Sufentanil Concentrations Research Articles

Long-term stability of sufentanil quantified by UPLC-MS-MS in human plasma frozen for 11 years at -20°C.

The long-term stability of drug concentrations in human plasma samples when stored under normal laboratory conditions over several years is important for research purposes and clinical re-evaluation, but also for forensic toxicology. Fifty human plasma samples from a former clinical trial were re-analyzed after storage at -20°C for 11 years. Plasma samples were extracted using solid-phase extraction. Isotope labelled sufentanil-D5 was used as internal standard. Sufentanil plasma concentrations were determined by ultra-performance liquid chromatography (UPLC) with gradient elution, followed by tandem mass spectrometry with electrospray ionization. The linear dynamic range (LDR) was 25 - 2500 pg/mL, the limit of detection was 10 pg/mL, and the lower limit of quantification was 25 pg/mL. Intra- and inter-assay error did not exceed 6%. The deviation of the measured sufentanil plasma concentrations between the reanalysis and the first analysis was -63 ± 14% (mean ± SD). Therefore, sufentanil concentrations in human plasma were not stable in samples frozen at -20°C over 11 years.

Population pharmacokinetic modeling of sufentanil in adult Korean patients undergoing cardiopulmonary bypass surgery.

Sufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed-effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two-compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80-fold during CPB and warming phases, while the central compartment volume increased 2.74-fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL-6, IL-8, and TNF-α during CPB. The simulation indicated a 30 μg loading dose and 40 μg/h maintenance infusion for target-controlled infusion. Additionally, a bolus dose of 60 μg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia.

Tilianin enhances the antitumor effect of sufentanil on non-small cell lung cancer.

Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 μM, and the IC50 of Tilianin for H1299 cells was 44.6 μM. Functionally, 0.5 nM sufentanil and 10 μM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 μM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 μM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 μM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.

The different doses of sufentanil combined with nalmefene in bronchoscopy: a systematic review and meta-analysis.

Bronchoscopy examination is a common clinical diagnostic method. However, due to its unique operational characteristics, the procedure often induces discomfort and pain in patients. The combined use of sufentanil and nalmefene offers advantages in effectively reversing opioid-induced respiratory depression without compromising analgesic effects. However, a comprehensive analysis report on the combined use of different doses of sufentanil and nalmefene in bronchoscopy examinations has not been reported. The aim of this subject is to investigate the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy. Using computer-based and manual methods to retrieve relevant keywords, we searched the databases of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang from inception to the present to find studies evaluating the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy examinations. The quality of the included studies was assessed, and meta-analysis was conducted using RevMan 5.3 software. A total of six English-language articles, involving randomized controlled trials and reviews, and comprising 774 participants, were finally included. The control group used conventional therapy, whereas the intervention group used different doses of sufentanil combined with nalmefene. Meta-analysis results indicated that compared to conventional therapy, this approach significantly improved vital signs such as systolic blood pressure [SBP; mean difference (MD) =21.44, P<1×10-5] and diastolic blood pressure (DBP; MD =22.52, P<1×10-5), heart rate (HR; MD =25.16, P<1×10-5), and oxygen saturation (SpO2; MD =30.16, P<1×10-5). A total of 4 studies focused on sedative effects, and that of sufentanil combined with nalmefene was significantly superior to conventional therapy (P<1×10-5). Analysis of adverse events showed that the combined therapy had better outcomes in terms of hypertension and tachycardia incidence compared to the control group (P<0.001, P<1×10-5), and Riker sedation-agitation scale (SAS score) was significantly reduced (P<0.05). However, there were no significant differences in other adverse events (P>0.05). Subgroup analysis showed fewer adverse reactions at 0.4 µg/kg sufentanil concentration compared to 0.2 and 0.8 µg/kg, with only hypertension differing significantly. In clinical practice, considering the use of sufentanil combined with nalmefene can improve patients' experience during bronchoscopy examinations. However, it should be noted that this approach may not be suitable for all patients, and clinicians need to choose appropriate analgesic and sedative methods for bronchoscopy examinations based on patients' conditions and individual differences. Furthermore, it is important to recognize that this study has some limitations and further research is needed to evaluate the efficacy and safety of this approach in other types of endoscopic examinations, as well as to compare the effects and safety of different drug combinations.

