Propofol Infusion Rate Research Articles

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.

Clinical evaluation of bispectral index‐guided closed‐loop infusion of propofol for preschool children: A multi‐center randomized controlled study

ABSTRACTImportanceThe closed‐loop infusion system can automatically adjust and maintain the depth of anesthesia by using the propofol target‐controlled infusion (TCI) model under the feedback guidance of the bispectral index (BIS).ObjectiveTo evaluate the safety and superiority of closed‐loop TCI of propofol guided by BIS during maintenance of generalized intravenous anesthesia for preschool children.MethodsA total of 120 children aged 1–6 years were enrolled and were divided into a closed‐loop feedback group (Group C) and an open‐loop manual control group (Group O), with 60 participants in each group. For anesthesia maintenance, the propofol infusion rate was adjusted by the injection system under the guidance of BIS in Group C and was manually adjusted by anesthesiologists according to the BIS and clinical experience in Group O, to maintain a BIS level of 50. The time ratio of adequate anesthesia (40 ≤ BIS ≤ 60), light anesthesia (BIS > 60), and deep anesthesia (BIS < 40) were recorded.ResultsA total of 119 patients (59 in Group C and 60 in Group O) were enrolled in the study. Group C demonstrated a higher time ratio of adequate anesthesia (P = 0.014) compared to Group O. The time ratio of light anesthesia and the global score was lower in Group C than in Group O (P = 0.010, P = 0.015, respectively). The frequency of adjustment per unit of time was higher in Group C for propofol (P < 0.001), while it was lower for remifentanil (P = 0.010).InterpretationBIS‐guided closed‐loop infusion of propofol is safe and effective for preschool children. The depth of anesthesia is controlled more accurately and smoothly.

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.

The effect of intravenous magnesium sulphate infusion on total intravenous anesthesia with propofol in adult dogs: A randomized, blinded trial

ObjectiveTo evaluate cardiopulmonary, arterial blood gas and propofol-sparing effects of magnesium sulfate (MgSO4) constant rate infusion (CRI) in mechanically ventilated dogs maintained under total intravenous anesthesia with propofol. Study designBlinded, randomized, clinical trial. AnimalsA total of 24 healthy adult dogs. MethodsDogs were premedicated with intramuscular acepromazine (0.05 mg kg–1) and morphine (0.5 mg kg–1), followed by an intravenous (IV) bolus of saline or MgSO4 (50 mg kg–1 over 15 minutes) and propofol (given to effect to induce anesthesia). Anesthesia was maintained with an IV propofol infusion (beginning at 0.3 mg kg–1 minute–1, adjusted as necessary). Concurrently, one of three IV infusions were administered: GS (0.9% NaCl), GM30 (MgSO4, 30 mg kg–1 hour–1) or GM80 (MgSO4, 80 mg kg–1 hour–1). Propofol induction and maintenance doses were recorded. The following variables were recorded at baseline (T0), after bolus treatment (T1), after beginning mechanical ventilation (T5) and every 15 minutes until the end of the procedure (T15–T120): mean arterial pressure, heart rate, peripheral oxygen saturation, end-tidal partial pressure of CO2, temperature, blood gas variables, indirect calorimetry and extubation time. Values of p < 0.05 were considered significant. ResultsPropofol induction bolus dose was lower in GM30 (31.2%, p = 0.04) and GM80 (38.9%, p = 0.003) than in GS. The maintenance propofol infusion rate in GM80 was 16.9% lower (p = 0.03), resulting in fewer propofol CRI rescues during the perioperative period. GM30 and GM80 exhibited faster extubation times than GS (46.2%, p = 0.002 and 48.9%, p = 0.001, respectively). Conclusions and clinical relevanceInfusion of a 50 mg kg–1 bolus, followed by CRI of MgSO4 (30 and 80 mg kg–1 hour–1), reduces the propofol induction and maintenance (CRI) requirement, maintaining cardiorespiratory stability and reducing the time required to extubation.

