Remifentanil Infusion Rate Research Articles

Fractional-Order Modeling of the Depth of Analgesia as Reference Model for Control Purposes

Little research has been carried out in terms of modeling and control of analgesia. However, emerging new technology and recent prototypes paved the way for several ideas on pain modeling for control. Recently, such an idea has been proposed for measuring the Depth of Analgesia (DoA). In this paper, that solution is further exploited towards obtaining a novel fractional-order model and dedicated controller for DoA. First, clinical data from patients undergoing general anesthesia are used to determine a commensurate fractional-order model of the skin impedance at each sampling period. Second, we provide a proof of concept indicating that fractional order changes due to variations in the infused opioid drug (Remifentanil). Third, a fractional-order model for DoA is developed correlating the changes in the pain index (as the output signal) and the Remifentanil infusion rate (as the input signal). Standard optimization routines are used to estimate the parameters. A database of 19 real patients is used. Lastly, a preliminary fractional-order controller is designed and tested in simulation for the 19 patients. The closed-loop simulation results correspond to the expected clinical outcomes.

Anesthetic-sparing effect of dexmedetomidine during total intravenous anesthesia for children undergoing dental surgery: A randomized controlled trial.

Dexmedetomidine, an α2-adrenergic agonist, reduces propofol and remifentanil requirements when used as an adjunct to total intravenous anesthesia in adults, but studies in a pediatric population are sparse. This study investigates the magnitude of dose-sparing effects of a postinduction dexmedetomidine bolus on propofol and remifentanil requirements during pediatric surgery. In this randomized, double-blind, controlled trial, children aged 2-10 years undergoing elective dental surgery were assigned to one of four groups: placebo, 0.25 mcg/kg dexmedetomidine, 0.5 mcg/kg dexmedetomidine, and 1 mcg/kg dexmedetomidine. Maintenance with fixed-ratio propofol and remifentanil total intravenous anesthesia followed a bispectral index (BIS)-guided algorithm designed to maintain a stable depth of anesthesia. The primary outcomes were time-averaged maintenance infusion rates of propofol and remifentanil. Secondary outcomes in the postanesthetic care unit included sedation scores, pain scores, and time to discharge. Data from 67 patients were available for analysis. The median [interquartile range] propofol infusion rate was lower in the 1 mcg/kg dexmedetomidine group (180 [164-185] mcg/kg/min) versus placebo (200 [178-220] mcg/kg/min): percent change -10.0%; 95% CI -2.4 to -19.8; p = 0.013. The remifentanil infusion rate was also lower in the 1 mcg/kg dexmedetomidine group (0.089 [0.080, 0.095] mcg/kg/min) versus placebo (0.103 [0.095, 0.106] mcg/kg/min): percent change, -13.7%; 95% CI -5.47 to -21.0; p = .022. However, neither propofol nor remifentanil infusion rates were significantly different in the 0.25 or 0.5 mcg/kg dexmedetomidine groups. In the postanesthesia care unit, there were no differences in pain or sedation scores, and time to discharge was not significantly prolonged in any dexmedetomidine group. Dexmedetomidine 1 mcg/kg reduced the propofol and remifentanil requirements during maintenance of anesthesia in children when administered as a postinduction bolus. ClinicalTrials.gov: NCT03422978, date of registration 2018-02-06.

High-Dose Remifentanil Anesthesia With Minimal Sedation in Neonates: A Single-Center Retrospective Study.

Introduction Remifentanil is an opioid with rapid onset and elimination. Theoretically, reducing sedation using high-dose remifentanil may contribute to early emergence and prevention of postanesthetic complications related to residual anesthesia. However, there have been few reports of high-dose remifentanil anesthesia in neonatal surgery. This study aims to describe the techniques of high-dose remifentanil anesthesia in neonates and their safety outcomes. Methods This is a single-center, retrospective observational study from January 2016 to February 2022. Medical records from neonatal surgical procedures performed using high-dose remifentanil anesthesia were reviewed. "High dose" was defined as 0.5 mcg/kg/min or more. Patient profiles, anesthetic drugs used, and intra- and post-operative adverse events, including cardiopulmonary complications, were abstracted. Results There were 15 neonatal abdominal operations performed under high-dose (>0.5 mcg/kg/min) remifentanil anesthesia during the study period. The average remifentanil infusion rate was 1.9 (0.68-3.1) mcg/kg/min. Hypotension occurred in two patients (13%). Bradycardia was not observed in any patients. The mean time for tracheal extubation was 16 minutes. Five patients (33%) received naloxone administration before extubation, and two patients (13%) experienced hypoxemia immediately after extubation. No patient had cardiorespiratory complications after leaving the operating room. Conclusions High-dose remifentanil can be used without impairing hemodynamic stability in neonatal surgery, although there is concern about respiratory depression. Further research is needed on its potential impact on long-term outcomes.

