Intravenous Target-controlled Infusion Research Articles

Effects of different remifentanil target concentrations on MACBAR of sevoflurane in patients with liver dysfunction under carbon dioxide pneumoperitoneum stimulus: A randomized controlled trial.

Remifentanil can effectively decrease the sevoflurane concentration to block sympathetic adrenergic response to CO2 pneumoperitoneum stimulus,and liver dysfunction will significantly reduce the MACBAR (minimum alveolar concentration for blocking adrenergic response) of sevoflurane. However, the effects of different remifentanil concentrations on the MACBAR of sevoflurane in patients with liver dysfunction are unclear. The aim of this study was to observe the effects of different remifentanil concentrations by intravenous target-controlled infusion on the MACBAR of sevoflurane in patients with grade B liver dysfunction under carbon dioxide pneumoperitoneum stimulus. Seventy-five patients with grade B liver dysfunction undergoing elective laparoscopic surgery were selected, and randomly divided into three groups with remifentanil plasma target concentrations of 0 (group R0 ), 1 (group R1 ) and 2 (group R2 ) ng/ml. Anaesthesia was induced by intravenous injection of propofol 2-3mg/kg, remifentanil 2μg/kg and cisatracurium 0.15mg/kg. All groups were inhaled different concentrations of sevoflurane. The determination of sevoflurane MACBAR in each group was used a method of sequential-allocation technique, and venous blood samples were taken before and after the creation of carbon dioxide pneumoperitoneum to determine plasma adrenaline and noradrenaline concentrations. The MACBAR of sevoflurane in groups R0 , R1 and R2 was 4.83%, 3.00% and 2.10%, respectively. The MACBAR of sevoflurane was significantly difference among the three groups. When a similar effect of MACBAR had achieved in each group, no significant differences were found in the changes of plasma adrenaline and noradrenaline concentrations before and after the creation of pneumoperitoneum. What is new and conclusion Target-controlled infusion of different concentrations of remifentanil can reduce sevoflurane MACBAR during pneumoperitoneum stimulation in patients with liver dysfunction in some degree. However, the changes of plasma adrenaline and noradrenaline concentrations are consistent in the three groups when patient's stress response was inhibited at the same degree.

High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design.

Severe chronic postsurgical pain has a prevalence of 4-10% in the surgical population. The underlying nociceptive mechanisms have not been well characterized. Following the late resolution phase of an inflammatory injury, high-dose μ-opioid-receptor inverse agonists reinstate hypersensitivity to nociceptive stimuli. This unmasking of latent pain sensitization has been a consistent finding in rodents while only observed in a limited number of human volunteers. Latent sensitization could be a potential triggering venue in chronic postsurgical pain. The objective of the present trial was in detail to examine the association between injury-induced secondary hyperalgesia and naloxone-induced unmasking of latent sensitization. Healthy volunteers (n = 80) received a cutaneous heat injury (47°C, 420 s, 12.5 cm2). Baseline secondary hyperalgesia areas were assessed 1 h post-injury. Utilizing an enriched enrollment design, subjects with a magnitude of secondary hyperalgesia areas in the upper quartile ('high-sensitizers' [n = 20]) and the lower quartile ('low-sensitizers' [n = 20]) were selected for further study. In four consecutive experimental sessions (Sessions 1 to 4), the subjects at two sessions (Sessions 1 and 3) received a cutaneous heat injury followed 168 h later (Sessions 2 and 4) by a three-step target-controlled intravenous infusion of naloxone (3.25 mg/kg), or normal saline. Assessments of secondary hyperalgesia areas were made immediately before and stepwise during the infusions. Simple univariate statistics revealed no significant differences in secondary hyperalgesia areas between naloxone and placebo treatments (P = 0.215), or between 'high-sensitizers' and 'low-sensitizers' (P = 0.757). In a mixed-effects model, secondary hyperalgesia areas were significantly larger following naloxone as compared to placebo for 'high-sensitizers' (P < 0.001), but not 'low-sensitizers' (P = 0.651). Although we could not unequivocally demonstrate naloxone-induced reinstatement of heat injury-induced hyperalgesia, further studies in clinical postsurgical pain models are warranted.

Remifentanil for Carboprost-Induced Adverse Reactions During Cesarean Delivery Under Combined Spinal-Epidural Anesthesia

PurposeCarboprost may induce adverse reactions when used to treat postpartum hemorrhage. We aimed to explore the effects of intravenous infusion of low-dose remifentanil to prevent such reactions.MethodsWe enrolled parturient patients scheduled for elective cesarean section. Anesthesiologist administered combined spinal epidurals at the L3/4 interspace, with 0.5% hyperbaric bupivacaine subarachnoid space injections (1.5–2.5 ml). We randomly divided parturient patients, administered carboprost during surgery, into the remifentanil group (group R) and the control group (group C). Patients in group R received an intravenous target-controlled infusion of remifentanil (target effect-site concentration, 1.5 ng/ml) simultaneously with a carboprost tromethamine injection (250 µg). Patients in group C received a normal saline infusion with carboprost. We recorded and analyzed the incidence of carboprost-related adverse reactions (vomiting, nausea, chest congestion, flushing, hypertension, tachycardia, cough, and shivering), and assessed patient comfort using a numerical rating scale ([NRS], on which 0 was very uncomfortable and 10 was very comfortable).ResultsAfter applying inclusion and exclusion criteria, we conducted statistical analysis of the data from 70 women. The incidence of vomiting was significantly lower in group R than in group C (14.3 vs. 51.4%, p < 0.01); and the incidence of nausea, chest congestion, facial flushing, and hypertension were significantly lower in group R than in group C (all p < 0.01). Furthermore, the patients’ comfort scores were significantly higher in group R than in group C (8.0 ± 1.8 vs. 3.6 ± 2.1, p < 0.01).ConclusionOur results demonstrate that an intravenous low-dose remifentanil infusion can effectively prevent carboprost-related adverse reactions during cesarean delivery under combined spinal and epidural anesthesia.Clinical Trial RegistrationWe pre-registered this study at http://www.chictr.org.cn/showproj.aspx?proj=27707 (ChiCTR1800016292).

Analysis of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope

Objective: To investigate the efficacy and safety of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope. Methods: One hundred patients undergoing radical resection of lung cancer under thoracoscope in Affiliated Cancer Hospital of Zhengzhou University from March to September in 2019, were randomly divided into control group (group C) and sugammadex group (group S). All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion of propofol and remifentanil, and intermittent intravenous injection of the neuromuscular block of rocuronium. During the operation, the bispectral index (BIS) was used to monitor the depth of anesthesia, and the neuromuscular block was assessed with TOF. Single-lung mechanical ventilation and double-lumen endotracheal intubation were carried out, and patient-controlled analgesia after operation were enforced. Patients in group C received neostigmine (2 mg) combined with atropine (0.5-1.0 mg) after thoracic closure, while patients in group S received sugammadex (2 mg/kg) at TOF count (≥2) after thoracic closure, and then double-lumen endotracheal tubes were extubated according to extubation indications. At these time points: T(0) (immediate before anesthesia induction), T(1) (immediate before tracheal intubation), T(2) (immediately after thoracic closure), T(3) (1 h after operation), T(4) (6 h after operation), T(5) (24 h after operation), T(6)(48 h after operation), the heart rate(HR) and mean arterial pressure (MAP) were recorded, QT interval (V3 ECG) were measured and calculated, indicators of liver function [alanine transaminase (ALT), aspartate transaminase(AST)], renal function [blood urea nitrogen (BUN), creatinine (Cre)] and clotting function [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The duration of operation, postoperative conditions within 48 hours after operation(the time of tracheal tube extubation, respiratory suppression/dysfunction, allergy, nausea and vomiting, itching of skin, abnormal sensation), pathological types and the postoperative hospital stay were recorded. Results: There were no significant differences of the age, sex ratio, body mass index (BMI), American Society of Anesthesiologists (ASA) grading ratio, duration of operation, pathological types and the postoperative hospital stay, HR, MAP and QT interval between two groups (all P>0.05). There were no remarkable differences of the levels of serum histamine, ALT, AST, BUN, Cre, TT, PT, APTT and FIB before and after administration of neuromuscular blockade antagonists (neostigmine or Sugammadex) in the same group patients (all P>0.05), also no significant differences between group C and group S at the same time points (all P>0.05). Average time of tracheal tube extubation in group S [(3.7±1.3) min] was sharply shorter than that in group C [(14.5±4.4) min, t=2.266, P<0.05)]. There were no patients with allergy, skin itching, sensory abnormality in these two groups. There were no significant difference of the incidence of postoperative nausea and vomiting between these two groups. There were 5 patients with respiratory depression in group C and no respiratory depression patient in group S, the difference was statistically significant between these two groups (χ(2)=5.263, P<0.05). Conclusion: Sugammadex is effective for antagonizing the neuromuscular blockade of rocuronium in patients with radical resection of lung cancer under thoracoscope, and can shorten the time of tracheal tube extubation after surgery.

