Plasma Concentrations Of Remifentanil Research Articles

Changes in the plasma protein-binding rate of remifentanil during cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) reduces the plasma protein-binding rate of some anaesthetics and can enhance their pharmacological effects by increasing the unbound drug fraction. However, whether these changes occur with remifentanil remains to be explored. We investigated the changes in the protein-binding rate of remifentanil during CPB compared with propofol. Thirteen patients (≥18 years old) who were scheduled to undergo cardiovascular surgery with CPB were included. Arterial blood samples were collected to measure the plasma concentrations of remifentanil and propofol before CPB (T1), 30 (T2) and 60 (T3) minutes after the start of CPB, and 30 min after CPB discontinuation (T4). The samples were immediately centrifuged to separate the plasma after blood collection. Equilibrium dialysis was used to separate the unbound fraction. The remifentanil and propofol concentrations were measured by liquid chromatography-mass spectrometry. The protein-binding rate was calculated based on the total and unbound fraction of each drug. The remifentanil protein-binding rates at each time point were 27.9% ± 11.2% (T1), 13.5% ±4.4% (T2), 14.0% ±3.3% (T3) and 24.5% ±6.9% (T4). The propofol protein-binding rates were 97.5% ±0.7% (n = 4; T1), 95.8% ±1.4% (T2), 95.3% ±1.3% (T3) and 95.8% ±1.1% (T4). The protein binding rates of both drugs decreased during CPB and reversed after CPB. The change in the unbound fraction was 1.2-fold for remifentanil and 1.7-1.9-fold for propofol. Unlike propofol, remifentanil might not demonstrate significantly enhanced pharmacological effects during CPB.

Prolonged Anesthesia Induction to Delivery Time Did Not Influence Plasma Remifentanil Concentration in Neonates.

Remifentanil, in combination with etomidate and sevoflurane, is commonly used in clinics for general anesthesia induction in cesarean section (CS). This study aimed to evaluate the correlation between the induction to delivery (I-D) time and neonatal plasma drug concentration and anesthesia, as well as its effects on neonates. Fifty-two parturients in whom general anesthesia was induced for CS were divided into group A (I-D<8 min) and group B (I-D≥8 min). Maternal arterial (MA), umbilical venous (UV), and umbilical arterial (UA) blood samples were collected at delivery to analyze the remifentanil and etomidate concentrations using liquid chromatography-tandem mass spectrometry. There were no statistically significant differences between the two groups in terms of plasma concentrations of remifentanil in the MA, UA, and UV blood (P > 0.05). The plasma concentration of etomidate in MA and UV was higher in group A than that in group B (P<0.05), whereas the UA/UV ratio of etomidate was higher in group B than that in group A (P<0.05). The Spearman rank correlation test showed no correlation between the I-D time and plasma remifentanil concentration in the MA, UA, and UV plasma (P>0.05). The concentrations of etomidate in the MA and UV were negatively correlated with the I-D time (P < 0.05). Prolonged I-D time did not significantly influence the maternal or neonatal plasma concentration of remifentanil. It is safe to administer remifentanil target-controlled infusion in combination with etomidate and sevoflurane for general anesthesia induction during CS.

Effects of remifentanil on brain responses to noxious stimuli during deep propofol sedation

BackgroundThe safety of anaesthesia has improved as a result of better control of anaesthetic depth. However, conventional monitoring does not inform on the nature of nociceptive processes during unconsciousness. A means of inferring the quality of potentially painful experiences could derive from analysis of brain activity using neuroimaging. We have evaluated the dose effects of remifentanil on brain response to noxious stimuli during deep sedation and spontaneous breathing. MethodsOptimal data were obtained in 26 healthy subjects. Pressure stimulation that proved to be moderately painful before the experiment was applied to the thumbnail. Functional MRI was acquired in 4-min periods at low (0.5 ng ml−1), medium (1 ng ml−1), and high (1.5 ng ml−1) target plasma concentrations of remifentanil at a stable background infusion of propofol adjusted to induce a state of light unconsciousness. ResultsAt low remifentanil doses, we observed partial activation in brain areas processing sensory-discriminative and emotional-affective aspects of pain. At medium doses, relevant changes were identified in structures highly sensitive to general brain arousal, including the brainstem, cerebellum, thalamus, auditory and visual cortices, and the frontal lobe. At high doses, no significant activation was observed. ConclusionsThe response to moderately intense focal pressure in pain-related brain networks is effectively eliminated with safe remifentanil doses. However, the safety margin in deep sedation-analgesia would be narrowed in minimising not only nociceptive responses, but also arousal-related biological stress.

