Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） rapid determination method for simultaneous analysis of 20 fentanyl-related substances in blood. Methods With fentanyl-D₅ as an internal standard, the blood was extracted by liquid-liquid extraction （LLE）, then separated with an ACQUITY UPLC HSS T₃ chromatographic column, and finally 20 fentanyl-related substances were simultaneously analyzed with multiple reaction monitoring （MRM） mode. Results The limits of detection （LOD） of all compounds were 0.02-0.03 ng/mL, and the limits of quantitation （LOQ） were 0.05-0.2 ng/mL. Within the mass concentration range of 0.05-40 ng/mL, 20 fentanyl-related substances had a good linear relationship, and correlation coefficients were larger than 0.99. The accuracy of the method was 87.69%-114.68% and the extraction recovery rate was 85.35%-101.80%, and no significant matrix effect was observed. The established method was successfully applied to the detection of sufentanil in rat blood after sufentanil was injected. Sufentanil could still be detected in blood of rats 10 h after sufentanil injection. Conclusion The established method has the advantages of simple pretreatment, high sensitivity and good selectivity, and can be used for the determination of fentanyl-related substances in forensic toxicology analysis.
Animals ; Chromatography, High Pressure Liquid ; Fentanyl/blood* ; Forensic Toxicology ; Rats ; Reproducibility of Results ; Sufentanil/blood* ; Tandem Mass Spectrometry

BACKGROUND: Combining adjunctive medications with patient-controlled analgesia (PCA) has been used to minimize opioid related side-effects. The aim of this study was to evaluate whether postoperative infusion of a sub-sedative dose of dexmedetomidine can reduce opioid consumption and opioid related side-effects. METHODS: We selected 60 patients from 18 to 60 years old with an American Society of Anesthesiologists physical status of 1–2 who were scheduled for elective surgery. The types of surgery were limited to thoracoscopic wedge resection of the lung and pulmonary wedge resection under a mini-thoracotomy. Patients received PCA with sufentanil upon arrival in the recovery room, along with a separate continuous infusion of dexmedetomidine that was not mixed in the PCA but started at the same time. Patients were randomly allocated to two groups: dexmedetomidine 0.15 μg/kg/h was administered to patients in group D and normal saline was administered to patients in group C. The visual analogue scale (VAS) pain score, blood pressure, pulse rate, and respiratory rate were measured at each assessment. PCA related side-effects were evaluated. RESULTS: The VAS pain score was significantly lower in the dexmedetomidine group. Patients in the dexmedetomidine group required significantly less PCA at postoperative 1–4, 4–8, and 8–24 h time intervals. The incidence of nausea was significantly less in the dexmedetomidine group, and levels of sedation and hemodynamic variables except for blood pressure at postoperative 8 h were similar between the groups. CONCLUSIONS: In conclusion, a postoperatively administered sub-sedative dose of dexmedetomidine reduces PCA sufentanil consumption and decreases nausea.
Analgesia, Patient-Controlled* ; Blood Pressure ; Dexmedetomidine* ; Heart Rate ; Hemodynamics ; Humans ; Incidence ; Lung ; Nausea ; Passive Cutaneous Anaphylaxis ; Recovery Room ; Respiratory Rate ; Sufentanil*

BACKGROUNDSpinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated, and there is no indwelling epidural catheter or contraindication to spinal anesthesia. However, the ideal dose of intrathecal bupivacaine has not been quantified for cesarean delivery for severe preeclamptic patients. This study aimed to determine the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery.

METHODSTwo hundred severely preeclamptic patients are undergoing elective cesarean delivery under combined spinal-epidural anesthesia enrolled in this randomized, double-blinded, dose-ranging study. Patients received 4 mg, 6 mg, 8 mg, or 10 mg intrathecal hyperbaric bupivacaine with 2.5 μg sufentanil. Successful spinal anesthesia was defined as a T6 sensory level achieved within 10 minutes after intrathecal drug administration and/or no epidural supplement was required during the cesarean section. The ED 50 and ED 95 were calculated with a logistic regression model.