Effect of different concentrations of sufentanil combined with ropivacaine on epidural fever during labor: A single-center retrospective study.

Labor epidural analgesia (LEA) is associated with increased maternal body temperature; however, the responsible mechanism is unknown. Recent studies suggest that changes in EA affect the incidence of fever and that epidural sufentanil supplementation enhances analgesia and reduces the amount of local anesthetic. The aim of this study was to evaluate the effect of different concentrations of sufentanil combined with ropivacaine on intrapartum fever during delivery. We performed a retrospective study comparing maternal fever rates in patients receiving labor analgesia between December 2018 and January 2019. Each patient receiving different concentrations of sufentanil in their EA received either proposal H (0.08% ropivacaine + 0.4 µg/mL sufentanil) or proposal L (0.08% ropivacaine + 0.2 µg/mL sufentanil), with the same nulliparous status. The primary outcome of this study was the incidence of intrapartum maternal fever, which was defined as any temperature ≥ 38°C during labor using Fisher exact test. Secondary outcome measures included visual analog scale (VAS) pain scores, birth events, and neonatal outcomes. We observed a perinatal fever incidence rate of 11.7% in the group receiving proposal L, while the incidence rate was 19.8% in the group receiving proposal H (P = .001). Five hours after administration, the average body temperature of the puerpera decreased significantly in the proposal L group compared with proposal H group. In addition, treatment with 0.2 µg/mL sufentanil provided satisfactory pain relief during labor, shortened the first stage of labor and total labor time, reduced oxytocin use, and had no significant adverse effects on neonatal outcomes. EA may increase the risk of intrapartum epidural-associated fever. Compared with the 0.4 µg/mL sufentanil group, the 0.2 µg/mL sufentanil group can provide better analgesia and improve maternal fever. These retrospective results highlighted the importance of prospective and mechanistic studies of maternal fever associated with intraspinal analgesia.

In Vitro Hepatotoxicity of Routinely Used Opioids and Sedative Drugs.

A hepatocyte cell line was used to determine the hepatotoxicity of sedatives and opioids, as the hepatotoxicity of these drugs has not yet been well characterized. This might pose a threat, especially to critically ill patients, as they often receive high cumulative doses for daily analgosedation and often already have impaired liver function due to an underlying disease or complications during treatment. A well-established biosensor based on HepG2/C3A cells was used for the determination of the hepatotoxicity of commonly used sedatives and opioids in the intensive care setting (midazolam, propofol, s-ketamin, thiopental, fentanyl, remifentanil, and sufentanil). The incubation time was 2 × 3 days with clinically relevant (Cmax) and higher concentrations (C5× and C10×) of each drug in cell culture medium or human plasma. Afterward, we measured the cell count, vitality, lactate dehydrogenase (LDH), mitochondrial dehydrogenase activity, cytochrome P 450 1A2 (CYP1A2), and albumin synthesis. All tested substances reduced the viability of hepatocyte cells, but sufentanil and remifentanil showed more pronounced effects. The cell count was diminished by sufentanil in both the medium and plasma and by remifentanil only in plasma. Sufentanil and remifentanil also led to higher values of LDH in the cell culture supernatant. A reduction of mitochondrial dehydrogenase activity was seen with the use of midazolam and s-ketamine. Microalbumin synthesis was reduced in plasma after its incubation with higher concentrations of sufentanil and remifentanil. Remifentanil and s-ketamine reduced CYP1A2 activity, while propofol and thiopental increased it. Our findings suggest that none of the tested sedatives and opioids have pronounced hepatotoxicity. Sufentanil, remifentanil, and s-ketamine showed moderate hepatotoxic effects in vitro. These drugs should be given with caution to patients vulnerable to hepatotoxic drugs, e.g., patients with pre-existing liver disease or liver impairment as part of their underlying disease (e.g., hypoxic hepatitis or cholestatic liver dysfunction in sepsis). Further studies are indicated for this topic, which may use more complex cell culture models and global pharmacovigilance reports, addressing the limitation of the used cell model: HepG2/C3A cells have a lower metabolic capacity due to their low levels of CYP enzymes compared to primary hepatocytes. However, while the test model is suitable for parental substances, it is not for toxicity testing of metabolites.

