Concentration Of Remifentanil Research Articles

Relationship between intraoperative requirement for anesthetics and postoperative analgesic consumption in laparoscopic colectomy: a randomized controlled double-blinded study.

This study investigated the relationship between intraoperative requirement for an inhalational anesthetic (sevoflurane) or an opioid (remifentanil) and postoperative analgesic consumption. The study included 200 adult patients undergoing elective laparoscopic colectomy. In the sevoflurane group, the effect-site concentration of remifentanil was fixed at 1.0 ng/ml, while the inspiratory sevoflurane concentration was adjusted to maintain an appropriate anesthetic depth. In the remifentanil group, the end-expiratory sevoflurane concentration was fixed at 1.0 vol.%, and the remifentanil concentration was adjusted. Pain scores and cumulative postoperative analgesic consumptions were evaluated at 2, 6, 24, and 48 h after surgery. Average end-tidal concentration of sevoflurane and effect-site concentration of remifentanil were 2.0 ± 0.4 vol.% and 3.9 ± 1.4 ng/ml in the sevoflurane and remifentanil groups, respectively. Cumulative postoperative analgesic consumption at 48 h postoperatively was 55 ± 26 ml in the sevoflurane group and 57 ± 33 ml in the remifentanil group. In the remifentanil group, the postoperative cumulative analgesic consumptions at 2 and 6 h were positively correlated with intraoperative remifentanil requirements (2 h: r = 0.36, P < 0.001; 6 h: r = 0.38, P < 0.001). However, there was no significant correlation in the sevoflurane group (r = 0.04, P = 0.691). The amount of intraoperative requirement of short acting opioid, remifentanil, is correlated with postoperative analgesic consumption within postoperative 6 h. It may be contributed by the development of acute opioid tolerance. However, intraoperative sevoflurane requirement had no effect on postoperative analgesic consumption.

Effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection: A prospective randomized, double-blind, placebo-controlled study.

Esketamine may reduce acute postoperative pain in several settings. However, the effects of low-dose esketamine on postoperative pain after vestibular schwannoma (VS) resection with propofol/remifentanil total intravenous anaesthesia (TIVA) are unclear. The aim of this study is to observe the effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection. This single-centre, randomized, placebo-controlled, double-blind trial included 90 adults undergoing VS resection via the retrosigmoid approach with TIVA. The patients were randomly allocated to two groups: esketamine or control (n = 45 in each group). Patients received low-dose esketamine (0.2 mg/kg) or a similar volume of normal saline after dural closure. The primary outcome was the pain score during movement (gentle head movement) at 24 h postoperatively. Secondary outcomes included recovery time, bispectral index (BIS) values and haemodynamic profiles during the first 30 min after esketamine administration, and adverse effects. Low-dose esketamine did not reduce pain scores at rest (P > .05) or with movement (P > .05) within the first 24 h after surgery. Esketamine moderately increased BIS values for at least 30 min after administration (P < .0001) but did not affect heart rate (P = .992) or mean arterial blood pressure (P = .994). Esketamine prolonged extubation time (P = .042, 95% confidence interval: 0.08 to 4.42) and decreased the effect-site concentration of remifentanil at extubation (P = .001, 95% confidence interval: -0.53 to -0.15) but did not affect the time to resumption of spatial orientation. Postoperative nausea and vomiting rates did not differ between groups, and no hallucinations or excessive sedation was observed. Intraoperative low-dose esketamine did not significantly reduce acute pain after VS resection with propofol/remifentanil TIVA. However, BIS values increased for at least 30 min after esketamine administration.

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.