Comparison of cardiopulmonary effects of propofol, ketamine–propofol and isoflurane anesthesia in the domestic chicken (Gallus gallus domesticus)

ObjectiveTo compare the effects of propofol, ketamine–propofol and isoflurane, at similar anesthetic depth, on cardiopulmonary variables in unpremedictated chickens. Study designProspective, randomized, crossover experimental trial. AnimalsA total of 10 male Leghorn domestic chickens, aged 3 months and body mass 1.4–2.0 kg. MethodsBirds were randomly assigned to each of three anesthetic protocols, 7 days apart: intravenous propofol, intravenous ketamine–propofol or isoflurane. Anesthesia was induced (indicated by loss of righting reflex and tracheal intubation) and maintained with propofol (10 mg kg–1 minute–1, then 1.1 mg kg–1 minute–1), ketamine–propofol (5 mg mL–1 ketamine and 5 mg mL–1 propofol combined; 10 mg kg–1 minute–1, then 1.1 mg kg–1 minute–1) or isoflurane [5% vaporizer setting initially, then end-tidal concentration (Fe′Iso) of 2%] for 65 minutes. Anesthesia was maintained at a similar anesthetic depth based upon positive or negative responses to toe pinch. Heart rate (HR), respiratory rate (fR), noninvasive arterial blood pressure and arterial blood gases were measured during anesthesia. Propofol or ketamine–propofol infusion rates and Fe′Iso required to prevent movement in response to a noxious stimulus and recovery times were recorded. ResultsAnesthesia induction dose was 9.0 ± 0.8 (mean ± SD) and 12.2 ± 0.3 mg kg–1 for propofol and ketamine–propofol, respectively. Propofol and ketamine–propofol infusion rates and Fe′Iso required to prevent movement in response to the noxious stimulus were 0.88 ± 0.14 mg kg–1 minute–1, 0.92 ± 0.14 mg kg–1 minute–1 and 1.45 ± 0.28%, respectively. Cardiopulmonary variables remained clinically acceptable, but ketamine–propofol was associated with a significantly higher HR (p = 0.0001) and lower fR (p = 0.0001). Time to extubation did not differ among treatments. Conclusions and clinical relevanceCardiovascular and respiratory variables were maintained within normal ranges in all treatments. Coadministration of ketamine with propofol significantly reduced the induction and maintenance dose of propofol.

Evaluation of the Impact of the Addition of Atypical Antipsychotics to Continuous Infusion Propofol Therapy.

Purpose: The administration of sedatives to critically ill patients is a common practice in intensive care units (ICU) and has been associated with negative outcomes. To mitigate this, atypical antipsychotics are utilized as adjunctive therapy. This study aims to review and quantify overall effectiveness of the atypical antipsychotics quetiapine, risperidone, and olanzapine on reduction in the amount of continuous infusion propofol utilized in the ICU. Methods: This was an observational study that took place from February 27, 2021 to December 31, 2022. The primary outcome of this study was the percentage change in average propofol infusion rate (mcg/kg/min) from baseline to the greater than 24 to 48 hours period after atypical antipsychotic initiation. Secondary outcomes included ICU length of stay, duration of mechanical ventilation, QTc interval monitoring, and continuation of the antipsychotic without a valid indication. Descriptive statistics were utilized for the statistical analysis. Results: A total of 47 patients were included in the study. The average baseline propofol rate was 31 mcg/kg/min, which reduced 8.6% to 28.35 mcg/kg/min over the 0 to 24 hours period, was reduced by 19.4% compared to baseline to a rate of 25 mcg/kg/min during the greater than 24 to 48 hours period, and finally a percent reduction of 54.2% seen during the greater than 48 to 72 hours period to a rate of 14 mcg/kg/min. Conclusions: Patients who received an adjunctive antipsychotic saw resulting propofol rate reductions of 8.6% at 24 hours, 19.4% at 48 hours, and 54.2% at 72 hours. However, research on this topic should not end here, as further investigation with higher-level study design is needed to determine the true impact of these agents for this indication.

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.

PIDA control of depth of hypnosis in total intravenous anesthesia

In this paper we discuss the use of a Proportional-Integral-Derivative-Acceleration (PIDA) controller for the Depth-of-Hypnosis (DoH) control in total intravenous anesthesia (TIVA). In particular, the infusion rate of the hypnotic drug propofol is the control variable and the bispectral index (BIS) is the controlled variable. The PIDA controller is tuned by using a population-based approach and its robustness is evaluated with a Monte Carlo method. The noise amplification is reduced by means of suitably designed low-pass filters. A comparison with a PID controller is performed, showing that the addition of the acceleration action allows us to design a more aggressive controller, thus reducing the risk of awareness of the patient in the maintenance phase.