Study of Total Intravenous Anaesthesia in laparoscopic Surgery

Background: Total intravenous anaesthesia in laparoscopic surgery is safer than open laparotomy operationsbecause propofol, a sedative hypnotic agent with excellent recovery drug and having anti-emetic properties, andnew synthetic opioids (fentanyl congeners) provide excellent analgesia; hence, TIVA has become more popular inlaparoscopic surgery.Method: 45 adult patients aged between 18 to 65 undergoing laparoscopic surgery were studied. A solutionof propofol containing different concentrations of sufentanil (1 μgm per ml and 2 μgmper ml) was infused.Patient’s HR, SBP, DBP, MAP, and peripheral O2 saturation from the anaesthesia monitor was taken as a baselinemeasurement. All the hemodynamic parameters were recorded intra-operatively at different intervals of duration.Results: The changes in mean values of hemodynamic values were insignificant, and only significant parameterswere noted. 158.12 (± 80.9) mean value time to rescue analgesia (in minutes) Post-surgical complications are 3(6.6%) Nausea and vomitingConclusion: Propofol, containing different concentrations of sufentanil, provides hemodynamic stability withthe least post-surgical complications; hence, total intravenous anaesthesia is an ideal substitute for inhalationanaesthesia in laparoscopic surgery because inhalation anaesthesia has a higher risk of hemodynamic instability.

Determination of Sufentanil in Human Plasma Using Ultra-high Performance Liquid Chromatography Coupled with Tandem Mass Spectrometry (UPLC–MS/MS)

Background: Sufentanil, an opioid analgesic, is used as an induction agent for general anesthesia during surgery. Sufentanil is more active than other anesthetics and has a narrow therapeutic range. Therefore, a precise dosage regimen is necessary when administering sufentanil. Objective: This study aimed to develop a bioanalytical method for the determination of sufentanil within the sensitive concentration range more than that in a previous study utilizing protein precipitation (PP) and determine the plasma concentration of sufentanil. Methods: A method for quantitating sufentanil was developed using ultra–high performance liquid chromatography coupled with mass spectrometry (UPLC–MS/MS) and detection by electrospray ionization (ESI). The internal standard was sufentanil-d5. Chromatographic separation was performed using an Acquity UPLC HSS T3 column (50 × 2.1 mm, 1.8 μm) from Waters (Milford, MA, USA). Protein precipitation (PP) was used for sample preparation, and gradient elution was conducted using a mobile phase consisting of 1 mL of 2M ammonium acetate in 99% formic acid in 1 L of water or in 1 L of acetonitrile. The total run time for the analysis was 5 min, and the flow rate was 0.4 mL/min. Results: Standard curves were linear over ranges of 0.025–30 ng/mL for sufentanil with a correlation coefficient (r2) greater than 0.9998. The lower limit of quantification (LLOQ) was 0.025 ng/mL. The intra– and inter–day accuracies were 97.66%–108.8% and 101.25%–103.17%, respectively, and the precision did not exceed 15% for sufentanil. Conclusion: This study developed a validated, simple, sensitive, and convenient UPLC–MS/MS method for quantifying sufentanil in human plasma. This method was applied to determine sufentanil concentration in the plasma of patients undergoing surgery. The bioanalytical method using PP showed a sufficiently sensitive concentration range. This method could be applied to various pharmacokinetic studies of sufentanil.