The optimal plasma concentration of remifentanil for target-controlled infusion to suppress extubation response in obese patients

Objective To investigate the optimal plasma concentration of remifentanil for target-controlled infusion (TCI) to inhibit extubation response in obese patients under general anesthesia. Methods A total of 70 obese patients, at ASA gradeⅠ, Ⅱ and with BMI of 30-35 kg/m2, were randomly divided into control group (n=20) and experimental group (n=50) undergoing elective anesthesia with laparoscopic cholecystectomy. The modified Dixon sequential method was used in the experimental group, and the median effective concentration (EC50) of remifentanil and its 95%CI were calculated with probit probability regression analysis. The extubation time in patients subjected to remifentanil at different concentrations for TCI was recorded and compared with that in the control group. Results The EC50 of plasma remifentanil for TCI to inhibit extubation reaction was 1.58 μg/L (95%CI was 1.40-1.81 μg/L) in obese patients under general anesthesia. The extubation time in patients received 1.40-1.81 μg/L remifentanil for TCI (8.5±0.4) min did not differ from that in control group (8.3±0.6) min (P>0.05). Conclusions Remifentanil at concentration of 1.58 μg/L for TCI inhibited extubation reaction but without affecting the extubation time in obese patients under general anesthesia. Key words: Remifentanil; Target controlled infusion; Extubation response; Median effective concentration

Performance of the Minto model for the target-controlled infusion of remifentanil during cardiopulmonary bypass.

We studied the predictive performance of the Minto pharmacokinetic model during cardiopulmonary bypass in patients undergoing cardiac surgery. Patients received remifentanil target-controlled infusion using the Minto model during total intravenous anaesthesia with propofol. From 56 patients, 275 arterial blood samples were drawn before, during and after bypass to determine the plasma concentration of remifentanil, and the predicted concentrations were recorded at each time. For pooled data, the median prediction error and median absolute prediction error were 21.3% and 21.8%, respectively, and 22.1% and 22.3% during bypass. Both were 148.4% during hypothermic circulatory arrest and measured concentrations were more than three times greater than predicted (26.9 (17.0) vs. 7.1 (1.6) ng.ml-1 ). The Minto model showed considerable bias but overall acceptable precision during bypass. The target concentration of remifentanil should be reduced when using the Minto model during hypothermic circulatory arrest.

Efecto de dos concentraciones plasmáticas de remifentanilo a través de TACAN sobre la frecuencia e intensidad de la tos durante la extubación: ensayo clínico controlado aleatorizado

IntroductionCough at the time of extubation may trigger anaesthesia-related adverse events. A technique that has been found to limit cough during this stage of the anaesthesia procedure is the use of remifentanil. ObjectiveTo compare cough frequency and intensity at the time of extubation with two different plasma concentrations of remifentanil, 3-4ng/ml and 2-3ng/ml, using target controlled anaesthesia. Materials and methodsRandomised controlled clinical trial carried out at the Institute for Blind and Deaf Children in Valle del Cauca, in patients taken to elective ear surgery. Patients were randomly assigned to one of two groups. The first group (T) received an infusion of remifentanil at a plasma concentration of 3-4ng/ml (n=50). The second group (U) received an infusion of remifentanil at a plasma concentration of 2-3ng/ml (n=51). Data were analysed using the Student t test and the non-parametric Mann Whitney U test; the Chi square test was used for determining associations. ResultsCough intensity and frequency were less in group T compared to group U (OR: 3.73; 95% CI: 1.3-10.7), and there was no difference between the two groups regarding emergence from anaesthesia. ConclusionsThe presence of at least one cough episode during extubation is less with plasma concentrations of remifentanil of 3-4ng/ml than 2-3ng/ml.

