Vasopressor Effects in Anesthetized Patients

Summary

Project title: Influence of Vasopressors on Brain Oxygenation and Microcirculation in Anesthetized Patients with Cerebral Tumors Sponsor-investigator: Klaus Ulrik Koch M.D. Sponsor: Department of Anesthesia Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark Objective: To investigate whether phenylephrine and ephedrine causes different alterations in microcirculation and oxygenation, as measured with MRI and PET, in anesthetized patients with brain tumors. Using MRI and PET, the study will assess whether there is a difference in deoxyhemoglobin concentration (Bold signal), CTTH, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) between ephedrine and phenylephrine Method: Double blinded controlled randomized clinical trial. Either phenylephrine or ephedrine are infused intravenously under general anesthesia. MRI is performed in 20 patients before and after infusion. PET/CT is performed in 20 patients before and after infusion. BIS and NIRS monitoring will be used in either scanner. After scanning patients are transported to the operating theatre and the craniotomy is performed. After removal of the bone flap subdural ICP is measured and recorded. MRI to analyze CBF, CTH, max.CMRO2, maxOEF, CBV and grey-scale ADC before and after ephedrine and phenylephrine. PET/CT to analyze CBF and CMRO2 before and after ephedrine and phenylephrine and calculation of OEF. During each PET/CT scan session oxygen saturation and hemoglobin concentration is measured. Data from the proposed studies will add substantial new knowledge to the investigators current understanding of the effects of vasopressors on cerebral circulation. This information will aid the neuroanesthesiologist, neurointensivist and the neurosurgeon in the choice of the optimal method to manage cerebral perfusion pressure during craniotomy for brain tumor.

Timeline

Start

2015-09

Primary completion

2017-11

Completion

2017-11

Publications

• Background Rasmussen M, Bundgaard H, Cold GE. Craniotomy for supratentorial brain tumors: risk factors for brain swelling after opening the dura mater. J Neurosurg. 2004 Oct;101(4):621-6. doi: 10.3171/jns.2004.101.4.0621.
• Background Rasmussen M, Juul N, Christensen SM, Jonsdottir KY, Gyldensted C, Vestergaard-Poulsen P, Cold GE, Ostergaard L. Cerebral blood flow, blood volume, and mean transit time responses to propofol and indomethacin in peritumor and contralateral brain regions: perioperative perfusion-weighted magnetic resonance imaging in patients with brain tumors. Anesthesiology. 2010 Jan;112(1):50-6. doi: 10.1097/ALN.0b013e3181c38bd3.
• Background Rasmussen M, Ostergaard L, Juul N, Gyldensted C, Poulsen PV, Cold GE. Do indomethacin and propofol cause cerebral ischemic damage? Diffusion-weighted magnetic resonance imaging in patients undergoing craniotomy for brain tumors. Anesthesiology. 2004 Oct;101(4):872-8. doi: 10.1097/00000542-200410000-00011.
• Background Dubin A, Pozo MO, Casabella CA, Palizas F Jr, Murias G, Moseinco MC, Kanoore Edul VS, Palizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care. 2009;13(3):R92. doi: 10.1186/cc7922. Epub 2009 Jun 17.
• Background Brain Trauma Foundation; American Association of Neurological Surgeons; Congress of Neurological Surgeons; Joint Section on Neurotrauma and Critical Care, AANS/CNS; Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW. Guidelines for the management of severe traumatic brain injury. XIV. Hyperventilation. J Neurotrauma. 2007;24 Suppl 1:S87-90. doi: 10.1089/neu.2007.9982. No abstract available.
• Background Boerma EC, Ince C. The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients. Intensive Care Med. 2010 Dec;36(12):2004-18. doi: 10.1007/s00134-010-1970-x. Epub 2010 Sep 2.
• Background Sahuquillo J, Amoros S, Santos A, Poca MA, Panzardo H, Dominguez L, Pedraza S. Does an increase in cerebral perfusion pressure always mean a better oxygenated brain? A study in head-injured patients. Acta Neurochir Suppl. 2000;76:457-62. doi: 10.1007/978-3-7091-6346-7_95.
• Background Hahn GH, Hyttel-Sorensen S, Petersen SM, Pryds O, Greisen G. Cerebral effects of commonly used vasopressor-inotropes: a study in newborn piglets. PLoS One. 2013 May 20;8(5):e63069. doi: 10.1371/journal.pone.0063069. Print 2013.
• Background Nissen P, Brassard P, Jorgensen TB, Secher NH. Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension. Neurocrit Care. 2010 Feb;12(1):17-23. doi: 10.1007/s12028-009-9313-x.
• Background Meng L, Cannesson M, Alexander BS, Yu Z, Kain ZN, Cerussi AE, Tromberg BJ, Mantulin WW. Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth. 2011 Aug;107(2):209-17. doi: 10.1093/bja/aer150. Epub 2011 Jun 3.
• Background Soeding PF, Hoy S, Hoy G, Evans M, Royse CF. Effect of phenylephrine on the haemodynamic state and cerebral oxygen saturation during anaesthesia in the upright position. Br J Anaesth. 2013 Aug;111(2):229-34. doi: 10.1093/bja/aet024. Epub 2013 Mar 21.
• Background Jespersen SN, Ostergaard L. The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism. J Cereb Blood Flow Metab. 2012 Feb;32(2):264-77. doi: 10.1038/jcbfm.2011.153. Epub 2011 Nov 2.
• Background Ostergaard L, Jespersen SN, Mouridsen K, Mikkelsen IK, Jonsdottir KY, Tietze A, Blicher JU, Aamand R, Hjort N, Iversen NK, Cai C, Hougaard KD, Simonsen CZ, Von Weitzel-Mudersbach P, Modrau B, Nagenthiraja K, Riisgaard Ribe L, Hansen MB, Bekke SL, Dahlman MG, Puig J, Pedraza S, Serena J, Cho TH, Siemonsen S, Thomalla G, Fiehler J, Nighoghossian N, Andersen G. The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model. J Cereb Blood Flow Metab. 2013 May;33(5):635-48. doi: 10.1038/jcbfm.2013.18. Epub 2013 Feb 27.
• Background Ostergaard L, Aamand R, Karabegovic S, Tietze A, Blicher JU, Mikkelsen IK, Iversen NK, Secher N, Engedal TS, Anzabi M, Jimenez EG, Cai C, Koch KU, Naess-Schmidt ET, Obel A, Juul N, Rasmussen M, Sorensen JC. The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2013 Dec;33(12):1825-37. doi: 10.1038/jcbfm.2013.173. Epub 2013 Sep 25.
• Background Ostergaard L, Engedal TS, Aamand R, Mikkelsen R, Iversen NK, Anzabi M, Naess-Schmidt ET, Drasbek KR, Bay V, Blicher JU, Tietze A, Mikkelsen IK, Hansen B, Jespersen SN, Juul N, Sorensen JC, Rasmussen M. Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury. J Cereb Blood Flow Metab. 2014 Oct;34(10):1585-98. doi: 10.1038/jcbfm.2014.131. Epub 2014 Jul 23.
• Background Petersen KD, Landsfeldt U, Cold GE, Petersen CB, Mau S, Hauerberg J, Holst P, Olsen KS. Intracranial pressure and cerebral hemodynamic in patients with cerebral tumors: a randomized prospective study of patients subjected to craniotomy in propofol-fentanyl, isoflurane-fentanyl, or sevoflurane-fentanyl anesthesia. Anesthesiology. 2003 Feb;98(2):329-36. doi: 10.1097/00000542-200302000-00010.
• Background Cold GE, Tange M, Jensen TM, Ottesen S. "Subdural' pressure measurement during craniotomy. Correlation with tactile estimation of dural tension and brain herniation after opening of dura. Br J Neurosurg. 1996 Feb;10(1):69-75. doi: 10.1080/02688699650040548.
• Background Ostergaard L, Weisskoff RM, Chesler DA, Gyldensted C, Rosen BR. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis. Magn Reson Med. 1996 Nov;36(5):715-25. doi: 10.1002/mrm.1910360510.
• Background Mouridsen K, Hansen MB, Ostergaard L, Jespersen SN. Reliable estimation of capillary transit time distributions using DSC-MRI. J Cereb Blood Flow Metab. 2014 Sep;34(9):1511-21. doi: 10.1038/jcbfm.2014.111. Epub 2014 Jun 18.
• Background Hansen B, Lund TE, Sangill R, Jespersen SN. Experimentally and computationally fast method for estimation of a mean kurtosis. Magn Reson Med. 2013 Jun;69(6):1754-60. doi: 10.1002/mrm.24743. Epub 2013 Apr 15.
• Background Blomqvist G. On the construction of functional maps in positron emission tomography. J Cereb Blood Flow Metab. 1984 Dec;4(4):629-32. doi: 10.1038/jcbfm.1984.89.
• Background Ohta S, Meyer E, Fujita H, Reutens DC, Evans A, Gjedde A. Cerebral [15O]water clearance in humans determined by PET: I. Theory and normal values. J Cereb Blood Flow Metab. 1996 Sep;16(5):765-80. doi: 10.1097/00004647-199609000-00002.
• Background Ohta S, Meyer E, Thompson CJ, Gjedde A. Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen. J Cereb Blood Flow Metab. 1992 Mar;12(2):179-92. doi: 10.1038/jcbfm.1992.28.
• Background Radiation dose to patients from radiopharmaceuticals (addendum 2 to ICRP publication 53). Ann ICRP. 1998;28(3):1-126. doi: 10.1016/s0146-6453(99)00006-8.
• Background Mak PH, Campbell RC, Irwin MG; American Society of Anesthesiologists. The ASA Physical Status Classification: inter-observer consistency. American Society of Anesthesiologists. Anaesth Intensive Care. 2002 Oct;30(5):633-40. doi: 10.1177/0310057X0203000516.
• Background Ngwenya LB, Chiocca EA. Editorial: postoperative ischemia. J Neurosurg. 2013 Apr;118(4):799-800; discussion 800. doi: 10.3171/2012.8.JNS121410. Epub 2013 Feb 1. No abstract available.
• Koch KU, Tietze A, Aanerud J, Oettingen GV, Juul N, Sorensen JCH, Nikolajsen L, Ostergaard L, Rasmussen M. 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 Nov 17;7(11):e018560. doi: 10.1136/bmjopen-2017-018560.

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Indications