Measurement of Sufentanil in Human Milk by Liquid Chromatography-Tandem Mass Spectrometry

A sensitive quantification method for sufentanil in human milk was developed. Samples were prepared by liquid-phase extraction. Analytes were chromatographically separated. The mobile phase contained 10 mM ammonium formate (A) and methanol (B). The ratios of A to B were 50:50, 10:90, and 50:50 sequentially. For LC-MS-MS detection, transition of the protonated precursor ions to product ions (sufentanil: m/z 387.2→m/z 238.2; internal control fentanil: m/z 337.2→m/z 158.2) was monitored. The linear quantification range of sufentanil concentration was 3.2–400 pg ·mL−1. The correlation coefficient (r2) was 0.996. The % RSD was less than 6.0% for intraday and less than 8.68% for interday precision. By this method, sufentanil contents were determined to be very low in the postnatal maternal milk samples.

Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats.

Stroke is a brain system disease with a high fatality rate and disability rate. About 80% of strokes are ischemic strokes. Cerebral ischemia-reperfusion injury (CIRI) caused by ischemic stroke seriously affects the prognosis of stroke patients. The purpose of this study is to investigate the effect of sufentanil (SUF) on CIRI model rats. We used middle cerebral artery occlusion (MCAO) to make the CIRI model in rats and monitored region cerebral blood flow (rCBF) to ensure that blood flow was blocked and recanalized. We used ELISA and RT-PCR to detect the expression of inflammatory factors in rat serum and brain tissue. In addition, we detected the expression of metalloproteinase (MMP) 2, MMP9 and collagen IV in brain tissues and performed Evans blue (EB) assay to determine the permeability of the blood-brain barrier (BBB). Finally, we clarified the apoptosis of brain tissue through the TUNEL staining and the detection of caspase 3, Bcl2 and Bax. Various concentrations of SUF, especially 5, 10 and 25μg/kg of SUF, all alleviated the infarct size, neurological function and brain edema of MCAO rats. SUF pretreatment also effectively reduced the expression of inflammatory cytokines in MCAO rats, including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α. In addition, SUF also inhibited MMP2 and MMP9 and promoted the expression of collagen IV, indicating that SUF attenuated the destruction of the BBB. SUF also inhibited caspase 3 and Bax rats and promoted Bcl2 in MCAO rats, thus inhibiting cell apoptosis. SUF pretreatment effectively improved the neurological function and cerebral infarction of MCAO rats, inhibited excessive inflammation in rats, protected the BBB, and inhibited cell apoptosis in brain tissue.

Sufentanil Inhibits the Proliferation and Metastasis of Esophageal Cancer by Inhibiting the NF-κB and Snail Signaling Pathways.

Sufentanil is a μ-opioid receptor agonist, widely used in intraoperative and postoperative analgesia of esophageal cancer. This study investigated the effects of sufentanil on the proliferation, invasion, and metastasis of esophageal carcinoma cells and its molecular mechanisms. Human esophageal carcinoma cells CaES-17 and Eca-109 were cultured in vitro. Different concentrations of sufentanil (1 and 10 μmol/L) were added to the experimental group. MTT was used to detect the proliferative activity of esophageal carcinoma cells. The migration ability of esophageal carcinoma cells was measured by the scratch test. Transwell was used to detect the invasive ability of esophageal carcinoma cells. The EMT marker expression was detected by qPCR. Meanwhile, effects of sufentanil on NF-κB and Snail expression and nucleation were evaluated. Establish a subcutaneous xenograft tumor model of nude mice with esophageal carcinoma cells and evaluate the antitumor effect of sufentanil. Sufentanil can inhibit the proliferation, invasion, and migration of CaES-17 and Eca-109 cells and has a dose-dependent relationship. The molecular mechanism showed that sufentanil could upregulate the expression of E-cadherin and inhibit the expression of vimentin. Sufentanil can inhibit the expression of NF-κB and Snail, as well as the nuclear expression of NF-κB and Snail. Xenograft tumor model results showed that sufentanil could inhibit tumor proliferation and NF-κB and Snail expression in tumor tissues of nude mice. Sufentanil inhibits esophageal cancer epithelial-mesenchymal transition (EMT) by acting on NF-κB and Snail signaling pathways to inhibit proliferation and metastasis of esophageal cancer.

Sufentanil Inhibits Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells by Upregulating miRNA-204

Sufentanil is a powerful analgesic that acts on μ-receptors, but there are few studies on sufentanil in cancer. The biological function and underlying mechanisms of sufentanil on the hepatocellular carcinoma (HCC) cells were explored in the present study. HCC cells were first treated with different concentrations of sufentanil and the most optimum concentration of sufentanil was determined. The expression of miR-204 in HCC cells was changed by transfected with miR-204 inhibitor and the transfection efficiency was assessed by qRT-PCR. CCK-8, wound-healing and Transwell assays were performed to evaluate the proliferation, migration and invasion of HCC cells, respectively. The level of AKT and PI3K phosphorylation (p-AKT and p-PI3K) were assessed by western blot analysis. Our results demonstrated that sufentanil effectively inhibited cell proliferation,migration and invasion in both Huh7 and Hep3B cells, and significantly decreased the expression of p-AKT and p-PI3K. In addition, miR-204 was upregulated in Huh7 and Hep3B cells treated with sufentanil, and low expression of miR-204 attenuated the damage of sufentanil on the viability of Huh7 and Hep3B cells. Taken together, sufentanil suppressed the proliferation, migration and invasion of HCC cells via inhibiting AKT/PI3K signaling pathway by targeting miR-204.

The Analgesic Effect of Different Concentrations of Epidural Ropivacaine Alone or Combined With Sufentanil in Patients After Cesarean Section.

Background: Patients experience moderate-high intensity postoperative pain after cesarean section (CS). The aim of this study was to investigate the optimal concentrations of ropivacaine and sufentanil for use in controlling pain after CS. Methods: One hundred and seventy-four women undergoing elective CS were randomly allocated to four groups. Epidural analgesia was administered with 0.1% ropivacaine in the R1 group, 0.15% ropivacaine in the R2 group, a combination of 0.1% ropivacaine and 0.5 μg/ml of sufentanil in the R1S group, and a combination of 0.15% ropivacaine and 0.5 μg/ml of sufentanil in the R2S group (at a basal rate of 4 ml/h, bolus dose of 4 ml/20 min as needed). Pain scores (numerical rating scale [NRS]: 0–10 cm) at rest (NRS-R), during movement (NRS-M), and when massaging the uterus (NRS-U) were documented at 6 and 24 h. We also recorded patient satisfaction scores, time to first flatus, motor deficits, and adverse drug reactions. Results: NRS (NRS-R, NRS-M, NRS-U) scores in the R2S group (2 [1–3], 4 [3–5], 6 [5–6], respectively) were lower than in the R1 group (3 [3–4], 5 [4–6], 7 [6–8], respectively) (p < 0.001, p < 0.05, p < 0.01, respectively) at 6 h; and patient satisfaction (9 [8–10]) was improved compared to the R1 group (8 [6–8]) (p < 0.01). The time to first flatus (18.7 ± 11.8 h) was reduced relative to the R1 group (25.9 ± 12.0 h) (p < 0.05). The time to first ambulation was not delayed (p > 0.05). However, the incidence of pruritus (4 [9.3%]) was increased compared to the R2 group (0 [0]) (p < 0.05) at 6 h, and the incidence of numbness (23 [53.5%], 23 [53.5%]) was increased compared to the R1 group (10 [23.3%], 10 [23.3%]) (all p < 0.01) at both 6 and 24 h. Conclusions: Although we observed a higher incidence of pruritus and numbness, co-administration of 0.15% ropivacaine and 0.5 μg/ml of sufentanil administered epidurally optimized pain relief after CS, with treated subjects exhibiting lower NRS scores, shorter time to first flatus, and higher patient-satisfaction scores.

