scholarly journals Carboxymethyl-γ-cyclodextrin, a novel selective relaxant binding agent for the reversal of neuromuscular block induced by aminosteroid neuromuscular blockers: an ex vivo laboratory study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ákos I. Fábián ◽  
Edömér Tassonyi ◽  
Vera Csernoch ◽  
Marianna Fedor ◽  
Tamás Sohajda ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Neuromuscular Block ◽  
Neuromuscular Blocking ◽  
Contraction Force ◽  
Binding Agent ◽  
Airway Complications ◽  
Binding Agents ◽  
Male Wistar Rats ◽  
Residual Neuromuscular Block ◽  
Stimulation Of

Abstract Background Residual neuromuscular block at the end of surgery may compromise the patient’s safety. The risk of airway complications can be minimized through monitoring of neuromuscular function and reversal of neuromuscular block if needed. Effective reversal can be achieved with selective relaxant binding agents, however, sugammadex is the only clinically approved drug in this group. We investigated the concentration–response properties of a novel selective relaxant binding agent, carboxymethyl-γ-cyclodextrin for the reversal of neuromuscular block. We evaluated the hypothesis that it is equally potent for reversing neuromuscular block as sugammadex. Methods Phrenic nerve – hemidiaphragm tissue preparations were isolated from male Wistar rats and suspended in a tissue holder allowing electrical stimulation of the nerve and monitoring of muscle contraction force. Concentration–response relationships were constructed for the neuromuscular blocking agents rocuronium, pipecuronium, and vecuronium. The half-effective concentrations of sugammadex and carboxymethyl-γ-cyclodextrin for reversal of neuromuscular block were determined. Results The half effective concentrations (95% confidence interval, CI) were 7.50 (6.93–8.12) μM for rocuronium, 1.38 (1.33–1.42) μM for pipecuronium, and 3.69 (3.59–3.80) μM for vecuronium. The half effective concentrations (95% CI) of carboxymethyl-γ-cyclodextrin and sugammadex were 35.89 (32.67–39.41) μM and 3.67 (3.43–3.92) μM, respectively, for the reversal of rocuronium-induced block; 10.14 (9.61–10.70) μM and 0.67 (0.62–0.74) μM, respectively, for the reversal of pipecuronium-induced block; and 376.1 (341.9–413.8) μM and 1.45 (1.35–1.56) μM, respectively, for the reversal of vecuronium-induced block. Conclusions Carboxymethyl-γ-cyclodextrin is an effective, but less potent agent for reversal of neuromuscular block than sugammadex.

Residual Block after Mivacurium with or without Edrophonium Reversal in Adults and Children

1996 ◽  
Vol 84 (2) ◽  
pp. 362-367. ◽  
Author(s):  
David R. Bevan ◽  
Raymond Kahwaji ◽  
John M. Ansermino ◽  
Eleanor Reimer ◽  
Michael F. Smith ◽  
...  
Keyword(s):  
Ulnar Nerve ◽  
Neuromuscular Block ◽  
Saline Group ◽  
Neuromuscular Blocking ◽  
Postanesthesia Care Unit ◽  
Random Allocation ◽  
Train Of Four ◽  
Residual Neuromuscular Block ◽  
Residual Block ◽  
Stimulation Of

Background The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. Methods In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. Results Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05). Conclusions This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

Reversal of Rocuronium-induced Neuromuscular Block by the Selective Relaxant Binding Agent Sugammadex

2006 ◽  
Vol 104 (4) ◽  
pp. 667-674 ◽  
Author(s):  
Iben F. Sorgenfrei ◽  
Kathrine Norrild ◽  
Per Bo Larsen ◽  
Jakob Stensballe ◽  
Doris Østergaard ◽  
...  
Keyword(s):  
Placebo Group ◽  
Renal Excretion ◽  
Neuromuscular Block ◽  
Neuromuscular Blocking ◽  
Dependent Manner ◽  
Binding Agent ◽  
Train Of Four ◽  
Time Required ◽  
To Receive ◽  
Dose Dependent

