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Differential effect of phenylephrine and ephedrine on cerebral haemodynamics before carotid cross-clamping during carotid endarterectomy

2012; Elsevier BV; Volume: 109; Issue: 5 Linguagem: Inglês

10.1093/bja/aes370

1471-6771

C.W.A. Pennekamp, Rogier V. Immink, Frans L. Moll, Wolfgang Bühre, Gert J. de Borst,

Cardiovascular Health and Disease Prevention

Editor—Internal carotid artery stenosis is often associated with impaired cerebral autoregulation, implying that cerebral blood flow depends on arterial pressure.1Diehl RR Linden D Lucke D Berlit P Phase relationship between cerebral blood flow velocity and blood pressure. A clinical test of autoregulation.Stroke. 1995; 26: 1801-1804doi:10.1161/01.STR.26.10.1801Crossref PubMed Scopus (342) Google Scholar, 2Reinhard M Gerds TA Grabiak D et al.Cerebral dysautoregulation and the risk of ischemic events in occlusive carotid artery disease.J Neurol. 2008; 255: 1182-1189doi:10.1007/s00415-008-0865-zCrossref PubMed Scopus (59) Google Scholar, 3Reinhard M Roth M Muller T Czosnyka M Timmer J Hetzel A Cerebral autoregulation in carotid artery occlusive disease assessed from spontaneous blood pressure fluctuations by the correlation coefficient index.Stroke. 2003; 34: 2138-2144doi:10.1161/01.STR.0000087788.65566.ACCrossref PubMed Scopus (117) Google Scholar To preserve cerebral perfusion and to prevent 'watershed' stroke during carotid endarterectomy (CEA), hypotension before and during cross-clamping needs to be avoided.4Stoneham MD Thompson JP Arterial pressure management and carotid endarterectomy.Br J Anaesth. 2009; 102: 442-452doi:10.1093/bja/aep012Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar Several short-acting agents, such as phenylephrine or ephedrine, are commonly used to correct intraoperative hypotension, but have different haemodynamic effects. Phenylephrine, an α-agonist, increases arterial pressure by arterial vasoconstriction, whereas ephedrine, an α- and β-agonist, increases arterial pressure by arterial vasoconstriction combined with an increase in heart rate and cardiac output (CO).5Dyer RA Reed AR van DD et al.Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery.Anesthesiology. 2009; 111: 753-765doi:10.1097/ALN.0b013e3181b437e0Crossref PubMed Scopus (213) Google Scholar In healthy anaesthetized subjects with intact cerebral autoregulation, frontal lobe cerebral tissue oxygenation (rSO2) declined after phenylephrine while it was preserved after ephedrine.6Meng L Cannesson M Alexander BS et al.Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients.Br J Anaesth. 2011; 107: 209-217doi:10.1093/bja/aer150Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar 7Nissen P Brassard P Jorgensen TB Secher NH Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.Neurocrit Care. 2010; 12: 17-23doi:10.1007/s12028-009-9313-xCrossref PubMed Scopus (85) Google Scholar To evaluate the effect of both ephedrine and phenylephrine on cerebral haemodynamics during CEA under general anaesthesia, we analysed the association between the increase in mean arterial pressure (MAP) induced by either ephedrine or phenylephrine and concurrent changes in cerebral haemodynamics using transcranial Doppler-derived mean middle cerebral artery blood velocity (Vmean) and near-infrared spectroscopy-derived rSO2. All patients were anaesthetized using the same anaesthetic regimen. In 11 patients undergoing CEA between February 2009 and June 2011, who all received either ephedrine (5–10 mg; n=7) or phenylephrine (50–100 µg; n=4) to correct relative hypotension (defined as >20% decrease in MAP when compared with preoperative MAP directly before cross-clamping). Three minutes after ephedrine or phenylephrine administration, MAP increased from [mean (sd)] 79 (12) to 89(11) mm Hg or from 84 (6) to 102 (6) mm Hg (both P=0.025), respectively (Fig. 1). Ephedrine raised heart rate from 55 (12) to 65 (17) beats min−1 (P=0.017), while phenylephrine declined heart rate from 74 (6) to 65 (5) beats min−1 (P=0.005). After ephedrine administration, rSO2 increased from 70 (7)% to 73 (6)% (P=0.002); however, phenylephrine decreased rSO2 from 71 (7)% to 66 (9)% (P=0.076). The Vmean remained constant after ephedrine [46 (14) cm s−1], but increased from 46 (13) to 49 (12) cm s−1 (P=0.035) after phenylephrine. The linear regression analysis showed that the absolute change from baseline in rSO2 was positively related to the change in MAP with ephedrine [0.108% per mm Hg increase, 95% confidence interval (CI) 0.058–0.159]. However, for a phenylephrine-induced increase in MAP, an inversely related change in rSO2 compared with MAP (−0.202% per mm Hg increase, 95% CI −0.278 to 0.126) was found. The mechanism of the reduction in rSO2 after phenylephrine and not after ephedrine is unclear. In patients with intact cerebral autoregulation, the decrease in rSO2 after phenylephrine was associated with concordant changes in CO, whereas rSO2 remained unchanged when CO remained constant after treatment with ephedrine.6Meng L Cannesson M Alexander BS et al.Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients.Br J Anaesth. 2011; 107: 209-217doi:10.1093/bja/aer150Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar This observation confirms that changes in CO, even independently from arterial pressure, affect cerebral haemodynamics.8Ogoh S Brothers RM Barnes Q et al.The effect of changes in cardiac output on middle cerebral artery mean blood velocity at rest and during exercise.J Physiol. 2005; 569: 697-704doi:10.1113/jphysiol.2005.095836Crossref PubMed Scopus (223) Google Scholar Cerebral arteries are abundantly innervated by sympathetic fibres.9Sandor P Nervous control of the cerebrovascular system: doubts and facts.Neurochem Int. 1999; 35: 237-259doi:10.1016/S0197-0186(99)00067-4Crossref PubMed Scopus (103) Google Scholar Therefore, the decrease in rSO2 after phenylephrine could be explained by a direct α-receptor-mediated cerebral vasoconstriction, as a decrease in middle cerebral artery diameter might result in a decreased blood flow, while Vmean remains constant or even increases. To our knowledge, this is the first report on the differential influence of phenylephrine and ephedrine on cerebral haemodynamics in patients undergoing CEA. Although the data are very limited, the observations were consistent, since no patients treated with phenylephrine showed an increase in cerebral oxygenation, and no patient in the ephedrine group showed a decrease. Therefore, based on this small case series, we conclude that the value of phenylephrine in terms of benefit for cerebral haemodynamics could be questioned. A controlled trial is warranted to clarify the effects of different vasoactive agents on cerebral oxygenation to determine the optimal agent to increase arterial pressure during CEA. None declared. The Invos Cerebral Oximeter (Somanetics Corporation, Troy, MI, USA) was provided free for the duration of the study by Covidien Nederland B.V., Zaltbommel, The Netherlands.