An Experimental Study to Optimize Neuromuscular Blockade Protocols in Cynomolgus Macaques: Monitoring, Doses, and Antagonism.

BACKGROUND: Neuromuscular blocking agents (NMBAs) are a crucial component of anesthesia and intensive care through the relaxation of skeletal muscles. They can lead to adverse reactions such as postoperative residual neuromuscular block. Only one agent is capable of an instant block reversal in deep block situations, but is restricted to aminosteroid agents. Among animal models, non-human primates are an essential model for a great diversity of human disease models. The main objective of this study was to establish a model for NMBA monitoring with current available drugs before testing new reversal agents. METHODS: Seven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anesthesia was maintained with isoflurane. Either rocuronium bromine (with or without sugammadex reversal) or atracurium besylate was evaluated. Monitoring was performed with two devices, TOF-Watch and ToFscan, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann-Whitney statistical analyses were done when indicated. RESULTS: NMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrode placement, to be efficient and valid in cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro-muscular block at equivalent doses to clinical doses in humans. The rocuronium-induced profound neuromuscular block could be reversed using the cyclodextrin sugammadex as a reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count. CONCLUSION: These results support the use of non-human primate models for neuromuscular block monitoring. This represented the first step before the forthcoming testing of new NMBA-reversal agents.

Assessing the clinical advantage of opioid-reduced anesthesia in thoracoscopic sympathectomy: a prospective randomized controlled trial.

BACKGROUND: Opioid-reduced multimodal analgesia has been used clinically for many years to decrease the perioperative complications associated with opioid drugs. We aimed to assess the clinical effects of opioid-reduced anesthesia during thoracoscopic sympathectomy. METHODS: Surgical patients (n = 151) with palmar hyperhidrosis were randomly divided into control (Group C, 73 patients) and test (Group T, 78 patients) groups. All patients were administered general anesthesia using a laryngeal mask. In Group C, patients received propofol, fentanyl, and cisatracurium for anesthesia induction, and maintenance was achieved with propofol and remifentanil, along with mechanical ventilation during the operation. In Group T, anesthesia was induced with propofol, dezocine, and dexmedetomidine (DEX) and maintained with propofol, DEX, and an intercostal nerve block, along with spontaneous breathing throughout the operation. Perioperative complications related to opioid use include hypotension, bradycardia, hypertension, tachycardia, hypoxemia, nausea, vomiting, urine retention, itching, and dizziness were observed. To assess the impact of these complications, we recorded and compared vital signs, blood gas indices, visual analogue scale (VAS) scores, adverse events, and patient satisfaction between the two groups. RESULTS: Perioperative complications related to opioid use were similar between groups. There were no significant differences in the type of perioperative sedation, analgesia index, respiratory and circulatory indicators, blood gas analysis, postoperative VAS scores, adverse reactions, propofol dosage, postoperative recovery time, and patient satisfaction. CONCLUSIONS: In minimally invasive surgeries such as thoracoscopic sympathectomy, opioid-reduced anesthesia was found to be safe and effective; however, this method did not demonstrate clinical advantages. TRIAL REGISTRATION: Chinese Clinical Trial Register: ChiCTR2100055005, on December 30, 2021.

Neurodevelopmental Outcomes after Premedication with Atropine/Propofol vs Atropine/Atracurium/Sufentanil for Neonatal Intubation: 2-Year Follow-Up of a Randomized Clinical Trial.

This study followed 173 newborn infants in the PREmedication Trial for Tracheal Intubation of the NEOnate multicenter, double-blind, randomized controlled trial of atropine-propofol vs atropine-atracurium-sufentanil for premedication before nonemergency intubation. At 2 years of corrected age, there was no significant difference between the groups in death or risk of neurodevelopmental delay assessed with the Ages and Stages Questionnaire. Trial registration Clinicaltrials.gov: NCT01490580.

Neuromuscular Blockade Monitoring in Acute Respiratory Distress Syndrome: Randomized Controlled Trial of Clinical Assessment Alone or With Peripheral Nerve Stimulation.

BACKGROUND: Whether train-of-four (TOF) monitoring is more effective than clinical monitoring to guide neuromuscular blockade (NMB) in patients with acute respiratory distress syndrome (ARDS) is unclear. We compared clinical monitoring alone or with TOF monitoring to guide atracurium dosage adjustment with respect to drug dose and respiratory parameters. METHODS: From 2015 to 2016, we conducted a randomized controlled trial comparing clinical assessments every 2 hours with or without corrugator supercilii TOF monitoring every 4 hours in patients who developed ARDS (Pao2/Fio2 <150 mm Hg) in a cardiothoracic intensive care unit. The primary outcome was the cumulative atracurium dose (mg/kg/h). Secondary outcomes included respiratory parameters during the neuromuscular blockade. RESULTS: A total of 38 patients in the clinical + TOF (C + TOF) group and 39 patients in the clinical (C) group were included in an intention-to-treat (ITT) analysis. The cumulative atracurium dose was higher in the C + TOF group (1.06 [0.75-1.30] vs 0.65 [0.60-0.89] mg/kg/h in the C group; P < .001) compared to C group, as well as the atracurium daily dose (C + TOF - C group mean difference = 0.256 mg/kg/h [95% confidence interval {CI}, 0.099-0.416], P = .026). Driving pressures during neuromuscular blocking agent (NMBA) administration did not differ between groups (P = .653). Intensive care unit (ICU) mortality was 22% in the C group and 27% in the C + TOF group (P = .786). Days on ventilation were 17 (8-26) in the C group and 16 (10-35) in the C + TOF group. CONCLUSIONS: In patients with ARDS, adding TOF to clinical monitoring of neuromuscular blockade did not change ICU mortality or days on mechanical ventilation (MV) but did increase atracurium consumption when compared to clinical assessment alone. TOF monitoring may not be needed in all patients who receive neuromuscular blockade for ARDS.

Lidocaine combined with magnesium sulfate preserved hemodynamic stability during general anesthesia without prolonging neuromuscular blockade: a randomized, double-blind, controlled trial.

BACKGROUND: Lidocaine and magnesium sulfate have become increasingly utilized in general anesthesia. The present study evaluated the effects of these drugs, isolated or combined, on hemodynamic parameters as well as on the cisatracurium-induced neuromuscular blockade (NMB). METHODS: At a university hospital, 64 patients, ASA physical status I and II, undergoing elective surgery with similar pain stimuli were randomly assigned to four groups. Patients received a bolus of lidocaine and magnesium sulfate before the tracheal intubation and a continuous infusion during the operation as follows: 3 mg.kg- 1 and 3 mg.kg- 1.h- 1 (lidocaine - L group), 40 mg.kg- 1 and 20 mg.kg- 1.h- 1 (magnesium - M group), equal doses of both drugs (magnesium plus lidocaine - ML group), and an equivalent volume of isotonic solution (control - C group). Hemodynamic parameters and neuromuscular blockade features were continuously monitored until spontaneous recovery of the train of four (TOF) ratio (TOFR > 0.9). RESULTS: The magnesium sulfate significantly prolonged all NMB recovery features, without changing the speed of onset of cisatracurium. The addition of lidocaine to Magnesium Sulfate did not influence the cisatracurium neuromuscular blockade. A similar finding was observed when this drug was used alone, with a significantly smaller fluctuation of mean arterial pressure (MAP) and heart rate (HR) measures during anesthesia induction and maintenance. Interestingly, the percentage of patients who achieved a TOFR of 90% without reaching T1-95% was higher in the M and ML groups. Than in the C and L groups. There were no adverse events reported in this study. CONCLUSION: Intravenous lidocaine plays a significant role in the hemodynamic stability of patients under general anesthesia without exerting any additional impact on the NMB, even combined with magnesium sulfate. Aside from prolonging all NMB recovery characteristics without altering the onset speed, magnesium sulfate enhances the TOF recovery rate without T1 recovery. Our findings may aid clinical decisions involving the use of these drugs by encouraging their association in multimodal anesthesia or other therapeutic purposes. TRIAL REGISTRATION: NCT02483611 (registration date: 06-29-2015).

Neuromuscular blockade with atracurium for ophthalmic surgery in horses-Effects on surgical and anesthetic characteristics and recovery quality.

OBJECTIVE: To study the surgical, anesthetic and recovery qualities of horses receiving either a neuromuscular blocking agent (atracurium) or intravenous lidocaine (treatment groups A and L, respectively). ANIMALS STUDIED: A total of thirty horses presented for ocular surgery were used in this study. PROCEDURE: Horses were randomly assigned to receive either atracurium (group A) or a lidocaine constant rate infusion (group L). Surgical quality was graded on a scale from 1 (excellent)-5 (poor). While anesthetized, the heart rate, oxygen saturation and mean arterial blood pressure, and end-expiratory carbon dioxide and desflurane concentration were monitored and recorded every 5 minutes. Recovery was scored on a scale from 10 (best)-115 (worst). RESULTS: Horses in treatment group A needed significantly less desflurane then horses in treatment group L (p = 0.04). Horses in treatment group A had a significantly better surgery score of 1 (1-2) (median and range) then horses in treatment group L (2.5; 1-5) (p = 0.02). The quality of recovery was significantly better in horses in treatment group A compared with treatment group L, and horses needed significantly less time to reach the standing position. CONCLUSIONS: Atracurium and lidocaine CRI are safe methods of anesthesia for equine patients undergoing ocular surgery. Horses receiving atracurium needed less desflurane and had better surgery and recovery scores than horses receiving a lidocaine constant rate infusion.

Supine versus semi-Fowler's positions for tracheal extubation in abdominal surgery-a randomized clinical trial.

BACKGROUND: Tracheal extubation is commonly performed in the supine position. However, in patients undergoing abdominal surgery, the supine position increases abdominal wall tension, especially during coughing and deep breathing, which may aggravate pain and lead to abdominal wound dehiscence. The semi-Fowler's position may reduce abdominal wall tension, but its safety and comfort in tracheal extubation have not been reported. We aimed to evaluate the safety and comfort of different extubation positions in patients undergoing abdominal surgery. METHODS: We enrolled 141 patients with an American Society of Anesthesiologists grade of I-III who underwent abdominal surgery. All patients were anesthetized with propofol, fentanyl, cisatracurium, and sevoflurane. After surgery, all patients were transferred to the post-anesthesia care unit (PACU). Patients were then randomly put into the semi-Fowler's (n = 70) or supine (n = 71) position while 100% oxygen was administered. The endotracheal tube was removed after the patients opened their eyes and regained consciousness. Vital signs, coughing, and pain and comfort scores before and/or after extubation were recorded until the patients left the PACU. RESULTS: In comparison with the supine position, the semi-Fowler's position significantly decreased the wound pain scores at all intervals after extubation (3.51 ± 2.50 vs. 4.58 ± 2.26, 2.23 ± 1.68 vs. 3.11 ± 2.00, 1.81 ± 1.32 vs. 2.59 ± 1.88, P = 0.009, 0.005 and 0.005, respectively), reduced severe coughing (8[11.43%] vs. 21[29.58%], P = 0.008) and bucking after extubation (3[4.29%] vs. 18[25.35%], P < 0.001), and improved the comfort scores 5 min after extubation (6.11 ± 2.30 vs. 5.17 ± 1.78, P = 0.007) and when leaving from post-anesthesia care unit (7.17 ± 2.27 vs. 6.44 ± 1.79, P = 0.034). The incidences of vomiting, emergence agitation, and respiratory complications were of no significant difference. CONCLUSION: Tracheal extubation in the semi-Fowler's position is associated with less coughing, sputum suction, and pain, and more comfort, without specific adverse effects when compared to the conventional supine position. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025566 . Registered on 1st September 2019.

A comparison between the flexor hallucis brevis and adductor pollicis muscles in atracurium-induced neuromuscular blockade using acceleromyography: A prospective observational study.

BACKGROUND: Neuromuscular blockade (NMB) monitoring is essential to avoid residual NMB. While the adductor pollicis is the recommended site for monitoring recovery, it is not always accessible. The flexor hallucis brevis could be an interesting alternative. OBJECTIVE: The aim of our study was to compare NMB onset and recovery at both sites. DESIGN: Prospective observational study. SETTING: Operating rooms at the University Hospital of Poitiers, France. PATIENTS: Sixty patients scheduled for surgery under general anaesthesia with neuromuscular blocking agents were enrolled from January 2016 to September 2017. Data from 56 patients were finally analysed. Among these, 11 patients received pharmacological reversal with neostigmine and atropine before emergence from anaesthesia. INTERVENTION: After atracurium injection, NMB onset and recovery at the adductor pollicis and flexor hallucis brevis were monitored simultaneously. MAIN OUTCOME MEASURES: The time to NMB onset, defined as a train-of-four (TOF) count equal to 0, and the times to NMB recovery: TOF = 1, TOF = 4, T4/T1 ratio = 0.75 and T4/T1 ratio more than 0.90. RESULTS: NMB onset was significantly slower at the flexor hallucis brevis with a mean onset time of 4.4 ±â€Š1.5 versus 3.7 ±â€Š1.2 min at adductor pollicis (P = 0.0001). Recovery to TOF = 1 was significantly slower at flexor hallucis brevis. No difference was found for TOF = 4. The full recovery of NMB (T4/T1 > 0.90) was significantly faster at flexor hallucis brevis with a mean time to recovery of 59.5 ±â€Š9.9 versus 64.5 ±â€Š10.7 min at adductor pollicis (P < 0.0001), a difference of 4.9 min between both sites. This difference was not present after pharmacological reversal with a mean time to recovery of 53.0 ±â€Š12.2 min at flexor hallucis brevis versus 54.0 ±â€Š12.4 min at adductor pollicis (P = 0.28). However, NMB onset and recovery did not follow the same pattern in individual patients. CONCLUSION: Flexor hallucis brevis could be an interesting alternative site for NMB monitoring when the adductor pollicis is not accessible. However, in the absence of pharmacological reversal, monitoring at the hallucis brevis muscle should be used with caution for the detection of residual paralysis. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02825121).

Investigation of intraoperative dosing patterns of neuromuscular blocking agents.

There is a growing body of literature documenting the use of deep neuromuscular block (NMB) during surgery. Traditional definitions of depth of NMB rely on train-of-four assessment, which can be less reliable in retrospective studies. The goal of our study was to investigate the real-world practice pattern of dosing of neuromuscular blocking agents (NMBA), utilizing the amount of NMBA used during the course of a case, adjusted for patient weight and case duration, as a surrogate measure of depth of NMB. We also aimed to identify case factors associated with larger NMBA doses. In this retrospective observational analysis of our anesthesia information management system, we analyzed all general endotracheal anesthesia cases from 2012 to 2015 in which an intermediate-acting NMBA was used. Cases using a long-acting NMBA or only succinylcholine were excluded. The expected duration of the case was calculated based on the cumulative dose of NMB used, normalized to the patient's ideal body weight and the ED95 of the drug. If the expected duration of the case was greater than the actual case duration documented in the case record, it was classified as higher dosing (HD). If the expected duration was equal to or less than the actual duration, it was considered predicted dosing (PD). Categorical comparisons between HD and PD groups were made for various patient, procedural, and provider factors. 72,684 cases were included in the final analysis, of which 46,358, or 64% of cases, used HD. Cases with patients who were morbidly obese, younger than 65 years, and who were lower ASA Physical Status classification (I or II) used more HD as opposed to PD. Cases that were non-open, used total intravenous anesthesia, emergent cases, or used non-rapid sequence anesthesia induction had higher rates of HD than their matched counterparts. All results were statistically significant. HD was more common in cases that documented train-of-four and used the reversal agent neostigmine. Approximately two-thirds of general endotracheal anesthesia cases using an intermediate-acting NMBA used HD. Cases with higher rates of HD may be those that are traditionally technically complex or emergent, would benefit from greater paralysis, or do not use adjunctive medications for muscle relaxation. Age greater than 65 years was shown to have lower rates of HD, likely due to provider awareness of age-related changes in pharmacokinetics and pharmacodynamics. Intraoperative monitoring and NMB antagonism with neostigmine were used more frequently with HD.

Paralytics, Sedation, and Steroids in Acute Respiratory Distress Syndrome.

In this article, we discuss the literature behind the use of paralytics, sedation, and steroids in acute respiratory distress syndrome. We explore the controversies and discuss the recommendations for the use of these agents.

Neuromuscular block monitoring after the administration of 1 mg/kg intravenous cis-atracurium in the anaesthetized pig.

Neuromuscular blocking agents should be included as part of a balanced anaesthetic protocol to improve anaesthetic management, although doses are not always established for each species. Cis-atracurium is a benzylisoquinolinium neuromuscular blocking agent with an intermediate duration of action devoid of significant adverse effects previously used in pigs with a wide dosage range. Cis-atracurium was administered at 1 mg/kg bolus to sixteen pigs to establish its time profile and effects. The pigs were premedicated intramuscularly with 4 mg/kg azaperone, 8 mg/kg ketamine and 0.2 mg/kg morphine IM and maintained with isoflurane in oxygen. After cis-atracurium administration, neuromuscular monitoring via acceleromyography was started until the recovery of the 90% of the train of four ratio. Complete decrease in the train of four ratio was accomplished in eleven pigs. Onset of action was 70 s, with a recovery of the fourth twitch at 26 min and a recovery of a train of four ratio greater than 90% in 60 min. In conclusion, 1 mg/kg intravenous cis-atracurium in the pig allowed for a rapid onset of action and a complete recovery after 60 min although high variability in the time profile is seen.

Effect of age on cis-atracurium besylate pharmacokinetics following a single 1 mg kg-1 intravenous bolus in young pigs.

OBJECTIVE: To determine the cis-atracurium pharmacokinetic data and laudanosine production of a single 1 mg kg-1 cis-atracurium dose in the pig and to compare the pharmacokinetics between two groups of different ages. STUDY DESIGN: Prospective experimental study. ANIMALS: Sixteen female pigs in two groups. Group A included eight animals aged 2.0-2.5 months and weighed 26.6 ± 3.6 kg. Group B included eight animals aged 4.0-5.0 months and weighed 57.4 ± 8.3 kg. METHODS: The pigs were anaesthetized and monitored throughout the procedure. Arterial blood samples collected at 0, 0.5, 1, 2, 5, 10, 20, 30, 45, 60, 90, 120 and 180 minutes after cis-atracurium injection were cooled and centrifuged. Plasma was acidified and stored at -20 °C for subsequent cis-atracurium and laudanosine analyses. RESULTS: Anaesthetic parameters were within normal ranges throughout the procedure. Plasma cis-atracurium and laudanosine concentrations were measured for the 16 pigs. Elimination rate constant, elimination half-life, area under the curve, mean residence time, distribution volume and total clearance were calculated for each pig. Statistical differences (p < 0.05) in the elimination rate constant, elimination half-life, mean residence time and distribution volume values were observed between the two groups. Elimination half-life, mean residence time and distribution volume values were higher and elimination rate constant lower in younger pigs than in older pigs. No plasma laudanosine concentrations were detected in any pig. CONCLUSION AND CLINICAL RELEVANCE: Longer duration of plasma cis-atracurium concentrations were observed in younger pigs. Distribution volume was also higher in younger pigs. Conversely, total clearance and area under the curve were similar between the two age groups. No laudanosine production was detected, suggesting a different cis-atracurium metabolism in the pig compared with other species.

[Effect of intraoperative warming on muscle relaxation recovery of cisatracurium in patients undergoing gastrointestinal surgery].

Objective: To investigate the effect of intraoperative warming on the postoperative relaxation recovery of cisatracurium in patients undergoing gastrointestinal surgery. Methods: Sixty ASA Ⅰ-Ⅱ patients, aged 20 to 60, undergoing elective gastrointestinal surgery in Cancer Hospital Chinese Academy of Medical Sciences from October, 2016 to March, 2019 were selected and they were randomly divided into two groups (n=30), N group and H group by random number table. N group was non-heat preserving group, and H group was heat preserving group. Tracheal intubation was induced by general anesthesia with cisatracurium 0.15 mg/kg, and the nasopharyngeal temperature were continuously monitored and recorded. Cisatracurium were infused 1-3 µg·kg(-1)·min(-1) by venous pump during operation with T1 at 1%-10% and stopped infusion 30 minutes before the end of surgery. The time when T1 recovered from 25% to 75%(muscle relaxation recovery index), and the time of T1 recovered to 25% to TOF ratios (TOFR, the ratio of the fourth muscle twitch height to T1 in TOF) recovery to 90% (full recovery time), cumulative drug use and surgery time were recorded. Results: There was no significant difference between the two groups in the cumulative drug dosage and operation time (P>0.05).The body temperature N group (35.7±0.2) ℃ was significantly lower than the H group (36.2±0.1) ℃ (t=13.940, P<0.01). The recovery index of N group (16.5±1.8) min was significantlyhigher than H group (10.5±2.1) min (t=12.094, P<0.01) and complete recovery time in N group (26.9±4.1) min was obviously longer than those in H group (15.0±2.9) (t=13.082, P<0.01). Conclusions: Patients with open gastrointestinal surgery are prone to hypothermia during surgery and heat protection is helpful to muscle relaxation recovery of cisatracurium.

Practice Change From Intermittent Medication Boluses to Bolusing From a Continuous Infusion in Pediatric Critical Care: A Quality Improvement Project.

OBJECTIVES: To determine whether implementing a guideline to bolus medications from continuous infusions in PICUs affects nursing satisfaction, patient safety, central line entries, medication utilization, or cost. DESIGN: This is a pre- and postimplementation quality improvement study. SETTING: An 11-bed ICU and 14-bed cardiac ICU in a university-affiliated children's hospital. PATIENTS: Patients less than 18 years old admitted to the PICU or pediatric cardiac ICU receiving a continuous infusion of dexmedetomidine, midazolam, fentanyl, morphine, vecuronium, or cisatracurium from May 2015 to May 2016, excluding November 2015 (washout period), were eligible for inclusion. INTERVENTIONS: Change in practice from administering bolus doses from an automated dispensing machine to administering bolus medications from continuous infusion in PICUs. MEASUREMENTS AND MAIN RESULTS: Timing studies were conducted pre- and post implementation in 29 and 26 occurrences, respectively. The median time from the decision to give a bolus until it began infusing decreased by 169 seconds (p < 0.01). Nursing satisfaction increased from 19.3% pre- to 100% post implementation. Safety was assessed via barcode scanning compliance, which decreased by 1.4% for patients and 1% for medications, and smart pump limit overrides. The percentage of infusion pump bolus overrides increased as expected, with the majority (99%) of these exceeding soft maximum limits by less than two-fold. Central line entries were unaffected post implementation. To assess medication utilization, a total of 50 patients in each intervention group were selected for retrospective chart review. Daily fentanyl boluses increased from one to three (p = 0.021). However, midazolam infusion dose and fentanyl infusion duration decreased (p = 0.026 and p = 0.005, respectively). Medication utilization was otherwise unchanged post implementation (p > 0.05). Annualized cost avoidance was $124,160. CONCLUSIONS: Implementation of bolus medications from continuous infusion in PICUs significantly decreased time to begin a bolus dose and increased nursing satisfaction. The practice change also improved medication utilization without negatively impacting patient safety.

Comparison of deep or moderate neuromuscular blockade for thoracoscopic lobectomy: a randomized controlled trial.

BACKGROUND: Laparoscopic surgery typically requires deep neuromuscular blockade (NMB), but whether deep or moderate NMB is superior for thoracoscopic surgery remains controversial. METHODS: Patients scheduled for thoracoscopic lobectomy under intravenous anesthesia were randomly assigned to receive moderate [train of four (TOF) 1-2] or deep NMB [TOF 0, post-tetanic count (PTC) 1-5]. Depth of anesthesia was controlled at a Narcotrend rating of 30 ± 5 in both groups. The primary outcome was the need to use an additional muscle relaxant (cisatracurium) during surgery. Secondary outcomes included surgeon satisfaction, recovery time of each stage after drug withdrawal [time from withdrawal until TOF recovery to 20% (antagonists administration), 25, 75, 90, 100%], blood gas data, VAS pain grade after extubation, the time it takes for patients to begin walking after surgery, postoperative complications and hospitalization time. Results were analyzed on an intention-to-treat basis. RESULTS: Thirty patients were enrolled per arm, and all but one patient in each arm was included in the final analysis. Among patients undergoing moderate NMB, surgeons applied additional cisatracurium in 8 patients because of body movement and 5 because of coughing (13/29, 44.8%). Additional cisatracurium was not applied to any of the patients undergoing deep NMB (p < 0.001). Surgeons reported significantly higher satisfaction for patients undergoing deep NMB (p < 0.001, Wilcoxon rank sum test). The mean difference between the two groups in the time from withdrawal until TOF recovery of 25% or 90% was 10 min (p < 0.001). The two groups were similar in other recovery data, blood gas analysis, VAS pain grade, days for beginning to walk and mean hospitalization time. CONCLUSIONS: Deep NMB can reduce the use of additional muscle relaxant and increase surgeon satisfaction during thoracoscopic lobectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR-15007117 , 22 September 2015.