Predicting the optimal concentration of remifentanil for skull pin fixation with hemodynamic and analgesia nociception index monitoring

Inadequate antinociception during skull pin fixation may cause hemodynamic instability in intracranial surgery. The optimal concentration of remifentanil to provide adequate antinociception and stable hemodynamics during skull pin fixation under analgesia nociception index monitoring is unknown. This study is to assess the 90% effective concentration of remifentanil for skull pin fixation under hemodynamic and analgesia nociception index monitoring. Twenty-six patients were enrolled for intracranial surgery, anesthesia was induced and maintained under total intravenous anesthesia using target-controlled infusion for remifentanil and propofol under analgesia nociception index and bispectral index monitoring. Skull pin fixation was performed at different effect-site concentrations of remifentanil required for Dixon's up-and-down method with a step size of 0.5 ng/ml under bispectral index 40–60. Inadequate antinociception is defined when either ANI < 30 or > 20% in hemodynamic changes from baseline (e.g. heart rate > 100 beats/min, or blood pressure > 180/100 mmHg) and the effect-site concentration of remifentanil is considered as failure. It is considered success as ANI > 30 and < 20% hemodynamic changes from baseline simultaneously. Seven pairs of failure/success were used for probit analysis. The 90% effective concentration of remifentanil for skull pin fixation with adequate antinociception and hemodynamic stability was 4.7 ng/ml.

Effect of remifentanil on three effect-site concentrations of propofol and their relationship during electroencephalography at loss of response, at maximum alpha power, and at onset of burst suppression: a prospective randomized trial.

The effect-site concentration (Ce) at loss of response (Ce-LOR) to propofol closely correlates both with Ce as electroencephalographic alpha power becomes highest (Ce-alpha) and with Ce at onset of burst suppression (BS) (Ce-OBS), when no opioids are administered. Co-administration of opioids dose-dependently decreases Ce-LOR. We investigated the influence of remifentanil on the relationship between these three Ces. After receiving approval from our local ethical committee, with written informed consent, we enrolled 90 participants (ASA-PS I or II) who were scheduled for elective surgery. Participants were randomly assigned to three groups: constant remifentanil Ce 0ng/ml (Remi_0); 1ng/mL (Remi_1); and 2ng/mL (Remi_2). We recorded both raw EEG and EEG-derived parameters on a computer. After reaching remifentanil equilibrium, we administered propofol using a target-controlled infusion pump such that propofol Ce increased to about 0.3μg/mL/min. After determining Ce-LOR, we administered 0.6mg/kg of rocuronium and started mask ventilation. The study protocol ended after observation of BS. Three participants were excluded. Ce-LOR in each group (Remi_0, Remi_1, Remi_2) was 2.00 ± 0.58μg/mL, 1.43 ± 0.49μg/mL, and 1.37 ± 0.42μg/mL. Ce-alpha was 2.91 ± 0.63μg/mL, 2.30 ± 0.41μg/mL, and 2.12 ± 0.39μg/mL. Ce-OBS was 3.80 ± 0.69μg/mL, 3.25 ± 0.68μg/mL, and 2.90 ± 0.57μg/mL. In three other instances, Ce was decreased by remifentanil. Generalized linear model analysis revealed that remifentanil had no influence on the relationship between the three Ces. During propofol anesthesia, even low concentrations of remifentanil shifted concentration-related electroencephalographic changes.

Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study

BackgroundThe aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care unit (ICU).MethodsThis was a multicenter, randomized, double-blinded, fentanyl-controlled, non-inferiority phase 3 study. Patients aged ≥ 20 years requiring 6 h to 10 days mechanical ventilation in an ICU and requiring pain relief were randomly assigned in a 1:1 ratio to receive either remifentanil (n = 98) or fentanyl (n = 98). Dose was titrated from an infusion rate of 1 mL/h (remifentanil: 0.025 µg/kg/min, fentanyl: 0.1 µg/kg/h) until the target level of analgesia (behavioral pain scale [BPS] ≤ 5 or numerical rating score [NRS] ≤ 3) was achieved by escalating the dose in 1 mL/h increasing. Administration was then adjusted to maintain the target level of analgesia until weaning from the ventilator. The primary endpoint was the proportion of patients who did not require rescue fentanyl. Safety was assessed according to standard procedures. PK of remifentanil in the arterial blood was assessed in 24 patients.ResultsThe proportion of patients achieving the primary endpoint in the remifentanil and fentanyl groups was 100% (92/92) and 97.8% (88/90), respectively. The difference between the groups was 2.2% (95% confidence interval, − 0.8–5.3) and non-inferiority of remifentanil to fentanyl was verified (p < 0.0001). The incidences of any adverse events in the remifentanil and fentanyl groups was 34 of 92 patients (37.0%) and 34 of 90 patients (37.8%), respectively. Adverse drug reactions was 12 in 92 patients (13.0%) and 15 in 90 patients (16.7%), respectively. In the PK analysis, blood remifentanil concentration decreased within 10 min to almost 50% of the end of administration, suggesting rapid offset of action following discontinuation of remifentanil.ConclusionsRemifentanil can be used safely for pain management in mechanically ventilated Japanese patients in the ICU.Trial registration: Japan Registry of Clinical Trials, jRCT2080224954. Registered 20 November 2019, https://jrct.niph.go.jp/latest-detail/jRCT2080224954.

