Sufentanil Concentrations Research Articles

Investigating propofol-sufentanil interaction using clinical endpoints and processed electroencephalography: a prospective randomized controlled trial.

Propofol and sufentanil target controlled infusion technology is used with increasing frequency. Drug interaction modelling, using clinical endpoints and processed electroencephalography helps determine optimal drug concentrations to assure adequate anesthesia. Sixty patients were randomized to receive a constant concentration of sufentanil (0.25 ng/mL (Group S0.25), 0.5 ng/mL (Group S0.5), 0 ng/mL (Group S0). Propofol was administered in steps of 0.5 µg/mL, up to 4 µg/mL. Processed EEG (Bispectral Index, Narcotrend Index) and auditory evoked potentials (composite A-Line autoregressive Index; cAAI), were recorded simultaneously. Sufentanil-propofol interaction was assessed by Probit - and nonlinear regression analysis. Sufentanil had a dose-dependent synergistic effect on the effect-site concentration of propofol (µg/mL) associated with a 50% probability (EC50) of loss of responsiveness to verbal command (S0: 2.84 µg/mL, R2 0.773; S0.25: 1.95 µg/mL, R2 0.862; S0.5: 1.48 µg/mL, R2 0.887) and noxious stimulation (S0: 3.46 µg/mL, R2 0.626 µg/mL; S0.25: 2.17 µg/mL, R2 0.853; S0.5: 1.69 µg/mL, R2 0.897). Non-linear regression analysis revealed a synergistic sufentanil effect on the propofol EC50 for BIS (S0: 3.36 µg/mL, R2 0.79; S0.25: 2.77 µg/mL, R2 0.86 µg/mL; S0.5: 2.6 µg/mL, R2 0.84), Narcotrend Index (S0: 3.57 µg/mL, R2 0.66; S0.25: 2.91 µg/mL, R2 0.70; S0.5: 2.02 µg/mL, R2 0.51) and cAAI (S0: 3.42 µg/mL, R2 0.59; S0.25: 3.00 µg/mL, R2 0.63; S0.5: 3.14 µg/mL, R2 0.59). Sufentanil has a synergistic effect on the clinically observed hypnotic properties of propofol. These findings apply also to the depth of hypnosis measured by the Bispectral Index, Narcotrend Index and cAAI.

Potentially clinically relevant concentrations of Cefazolin, Midazolam, Propofol, and Sufentanil in auto-transfused blood in congenital cardiac surgery

BackgroundUse of donor blood in congenital cardiac surgery increases the risk for post-operative morbidity and mortality. To reduce the need for allogenic blood transfusion a technique for peri-operative mechanical red cell salvage is applied. Blood from the operation site is collected in a reservoir, processed, passed through a lipophilic filter and returned to the patient. Influence of this cellsaver system on coagulation, fibrinolysis and inflammatory markers is known. To our knowledge no studies have been performed on the effects of autotransfusion on drug concentrations. A clinically relevant drug dose could potentially be returned to the patient through the auto-transfused blood, leading to unwanted drug reactions post-operatively. We aimed to measure drug concentrations in blood salvaged from the operation site and in the auto-transfused blood to determine if a clinically relevant drug dose is returned to the patient.MethodsThe study was performed at the Department of Cardiothoracic Surgery of a tertiary university hospital. Blood samples were taken from the reservoir, after processing before the lipophilic filter, the auto-transfused blood, and the waste fluid. Samples were stored at − 80 C and drug concentration for sufentanil, propofol, midazolam and cefazolin were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Drug concentrations measured in the reservoir and the auto-transfused blood were compared and the relative reduction was calculated for each patient.ResultsBlood samples were taken from 18 cellsaver runs in 18 patients, age 0–13 years. Drug concentrations in the reservoir were comparable to concomitant concentrations in the patient. For sufentanil 34% (median, IQR 27–50) of drug concentration was retained from the reservoir in the auto-transfused blood, for midazolam 6% (median, IQR 4–10), for cefazolin 5% (median, IQR 2–6) and for propofol 0% (median, IQR 0–0) respectively.ConclusionDepending on the drug, up to 34% of the drug concentration salvaged from the operation site is returned to the patient through autotransfusion, potentially causing unwanted drug reactions post-operatively. Additionally, influence of a cellsaver system should be considered in pharmacological research during and after congenital cardiac surgery and could result in dose adjustments in the postoperative phase.Trial registrationRegistration at the Dutch Trial Registry (NTR3579) at August 14 2012.

Influence of Cardiac Output on the Pharmacokinetics of Sufentanil in Anesthetized Pigs.

