Effect Of Dexmedetomidine On The EC₅₀ Of Propofol Target-controlled Infusion For Respiratory Depression

BackgroudPropofol is widely used for the induction and maintenance in clinical anesthesia and sedation in out-patient clinic, neuraxial anesthesia and nerve blocking anesthesia for its short-acting and non-accumulation characteristics.The technique of target-controlled infusion(TCI) was an intravenous infusion system controlled by computer and based on pharmacokinetic-pharmacodynamic principle, it was a smart semi-automic regulative drug delivery system which was targeted for plasma or effect-site concentration of patient. TCI enable the plasma concentration or effect-site concentration to reach the setting concentration rapidly and keep the anesthesia and sedation stability. The technique of propofol TCI was convenient and could keep the hemodynamics stability, so it was widely used in clinical anesthesia.Dexmedetomidine (DEX), the pharmacologically active dextroisomer of medetomidine, an efficient and highly selective alpha-2 adrenoceptor agonist, was recently introduced into clinical practice(clinical anesthesia and intensive care unit) for its sedative, analgesic, and sympatholytic properties, with few adverse effect. Reports indicated that dexmedetomidine decreased opioids or sedatives requirements during surgery, restrained the stress reaction of patients during the tracheal intubation, lowered the intraocular pressure, reduced the incidence of restlessness, nausea and vomiting during emergence and recovery from anaesthesia, and provided postoperative analgesia. It is a perspective adjunctive anesthetics. When administered combining with propofol, dexmedetomidine decreased the dose of propofol for induction and maintenance for clinical anaesthesia, and decreased the target plasma concentration of propofol TCI. However, up to now, conclusions of research on the effect of dexmedetomidine on respiratory function showed contrary because of the difference among the research methods and the dosage of dexmedetomidine, or the effect of the drug combination .Thus, the aim of present study is to measure the EC50 of propofol administered by target-controlled infusion for respiratory depression, and determine the effect of systemic dexmedetomidine on the EC50 of propofol using target-controlled infusion for respiratory depression.Effect of Dexmedetomidine on the EC50 of propofol target-controlled infusion for respiratory depressionObjectiveTo determine the effect of systemic dexmedetomidine on the EC50 of propofol target-controlled infusion for respiratory depression with Dixon up-and-down method, and to evaluate the safety of systemic administering dexmedetomidine with propofol during clinical practice.Methods56 ASAâ… -â…¡patients aged 18⁵5 yrs, weighing 52⁷4 kg scheduled for elective surgery were randomly allocated to receive dexmedetomidine(Dexmedetomidine group, group D) and sodium chloride(Control group, group C) before propofol TCI. Respiratory function was monitored by side stream method ( FiO2:1.0 ) with Detex-Ultima breathing mechanics monitoring device. The depth of sedation was assessed using observer assessment of the alertness/sedation scale(OAA/S) and the value of BIS. 27 patients in the group D received intravenous infusion of 0.4μɡ/kg dexmedetomidine (which was diluted to 5ml with normal saline) and 29 patients in the group C received intravenous infusion of 5ml normal saline for 5 minutes. 10 minutes later propofol TCI was administrated. BIS, HR, SBP, DBP, ECG, VT, MV, PETCO₂, RR, SpO₂ were monitored. BIS, OAA/S were recorded before drug delivery(T₀) , 1min(T_d1),5min(T_d5) and 10min(T_d10)after dexmedetomidine infusion and 1min(T₁),5min(T₅) after propofol TCI and termination of the study. A target-controlled infusion of propofol was commenced at a target determined by the response of the previous patient in the group (Dixon up-and-dowm method). The target propofol plasma concentration in the first patient was set to 3μɡ/ml. Subsequent target concentration was increased or decreased by 0.1μɡ/ml, on the basis of the response of the previous patientin in the group. Time was allowed for effect-site concentration to equal target pasma concentration. A positive response was recorded if the patient showed respiratory depression. The study was terminated when the patient showed respiratory depression or 15 minutes after the propofol TCI. The routine anesthesia was then followed in order to satisfied the operation condition. The EC50 and confidence interval was calculated.ResultsThere were 22 and 19 patients were enrolled into for calculating EC50 and confidence interval in group C and group D respectively. EC₅₀ of propofol TCI for respiratory depression was 2.62μg/ml (95%confidence interval was 2.53².72μɡ/ml) of the patients in group C and 2.35μɡ/ml (95% confidence interval was 2.31².38μɡ/ml) of the patients in group D, The EC50 of propofol TCI for respiratory depression in group D was lower than it in group C(P<0.05). The incidence of bradycardia and hypotension of the patients in group D were 31.6% and 21.1% respectively , and hypotension was found in one patient in group C. The BIS value and OAA/S of patients in group D were lower than those in group C(P<0.05).Conclusions0.4μɡ/kg dexmedetomidine given intravenously before propofol target-controlled infusion decreased the propofol EC50 for respiratory depression,and increased the depth of sedation. It is necessary to decrease the plasma target concentration of propofol TCI and reinforce monitoring when propofol was used combining with dexmedetomidine intravenous infusion.