Effect on cough frequency and intensity during extubation of two plasma concentrations of remifentanil using TACAN: Randomised controlled clinical trial

IntroductionCough at the time of extubation may trigger anaesthesia-related adverse events. A technique that has been found to limit cough during this stage of the anaesthesia procedure is the use of remifentanil. ObjectiveTo compare cough frequency and intensity at the time of extubation with two different plasma concentrations of remifentanil, 3–4ng/ml and 2–3ng/ml, using target controlled anaesthesia. Materials and methodsRandomised controlled clinical trial carried out at the Institute for Blind and Deaf Children in Valle del Cauca, in patients taken to elective ear surgery. Patients were randomly assigned to one of two groups. The first group (T) received an infusion of remifentanil at a plasma concentration of 3–4ng/ml (n=50). The second group (U) received an infusion of remifentanil at a plasma concentration of 2–3ng/ml (n=51). Data were analysed using the Student t test and the non-parametric Mann Whitney U test; the Chi square test was used for determining associations. ResultsCough intensity and frequency were less in group T compared to group U (OR: 3.73; 95% CI: 1.3–10.7), and there was no difference between the two groups regarding emergence from anaesthesia. ConclusionsThe presence of at least one cough episode during extubation is less with plasma concentrations of remifentanil of 3–4ng/ml than 2–3ng/ml.

Preliminary Intraoperative Validation of the Nociception Level Index: A Noninvasive Nociception Monitor.

The nociception level (NoL) index is an index of nociception based on nonlinear combination of heart rate, heart rate variability, photoplethysmograph wave amplitude, skin conductance, skin conductance fluctuations, and their time derivatives. The authors evaluated the abilities of the NoL index and other measures of nociception to discriminate between noxious and nonnoxious stimuli, to progressively respond to graded stimuli, and to respond to opioid administration. Intraoperative NoL was compared to heart rate, pulse plethysmograph amplitude, noninvasive blood pressure, and the surgical pleth index around five specific stimuli: tetanic stimulation with and without fentanyl analgesia, intubation, first incision/trocar insertion, and a nonnoxious period. The response around first incision was analyzed at two target plasma concentrations of remifentanil. In 58 patients, the NoL index responded progressively to increased stimulus intensity and remained unchanged in response to nonnoxious stimuli. Compared to other accepted measures of nociception, the NoL index better discriminated noxious from nonnoxious stimuli with an area under the curve of 0.93 (95% CI, 0.89 to 0.97) and a sensitivity of 87% at a specificity of 84%. The NoL index was the only measure that reliably reflected two different analgesic concentrations of remifentanil during initial skin incision or trocar insertion. The NoL index changes proportionately with patients' response to various clinical and experimental noxious stimuli and discriminates noxious from nonnoxious stimuli with high sensitivity and specificity. The NoL index also responds progressively to increasing stimuli intensity and is appropriately blunted by analgesic administration. The NoL index was superior to other compared measures and appears to accurately characterize nociception during general anesthesia.