Sufentanil is used for general anesthesia and analgesia. The study aim was to determine the effect of pharmacologically induced changes in cardiac output on the pharmacokinetics of sufentanil in anesthetized pigs. Twenty-four pigs were randomly assigned to low, high, and control cardiac output groups. Cardiac output was decreased or increased from baseline by at least 40%, or maintained within ± 10% of baseline, respectively. Sufentanil was administered as a bolus followed by a continuous infusion for 120 min. Timed arterial samples were drawn for sufentanil concentration measurements. Data from 20 animals were analyzed. The cardiac outputs (means ± SD) were 2.9 ± 0.7, 5.4 ± 0.7, and 9.6 ± 1.6 l/min in the low, control, and high cardiac output groups, respectively. The parameters of the two-compartment pharmacokinetic model for these cardiac outputs were: CL1: 0.9, 1.2, and 1.7 l/min; CL2: 0.9, 3.1, and 6.9 l/min; V1: 1.6, 2.9, and 5.2 l; and V2: 27.5, 47.0, and 79.8 l, respectively. Simulated sufentanil doses to maintain a target plasma concentration of 0.5 ng/ml for 3 h were 99.5, 128.6, and 157.6 μg for cardiac outputs of 3, 5, and 7 l/min, respectively. The context-sensitive half-times for these cardiac outputs increased from 3.1 to 19.9 and 25.9 min, respectively. Cardiac output influences the pharmacokinetics of sufentanil. Simulations suggest that in the case of increased cardiac output, the dose should be increased to avoid inadequate drug effect at the expense of prolonged recovery, whereas for low cardiac output the dose should be reduced, and a faster recovery may be expected.

Half-effective target effect-site concentration of sufentanil inhibiting responses to insertion of SLIPA when combined with propofol given by target-controlled infusion

Objective To determine the half-effective target effect-site concentration(EC50)of sufentanil inhibiting responses to insertion of Streamlined Liner of the Pharynx Airway(SLIPA)when combined with propofol given by target-controlled infusion(TCI). Methods Twenty-eight patients, aged 35-55 yr, with body mass index<30 kg/m2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective hysteroscopic surgery, were selected.Sufentanil was administered by TCI at a concentration for 4 min, and then propofol was given by TCI at a target effect-site concentration of 4 μg/ml.When the patients lost consciousness(bispectral index value<60)and the corresponding target effect-site concentrations of two drugs were achieved, SLIPA was inserted.Using the up-and-down sequential trial, the target effect-site concentration of sufentanil was determined according to patient′s responses to SLIPA insertion.The initial target effect-site concentration of sufentanil was 0.3 ng/ml, and the ratio between the two successive concentrations was 1.1.The EC50 and 95% confidence interval of sufentanil inhibiting responses to SLIPA insertion were calculated by using Dixon-Mood formula. Results The EC50 of sufentanil inhibiting responses to SLIPA insertion was 0.17 ng/ml, and the 95% confidence interval was 0.15-0.19 ng/ml. Conclusion When combined with propofol(target effect-site concentration 4 μg/ml)given by TCI, the EC50 of sufentanil inhibiting responses to SLIPA insertion is 0.17 ng/ml. Key words: Sufentanil; Propofol; Laryngeal masks; Dose-response relationship, drug; Drug delivery systems

Sufentanil protects the rat myocardium against ischemia-reperfusion injury via activation of the ERK1/2 pathway.

Sufentanil, a lipophilic opioid, is the most frequently used clinical drug for ischemic heart disease. The effects of sufentanil on MAPK signaling in ischemic heart disease were explored. The effects of sufentanil on ischemia-reperfusion (IR)-induced myocardial injury in a rat model were examined. The serum levels of CK, LDH, MDA and SOD, and the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase were measured. The levels of total and phosphorylated ERK1/2, JNK, and p38 were measured by western blotting in the heart, and the myocardial H9C2 cell line was studied. Using the Cell Counting Kit-8, the growth rate of H9C2 cells affected by sufentanil was studied. The serum levels of CK, LDH and MDA were higher in the IR group than in the SO and SUF groups. The SOD level, as well as the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase, were lower in the SO and SUF groups than in the IR group. The phosphorylated ERK1/2 level was lower in the IR group than in the SO and SUF groups. The growth rate of H9C2 cells increased with the concentration of sufentanil and the exposure time. The phosphorylated ERK level was upregulated by 4-12h of sufentanil exposure, indicating that the effects were time-dependent. Furthermore, an inhibition of ERK signaling by chemical inhibition suppressed the sufentanil-mediated increase in the growth rate of H9C2 cells. Sufentanil appears to be beneficial for cases of worsening ischemic heart disease. Further studies are necessary before a clinical application is considered.

