Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author SILVA-FILHO, Carlos R.
BARBOSA, Ricardo Antonio G. FMUSP-HC
SILVA- JR., Carlindo V.
MALBOUISSON, Luiz M. S. FMUSP-HC
CARMONA, Maria Jose C. FMUSP-HC
JORGE-SANTOS, Silvia Regina C.
dc.date.issued 2018
dc.identifier.citation CLINICS, v.73, 2018
dc.identifier.issn 1807-5932
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/26217
dc.description.abstract OBJECTIVES: The objective of this study was to apply a pharmacokinetics-pharmacodynamics approach to investigate the free propofol plasma levels in patients undergoing coronary artery bypass grafting under hypothermic conditions compared with the off-pump procedure. METHODS: Nineteen patients scheduled for on-pump coronary artery bypass grafting under hypothermic conditions (n=10) or the equivalent off-pump surgery (n=9) were anesthetized with sufentanil and propofol target-controlled infusion (2 mg/mL) during surgery. The propofol concentration was then reduced to 1 mu g/mL, and a pharmacokinetics-pharmacodynamics analysis using the maximum-effect-sigmoid model obtained by plotting the bispectral index values against the free propofol plasma levels was performed. RESULTS: Significant increases (two-to five-fold) in the free propofol plasma levels were observed in the patients subjected to coronary artery bypass grafting under hypothermic conditions. The pharmacokinetics of propofol varied according to the free drug levels in the hypothermic on-pump group versus the off-pump group. After hypothermic coronary artery bypass was initiated, the distribution volume increased, and the distribution half-life was prolonged. Propofol target-controlled infusion was discontinued when orotracheal extubation was indicated, and the time to patient extubation was significantly higher in the hypothermic on-pump group than in the off-pump group (459 versus 273 min, p=0.0048). CONCLUSIONS: The orotracheal intubation time was significantly longer in the hypothermic on-pump group than in the off-pump group. Additionally, residual hypnosis was identified through the pharmacokinetics-pharmacodynamics approach based on decreases in drug plasma protein binding in the hypothermic on-pump group, which could explain the increased hypnosis observed with this drug in this group of patients.
dc.language.iso eng
dc.publisher HOSPITAL CLINICAS, UNIV SAO PAULO
dc.relation.ispartof Clinics
dc.rights openAccess
dc.subject Coronary Artery Bypass; Cardiopulmonary Bypass; Propofol; Protein Binding; Pharmacokinetics; Pharmacodynamics
dc.subject.other performance liquid-chromatography; controlled infusion; cardiac-surgery; protein-binding; parameter sets; drug; fraction
dc.title Application of a pharmacokinetics-pharmacodynamics approach to the free propofol plasma levels during coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass
dc.type article
dc.rights.holder Copyright HOSPITAL CLINICAS, UNIV SAO PAULO
dc.description.group LIM/08
dc.identifier.doi 10.6061/clinics/2018/e178
dc.identifier.pmid 29451620
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author BARBOSA, Ricardo Antonio G.:HC:ICHC
hcfmusp.author MALBOUISSON, Luiz M. S.:HC:ICHC
hcfmusp.author CARMONA, Maria Jose C.:FM:MCG
hcfmusp.author.external · SILVA-FILHO, Carlos R.:Univ Sao Paulo, Fac Ciencias Farmaceut, Sao Paulo, SP, Brazil
· SILVA- JR., Carlindo V.:Univ Sao Paulo, Fac Ciencias Farmaceut, Sao Paulo, SP, Brazil
· JORGE-SANTOS, Silvia Regina C.:Univ Sao Paulo, Fac Ciencias Farmaceut, Sao Paulo, SP, Brazil
hcfmusp.origem.id WOS:000425353700001
hcfmusp.origem.id 2-s2.0-85042375634
hcfmusp.origem.id SCIELO:S1807-59322018000100202
hcfmusp.publisher.city SAO PAULO
hcfmusp.publisher.country BRAZIL
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dc.description.index MEDLINE
dc.identifier.eissn 1980-5322
hcfmusp.citation.scopus 0
hcfmusp.citation.wos 0
hcfmusp.affiliation.country Brasil


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