Anesthetic drug concentrations and placental transfer rate in fetus between term and preterm infants, twins, and singletons.

Objective: This study aims to determine the drug concentration of etomidate, remifentanil, and rocuronium bromide for general anesthesia in fetus as well as the placental transport rate between term and preterm delivery, twins, and singleton. Study design: Sixty parturients with 72 fetuses undergoing cesarean section under general anesthesia were included. According to whether the fetus was a twin or premature, parturients were divided into Group I (term singleton), Group II (premature singleton), Group III (term twins), and Group IV (premature twins). The preoperative demographic characteristics and laboratory examination of parturients, hemodynamic indicators, the Apgar score of neonates at 1, 5, and 10min after delivery and at specific assigned values, umbilical artery blood gas analysis results, neonatal weight, and resuscitative measures were recorded. Anesthetic drug concentrations in maternal arterial (MA), umbilical arterial (UA), and umbilical venous (UV) blood were detected by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Result: No significant differences were observed in the concentrations of etomidate, remifentanil, and rocuronium bromide in MA, UV, and UA blood, or in the UV/MA and UA/UV ratios between term and preterm infants, twins, and singletons. Moreover, there was no variation in the anesthetic drug concentration among each pair of twins. Additionally, no correlation was found between the neonatal weight and the plasma concentrations of anesthetic drugs in UV and UA blood, except for remifentanil in UA blood. Conclusion: Preterm or twin deliveries do not affect the neonatal concentration of etomidate, remifentanil, and rocuronium bromide used in general anesthesia for cesarean sections. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2100046547.

Randomized comparison of effects of two different remifentanil dose on surgical conditions during endoscopic sinus surgery

BackgroundThe combination of propofol and remifentanil results in better surgical field conditions during endoscopic sinus surgery than inhalation anesthesia. This study compared surgical field conditions between two groups receiving low or high concentration of remifentanil and hemodynamic variables using non-invasive cardiac monitoring.MethodsFifty-four patients between ASA I or II, were randomly assigned to either the high-concentration remifentanil group (HR), effect-site concentration of 8 ng/mL or the low-concentration remifentanil group(LR), effect-site concentration of 4 ng/mL. Surgical condition was evaluated using the Boezaart Surgical Field Grading Scale presented by Boezaart. Cardiac output was measured using non-invasive cardiac monitoring (CSN-1901).ResultsIn terms of surgical conditions, the HR group showed significantly lower values than the LR group (p = 0.021) at 90 min after the start of surgery. Heart rate was significantly lower in the HR group than the LR group at 30, 60, and 90 min after the start of surgery (30 min; p = 0.005, 60 min; p = 0.002, 90 min; p = 0.001). There was a statistically significant decrease of cardiac output in the HR group compared to the LR group immediately after endotracheal intubation and at 30, 60, and 90 min after the start of surgery (Base; P = 0.222, Intubation; P = 0.016, 30 min; p = 0.014, 60 min; P = 0.012, 90 min; P = 0.008). However, in the case of stroke volume, there was no significant difference between the two groups in all measurements.ConclusionWhen comparing the HR group and the LR group, the surgical condition was improved at 90 min after the start of surgery. MAP was lower in the HR group and this was a result of reduction in cardiac output primarily attributed to the decrease in heart rate rather than a decrease in stroke volume.Trial registrationClinical Trial Registry of the Republic of Korea (KCT0006453).

Total Intravenous Anesthesia Protocol for Decreasing Unacceptable Movements during Cerebral Aneurysm Clipping with Motor-Evoked Potential Monitoring: A Historical Control Study and Meta-Analysis.

