RESUMO
Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown. Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function. A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04). There were no differences between clonidine and placebo among patients with COMT low-activity alleles. Similar gene-drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine-COMT interaction effects in other conditions.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Catecol O-Metiltransferase/genética , Clonidina/uso terapêutico , Síndrome de Fadiga Crônica/tratamento farmacológico , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Criança , Clonidina/efeitos adversos , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/enzimologia , Síndrome de Fadiga Crônica/genética , Feminino , Estudos de Associação Genética , Homozigoto , Humanos , Masculino , Noruega , Intolerância Ortostática/induzido quimicamente , Intolerância Ortostática/enzimologia , Intolerância Ortostática/genética , Farmacogenética , Fenótipo , Qualidade de Vida , Medição de Risco , Fatores de Risco , Sono/efeitos dos fármacos , Resultado do TratamentoRESUMO
PURPOSE: Early ambulation is essential for rapid functional recovery after surgery; however, orthostatic intolerance may delay recovery and cause syncope, leading to potential serious complications such as falls. Opioids may contribute to orthostatic intolerance because of reduced arterial pressure and associated reduction in cerebral blood flow and oxygenation. This study aimed to examine the effect of postoperative continuous infusion of fentanyl on orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery. METHODS: In this retrospective cohort study, data from 195 consecutive patients who underwent gynecologic laparoscopic surgery were analyzed to evaluate the association between postoperative continuous infusion of fentanyl and the incidence of orthostatic intolerance or delayed ambulation. The primary outcome was defined as delayed ambulation, an inability to ambulate on postoperative day 1. The secondary outcome was defined as orthostatic intolerance and symptoms associated with ambulatory challenge, including dizziness, nausea and vomiting, feeling hot, blurred vision, and eventual syncope. Multivariate logistic regression was used to determine the independent predictors of delayed ambulation and orthostatic intolerance. RESULTS: There were 24 cases with documented orthostatic intolerance and 5 with delayed ambulation. After multivariate logistic regression modeling, postoperative continuous infusion of fentanyl was found to be significantly associated with both orthostatic intolerance [adjusted odds ratio (95% confidence interval), 34.78 (11.12-131.72)] and delayed ambulation [adjusted odds ratio (95% confidence interval), 8.37 (1.23-72.15)]. CONCLUSION: Postoperative continuous infusion of fentanyl is associated with increased orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery.