Atracurium Research Articles

Lethal Self-Administration of Atracurium: A Rarely Reported Case with Review of Literature.

Atracurium besylate is a nondepolarizing skeletal muscle relaxant first introduced in 1980. It is used during endotracheal intubation. It causes muscle relaxation during surgery or mechanical ventilation. When people consider suicide, they employ drugs found in their surroundings but not usually injectable muscle relaxants, which are not widely available. Studies on their use in suicide are rarely reported worldwide. This was a case of a 34-year-old male nursing staff, working in the general surgery department's operation theater complex, who was found unconscious in bed in his room in the morning with an empty syringe by the bedside. He was declared dead when brought to the emergency department. Forensic autopsy was conducted, and during the external examination, a needle puncture wound was found over the left cubital fossa. No other external other injuries were observed throughout the body. The toxicological analysis report indicated the presence of laudanosine in the vitreous humor, blood, urine, and skin from the puncture site and underneath vein. Also, the toxicological analysis of the empty syringe found at the crime scene revealed the presence of atracurium, confirming that the victim had administered a lethal dose of atracurium.

Pharmacokinetics study of atracurium, dexmedetomidine, midazolam and 1-hydroxymidazolam in patients undergoing acute aortic dissection surgery.

An UPLC-MS/MS method was developed and validated for simultaneous determination of atracurium (ATC), dexmedetomidine (DEX), midazolam (MDZ) and 1-hydroxymidazolam (1-OH-MDZ) and the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were investigated. The analytes were extracted by acetonitrile precipitation and separated on an Acquity UPLC BEH C18 column (2.1mm × 50mm, 1.7μm) with a mobile phase of acetonitrile-0.1% formic acid and a gradient mode. In the positive ion mode, the following mass transition pairs were monitored by multiple reaction monitoring (MRM) for the four analytes and IS: m/z 385.1→206.2 for ATC, m/z 201.2→95.1 for DEX, m/z 326.1→291.1 for MDZ, m/z 341.9→324.0 for 1-OH-MDZ, and 284.9→153.9 for diazepam (IS). Seven male patients undergoing aortic dissection surgery received general anesthesia and intravenous administration of ATC, DEX, and MDZ during the surgery. Venous blood was collected at different time points at the end of surgery and after surgery. The concentrations of ATC, DEX, MDZ, and 1-OH-MDZ were detected, and the pharmacokinetic parameters were calculated. The method showed good linearity for each analyte. The inter-batch precision ranged from 1.37% to 9.87% and the intra-batch precision ranged from 2.41% to 10.72%; the accuracy ranged from 94.33% to 104.51%. Finally, the matrix effect, extraction recovery and stability data met the FDA recommended acceptance criteria for validation of bioanalytical methods. The t1/2 of ATC, DEX, MDZ and 1-OH-MDZ was (6.74 ± 2.27) h, (9.55 ± 4.93) h, (10.17 ± 5.35) h, and (6.90 ± 2.38) h, the Cmax, of ATC, DEX, MDZ and 1-OH-MDZ was (1054.20 ± 202.37) ng/mL, (1.93 ± 1.07) ng/mL, (1256.57 ± 389.09) ng/mL, and (1034.39 ± 292.92) ng/mL in patients undergoing aortic dissection surgery, respectively. The developed UPLC-MS/MS method for simultaneous determination of ATC, DEX, MDZ and 1-OH-MDZ in patient plasma was accurate, reproducible, specific. After continuous administration of ATC, DEX, and MDZ to patients undergoing surgery for acute aortic dissection, the pharmacokinetics of ATC, DEX, MDZ and 1-OH-MDZ in patients undergoing aortic dissection surgery were studied.

Efficacy of Cis-Atracurium vs Atracurium in Patients undergoing Abdominal Procedures: A Randomised Clinical Study

Introduction: Cis-atracurium has a neuromuscular blocking capacity approximately three times that of atracurium besylate. The Effective Dose (ED) 95 of cis-atracurium is 0.04 mg/kg, while that of atracurium is 0.2 mg/kg. Cis-atracurium is preferred over atracurium due to the lack of histamine release, providing better cardiovascular stability. This study compares these two drugs in terms of haemodynamic parameters, neuromuscular blocking properties, intubating conditions, and safety profiles. Aim: To assess the efficacy of atracurium and cis-atracurium from various perspectives, including neuromuscular blockade, haemodynamic stability, and safety profiles. Materials and Methods: A double-blinded, randomised clinical study was conducted from January 2019 to October 2019 in Rajkot, Gujarat, India. Sixty patients undergoing abdominal surgeries under general anaesthesia were allocated to two groups. Group A received a loading dose of atracurium 0.5 mg/kg followed by a maintenance dose of 0.1 mg/kg, while Group B received a loading dose of cis-atracurium 0.2 mg/ kg followed by a maintenance dose of 0.03 mg/kg. During the surgical procedure, parameters studied included neuromuscular blockade, hemodynamic changes, intubating conditions, and safety profiles in terms of complications. Student’s t-test was used to analyse normally distributed continuous variables, and the chi-square test was used for qualitative variables. Results: The demographic profiles were comparable in both groups in terms of age (p-value=0.800), sex (p-value=0.393), weight (p-value=0.101), and American Society of Anaesthesiologists (ASA) grading (p-value=0.509). A significant increase in heart rate (99.46±8.06 (/minute) vs. 91.66±9.11 (/ minute)) and mean arterial blood pressure (104.44±10.16 (mm of Hg) vs. 93.4±12.77 (mm of Hg)) was noted post-intubation in Group A compared to Group B. Patients in Group A (3.5±0.62 minutes) had a faster onset of neuromuscular blockade compared to Group B (4.6±0.49 (minutes)), while the duration of action of the first loading dose and the 25% recovery time from the last supplemental dose was longer in Group B (52.86±5.18 minutes and 41.66±3.60 minutes) than in Group A (31.2±4.82 minutes and 20.86±4.37 minutes). Fewer patients experienced complications (hypotension, erythema of the skin) in Group A compared to Group B. Conclusion: Cis-atracurium releases less histamine compared to atracurium and has a longer duration of action. Cis-atracurium can be a better alternative to atracurium as it offers better haemodynamic, neuromuscular, and safety profiles with similar intubating conditions.

Comparative study for chiral separation of Atracurium besylate isomers: Eco-friendly HPLC using Lux Cellulose-3 chiral column, and TLC-Densitomerty approaches

Liquid chromatography offers an efficient strategy for chiral drug separation using specific stationary phases or mobile solvent additives. Two approaches are performed for Atracurium besylate (ATR) chiral separation involving three isomers (cis-cis, cis-trans, trans-trans isomers). The initial method depended on reversed phase High Performance Liquid Chromatography (HPLC) employing Lux Cellulose-3 as a chiral stationary phase (CSP) and acetonitrile: water (90:10, v/v) as a mobile phase at a flow rate of 0.7 mL min−1 with UV detection at 280.0 nm. The obtained peaks of ATR isomers were fairly separated with excellent resolution values. The isomer ratio was found to be 57.89% cis-cis, 36.57% cis-trans, 5.54% trans-trans (expected ratio 55.0–60.0%: 34.5–38.5%: 5.00–6.50%, respectively). Linearity, precision and accuracy were proven to be acceptable over the concentration range of (10.0–100.0 μg mL−1) ATR. Utilizing CSP provided the best separation within short analysis time (3 min) and decreased the waste generation when compared to other reported methods. The alternative method was based on thin layer chromatography (TLC) chiral separation using β-cyclodextrin sulphated sodium salt (S-β-CD) as a chiral mobile phase additive. The separation was achieved on silica gel plates using acetonitrile: methanol: water: ethyl acetate: 1% acetic acid (5:2:1.5:1:0.5, by volume) as a developing system. The linear regression analysis data were assessed for the regression line in the range (1.0–15.0 μg band−1) of racemic ATR. The two proposed methods have been validated for ATR chiral separation in commercial vials, following the relevant FDA and ICH guidelines. The obtained results were statistically compared with those of the official HPLC method showing that there was no significant difference.

To Compare Isobaric Thoracic Spinal Anesthesia Versus General Anesthesia in Laparascopy Cholecystectomy

Background: The laparoscopic cholecystectomy procedure is typically carried out under general anesthesia, but regional techniques, such as low thoracic isobaric spinal anesthesia, have been used to manage patients with significant medical problem like coexisting systemic disease, who are deemed to be high risk in general anesthesia. Segmental spinal anesthesia has great outcomes in terms of post-operative discomfort, the need for analgesics, relatively fewer complications, and shorter hospital stays. Thus the aim of this study to avoid and minimize the risk of general anesthesia who does not have any significant comorbidity. So it might be a substitute for a standard laparoscopic cholecystectomy. Material and Methods: Total 60 adult patient with ASA1 & I I, 18-60 years, with normal coagulation profile, is divided into 2 groups. Group IS (Isobaric) - given 2.5 ml of isobaric preservative free bupivacaine 0.5% (levobupivacaine) + 0.5 mg of Fentanyl at T9-T10/T10-T11 into sub arachnoid space. Group GA – given general anesthesia using propofol, fentanyl citrate and atracurium besylate. After intubation, ventilation was controlled and balanced anesthesia was continued with isoflurane. After completion, neuromuscular block was anatagonized neostigmine methylsulfate and glycopyrrolate at the end of surgery. Results: Isobaric spinal anesthesia showed good control in intraoperative as well as postoperative pain control as compared to general anesthesia. In few patients, there were minor degrees of nausea, vomiting, abdominal pain, shoulder pain, patient anxiety or itchng which were treated with standard medication like fentanyl and midazolam. All patients can resume oral intake on the day of surgery. Conclusions: In conclusion, this study provide evidence that segmental spinal anesthesia can be used in place of general anesthesia in healthy individuals also.

Analysis of the effect of dexmedetomidine combination with regional anesthesia on the cognitive state in the post-anesthesia period in ophthalmic surgery

Given a reduced cognitive reserve in patients in ophthalmic surgery, an anesthesiologist should pay special attention when choosing a method of anesthesia to prevent the development of postoperative cognitive dysfunction. The concept of multimodal anesthesia makes it possible to reduce the total number of narcotic analgesics and ataractics used intraoperatively while maintaining an adequate level of anesthesia and sedation, both intraoperatively and in the postoperative period. In ophthalmic surgery, regional anesthesia (pterygopalatine fossa blockade) is used before surgery in combination with infusion of dexmedetomidine. Materials and methods. The study was conducted at the premises of Dnipropetrovsk Regional Clinical Ophthalmologic Hospital, 61 patients were examined after penetrating keratoplasty. The age of the subjects ranged from 18 to 60 years (mean age of 52.1 ± 2.0 years). Patients were randomized into two groups. Group d (n = 30) are patients who received anesthesia according to the following scheme: premedication for 40 min — infusion of dexmedetomidine, ondansetron 4 mg, dexamethasone 4 mg, ketorolac 30 mg intravenously; induction — propofol 2–2.5 mg/kg fractionally until the onset of the clinical signs of anesthesia, fentanyl 0.005% 0.1 mg; relaxation on the background of atracurium besylate 0.3–0.6 mg/kg, tracheal intubation; maintenance of anesthesia: oxygen — sevoflurane mixture with FiO2 50–55 %, end-expired sevoflurane 1.4–1.8 vol.% (1–1.5 minimum alveolar concentration), use of low-flow technique. In the second group (db, n = 31), anesthesia was performed as in group d with the addition of pterygopalatine fossa blockade. Group d included 18 (60 %) men and 12 (40 %) women, mean age of 49.5 ± 2.5 years; db group — 16 (51.61 %) men and 15 (48.39 %) women (p = 0.583 according to the chi-square), mean age of 55.5 ± 3.2 years (p = 0.142 according to the t-test). Results. A comparative analysis of changes in cognitive status between db and d groups has shown no significant changes (p < 0.05) at different stages of neuropsychological testing. When considering the results of testing to assess short-term verbal memory in db and d groups, there was a 25 % decrease in the first 6 hours after surgery. After all, in d group, the indicators remained low compared to baseline until the 7th day of the postoperative period, while in the db group the recovery of short-term memory occurred one day after surgery. In both groups, the result of the Luria test on day 21 exceeded the baseline by 12.5 % in both groups. Examination using visual analogue scale has demonstrated that patients in db group felt better than those in d group. Conclusions. Thus, we see that the combination of dexmedetomidine with regional anesthesia in addition to less impact on the cognitive state improves the subjective well-being in the postoperative period in patients in ophthalmic surgery. Due to this, another link of influence on the etiological factors of postoperative cognitive dysfunction formation seems to appear.

Ventilation through laryngeal mask in patient with severe laryngeal stenosis

Introduction: Patients with an advanced airway obstruction and inspiratory stridor at rest comprise some of the most feared and complicated cases for the anesthesiologist. Case description: A 45-year-old female patient (weight 54 kg, height 166 cm), ASA III, was admitted to our hospital for tracheostomy and microlaryngeal surgery because of stenosis of the larynx. A general anesthesia was scheduled for this patient. Fentanyl 0.3 mg, propofol 200 mg and succinylcholine 100 mg were administered for anesthesia induction. After intubation 2.5% sevoflurane was used for anesthesia maintenance. Additional 0.15 mg of fentanyl was administered for pain relief. Muscle relaxation was provided with 40 mg of atracurium besilate. The operation finished successfully within 80 min. Ventilation for tracheostomy was successfully performed through flexible laryngeal mask airway (FLMA) № 3. Discussion: Patients presenting for microlaryngeal surgery frequently have a difficult airway. The chosen approach to this airway depends on the pathology and the patient’s symptoms. Acceptance of the LMA as a safe practical alternative to tracheal intubation for laryngeal stenosis requires that placement be relatively facile, that position of the mask be stable throughout surgery, and that the airway be protected from the risk of aspiration. In our study during maintenance of anesthesia, there was no evidence of instability of the LMA or increased contamination of the lower respiratory tract. Conclusion: Ventilation through LMA can be safely used during tracheostomy in patients with severe laryngeal stenosis.