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.

Effect of fentanyl constant-rate infusions with or without medetomidine on the minimum infusion rate of propofol required to prevent motor movement in dogs.

Propofol is a potential injectable anesthetic agent used in total intravenous anesthesia. However, the sparing effect of fentanyl and medetomidine on the required propofol dose in dogs remains unclear. We aimed to investigate the effect of fentanyl constant-rate infusion (CRI) with or without medetomidine on the minimum infusion rate of propofol required to prevent motor movement (MIRNM) in dogs. Six healthy purpose-bred dogs were anesthetized on three occasions with propofol alone (loading dose [LD], 8 mg/kg to effect; initial infusion rate [IR], 0.70 mg/kg/min); propofol (LD, 6 mg/kg to effect; IR, 0.35 mg/kg/min) and fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min); or propofol (LD, 4 mg/kg to effect; IR, 0.25 mg/kg/min), fentanyl (LD, 2 µg/kg; IR, 0.10 µg/kg/min), and medetomidine (LD, 2 µg/kg; IR, 0.5 µg/kg/hr) under controlled ventilation. The MIRNM was determined by observing the response to a noxious electrical stimulus. Heart rate, blood pressure, and blood gas analyses were performed at 1, 2, 3, and 4 hr after initiating CRI. The MIRNM (mean [range]) was significantly lower in the propofol-fentanyl-medetomidine group (0.16 [0.10-0.27] mg/kg/min) than that in the propofol-alone group (0.63 [0.47-0.82] mg/kg/min) (P=0.0004). Fentanyl combined with medetomidine did not significantly decrease the mean arterial pressure in dogs receiving propofol CRI 1-3 hr after initiating CRI compared with propofol CRI alone (P>0.9999, P=0.1536, and P=0.0596, respectively), despite inducing a significantly lower heart rate.

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.

Propofol’s EEG Fast Activity is Dose-Dependent

Introduction: For patients with a first-time suspected seizure, electroencephalograms (EEG) are part of the initial evaluation. Most sedatives result in EEG artifact “fast activity” (FA), making the EEG difficult to read. During propofol-sedated EEGs, we noticed that FA would diminish when the propofol infusion rate was low. The purpose of this study is to investigate propofol dosing and its relationship to EEG FA artifact. Methods: This study involved retrospective chart reviews of a pediatric database for sedated EEG encounters in patients under 7 years of age. Data was collected from a total of 55 charts. Total doses of propofol (mg/kg/hr) were calculated for the first half and second half. The actual EEGs were reviewed by a pediatric neurologist study investigator, to classify the degree of FA as: none, mild, moderate, severe. We then examined whether total doses of propofol given during the EEG (mg/kg/hr) halves affected the severity of FA using ordinal logistic regression. Results: The results are summarized in Table 1, which shows that propofol doses (paired T-test, p&lt;0.001) and EEG FA (Bowker’s test of symmetry, p=0.002) were higher in the first half compared to the second half. Figure 1 graphs each data point independently, which shows via linear and ordinal logistic regression a positive relationship between propofol dosing and FA severity (p=0.0014, OR=1.20, 95% CI=1.08-1.34, respectively). Results: The results are summarized in Table 1, which shows that propofol doses (paired T-test, p&lt;0.001) and EEG FA (Bowker’s test of symmetry, p=0.002) were higher in the first half compared to the second half. Figure 1 graphs each data point independently, which shows via linear and ordinal logistic regression a positive relationship between propofol dosing and FA severity (p=0.0014, OR=1.20, 95% CI=1.08-1.34, respectively).

Use of a propofol infusion for anaesthetic maintenance in Guinea pigs (Cavia porcellus): a retrospective case series

