Influência dos receptores opioides no efeito hipotensor arterial do propofol em humanos

Abstract

Propofol is a sedative-hypnotic drug widely used in anesthesiology due to its high hypnotic efficiency and a rapid awakening practically free of residual effects. Cardiovascular depression, which is the most important and undesirable side effect of propofol, seems to be closely related to the administered dose, drug injection speed, age and physical condition of patients as well as their blood volume and cardiovascular reserve and can be intensified also by the association of an opioid drug to propofol. Propofol-induced hypotension (PIH) seems to have a multifactorial origin, as has been evidenced the participation of several systems in the effects produced by propofol, including the participation of opioid via the analgesic effect of the drug. Therefore, the objective of this study was to demonstrate the involvement of the opioid system in the origin of PIH in humans. The design of the study was randomized, cross-sectional, open and comparative. It included 40 adults, ASA physical status 1, submitted to general anesthesia for elective surgery. The outcomes evaluated in this study were the systolic (SBP), diastolic (DBP) and mean (MAP), central venous pressure (CVP) and heart rate (HR). Therefore, after the continuous monitoring of patients with cardioscopy with ST analyses, invasive blood pressure, central venous pressure, oxicapnometria, EEG bispectral analysis (BIS) and arterial and venous blood gases, these were divided randomly through computer-generated randomization schedule in accordance with the 5 studied groups (n = 8 for all groups). PC group received saline, and premedicated groups PN1 e PN3 received naloxone, 1 or 3 μg/kg iv, respectively, in T0 and 2,5 mg/kg of propofol iv in T2. The controls of response to naloxone; and premedicated with naloxone 1 or 3 μg/Kg in T0 (NC1 e NC3); and did not receive propofol in T2. The results showed that PIH was composed of a quick and initial opioid-independent reduction of MAP and a slow late reduction of MAP, which was at least partially, dependent on opioid action. Propofol 2.5 mg/Kg iv significantly reduced SAP, DAP and MAP in an independent way of hypnotic effect, initial CVP values or changes in patient s HR, despite the occurrence of baroreflex inhibition. However, this late hypotensive effect of propofol could be reduced by a prior administration of intravenous naloxone, which the lowest effective dose was of 3 μg/Kg. The effect of naloxone on MAP occurred by a significant increase of DAP, and it was produced independently of important modifications in patients SAP, HR, CVP, BIS or ECG. In conclusion, PIH has a multifactorial origin, in part produced by a mechanism that is opioid-dependent and sensitive to the pretreatment with naloxone. Our study received no external funding.