Novel approach for chromatographic separation of atracurium and thiopental using factorial model

For the first time, a new optimization proposal was investigated for the simultaneous measurement and separation of the co-administered drugs Atracurium (ATR) and Thiopental (THI) by HPLC/ UV method. The separation was performed by an eluent system consisting of 80% methanol: 20% 0.1 M phosphate buffer (pH 6.5) (v/v). UV detection wavelength was set at 240 nm. Using Promosil C18 column, the two drugs were separated within less than 6 min. The method showed linear response through the ranges of concentration of 2.0–30.0 μg/mL and 0.10–12.0 μg/mL for ATR and THI, respectively. The excellent sensitivity was clearly established by reaching limits of detection of 0.24, 0.02 μg/mL, and limits of quantification of 0.73, 0.06 μg/mL for ATR and THI, respectively. This sensitivity was exploited in estimating of ATR and THI in spiked plasma samples with acceptable recoveries ranged from 96.05 to 104.64%.

Comparison between cisatracurium and atracurium during general anaesthesia for abdominal surgery

Background: Neuromuscular blockers (NMB) are very important adjuvant to general anesthesia, Atracurium (benzyl isoquinoline NMB) and cisatracurium besylate (benzyl isoquinoline NMB) are intermediate acting non-depolarizing muscle relaxants. In a prospective randomized study we had compared both drug at a dose of 2xED95 for Atracurium and 6xED95 for Cisatracurium as regard the onset of action, intubating conditions, clinical duration, hemodynamic changes, and adverse effects.Method: 60 patients, ASA I&II, 20-60 year old underwent elective abdominal surgerical procedure under general anesthesia (GA) were randomly assigned into 2 equal groups. Group A where 0.5mg/kg atracurium was given and Group C, where 0.3mg/kg cisatracurium was given. Neuromuscular monitoring was done by stimulating ulnar nerve and recording the action potential of adductor pollicis using TOF count. Standardized GA was given to all patients as follows, fentanyl 2mcg/kg, propofol 2mg/kg, followed by NMB agent of corresponding group at designated dose, patient will be ventilated till TOF count reaches 0, intubation was tried by the anaesthesiologist who was blind to the given NMB, intubation was done if the intubating condition was acceptable (excellent or good), and it was re-attempted every 30 sec if it was poor or inadequate. Anesthesia was maintained by N2O, O2 and sevoflurane to a total MAC 1, controlled ventilation was adjusted to normocarbia. Mean arterial blood pressure (MAP), heart rate, and intubating conditions were recorded. Interpretation of TOF count for the onset of action, clinical duration, recovery index was done.Results: Clinically acceptable intubating conditions were achieved after 120 sec more frequently after Cisatracurium (85%) than after atracurium (0%) and after 180 sec Cisatracurium (100%) and atracurium (80%). Cisatacurium had a significant shorter onset time than atracurium (120±30 versus 180±30sec), Atracurium had a significant shorter duration of action than cisatracurium (30±5 versus 60±5min). There were no evidences of any significant clinical cardiovascular changes in both groups. Conclusion: Cisatracurium has a rapid onset of action with good intubating conditions, atracurium has an intermediate duration of action, both are potent and safe with excellent cardiovascular stability.

Construction of enzalutamide-resistant cell model of prostate cancer and preliminary screening of potential drug-resistant genes.

Among many factors of causing castration-resistant prostate cancer (CRPC) progression, a growing number of evidences have shown androgen receptors play a critical role. Therefore, blocking androgen receptor remains a therapeutic goal of CRPC. However, resistance to androgen receptor inhibitors, for example, enzalutamide, limits therapeutic efficacy for many patients. In this study, to develop an enzalutamide-resistant cell model for molecular mechanism investigation of enzalutamide-resistance, we continuously treated C4-2B cells with multiplied concentrations of enzalutamide. The IC50 of resistant cells was identified as 14.7705 µM, and the resistance index was calculated as 12.4. In addition, we verified the resistance of resistant cells through experiments in vivo and found the genes in androgen receptor signaling pathway (androgen receptor, Jagged1, Notch1) and those in androgen receptor alternative signaling pathways behaved the opposite. For some of the former, their mRNA and protein expression reduced markedly while for the latter, for example, CXCR7, AKT, STAT3, FOXP3, they rose dramatically in the expression level of protein and mRNA. More importantly, the tumor volume, tumor wet weight, PSA and VEGF secretion level, positive staining rate of Ki67 nuclei in resistant strain heterogeneous tumor treated with enzalutamide were significantly higher than those of maternal cell heterogeneous tumor treated with enzalutamide, whereas no obvious difference was detected between resistant strain heterogeneous tumor treated with enzalutamide and those of the resistant strain treated with reference drug. Finally, we identified 654 differentially expression genes and 2 compounds (atracurium besilate, methotrexates) associated with the amelioration of enzalutamide-resistance. Overall, we successfully established an enzalutamide-resistance cell model and screened out some resistance genes and candidate small molecule drugs.

