RESUMO
The use of sedation for diagnostic procedures including gastrointestinal endoscopy is rapidly growing. Recovery of cognitive function after sedation is important because it would be important for most patients to resume safe, normal life soon after the procedure. Computerized tests have shown being accurate descriptors of cognitive function. The purpose of the present study was to evaluate the time course of cognitive function recovery after sedation with propofol and remifentanil. A prospective observational double blind clinical study conducted in 34 young healthy adults undergoing elective outpatient colonoscopy under sedation with the combination of propofol and remifentanil using a target controlled infusion system. Cognitive function was measured using a validated battery of computerized cognitive tests (Cogstate™, Melbourne, Australia) at different predefined times: prior to starting sedation (Tbaseline), and then 10 min (T10), 40 min (T40) and 120 min (T120) after the end of colonoscopy. Tests included the assessment of psychomotor function, attention, visual memory and working memory. All colonoscopies were completed (median time: 26 min) without significant adverse events. Patients received a median total dose of propofol and remifentanil of 149 mg and 98 µg, respectively. Psychomotor function and attention declined at T10 but were back to baseline values at T40 for all patients. The magnitude of psychomotor task reduction was large (d = 0.81) however 100% of patients were recovered at T40. Memory related tasks were not affected 10 min after ending sedation. Cognitive impairment in attention and psychomotor function after propofol and remifentanil sedation was significant and large and could be easily detected by computerized cognitive tests. Even though, patients were fully recovered 40 min after ending the procedure. From a cognitive recovery point of view, larger studies should be undertaken to propose adequate criteria for discharge after sedation.
Assuntos
Cognição/efeitos dos fármacos , Colonoscopia , Sedação Profunda/métodos , Propofol/administração & dosagem , Remifentanil/administração & dosagem , Idoso , Anestesia , Período de Recuperação da Anestesia , Anestésicos Intravenosos/administração & dosagem , Diagnóstico por Computador , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Tamanho da Amostra , Software , Adulto JovemRESUMO
Respiratory depression is a common adverse effect of propofol and remifentanil. We aimed to develop a model for respiratory depressant effects of propofol with remifentanil in patients undergoing endoscopy with sedation. Data were available for 136 patients undergoing endoscopy with sedation. Participants randomly received infusions of propofol and remifentanil. Predicted plasma concentrations, outputted by infusion pumps, were available. Transcutaneous arterial pressure of carbon dioxide (pCO2) was measured. Data were analyzed using nonlinear mixed-effects modeling methods. Covariate relationships were investigated for age, noxious stimuli (endoscopy tube insertion), and A118G genotype for the µ-opioid receptor (OPRM1). Participants had a median (range) age of 64.0 (25.0-88.0) years, weight of 70.0 (35.0-98.0) kg, and height of 164.0 (147.0-190.0) cm. Seven percent were recessive homozygous for OPRM1 polymorphism. An indirect-effect model with a "modulator" compartment best described pCO2 data (P < 0.001) over a direct-effect model. Remifentanil inhibited pCO2 removal with an IC50 of 1.13 ng/ml and first-order rate constant (ke 0) of 0.28 minute(-1). Propofol affected the modulator compartment with an IC50 of 4.97 µg/ml (no effect-site compartment). Propofol IC50 and remifentanil ke 0 were reduced with increasing age. Noxious stimuli and genotype were not significant covariates. An indirect-effect model with a rebound mechanism can describe remifentanil- and propofol-induced changes in pCO2 in patients undergoing noxious procedures. The model may be useful for identifying optimal dosing schedules for these drugs in a combination that provides adequate sedation but avoids respiratory depression.