Injury can occur during intraoperative transcranial motor-evoked potential (MEP) monitoring caused by patient movement related to insufficient neuromuscular blocking agent use. Here, we evaluated the incidence of unacceptable movements in patients undergoing intraoperative MEP monitoring following our anesthetic protocol. We reviewed the anesthesia records of 419 patients who underwent unruptured cerebral aneurysm clipping with intraoperative MEP monitoring. The anesthetic protocol included target-controlled infusion with a fixed effect-site propofol concentration of 3 μg/mL and an adjustable effect-site remifentanil concentration of 10-12 ng/mL. We compared our findings of the intraoperative parameters and incidence of spontaneous movement and respiration with those of published meta-analysis studies. Spontaneous movement and respiration occurred in one (0.2%) patient each. The meta-analysis included six studies. The pooled proportions of spontaneous movement and respiration were 6.9% (95% confidence interval [CI], 1.3-16.5%) and 4.1% (95% CI, 0.5-14.1%), respectively. The proportion of spontaneous movement in our study was significantly lower than that in previous studies (p = 0.013), with no significant difference in spontaneous respiration (p = 0.097). Following our center's anesthesia protocol during cerebral aneurysm clipping resulted in a low incidence of spontaneous respiration and movement, indicating its safety for patients undergoing intraoperative MEP monitoring.

Effect-site concentrations of remifentanil for smooth emergence from combined epidural–general anesthesia or general anesthesia in patients using video double-lumen tube: A randomized trial

ObjectiveThe present study aimed to determine the effect-site concentration of remifentanil of 90% (EC90) for smooth emergence in patients with a video DLT (VDLT) under sevoflurane-maintained general anesthesia and to investigate whether the EC90 was affected by epidural anesthesia. MethodsOne hundred and twenty patients who underwent video-assisted thoracic surgery (VATS) were enrolled. Patients received either general anesthesia combined with epidural anesthesia (PEA group, n = 60) or general anesthesia (GA group, n = 60). The primary outcome was the EC90 for smooth emergence in both groups. The secondary outcomes were intraoperative emergence, smooth emergence, recovery, and hemodynamic profiles in both groups. ResultThe EC90 values for smooth emergence in patients using VDLT were 3.5 ng/ml (95% confidence interval [CI], 3.3–4.4 ng/ml) in the PEA group and 2.7 ng/ml (95% CI, 2.5–3.2 ng/ml) in the GA group. The total amount of remifentanil infusion during emergency was significantly higher in the PEA group (164.6 ± 47.9 μg) than in the GA group (127.1 ± 30.4 μg) (P < 0.001). The number of patients who experienced hypotension during emergency in the PEA group was higher than that in the GA group (46.7% versus 13.3%, P < 0.001). ConclusionThe EC90 of remifentanil for smooth emergence in patients with VDLT under general anesthesia combined with epidural anesthesia (3.5 ng/ml) was higher than that under general anesthesia (2.7 ng/ml). Trial registrationChinese Clinical Trial Registry, ChiCTR2100054230.

The effect-site concentration of remifentanil blunting endotracheal intubation responses during anesthesia induction with etomidate: a dose-finding study

BackgroundRemifentanil can inhibit the hemodynamic responses caused by endotracheal intubation, but the effect-site concentration of it required to control intubation responses when combined with etomidate has not been demonstrated. The purpose of this study was to determine the effect-site concentration of remifentanil blunting tracheal intubation responses in 50% and 95% of patients (EC50 and EC95) during etomidate anesthesia.MethodsAmerican Society of Anesthesiologists physical status (ASA) I-II elective surgical patients receiving target-controlled infusion (TCI) of remifentanil, followed by etomidate and rocuronium for anesthesia were enrolled. The Belive Drive A2 monitor was used to calculate the MGRSSI (Maygreen Sedative state index) of hypnotic effect and the MGRNOX (Maygreen Nociception index) of nociception. The MGRSSI and the MGRNOX value were generated every 1 s. Mean arterial pressure (MAP) and heart rate (HR) were measured every minute, noninvasively. Using the modified Dixon’s up-and-down method, the concentration of remifentanil was determined based on the intubation response of the previous patient. The cardiovascular response during endotracheal intubation was defined as positive when MAP or HR is 20% higher than the pre-intubation value. A probit analysis was used for calculating EC50, EC95 and 95% confidence interval (CI).ResultsThe EC50 and EC95 of remifentanil blunting tracheal intubation responses were found to be 7.731 ng/ml (95%CI: 7.212–8.278 ng/ml) and 8.701 ng/ml (95%CI: 8.199–11.834 ng/ml). There were statistically significant increases in HR, MGRSSI and MGRNOX value to tracheal intubation in the positive responses group compared to the negative group. The most common adverse event was postoperative nausea and vomiting, which occurred in 3 patients.ConclusionRemifentanil effect-site concentration of 7.731 ng/ml is effective in blunting sympathetic responses to tracheal intubation in 50% of patients when combined with etomidate anesthesia.Trial registrationThe trial was registered at the Chinese Clinical Trials Registry (www.chictr.org.cn, registration number: ChiCTR2100054565, date of registration: 20/12/2021).