Compulsive-Like Sufentanil Vapor Self-Administration in Rats.

Opioid misuse is at historically high levels in the United States, with inhalation (ie, smoking and vaping) being one of the most common routes of consumption. We developed and validated a novel preclinical model of opioid self-administration by inhalation that does not require surgery and reliably produces somatic and motivational signs of dependence. Rats were trained to perform an operant response (nosepoke) to receive 10 s of vaporized sufentanil, a potent opioid, in 2 h daily sessions. Rats readily and concentration-dependently self-administered vaporized sufentanil. Rats exhibited a significant increase in responding for sufentanil when given the preferential μ-opioid receptor inverse agonist naloxone, suggesting the participation of μ-opioid receptors in the reinforcing properties of sufentanil vapor. Serum sufentanil concentrations significantly correlated with the number of sufentanil vapor deliveries. Rats that were given long access (LgA; 12 h/day) but not short access (ShA; 1 h/day) to vaporized sufentanil escalated their drug intake over time and exhibited both naloxone-precipitated somatic signs of opioid withdrawal and spontaneous withdrawal-induced mechanical hypersensitivity. After 6 months of forced drug abstinence, LgA rats returned to pre-escalation baseline levels of responding for sufentanil and mechanical sensitivity. Upon subsequent re-escalation (ie, after the return to extended access to sufentanil vapor), LgA rats again developed naloxone-precipitated somatic signs of withdrawal and spontaneous withdrawal-induced mechanical hypersensitivity. These findings demonstrate that the operant sufentanil vapor self-administration model has both face and construct validity and therefore will be useful for investigating the neurobiological basis of opioid addiction.

The effect of different concentrations of sufentanil on interleukin-6 and tumor necrosis factor-α concentrations in peripheral blood induced by lipopolysaccharide

Objective Investigating the effect of different concentration of sufentanil on IL-6 and TNF-α concentrations in human peripheral blood induced by lipopolysaccharide(LPS). Methods Every blood sample were collected from 30 healthy volunteers. Using a completely randomized design grouping method. Samples were randomized assigned in eight groups. Venous blood 5 ml from every volunteers were collected. 100 μl of the venous blood from every sample were put in eight ethylenediaminete-traacetic acid-vitro ready tubes labeled(A, B, C1, C2, C3, D1, D2, D3) by using precision pipette. Groups are: group A for the saline group(control), group B joined LPS 100 mg/L, group C includes C1, C2, C3, respectively fentanyl 0.05, 0.50, 5.00 μg/L, group D includes the D1, D2, D3 fentanyl 0.05, 0.50, 5.00 μg/L and LPS 100 mg/L, respectively. The IL-6 and TNF-α ELISA kit were used to detect supernatant concentrations of IL-6 and TNF-α. Results Group A and group C in peripheral blood IL-6 and TNF-α concentration were not significantly different(P>0.05). Plus LPS of group B and group D of IL-6, of TNF-α concentrations were significantly increased(P<0.05). Group D and group B, the peripheral blood of IL-6 and TNF-α concentrations were significantly lower(P<0.05). Group D2, D3 peripheral IL-6 and TNF-α concentration reduction are greater than the group D1(P<0.05). Group D3 peripheral blood IL-6 and TNF-α concentration were greater than group D2 reduction(P<0.05). Conclusions LPS can promote isolated human peripheral blood inflammatory cytokine IL-6 and TNF-α concentration increasing. Sufentanil inhibited LPS-induced, IL-6 and TNF-α concentration increase in a dose-dependent manner from the peripheral blood. Sufentanil had no effect on IL-6 and TNF-α concentration the peripheral blood drawn away from people. Key words: Sufentanil; Lipopolysaccharide; Peripheral blood; Interleukin-6; Tumor necrosis factor-α

Observation on Clinical Effects of Postoperative Analgesia with Sufentanil After Upper and Lower Abdominal Surgery: A Prospective Study