RESULTSED 50 and ED 95 of intrathecal bupivacaine for successful spinal anesthesia were 5.67 mg (95% confidence interval [CI]: 5.20-6.10 mg) and 8.82 mg (95% CI: 8.14-9.87 mg) respectively. The incidence of hypotension in Group 8 mg and Group 10 mg was higher than that in Group 4 mg and Group 6 mg (P < 0.05). The sensory block was significantly different among groups 10 minutes after intrathecal injection (P < 0.05). The use of lidocaine in Group 4 mg was higher than that in other groups (P < 0.05). The use of phenylephrine in Group 8 mg and Group 10 mg was higher than that in the other two groups (P < 0.05). The lowest systolic blood pressure before the infant delivery of Group 8 mg and Group 10 mg was lower than the other two groups (P < 0.05). The satisfaction of muscle relaxation in Group 4 mg was lower than other groups (P < 0.05). There was no significant difference in patients' satisfaction and the newborns' Apgar score and the blood gas analysis of umbilical artery serum (P > 0.05).

CONCLUSIONOur study showed that the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery were 5.67 mg and 8.82 mg, respectively. In addition, decreasing the dose of intrathecal bupivacaine could reduce the incidence of maternal hypotension.

Adult ; Anesthesia, Epidural ; Anesthesia, Spinal ; adverse effects ; methods ; Blood Pressure ; physiology ; Bupivacaine ; administration & dosage ; adverse effects ; therapeutic use ; Cesarean Section ; Double-Blind Method ; Female ; Humans ; Male ; Sufentanil ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUND: Propofol is used as an induction and maintenance agent for general anesthesia but it can cause adverse reactions like hyperlipidemia, growth of microorganisms, and pulmonary embolisms. Microemulsion propofol was developed to avoid these side effects but incidence and severity of pain on injection is higher than with lipid emulsion propofol. We aimed to compare the effects of sufentanil in analgesic doses for reducing the injection pain of microemulsion propofol. METHODS: The candidates included eighty patients, 19-60 years old and ASA I-II. They were randomly classified into four groups and pretreated with normal saline, sufentanil 0.1 microg/kg, 0.2 microg/kg or 0.3 microg/kg before injection of microemulsion propofol. Five minutes after receiving pretreatment drug, 2 mg/kg of microemulsion propofol was injected and VAS was recorded. RESULTS: There were no significant differences in the incidence of injection pain among the groups. Severity of injection pain was significantly lower in the sufentanil 0.3 microg/kg group than normal saline and sufentanil 0.1 microg/kg group. Significant differences in blood pressure and heart rate were observed in sufentanil groups only after endotracheal intubation. One patient each in sufentanil 0.1 microg/kg and 0.3 microg/kg group experienced mild cough, one from sufentanil 0.3 microg/kg group experienced dizziness and another showed signs of hypoxia. One patient each in normal saline and sufentanil 0.1 microg/kg group showed clinical symptoms of phlebitis in the injection area. CONCLUSIONS: Pretreatment with sufentanil 0.3 microg/kg reduced the severity of microemulsion propofol injection pain without increasing arterial blood pressure and heart rate after endotracheal intubation.
Anesthesia, General ; Anoxia ; Arterial Pressure ; Blood Pressure ; Cough ; Dizziness ; Heart Rate ; Humans ; Hyperlipidemias ; Incidence ; Intubation, Intratracheal ; Phlebitis ; Propofol ; Pulmonary Embolism ; Sufentanil

BACKGROUNDTarget-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients.

METHODSThe pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples (1.5 ml) were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program.

RESULTSThe pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters: the central volume of distribution (V(1))=5.4 L, the volume of distribution at steady-state (Vdss)=195.4 L, systemic clearance (Cl(1))=1.10 L/min, and elimination half-life (t(1/2) gamma)=271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance (Cl(2)) was negatively correlated with patient age, and the volume of slowly equilibrating compartment (V(3)) was positively correlated with age. The Cl(2) and the volume of rapidly equilibrating compartment (V(2)) were influenced by gender with male patients showing higher values of Cl(2) and V(2) than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied.

CONCLUSIONSThe pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinetics adjusted to the individual patient should improve the accuracy of TCI systems.