Background Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block. Methods Twenty-seven male surgical patients aged 18-64 yr were randomly assigned to receive placebo or sugammadex (0.5, 1.0, 2.0, 3.0, or 4.0 mg/kg) for reversal of 0.6 mg/kg rocuronium-induced neuromuscular block. Anesthesia was induced and maintained using intravenous fentanyl and propofol. Neuromuscular function was assessed using acceleromyography. Sugammadex or placebo was administered at reappearance of T2 of the train-of-four. The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9. Results Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex. Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min. A median of 59-77% of sugammadex was excreted unchanged in the urine within 16 h, mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine (from a median of 19% in the placebo group to 53% in the 4.0-mg/kg group within 16 h). Sugammadex was safe and well tolerated. No evidence of recurarization was observed in any patient. Conclusion At doses of 2.0 mg/kg or greater, sugammadex safely reversed 0.6 mg/kg rocuronium-induced neuromuscular block in a dose-dependent manner. Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys.

Quantitative Neuromuscular Monitoring and Postoperative Outcomes: A Narrative Review

2021 ◽  
Author(s):  
Glenn S. Murphy ◽  
Sorin J. Brull
Keyword(s):  
Neuromuscular Block ◽  
Meta Analysis ◽  
Blocking Agent ◽  
Neuromuscular Blocking ◽  
Neuromuscular Monitoring ◽  
Postanesthesia Care Unit ◽  
Clinical Practices ◽  
Residual Neuromuscular Blockade ◽  
Quantitative Monitoring ◽  
Residual Neuromuscular Block

Over the past five decades, quantitative neuromuscular monitoring devices have been used to examine the incidence of postoperative residual neuromuscular block in international clinical practices, and to determine their role in reducing the risk of residual neuromuscular block and associated adverse clinical outcomes. Several clinical trials and a recent meta-analysis have documented that the intraoperative application of quantitative monitoring significantly reduces the risk of residual neuromuscular blockade in the operating room and postanesthesia care unit. In addition, emerging data show that quantitative monitoring minimizes the risk of adverse clinical events, such as unplanned postoperative reintubations, hypoxemia, and postoperative episodes of airway obstruction associated with incomplete neuromuscular recovery, and may improve postoperative respiratory outcomes. Several international anesthesia societies have recommended that quantitative monitoring be performed whenever a neuromuscular blocking agent is administered. Therefore, a comprehensive review of the literature was performed to determine the potential benefits of quantitative monitoring in the perioperative setting.

Early Platelet-Collagen Interactions in Whole Blood and Their Modifications by Aspirin and Dipyridamole Evaluated by a New Method (Basic Wave)

1985 ◽  
Vol 54 (04) ◽  
pp. 799-803 ◽  
Author(s):  
José Luís Pérez-Requejo ◽  
Justo Aznar ◽  
M Teresa Santos ◽  
Juana Vallés
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
White Blood Cells ◽  
Reversible Aggregation ◽  
Inhibitory Compounds ◽  
Rapid Generation ◽  
Stimulation Of ◽  
Collagen Stimulation

SummaryIt is shown that the supernatant of unstirred whole blood at 37° C, stimulated by 1 μg/ml of collagen for 10 sec, produces a rapid generation of pro and antiaggregatory compounds with a final proaggregatory activity which can be detected for more than 60 min on a platelet rich plasma (PRP) by turbidometric aggregometry. A reversible aggregation wave that we have called BASIC wave (for Blood Aggregation Stimulatory and Inhibitory Compounds) is recorded. The collagen stimulation of unstirred PRP produces a similar but smaller BASIC wave. BASIC’s intensity increases if erythrocytes are added to PRP but decreases if white blood cells are added instead. Aspirin abolishes “ex vivo” the ability of whole blood and PRP to generate BASIC waves and dipyridamole “in vitro” significantly reduces BASIC’s intensity in whole blood in every tested sample, but shows little effect in PRP.

scholarly journals Protein recycling and limb muscle recovery after critical illness in slow- and fast-twitch limb muscle

2019 ◽  
Vol 316 (5) ◽  
pp. R584-R593 ◽  
Author(s):  
Sebastien Preau ◽  
Michael Ambler ◽  
Anna Sigurta ◽  
Anna Kleyman ◽  
Alex Dyson ◽  
...  
Keyword(s):  
Critical Illness ◽  
Functional Disability ◽  
Ex Vivo ◽  
Therapeutic Option ◽  
Limb Muscle ◽  
Fungal Cell ◽  
Hindlimb Muscles ◽  
Initial Reduction ◽  
Male Wistar Rats

An impaired capacity of muscle to regenerate after critical illness results in long-term functional disability. We previously described in a long-term rat peritonitis model that gastrocnemius displays near-normal histology whereas soleus demonstrates a necrotizing phenotype. We thus investigated the link between the necrotizing phenotype of critical illness myopathy and proteasome activity in these two limb muscles. We studied male Wistar rats that underwent an intraperitoneal injection of the fungal cell wall constituent zymosan or n-saline as a sham-treated control. Rats ( n = 74) were killed at 2, 7, and 14 days postintervention with gastrocnemius and soleus muscle removed and studied ex vivo. Zymosan-treated animals displayed an initial reduction of body weight but a persistent decrease in mass of both lower hindlimb muscles. Zymosan increased chymotrypsin- and trypsin-like proteasome activities in gastrocnemius at days 2 and 7 but in soleus at day 2 only. Activated caspases-3 and -9, polyubiquitin proteins, and 14-kDa fragments of myofibrillar actin (proteasome substrates) remained persistently increased from day 2 to day 14 in soleus but not in gastrocnemius. These results suggest that a relative proteasome deficiency in soleus is associated with a necrotizing phenotype during long-term critical illness. Rescuing proteasome clearance may offer a potential therapeutic option to prevent long-term functional disability in critically ill patients.

scholarly journals Spatially resolved microfluidic stimulation of lymphoid tissue ex vivo

The Analyst ◽  
2017 ◽  
Vol 142 (4) ◽  
pp. 649-659 ◽  
Author(s):  
Ashley E. Ross ◽  
Maura C. Belanger ◽  
Jacob F. Woodroof ◽  
Rebecca R. Pompano
Keyword(s):  
Lymph Node ◽  
Targeted Delivery ◽  
Lymphoid Tissue ◽  
Ex Vivo ◽  
Tissue Slices ◽  
Microfluidic Platform ◽  
Spatially Resolved ◽  
Local Stimulation ◽  
Stimulation Of

We present the first microfluidic platform for local stimulation of lymph node tissue slices and demonstrate targeted delivery of a model therapeutic.

Effects of cannabinoid and vanilloid receptor agonists and their interaction on learning and memory in rats

2017 ◽  
Vol 95 (4) ◽  
pp. 382-387 ◽  
Author(s):  
Mariam Shiri ◽  
Alireza Komaki ◽  
Shahrbanoo Oryan ◽  
Masoumeh Taheri ◽  
Hamidreza Komaki ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Cannabinoid Receptor ◽  
Vanilloid Receptor ◽  
Interactive Effects ◽  
Control Group ◽  
Acute Administration ◽  
Male Wistar Rats ◽  
Agonistic Effect ◽  
Stimulation Of

Despite previous findings on the effects of cannabinoid and vanilloid systems on learning and memory, the effects of the combined stimulation of these 2 systems on learning and memory have not been studied. Therefore, in this study, we tested the interactive effects of cannabinoid and vanilloid systems on learning and memory in rats by using passive avoidance learning (PAL) tests. Forty male Wistar rats were divided into the following 4 groups: (1) control (DMSO+saline), (2) WIN55,212–2, (3) capsaicin, and (4) WIN55,212–2 + capsaicin. On test day, capsaicin, a vanilloid receptor type 1 (TRPV1) agonist, or WIN55,212–2, a cannabinoid receptor (CB1/CB2) agonist, or both substances were injected intraperitoneally. Compared to the control group, the group treated with capsaicin (TRPV1 agonist) had better scores in the PAL acquisition and retention test, whereas treatment with WIN55,212–2 (CB1/CB2 agonist) decreased the test scores. Capsaicin partly reduced the effects of WIN55,212–2 on PAL and memory. We conclude that the acute administration of a TRPV1 agonist improves the rats’ cognitive performance in PAL tasks and that a vanilloid-related mechanism may underlie the agonistic effect of WIN55,212–2 on learning and memory.

Sign in / Sign up

Export Citation Format

Share Document