scholarly journals Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours: study protocol for a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e018560 ◽  
Author(s):  
Klaus Ulrik Koch ◽  
Anna Tietze ◽  
Joel Aanerud ◽  
Gorm von Öettingen ◽  
Niels Juul ◽  
...  

IntroductionDuring 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 analysisThis 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 disseminationThis 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 numberNCT02713087; Pre-results. 2015-001359-60; Pre-results.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1387-1387
Author(s):  
Adam M Bush ◽  
Matthew Borzage ◽  
Soyoung Choi ◽  
Thomas Coates ◽  
John C Wood

Abstract Introduction Chronic Transfusion Therapy (CTT) has been successful in decreasing stroke frequency in patients with sickle cell disease (SCD). Despite this, indication for CTT is largely based on empirical evidence and the mechanisms by which CTT protects the brain remain unclear. CTT improves oxygen carrying capacity and lowers hemoglobin S%, but the corresponding impact on cerebral blood flow(CBF), cerebral metabolic rate (CMRO2), and oxygen extraction fraction (OEF) is unknown. Understanding the impact of these competing influences in non-transfused (NT) and chronically transfused (CT) SCD patients will inform stroke prevention. Thus, we measured CBF, CMRO2, and OEF, in NT and CT patients with SCD using magnetic resonance imaging (MRI). Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Fourteen (6 NT, 8 CT) patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. Complete blood count and hemoglobin electrophoresis were performed. Arterial oxygen saturation (SaO2) was measured via peripheral pulse oximetery. CaO2 was calculated as the product of hemoglobin, SaO2 and the oxygen density of hemoglobin (1.36 ml/g). Phase contrast imaging of the carotid and vertebral arteries was used to measure global CBF. T2 Relaxation Under Spin Tagging (TRUST) was used to measured T2 relaxation of blood within the sagittal sinus. T2 relaxation was converted to SvO2 via previously validated calibration curves. OEF represented the difference of SaO2 andSvO2 divided bySaO2. CMRO2 was calculated as the product of CBF and OEF. High resolution, 3D, T1 weighted images were used for brain volume calculation using BrainSuiteñ software. Results Table 1 summarizes the results. Hemoglobin and oxygen content were well matched between transfused and non transfused SCD patients. Cerebral metabolic rate was also nearly identical in the two groups. However, CT patients exhibited 25% higher CBF than NT SCD patients, allowing them to have a normal oxygen extraction fraction ~30%. In contrast, OEF in NT SCD patients was abnormally high (37.8%), suggesting a decreased extraction reserve. Total oxygenation index (TOI) by NIRS also trended lower in NT SCD patients, consistent with the greater oxygen extraction and lower cerebral venous saturations observed. Abstract 1387. TableCTL (reference)NTCTp value (NT vs CT)Hemoglobin (g/dl)13.5 ± 1.229.7 ± 1.259.7 ± 1.05nsCaO2 (umol O2/ml)9.85 ± .996.84 ± 1.176.95 ±.71nsCMRO2 (umol O2/100g/min)193.1 ± 44.9239.7 ± 35.3238.6 ± 38.3nsCBF (ml/100g/min)70.0 ± 12.8101.5 ± 16.6127.1 ± 23.5< 0.05OEF (%)30.0 ± 7.137.8. ± 3.0629.7 ± 7.53< 0.05NIRS TOI56.0 ± 4.0948.5 ± 4.2153.5 ± 8.760.076SvO2 (%)65.6 ± 6.856.2 ± 5.267.1 ± 6.7< 0.05 Discussion: Chronically transfused SCD patients achieve normal brain oxygenation metrics (SvO2, OEF, and NIRS) but require very high CBF to achieve this balance (lowering flow reserve). In contrast, NT SCD patients have smaller increases in CBF but require greater oxygen extraction to meet cerebrovascular demands (lowering extraction reserve). Hemoglobin S mediate changes in oxygen dissociation, blood viscosity, red cell deformability and microvascular damage potentially mediate these differences but their interplay is complicated and requires further study. Disclosures Coates: novartis: Consultancy, Honoraria, Speakers Bureau; shire: Consultancy, Honoraria; apo pharma: Consultancy, Honoraria; acceleron: Consultancy, Honoraria.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Takahisa Mori ◽  
Tomonori Iwata ◽  
Yuhei Tanno ◽  
Shigen Kasakura ◽  
Yoshinori Aoyagi ◽  
...  