Https://medcraveonline.com/JACCOA/anesthetic-and-hemodynamic-management-in-patients-with-different-approaches-for-multiple-neurological-pathologies-case-report.html

Purpose: To evaluate the impact of three different effect-site concentrations of remifentanil [1.0, 2.0 and 2.5 ng.ml-1] on cough, heart rate and systolic blood pressure during extubation after balanced anesthesia with desflurane or sevoflurane. Design: Double-blinded controlled trial. Setting: Operating room. Patients: ASA I-II adults (n=451) who underwent elective procedures. Interventions: Subjects were randomly assigned to maintain remifentanil effect-site concentrations at 1.0, 2.0 and 2.5 ng.ml-1 by a target control infusion system after receiving balanced general anesthesia with remifentanil and sevoflurane vs. desflurane. Measurements: Cough severity (using a four-point intensity scale), heart rate and systolic blood pressure were registered during eye opening, tracheal extubation and 2.5 minutes after. Main Results: Cough was significantly reduced in all groups of remifentanil at 2.0 and 2.5 ng.ml-1 during eye opening, tracheal extubation and 2.5 minutes after, when compared with 1.0 ng.ml-1 [Risk ratio (95% CI) at tracheal extubation 0.35 (0.23-0.53) and 0.33 (0.21-0.52) for desflurane; 0.50 (0.35-0.73) and 0.45 (0.30-0.73) for sevoflurane, respectively. P &lt; 0.001]. There were no significant differences on heart rate or systolic blood pressure values at these time points for any of the studied groups. Conclusion: In adult patients of elective procedures under balanced general anesthesia with sevoflurane or desflurane, maintaining a remifentanil effect-site concentration at 2.0-2.5ng.ml-1 significantly reduce the risk of cough but not hemodynamic responses during tracheal extubation.

Pharmacodynamic mechanism-based interaction model for the haemodynamic effects of remifentanil and propofol in healthy volunteers

BackgroundPropofol and remifentanil are frequently combined for the induction and maintenance of general anaesthesia. Both propofol and remifentanil cause vasodilation and potentially reduce arterial BP. We aimed to develop a mechanism-based model that characterises the haemodynamic interactions between remifentanil and propofol. MethodsData from two clinical trials in healthy volunteers were analysed using remifentanil-alone, propofol-alone, and combination groups. We evaluated remifentanil effects on haemodynamics using a previously developed mechanism-based haemodynamic model of propofol. The interaction between propofol and remifentanil was explored using the principles of the general pharmacodynamic interaction (GPDI) model. ResultsRemifentanil alone increased the dissipation rate of total peripheral resistance by 50% at 3.0 ng ml−1. Additionally, the dissipation rates of HR and stroke volume were attenuated by 4.8% and 4.9% per 1 ng ml−1 increase in remifentanil concentration, respectively. The maximal effect of propofol alone in decreasing the production rate of total peripheral resistance was 78%, which decreased to 32% when combined with remifentanil 4 ng ml−1. The effects of remifentanil on HR and stroke volume were attenuated by propofol with maximum decreases of 11.9% and 21.2%, respectively. Goodness-of-fit plots and prediction-corrected visual predictive check plots showed good predictive performance of the models. ConclusionsThe structure of the previous mechanism-based haemodynamic model for propofol was able to describe the effects of remifentanil alone on haemodynamic variables. The GPDI model provided a good framework for characterising the pharmacodynamic interaction between remifentanil and propofol on haemodynamic properties. Clinical trial registrationNCT02043938; NCT03143972.