Adult ; Aged ; Asian Continental Ancestry Group ; Female ; Humans ; Infusions, Intravenous ; methods ; Male ; Middle Aged ; Sufentanil ; administration & dosage ; blood ; pharmacokinetics ; Young Adult

BACKGROUND: Additive opioids in spinal anesthesia of cesarean section decrease the dose of local anesthetics and increase the quality of anesthesia. There were comparative studies about morphine, fentanyl, and sufentanil as an additive opioid in spinal anesthesia of cesarean section, but few studies about alfentanil. In this study we compared the effect of alfentanil with fentanyl as an additive opioid in spinal anesthesia for cesarean section. METHODS: Sixty nine pregnant women, American Society of Anesthesiologist (ASA) I-II, who were scheduled for elective cesarean section under spinal anesthesia, were randomly allocated into two groups: group F received 8 mg (1.6 ml) of bupivacaine and 15microg of fentanyl (0.3 ml) intrathecally, and group A received 8 mg of bupivacaine and 150microg of alfentanil (0.3 ml). Sensory block defined by pin-prick, intraoperative patient satisfaction for analgesia by visual analogue scale (VAS), blood pressure, and side effects were assessed. Apgar score and umbilical arterial blood gas analysis were also assessed. RESULTS: The analgesic effect of alfentanil was as good as fentanyl and VAS for satisfaction was 97.1 +/- 7.6 and 96.5 +/- 8.0 each. Time to achieve anesthetic level of T6 (6.2 vs 6.7 min), maximal block level (T3.7 vs T3.8), lowest blood pressure during the operation (60.0 vs 61.0 mmHg), duration of analgesia (77.2 vs 70.0 min), and fetal assessment were not different from those of group F, either. The incidence of nausea during operation was 48.6% in group F and 26.4% in group A (P = 0.14). CONCLUSIONS: The addition of alfentanil is comparable to fentanyl in analgesia, maternal and fetal effects in spinal anesthesia for cesarean section.
Alfentanil ; Analgesia ; Analgesics, Opioid ; Anesthesia ; Anesthesia, Spinal ; Anesthetics, Local ; Apgar Score ; Blood Gas Analysis ; Blood Pressure ; Bupivacaine ; Cesarean Section ; Female ; Fentanyl ; Humans ; Incidence ; Morphine ; Nausea ; Patient Satisfaction ; Pregnancy ; Pregnant Women ; Sufentanil

BACKGROUND: Some opioids have been shown to attenuate an ischemia-reperfusion injury in an isolated-heart model. The aim of this study was to evaluate the effect of sufentanil on the cardiac function in isolated-heart models when given before and after prolonged periods of low flow ischemia. METHODS: Isolated rat hearts were stabilized for 30 minutes and subdivided into four groups (each n = 7). The control group was subjected to low flow ischemia (LFI 0.3 ml/min) of 5% dextrose water for 30 minutes, followed by perfusion with a modified Krebs solution at a constant pressure for 60 minutes. In the sufentanil groups, different sufentanil (12.5 mg/L, 25 mg/L, 50 mg/L) doses were administered with the modified Krebs solution after 30 minutes of stabilization until the end of the experiment with the exception of the LFI group. The left ventricular end systolic pressure (LVESP), dP/dt max, heart rate and coronary flow were measured. After reperfusion, the infarct size of all groups was measured. RESULTS: The control and the sufentanil groups had a lower LVESP, dP/dt max, coronary effluent flow and arrhythmia duration after ischemia and reperfusion than those before ischemia. The infarct sizes in the sufentanil groups were smaller than those in the control group. However the infarct sizes of the sufentanil groups were similar. CONCLUSION: Sufentanil reduces the infarct size but does not improve the post-ischemic functional dysfunction.
Analgesics, Opioid ; Animals ; Arrhythmias, Cardiac ; Blood Pressure ; Glucose ; Heart ; Heart Rate ; Ischemia ; Models, Animal* ; Perfusion ; Rats* ; Reperfusion ; Reperfusion Injury ; Sufentanil* ; Ventricular Function, Left ; Water