Effect of dexmedetomidine on perioperative stress and postoperative pain in patients with radical resection of esophageal cancer under combined thoracoscope and laparoscope

Objective: To investigate the effects of dexmedetomidine on perioperative stress and postoperative pain in patients with radical resection of esophageal cancer under combined thoracoscope and laparoscope. Methods: In this prospective study, one hundred patients undergoing radical resection of esophageal cancer in Affiliated Cancer Hospital of Zhengzhou University from January 2016 to October 2017, were randomly divided into control group (group C) and dexmedetomidine group (group D), n=50. All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion(TCl) of propofol and remifentanil, and intermittent intravenous injection of cisatracuriumbesylate. Bispectral index(BIS) was used to monitor the depth of anesthesia and maintained between 45-60 during operation.All patients received sufentanil (0.3 μg/kg) 30 min before the end of the operation and then received intravenous analgesia pump for postoperative patient controlled analgesia(PCA). Patients in group D received intravenous infusion of dexmedetomidine(1 μg/kg) 20 min before anesthesia induction, followed by intravenous pumping of dexmedetomidine(0.2 μg·kg(-1)·h(-1)) intraoperatively.Postoperative intravenous patient-controlled analgesia(PCA) was performed in all patients, with background doses of sufentanil 0.04 μg· kg(-1)·h(-1) for patients in group C, and sufentanil 0.025 μg·kg(-1)·h(-1) plus dexmedetomidine 0.1 μg· kg(-1)·h(-1) for patients in group D. The operation time, liquid input and output during operation, the number of PCA pressings after operation were recorded. At these time points: T(0)(the day before operation), T(1)(immediate before anesthesia induction), T(2)(1 h after emergence), T(3)(24 h after operation), T(4)(3 d after operation), T(5)(7 d after operation), T(6)(one month after operation), T(7)(3 months after operation) and T(8)(6 month after operation) , venous blood samples of patients were collected for detection of epinephrine, norepinephrine and corticosterone. The pain visual analogue scale(VSA) was used to assess pain levels in patients at T(2), T(3), T(4), T(5), T(6), T(7), T(8). Results: The age, sex ratio, body mass index (BMI) and ASA grading ratio in two groups were not significantly different(all P>0.05). There were no Significant differences in operation time, liquid input and blood output between group C and group D(all P>0.05). Within 24 h after operation, the sufentanil consumption in group D[(35.86±8.65)μg]was significantly less than that in group C[(59.53±15.26) μg, t=7.061, P<0.05], and the number of PCA pressing in group D(2.15±1.38) was obviously less than that in group C(5.85±2.16, t=4.971, P<0.05). Compared with group C, serum norepinephrines in group D was significantly less (t=13.276, 16.027, 14.319, 12.771, 12.296, respectively; all P<0.05) at T(1), T(2), T(3), T(4), T(5).And there were no difference between these two groups at T(0), T(6), T(7), T(8)(all P>0.05). Serum epinephrine in group D were significantly lower than them in group C at T(2), T(3), T(4), T(5) (t=6.153, 8.774, 9.127, 8.409, respectively; all P<0.05), but there were no difference between these two groups at T(0), T(1), T(6), T(7), T(8)(all P>0.05). Serum corticosterone in group D were sharply less than them in group C at T(2), T(3), T(4), T(5) (t=16.364, 15.306, 12.153, 12.592, respectively; all P<0.05), but at T(0), T(1), T(6), T(7), T(8), there were no difference between these two groups (all P>0.05). Compared with group C, the number of patients with postoperative pain(VAS score≥4) in group D was obviously less at T(6), T(7), T(8)(10 vs 20, 4 vs 12, 3 vs 10; χ(2)=4.762, 4.762, 4.332, respectively; all P<0.05). Conclusion: Perioperative application of dexmedetomidine can effectively decrease the perioperative stress response, obviously cut down the perioperative opioid consumption, and prevent the transition from postoperative acute pain to chronic pain in patients with radical resection of esophageal cancer under combined thoracoscope and laparoscope.