Effect of A118G (rs1799971) single-nucleotide polymorphism of the μ-opioid receptor OPRM1 gene on intraoperative remifentanil requirements in Japanese women undergoing laparoscopic gynecological surgery.

Abundant data are available on the effect of the A118G (rs1799971) single-nucleotide polymorphism (SNP) of the μ-opioid receptor OPRM1 gene on morphine and fentanyl requirements for pain control. However, data on the effect of this SNP on intraoperative remifentanil requirements remain limited. We investigated the effect of this SNP on intraoperative remifentanil requirements. We investigated 333 Japanese women, aged 21-69 years, who underwent laparoscopic gynecological surgery for benign gynecological disease under total intravenous anesthesia at Juntendo University Hospital. Average infusion rates of propofol and remifentanil during anesthesia and the average bispectral index (BIS) during surgery were recorded. Associations among genotypes of the A118G and phenotypes were examined with the Mann-Whitney U test. The average propofol infusion rate was not different between patients with different genotypes. The average remifentanil infusion rate was significantly higher in patients with the AG or GG genotype than the AA genotype (p = 0.028). The average intraoperative BIS was significantly higher in patients with the GG genotype than the AA or AG genotype (p = 0.039). The G allele of the A118G SNP was associated with higher intraoperative remifentanil requirements and higher intraoperative BIS values but was not associated with propofol requirements. Given that remifentanil and propofol act synergistically on the BIS, these results suggest that the G allele of the A118G SNP is associated with lower effects of remifentanil in achieving adequate intraoperative analgesia and in potentiating the sedative effect of propofol on the BIS.

Target-controlled infusion of remimazolam effect-site concentration for total intravenous anesthesia in patients undergoing minimal invasive surgeries.

Although pharmacokinetic and pharmacodynamic models of remimazolam have been developed, their clinical application remains limited. This study aimed to administer a target-controlled infusion (TCI) of remimazolam at the effect-site concentration (Ce) in patients undergoing general anesthesia and to investigate the relationship of the remimazolam Ce with sedative effects and with recovery from general anesthesia. Fifty patients aged 20-75 years, scheduled for minimally invasive surgery under general anesthesia for less than 2 h, were enrolled. Anesthesia was induced and maintained using Schüttler's model for effect-site TCI of remimazolam. During induction, the remimazolam Ce was increased stepwise, and sedation levels were assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale and bispectral index (BIS). Following attainment of MOAA/S scale 1, continuous infusion of remifentanil was commenced, and rocuronium (0.6 mg/kg) was administered for endotracheal intubation. The target Ce of remimazolam and the remifentanil infusion rate were adjusted to maintain a BIS between 40 and 70 and a heart rate within 20% of the baseline value. Approximately 5 min before surgery completion, the target Ce of remimazolam was reduced by 20-30%, and anesthetic infusion ceased at the end of surgery. Nonlinear mixed-effects modeling was employed to develop pharmacodynamic models for each sedation level as well as emergence from anesthesia. The remimazolam Ces associated with 50% probability (Ce50) of reaching MOAA/S scale ≤4, 3, 2, and 1 were 0.302, 0.397, 0.483, and 0.654 μg/mL, respectively. The Ce50 values for recovery of responsiveness (ROR) and endotracheal extubation were 0.368 and 0.345 μg/mL, respectively. The prediction probabilities of Ce and BIS for detecting changes in sedation level were 0.797 and 0.756, respectively. The sedation scale significantly correlated with remimazolam Ce (r = -0.793, P < 0.0001) and BIS (r = 0.914, P < 0.0001). Age significantly correlated with Ce at MOAA/S1 and ROR. Effect-site TCI of remimazolam was successfully performed in patients undergoing general anesthesia. The remimazolam Ce significantly correlated with sedation depth. The Ce50 for MOAA/S scale ≤1 and ROR were determined to be 0.654 and 0.368 μg/mL, respectively.