ObjectiveTo retrospectively evaluate the feasibility of a propofol infusion for anaesthetic maintenance in guinea pigs. Study designRetrospective case series. AnimalsClient-owned guinea pigs undergoing general anaesthesia. MethodsAnaesthetic records of guinea pigs anaesthetized between March 2015 and March 2018 were reviewed. Animals administered a propofol infusion for > 20 minutes were identified and evaluated. Procedure performed, pre-anaesthetic medication, preoperative and intraoperative respiratory rate (fR) and heart rates (HRs), total amount of propofol administered, total anaesthesia and recovery times were extracted from the records and analysed using descriptive statistics and Pearson correlation tests. Data are reported as mean (range). ResultsRecords of 14 animals meeting the criteria were identified. Following drug combinations were administered for premedication: butorphanol 0.43 (0.3–0.5) mg kg–1, medetomidine 0.1 (0.05–0.2) mg kg–1 and midazolam 1 (0.5–2) mg kg–1 (n = 3); methadone 0.33 (0.25–0.5) mg kg–1, medetomidine 0.07 (0.01–0.1) mg kg–1 and midazolam 0.66 (0.5–1) mg kg–1 (n = 3); butorphanol 0.5 mg kg–1, medetomidine 0.05 mg kg–1 and ketamine 5 mg kg–1 (n = 2); buprenorphine 0.01 mg kg–1, medetomidine 0.07 (0.04–1) mg kg–1 and ketamine 4 (3–5) mg kg–1 (n = 3); butorphanol 0.5 mg kg–1, alfaxalone 1 mg kg–1 and midazolam 0.5 mg kg–1 (n = 1); and methadone 0.38 (0.25–0.5) mg kg–1, medetomidine 0.08 (0.06–1) mg kg–1 with midazolam 0.75 (0.5–1) mg kg–1 (n = 2).Preoperative and intraoperative HRs were 240 (160–300) and 170 (140–200) beats minute–1, respectively. Preoperative and intraoperative fR were 63 (50–86) and 37 (18–80) breaths minute–1, respectively. The propofol infusion rate was 0.45 (0.17–0.80) mg kg–1 minute–1. Total anaesthesia and recovery times were 60 (25–145) and 17 (8–60) minutes, respectively. A slight correlation was found between total propofol dose infused and recovery time (r = 0.58). Conclusion and clinical relevancePropofol infusions may be a useful alternative to inhalant anaesthetics.

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

Accuracy of closed-loop and open-loop propofol delivery systems by bispectral index monitoring in breast surgery patients: a prospective randomized trial

BackgroundThis randomized and controlled prospective study tested the hypothesis that closed-loop Target-Controlled Infusion (TCI) of propofol would be associated with better system performance when compared with open-loop controlled delivery of propofol. MethodsPatients scheduled for elective breast surgery were randomly assigned to two groups: a closed-loop group, in which propofol infusion was performed by a closed-loop TCI system that used the Bispectral Index (BIS) as a feedback parameter to titrate the rate of propofol infusion, and an open-loop group, in which propofol infusion was performed manually and guided by the bispectral index. ResultsA total of 156 patients were recruited for this study (closed-loop group n = 79; open-loop group n = 77). The Global Score (GS) of the closed-loop group was lower than that of the open-loop group (34.3 and 42.2) (p = 0.044). The proportions of time with a BIS value between 40 and 60 were almost identical in the closed-loop group and the open-loop group (68.7 ± 10.6% and 66.7 ± 13.3%) (p = 0.318). The individuals in the closed-loop group consumed more propofol compared with those in the open-loop group (7.20 ± 1.65 mg.kg−1.h−1 vs. 6.03 ± 1.31 mg.kg−1.h−1, p < 0.001). No intraoperative recall, somatic events or adverse events occurred. No significant difference in heart rate was observed between the two groups (p = 0.169). ConclusionThe closed-loop protocol was associated with lower BIS variability and lower out-of-range BIS values, at the cost of a greater consumption of propofol when compared to the open loop group. Register numberChiCTR-INR-17010399.

Increased Perirolandic Cortical Excitability May Facilitate Sensory Motor Mapping in Children (P13-1.003)