Post-operative analgesia is crucial to facilitate early ambulation, prevent complications, increase patient satisfaction while ensuring a faster recovery pace. Opioid analgesics have been recognized as the mainstay for treatment of acute pain in a majority of postoperative care units. Intravenous patient-controlled analgesia (IVPCA) with the opioids drugs sufentanil and fentanyl has proven to be effective when used in the immediate postoperative period. The aim of the study was to determine the efficacy and safety of sufentanil for postoperative analgesia based on the same principle, and, fentanyl citrate was chosen as a control drug for upper and lower abdominal operations under general anesthesia. Methodology; It was a prospective clinical study carried out at Union hospital, from December 2014 to March 2015. 240 patients were scheduled for upper and lower abdominal surgery requiring general anesthesia. They were divided into four groups: test group (A) and control group (B); (C) and (D), and are given fentanyl and sufentanil by IVPCA for postoperative analgesia relief following surgery. Pain was assessed by the visual analogue Scale. The determined pain relief; pulse rate, BP, ECG, sedation score, SPO2, pruritus score, nausea score and vomiting score were all recorded for each patient. Results The pressing times values show that fentanyl (A) and high dose sufentanil (C, D) both provided a satisfactory level of analgesia. Moreover, VAS scores of the patients on high dose sufentanil (C, D) were lower, implying superior analgesic effects at these doses. However, low dose sufentanil (B) may only provide limited and inadequate analgesia. The degree of pruritus was less marked in patients on sufentanil than those on fentanyl as demonstrated by the lower Pruritus scores in sufentanil groups (B, C, D). Low dose sufentanil and fentanyl have shown to have similar extent of side effects overall. Conclusion It was found that sufentanil had superior analgesic effect to that of fentanyl in patients who had undergone open abdominal surgery. The extent of the occurrence of adverse reactions to light in the low-dose sufentanil group (B) is less than that in the high-dose groups (C, D), the concentration of persistent postoperative analgesia sufentanil should reach 0.02μg / (kg ml), and the flow rate maintained at 2ml / h.

Pharmacokinetics of sufentanil during long-term infusion in critically ill pediatric patients.

The aim of this study was to develop a population pharmacokinetic model of sufentanil and to assess the influence of covariates in critically ill children admitted to a pediatric intensive care unit. After institutional approval, 41 children were enrolled in the study. Blood samples for pharmacokinetic (PK) assessment were collected from routinely placed arterial catheters during and after discontinuation of infusion. Population nonlinear mixed-effects modeling was performed using NONMEM. A 2-compartment model described sufentanil PK sufficiently. Typical values of the central and peripheral volume of distribution and the metabolic and intercompartmental clearance for a theoretical patient weighing 70 kg were VC = 7.90 l, VT = 481 L, Cl = 5.3 L/h, and Q = 38.3 L/h, respectively. High interindividual variability of all PK parameters was noted. Allometric/isometric principles to scale sufentanil PK revealed that to achieve the same steady-state sufentanil concentrations in plasma for pediatric patients of different body weights, the infusion rate should follow the formula (infusion rate for a 70-kg adult patient, μg/h) × (body weight/70 kg)(0.75). Severity of illness described by PRISM score, the monitored physiological and laboratory parameters, and coadministered drugs such as vasopressors were not found to be significant covariates.

Intraoperative and postoperative anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation combined with sufentanil anaesthesia in patients undergoing supratentorial craniotomy.

To investigate the anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation (TEAS) during supratentorial tumour resection for postoperative recovery and side effects. In a blinded clinical trial, 92 patients scheduled for supratentorial craniotomy under general anaesthesia were randomly allocated into either a multipoint TEAS (n=46) or a sham TEAS group (n=46). All patients received total intravenous anaesthesia (TIVA) with propofol and sufentanil. The target concentration of sufentanil was adjusted and recorded according to mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). Patients in the TEAS group received TEAS 30 min before anaesthesia induction and this was maintained throughout the operation at four pairs of acupuncture points. Postoperative pain, recovery and side effects were evaluated. Eighty-eight patients completed the study. Continuous monitoring of MAP, HR and BIS showed stable values with no significant differences between the two groups (p>0.05). Sufentanil target plasma concentration in TEAS patients was significantly lower at some time points during supratentorial craniotomy, and total sufentanil consumption was significantly higher in the sham group (p<0.05). Postoperative recovery and pain were significantly improved by TEAS (p<0.001), without the postoperative side effects. Multipoint TEAS at both proximal and distal points combined with TIVA can significantly decrease intraoperative sufentanil requirements, increase pain relief on postoperative day 1 and improve postoperative recovery of patients during supratentorial tumour resection, with no significant increase of side effects. These findings suggest that multipoint TEAS may be clinically effective as an adjunct to analgesia in intraoperative anaesthesia and postoperative pain treatment and may speed recovery. Chinese Clinical Trial Registry (registration number ChiCTR-TRC-10001078).