Effects of different remifentanil target concentrations on MAC BAR of sevoflurane in gynaecological patients with CO2 pneumoperitoneum stimulus

To investigate the effects of different target plasma remifentanil concentrations on the minimum alveolar concentration of sevoflurane (MAC) for blocking adrenergic response (BAR) during laparoscopic gynaecological surgery with carbon dioxide insufflation. Seventy-five gynaecological patients with ASA I-II undergoing laparoscopic surgery were randomly assigned to three groups. Anaesthesia was induced by sevoflurane, and 0.1 mg kg(-1) of vecuronium i.v. was injected to facilitate tracheal intubation. After intubation the target plasma concentrations of remifentanil in Groups 1, 2, and 3 were adjusted to 0, 1, and 2 ng ml(-1), respectively. The changes in haemodynamics were observed before and after the creation of carbon dioxide pneumoperitoneum. The MAC BAR of sevoflurane in each group was determined by using an up-and-down sequential-allocation technique, and blood samples were collected at corresponding time points to determine the concentrations of remifentanil, norepinephrine, and epinephrine. In Groups 1, 2 and 3, the MAC BAR of sevoflurane was 4.6% (CI 95%: 4.3-4.9%), 2.4% (CI 95%: 2.2-2.6%), and 1.7% (CI 95%: 1.4-2.1%), respectively. No significant differences were found in the increase of norepinephrine, epinephrine, and mean arterial pressure after compared with before insufflation of pneumoperitoneum among the three groups. Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus. At similar MAC BAR the haemodynamic and adrenergic response is not affected by the infused remifentanil concentration. The number of this clinical trial registry is ChiCTR-TRC-13004005, and the Universal Trial Number is U1111-1151-5630.

Predication of plasma concentration of remifentanil based on Elman neural network

Due to the nature of ultra-short-acting opioid remifentanil of high time-varying, complex compartment model and low-accuracy of plasma concentration prediction, the traditional estimation method of population pharmacokinetics parameters, nonlinear mixed effects model (NONMEM), has the abuses of tedious work and plenty of man-made jamming factors. The Elman feedback neural network was built. The relationships between the patients’ plasma concentration of remifentanil and time, patient’ age, gender, lean body mass, height, body surface area, sampling time, total dose, and injection rate through network training were obtained to predict the plasma concentration of remifentanil, and after that, it was compared with the results of NONMEM algorithm. In conclusion, the average error of Elman network is −6.34%, while that of NONMEM is 18.99%. The absolute average error of Elman network is 27.07%, while that of NONMEM is 38.09%. The experimental results indicate that Elman neural network could predict the plasma concentration of remifentanil rapidly and stably, with high accuracy and low error. For the characteristics of simple principle and fast computing speed, this method is suitable to data analysis of short-acting anesthesia drug population pharmacokinetic and pharmacodynamics.

Effects of target controlled infusion of remifentanil during emergence on the recovery profiles of tracheal extubation from anaesthesia

Objective The trial was designed to examine the effects of target controlled infusion of remifentanil on recovery profiles such as cardiovascular responses and coughing after anaesthesia for thyroidectomy.Methods Eighty ASA Ⅰ or Ⅱ patients undergoing thyroidectomy surgery were randomly assigned to RF0.0 group,RF1.5 group,RF2.0 group,RF2.5 group.Each group contained 20 subjects.General anesthesia was maintained by total intravenous anesthesia (propofol and remifentanil).The target plasma concentrations of remifentanil were 0(RF0.0 group),1.5(RF1.5 group),2.0 (RF2.0 group),and 2.5 μg/L (RF2.5 group) during emergence from anesthesia.At the end of surgery,propofol was ceased.The infusion of remifentanil was stopped in RF0.0 group while maintained in the other 3 groups at a target plasma concentration of 1.5,2.0 μg/L or 2.5 μg/L till extubation.Heart rate (HR),mean arterial pressure (MAP),incidence and severity of coughing were recorded.Results The incidence and severity of coughing were lower in RF2.5 group and RF2.0 group compared with RF0.0 group(P＜0.05).MAP[(95±4),(87±4) mm Hg and(82±4) mm Hg (1 mm Hg=0.133 kPa)] and HR [(96.1±3.4),(85.2±3.0) and (79.9±2.4) bpm] values were significantly lower in the 3 groups rather than in RF0.0 group [MAP,(100±5) mm Hg and HR,(105±4) bpm] at the moment of tracheal extubation(P＜0.05).MAP [(100±3),(90±4) mm Hg and (86±4) mm Hg] and HR [(103±3),(92±3) bpm and (84±3) bpm] values were significantly lower in the 3 groups compared with the RF0.0 group [(100±5) mm Hg and(105±4) mm Hg] at 1 min after tracheal extubation(P＜0.05).MAP [(82.4±4.3) mm Hg and (85.7±4.0) mm Hg] and HR [(79.9±2.4) bpm and (84.4±3.3) bpm] values were significantly lower in RF2.5 group compared with RF1.5 group[(95±4) mm Hg and (100±3) mm Hg][(96.1±3.4) bpm and (103±3) bpm] or RF2.0 group [(87±4) mm Hg and (90±4) mm Hg] [(85.2±3.0) bpm and (92±3) bpm] at the moment or 1 min after tracheal extubation (P＜0.05).But time to eye opening and extubation were prolonged in RF2.5 group [(8.3±0.5) min and (11.6±0.7) min] compared with the RF0.0 group[(8.0±0.6) min and (9.8±0.5) min](P＜0.05).Conclusions Maintaining a remifentanil plasma concentration by TCI may reduce haemodynamic changes and incidence of coughing which associated with tracheal extubation in patients undergoing thyroidectomy.However,awakening may be delayed due to the relative higher remifentanil dose. Key words: Remifentanil; Target-controlled infusion; Tracheal extubation; Total intravenous anesthesia

