scholarly journals Effects of hydrocortisone-presensitized sugammadex on recovery from neuromuscular blockade induced by rocuronium: a rodent in vivo study

Author(s):  
Hey-Ran Choi ◽  
Hong-Seuk Yang ◽  
Jae-Moon Choi ◽  
Chungon Park ◽  
Junyong In ◽  
...  

Background: Sugammadex is a specific antagonist of aminosteroidal neuromuscular blocking agents with 1:1 binding to guest molecules. Sugammadex can also bind to other drugs having a steroid component in its chemical structure. In this in vivo experiment, we investigated the differences in the recovery of rocuronium-induced neuromuscular blockade using sugammadex pre-exposed with two different concentrations of hydrocortisone.Methods: The sciatic nerves and tibialis anterior muscles of 30 adult Sprague–Dawley rats were prepared for the experiment. The sciatic nerves were stimulated using a train-of-four (TOF) pattern with indirect supramaximal stimulation at 20 s intervals. After 15 min of stabilization, a 250 μg loading dose and 125 μg booster doses of rocuronium were serially administered until > 95% depression of the first twitch tension of TOF stimulation (T1) was confirmed. The study drugs were prepared by mixing sugamadex with the same volume of three different stock solutions (0.9% normal saline, 10 mg/ml hydrocortisone, and 100 mg/ml hydrocortisone). The recovery of rats from neuromuscular blockade was monitored by assessing T1 and the TOF ratio (TOFR) simultaneously until T1 was recovered to > 95% and TOFR to > 0.9.Results: In the group injected with sugammadex premixed with a high concentration of hydrocortisone, statistically significant intergroup differences were observed in the recovery progression of T1 and TOFR (P < 0.050).Conclusions: When sugammadex was pre-exposed to a high dose of hydrocortisone only, recovery from neuromuscular blockade was delayed. Delayed recovery from neuromuscular blockade is not always plausible when sugammadex is pre-exposed to steroidal drugs.

2021 ◽  
Author(s):  
Ha Yeon Park ◽  
Heyran Choi ◽  
Yong Beom Kim ◽  
Seok Kyeong Oh ◽  
Taehoon Kim ◽  
...  

Abstract Background: Chronic exposure to glucocorticoids is associated with resistance to nondepolarising neuromuscular blocking agents. Therefore, we hypothesised that sugammadex-induced recovery in subjects with chronic exposure to dexamethasone was faster than that in subjects without dexamethasone exposure. Objective: To evaluate the recovery profile of rocuronium-induced neuromuscular blockade after sugammadex administration in rats. Design: An in vivo study on rats.Setting: Asan Institute for Life Sciences, Asan Medical Center, Korea, from April 2017 to October 2017.Animals: Thirty-six male Sprague-Dawley rats.Intervention: Sprague–Dawley rats were allocated to three groups (dexamethasone group, control group, and pair-fed group) for the in vivo study. Dexamethasone group received daily intraperitoneal injections of dexamethasone 500 μg kg-1 or 0.9% saline for 15 days. On the sixteenth day, 3.5 mg kg-1 of rocuronium was administered to achieve complete neuromuscular blockade. Main outcome measures: The recovery time to a train-of-four ratio Results: There were no significant differences in the recovery time to train-of-four ratio to 0.9 among the groups (P = 0.531). The time to second twitch of train-of-four recovery that indicated the duration of rocuronium-induced neuromuscular blockade was significantly shorter in Group D than in Groups C and P (P = 0.001). Conclusion: As previously reported, resistance to rocuronium was observed in rats with chronic exposure to dexamethasone. However, the neuromuscular recovery time after sugammadex administration was not significantly different between groups.