Good correlation between necessary remifentanil concentrations in individual patients determined from sedative-analgesic interactions using pharmacokinetic simulations and the remifentanil concentrations used at anesthesiologists’ discretion

Background: Analgesic and sedative agents interact with each other, and their relationship is explained in a curve convex below. In the automated control anesthesia system based on this relationship that we developed, the dose of analgesic is adjusted with the necessary remifentanil concentration, determined with propofol-remifentanil interactions, as an estimated maximal individual concentration (esMIC). With the system, a study in patients under anesthesia management by an anesthesiologist was conducted to compare the effect-site concentration (ESC) of remifentanil administered at the anesthesiologist’s discretion and the esMIC calculated with drug-drug interactions for their relationship and to assess whether the analgesic dose administered based on esMIC is appropriate.&#x0D; Methodology: In the present study involving 20 patients, anesthesiologists changed the propofol (P) infusion rate and remifentanil (R) infusion rate to maintain BIS value of 45. The estimated target-effect-site concentration of propofol for maintaining BIS 45 and the ESC of remifentanil (ESC_R) based on the model by Minto et al. were calculated. Moreover, with these data sets, the isodynamic curve of ESC of propofol (ESC_P) for maintaining BIS 45 (Y) and ESC_R (X) was determined to be an equilateral hyperbola (Y = c/(X-a) + b). With the ESC_R at which even raising ESC_R would result in small decreases in ESC_P considered the esMIC, the ESC_R at the point at which the slope of this curve is apos;1 (neutral point) and at the point of the curve where the y-component deviation of the asymptote (y = b) is 20% (esMIC20) calculated every 6 sec. The ESC_R at the time point of an adequate analgesic state as deemed by the anesthesiologist after anesthesia had been started for 15 min was compared with the esMIC20 determined by objective calculations.&#x0D; &#x0D; Results: The ESC_R and esMIC were 11.9 ± 2.4 and 11.6 ± 2.0 ng/ml, respectively. Moreover, the median ESC_R and esMIC in the patients showed a very good correlation (correlation coefficient R² = 0.88, p &lt; 0.01).&#x0D; Conclusion: The necessary analgesic concentrations estimated with drug-drug interactions did not contradict those determined at anesthesiologists’ discretion and are considered to assure a reasonable analgesic state.&#x0D; Key words: Analgesia; Sedation; Remifentanil; Effect-Site Concentrations&#x0D; Citation: Matsuki Y, Nagata O, Shigemi K. Good correlation between necessary remifentanil concentrations in individual patients determined from sedative-analgesic interactions using pharmacokinetic simulations and the remifentanil concentrations used at anesthesiologists’ discretion. Anaesth. pain intensive care 2023;27(5):491−494; DOI: 10.35975/apic.v27i5.2300&#x0D; Received: April 04, 2023; Reviewed: May 13, 2023; Accepted: June 16, 2023

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

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

EEG responses to standardised noxious stimulation during clinical anaesthesia: a pilot study.

During clinical anaesthesia, the administration of analgesics mostly relies on empirical knowledge and observation of the patient's reactions to noxious stimuli. Previous studies in healthy volunteers under controlled conditions revealed EEG activity in response to standardised nociceptive stimuli even at high doses of remifentanil and propofol. This pilot study aims to investigate the feasibility of using these standardised nociceptive stimuli in routine clinical practice. We studied 17 patients undergoing orthopaedic trauma surgery under general anaesthesia. We evaluated if the EEG could track standardised noxious phase-locked electrical stimulation and tetanic stimulation, a time-locked surrogate for incisional pain, before, during, and after the induction of general anaesthesia. Subsequently, we analysed the effect of tetanic stimulation on the surgical pleth index as a peripheral, vegetative, nociceptive marker. We found that the phase-locked evoked potentials after noxious electrical stimulation vanished after the administration of propofol, but not at low concentrations of remifentanil. After noxious tetanic stimulation under general anaesthesia, there were no consistent spectral changes in the EEG, but the vegetative response in the surgical pleth index was statistically significant (Hedges' g effect size 0.32 [95% confidence interval 0.12-0.77], P=0.035). Our standardised nociceptive stimuli are not optimised for obtaining consistent EEG responses in patients during clinical anaesthesia. To validate and sufficiently reproduce EEG-based standardised stimulation as a marker for nociception in clinical anaesthesia, other pain models or stimulation settings might be required to transfer preclinical studies into clinical practice. DRKS00017829.