Median effective effect-site concentration of sufentanil for wake-up test in adolescents undergoing surgery: a randomized trial.

BackgroundTo determine the median effective concentration of sufentanil as an analgesic during wake-up tests after sevoflurane anesthesia during surgery for adolescent idiopathic scoliosis (AIS).MethodsThis is a randomised controlled trial. Sixty patients aged 13–18 years scheduled for AIS surgery were randomized into six groups of 10 patients each to receive target effect-site concentrations of sufentanil of 0.19, 0.1809, 0.1723, 0.1641, 0.1563, and 0.1489 ng/ml (target concentration ratio, 1.05). Wake-up time was recorded. Median EC50 and 95% confidence interval (CI) for sufentanil target-controlled infusion (TCI) were determined using Kärber’s method. The primary outcome was median EC50 for sufentanil TCI as an analgesic during the wake-up test after sevoflurane anesthesia during surgery for AIS.ResultsThe EC50 and 95% CI of sufentanil TCI were 0.1682 ng/ml and 0.1641 ~ 0.1724 ng/ml, respectively.ConclusionsThe EC50 of sufentanil TCI was 0.1682 ng/ml (95% CI: 0.1641 ~ 0.1724 ng/ml) during sevoflurane anesthesia in adolescents undergoing surgery for idiopathic scoliosis with intraoperative wake-up tests.Trial registrationClinicaltrials.gov identifier: ChiCTR-TTRCC-12002696.

Divergent Effect of Dezocine, Morphine and Sufentanil on Intestinal Motor Function in Rats

Background: Opioid induced bowel dysfunction is the most common side effect of preoperatively administrated morphine, fentanyl and its derivative. However, the influence of dezocine on intestinal mobility is rarely reported. This study was designed to investigate the effects of dezocine, morphine and sufentanil on both intestinal smooth muscle contraction and propulsion in rats.Methods: Contractile tension and frequency of isolated rat small intestine smooth muscle were measured using tension transducer after incubation with different concentrations of dezocine, morphine and sufentanil. The propulsive rate of methylene blue in rat intestinal tract was measured 30 minutes after intraperitoneal injection of morphine, sufentanil and dezocine. Percent of change in contractile tension and contraction frequency compared to baseline level were calculated to evaluate muscle contraction. Propulsive rate of methylene blue was calculated as the percentage of methylene blue moving distance in intestinal tract compared to the length of the small intestine.Results: Morphine and sufentanil significantly increased the contractile tension of isolated small intestine smooth muscle at high doses. The contraction frequency did not change significantly among the 3 tested doses. Increasing the dose of dezocine from 1.7 mg.L-1 to 10.2 mg.L-1 did not change either the contractile tension or the contraction frequency. The propulsive rate of methylene blue in intestinal tract was significantly decreased after the treatment with morphine, sufentanil and dezocine (45.6%, 43.7%, and 42.1% respectively) compared to control group(57.1%), while the difference among the 3 drug groups were not significant.Conclusion: Morphine and sufentanil may dose dependently increase the contractile tension and contraction ability of isolated rat small intestine smooth muscle, while dezocine has no significant effect on intestine smooth muscle contraction. However, all these opioids might impair small intestinal propulsion.

Accuracy of target-controlled infusion of sufentanil from termination of cardiopulmonary bypass until the end of surgery in patients undergoing cardiac surgery

Objective To evaluate the accuracy of target-controlled infusion (TCI) of sufentanil from termination of cardiopulmonary bypass (CPB) until the end of surgery in the patients undergoing cardiac surgery.Methods Twenty adult patients,aged 25-64 yr,of ASA physical status Ⅱ or Ⅲ,scheduled for elective coronary artery bypass graft under CPB,were enrolled in the study.Immediately after termination of CPB,sufentanil was given by TCI using Gepts pharmacokinetic parameters.The initial target effect-site concentration (Ce) of sufentanil was 0.4 ng/ml.The Ce increased by 0.2 ng/ml every 10 min until it finally decreased to 0.8 ng/ml,and then the Ce decreased by 0.2 ng/ml every 10 min until it finally decreased to 0.4 ng/ml which was maintained until the end of surgery.At 10 min of infusion at each preset target Ce 0.4,0.6,0.8 and 0.6 ng/ml (T1-4) and 1,3,5,10,20,40 and 60 min of infusion at the last concentration of 0.4 ng/ml (T5-11),arterial blood samples were collected for measurement of sufentanil concentrations by using ELISA.For each sample,the bias,accuracy and wobble were calculated.Results Compared with the predicted plasma concentrations of sufentanil,the measured plasma concentrations of sufentanil were significantly decreased at T1-11.The bias,accuracy and wobble were-37.63 ％,37.63％ and 5.09％,respectively.Conclusion The accuracy of sufentanil TCI using Gepts pharmacokinetic parameters is not high from termination of CPB until the end of surgery in the patients undergoing cardiac surgery. Key words: Sufentanil; Drug delivery systems; Coronary artery bypass

