal. Compared with patients without biomarker elevation, mortality was higher over 4 years for those with MI (hazard ratio, 3.40; 95% confidence interval, 1.67 to 6.92) or biomarker+ only (hazard ratio, 3.57; 95% confidence interval, 1.46 to 8.68). After adjustment for baseline risk factors, both MI and biomarker+ only remained independently associated with increased mortality.ConclusionsIn patients randomized to carotid endarterectomy versus carotid artery stenting, both MI and biomarker+ only were more common with carotid endarterectomy. Although the levels of biomarker elevation were modest, both events were independently associated with increased future mortality and remain an important consideration in choosing the mode of carotid revascularization or medical therapy.Clinical trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00004732.

Project description:BackgroundCarotid-artery stenting and carotid endarterectomy are both options for treating carotid-artery stenosis, an important cause of stroke.MethodsWe randomly assigned patients with symptomatic or asymptomatic carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization.ResultsFor 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85).ConclusionsAmong patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)

Project description:ObjectiveMost studies based on state and nationwide registries evaluating perioperative outcome after carotid endarterectomy (CEA) rely on hospital discharge data only. Therefore, the true 30-day complication risk after carotid revascularization may be underestimated.MethodsWe used the National Surgical Quality Improvement Program database 2005-2010 to assess the in-hospital and postdischarge rate of any stroke, death, cardiac event (new Q-wave myocardial infarction or cardiac arrest), and combined stroke/death and combined adverse outcome (S/D/CE) at 30 days following CEA. Multivariable analyses were used to identify predictors for in-hospital and postdischarge events separately, and in particular, those that predict postdischarge events distinctly.ResultsA total of 35,916 patients who underwent CEA during 2005-2010 were identified in the National Surgical Quality Improvement Program database; 59% were male, median age was 72 years, and 44% had a previous neurologic event. Thirty-day stroke rate was 1.6% (n = 591), death rate was 0.8% (n = 272), cardiac event rate was 1.0% (n = 350), stroke or death rate was 2.2% (n = 794), and combined S/D/CE rate was 2.9% (n = 1043); 33% of strokes, 53% of deaths, 32% of cardiac events, 40% of combined stroke/death, and 38% of combined S/D/CE took place after hospital discharge. Patients with a prior stroke or transient ischemic attack had similar proportions of postdischarge events compared with patients without prior symptoms. Independent predictors for postdischarge events, but not for in-hospital events were female sex (stroke [odds ratio (OR), 1.6; 95% confidence interval (CI), 1.2-2.1] and stroke/death [OR, 1.4; 95% CI, 1.1-1.7]), renal failure (stroke [OR, 3.0; 95% CI, 1.4-6.2]) and chronic obstructive pulmonary disease (death [OR, 2.5; 95% CI, 1.6-3.7], stroke/death [OR, 1.8; 95% CI, 1.4-2.4], and S/D/CE [OR 1.8, 95% CI 1.4-2.3]).ConclusionsWith 38% of perioperative adverse events after CEA happening posthospitalization, regardless of symptoms status, we need to be alert to the ongoing risks after discharge particularly in women, patients with renal failure, or chronic obstructive pulmonary disease. This emphasizes the need for reporting and comparing 30-day adverse event rates when evaluating outcomes for CEA, or comparing carotid stenting to CEA.

Project description:Carotid endarterectomy (CEA) is usually performed under general anesthesia (GA), although some advocate regional anesthesia (RA) to reduce hemodynamic instability and allow neurologic monitoring and selective shunting. RA does not reduce risk of periprocedural stroke or death, although some series show a reduction in myocardial infarction (MI). We investigated the association of anesthesia type and periprocedural MI among patients receiving GA or RA for CEA and patients undergoing carotid artery stenting (CAS) in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST).Between 2000 and 2008, 1151 patients underwent CEA (anesthetic type available for 1149 patients), and 1123 patients underwent CAS ?30 days of randomization in CREST. CEA patients were categorized by anesthetic type (GA vs RA). CREST defined protocol MI as chest pain or electrocardiogram change plus biomarker evidence of MI, and total MI was defined as protocol MI plus biomarker-positive (+)-only MI. The incidence of protocol MI and total MI in patients undergoing CEA under GA and RA were compared with those undergoing CAS. Other study end points were similarly compared. Differences in baseline characteristics and periprocedural events were evaluated among the three groups. Logistic regression, adjusting for age and symptomatic status, was used to assess group differences.The three groups had similar demographic risk factors, except for prevalence of symptomatic carotid stenosis, which was lowest in the CEA-RA group (P = .03). Of the 111 patients in the CEA-RA group, no protocol MIs occurred and only two biomarker+-only MIs, for an overall incidence of 1.8%, similar to the 1.7% overall incidence in patients undergoing CAS. In contrast, the combined incidence of protocol and biomarker+-only MIs in the 1038 patients in the CEA-GA group was significantly higher at 3.4% (P = .04), twice the risk of protocol MI and biomarker+-only MI compared with those undergoing CAS (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.14-3.54). Direct comparison of the MI incidence between CEA-RA and CEA-GA showed no statistical difference. Patients undergoing CEA-GA had lower odds of a periprocedural stroke (OR, 0.48; 95% CI, 0.28-0.79) and stroke or death (OR, 0.46; 95% CI, 0.27-0.76) compared with those undergoing CAS but were not significantly different from those undergoing CEA-RA.Patients in CREST undergoing CEA-RA had a similar risk of periprocedural MI as those undergoing CAS, whereas the risk for CEA-GA was twice that compared with patients undergoing CAS. Nevertheless, because periprocedural MI is one of the few variables favoring CAS over CEA and has been associated with decreased long-term survival, RA should be seriously considered for patients undergoing CEA.

Dataset Information

Phenylephrine versus ephedrine on cerebral perfusion during carotid endarterectomy (PEPPER): study protocol for a randomized controlled trial.

Publications

Phenylephrine versus ephedrine on cerebral perfusion during carotid endarterectomy (PEPPER): study protocol for a randomized controlled trial.

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