Altered pharmacodynamics and pharmacokinetics of cisatracurium in patients with severe mitral valve regurgitation during anaesthetic induction period.

AIM: The aim of the current study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cisatracurium in patients with severe mitral valve regurgitation (MR) during the anaesthetic induction period. METHODS: Thirty patients in the clinical trial were divided into two groups: the MR group (n = 15) and the control group (n = 15). Arterial blood samples were obtained before (time 0) and at 1, 2, 4, 6, 8, 10, 15 and 20 min after intravenous injection of 0.15 mg kg-1 cisatracurium. The degree of neuromuscular block was measured by train of four (TOF) testing. The concentration of cisatracurium in the plasma was determined by high-performance liquid chromatography. A conventional two-compartment model and integrated PK/PD model were applied to PK and PD data analysis, respectively. RESULTS: The results of PK model fitting demonstrated that severe MR reduced the distribution rate of cisatracurium from the central to peripheral compartment, resulting in a higher concentration of the drug in the plasma. The time to the maximal neuromuscular blocking effect of cisatracurium was delayed in the MR group (2.08 min in the control group vs. 4.12 min in the MR group). The PK/PD model indicated that the distribution rate of cisatracurium from the blood to the effect compartment was decreased in the MR group. CONCLUSIONS: The present study suggested that the PK and PD of cisatracurium were significantly altered in patients with severe MR. The study has the potential to improve the safety of anaesthetic induction in patients with severe MR through accurate prediction of the PD responses of cisatracurium using the established PK/PD model.

Case report: anaesthetic management of radical gastrectomy for gastric cancer associated with anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare neurological disorder that is caused by the production of antibodies against NMDARs. As many anaesthetic drugs interact with NMDARs and may worsen the disease and because the disease poses risks, such as cardiovascular events, hyperthermia and respiratory insufficiency, while under anaesthesia, administering anaesthesia to patients with this disorder is clinically challenging. CASE PRESENTATION: A 55-year-old man with gastric cancer associated with anti-NMDAR encephalitis who was diagnosed 8 months prior was admitted to Peking University Cancer Hospital for tumour resection. Before surgery, the patient's symptoms had been successfully controlled via aggressive immunotherapy. Radical gastrectomy was performed under general anaesthesia induced with remifentanil, propofol, and cisatracurium and maintained with sevoflurane and remifentanil. The patient had a favourable recovery without any adverse symptoms or post-operative complications. CONCLUSIONS: Adequate preparation for surgery is essential for the anaesthetic management of patients with anti-NMDAR encephalitis. These rare patients may benefit from general anaesthesia induced using remifentanil, propofol and cisatracurium and maintained using sevoflurane and remifentanil. Additionally, the use of NMDA antagonists, such as ketamine, nitrous oxide and tramadol, should be avoided.

Sugammadex at both high and low doses does not affect the depth of anesthesia or hemodynamics: a randomized double blind trial.