Analysis of the experience of anesthetic management during endovascular mechanical thrombectomy in ischemic cerebral stroke

Objective ‒ to analyze our own experience of anesthetic management during mechanical thrombectomy (MTE) in patients with acute ischemic stroke (AIS) caused by large cerebral vessels occlusion. Materials and methods. Treatment of patients with AIS caused by large cerebral vessels occlusion was carried out in accordance with the recommendations of the European Stroke Organization (ESO). MTE was performed in 63 patients (23 women and 40 men aged 36 to 82 years, mean age ‒ 62.00 ± 16.31 years). The severity of neurological symptoms in the acute period of ischemic stroke was assessed over time using the National Institutes of Health Stroke Scale (NIHSS). The degree of disability due to stroke was assessed using a modified Rankine scale (mSR) before discharge and after 90 days. The results by mRS after 90 days were the most indicative. Early ischemic changes in the brain on computed tomograms were assessed using the Alberta Stroke Program Early CT score (ASPECTS). To reduce the time «onset-to groin time» (puncture of the femoral artery), all patients were immediately sent to the operating room upon hospitalization after neuroimaging. For MTE in 50 (79 %) cases conscious sedation with local anesthesia (sibazon, fentanyl) was used, in 13 (21%) cases ‒ general anesthesia (propofol, fentanyl, atracurium besylate). Regardless of the anesthesia method, vital signs were monitored and postoperative complications were assessed. The assessment of other important indicators related to the expiration of anesthesia was carried out: the time «onset-the the groin time» the time «from groin – to recanalization», the level of saturation, the stability of mean arterial pressure, the use of vasopressors or labetolol, the number of postoperative complications (pneumonia, dislocation with decompression craniotomy, nausea, myocardial infarction). Results. The algorithm for anesthetic management of the perioperative period included the anesthesia during MTE, postoperative anesthetic monitoring and correction of deviations over the next 72 hours. Mandatory components of anesthetic support of MTE were to maintain blood pressure of at least 140/90 mm Hg. before reperfusion and FiO2 0.45‒0.5%. Anesthetic management also included infusion therapy, prevention of vomiting and regurgitation, and symptomatic therapy. Special attention was paid to the control of hemodynamics in the postoperative period. The results of treatment according to mRS after 90 days showed that more than half of the patients ‒ 32 (50.8%) after MTE were independent of outside help (0‒2 points), 24 (38.1 %) ‒ 3‒5 points, 6 points (mortality) ‒ 7 (11.1 %). After general anesthesia during MTE, 2 (15.4 %) deaths were registered, after MTE with conscious sedation using ‒ 5 (10.0%). There more patients with the vasopressors or labetalol using and the number of postoperative pneumonia were identified in the group with general anesthesia. For other indicators, there was no statistically significant difference in the results depending on the type of anesthesia. There was no statistically significant difference in the results in depending on anesthesia method. Conclusions. The choice of the anesthesia method during MTE for large cerebral vessels should be individual. There was no statistically significant difference in the results in treatment of patients with AIS using MTE (in particular, in mortality), depending on the type of anesthetic management. It is also wasn’t found in the time «onset – to groin time» and the time «groin – to recanalization» with various methods of anesthesia. Indications of vital functions, saturation, mean arterial pressure in patients did not have a significant difference. Differences were revealed in terms of the vasopressors or labetolol using and the number of postoperative pneumonia, depending on the anesthesia type. The anesthesia team should be involved in patient management from the moment of hospitalization, regardless of the method of anesthesia. The results of AIS treatment depend on the initial NIHSS and ASPECTS scores, comorbidity, collateral development, perioperative complications, and the degree of reperfusion after surgery. Special attention should be paid to hemodynamics before and after reperfusion recovery after vessel recanalization, taking into account the degree of reperfusion. The influence of the type of anesthesia on the results of the treatment of AIS with the MTE using remains under the further discussion.

The choice of optimal modern muscle relaxants (rocuronium bromide, atracurium besilate and cisatracurius besilate) in one-day surgery in children

The choice of optimal modern muscle relaxants (rocuronium bromide, atracurium besilate and cisatracurius besilate) in one-day surgery in children

Effects of neuromuscular blocking drugs on viability of human umbilical vein endothelial cells (HUVECs).

ObjectiveThis study aimed to investigate the effects of neuromuscular blocking drugs on the viability of human umbilical vein endothelial cells (HUVECs) and to investigate whether they cause vascular complications due to cell proliferation.MethodsHUVECs were cultivated with 5% CO2 at 37°C in a predefined supplemented medium over 7 days until confluence of cell monolayers. Assays were conducted during the exponential growth phase. Suxamethonium chloride, vecuronium bromide, atracurium besylate, and rocuronium bromide were used at concentrations of 10–5, 10–6, and 10–7 M in proliferation assays in which cells were incubated with these drugs for 24, 48, and 72 hours. All experiments were performed in four replicates.ResultsThe neuromuscular blocking drugs used had comparable effects on the survivability of HUVECs. Overall, no significant difference was observed in the survivability of HUVECs in a dose-dependent manner after exposure to the study drugs. However, some significant differences in the viability of HUVECs were found among the different measurement times.ConclusionsThe findings of the current study support the safety of the studied neuromuscular blocking drugs in clinically relevant concentrations regarding their effects on endothelial cell proliferation.