Abstract PR344

Background & Objectives: Bispectral index (BIS) is considered very useful to guide anaesthesia care in elderly patients, but it is controversial for the evaluation of the adequacy of analgesia. This study compared the BIS changes in response to loss of consciousness (LOC) and loss of somatic response (LOS) to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion (TCI) of propofol and remifentanil. Materials & Methods: This study was performed on 52 elderly patients (aged 65~78 yr) and 52 young patients (aged 25~58 yr), ASA physical status I or II. Anaesthesia was induced with propofol administered by TCI. A standardized noxious electrical stimulus (transcutaneous electrical nerve stimulation, TENS) was applied (50 Hz, 80 mA, 0.25 ms pulses for 4 s) to the ulnar nerve at increasing remifentanil effective-site concentration (Ce) until patients lost somatic response to TENS. Changes in awake, prestimulus, poststimulus BIS, heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation (SpO2), predicted plasma concentration (Cp), predicted effective-site concentration (Ce) of propofol and remifentanil at both LOC and LOS clinical points were investigated. Results: BISLOC in elderly group 65.4±9.7 was higher than that in young patient group (65.4±9.7 vs 57.6±12.3) (t=21.58, P<0.0001) after TCI propofol, and the propofol Ce at LOC was 1.6±0.3 μg/ml in elderly patients, which was significantly lower than that in young patients (2.3±0.5 μg/ml) (t=7.474, P<0.0001). As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups (t=8.902 and t=8.019, P<0.0001). With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOS was the same as the BISLOC in elderly patients (65.6±10.7 vs 65.4±9.7), and there were no marked differences between elderly and young patient groups in BISawake, BISLOS and Ce of remifentanil required for LOS. Conclusion: In elderly patients, BIS can be used as indicator for hypnotic-analgesic balance, and be helpful to guide the optimal administration of propofol and remifentanil individually. Disclosure of Interest: None declared

A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience.

The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel “alternate universe,” often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient “beings.” The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 min—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

Remifentanil alters sensory neuromodulation of swallowing in healthy volunteers: quantification by a novel pressure-impedance analysis.

Exposure to remifentanil contributes to an increased risk of pulmonary aspiration, likely through reduced pharyngeal contractile vigor and diminished bolus propulsion during swallowing. We employed a novel high-resolution pressure-flow analysis to quantify the biomechanical changes across the upper esophageal sphincter (UES). Eleven healthy young (23.3 ± 3.1 yr old) participants (7 men and 4 women) received remifentanil via intravenous target-controlled infusion with an effect-site concentration of 3 ng/ml. Before and 30 min following commencement of remifentanil administration, participants performed ten 10-ml saline swallows while pharyngoesophageal manometry and electrical impedance data were recorded using a 4.2-mm-diameter catheter housing 36 circumferential pressure sensors. Remifentanil significantly shortened the duration of UES opening (P < 0.001) and increased residual UES pressure (P = 0.003). At the level of the hypopharynx, remifentanil significantly shortened the latency from maximum bolus distension to peak contraction (P = 0.004) and significantly increased intrabolus distension pressure (P = 0.024). Novel mechanical states analysis revealed that the latencies between the different phases of the stereotypical UES relaxation sequence were shortened by remifentanil. Reduced duration of bolus flow during shortened UES opening, in concert with increased hypopharyngeal distension pressures, is mechanically consistent with increased flow resistance due to a more rapid bolus flow rate. These biomechanical changes are congruent with modification of the physiological neuroregulatory mechanism governing accommodation to bolus volume.

Changes in the Bispectral Index in Response to Loss of Consciousness and No Somatic Movement to Nociceptive Stimuli in Elderly Patients.

