Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging

Abstract

Background This study compared ephedrine versus phenylephrine treatment on cerebral macro- and microcirculation, measured by cerebral blood flow, and capillary transit time heterogeneity, in anesthetized brain tumor patients. The hypothesis was that capillary transit time heterogeneity in selected brain regions is greater during phenylephrine than during ephedrine, thus reducing cerebral oxygen tension. Methods In this single-center, double-blinded, randomized clinical trial, 24 anesthetized brain tumor patients were randomly assigned to ephedrine or phenylephrine. Magnetic resonance imaging of peritumoral and contralateral hemispheres was performed before and during vasopressor infusion. The primary endpoint was between-group difference in capillary transit time heterogeneity. Secondary endpoints included changes in cerebral blood flow, estimated oxygen extraction fraction, and brain tissue oxygen tension. Results Data from 20 patients showed that mean (± SD) capillary transit time heterogeneity in the contralateral hemisphere increased during phenylephrine from 3.0 ± 0.5 to 3.2 ± 0.7 s and decreased during ephedrine from 3.1 ± 0.8 to 2.7 ± 0.7 s (difference phenylephrine versus difference ephedrine [95% CI], −0.6 [−0.9 to −0.2] s; P = 0.004). In the peritumoral region, the mean capillary transit time heterogeneity increased during phenylephrine from 4.1 ± 0.7 to 4.3 ± 0.8 s and decreased during ephedrine from 3.5 ± 0.9 to 3.3 ± 0.9 s (difference phenylephrine versus difference ephedrine [95%CI], −0.4[−0.9 to 0.1] s; P = 0.130). Cerebral blood flow (contralateral hemisphere ratio difference [95% CI], 0.3 [0.06 to 0.54]; P = 0.018; and peritumoral ratio difference [95% CI], 0.3 [0.06 to 0.54; P = 0.018) and estimated brain tissue oxygen tension (contralateral hemisphere ratio difference [95% CI], 0.34 [0.09 to 0.59]; P = 0.001; and peritumoral ratio difference [95% CI], 0.33 [0.09 to 0.57]; P = 0.010) were greater during ephedrine than phenylephrine in both regions. Conclusions Phenylephrine caused microcirculation in contralateral tissue, measured by the change in capillary transit time heterogeneity, to deteriorate compared with ephedrine, despite reaching similar mean arterial pressure endpoints. Ephedrine improved cerebral blood flow and tissue oxygenation in both brain regions and may be superior to phenylephrine in improving cerebral macro- and microscopic hemodynamics and oxygenation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Vasopressor Effects on Cerebral Microcirculation: Reply

“…We thank Bombardieri and Tsui 1 for their excellent comments and interest in our study. 2 We agree with Bombardieri and Tsui that the deterioration of microperfusion and possibly tissue oxygenation after phenylephrine administration in the “healthy” brain hemisphere 2 indicates that different vasopressors may also have a different influence on microperfusion and tissue oxygenation in the healthy anesthetized brain and should be further explored. 3 In our opinion, future studies on the effects of different vasopressors on the cerebral macro- and microcirculation should be considered in the context of their different effects on the systemic circulation to provide a fully integrated picture of their influence on organ perfusion and oxygenation.…”

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“…Many researchers in recent times have also reported that the drug ephedrine could be a clinical neuroprotective candidate for treatment of cerebral ischemic stroke 34 and brain injury 35 . Also, ephedrine could exhibit protective effects against chronic obstructive pulmonary disease 36 and one of the standard choices of vasopressor agents to offset the consequences of life-threatening illnesses such as infection, heart failure, and anaphylaxis during surgical procedures 37 , 38 . Owing to its significant impact in medical field, the drug ephedrine is being listed under the WHO’s 21st edition of model list of essential medicines 39 .…”

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“…In our study, ephedrine was the fi rst-line drug. Koch et al [9] discovered that ephedrine improves brain blood fl ow and tissue oxygenation and may be more eff ective than phenylephrine at improving brain hemodynamics and oxygenation. Thus, we believe that we can omit the infl uence of vasomotor agents on brain saturation, mainly since we analyzed the relationship between rSO2 and MAP.…”