EFFICACY OF ATRACURIUM VERSUS CISATRACURIUM IN PATIENTS UNDERGOING RETROGRADE CHOLANGIOPANCREATOGRAPHY PROCEDURE UNDER GENERAL ANAESTHESIA – A COMPARATIVE STUDY

Objectives: The objectives of the study were to compare the efficacy of injection atracurium 0.5 mg/kg intravenous (IV) versus injection cisatracurium 0.2 mg/kg IV for intubation in patients undergoing endoscopic retrograde cholangiopancreatography procedure (ERCP).
 Methods: Hundred adult patients of both sexes in the age group of 18–60 years belonging to the American Society of Anesthesiologists I/II category posted for ERCP procedures under general anesthesia were randomly allocated into two groups of 50 each. Group A received injection atracurium besylate 0.5 mg/kg intravenously and Group B received injection cisatracurium besylate 0.2 mg/kg intravenously. Parameters observed were time to the maximum blockade, intubating condition, time required for intubation, duration of action, hemodynamic parameters during intubation, and after 1, 2, 3, 5, and 15 min and any adverse effects.
 Results: Demographic profile was comparable between the groups. Intubating condition as per Cooper et al. score was excellent in 36 patients in cisatracurium group as compared to 19 patients in atracurium group. The overall intubating condition was found to be better in Group B (p=0.00001). Time to the maximum blockade was significantly high with atracurium as compared to cisatracurium. The mean of intubation time was less with cisatracurium (135±11.1) than that of atracurium (144±9.48) in seconds, which was statistically significant. Duration of neuromuscular blockade was found to be prolonged in Group B as compared to Group A (p=0.000). Hemodynamic parameters during intubation and after 1, 2, 3, 5, and 15 min were comparable between the groups. No adverse effect was seen in both groups.
 Conclusion: Cisatracurium 0.2 mg/kg provides excellent intubating conditions with rapid onset of action, longer duration of action, and no significant hemodynamic changes as compared with atracurium 0.5 mg/kg for ERCP procedures without any adverse effects.

PD24-10 NICOTINIC RECEPTORS ON NERVE TERMINALS INDUCE ACETYLCHOLINE RELEASE IN CANINE BLADDER

INTRODUCTION AND OBJECTIVE: Carbachol, a mixed muscarinic and nicotinic agonist similar to acetylcholine, is often used for in-vitro bladder contraction with the implicit assumption that it causes contraction by only activating bladder smooth muscle muscarinic receptors. We sought to determine whether nicotinic receptors may also be involved in canine detrusor muscle contractions in- vitro. METHODS: Mucosa denuded canine bladder muscle strips from sham operated animals were used from a larger study of nerve transfer for bladder reinnervation. Strips were fixed between force transducers and positioners and suspended in Tyrode's solution bubbled with 95% O2/5% CO2 at 37 C. After stretching to a length of optimal force production, maximal responses to 120 mM KCl were determined then various agents were added for 20 minutes before inducing contraction with the nicotinic agonists epibatidine and nicotine. RESULTS: Epibatidine induced contractions that were approximately 40% of the maximal response to 120 mM KCl whereas nicotine only induced contractions that were 20% of KCl. The muscarinic receptor antagonist atropine (10 uM) completely blocked 10 uM epibatidine or 1 mM nicotine induced contractions but desensitization of purinergic receptors with 10 uM α,β methylene ATP only blocked these contractions by 40%. Blocking sodium channels with 1 uM tetrodotoxin (TTX) had no statistically significant inhibitory effect on epibatidine or nicotine induced contractions. The α7 nAChR-selective agonist AR-R17779 had no effect and the α7 selective antagonist MLA had no effect at α7 selective concentrations on epidbatidine induced contractions. The α4β2 selective agonist TC2559 also had no effect whereas the α3β4 selective agonist NS3861 and the non-selective ganglionic receptor agonist DMPP induced small contractions. Also, the α3β4 selective antagonist SR-16584 (1-3 uM) blocked eipibatidine induced contractions by 50% . At relatively high concentrations, the skeletal muscle neuromuscular junction nicotinic receptor antagonists atracurium besylate (5 uM) and tubocurarine (0.1 uM) blocked epibatidine induced contractions. At concentrations reported to be selective for ganglionic nicotinic receptors, the neuronal nicotinic receptor antagonists hexamethonium (100 uM) and mecamylamine (10uM) blocked epibatidine induced contractions. CONCLUSIONS: Because of atropine blockade but only minor blockade by α,β methylene ATP desensitization, the nicotinic agonists induce bladder contractions indirectly by releasing predominately acetylcholine from intramural nerve terminals. Because TTX was ineffective, these nicotinic receptors do not need to induce action potentials and thus are likely located near the neuromuscular junction. Based on the pharmacological data, the α3β4 receptor subtype is likely involved in contraction of the canine bladder. Source of Funding: NINDS R01NS070267

Application of rapid induction of intubation by sedatives combined with cis-atracurium in the emergency department

Objective To study the effect of sedative combined with cis-atracurium in rapid induction intubation in emergency department. Methods From October 15, 2017 to April 15, 2019, 52 critically ill patients who needed tracheal intubation in emergency department of the People's Hospital of Changzhi were selected.And the patients were numbered according to the time sequence of enrollment, and then randomly divided into group A and group B according to the random number table, with 26 cases in each group.Group A was given sedatives combined with cis-atracurium to induce rapid intubation.Group B only received sedatives to induce intubation.The success rate of intubation, successful intubation time were compared between the two groups.Before and after endotracheal intubation, the heart rate, mean arterial blood pressure, pulse oxygen concentration and the change of catecholamine concentration were compared. Results The success rate of intubation in group A was 100.0%, which in group B was 76.9%, the difference between the two groups was statistically significant (χ2=12.15, P 0.05). The serum adrenaline level was higher compared with before intubation, but there was no statistically significant difference (t=-1.03, P>0.05). In group B, the pulse oxygen concentration was significantly increased after intubation compared with before intubation (t=5.74, P 0.05). Conclusion In the airway management of critically ill patients in emergency department, the application of sedatives combined with cis-atracurium to rapidly induce intubation can improve the hypoxia symptoms of patients more rapidly and can keep patients' hemodynamics, catecholamine concentration is relatively stable, it has the characteristics of safety and efficiency. Key words: Emergency service, hospital; Emergencies; Critical illness; Airway management; Intubation, intratracheal; Atracurium; Hypnotics and sedatives; Hemodynamics

A prospective randomized comparative study of the efficacy of atracurium and cisatracurium during general anaesthesia

Introduction: The neuromuscular blocking drugs (NMBDs) has revolutionized the management of balanced General Anaesthesia (GA). Atracurium and Cisatracurium are intermediate-acting muscle relaxants without any much side effects and recovery due to non-organ dependent elimination. Aim: To compare the efficacy of Atracurium and Cisatracurium in general anaesthesia with endotracheal intubation.Methods: In this prospective randomized comparative study 156 patients who fulfilled the eligibility criteria were systematically randomized into two groups of 78 each, Group. A (Atracurium) and Group B (cisatracurium). Patients' duration of surgery, vital parameters, intubation score were recorded. Results: Cisatracurium Besylate subjects had a mean onset time of 165.95 seconds, mean duration of action of 57.41 minutes and mean recovery time of 121.62 minutes. Similarly group Atracurium Besylate subjects had a mean onset time of 196.95 seconds, mean duration of action of 34.58 minutes and mean recovery time of 150.65 minutes. Cisatracurium Besylate subjects had a mean jaw relaxation score of 2.90, mean vocal cord score of 2.77, mean intubation response score of 2.85 and mean intubating score of 8.51. Similarly, group Atracurium Besylate subjects had a mean jaw relaxation score of 2.55, mean vocal cord score of 2.42, mean intubation response score of 2.43 and mean intubation score of 7.38. There were no adverse drug reactions observed in both groupsConclusion: Cisatracurium with lesser side effects and a better hemodynamic profile is safe and more efficacious as compared to atracurium.

Pharmacodynamics of cisatracurium intravenously infused during liver transplantation

Objective To evaluate the pharmacodynamics of cisatracurium intravenously infused during liver transplantation. Methods Twenty American Society of Anesthesiologists physical status Ⅲ or Ⅳ patients of both sexes, aged 18-60 yr, with body mass index of 20-30 kg/m2, scheduled for elective living donor liver transplantation, were enrolled in this study.Total intravenous anesthesia was used.The induction dose of cisatracurium for anesthesia was 0.15 mg/kg.When T1/T0 was restored to 10%, cisatracurium was injected intravenously at an initial rate of 1.5 μg·kg-1·min-1.The infusion rate was adjusted according to the monitoring results of muscle relaxation, and T1/T0 was maintained at 10%.The total amount of cisatracurium infused and infusing time were recorded during dissection phase, anhepatic phase and neohepatic phase, and the consumption of cisatracurium per unit time was calculated.Before skin incision, at 5 and 30 min of anhepatic phase, at 5 and 30 min of neohepatic phase and at the end of operation, the body temperature and stroke volume variation were recorded, blood samples were collected from the radial artery for blood gas analysis and for measurement of blood K+, Mg2+ and Ca2+ concentrations, and blood samples were collected from the internal jugular vein for determination of serum creatinine (Cr), urea nitrogen (BUN) and β2 microspheres protein (β2-MG) concentrations. Results There was no significant difference in the amount of cisatracurium per unit time between dissection phase and anhepatic phase (P>0.05). The amount of cisatracurium per unit time was significantly higher in neohepatic phase than in dissection phase and anhepatic phase (P<0.05). Compared with baseline before skin incision, blood pH value was significantly decreased at 30 min of anhepatic phase and 5 min of neohepatic phase, serum Mg2+ concentrations were decreased at 5 and 30 min of neohepatic phase and at the end of operation, the serum Cr, BUN and β2-MG concentrations were increased, the serum Ca2+ concentration was decreased at 5 min of anhepatic phase, and SVV was increased at 5 and 30 min of anhepatic phase (P< 0.05 or 0.01). Conclusion Muscle relaxation induced by cisatracurium infused intravenously in the anhepatic phase of liver transplantation is weakened. Key words: Atracurium; Liver transplantation; Infusions, intravenous; Dose-response relationship, drug

Lethal self-administration of propofol and atracurium: Two case reports and literature review

Propofol is an intravenous anesthetic agent widely used in the induction and maintenance of general anesthesia. Acute intoxications with propofol are rare and remain primarily related to the acquisition of the product in hospital. If propofol can induce fatal respiratory depression alone, in a number of cases the clinical situation is exacerbated by the presence of other drugs like neuromuscular-blocking agents. Laudanosine, the circulating form of atracurium or cisatracurium, two non-depolarizing neuromuscular-blocking agents, is more frequently observed in toxicology. Such agents are widely used for tracheal intubations. Laudanosine has no pharmacological activity, which is exclusively due to the parent drugs. These agents can be fatal at any concentration, due to respiratory failure. Here, two cases of anesthesiologists’ suicide following self-administration of propofol-atracurium combination are reported. Case 1: a 48-years-old anesthesiologist was found without vital signs at his office. The drugs and paraphernalia used for delivery were discovered at the scene. Case 2: a 61-years-old anesthesiologist was found dead at home with a cannula connected to an infusion set at the bend of the elbow. Next to the body several empty ampoules of Diprivan ® and Atracurium besylate ® were found. For both cases, several biological specimens were collected for toxicological investigation. Comprehensive screenings of drugs and toxic compounds were performed using LC-DAD and GC-MS. Ethanol concentrations were determined using GC-FID. Laudanosine was quantified using LC-DAD. Propofol was quantified using GC-MS and LC-MS/MS. Propofol blood concentrations were 1 and 1.91 mg/L for case 1 and case 2, respectively (therapeutic range: 2–8 mg/L). Laudanosine blood concentrations were 0.13 and 1.18 mg/L for case 1 and case 2, respectively. Paroxetine, N-demethyldiazepam and ethanol were detected in the first case. Hydroxyzine was detected in the second case. In both cases, levels of these substances could not explain the death. Propofol related fatalities are rare, even more when combined with neuromuscular- blocking agents [1] . Propofol and atracurium concentrations documented here, are in agreement with those reported in the literature, these being characterized by a high inter-individual variability [2] . However, the concentrations observed in suicide cases compared to those observed in accidental fatalities (chronic abusers) appear to be much higher. In fact, three manners of death have been described with propofol: suicide, accidental overdose in chronic abusers, and more exceptionally, murder [3] . In the cases described here, circumstances and the use of atracurium suggest suicide. It should be noted that the concentrations of laudanosine and propofol observed here are in the usual anesthetic range. Albeit, it should be pointed out that for anesthetic agents, therapeutic concentrations are established for patients being supported respiratory-wise, while in non-supported or non-intubated patients such concentrations may be fatal. Therefore, the interpretation of the blood concentration in the forensic toxicological analysis must take into account the context and the circumstances of the death.

Effects of atracurium besylate on corneal endothelium of chickens: in vitro study

ABSTRACT: The aim of this study was to investigate the acute effects of atracurium besylate on cellular damage in corneal endothelium of chickens. Twenty healthy chicken eyes were assigned to the following groups: Group 1 (G1), experimental group (n=10); and Group 2 (G2), control (n=10). Excised corneoscleral buttons were immediately placed on glass microscopy slides with endothelial region faced up. Corneal endothelium of eyes in G1 were covered with AB (0.2mL, 10mg/mL) for 3 min and then rinsed with balanced salt solution (BSS), while the corneal endothelium of eyes in G2 were covered with BBS for 3 min. Corneas from both groups were stained with alizarin red/trypan blue and visualized by light microscopy. Ten random photographs were taken from each cornea. The area of cellular damage was measured by software in all samples and cell loss of each group was averaged and compared. Endothelial area of denudation and Descemet’s membrane exposure were higher in G1 than G2. In conclusion, atracurium besylate induced an acute damage on corneal endothelium of chickens.