2021 ◽  
Vol 9 (2) ◽  
pp. 21
Author(s):  
Cyrus Motamed ◽  
Migena Demiri ◽  
Nora Colegrave

Introduction: This study was designed to compare the Datex neuromuscular transmission (NMT) kinemyography (NMTK) device with the TOFscan (TS) accelerometer during the onset and recovery of neuromuscular blockade. Patients and methods: This prospective study included adult patients who were scheduled to undergo elective surgery with general anesthesia and orotracheal intubation. The TS accelerometer was randomly placed at the adductor pollicis on one hand, and the NMTK was placed on the opposite arm. Anesthesia was initiated with remifentanil target-controlled infusion (TCI) and 2.0–3.0 mg/kg of propofol. Thereafter, 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium was injected. If needed, additional neuromuscular blocking agents were administered to facilitate surgery. First, we recorded the train of four (TOF) response at the onset of neuromuscular blockade to reach a TOF count of 0. Second, we recorded the TOF response at the recovery of neuromuscular blockade to obtain a T4/T1 90% by both TS and NMTK. Results: There were 32 patients, aged 38–83 years, with the American Society of Anesthesiologists (ASA) Physical Status Classification I–III included and analyzed. Surgery was abdominal, gynecologic, or head and neck. The Bland and Altman analysis for obtaining zero responses during the onset showed a bias (mean) of 2.7 s (delay) of TS in comparison to NMTK, with an upper/lower limit of agreement of [104; −109 s] and a bias of 36 s of TS in comparison to NMTK, with an upper/lower limit of agreement of [−21.8, −23.1 min] during recovery (T4/T1 > 90%). Conclusions: Under the conditions of the present study, the two devices are not interchangeable. Clinical decisions for deep neuromuscular blockade should be made cautiously, as both devices appear less accurate with significant variability.


2016 ◽  
Vol 125 (4) ◽  
pp. 732-743 ◽  
Author(s):  
Hiroshi Sunaga ◽  
John J. Savarese ◽  
Jeff D. McGilvra ◽  
Paul M. Heerdt ◽  
Matthew R. Belmont ◽  
...  

Abstract Background CW002, a novel nondepolarizing neuromuscular blocking agent of intermediate duration, is degraded in vitro by l-cysteine; CW002-induced neuromuscular blockade (NMB) is antagonized in vivo by exogenous l-cysteine.1 Further, Institutional Animal Care and Use Committee–approved studies of safety and efficacy in eight anesthetized monkeys and six cats are described. Methods Mean arterial pressure, heart rate, twitch, and train-of-four were recorded; estimated dose producing 95% twitch inhibition (ED95) for NMB and twitch recovery intervals from 5 to 95% of baseline were derived. Antagonism of 99 to 100% block in monkeys by l-cysteine (50 mg/kg) was tested after bolus doses of approximately 3.75 to 20 × ED95 and after infusions. Vagal and sympathetic autonomic responses were recorded in cats. Dose ratios for [circulatory (ED20) or autonomic (ED50) changes/ED95 (NMB)] were calculated. Results ED95s of CW002 in monkeys and cats were 0.040 and 0.035 mg/kg; l-cysteine readily antagonized block in monkeys: 5 to 95% twitch recovery intervals were shortened to 1.8 to 3.6 min after 3.75 to 10 × ED95 or infusions versus 11.5 to 13.5 min during spontaneous recovery. ED for 20% decrease of mean arterial pressure (n = 27) was 1.06 mg/kg in monkeys; ED for 20% increase of HR (n = 27) was 2.16 mg/kg. ED50s for vagal and sympathetic inhibition in cats were 0.59 and &gt;&gt;0.80 mg/kg (n = 14 and 15). Dose ratios for [circulatory or autonomic changes/ED95 (NMB)] were all more than 15 × ED95. Conclusions The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by l-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.


2017 ◽  
Vol 37 (1) ◽  
pp. 1
Author(s):  
Agus Slamet ◽  
Bayu Kanetro

Protein content of winged bean is almost the same as soybean, but the beany flavor is more poweful than soybean. Therefore the protein of winged bean was isolated prior to use as raw material of yogurt. This research was aimed to determine the potency of  hypocholestrolemic activity of yogurt protein isolate of winged  bean through in vivo bioassay by using Sprague Dawley male rats. The treatments of the research were yogurt feed treatment with concentration of yogurt 0 (standard feed without yogurt as a control), 2, and 4 g yogurt/day as low and high concentration treatment respectively for 4th weeks after hypercholesterol feed  treatment for 1 week. The blood lipid profile of rats, including triglyceride, cholesterol total, High Density Lipoprotein (HDL), Low  Density Lipoprotein (LDL) cholesterol were analysed on the 2nd  and 4th weeks for the yogurt feed treatment while for before  yogurt feed treatment, the evaluation were based on the  adaptation phase and the 1st week for hypercholesterol phase.  The result of this research showed that the blood triglyceride,  cholesterol total, LDL increased, and the blood HDL decreased in hypercholesterol phase before yogurt feed treatment. The potency of hypocholestrolemic of yogurt from protein isolate of winged  bean was shown by the decreasing of blood triglyceride,  cholesterol total, LDL and increasing the HDL cholesterol after the yogurt feed treatment with low and high concentration. That  indicated that yogurt that was made of protein isolate of winged  bean could reduced cholesterol. ABSTRAKBiji kecipir memiliki kadar protein yang hampir sama dengan  kedelai, namun bau langunya lebih tajam daripada kedelai,  sehingga perlu diisolasi proteinnya sebelum digunakan sebagai  bahan baku yogurt. Tujuan penelitian ini adalah menentukan  potensi hipokolesterolemik yogurt isolat proteun biji kecipir  melalui uji biologis in vivo menggunakan tikus jantan Sprague Dawley. Perlakuan penelitian ini adalah perlakuan pakan yogurt  dengan konsentrasi 0 (pakan standar tanpa penambahan yogurt sebagai kontrol), 2, dan 4 g yogurt/hari berturut-turut sebagai  perlakuan konsentrasi rendah dan tinggi selama 4 minggu  perlakuan pakan yogurt sesudah pemberian pakan hiperkolesterol selama 1 minggu. Profil lipida darah tikus meliputi kadar trigliserida, total kolesterol, kolesterol High Density  Lipoprotein (HDL), dan Low Density Lipoprotein (LDL) dianalisis  pada minggu ke 2 dan 4 minggu selama perlakuan pakan yogurt  dan sebelum perlakuan pakan yogurt yaitu pada fase pemeliharaan adaptasi dan 1 minggu pada fase pemeliharan  hiperkolesterol. Hasil penelitian ini menunjukkan bahwa  trigliserida, total kolesterol, dan kolesterol LDL meningkat dan kolesterol HDL menurun selama fase pemberian pakan  hiperkolesterol sebelum perlakuan pakan yogurt. Potensi  hipokolesterol yogurt isolat protein biji kecipir ditunjukkan dengan penurunan trigliserida, total kolesterol, dan kolesterol LDL, serta peningkatan kolesterol HDL sesudah perlakuan pakan yogurt dengan konsentrasi rendah maupun tinggi. Hal tersebut mengindikasikan bahwa yogurt isolat protein biji kecipir mampu menurunkan kolesterol.


1996 ◽  
Vol 5 (6) ◽  
pp. 449-454 ◽  
Author(s):  
R Kleinpell ◽  
C Bedrosian ◽  
L McCormick ◽  
M Kremer ◽  
L Bujalski ◽  
...  

BACKGROUND: Neuromuscular blockade is a frequently used therapy in the ICU. However, recent reports of prolonged paralysis and general muscular weakness in patients treated with this procedure have raised concerns about its use in intensive care. OBJECTIVE: The purpose of this study was to assess current monitoring practices of nurses who care for patients treated with neuromuscular blockade. METHODS: In January 1995, questionnaires were mailed to a random national sample of 2000 critical care nurses. Of the 2000 questionnaires mailed, 744 were returned. RESULTS: The number of patients per month who were treated with neuromuscular blockade in ICU settings ranged from 0 to 75 (mean = 6.82, SD = 9.15). For each patient, the average number of days of blockade ranged from less than 1 to 63 (mean = 4.12, SD = 3.36). The most common indications for neuromuscular blockade were to assist in mechanical ventilation, reduce oxygen consumption, and treat agitation. Only 41% of respondents (n = 306) reported using train-of-four stimuli and a peripheral nerve stimulator to monitor patients. Depth of neuromuscular blockade was routinely monitored by using clinical assessment (31%), a peripheral nerve stimulator (16%), or both (52%). CONCLUSIONS: Among the respondents, variations existed in monitoring practices and in the use of peripheral nerve stimulators, including the frequency of monitoring and use of the baseline milliamperage. Appropriate monitoring and titration of neuromuscular blocking agents by ICU nurses may aid in preventing adverse effects, including the potential for prolonged neuromuscular blockade. The existing variations in practice may affect patients' outcomes.


2004 ◽  
Vol 287 (3) ◽  
pp. H1286-H1295 ◽  
Author(s):  
Sarah J. Canyon ◽  
Geoffrey P. Dobson

Despite decades of research, there are few effective ways to treat ventricular fibrillation (VF), ventricular tachycardia (VT), or cardiac ischemia that show a significant survival benefit. Our aim was to investigate the combined therapeutic effect of two common antiarrhythmic compounds, adenosine and lidocaine (AL), on mortality, arrhythmia frequency and duration, and infarct size in the rat model of regional ischemia. Sprague-Dawley rats ( n = 49) were anesthetized with pentobarbital sodium (60 mg·ml−1·kg−1 ip) and instrumented for regional coronary occlusion (30 min) and reperfusion (120 min). Heart rate, blood pressure, and a lead II electrocardiogram were recorded. Intravenous pretreatment began 5 min before ischemia and extended throughout ischemia, terminating at the start of reperfusion. After 120 min, hearts were removed for infarct size measurement. Mortality occurred in 58% of saline controls ( n = 12), 50% of adenosine only (305 μg·kg−1·min−1, n = 8), 0% in lidocaine only (608 μg·kg−1·min−1, n = 8), and 0% in AL at any dose (152, 305, or 407 μg·kg−1·min−1 adenosine plus 608 μg·kg−1·min−1 lidocaine, n = 7, 8, and 6). VT occurred in 100% of saline controls (18 ± 9 episodes), 50% of adenosine-only (11 ± 7 episodes), 83% of lidocaine-only (23 ± 11 episodes), 60% of low-dose AL (2 ± 1 episodes, P < 0.05), 57% of mid-dose AL (2 ± 1 episodes, P < 0.05), and 67% of high-dose AL rats (6 ± 3 episodes). VF occurred in 75% of saline controls (4 ± 3 episodes), 100% of adenosine-only-treated rats (3 ± 2 episodes), and 33% lidocaine-only-treated rats (2 ± 1 episodes) of the rats tested. There was no deaths and no VF in the low- and mid-dose AL-treated rats during ischemia, and only one high-dose AL-treated rat experienced VF (25.5 sec). Infarct size was lower in all AL-treated rats but only reached significance with the mid-dose treatment (saline controls 61 ± 5% vs. 38 ± 6%, P < 0.05). We conclude that a constant infusion of a solution containing AL virtually abolished severe arrhythmias and prevented cardiac death in an in vivo rat model of acute myocardial ischemia and reperfusion. AL combinational therapy may provide a primary prevention therapeutic window in ischemic and nonischemic regions of the heart.


1999 ◽  
Vol 91 (6) ◽  
pp. 1648-1648 ◽  
Author(s):  
Rafael Miguel ◽  
Thomas Witkowski ◽  
Hideo Nagashima ◽  
Robert Fragen ◽  
Richard Bartkowski ◽  
...  

Background This study compares the neuromuscular blocking and cardiovascular effects of rapacuronium (ORG 9487), a new aminosteroid nondepolarizing muscle relaxant, to recommended intubating doses of succinylcholine and mivacurium. Methods Adult patients were randomized in an open-label fashion to receive 1-5 microg/kg fentanyl before 1.5 mg/kg propofol induction followed by 1.5 or 2.5 mg/kg rapacuronium, 1.0 mg/kg succinylcholine, or 0.25 mg/kg mivacurium (i.e., 0.15 mg/kg followed by 0.1 mg/kg 30 s later). Results Patient neuromuscular blockade status was monitored by measuring the train-of-four response to a supramaximal stimulus at the ulnar nerve every 12 s. Percentage of the first twitch of the train-of-four (T1) at 60 s was similar in patients receiving 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine and was significantly less than in patients in the mivacurium group (26, 16, and 18%, respectively, vs. 48%; P &lt; 0.01). Times to 80% T1 depression were also similar among patients in the 1.5 mg/kg rapacuronium, 2.5 mg/kg rapacuronium, and succinylcholine groups and significantly longer in the mivacurium group (62, 54, and 54 s, respectively, vs. 112 s; P &lt; 0.01). Clinical duration was longer in all groups compared with the succinylcholine group; however, clinical duration in the 1.5 mg/kg rapacuronium group was shorter compared with the mivacurium group (15 vs. 21 min, respectively; P &lt; 0.01). Heart rate changes were mild in the 1.5 mg/kg rapacuronium, succinylcholine, and mivacurium groups. The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group. No differences were found in blood pressure changes among patients in the four groups. Conclusions Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium. Although succinylcholine continued to show the shortest duration, 1.5 mg/kg rapacuronium used a rapid onset and a relatively short duration and may be considered an alternative to succinylcholine.


2020 ◽  
Author(s):  
Yong Beom Kim ◽  
Jae-Moon Choi ◽  
Chungon Park ◽  
Hey-Ran Choi ◽  
Junyong In ◽  
...  

Abstract Background: Sevoflurane affects on the A1 receptor in the central nervous system (CNS) and potentiates the action of neuromuscular blocking agents. In the present study, we investigated whether sevoflurane (SEVO) has the ability to potentiate the neuromuscular blocking effect of rocuronium and if the specific antagonist of adenosine receptor (SLV320) can reverse this effect. Methods: Phrenic nerve–hemidiaphragm tissue specimens were obtained from forty Sprague-Dawley (SD) rats. The specimens were immersed in an organ bath filled with Krebs buffer and stimulated by a train-of-four (TOF) pattern using indirect supramaximal stimulation at 20 s intervals. The specimens were randomly allocated to control, 2-chloroadenosine (CADO), SEVO, or SLV320+SEVO groups. In the CADO and SLV320+SEVO groups, CADO and SLV320 were added to the organ bath from the start to a concentration of 10 μM and 10 nM, respectively. We then proceeded with rocuronium-induced blockade of >95% depression of the first twitch tension of TOF (T1) and TOF ratio (TOFR). In the SEVO and SLV320+SEVO groups, SEVO was added to the Krebs buffer solution to concentration of 400 - 500 μM for 10 min. Sugammadex-induced T1 and TOFR recovery was monitored for 30 min until >95% of T1 and >0.9 of TOFR were confirmed, and the recovery pattern was compared by plotting these data. Results: There were no significant differences in the recovery pattern between the control and SEVO groups. However, there were significant differences between the SEVO and SLV320+SEVO groups. Conclusion: Sevoflurane potentiates of rocuronium-induced neuromuscular blocking effect and delays sugammadex-induced recovery from neuromuscular blockade.


2008 ◽  
Vol 62 (3) ◽  
pp. 197-204 ◽  
Author(s):  
Rade Injac ◽  
Aleksandar Djordjevic ◽  
Borut Strukelj

The therapeutic utility of the anthracycline antibiotic doxorubicin is limited due to its cardiotoxicity. Our aim was to investigate the efficacy of fullerenol C60(OH)24 in preventing single, high-dose doxorubicin-induced cardiotoxicity in rats with malignant neoplasm. In vitro and in vivo studies have shown that fullerenol C60(OH)24, has strong antioxidative potential. Experiment was performed on adult female Sprague Dawley rats with chemically induced mammary carcinomas. All 32 rats (2-5 groups) received i.p. applications of 1-methyl-l-nitrosourea (MNU; 50 mg/kg body weight) on the 50th and 113th day of age. Animals were randomly divided into five groups as follows: (1) Untreated control group - rats received saline only; (2) Cancer control group - rats received MNU and saline; (3) Dox group - rats received MNU and Dox 8 mg/kg; (4) Full/Dox group -rats received MNU and Full 100 mg/kg 30 min before Dox 8 mg/kg; (5) Full group - rats received MNU and Full 100 mg/kg. Tumor incidence was 4.94 +- 0.576 per rat. The animals were sacrificed 2 days after the application of doxorubicin and/or fullerenol, and the serum activities of CK, LDH and ?-HBDH, as well as the levels of MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS in the heart, were determined. The results obtained from the enzymatic activity in the serum show that the administration of a single dose of 8 mg/kg in all treated groups induces statistically significant damage. There are significant changes in the enzymes of LDH and CK (p < 0.05), after an i.p. administration of doxorubicin/fullerenol and fullerenol. Comparing all groups with untreated control group, point to the conclusion that in the case of a lower oc-HBDH/LDH ratio, results in more serious the liver parenchymal damage. The results revealed that doxorubicin induced oxidative damage and that the fullerenol antioxidative influence caused significant changes in MDA, GSH, GSSG, GSH-Px, SOD, CAT, GR and TAS level in the heart (p < 0.05). Ultra structural analysis of heart tissues from rats treated with doxorubicin and indicated that the hearts of the rats were protected from doxorubicin-induced subcellular damage. Doxorubicin/fullerenol rats did not appear to show significant cardiac damage although occasional focal loss of cristae in the mitochondria was observed. Therefore, it is suggested that fullerenol might be a potential cardioprotector in doxorubicin-treated individuals.


2018 ◽  
Vol 24 (13) ◽  
pp. 1395-1404
Author(s):  
Elham Bagheri ◽  
Kamelia Saremi ◽  
Fatemeh Hajiaghaalipour ◽  
Fadhil Lafta Faraj ◽  
Hapipah Mohd Ali ◽  
...  

Quinazoline is an aromatic bicyclic compound exhibiting several pharmaceutical and biological activities. This study was conducted to investigate the potential wound healing properties of Synthetic Quinazoline Compound (SQC) on experimental rats. The toxicity of SQC was determined by MTT cell proliferation assay. The healing effect of SQC was assessed by in vitro wound healing scratch assay on the skin fibroblast cells (BJ-5ta) and in vivo wound healing experiment of low and high dose of SQC on adult Sprague-Dawley rats compared with negative (gum acacia) and positive control (Intrasite-gel). Hematoxylin and Eosin (H&E), Masson’s Trichrome (MT) staining and immunohistochemistry analysis were performed to evaluate the histopathological alterations and proteins expression of Bax and Hsp70 on the wound tissue after 10 days. In addition, levels of antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase), and malondialdehyde (MDA) were measured in wound tissue homogenates. The SQC significantly enhanced BJ-5ta cell proliferation and accelerated the percentage of wound closure, with less scarring, increased fibroblast and collagen fibers and less inflammatory cells compared with the negative control. The compound also increases endogenous enzymes and decline lipid peroxidation in wound homogenate.


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