Effect of CYB2B6 (c.516G>T), CYP2C9 (c.1075A>C) and UGT1A9 (c.98T>C) polymorphisms on propofol pharmacokinetics in patients submitted to colonoscopy: a cohort study.

BACKGROUND: The aim of this study was to investigate the effect of CYB2B6 (c.516G>T, rs3745274), CYP2C9 (c.1075A>C, rs1057910) and UGT1A9 (c.98T>C, rs72551330) polymorphisms on the pharmacokinetics of single-drug propofol in adult patients undergoing intravenous sedation. METHODS: In this prospective clinical study, a total of 124 patients undergoing anaesthesia with propofol, as a single drug, were evaluated when undergoing colonoscopy procedure. Clinical variables were obtained from the patient's anamnesis prior to performing the anaesthetic procedure, in the moment of the patient's loss of consciousness, during the colonoscopy exam (recorded every 5 min) and in the awakening time. RESULTS: Polymorphic genotypes for the rs3745274 and rs1057910 polymorphisms were associated with bispectral index, target-controlled infusion (TCI)/effector concentration of propofol and TCI/plasma concentration of propofol values. Based on multivariate analysis, it was observed that weight, age, surgery time, systolic blood pressure and the rs1057910 polymorphism corresponded to predictive values for the dose of propofol used. Weight (B = 4.807±0.897), age (B = 1.834±0.834) and duration of surgery (B = 8.164±1.624) corresponded to factors associated with increased propofol dose, while systolic blood pressure (B = -1.892±0.679) and the genotypes (AA vs CA) of the single nucleotide polymorphism (SNP) rs1057910 CYPP2C9 gene (B = -74.161±26.820) decreased the total dose of propofol used. CONCLUSION: We concluded that the rs1057910 and rs3745274 polymorphisms affect the metabolism of propofol in patients exclusively submitted to this drug. Thus, the knowledge of the polymorphic genotypes of the CYPP2C9 and CYB2B6 genes may be predictive of different metabolising phenotypes, suggesting expected behaviours of BIS parameter in the anaesthetic procedure, which contributes to safer monitoring by anaesthesiologists during the clinical intervention.

Effect of CYB2B6 (c.516G>T), CYP2C9 (c.1075A>C) and UGT1A9 (c.98T>C) polymorphisms on propofol pharmacokinetics in patients submitted to colonoscopy: a cohort study.

BACKGROUND: The aim of this study was to investigate the effect of CYB2B6 (c.516G>T, rs3745274), CYP2C9 (c.1075A>C, rs1057910) and UGT1A9 (c.98T>C, rs72551330) polymorphisms on the pharmacokinetics of single-drug propofol in adult patients undergoing intravenous sedation. METHODS: In this prospective clinical study, a total of 124 patients undergoing anaesthesia with propofol, as a single drug, were evaluated when undergoing colonoscopy procedure. Clinical variables were obtained from the patient's anamnesis prior to performing the anaesthetic procedure, in the moment of the patient's loss of consciousness, during the colonoscopy exam (recorded every 5 min) and in the awakening time. RESULTS: Polymorphic genotypes for the rs3745274 and rs1057910 polymorphisms were associated with bispectral index, target-controlled infusion (TCI)/effector concentration of propofol and TCI/plasma concentration of propofol values. Based on multivariate analysis, it was observed that weight, age, surgery time, systolic blood pressure and the rs1057910 polymorphism corresponded to predictive values for the dose of propofol used. Weight (B = 4.807±0.897), age (B = 1.834±0.834) and duration of surgery (B = 8.164±1.624) corresponded to factors associated with increased propofol dose, while systolic blood pressure (B = -1.892±0.679) and the genotypes (AA vs CA) of the single nucleotide polymorphism (SNP) rs1057910 CYPP2C9 gene (B = -74.161±26.820) decreased the total dose of propofol used. CONCLUSION: We concluded that the rs1057910 and rs3745274 polymorphisms affect the metabolism of propofol in patients exclusively submitted to this drug. Thus, the knowledge of the polymorphic genotypes of the CYPP2C9 and CYB2B6 genes may be predictive of different metabolising phenotypes, suggesting expected behaviours of BIS parameter in the anaesthetic procedure, which contributes to safer monitoring by anaesthesiologists during the clinical intervention.

High risk pregnancy referrals adequacy in the Basic Health Services of Sobral, Ceará, Brazil / Adequação dos encaminhamentos de gestações de alto risco na Rede Básica de Atenção à Saúde de Sobral, Ceará, Brasil

Objective: To describe the appropriateness of referrals of high-risk pregnancies in the basic healthcare network of Sobral, in Ceará, Brazil. Methods: A descriptive quantitative study. The medical files of 173 pregnant patients referred to the high-risk outpatient clinic of Centro de Especialidades Médicas of Sobral, during the period from July 2006 to April 2007, were analyzed. Variables analyzed were correctness of the referrals, professionals who made them, causes and origins of the referrals, and age bracket of the patients referred. The referrals were divided into ?appropriate? and ?inappropriate?, according to the classification of risk established by the technical manual of the Ministry of Health. Results: Of the 173 cases, 102 (59%) were considered appropriate/correct, and 71 (41%) referrals were considered inappropriate/incorrect. The referrals were divided according to the professional class of the referring individuals: physicians or nurses. Of the 173 referrals, 49 (28.3%) were made by physicians, and 124 (71.7%) by nurses. Of the 49 patients referred by physicians, 39 (79.6%) were considered correct. Of the 124 referrals made by nurses, 63 (50.8%) were considered incorrect, revealing a significant difference between the groups (p < 0.00001). The most common causes of referrals of pregnant patients were hypertensive syndromes (23.6%), physiological modifications of pregnancy (22.6%), prolonged pregnancy (15.1%), and diabetes (12.3%). Conclusions: There was a low rate of appropriate/correct referrals. There is a need for training in the basic healthcare network for quality prenatal care, with special emphasis on referring nurses.

Objetivo: Descrever a adequação dos encaminhamentos de gestações de alto risco na rede básica de atenção à saúde de Sobral, no Ceará, Brasil. Métodos: Estudo descritivo, de natureza quantitativa. Foram revisados 173 prontuários de gestantes referenciadas ao ambulatório de alto risco do Centro de Especialidades Médicas de Sobral, no período de Julho de 2006 a Abril de 2007. As variáveis analisadas foram: adequação dos encaminhamentos, profissional que encaminhou, causas e origem dos encaminhamentos e faixa etária das gestantes referenciadas. Os encaminhamentos foram divididos em “adequados” e “inadequados”, segundo a classificação de risco estabelecido pelo manual técnico do Ministério da Saúde. Resultados: Dos 173, 102 (59%) foram considerados adequados e 71 (41%) encaminhamentos inadequados. Os encaminhamentos foram divididos conforme a classe profissional que referenciou: médicos ou enfermeiros. Dos 173 encaminhamentos, 49 (28,3%) foram por médicos e 124 (71,7%) por enfermeiros. Dos 49 encaminhados por médicos, 39 (79,6%) foram adequados. Dos 124 encaminhamentos por enfermeiros, 63 (50,8%) foram adequados, sendo observada diferença significante entre os grupos (p < 0,00001). As causas mais frequentes de encaminhamentos das gestantes foram: síndromes hipertensivas (23,6%), alterações fisiológicas da gestação (22,6%), gravidez prolongada (15,1%) e diabetes (12,3%). Conclusões: Houve baixa adequação de encaminhamentos. Há necessidade de capacitação dos serviços da rede básica para realização de pré-natal com qualidade, com ênfase especial aos referenciadores enfermeiros.