PID control of data-driven patient response with fixed ratio co-administration of drugs for depth of hypnosis

In this work we make use of knowledge from clinical practice to deliver a trusted environment for feedback control of co-administration of two drugs to induce depth of hypnosis during general anesthesia. The clinical data we have provides valuable insight into the ratio used to determine the Propofol and Remifentanil infusion rates by means of specifying their corresponding effect site concentrations. A feedback closed loop with a fixed parameter PID controller tuned on population dynamics is used. To account the strong variations in gain of the system (patient) we propose an online identification of the dose-effect response from clinical data available during clinical protocol. Theoretical analysis is provided to justify the approach and simulations with real data from patient are given to support the theoretical insight. Limitations of this approach are discussed as to justify why ratio based co-administration is used in practice solely during the induction phase of general anesthesia.

A PID-based Structure for MISO Approach to Anaesthesia Control Problem

This work introduces a control architecture based on Proportional-Integral-Derivative (PID) controller addressing drugs co-administration in the total intravenous anaesthesia process. The control problem focuses on a multiple-input-single-output nonlinear process, where the infusion rates of propofol and remifentanil are the control variables and the Bispectral Index Scale (BIS) is the controlled variable. The analyzed structure exploits an external predictor of the patient state that converts the control problem to the linear case. The interaction between the used drugs is handled by a reference converter element through continuous re-computation of the setpoint. The proposed control system is evaluated by exploiting a set of virtual patients that are representative of a wide population. The scenario considers induction and maintenance phases, as both of them are important from a practical point of view. The obtained results show that the PID controller in combination with the external predictor is able to meet all the clinical requirements, which is confirmed through the analysis of process specific performance indexes.

The Influence of Audiovisual Distraction on Pain Reduction During Transcatheter Aortic Valve Implantation Under Monitored Anesthesia Care: A Prospective Randomized Trial

To investigate the effect of an audiovisual distraction system on the dose of remifentanil for perioperative sedation during transcatheter aortic valve implantation under monitored anesthesia care. Single-center prospective randomized nonblinded study. Tertiary referral academic hospital. Ninety patients who underwent transfemoral transcatheter aortic valve implantation between July 2019 and July 2021. Patients were randomized to use either a novel audiovisual distraction system during the intervention (n = 45) or standard care without an audiovisual distraction system (n = 45). Standardized questionnaires were given to each patient at admission and before and after the intervention to assess their levels of anxiety. Primary endpoints were the average and peak infusion rates of remifentanil. All patients were considered for the final analysis according to an intention-to-treat design. No relevant differences in pre- and postinterventional anxiety status were observed between the groups. Similarly, there were no significant differences in reported pain scores (p = 0.364). The average infusion rate (p = 0.028) and peak infusion rate (p = 0.025) of remifentanil were lower in the group with an audiovisual distraction system. Audiovisual distraction is a useful adjunct to reduce the dose of remifentanil under monitored anesthesia care during transcatheter aortic valve implantation. Larger studies are needed to evaluate potential positive effects on patient satisfaction, incidence of delirium, and possible economic benefits.

Drug co‐administration in anesthesia using event‐based MPC

AbstractIn this article, a predictive event‐based control architecture for multivariable drug infusion in the anesthesia process is presented. The control scheme considers a multiple‐input single‐output process, where the depth of hypnosis is the controlled variable and the infusion rates of propofol and remifentanil, which are co‐administered by imposing a fixed ratio between them, are the control variables. The control system is built on the top of a nonlinear pharmacokinetic/pharmacodynamic model for drug co‐administration that reflects the super‐additive effect of both drugs on the bispectral index scale (BIS), which is a measure of the hypnotic state of the patient. Further, in order to compensate the nonlinear behavior of the system, it exploits an external predictor that is designed to increase the robustness to inter‐/intra‐patient variability. The overall controller parameters are tuned by applying an optimization method on a representative set of virtual patients. The main feature of the proposed control algorithm consists in its asynchronous execution, which can be beneficial in reducing control signal changes due to the noisy measurements of the BIS. The evaluation of the analyzed control architecture through a simulation study reveals that control action variations can be reduced by about 48% on average with respect to its time‐based counterpart. This reduction is obtained at the expense of a lower control accuracy, resulting in a degradation of 18% in terms of integrated absolute error. Results are acceptable from a clinical practice perspective proving that the proposed approach is a feasible alternative to classical time‐based predictive controllers.