Analgesic efficacy of sufentanil in dressings after surgical treatment of burn wounds

BackgroundThe aim of this study was to assess the analgesic efficacy of sufentanil in dressings after surgical treatment of burn wounds. Patients and methodsTwenty adult patients, who underwent surgical treatment of third–degree burn wounds under general anesthesia, were included. Two of the patients underwent surgery twice. During surgery, patients received 50–100 μg fentanyl every 20–30 min and, after surgery, patients received 100 mg ketoprofen twice daily. Additionally, ten patients (group 1) received 50 μg sufentanil added to the burn wound dressings soaked in octenidine and phenoxyethanol while 10 patients (group 2) received 25 μg sufentanil added to the same dressings. The rescue analgesic, which was administered when pain intensified, was 5 mg subcutaneous morphine. Plasma sufentanil concentrations were assayed at 1, 2, 3, and 6 h after surgery completion and when pain was reported, along with pain intensity evaluation. ResultsSufentanil was not detected in the serum of any patients. Rescue morphine was given during the postoperative period (24 h) in one patient in group 1 (who underwent surgery twice) and three patients in group 2. The mean sufentanil concentration in dressings was higher in group 1 (0.13 ± 0.03) than group 2 (0.06 ± 0.03 μg/mL; p < 0.001). The group 1 patient who received rescue morphine had a sufentanil concentration of 0.10 μg/mL, which was the lowest concentration in group 1. Group 2 patients who received rescue morphine had sufentanil concentrations of at least two–fold lower (0.03–0.05 μg/mL). No adverse effects were observed. ConclusionsSufentanil in dressings after burn wound surgery provides effective and safe analgesia and the sufentanil concentration in dressings should be ≥0.10 μg/mL in a solution of octenidine and phenoxyethanol.

Effects of different sufentanil target concentrations on the MACBAR of sevoflurane in patients with carbon dioxide pneumoperitoneum stimulus

BackgroundThis study aims to observe the effects of different target controlled plasma sufentanil concentrations on the minimum alveolar concentration (MAC) of sevoflurane for blocking adrenergic response (BAR) in patients undergoing laparoscopic cholecystectomy with carbon dioxide pneumoperitoneum stimulation.MethodsEighty-five patients undergoing laparoscopic cholecystectomy, aged 30–65 years, with American Society of Anesthesiologists physical status I-II, were enrolled in this study. All the patients were randomly divided into 5 groups (S0, S1, S2, S3, S4) with different sufentanil plasma target concentration (0.0, 0.1, 0.3, 0.5, 0.7 ng ml− 1). Anesthesia was induced by inhalation of 8% sevoflurane in 100% oxygen, and 0.6 mg kg− 1 of rocuronium was intravenously injected to facilitate the insertion of a laryngeal mask airway. The end-tidal sevoflurane concentration and sufentanil plasma target concentration were adjusted according to respective preset value in each group. The hemodynamic response to pneumoperitoneum stimulus was observed after the end-tidal sevoflurane concentration had been maintained stable at least for 15 min. The MACBAR of sevoflurane was measured by a sequential method. Meanwhile, epinephrine (E) and norepinephrine (NE) concentrations in the blood were also determined before and after pneumoperitoneum stimulus in each group.ResultsWhen the method of independent paired reversals was used, the MACBAR of sevoflurane in groups S0, S1, S2, S3, S4 was 5.333% (confidence interval [CI] 95%: 5.197–5.469%), 4.533% (95% CI: 4.451–4.616%), 2.861% (95% CI: 2.752–2.981%), 2.233% (95% CI: 2.142–2.324%) and 2.139% (95% CI: 2.057–2.219%), respectively. Meanwhile, when the isotonic regression analysis was used, the MACBAR of sevoflurane in groups S0, S1, S2, S3, S4 was 5.329% (95% CI: 5.321–5.343%), 4.557% (95% CI: 4.552–4.568%), 2.900% (95% CI: 2.894–2.911%), 2.216% (95% CI: 2.173–2.223%) and 2.171% (95% CI: 2.165–2.183%), respectively. The MACBAR was not significantly different between groups S3 and S4 when using 0.5 and 0.7 ng ml− 1 of sufentanil plasma target concentrations. No significant difference was found in the change of E or NE concentration between before and after pneumoperitoneum stimulation in each group.ConclusionsThe MACBAR of sevoflurane can be decreased with increasing sufentanil plasma target concentrations. A ceiling effect of the decrease occurred at a sufentanil plasma target concentration of 0.5 ng ml− 1. When the sympathetic adrenergic response was inhibited in half of the patients to pneumoperitoneum stimulation in each group, the changes of E and NE concentrations showed no significant differences.Trial registrationThe study was registered at http://www.chictr.org.cn (ChiCTR1800015819, 23, April, 2018).