<h3>Objective:</h3> We are hereby describing a case of refractory pediatric epilepsy where resection of perirolandic seizure foci was performed successfully under neurophysiologic guidance. <h3>Background:</h3> Pediatric neurophysiologic sensory-motor mapping is frequently unsuccessful, due to inability to localize central sulcus (CS) and primary motor cortex (M1). These shortcomings result from poor somatosensory evoked potentials (SSEP) and high M1 depolarization thresholds respectively, both reflections of the immaturity of the central nervous system. <h3>Design/Methods:</h3> Case report <h3>Results:</h3> An 8-year-old boy with developmental delay, debilitating focal epilepsy and epileptic encephalopathy underwent phase 2 video EEG monitoring. The recordings showed seizures with early involvement of several depth electrodes located within the right parieto-frontal regions, and an early motor semiology involving the left arm. The patient underwent neurophysiologically guided resection of the seizure foci under general anesthesia. Pre-resection electrocorticography (ECoG) via a 64 contact grid showed abundant perirolandic epileptiform discharges (ED), maximal postcentrally. Cortical recordings of high amplitude median SSEP and a low depolarization threshold led to successful CS localization and identification of M1, respectively. A subdural strip electrode placed over the precentral gyrus and secured in position, allowed simultaneous ECoG and motor monitoring during the resection of the postcentral foci. Initially, ECoG showed near continuous runs of ED, unchanged by cortical electrical stimulation. Under steady state anesthesia, at a constant propofol infusion rate, this activity decreased in frequency and stopped altogether towards the end stages of the resection, as the M1 threshold increased by 7 mA. Post-resection fronto-parietal ECoG recordings were quiet. Post-operatively, the patient became seizure free, showed cognitive improvement and no motor deficits. <h3>Conclusions:</h3> Increased cortical excitability may lead to successful functional mapping in children. Under steady anesthetic conditions, increases in the M1 threshold during resection of nearby epileptic foci may be an early sign of decrease in the abnormal regional cortical excitability. <b>Disclosure:</b> Dr. Alzahrany has nothing to disclose. Dr. Simon has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Risk Management Foundation of the Harvard Institutions Incorporated. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MCIC Vermont. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Aaronson, Rappaport, Feinstein&amp; Deutch. Dr. Simon has received publishing royalties from a publication relating to health care. Dr. Simon has received personal compensation in the range of $0-$499 for serving as a Speaker with American Clinical Neurophysiology Society . Dr. Simon has a non-compensated relationship as a Speaker with International Society of Intraoperative Neurophysiology that is relevant to AAN interests or activities. Dr. Simon has a non-compensated relationship as a Speaker with Brazilian Congress of Neurology that is relevant to AAN interests or activities.

Determination of minimum infusion rate of propofol in combination with electroacupuncture in goats

Total intravenous anesthesia (TIVA) is frequently used anesthetic protocol in animals when inhalation anesthesia is not available. To date, it has not yet been known whether electroacupuncture (EA) can affect propofol-based TIVA in goats. Therefore, the present paper aims to determine the minimum infusion rate (MIR) of propofol, in combination with EA, required to preclude purposeful movement of the extremities in response to standardized noxious stimulation in goats. Twelve clinically healthy goats weighing 17.45 ± 2.15 kg were randomly allocated into two groups with six goats each. Propofol alone (P group) and propofol combined with EA (EA-P group). In the EA-P, propofol was given 30 min after EA stimulation. For induction of anesthesia, a bolus of propofol was administered at 4 mg/kg IV, and an infusion dose of 0.4 mg/kg/min was initially set for maintenance. The MIR of propofol in both groups was determined by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) at 10-min intervals after inducing anesthesia until the end period of the experiment. Cardiorespiratory variables and nociceptive threshold were measured throughout anesthesia. The median propofol MIR was significantly lower in the EA-P group than the P group [0.520 (0.467–0.572) and 0.650 (0.600–0.677)], respectively; p = 0.0013). In the P group, goats anesthetized with MIR showed a significant increase in heart rate and cardiac index (p = 0.0010 and p < 0.0001, respectively), and a decrease in respiratory rate (p = 0.0001). Additionally, the EA-P showed a significant decrease in hemoglobin oxygen saturation following the initial infusion rate at 2 min (p = 0.0023) and 10 min (p = 0.0007) as compared to the P group. A significant increase in nociceptive threshold was recorded in the EA-P threshold than that of the P group (p < 0.005). EA combined with propofol provides antinociception, decreases the MIR of propofol-based TIVA, and subsequently lessens the negative cardiorespiratory consequences related to propofol anesthesia in goats.

The safety and efficacy of remimazolam tosylate for induction and maintenance of general anesthesia in pediatric patients undergoing elective surgery: Study protocol for a multicenter, randomized, single-blind, positive-controlled clinical trial.