Effects of different target remifentanil concentrations on MACBAR of sevoflurane and catecholamineRAR in gynecological patients undergoing laparoscopic surgery

Objective To investigate the effects of different targeted plasma remifentanil concentrations on the minimum alveolar concentration of sevoflurane (MACBAR) and minimum plasma catecholamine concentration for blocking adrenergic response (CatecholamineBAR: NEBR, EBAR) in gynecological patients undergoing laparoscopic surgery using carbon dioxide pneumoperitoneum.Methods Seventy five gynecological patients undergoing laparoscopic surgery, ASA physical status Ⅰ -Ⅱ, were randomly assigned to three groups: control group (R0) and 2 remifentanil groups (R1, R2). Anesthesia was induced by target controlled infusion with remifentanil (plasma concentration 2 μg/L), and intravenous infection with 0.3 mg/kg etomidate. Vecuronium 0.1 mg/kg was administered to facilitate tracheal intubation. After intubation anesthesia was maintained with sevoflurane in all groups. But in R0, R1and R2, the targeted plasma concentration of remifentanil was adjusted to 0, 1 μg/L and 2 μg/L, respectively. The MACBAR of sevoflurane was determined by using a sequential design and pneumoperitoneum stimulation in each group, while blood samples were collected at corresponding time points to determinate catecholamine concentrations and the values of NEBAR, EBAR were calculated.Results In group R0, R1 and R2, the MACBARs of sevoflurane were (4.60±0.30)％, (2.37±0.21) ％ and(1.70±0.28) ％, respectively.No significant differences were found in NEBAR, EBAR and minimum MAP among the three groups. Conclusion The targeted plasma concentrations of remifentanil at 1 μg/L and 2 μg/L can significantly reduce MACBAR of sevoflurane by 48％ and 63％ respectively in gynecological patients undergoing laparoscopic surgery. However, the value of catecholamineBAR was not influenced by the changes of remifentanil's target plasma concentration and the end-tidal sevoflurane concentration. Key words: Sevoflurane; Remifentanil; MAC ; Adrenergic response; Catecholamine; Pneumoperitoneum

Comparison of pharmacokinetics of remifentanil during general anesthesia in children and adults