Previous studies have shown that sugammadex decreases the anesthetic depth when administered to reverse the neuromuscular blockade produced by rocuronium/vecuronium. The aim of the present study was to investigate the effect of sugammadex alone on anesthetic depth and hemodynamics. Sixty patients scheduled for abdominal surgery participated in the study. Anesthesia was induced with thiopental/fentanyl and maintained with N2O/oxygen and sevoflurane concentrations adjusted to maintain Entropy and Bispectral Index (BIS) values between 40 and 50. Cis-atracurium 0.2 mg/kg was administered for neuromuscular blockade which was monitored with a TOF-Watch® SX acceleromyograph. State entropy (SE), response entropy (RE), Bispectral Index (BIS), systolic (SAP) and diastolic blood pressure (DAP), heart rate (HR), SpO2, end-tidal CO2 and sevoflurane concentrations were recorded every 3 min intraoperatively. Sugammadex 2 mg/kg (Group-2), 4 mg/kg (Group-4) or 16 mg/kg (Group-16) was given intravenously when a count of two responses of the train-of-four (TOF) or a post-tetanic count (PTC) 1-3 appeared or when no response at all (PTC = 0) was observed, respectively. The overall SE values, thus the primary outcome of the study, were 44 ± 11, 43 ± 10 and 43 ± 11 for Group-2, Group-4 and Group-16, respectively (p = 0.812). Also, the secondary endpoints, namely RE, BIS, SAP and DAP, HR and SpO2 did not differ between the three groups. Comparisons between Group-2 versus Group-4, Group-2 versus Group-16 and Group-4 versus Group-16 showed no differences (p > 0.05) for all the studied variables. Sugammadex alone at low, medium or high clinical doses has no effect on anesthetic depth as assessed by Entropy and BIS or on hemodynamics.

Use of cis-atracurium to maintain moderate neuromuscular blockade in experimental pigs.

OBJECTIVE: To determine the dose of cis-atracurium needed to produce a moderate neuromuscular blockade (NMB) in pigs. STUDY DESIGN: Prospective experimental study. ANIMALS: Seven pigs [five females and two males; median (range) body weight: 47 (36-64) kg]. METHODS: Pigs were premedicated with intramuscular midazolam (0.3 mg kg-1) and ketamine (7 mg kg-1). Anaesthesia was induced with intravenous (IV) propofol 3 (1-4) mg kg-1 and maintained with isoflurane in oxygen. Based on a preliminary study, the subjects were administered 0.3 mg kg-1 cis-atracurium followed by 0.48 mg kg-1 hour-1 constant rate infusion (CRI) IV. A moderate NMB was defined as a train-of-four (TOF) count of ≤2 by acceleromyography. When the TOF count was >2, 0.1 mg kg-1 cis-atracurium was administered and the CRI was increased. The cis-atracurium CRI was decreased when the TOF count was under 2 for more than 15 minutes. The total dose of cis-atracurium required to maintain a moderate NMB was calculated as the total amount of cis-atracurium used (both CRI and supplementary boluses) divided by the administration time. RESULTS: The cis-atracurium CRI lasted for 87 (76-151) minutes. To induce and maintain a moderate neuromuscular blockade, the initial dose of cis-atracurium was 0.3 (0.3- 0.5) mg kg-1 and the CRI was 0.71 (0.37-0.98) mg kg-1 hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: The doses described in our study may help researchers obtain a moderate NMB using cis-atracurium in pigs.

Preoperative and intraoperative continuous use of dexmedetomidine on hyperalgesia after patients' remifentanil anesthesia.

OBJECTIVE: Analyze clinical use of dexmedetomidine to relieve prognosis of remifentanil anesthesia recovery and analyze intervention effect. MATERIALS AND METHODS: Choose 3600 cases of cerebral functional area operation patients treated in different hospitals during June 2011 and December 2015 for general analysis, group the patients by considering relevant parting of anesthesia recovery by American Society of Anesthesiologists, and divide the patients into dexmedetomidine group and control group according to different use of drugs. The two groups of patients are anesthetized, patients' anesthesia wake-up time and wake-up success rate are recorded, and effect of two types of anesthesia wake-up way are compared. RESULTS: There exists no significant statistical difference in wake-up success rate of the two groups of patients, wake-up time has small difference, but anesthesia recovery quality of dexmedetomidine group is higher, which is conducive to physical rehabilitation of patients and minimize the effects of anesthetics on patients. CONCLUSION: In clinical surgery, after use of remifentanil anesthesia on patients, use of dexmedetomidine for anesthesia recovery can minimize adverse effects of drugs on patients and thus is worthy to be effectively promoted in clinics.