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

Effects of deep neuromuscular block on surgical pleth index-guided remifentanil administration in laparoscopic herniorrhaphy: a prospective randomized trial

Deep neuromuscular block (NMB) has been increasingly utilized, but its role in reducing intraoperative opioid requirement has yet to be investigated. Surgical pleth index (SPI) quantifies nociception. We investigated the effects of deep NMB on SPI-guided remifentanil administration in laparoscopic herniorrhaphy. Total 128 patients undergoing laparoscopic inguinal herniorrhaphy were randomly allocated to two groups of NMB: deep (n = 64) and moderate (n = 64). The remifentanil dose was assessed during intubation, from skin incision until CO2 insertion, and pneumoperitoneum. Mean infusion rate of remifentanil during pneumoperitoneum was higher in moderate NMB group than in deep NMB group (0.103 [0.075–0.143] µg/kg/min vs. 0.073 [0.056–0.097] µg/kg/min, p < 0.001). Consequently, median infusion rate of remifentanil during anesthesia was higher in moderate NMB group (0.076 [0.096–0.067] µg/kg/min vs. 0.067 [0.084–0.058] µg/kg/min, p = 0.016). The duration of post-anesthesia care unit stay was longer in the moderate NMB group (40 [30–40] min vs. 30 [30–40] min, p = 0.045). In conclusion, deep NMB reduced the remifentanil requirement compared with moderate NMB in SPI-guided anesthesia for laparoscopic herniorrhaphy.

ED50 value of remifentanil in inhibiting coughing during extubation in children with snoring

Objective: This study aimed to determine the effective dose 50% (ED50) value of remifentanil in inhibiting coughing during extubation in children with snoring. Methods: The subjects were children who scored a grade I in the American Society of Anesthesiology (ASA) metric and who were undergoing tonsillectomy (with or without adenoidectomy) under general anesthesia. Using Dixon’s up-and-down sequential method, the initial infusion rate of remifentanil was 0.06 μg/kg/min, and the difference between the infusion rates of the two adjacent groups was 0.01 μg/kg/min. If a child had no cough response during extubation, the infusion rate for the next child was reduced by 0.01 μg/kg/min. If that child had cough response, the infusion rate for the next child was increased by 0.01 μg/kg/min, and the test was terminated when seven pairs of children with positive-negative alternating results were obtained. The ED50 value and its 95% confidence interval (CI) were calculated by probit regression. The times for extubation, awakening, agitation, and respiratory complications after extubation were compared between the two groups. Results: 1) The ED50 value of a continuous infusion of remifentanil required to inhibit the cough response of children during extubation was 0.042 μg/kg/min, and the 95% confidence interval was 0.025–0.062 μg/kg/min. 2) The total dosage and infusion rate of remifentanil in the cough suppression group were higher than those in the cough group (p < 0.05), but the differences in the times for extubating and awakening between the two groups were not statistically significant (p > 0.05). 3) There was no correlation between the infusion rate of remifentanil and the time for extubating and awakening in the cough suppression group; the r values were 0.13 and 0.12, respectively, and p > 0.05. 4) The differences in postoperative respiratory complications between the two groups were not statistically significant (p > 0.05). Conclusion: The ED50 value of a continuous infusion of remifentanil required to inhibit the cough response of children during extubation after tonsillectomy (with or without adenoidectomy) was 0.042 μg/kg/min, and a low-dose infusion of remifentanil does not affect the times for awakening and extubating in children.

Effect of dexamethasone on intraoperative remifentanil dose in total knee arthroplasty surgery under general anaesthesia.

