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dc.contributor.advisorNancy Morris
dc.contributor.authorAroke, Edwin N.
dc.date2022-08-11T08:09:03.000
dc.date.accessioned2022-08-23T16:16:42Z
dc.date.available2022-08-23T16:16:42Z
dc.date.issued2016-04-21
dc.date.submitted2016-07-14
dc.identifier.doi10.13028/wshx-0a80
dc.identifier.urihttp://hdl.handle.net/20.500.14038/34390
dc.description<p>Material from this dissertation has been published in: Aroke EN, Crawford SL, Dungan JR. Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study. Nurs Res. 2017 Mar/Apr;66(2):105-114. doi: 10.1097/NNR.0000000000000197. PubMed PMID: 28252572.</p>
dc.description.abstractBackground: Up to 55% of patients administered ketamine, experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury. While genetics accounts for about 50% of severe adverse drug reactions, no studies have investigated genetic association of ketamine-induced EP in healthy patients. Ketamine is metabolized by CYP 2B6 enzymes and CYP 2B^8^ allele significantly alter ketamine metabolism. In addition, ketamine exerts most of its effects by inhibiting the N-methyl-D-aspartate receptor (NMADR), and NMDAR genes (GRIN2B) are associated with learning and memory impairment and schizophrenia. Purpose: To investigate the relationship between CYP2B6*6 and GRIN2B single nucleotide polymorphisms (SNPs) and ketamine-induced emergence phenomena (EP). Methods: This cross-sectional pharmacogenetic study recruited 75 patients having minor orthopedic, hand, foot, anorectal surgeries from two outpatient surgical centers. EP was measured with the Clinician Administered Dissociative State Scale (CADSS). DNA was genotyped using standard Taqman assays and protocols. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 & rs1806191) SNPs and ketamine induced EP occurrence and severity were tested using multivariate logistic and linear regression, adjusting for age, ketamine dose, duration of anesthesia, and time since ketamine administration. Results: Forty-seven patients (63%) received ketamine and were genotyped. Nineteen EP cases were identified (CADSS > 4), leaving 28 non-EP controls. For our population, CADSS has an internal consistency reliability Cronbach’s alpha of 0.82, and could reliably distinguish ketamine from non-ketamine cases. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p > 0.1). Models removing genotype and containing age, ketamine dose, duration of v anesthesia, and time since ketamine administration significantly predicted EP occurrence (p = 0.001) and severity (p = 0.007). Presence and severity of EP did not affect patient satisfaction with care. Discussion: Younger age, higher dose and longer duration of anesthesia significantly predicted EP occurrence and severity among our sample. This study provides effect size estimates useful for the design of adequately powered future genetic association studies. The feasibility of recruitment from patients undergoing elective, outpatient surgeries and ease of post-operative EP assessment with CADSS supports our approach. However, the small sample size may have limited about ability to determine significant differences. Conclusion: Fully powered studies are needed to investigate this important phenomena. Determining factors for anesthesia-related EP symptoms may reduce risks and costs associated with this adverse medication effect.
dc.language.isoen_US
dc.relation<p><a href="http://escholarship.umassmed.edu/gsn_pp/53/">Published article based on this dissertation</a></p>
dc.rightsCopyright by Edwin N. Aroke 2016. All Rights Reserved.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectemergence phenomena
dc.subjectgenetics
dc.subjectKetamine
dc.subjectAnesthesia
dc.subjectPostoperative Complications
dc.subjectAnesthesia Recovery Period
dc.subjectDrug-Related Side Effects and Adverse Reactions
dc.subjectPharmacogenetics
dc.subjectAnesthesiology
dc.subjectChemical and Pharmacologic Phenomena
dc.subjectMedical Pharmacology
dc.subjectNursing
dc.subjectPharmaceutical Preparations
dc.subjectPharmacology
dc.subjectPsychiatry and Psychology
dc.titleA Pilot Study of the Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1054&amp;context=gsn_diss&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsn_diss/43
dc.legacy.embargo2017-11-18T00:00:00-08:00
dc.identifier.contextkey8835083
refterms.dateFOA2022-08-24T04:06:43Z
html.description.abstract<p>Background: Up to 55% of patients administered ketamine, experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury. While genetics accounts for about 50% of severe adverse drug reactions, no studies have investigated genetic association of ketamine-induced EP in healthy patients. Ketamine is metabolized by CYP 2B6 enzymes and CYP 2B^8^ allele significantly alter ketamine metabolism. In addition, ketamine exerts most of its effects by inhibiting the N-methyl-D-aspartate receptor (NMADR), and NMDAR genes (GRIN2B) are associated with learning and memory impairment and schizophrenia.</p> <p>Purpose: To investigate the relationship between CYP2B6*6 and GRIN2B single nucleotide polymorphisms (SNPs) and ketamine-induced emergence phenomena (EP).</p> <p>Methods: This cross-sectional pharmacogenetic study recruited 75 patients having minor orthopedic, hand, foot, anorectal surgeries from two outpatient surgical centers. EP was measured with the Clinician Administered Dissociative State Scale (CADSS). DNA was genotyped using standard Taqman assays and protocols. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 & rs1806191) SNPs and ketamine induced EP occurrence and severity were tested using multivariate logistic and linear regression, adjusting for age, ketamine dose, duration of anesthesia, and time since ketamine administration.</p> <p>Results: Forty-seven patients (63%) received ketamine and were genotyped. Nineteen EP cases were identified (CADSS > 4), leaving 28 non-EP controls. For our population, CADSS has an internal consistency reliability Cronbach’s alpha of 0.82, and could reliably distinguish ketamine from non-ketamine cases. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p > 0.1). Models removing genotype and containing age, ketamine dose, duration of v anesthesia, and time since ketamine administration significantly predicted EP occurrence (p = 0.001) and severity (p = 0.007). Presence and severity of EP did not affect patient satisfaction with care.</p> <p>Discussion: Younger age, higher dose and longer duration of anesthesia significantly predicted EP occurrence and severity among our sample. This study provides effect size estimates useful for the design of adequately powered future genetic association studies. The feasibility of recruitment from patients undergoing elective, outpatient surgeries and ease of post-operative EP assessment with CADSS supports our approach. However, the small sample size may have limited about ability to determine significant differences.</p> <p>Conclusion: Fully powered studies are needed to investigate this important phenomena. Determining factors for anesthesia-related EP symptoms may reduce risks and costs associated with this adverse medication effect.</p>
dc.identifier.submissionpathgsn_diss/43
dc.contributor.departmentGraduate School of Nursing


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Copyright by Edwin N. Aroke 2016. All Rights Reserved.
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