Different dosage of sufentanil for postoperative patient-controlled intravenous analgesia after gynecologic surgery

Objective Postoperative analgesia is one of the concerns of anesthesiologists and patients.The aim of this study is to investigate the effect and safety of different concentration of sufentanil for postoperative patient-controlled intravenous analgesia (PCIA) after gynecologic surgery,providing the basis of individualized dosage for future clinical applications.Methods Forty-eight ASA Ⅰ-Ⅱ patients (18 y-65 y of age) scheduled for elective gynecological surgery were recruited and randomly assigned to three groups receiving patient-controlled analgesia (n =16),the Suf1 group (loading dose of sufentanil 0.25 μg/kg,the concentration of sufentanil is 0.02 μg ·kg-1 ·ml-1),the Suf2 group (loading dose of sufentanil 0.25 μg/kg,with sufentanil's concentration 0.022 5 μg· kg-1· ml1),and the control group (the first dose of fentanyl 2.5 μg/kg,fentanyl 0.2 μg· kg-1· ml-1).PCIA was administrated with continual infusion rate of 2 ml/h,bolus injection of 0.5 ml and lockout time of 15 min.Visual analogue scale (VAS) at rest and on movement and sedation scores were assessed at 1,2,4,8,12,24 h and 48 h postoperatively.For each pain assessment,the patient's vital signs and the side-effects from sufentanil (including nausea,emesis,pruritus,and respiratory depression) were recorded.Results Compared to the control group,the Suf2 group showed significant lower VAS scores at rest 12 h postoperatively[VAS in Control group:(2.0±0.6),VAS in Suf2 group:(0.9±0.6),P＜0.05] and VAS scores on movement 24 h postoperatively [such as 24 h after the postoperative analgesia,control group:(2.6±0.7),Suf2 group:(2.0±1.0),P＜0.05].Compared to the Suf1 group,both the VAS scores at rest[such as 48 h after the postoperative analgesia,Suf1 group:(1.2±0.5),Suf2 group:(0.5±0.7),P＜0.05] and on movement [such as 48 h after the postoperative analgesia,Suf1 group:(2.1±0.6),Suf2 group:(1.8±0.8),P＜0.05] decreased significantly in the Suf2 group (P＜0.05).All these data indicated that the concentration of sufentanil used in the Suf2 group could provide adequate pain control during 12 h after postoperative analgesia compaed to the other two groups.Conclusions The dosage of sufentanil of 0.022 5 μg· kg-1· ml-1 could provide better analgesia,sedation,with lower incidence of sideeffects in postoperative pain relief after gynecologic surgery. Key words: Sufentanil; Patient-controlled intravenous analgesia; Gynecological

Influence of intensive care treatment on the protein binding of sufentanil and hydromorphone during pain therapy in postoperative cardiac surgery patients

Our objective was to evaluate the effect of intensive care treatment on the protein binding of sufentanil and hydromorphone in cardiac surgery patients during postoperative analgesia using a target-controlled infusion (TCI) and patient-controlled analgesia (PCA). Fifty adult patients were enrolled in this prospective randomized study; of which, 49 completed the study (age range 40-81 yr). Sufentanil was administered as an analgesic intraoperatively, and hydromorphone was dosed after operation with TCI and PCA until 8 a.m. on the first postoperative day. Arterial plasma samples were collected for drug and protein concentration measurements up to 24 h after cardiac surgery. Corresponding patient data were collected from the electronic patient data system. After explorative data analysis with principal component analysis, multivariate regression analysis and non-linear mixed effects modelling was used to study the effect of treatment on protein binding. Data of 35 patients were analysed. The median protein binding of sufentanil and hydromorphone was 88.4% (IQ range 85.7-90.5%) and 11.6% (IQ range 9.5-14.3%), respectively. Free fraction of sufentanil increased towards the end of the study period, whereas hydromorphone free fraction remained nearly constant. The total sufentanil concentration and volume balance were identified as significant covariates for the protein binding of sufentanil. For the protein binding of hydromorphone, no significant covariate effects were found. Sufentanil protein binding was significantly dependent on changes in the total drug concentration and volume balance addressing the importance of adequate dosing and fluid-guided therapy. Hydromorphone protein binding was nearly constant throughout the study period. EudraCT 2011-003648-31 and ClinicalTrials.gov: NCT01490268.