Background: It is required to anticipate cerebral hyperperfusion syndrome (CHS) following carotid artery stenting (CAS). Purpose: The purpose of our retrospective study was to investigate whether or not blood sampling oxygen extraction fraction (OEF) and post-CAS CBF increase in SPECT had relation to CHS following CAS. Methods: Included in our analysis were patients (1) who underwent elective CAS in our institution between October 2010 and May 2014, and (2) who underwent blood sampling for OEF calculation before and immediately after CAS, and (3) who underwent SPECT before and just after CAS. OEF was calculated from cerebral arteriovenous oxygen difference. Arterial blood was sampled from the common carotid artery and venous blood from the dominant-sided superior jugular bulb. CHS was defined as pulsatile headaches, restlessness, convulsion, and/or new neurological symptoms not due to cerebral ischemia within seven days following CAS. CBF was measured before and just after CAS. CBF increase in the CAS side was defined as follows; (post-CAS CBF ratio - pre-CAS CBF ratio) of more than 10%, where CBF ratio was defined as CAS-sided fronto-parietal CBF divided by ipsilateral cerebellar CBF (%). Evaluated were baseline features in patients, pre-CAS OEF, post-CAS OEF, CBF ratio, CBF increase and CHS. Results: During the study period, 134 patients matched our criteria for analysis. Pre-CAS OEF was 0.41+-0.06, post-CAS OEF was 0.42+-0.08, pre-CAS CBF ratio: 88.7+-15.4%, CBF increase: 1.86+-12.3%. Nine patients presented CHS. Among them, pre-CAS OEF, CBF ratio and CBF increase were significant. ROC curves showed that pre-CAS OEF of 0.46 (p<0.001, OR: 9.3), CBF ratio of 92%(p<0.05, OR: 6.5), CBF increase of 8.8% (p<0.005, OR: 6.6) were cut-off values. Among 10 patients with pre-CAS OEF of more than 0.46 and CBF increase of more than 8.8%, 4 patients presented CHS (p<0.0001, OR;15.9). Conclusion: Elevation of pre-CAS OEF and increase of post-CAS CBF were strongly related to CHS.


1992 ◽  
Vol 12 (2) ◽  
pp. 193-203 ◽  
Author(s):  
W.-D. Heiss ◽  
M. Huber ◽  
G. R. Fink ◽  
K. Herholz ◽  
U. Pietrzyk ◽  
...  

Sixteen patients were studied by multitracer positron emission tomography (PET) within 6–48 (mean of 23) h of onset of a hemispheric ischemic stroke and again 13–25 (mean of 15.6) days later. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral metabolic rate of glucose (CMRglc) were measured each time by standard methods, and the sets of brain slices obtained at the two studies were matched using a three-dimensional alignment procedure. On matched brain slices, regions of interest (ROIs) for infarct and peri-infarct tissue, contralateral mirror regions, and major brain structures were outlined. In the core of infarction, blood flow and metabolism were significantly lower than in the corresponding contralateral regions at the first study, and did not change during the observation period. In the peri-infarct tissue, CMRO2 was moderately decreased at the first measurement; over time, the CMRO2 deteriorated progressively while flow did not change. When peri-infarct regions were selected on the basis of increased OEF (25 ± 29.8% above corresponding contralateral regions) on the early scans, the CBF was significantly decreased (23 ± 6.6%) while the CMRO2 showed only a slight difference from the mirror region. Within the observation period, the CBF improved but the CMRO2, OEF, and CMRglc deteriorated. Only in a few regions with increased OEF and slightly impaired CMRO2 was metabolism preserved close to normal values. These data from repeat PET studies in reproducibly defined tissue compartments furnish evidence of viable tissue in the border zone of ischemia up to 48 h after stroke. While this viable peri-infarct tissue exhibits some potential for effective treatment of ischemic stroke, therapeutic routines available today cannot prevent subsequent metabolic derangement and progression to necrosis. Multitracer PET studies identifying viable tissue could be of value in the development of effective treatment of ischemic stroke.


2019 ◽  
Vol 40 (7) ◽  
pp. 1492-1500
Author(s):  
Dengrong Jiang ◽  
Zixuan Lin ◽  
Peiying Liu ◽  
Sandeepa Sur ◽  
Cuimei Xu ◽  
...  

Cerebral oxygen extraction fraction is an important physiological index of the brain’s oxygen consumption and supply and has been suggested to be a potential biomarker for a number of diseases such as stroke, Alzheimer’s disease, multiple sclerosis, sickle cell disease, and metabolic disorders. However, in order for oxygen extraction fraction to be a sensitive biomarker for personalized disease diagnosis, inter-subject variations in normal subjects must be minimized or accounted for, which will otherwise obscure its interpretation. Therefore, it is essential to investigate the physiological underpinnings of normal differences in oxygen extraction fraction. This work used two studies, one discovery study and one verification study, to examine the extent to which an individual’s end-tidal CO2 can explain variations in oxygen extraction fraction. It was found that, across normal subjects, oxygen extraction fraction is inversely correlated with end-tidal CO2. Approximately 50% of the inter-subject variations in oxygen extraction fraction can be attributed to end-tidal CO2 differences. In addition, oxygen extraction fraction was found to be positively associated with age and systolic blood pressure. By accounting for end-tidal CO2, age, and systolic blood pressure of the subjects, normal variations in oxygen extraction fraction can be reduced by 73%, which is expected to substantially enhance the utility of oxygen extraction fraction as a disease biomarker.


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