BackgroundThe effects of glucocorticoids may include both genomic and rapid nongenomic effects. The potential rapid analgesic effect during surgery has not previously been investigated. We aimed to explore the effect of dexamethasone on intraoperative infusion rate of remifentanil in patients undergoing total knee arthroplasty (TKA) surgery under general anaesthesia.MethodsIn this post hoc subgroup analysis, we included patients randomised in the DEX‐2‐TKA trial, who were operated under total intravenous anaesthesia with remifentanil and propofol. Trial medication, intravenous dexamethasone 24 mg or placebo, was administered immediately after anaesthesia onset. The primary outcome was the median weight‐corrected infusion rate of remifentanil during surgery. Secondary outcomes included median weight‐corrected infusion rate of propofol, median intraoperative bispectral index and time spent in the post‐anaesthesia care unit.ResultsEighty‐seven patients were included in the analysis of the primary outcome. A significantly higher remifentanil infusion rate was observed in the dexamethasone group compared with the placebo group, p = .02. None of the secondary outcomes resulted in statistically significant differences between groups.ConclusionThis explorative post hoc analysis of the randomised DEX‐2‐TKA trail showed that patients undergoing TKA surgery under general anaesthesia and who received dexamethasone seemed to have a higher remifentanil infusion rate compared with patients who received placebo. The clinical implications of the potentially increased remifentanil infusion rate need to be validated and explored further.Clinical trial registration ClinicalTrials.gov Identifier: NCT05002361 (12 August 2021).

Comparison of Analgesic Efficacy of Local Anesthetic Infiltration and Ultrasound-guided Abdominal Wall Nerve Block in Children Undergoing Ambulatory Inguinal Hernia Repair

PurposePlacement of local anesthetics either as infiltration (LAI) or as abdominal wall nerve block (AWNB) has been shown to reduce postoperative pain following laparoscopic surgery. We aimed to compare intraoperative remifentanil consumption and postoperative pain of AWNB and LAI in children undergoing ambulatory two-port laparoscopic inguinal hernia surgery with propofol-remifentanil based general anesthesia. DesignRandomized controlled trial. MethodsChildren aged between 1 and 6 years undergoing two-port laparoscopic inguinal hernia repair were enrolled for analysis. These children received one of the three anesthesia regimens (1) standard general anesthesia (SGA); (2) SGA with preemptive LAI; (3) SGA with preemptive AWNB; and were categorized accordingly. Primary outcome variable were intraoperative average infusion rate of remifentanil and postoperative FLACC (Face, Legs, Activity, Cry, and Consolability) pain score. Secondary outcome data included demographics, intraoperative variables (hemodynamics and bispectral index score recorded at three different time points), and duration of surgery. FindingsA total of 90 children (30 in each group) were included in the analysis. General information, intraoperative hemodynamic variables, bispectral index score, and duration of surgery were not significantly different among groups. The intragroup variation of hemodynamic variables were less stable in the SGA group compared with the other two groups, while BIS score was similar among groups. The intraoperative infusion rate of remifentanil was significantly lower in the AWNB group than in the SGA or the LAI group (median [25th to 75th centiles]: 0.11[0.11 to 0.11] µg/kg/min, 0.33[0.33 to 0.33] µg/kg/min; 0.17[0.17 to 0.20] µg/kg/min, respectively, P < .001 for both), and lower in the LAI group than in the SGA group (P < .001). The postoperative FLACC pain score was significantly lower in the AWNB group than in the SGA or the LAI group (P < .001 for both). ConclusionsAWNB is associated with a lower intraoperative remifentanil requirement and a lower postoperative FLACC pain score compared with LAI in children undergoing laparoscopic inguinal hernia repair with propofol-remifentanil based general anesthesia.

Comparison of the efficacy and safety of sedation protocols with the use of dexmedetomidine\u2013remifentanil and propofol\u2013remifentanil during percutaneous closure of atrial septal defects: a randomized clinical trial