Introduction: Remimazolam is an ultra-short-acting benzodiazepine sedative agent commonly used in general anesthesia, procedural sedation, and intensive care unit (ICU) sedation. This study aimed to explore the efficacy and safety of remimazolam versus propofol for the induction and maintenance of general anesthesia in preschool-age children undergoing elective surgery. Methods and analysis: In this multicenter, randomized, single-blind, positive-controlled non-inferior clinical trial, one hundred ninety-two children aged 3-6years will be randomly allocated as a 3:1 ratio into two groups: Group R with an intravenous dose of remimazolam 0.3mg/kg for the induction of anesthesia followed by a constant infusion rate of remimazolam 1-3mg/kg/h to maintain anesthesia, and Group P with an intravenous dose of propofol 2.5mg/kg for the induction of anesthesia followed by a constant infusion rate of propofol 4-12mg/kg/h to maintain anesthesia. The primary outcome will be the rate of the successful induction and maintenance of anesthesia. The secondary outcomes will include the time to LoC, the Bispectral Index (BIS) value, awakening time, extubation time, post-anesthesia care unit (PACU) discharge time, usage of additional sedative drugs during the induction period, usage of remedial drugs in PACU, emergence delirium, pain in PACU, behavior scores at day 3 after surgery, parental and anesthesiologists' satisfaction, and adverse events. Ethics and dissemination: This study has been approved by the ethics review boards at all participating hospitals. The Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Reference No. LCKY 2020-380, November 13, 2020) is the central ethics committee.

The effect of melatonin administration on sedation level as adjuvant to propofol in mechanically ventilated traumatic brain injury patients

ABSTRACT Background Melatonin is a pineal gland neuro-hormone influencing the biological regulations of the circadian rhythm. Numerous investigations have revealed variable effects of melatonin in vivo, including anti-inflammatory, antioxidant, sedative, and anxiolytic effects. The effects of using exogenous melatonin as an adjuvant to propofol on the degree of sedation in patients were investigated. Aim We aimed to test the feasibility of melatonin as a sedative agent in traumatic brain injury patients. Methods This research was a double-blinded clinical trial conducted on 38 participants suffering from traumatic brain injuries necessitating sedation and mechanical ventilation. Participants were assigned randomly into two groups. Both groups were sedated by propofol infusion and monitored by bispectral index (BIS). Nineteen patients received 10 mg of melatonin, and 19 patients received a placebo (control). Propofol infusion rate and BIS values were recorded each 30 minutes for 12 hours. Results Exogenous melatonin administration led to a significant decrease in the amount of infused propofol necessary to attain the desired level of sedation. The propofol infusion rates were 4.87 ± 2.91 ml/h in the melatonin group and 6.37 ± 2.87 ml/h in the control group (P- values = 0.001). Conclusion Exogenous melatonin acts as an adjuvant to propofol in sedation, reducing the amount of propofol infusion needed.

Comparison of propofol infusion rate required to abolish swallowing or pedal withdrawal reflexes in dogs.

In a prospective, randomized, experimental non-blinded study, the continuous infusions rates of propofol required to prevent swallowing (P-SR) or pedal withdrawal reflex (P-WR) were evaluated in healthy premedicated dogs. Dogs were randomly assigned to one of two treatments at weekly intervals. Following premedication with a combination of acepromazine and methadone, anesthesia was induced with propofol (4.00 mg kg-1 per min) and was maintained for 90 min. The propofol infusion rate was increased or decreased by 0.05 mg kg-1 per min based on positive or negative swallowing (P-SR) or pedal withdrawal reflexes (P-WR). Propofol induction doses were 2.12 ± 0.43 mg kg-1 (P-SR) and 2.14 ± 0.31 mg kg-1 (P-WR), which were not significantly different. The mean (±SD) propofol infusion rate was significantly higher for P-WR (0.26 ± 0.10 mg kg-1 per min) when compared to P-SR (0.22 ± 0.12 mg kg-1 per min). During the last 30 min, the mean propofol infusion rates were 0.09 ± 0.02 and 0.18 ± 0.03 mg kg-1 per min for P-SR and P-WR, respectively. There were no significant differences between treatments with respect to heart rate (HR), respiratory rate, arterial blood pressure, end-tidal CO2 partial pressure, hemoglobin oxygen saturation, partial pressures of oxygen or pH. Transient apnea lasting up to three minutes was observed in three dogs with each treatment. Propofol infusion rate of 0.22 ± 0.12 mg kg-1 per min can be used in premedicated dogs requiring tracheal intubation and undergoing mechanical ventilation, non-painful procedures or painful procedures with local anesthetic techniques.