Effect of sufentanil on contraction and anti peroxidative ability of thoracic aorta isolated from rats with diabetes mellitus

Objective To investigate the effect of sufentanil on contraction and anti peroxidative ability of thoracic aorta isolated from rats with diabetes mellitus.Methods Eight male rats with diabetes were decapitated and their thoracic aorta were i solated.The aortic rings obtained from diabetes rat were divided into 4 groups(n=8):control group and 3 sufentanil groups (7×10-11,2×10-10,1×10-9 mol/L).Vitro vascular experimental method was used to observe the effect of different concentrations of sufentanil on the norepinephrine(NE)-induced contraction of thoracic aorta from diabetic rats and the content of nitrogen monoxide(NO),maleic dialdehyde(MDA) and superoxide dismutase(SOD) on the vascular ring.Results The contraction amplitude of 3 sufentanil groups was orderly (25.4±4.0)％,(21.3±3.5)％ and (17.4±2.4)％.The SOD activity of 3 sufentanil groups was orderly (3.8±1.2),(4.9±0.8) U/mgprot and (6.1±0.3) U/mgprot.The contraction amplitude of thoracic aorta from 3 sufentanil groups was significantly lesser than that from control group,the level of SOD activity was higher in 3 sufentanil groups than in control group.Sufentanil significantly inhibited the NE-induced aortic contraction and changed the SOD activity in proportion to concentration.Conclusions Sufentanil can inhibit NE-induced contraction and change the anti peroxidative ability of thoracic aorta isolated from rats with diabetes mellitus in a concentration-dependent manner. Key words: Sufentanil; Diabetes mellitus; Nitrogen monoxide; Maleic dialdehyde; Superoxide dismutase

Effects of different target effect-site concentrations of sufentanil on MACBAR of desflurane in patients undergoing abdominal surgery

Objective To evaluate the effects of different target effect-site concentrations (Ces) of sufentanil on the minimum alveolar concentration of desflurane inhibiting stress responses to skin incision (MACsAR) in 50％ of patients undergoing abdominal surgery.Methods Eighty-three patients,aged 20-60 yr,scheduled for elective abdominal surgery with an expected incision longer than 10 cm,were enrolled in the study.All the patients were randomly allocated to one of three groups using a random number table:control group (group C,n =28),sufentanil with target Ce of 0.1 ng/ml group (group S1,n =27),and sufentanil with target Ce of 0.3 ng/ml group (group S2,n =28).After tracheal intubation,desflurane inhalation was started,and sufentanil was infused at the preset target Ces in S1 and S2 groups.The initial end-tidal concentration of desflurane was 9.0％ in group C,and 6.0％ in S1 and S2 groups.The target concentration was maintained at least for 15 min.The modified up-and-down method was used to perform the test.The end-tidal concentration of desflurane was adjusted in the next patients according to the response to skin incision.The MACBAR and 95％ confidence interval of desflurane was calculated according to the up-and-down method.Mean arterial pressure and heart rate were monitored and recorded and rate-pressure product was calculated.Results The MACBAR (95％ confidence interval) ofdesflurane was 11.2％ (11.1％-11.3％),7.8％ (7.7％-7.9％),and 4.2％ (4.1％-4.3％) in C,S1 and S2 groups,respectively.MACBAR and rate-pressure product of desflurane were significantly lower in S1 and S2 groups than in C group,and in S2 group than in S1 group (P ＜ 0.05 or 0.01).Conclusion The optimum target Ce of sufentanil is 0.3 ng/ml when combined with desflurane in the patients undergoing abdominal surgery. Key words: Anesthetics, inhalation ; Sufentanil; Dose-response relationship, drug; Stress

Pharmacokinetics of sufentanil administered with 0.2% ropivacaine as a continuous epidural infusion for postoperative pain relief in infants.