BackgroundThe study was aimed to compare the efficacy and safety of different sedation protocols of dexmedetomidine–remifentanil and propofol–remifentanil for percutaneous closure of atrial septal defects (ASD) under transthoracic echocardiography (TTE) guidance.Material and methodsFrom March 2020 to January 2021, of 114 patients screened, 59 ASD patients scheduled for percutaneous closure under TTE guidance were randomly allocated into the dexmedetomidine–remifentanil (D–R) group (n = 29) and the propofol–remifentanil (P–R) group (n = 30). The incidence of hemodynamic and respiratory adverse events, arterial blood gas analysis, induction and recovery time, pain score, infusion rate of remifentanil, satisfaction of the surgeon and patient, additional sedatives were collected for analysis and comparison.ResultsThe induction time was longer in the D–R group than that in the P–R group (17.66 ± 2.65 min vs 11.43 ± 1.48 min; difference, 6.22 min; 95% CI 5.10 to 7.35; P < 0.001). No differences were observed in the 2 groups in terms of the additional sedatives, infusion rate of remifentanil, pain score, recovery time (P > 0.05). There was no difference between the two groups regarding the incidence of cardiovascular adverse events (6 [20.7%] vs 4 [13.3%]; difference, 7.4%; 95% CI − 11.7 to 26.5%; P = 0.506). Respiratory adverse events occurred in 1 patient (3.4%) in the D–R group, and 8 patients (26.7%) in the P–R group (difference, 23.3%; 95% CI 6.2 to 40.5%; P = 0.026). The incidence of hypercapnia was significantly lower in the D–R group (4 [13.8%]) than in the P–R group (13 [43.3%]; difference, 29.5%; 95% CI 7.8 to 51.2%; P = 0.012).ConclusionsExcept for more rapid the induction time and higher the surgeon satisfaction score in the propofol–remifentanil protocol, the efficacy was similar between two sedation protocols. The hemodynamic stability was comparable, the dexmedetomidine–remifentanil protocol had superior airway security due to fewer hypercapnia and respiratory adverse events.

Prospective evaluation of remifentanil-propofol mixture for total intravenous anesthesia: A randomized controlled study.

Application of total intravenous anesthesia (TIVA) may be considered as unpractical when compared with inhalational anesthesia. Although it is mostly not recommended, mixing intravenous agents is popular in clinical practice. The aim of the present study was to investigate the suitability of using remifentanil-propofol mixture (MIXTIVA) for TIVA. Adult patients with an American Society of Anesthesiologists grade of I-II scheduled for elective thyroidectomy were randomly allocated to 3 groups (n=32 for each) to receive TIVA with remifentanil and propofol infusions separately (control group, Group I) or with MIXTIVA infusion that contained remifentanil/propofol at a proportion of 2/1,000 or 3/1,000 (remifentanil concentration, 20 or 30 µg/ml in 1% propofol in Group II or Group III, respectively). The extubation time (the primary outcome of the study), the orientation time and number of patients in whom intraoperative hypotension, hypertension or bradycardia episodes were encountered during anesthesia were comparable among the groups. The mean remifentanil infusion rate in Group III was significantly higher than that in the other groups. The mean propofol infusion rates and mean bispectral index (BIS) scores during anesthesia were comparable among groups. Hypotension accompanied with a high BIS was encountered in one patient in Group III. In conclusion, compared to the standard TIVA technique using separate drug infusions, MIXTIVA infusion used for thyroidectomies did not result in any statistically significant difference in recovery and clinical outcomes. This technique may be considered as a practical implementation for busy ambulatory centers performing general anesthesia. The present study was retrospectively registered at clinicaltrials.gov (trial registration no. NCT04394897).

The usefulness of Smart Pilot View for fast recovery from desflurane general anesthesia.

Smart Pilot View (SPV) (Dräger Medical) provide information about the estimated drug effect of anesthetic drugs. We conducted a prospective randomized trial to evaluated the recovery time in SPV-guided general anesthesia compared with usual practice in patients with desflurane general anesthesia. Thirty-four American Society of Anesthesiologist's physical status I-II patients scheduled for elective surgery under general anesthesia were enrolled in the study. The patients were allocated to one of the following two groups: the Smart Pilot View group (group SPV) or the control group (group C). General anesthesia was induced by propofol and maintained by desflurane end-tidal concentration of 4.2%. During the procedure, desflurane concentration was adjusted to maintain BIS values between 40 and 60 and above MAC 90. In group SPV, desflurane concentration and infusion rate of remifentanil were decreased to achieve MAC 90 about 10min before the end of the procedure. In group C, the desflurane concentration and infusion rate of remifentanil were maintained unchanged until the end of the procedure. Fifteen patients were enrolled in group C, and seventeen of these were enrolled in group SPV. The time taken for the opening of the patient's eyes was 292 ± 53s in group C and 218 ± 44s in group SPV. The time taken for recovery of orientation was 451 ± 100s in group C and 316 ± 57s in group SPV. Both times were significantly faster in the group SPV. Smart Pilot View guided anesthesia enabled faster recovery from desflurane general anesthesia.