Background:Bispectral index (BIS) is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia. This study compared the BIS changes in response to loss of consciousness (LOC) and loss of somatic response (LOS) to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion (TCI) of propofol and remifentanil.Methods:This study was performed on 52 elderly patients (aged 65–78 years) and 52 young patients (aged 25–58 years), American Society of Anesthesiologists physical status I or II. Anesthesia was induced with propofol administered by TCI. A standardized noxious electrical stimulus (transcutaneous electrical nerve stimulation, [TENS]) was applied (50 Hz, 80 mA, 0.25 ms pulses for 4 s) to the ulnar nerve at increasing remifentanil predicted effective-site concentration (Ce) until patients lost somatic response to TENS. Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated.Results:BISLOC in elderly group was higher than that in young patient group (65.4 ± 9.7 vs. 57.6 ± 12.3) (t = 21.58, P < 0.0001) after TCI propofol, and the propofol Ce at LOC was 1.6 ± 0.3 μg/ml in elderly patients, which was significantly lower than that in young patients (2.3 ± 0.5 μg/ml) (t = 7.474, P < 0.0001). As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups (t = 8.902 and t = 8.019, P < 0.0001). With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOS was the same as the BISLOC in elderly patients (65.6 ± 10.7 vs. 65.4 ± 9.7), and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS.Conclusion:In elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually.Trial Registration:CTRI Reg. No: ChiCTR-OOC-14005629; http://www.chictr.org.cn/showproj.aspx?proj=9875.

Bispectral index for monitoring anesthetic depth in patients with severe burns receiving target-controlled infusion of remifentanil and propofol.

This study evaluated the feasibility and effectiveness of using the bispectral index (BIS) to monitor anesthetic depth in patients with severe burns receiving intravenous target-controlled infusion (TCI) of remifentanil and propofol. We randomly assigned 80 patients undergoing elective escharectomy (<1 week) to BIS (A) and control (B) groups. All patients received remifentanil and propofol as intravenous TCI anesthesia. Clinical data were recorded at different time points. The time from drug withdrawal to eye opening upon the patient hearing his/her name called and upon reaching an Aldrete score of 9 points was also recorded. During anesthesia maintenance, the target concentrations of remifentanil and propofol in group A were significantly lower than that in group B (2.12 ± 0.35 vs 2.50 ± 0.21 ng/mL and 2.54 ± 0.22 vs 2.86 ± 0.31 μg/mL, respectively; P < 0.01). The time from drug withdrawal to eye opening upon the patient hearing his/her name called and reaching an Aldrete score of 9 points in group A was considerably shorter than that in group B (7.90 ± 0.58 vs 8.35 ± 0.66 min and 9.15 ± 0.69 vs 11.13 ± 0.96 min, respectively; P < 0.01). In both groups, mean arterial pressure and heart rate values at each time point after loss of consciousness were significantly lower than the baseline values (P < 0.05), with the exception of 2 min after intubation. The use of BIS to monitor anesthetic depth in patients with severe burns receiving TCI of remifentanil and propofol during the perioperative period reduces propofol consumption and shortens the consciousness recovery time in patients.

Total Intravenous Anesthesia with Target-Controlled Infusion of Remifetanil and Propofol for Ablation of Atrial Fibrillation

Although ablation of atrial fibrillation (AF) is common in other centers, among us it is a new procedure. The choice of anesthesia, monitors, and anesthesiologic care for this procedure performed outside the surgical center has not been described. The objective of this report was to describe an anesthesia technique for ablation of AF. This is a 49-year old female weighing 73 kg, 155 cm, and ASA II due to hypertension. The patient was monitored with a 12-lead ECG, pulse oximetry, heart rate, bispectral electroencephalography for BIS measurement, suppression rate (SR), and SEF95, and mean arterial pressure (MAP). Intravenous target-controlled infusion (TCI) of propofol with a target of 4 microg x mL(-1), intravenous TCI of remifentanil with a target of 3 ng x mL(-1), and intravenous bolus of rocuronium 0.2 mg x kg(-1) were used for induction of anesthesia. The pharmacokinetic model of propofol described by Marsh was used and incorporated into the propofol PFS pump. The pharmacokinetic model of remifentanil described by Minto was incorporated into the Alaris PK infusion pump. Local effector, or biophase, concentrations corresponded to the information obtained from the infusion pumps and represented predictive measurements of the concentrations of both drugs on their sites of action. The concentrations of propofol and remifentanil were regulated according to BIS and MAP, respectively. Total intravenous anesthesia for ablation of AF can be a safe option considering the lack of electrophysiological changes in accessory pathways. The literature on this subject is scarce and new publications could justify, or not, this type of anesthesia during ablation of AF.

Low-dose Propofol Infusion for Controlling Acute Hyperspasticity after Withdrawal of Intrathecal Baclofen Therapy

Low-dose Propofol Infusion for Controlling Acute Hyperspasticity after Withdrawal of Intrathecal Baclofen Therapy