BACKGROUND: Various anesthetic agents have been used in laryngeal microscopic surgery, because the airway is shared with the surgeon, there is a short operation duration and intense cardiovascular stimulation occurs during the surgery. Sufentanil is superior than other anesthetic agents in blocking the cardiovascular response to the airway stimulation and a short duration of effects. METHODS: Thirty patients undergoing elective laryngeal microscopic surgery were randomized to receive sufentanil 0.125 microgram/kg (group 1, n = 10), sufentanil 0.25 microgram/kg (group 2, n = 10) or sufentanil 0.5 microgram/kg (group 3, n = 10). The bispectral index score, blood pressure, heart rate, recovery time from general anesthesia, the need for additional analgesics and naloxone and the postoperative complications associated with sufentanil were measured. RESULTS: The bispectral index, blood pressure and heart rate were similar in the three groups. Only four patients in group 3 required naloxone (P < 0.05). Three patients in group 1, one in group 2 and 0 in group 3 required an additional dose of sufentanil. Postoperative sore throat was detected in 6 patients in the immediate postoperative period and in 8 patients 6 hours after the end of anesthesia in group 1 (P < 0.05). CONCLUSIONS: Sufentanil is an effective analgesic for attenuating the cardiovascular responses of airway stimulation in laryngeal microscopic surgery. In addition, sufentanil 0.25 microgram/kg is an appropriate dose for the rapid recovery and attenuation of the cardiovascular response in laryngeal microscopic surgery.
Analgesics ; Anesthesia ; Anesthesia, General ; Anesthetics ; Blood Pressure ; Heart Rate ; Humans ; Naloxone ; Pharyngitis ; Postoperative Complications ; Postoperative Period ; Sufentanil*

BACKGROUND: Laryngoscopy and tracheal intubation usually induce tachycardia and hypertension. Various drugs including esmolol and fentanyl have been employed to reduce the cardiovascular response accompanying laryngoscopy and intubation. The purpose of this study is to assess the efficacy of low dose sufentanil with esmolol in reducing hypertension and tachycardia induced by endotracheal intubation. METHODS: Forty surgical patients from Kosin medical hospital were randomly assigned to receive either normal saline (n = 20, control group) or sufentanil (0.3 microgram/kg) with esmolol (1 mg/kg) (n = 20, S & E group) before anesthetic induction. Anesthesia was induced intravenously with pentothal sodium 4 mg/kg followed by endotracheal intubation after succinylcholine 1 mg/kg. Changes in systolic blood pressure, mean arterial blood pressure, diastolic blood pressure, heart rate, and SpO2 (arterial oxygen saturation by pulse oximeter) were measured at 30 seconds, 1 minute, 2 minutes, 3 minutes, 4 minutes and 5 minutes following intubation. The values of each group were compared with preinduction baseline values, and the S&E group was compared with the control group. Data were analyzed for statistical significance using repeated measures of ANOVA and chi-square test. RESULTS: In the S&E group, the systolic and mean arterial pressures at 30 seconds and 1 minute, and diastolic blood pressure at 30 seconds after intubation were significantly lower than the values of the control group (P < 0.01). The heart rates at 30 seconds, 1 minute were significantly lower compared to the control group (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: The results suggest that pretreatment of low dose sufentanil with esmolol is effective to reduce the elevation of blood pressure and heart rate due to laryngoscopy and intubation.
Anesthesia ; Arterial Pressure ; Blood Pressure* ; Fentanyl ; Heart Rate* ; Heart* ; Humans ; Hypertension ; Intubation ; Intubation, Intratracheal* ; Laryngoscopy ; Oxygen ; Sodium ; Succinylcholine ; Sufentanil* ; Tachycardia ; Thiopental

BACKGROUND: There are quite a few studies examining the relative efficacy of different doses of intrathecal sufentanil for labor analgesia. The authors designed this prospective, randomized, double blind study to compare the efficacy and side effects of 5 and 10 microgram intrathecal sufentanil. METHODS: Forty healthy, laboring, term parturients, in the active phase of labor participated in this study. In a randomized, double-blind fashion, patients received 5 or 10 microgram intrathecal sufentanil as a part of combined spinal-epidural technique. Scores of pain, itching, nausea, and sedation were taken on visual analog scales before and every 10 minutes after drug injection for one hour. We also recorded maternal blood pressure, respiratory rate and peripheral oxygen saturation during the same time period. RESULTS: Both doses of sufentanil provided adequate analgesia. Although 10 microgram sufentanil produced a slightly more profound analgesia, the duration of pain relief did not differ between the two groups. Both drug doses were associated with significant increase in itching. The 10 microgram dose was associated with more sedation and a greater decrease in arterial oxygen saturation (SaO2). CONCLUSIONS: Both 5 and 10 microgram intrathecal sufentanil provided adequate labor analgesia. Both doses were associated with increased spinal (itching) and supraspinal (sedation, respiratory depression) side effects, the intensity of which appeared to be more profound in the 10 microgram group.
Analgesia* ; Blood Pressure ; Double-Blind Method ; Humans ; Nausea ; Oxygen ; Prospective Studies ; Pruritus ; Respiratory Rate ; Sufentanil* ; Visual Analog Scale