Effects of Remifentanil on Cardiovascular Stimulation Caused by Local Anesthetic With Epinephrine: A Power Spectral Analysis.

The objectives of this research were to investigate (a) what was the most effective infusion rate of remifentanil and (b) the degree to which sympathomimetic effects were involved with cardiovascular stimulation by using a power spectral analysis of heart rate variability (HRV). A total of 63 healthy individuals scheduled for sagittal split ramus osteotomy were enrolled and randomly allocated to 1 of 3 groups: remifentanil infusion rate of 0.1, 0.2, or 0.4 μg/kg/min. Anesthesia was maintained with remifentanil and propofol. Before the surgical procedure, 2% lidocaine containing 12.5 μg/mL epinephrine was administered in the surgical field for local anesthesia. Systolic blood pressure (SBP), heart rate (HR), low-frequency (LF) and high-frequency (HF) components in HRV power spectral analysis, and the LF/HF ratio were analyzed. Increases in SBP and HR were observed after local anesthesia in all 3 groups, but no significant differences were observed between the groups. Remifentanil infusion at 0.1 μg/kg/min may be appropriate to minimize cardiovascular stimulation caused by exogenous epinephrine from local anesthesia. Although a rise in the LF/HF ratio was observed after local anesthesia in all groups, no relationship was observed between the cardiovascular changes and the increase in LF/HF ratio. This suggests that sympathomimetic effects are involved to a lesser extent with the cardiovascular stimulation caused by exogenous epinephrine.

Effects of constant rate infusions of dexmedetomidine, remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs

ObjectiveTo evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs. Study designRandomized crossover experimental study. AnimalsA total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg. MethodsAnesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg–1 hour–1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 μg kg–1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 μg kg–1 hour–1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 μg kg–1 minute–1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED50) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 μg kg–1 hour–1, obtained using log-linear regression analysis. ResultsThe sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED50 values were lower when combined with dexmedetomidine than those obtained during saline–remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 μg kg–1 hour–1. Conclusions and clinical relevanceCombined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.

Effect of remifentanil on intraoperative fluid balance: a retrospective statistical examination of factors contributing to fluid balance

BackgroundPostoperative fluid retention is a factor that causes delay in recovery and unexpected adverse events. It is important to prevent intraoperative fluid retention, which is putatively caused by intraoperative release of stress hormones, such as ADH (anti-diuretic hormone) or others. We hypothesized that intraoperative analgesia may prevent pathological fluid retention. We retrospectively explored the relationship between analgesics and in-out balance in surgical patients from anesthesia records.MethodsAnesthetic records of 80 patients who had undergone orthognathic surgery were checked in this study. Patients were anesthetized with either TIVA (propofol and remifentanil) or inhalational anesthesia (sevoflurane and remifentanil). During surgery, acetated Ringer's solution was infused for maintenance at a rate of 3–5 ml/kg/h at the discretion of the anesthetist. The perioperative parameters, including the amount of crystalloid and colloid infused, and the amount of urine and bleeding were checked. Furthermore, we checked the amount and administration rate of remifentanil during the surgical procedure. The correlation coefficient between the remifentanil dose and the in-out balance or the urinary output was analyzed using the Pearson correlation coefficient. The contributing factor to fluid retention, including urinary output, was statistically examined by means of multivariate logistic regression analysis.ResultsA significant positive correlation was found between remifentanil dose and urinary output. Urinary output less than 0.04 ml/kg/min was suggested to cause positive fluid balance. Although in-out balance approaches zero balance with increase in remifentanil administration rate, no contributing factor for near-zero fluid balance was statistically picked up. The remifentanil administration rate was statistically picked up as the significant factor for higher urinary output (> 0.04 ml/kg/min) (OR, 2,644; 95% CI, 3.2–2.2 × 106) among perioperative parameters.ConclusionsIn conclusion, remifentanil contributes in maintaining the urinary output during general anesthesia. Although further prospective study is needed to confirm this hypothesis, it was suggested that fluid retention could be avoided through suppressing intraoperative stress response by means of appropriate maintenance of remifentanil infusion rate.