Effect of Phenylephrine and Ephedrine on Cerebral (Tissue) Oxygen Saturation During Carotid Endarterectomy (PEPPER): A Randomized Controlled Trial

Leonie M M Fassaert, Gert J de Borst, Claire W A Pennekamp, Jantine C Specken-Welleweerd, Frans L Moll, Wilton A van Klei, Rogier V Immink, Leonie M M Fassaert, Gert J de Borst, Claire W A Pennekamp, Jantine C Specken-Welleweerd, Frans L Moll, Wilton A van Klei, Rogier V Immink

Abstract

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.

Keywords: Carotid endarterectomy; Cerebral; Cerebral autoregulation; Oxygen; Vasopressors.

Conflict of interest statement

Leonie MM Fassaert declares that she has no conflict of interest. Gert J de Borst declares that he has no conflict of interest. Claire WA Pennekamp declares that she has no conflict of interest. Jantine C Specken-Welleweerd declares that she has no conflict of interest. Frans L Moll declares that he has no conflict of interest. Wilton A van Klei declares that he has no conflict of interest. Rogier V Immink declares that he has no conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart of study
Fig. 2
Fig. 2
Percentile changes in mean arterial blood pressure (MAP) (A–B) and rSO2 ipsilateral (%) (C–D) individually and mean for both ephedrine and phenylephrine over time (s). Data in mean.
Fig. 3
Fig. 3
Changes in mean arterial blood pressure (MAP) (A), heart rate (HR) (B), percentile change in cardiac output (CO) (C), and frontal cerebral lobe oxygenation ipsilateral (D) and contralateral (E) during intravenously administration of ephedrine (filled circles) and phenylephrine (open circles) over time. Data in mean.

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