Investigation of the Minimum Local Analgesic Concentration of Epidural Sufentanil Combined With Ropivacaine for Labor Analgesia

Worldwide, there are only few studies focusing on labor analgesia on the MLAC (minimum local analgesic concentration) or EC50 (median effective concentration) of sufentanil and ropivacaine. Therefore, we determine the MLAC or EC50 of sufentanil and ropivacaine for epidural analgesia by using an up-down sequential allocation and survey its adverse effect in a prospective blinded randomized trial. Sixty nulliparous full-term parturients who required labor analgesia were recruited and randomly divided into the sufentanil and ropivacaine groups. The formulation was 25 μg sufentanil combined with 0.1% ropivacaine (added 0.9% normal saline to 75 ml). According to the response of a previous parturient, the dosage of sufentanil was increased or decreased by 5 μg in the sufetanil group; meanwhile, we also administrated an initial concentration of 0.1% ropivacaine combined with 22.5 μg sufentanil (added 0.9% normal saline to 75 ml) in the ropivacaine group. The concentration of ropivacaine was increased or decreased by 0.01% following the response of the previous parturient. The Brownlee up-down sequential allocation was used to estimate the MLAC of epidural ropivacaine and its 95% confidence intervals in labor analgesia. There were no significant changes for the two groups, including for age, height weight, active stage, second stage of labor, and gestational weeks (P = 0.769, 0.900, 0.603, 0.441, 0.577, and 0.695, respectively). The VAS scores of the parturient decreased to varying degrees (P < 0.0001) after labor analgesia compared with VAS before labor analgesia, and the most effective analgesia was reached in 60 min. The EC50 dose of epidural ropivacaine combined with 0.3 μg/mL sufentanil was 0.09687%, and the 95% CI was 0.08944%~0.1043%. Five parturients had PONV, and the incidence rate was 16.7%; one parturient had pruritus, so the incidence rate was 3.3%. The EC50 dose of epidural sulfetanil combined with 0.1% ropivacaine was 18.76 μg with a 95% confidence interval of 13.5-24.48 μg. There were no significant differences in the active stage, second stage of labor, and maternal and fetal hemodynamic data between the two groups. Notably, the Apgar scores for 1min and 5min were 10scoresfor almost allof thesepatients. There were no significant differences between the two groups for maternal and fetal side effects, which had very low incidence rates. The MLAC of epidural sufentanil or ropivacaine could provide satisfactory and safe analgesia for parturients while having a low incidence rate of side effects.

Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy

BackgroundSufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are scarce. Here, we aimed to develop a population PK model of sufentanil in ECMO patients and to suggest dosing recommendations.MethodsThis prospective cohort PK study included 20 patients who received sufentanil during venoarterial ECMO (VA-ECMO). Blood samples were collected for 96 h during infusion and 72 h after cessation of sufentanil. A population PK model was developed using nonlinear mixed effects modelling. Monte Carlo simulations were performed using the final PK parameters with two typical doses.ResultsA two-compartment model best described the PK of sufentanil. In our final model, increased volume of distribution and decreased values for clearance were reported compared with previous PK data from non-ECMO patients. Covariate analysis showed that body temperature and total plasma protein level correlated positively with systemic clearance (CL) and peripheral volume of distribution (V2), respectively, and improved the model. The parameter estimates of the final model were as follows: CL = 37.8 × EXP (0.207 × (temperature − 36.9)) L h−1, central volume of distribution (V1) = 229 L, V2 = 1640 × (total plasma protein/4.5)2.46 L, and intercompartmental clearance (Q) = 41 L h−1. Based on Monte Carlo simulation results, an infusion of 17.5 μg h−1 seems to reach target sufentanil concentration (0.3–0.6 μg L−1) in most ECMO patients except hypothermic patients (33 °C). In hypothermic patients, over-sedation, which could induce respiratory depression, needs to be monitored especially when their total plasma protein level is low.ConclusionsThis is the first report on a population PK model of sufentanil in ECMO patients. Our results suggest that close monitoring of the body temperature and total plasma protein level is crucial in ECMO patients who receive sufentanil to provide effective analgesia and sedation and promote recovery.Trial registrationClinicaltrials.gov NCT02581280, December 1st, 2014.