Our objective was to assess plasma sufentanil concentrations and postinfusion pharmacokinetics in infants receiving 0.2% ropivacaine with sufentanil as a continuous epidural infusion for postoperative pain relief. With consent of local ethics committee and informed parental consent, 20 infants 3-36months old (m.o.) (median 9.3m.o., 9.0 [3.5-15] kg, ASA PS I/II) were enrolled. Epidural catheter was placed under general anesthesia in L3-L4, L4-L5, or L2-L3 interspace and threaded not farther than 4cm into epidural space. After initial bolus of 0.2% ropivacaine, 0.5ml·kg(-1) and sufentanil 200ng·kg(-1) , continuous infusion of 0.2% ropivacaine, 0.3mg·kg(-1) ·h(-1) with sufentanil 112ng·kg(-1) ·h(-1) was started. For the postoperative period, sufentanil dose was reduced to 37ng·kg(-1) ·h(-1) . Blood samples were drawn at the end of surgery, 24h later, by the end of 2nd day of infusion and after 3, 6, and 18h from the end of infusion. Sufentanil was measured using liquid-liquid extraction (LLE) procedure and HPLC-MS/MS method with LOQ=5pg·ml(-1) . Elimination of sufentanil following epidural administration was very slow, with MRT=28.25 [18.36-44.75] h and t1/2 MRT =19.57 [12.72-31.01] h. In infants, during a long-term infusion of sufentanil with ropivacaine, the opioid concentration in plasma increases during the postoperative infusion itself, then increases even further after discontinuation of the infusion, in some cases reaching the values consistent with a potential risk of respiratory depression. Meticulous monitoring of the infants' vital signs is therefore mandatory not only during the infusion, but also for several hours after its discontinuation.

Application of a UHPLC MS/MS–Based Multianalyte Approach for Screening and Validated Quantification of Drugs in Human Blood Plasma Often Requested in the Context of Brain Death Diagnosis

A multianalyte procedure (MAP) for the screening and quantification of drugs of different classes using ultra-high-performance liquid chromatography with tandem-mass spectrometric detection (UHPLC-MS/MS) was established. The aim was to elucidate whether this general approach could be transferred to the determination of drugs relevant for brain death diagnosis (BDD). This part of the MAP should cover alfentanil, etomidate, fentanyl, ketamine, morphine, piritramide, and sufentanil as an addition to the established gas chromatographic-mass spectrometric approach for the determination of propofol, barbiturates, and some benzodiazepines. This UHPLC-MS/MS approach based on liquid-liquid extraction was validated with respect to selectivity, recovery, matrix effects, process efficiency, ion suppression/enhancement, accuracy and precision, stabilities, and limits of quantification. The approach was selective for the tested analytes. Accurate and precise quantification was achieved for all analytes with the exception of alfentanil and morphine. Validation data for fentanyl, piritramide, and sufentanil were acceptable, but the lowest calibrator concentration had to be set higher than half of the lower therapeutic range as recommended for BDD. Only etomidate and ketamine fulfill both validation and BDD criteria. Nevertheless, the MAP allowed the simultaneous screening and quantification of >90 other central nervous system-suppressing drugs with the same extract in the same run. For the screening and accurate and precise quantification of low concentrations of alfentanil, fentanyl, morphine, piritramide, and sufentanil, methods with alternative sample preparation and analysis techniques must be developed.

The optimal effect-site concentration of sufentanil for laryngeal mask insertion during induction with target-controlled propofol infusion at 4.0 μg/mL.

Objective:The objective of this study is to determine the optimal effect-site concentration (Ce) of sufentanil for satisfactory insertion of laryngeal mask airway (LMA) when administered with a target-controlled infusion (TCI) of propofol at 4.0 μg/mL.Materials and Methods:A total of 25 adult patients scheduled for minor elective surgery were enrolled in this study. All patients received induction with a combination of propofol and sufentanil TCI. The TCI of sufentanil was started at a target Ce of 0.1 ng/mL. After equilibrium with the plasma concentration, the TCI of propofol was initiated, targeting a preset Ce of 4.0 μg/mL. After the loss of consciousness, LMA was inserted and assessed by an experienced Anesthesiologist. The Ce of sufentanil for the next patient was guided by modified Dixon's up-and-down method using 0.05 ng/mL as a step size. The Ce of sufentanil required for successful LMA insertion in 50% of adults (EC50) was determined by calculating the midpoint concentration of all independent pairs of patients after at least seven crossover points.Results:The optimal Ce (EC50) of sufentanil for LMA insertion during propofol induction using target Ce of 4 μg/mL was 0.16 ng/mL (95% confidence interval [CI] = 0.12-0.20). There was a significant reduction in propofol induced pain score P = 0.0275 and insignificant hemodynamic changes.Conclusion:Ce of sufentanil required for successful LMA insertion in 50% of patients (EC50) using propofol target Ce of 4.0 μg/mL was 0.16 ng/mL (95% CI = 0.12-0.20) with a significant reduction in the propofol induced pain and hemodynamic stability.