Objective To compare the pharmacokinetics of remifentanil during general anesthesia in children and adults.Methods Eight children(4 male,4 female)and 8 adults(4 male,4 female),undergoing elective operation under general anesthesia,were randomly divided into 2 groups(n=8 each):group adults(aged 19-60 yr,weighing 45-81 kg)and group children(aged 10 months-7 yr,weighins 7.2-21.0 kg).Remifentanil 5μg/kg was injected intravenously during induction of anesthesia.Arterial blood samples 1.0 ml were taken at 1,2,3,5,7,10,15,20,25,30,45 and 60 min after injection for determination of the plasma concentrations of remifentanil.The pharmacokinetic parameters were calculated using software 3P97.Results Elimination half-life was significantly shorter and apparent volume of distribution and clearance were significantly greater in children than in adults(P 0.05).Conclusion There is difference in the pharmacokineties of remifentanil during general anesthesia between children and adults.The plasma concentration of remifentanil is lower in children than in adults after using the same dose,and the dose should be increased appropriately. Key words: Child; Adult; Piperidines; Pharmacokinetics

The influence of age and gender on remifentanil EC50for preventing rocuronium induced withdrawal movements

BackgroundRocuronium-induced withdrawal movements can be harmful to patients during the induction period. Remifentanil has been reported to reduce these movements effectively. In this study, we determined the EC50 of remifentanil for the prevention of rocuronium induced withdrawal movements in male, female, old and child group.MethodsWe included patients scheduled for general anesthesia and assigned them into 4 groups depending on their age and gender: male group (20-60 yr), female group (20-60 yr), old group (>65 yr) and child group (6-12 yr). Remifentanil was administered by target controlled infusion. Propofol 2 mg/kg was then administered after equilibration between the effect and plasma concentration of remifentanil was reached. After loss of consciousness, rocuronium 0.6 mg/kg was administered. Patient's response to the rocuronium was graded using a 4 point scale in a blinded manner. The EC50 of remifentanil for preventing rocuronium induced withdrawal movements was determined using Dixon's up-and -down method.ResultsThe EC50 of remifentanil for preventing rocuronium induced withdrawal movements was 1.8 ± 0.5 ng/ml [95% confidence interval 1.3-2.2] in the male group, 2.3 ± 1.0 ng/ml [1.3-3.2] in the female group, 0.5 ± 0.4 ng/ml [0.2-0.8] in the old group and 2.8 ± 0.8 ng/ml [2.1-3.5] in the child group.ConclusionsThe EC50 of remifentanil for preventing rocuronium induced withdrawal movements was lowest in the elderly and higher in children than male adult patients. No difference in the EC50 of remifentanil was seen between male and female adult patients.

Effects of different target plasma concentrations of remifentanil on minimum alveolar concentration of sevoflurane for tracheal intubation in children

Objective To investigate the effects of different target plasma concentrations of remifentanil given by TCI on the minimum alveolar concentration(MAC)of sevoflurane for induction of tracheal intubation in children.Methods One hundred and twenty.six ASA Ⅰ or Ⅱ children aged 3-8 yr undergoing elective surgery under general anesthesia were randomly divided into 4 groups:control group(C,n=30),and target plasma concentration of remifentanil 1 ng/group(R1,n=30),2 ng/ml group(B2,n=30)and 3 ng/ml group(R3,n=36).Anesthesia WM induced with 5% sevoflurane.A catheter connected to gas analyzer was inserted into nasal cavity when the children lost eyelash reflex.Venous access was established,atropine 0.01 mg/kg was injected iv in group C,and remifentanil was given by TCI in group R1-3. After atropine Was injected in group C and the plasma and effect-site concentrations of remifentanil reached the balance,the up-and-down sequential experiment was performed.The initial end-tidal concentration of sevoflurane was and the ratio of the two 8uccessive concentrations was 1.2. After the end.tidal concentration of sevoflurane reached the predetermined value.it was maintained for 10 rain and tracheal intubation Was then performed.Satisfactory tracheal intubation condition was defined as the inlubation score = 6. MAC of sevoflurane in each group was calculated. Adverse effect were also recorded.Results The MAC of sevoflurane for tracheal intubation was 5%,3%,2%and 1% in group C and B1-3 respectively.No bradycardia and hypotension occurred in all the children.Tracheal intubation of 3 cases in group R2 and 8 cases in group R3 Was facilitated with iv injection of vecuronium because laryngoscope could not be inserted or the glottis was closed. Conclusion Remifentanil 1 ng/ml can reduce the MAC of sevoflurane for tracheal intubation and has less adverse effect in children. Key words: Piperidines; Drug delivery systems; Anesthetics, inhalation; Dose-response relationship, drug; Intubation, intracheal; Child

