Article Text
Abstract
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.
- phenylephrine
- ephedrine
- cerebral microcirculation
- brain oxygenation
- magnetic resonance imaging
- positron emission tomography
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Footnotes
Contributors KUK, AT, JA and MR made substantial contribution to the conception and design of this study. KUK drafted the manuscript, with input from AT, JA, MR and LN. LN, JCHS and LØ were senior supervisors. GvO and NJ contributed to conduction of the clinical studies. KUK is the chief investigator and has the overall responsibility for the study. All authors participated in the preparation of, and approved for publication, the final manuscript.
Funding This work was supported by funding from Lundbeckfonden (ref R164-2013-15390), Toyota Fonden (ref KJ/BG 8864 F) and the AP Moeller Foundation for the Advancement of Medical Science (ref 1718/NK PhD Vasobrain), Denmark. The study received institutional support from the Center of Functionally Integrative Neuroscience at Aarhus University and the Department of Neuroanesthesia at Aarhus University Hospital.
Competing interests None declared.
Ethics approval The study has been reported to the local GCP Unit, which is monitoring the trial. The study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). The trial has been approved by the Danish Health and Medicines Authority (16 June 2015, 2015042707) and the data monitoring committee Danish Data Protection Agency (2 July 2015, 1-16-02-291-15) independent from sponsor and without competing interests.
Provenance and peer review Not commissioned; externally peer reviewed.