Comparison of the feasibility and validity of a one-level and a two-level erector spinae plane block combined with general anesthesia for patients undergoing lumbar surgery.

Spinal surgery causes severe postoperative pain. An erector spinae plane (ESP) block can relieve postoperative pain, but the optimal blocking method has not been defined. The aim of this study is to compare the feasibility of a one-level and a two-level lumbar ESP block and their effect on intraoperative and postoperative analgesia in lumbar spinal surgery. A total of 83 adult patients who were scheduled for posterior lumbar interbody fusion were randomly divided into two groups. Patients in Group I (n = 42) received an ultrasound-guided bilateral one-level ESP block with 0.3% ropivacaine, while patients in Group II (n = 41) received a bilateral two-level ESP block. Blocking effectiveness was evaluated, including whether a sensory block covered the surgical incision, sensory decrease in anterior thigh, and quadriceps strength decrease. Intraoperative anesthetic dosage, postoperative visual analogue scale scores of pain, opioid consumption, rescue analgesia, and opioid-related side effects were analyzed. Of the total number, 80 patients completed the clinical trial and were included in the analysis, with 40 in each group. The time to complete the ESP block was significantly longer in Group II than in Group I (16.0 [14.3, 17.0] min vs. 9.0 [8.3, 9.0] min, P = 0.000). The rate of the sensory block covering the surgical incision at 30 min was significantly higher in Group II than in Group I (100% [40/40] vs. 85.0% [34/40], P = 0.026). The rate of the sensory block in the anterior thigh was higher in Group II (43.8% [35/80] vs. 27.5% [22/80], P = 0.032), but the rate of quadriceps strength decrease did not differ significantly between the groups. The mean effect-site remifentanil concentration during intervertebral decompression was lower in Group II than in Group I (2.9 ± 0.3 ng/ml vs. 3.3 ± 0.5 ng/ml, P = 0.007).There were no significant differences between the groups in terms of intraoperative analgesic consumption, postoperative analgesic consumption, and postoperative VAS pain scores at rest and with movement within 24 h. There were no block failures, block-related complications, and postoperative infection. Among patients undergoing posterior lumbar interbody fusion, the two-level ESP block provided a higher rate of coverage of the surgical incision by the sensory block when compared with the one-level method, without increasing the incidence of procedure-related complications. www.chictr.org.cn, identifier: ChiCTR2100043596.

Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells.

Remifentanil is a widely used in general anesthetic that has been found to suppress the inflammatory response in aortic endothelial cells. Therefore, it was hypothesized that remifentanil can inhibit inflammatory dysfunction in lung epithelial cells to alleviate acute lung injury (ALI). The present study aimed to examine the effects of remifentanil on inflammatory injury, MMP-9/tissue inhibitor of metalloproteinase 1 (TIMP1) balance and the potential associated regulatory pathways in A549 cells. Lipopolysaccharide (LPS) was used to treat A549 cells to establish ALI models. The possible roles of different concentrations of remifentanil in cell viability was then determined by CCK-8 and Lactate dehydrogenase release assay. Apoptosis was assessed by flow cytometry analysis and western blotting. Inflammation and oxidative stress were measured by ELISA and corresponding kits respectively. Subsequently, the effects of remifentanil on Toll-like receptor 4 (TLR4) expression and the MMP-9/TIMP1 balance were assessed by western blotting and ELISA. In addition, the effects of remifentanil on NF-κB/STAT3 signaling were evaluated by measuring the protein expression levels of associated pathway components and the degree of NF-κB nuclear translocation using western blotting and immunofluorescence respectively. Remifentanil was found to increase cell viability whilst reducing apoptosis, inflammation and oxidative stress in the LPS-treated cells. In addition, TLR4 inhibitor CLI-095 suppressed MMP-9 expression and secretion while potentiating TIMP1 expression and secretion in LPS-challenged cells. Remifentanil treatment was able to modulate TLR4 to mediate LPS-induced MMP-9/TIMP1 imbalance and suppress the phosphorylation of NF-κB/STAT3 signaling components, in addition to inhibiting NF-κB nuclear translocation. Taken together, remifentanil downregulated TLR4 to reduce MMP-9/TIMP1 imbalance to inhibit inflammatory dysfunction in LPS-treated A549 cells, by regulating NF-κB/STAT3 signaling.