Dose determination of sufentanil for intravenous patient-controlled analgesia with background infusion in abdominal surgeries: A random study.

ObjectivesSufentanil has been widely used in epidural PCA, while its use in intravenous PCA has rarely been reported. Based on its use in target controlled infusion, we reckoned that the effect-site concentration of sufentanil would be steady if background infusion is given in intravenous PCA. This prospective, single center, randomized study with a three arm parallel group design aims to find out the appropriate dose of sufentanil when used in intravenous PCA with background infusion in abdominal surgeries.MethodsPatients diagnosed with gastrointestinal cancer and consented to the study were recruited. The analgesia pump with one of three different doses of sufentanil (1.5, 2.0 or 2.5 μg/kg) was attached to the patient through peripheral venous line right after surgery. The primary endpoint was pain scale VAS up to 48 hours postoperatively.ResultsIn our study 90 patients were analyzed. In group B (SF 2.0) and C (SF2.5), patients had better pain relief than in group A (SF 1.5). There was no difference between group B and C in pain intensity at rest. While in group C more patients got pain relived at activity than in group B. All three groups had low and similar incidence of adverse effects of sufentanil.ConclusionThe dose 2.5 μg/kg of sufentanil with background infusion is preferred because of better pain alleviation at activity without increase of adverse effects up to 48 hours after surgery.

Comparison of different sufentanil-tramadol combinations for pain relief within the first 24 hours after cesarean section: a retrospective study.

IntroductionPostcesarean section pain management is important for both the mother and the newborn. This study compared the analgesic effects and incidence of adverse events associated with intravenous patient-controlled analgesia (iv-PCA), using different sufentanil–tramadol combinations for postoperative pain control.MethodsParturients (n=5,794) who had been scheduled for cesarean section under neuraxial anesthesia and had received iv-PCA between September 2013 and March 2017 were retrospectively analyzed. These patients were assigned to three groups, based on different sufentanil–tramadol combinations: ST1 (n=1,347), ST2 (n=2,401), and ST3 (n=2,046). The analgesic efficacy, total drug consumption, and incidence of adverse effects within 24 hours after surgery were compared among the three groups.ResultsThe ST3 group had lower visual analog scale pain scores at rest and with movement at all time points during the first 24 hours postoperatively than the other two groups (P<0.01, Bonferroni corrected). The sufentanil dosage administered to the ST3 group was lower, and the tramadol dosage was higher than those administered to the other groups within 24 hours after surgery (P<0.01, Bonferroni corrected). Moreover, all parturients scored 2 points on the Ramsay sedation scale. Adverse reactions such as pruritus and respiratory depression were not observed in any group. No significant differences were noted in the incidence of nausea/vomiting, abdominal distension, and dizziness among the three groups (P>0.05).ConclusionThe visual analog scale scores for postoperative pain decreased as the concentrations of sufentanil and tramadol administered in iv-PCA moderately increased over 24 hours after surgery. This analgesic strategy resulted in a significant reduction in the total sufentanil requirement without increasing the incidence of adverse effects.

Monitoring of sedation depth in intensive care unit by therapeutic drug monitoring? A prospective observation study of medical intensive care patients

BackgroundAnalgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures.MethodsForty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman’s rank correlation coefficient rho (ρ).ResultsAverage age of the population was 57.8 ± 16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS (ρ = − 0.467) and Ramsay Scores (ρ = 0.476). Serum concentrations of sufentanil correlated weakly with RASS (ρ = − 0.312) and Ramsay Scores (ρ = 0.295). Correlations between BIS index and serum concentrations of midazolam (ρ = − 0.252) and sufentanil (ρ = − 0.166) were low.ConclusionCorrelations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients.