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The influence of CYP2B6 variants on traumatic brain injury patient outcome after rapid sequence intubation

O'Meara, Katherine (2022) The influence of CYP2B6 variants on traumatic brain injury patient outcome after rapid sequence intubation. Undergraduate Thesis, University of Pittsburgh. (Unpublished)

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A traumatic brain injury (TBI) is a disruption in normal brain function due to any disturbance to the head. These injuries are usually devastating; leading to lifetime disability or early death. It has been found that genetic polymorphisms can impact outcomes after a TBI. A treatment that is commonly used in these patients is sedation – usually with an opioid or propofol. This study aimed to investigate the relationship of the CYP2B6 polymorphism and the outcomes of TBI patients while also considering propofol administration. The cytochrome P450 enzyme CYP2B6 is involved in the biotransformation of many drugs, including anesthetic agents. Studies have found that variants of CYP2B6 can lead to decreased systematic clearance of propofol. This could potentially lead to life-threatening complications. Despite this knowledge there have been no formal investigations regarding this polymorphism’s effect on drug administration and TBI patient outcome, warranting a need for a study of this nature.
This study is a retrospective analysis of prospectively collected participants from the Brain Trauma Research Center (BRTC) in the Department of Neurosurgery at the University of Pittsburgh Medical Center (UPMC) Presbyterian Hospital. Inclusion criteria for this database included: a severe blunt TBI, Glasgow Coma Scale (GCS) score 3-8, and not following commands. Participants also met the additional inclusion criteria of permission to obtain a genetic sample. With this criteria, participants (n=440) were further phenotyped by collecting the drugs admitted to each patient during their hospital stay. Allelic Discrimination of CYP2B6 was performed using two SNPs (rs2279343 and rs3745274) through Taqman Assays. Neurological outcomes were evaluated using the Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS). Individuals with the rs3745274 TT genotype and rs2279343 GG genotype were more likely to have worse outcomes. This could be due to decreased metabolism or systematic clearance of drugs. These findings suggest that CYP2B6 may impact patient outcome through drug metabolism and further investigation should be done regarding the role of CYP2B6 variants on TBI patient outcome.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
O'Meara, Katherinekno9@pitt.edukno9
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairConley,
Committee MemberPuccio,
Committee MemberRen,
Committee MemberJha,
Date: 13 December 2022
Date Type: Publication
Defense Date: 22 November 2022
Approval Date: 13 December 2022
Submission Date: 11 December 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 35
Institution: University of Pittsburgh
Schools and Programs: David C. Frederick Honors College
School of Nursing > Nursing
Degree: BSN - Bachelor of Science in Nursing
Thesis Type: Undergraduate Thesis
Refereed: Yes
Uncontrolled Keywords: propofol; genetics; drug metabolism
Date Deposited: 13 Dec 2022 19:28
Last Modified: 13 Dec 2022 19:28

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