The effect of remifentanil infusion on sevoflurane minimum alveolar concentration–no movement (MACNM) and bispectral index in dogs

ObjectiveTo determine the effect of remifentanil infusion on the minimum alveolar concentration of sevoflurane preventing movement (SEVOMACNM) and bispectral index (BIS) in dogs. Study designProspective, unmasked study. AnimalsA total of 10 adult Beagle dogs weighing 9.0 ± 1.1 kg. MethodsDogs were anesthetized with sevoflurane and baseline SEVOMACNM was determined. Remifentanil was infused at 5, 10 and 20 μg kg–1 hour–1, in sequence, with 20 minutes washout between infusions. Variables monitored throughout anesthesia included heart rate (HR), oscillometric blood pressure, end-tidal partial pressure of carbon dioxide, end-tidal sevoflurane concentration (Fe′Sevo) and BIS. SEVOMACNM after remifentanil infusion (SEVOMACNM-REMI) determination started 20 minutes after the start of each infusion. Venous blood samples were collected for plasma remifentanil concentration determination at baseline, SEVOMACNM-REMI determination time points, and 20 minutes after each infusion was stopped. A mixed model analysis was used to determine the effect of remifentanil infusion on response variables. The relationships between BIS and Fe′Sevo, plasma remifentanil concentrations and the percentage decrease in baseline SEVOMACNM were evaluated (p < 0.05). ResultsThe overall SEVOMACNM at baseline was 2.47 ± 0.11%. Addition of remifentanil at all infusion rates significantly decreased SEVOMACNM, but the medium and high doses resulted in significantly greater decreases in SEVOMACNM than the lower dose. There was no difference in SEVOMACNM percentage change between infusions 10 and 20 μg kg–1 hour–1. Plasma remifentanil concentrations were significantly different in all infusion rates. Baseline BIS value was 70 ± 1 and was lower than the BIS values recorded during all remifentanil infusions. BIS values were not significantly different among infusion rates. HR was lower and mean arterial pressure was higher during remifentanil infusions than at baseline. Conclusions and clinical relevanceAll remifentanil infusions decreased SEVOMACNM in dogs. Remifentanil infusion at any rate studied did not reduce BIS values.

Abdominal Wall Block Decreases Intraoperative Opioid Con-Sumption by Surgical Pleth Index-Guided Remifentanil Administration in Single-Port Laparoscopic Herniorrhaphy: A Prospective Randomized Controlled Trial

Abdominal wall blocks (AWBs) can reduce pain during surgery and lessen opioid demand. Since it is difficult to know the exact level of intraoperative pain, it is not known how much the opioid dose should be reduced. In this study, using the surgical pleth index (SPI), which indicates pain index from sympathetic fibers, the amount of remifentanil consumption was investigated. We conducted single-port laparoscopic hernia repair in 64 patients, as follows: the regional block group (R group) was treated with AWB, while the control group (C group) was only subjected to general anesthesia. In both groups, the remifentanil concentration was adjusted to maintain the SPI score between 30 and 40 during surgery. The primary parameter was the amount of remifentanil. A total of 52 patients completed the study (24 in the R group, 28 in the C group). The remifentanil dose during surgery was decreased in the R group (29 ± 21 vs. 56 ± 36 ng/kg/min; p = 0.002). Visual analogue scale score and additional administrated analgesics were also low in the R group. As such, AWB can reduce the remifentanil dose while maintaining the same pain level.