Maternal and Neonatal Effects of Remifentanil at Induction of General Anesthesia for Cesarean Delivery

Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study. In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 microg/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil. The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, -17 to 31] mmHg) compared with the control group (42 [6-73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23-45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23). A single bolus of 1 microg/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.

Concentration of remifentanil needed for tracheal intubation with sevoflurane at 1 MAC in adult patients

Inhalation induction with sevoflurane provides acceptable conditions for tracheal intubation. Opioids significantly decrease the alveolar concentration needed to achieve tracheal intubation. The purpose of this study was to determine the target concentration of remifentanil providing excellent conditions for tracheal intubation with sevoflurane at 1 minimum alveolar concentration without muscle relaxant. Twenty-four consecutive patients, aged 18-50 yr, ASA I or II, were studied. Induction of anaesthesia was performed with sevoflurane at age-adjusted minimum alveolar concentration. Remifentanil was simultaneously administered using target-controlled infusion with the Minto model. Target plasma concentration of remifentanil was selected for each patient according to an up-and-down method. The mean target concentration of remifentanil for successful tracheal intubation was 3.3 ng mL(-1) (95% confidence interval: 2.6-3.9 ng mL(-1)). Arterial pressure, heart rate and bispectral index did not increase after tracheal intubation in the group of patients with successful intubation. Remifentanil at 3.3 ng mL(-1) together with sevoflurane at 1 minimum alveolar concentration provides excellent conditions for tracheal intubation in 50% of patients.

Target-controlled infusion of remifentanil and propofol during operation with suspension laryngoscopy

To evaluate target-controlled infusion (TCI) of remifentail-propofol and the balanced anesthesia of fentanyl-isoflurane during the operation with suspension laryngscope. Sixty ASA I-II patients scheduled for the surgery through suspension laryngoscopy were randomly divided into two groups: TCI group and control group. In TCI group, anesthesia was maintained with TCI remifentanil-propofol which was stopped at the end of operation. The target plasma concentration of remifentanil was set at 6 microg/L and propofol at 3 mg/L. In control group, anesthesia was induced with intravenous fentanl 2.5 microg/kg and propofol 1-2 mg/kg, maintained with fentanl 0.03 microg.kg(-1). min(-1) and 1% isoflurane which was stopped at the end of surgery. Intubation was facilitated with succinylcholine 1-1.5 mg/kg.MAP, HR, ECG, S(p)O(2) and P(ET)CO(2) were monitored during anesthesia. The following parameters were recorded and compared between two groups: (1) the changes in blood pressure (BP), heart rate(HR) and S(p)O(2) at different time point; (2) recovery profile including the time of response to verbal commands, autonomous breathing, tracheal extubation, orientation recovery, discharging from PACU after operation; (3) OAAS scores after operation; (4) postoperative complications; (5) unexpected events and awareness during operation. (1) The hemodynamics were stable while the target plasma concentration of remifentanil was set at 6 microg/L and propofol at 3 mg/L. (2) During tracheal intubation, suspension laryngoscope was inserted, and extubation MAP was significantly lower in TCI group than that in control group; (3) There were no significant differences in hemodynamic values and S(p)O(2) of different time points between two groups. Study group was faster than control group on recovery profile including the time of response to verbal commands, autonomous breathing, tracheal extubation, orientation recovery and discharging from PACU. There was respectively one unexpected event in both groups. Remifentanil supplemented with isoflurane anesthesia can achieve the optimal hemodynamic stability during the operation with suspension laryngoscopy and better recovery profile from anesthesia than fentanyl.

The μ-opioid agonist remifentanil attenuates hyperalgesia evoked by blunt and punctuated stimuli with different potency: a pharmacological evaluation of the freeze lesion in humans

Experimental pain models inducing hyperalgesia, i.e. an increased sensitivity to noxious stimuli often present in clinical pain, are important tools for studying antinociceptive drug profiles. The correct interpretation of results obtained in these models necessitates their mechanistic understanding. This study evaluated the freeze lesion, an experimental model of hyperalgesia, in humans. Twelve healthy subjects were tested with mechanical (brush, punctuated and blunt) and electrical (5, 250, and 2000 Hz sine wave current) stimuli before and after freezing the skin, and during a computer-controlled infusion of the μ-opioid agonist remifentanil targeting five different plasma concentrations between 0 and 6 ng/ml in a two-staged, single occasion, randomized, and double blind study design. Pharmacodynamic modeling techniques were used to describe the effect of freezing and drug administration on the mechanical and electrical pain thresholds. Freezing the skin resulted in hyperalgesia to blunt and punctuated stimuli and lowered the respective pain threshold by 29 and 73%. Hyperalgesia to brushing or electrical stimuli was not detected. Remifentanil attenuated hyperalgesia to blunt stimuli about twice as potently as hyperalgesia to punctuated stimuli, as indicated by a significantly steeper linear relationship between the remifentanil plasma concentration and the increase of the pain threshold to blunt stimuli. Remifentanil attenuated electrical pain with greater potency for low frequency stimulation. The potency difference of remifentanil suggests that different neuronal mechanisms mediate hyperalgesia to blunt and punctuated stimulation. Absence of brush-evoked and electrical hyperalgesia is compatible with the view that mechanical hyperalgesia to blunt and punctuated stimulation of the freeze lesion is predominantly caused by a peripheral mechanism.

HEMODYNAMIC EFFECTS AND PLACENTAL TRANSFER AFTER CONTINUOUS INTRAVENOUS APPLICATION OF REMIFENTANIL IN THE CHRONIC MATERNAL-FETAL SHEEP PREPARATION

S252 Remifentanil is a new ultrashort-acting anilidopiperidine with a [micro sign]-specific opioid action. Remifentanil with its unique properties could be of particular use for fetal and maternal analgesia during fetal surgery. However, the hemodynamic changes and pharmacokinetic behavior of remifentanil in the pregnant patient have not been studied in depth. METHODS: Using the chronic maternal-fetal sheep preparation, a continuous infusion of remifentanil 0.33 [micro sign]g/kg/min was administered intravenously over 60 min. Fetal and maternal arterial blood samples were obtained for remifentanil levels before and at 5, 15, 30, 60, 65, 75 and 120 min following start of the infusion. At regular intervals, arterial blood samples were drawn to determine blood gases and acid-base status of mother and fetus. Maternal mean arterial pressure (MMAP), uterine bloodflow (UBF), maternal heart rate (MHR), fetal mean arterial pressure (FMAP) and fetal heart rate (FHR) were recorded continuously. Statistical analyses were performed using repeated measures of ANOVA followed by Dunnett t-testing. A p value < 0.05 was considered significant. RESULTS: Eight experiments were performed in eight ewes. MMAP, MHR FHR, FMAP and UBF or blood-gases and acid-base status in mother or fetus did not change significantly during remifentanil infusion. Peak levels of remifentanil were detected in maternal plasma after 30 min. and reached 3.5 ng/ml. Peak fetal plasma levels of 0.36 ng/ml were attained after 60 min. (Figure 1)Figure 1CONCLUSION: This study indicates that intravenous aplication of remifentanil has not any significant effect on maternal and fetal cardiovascular and acid-base status in the pregnant ewe. Peak fetal plasma concentration of remifentanil reached 14% of the peak maternal placental concentration.