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.

A new pharmacological approach for tracheal intubation?

Anaesthesia induced with remimazolam and a fentanyl-series opioid can be reversed with flumazenil and naloxone. Concomitant paralysis with rocuronium can facilitate tracheal intubation whilst being reversible with sugammadex. Together, this combination might offer full reversibility of a 'routine' or a 'rapid-sequence' induction anaesthesia. Whether this is useful, or even safe, requires careful evaluation.

Navigating Anesthesia: Muscle Relaxants and Reversal Agents in Patients with Renal Impairment.

This comprehensive review explores the interaction between neuromuscular blocking agents, reversal agents, and renal function, focusing on various drugs commonly used in anesthesia and their effects on kidney health. Succinylcholine, commonly used for anesthesia induction, can trigger elevated potassium levels in patients with specific medical conditions, leading to serious cardiac complications. While studies suggest the use of succinylcholine in patients with renal failure is safe, cases of postoperative hyperkalemia warrant further investigation. Some agents, such as atracurium and mivacurium, are minimally affected by impaired kidney function, whereas others, such as cisatracurium and rocuronium, can have altered clearance, necessitating dose adjustments in patients with renal failure. The reversal agents neostigmine and sugammadex affect renal markers, while cystatin C levels remain relatively stable with sugammadex use, indicating its milder impact on glomerular function, compared with neostigmine. Notably, the combination of rocuronium and sugammadex in rat studies shows potential nephrotoxic effects, cautioning against the simultaneous use of these agents. In conclusion, understanding the interplay between neuromuscular blocking agents and renal function is crucial for optimizing patient care during anesthesia. While some agents can be used safely in patients with renal failure, others can require careful dosing and monitoring. Further research is needed to comprehensively assess the long-term impact of these agents on kidney health, especially in high-risk patient populations. This article aims to review the use of muscle relaxants and reversal for anesthesia in patients with impaired renal function.

Sugammadex for reversal of moderate-to-deep rocuronium block in a clinical setting: A retrospective report of 10 dogs.

OBJECTIVE: To compare recovery times of sugammadex with spontaneous recovery from rocuronium-induced neuromuscular block (NMB) in dogs. STUDY DESIGN: Retrospective, unmatchedcase-control study. ANIMALS: A total of 10 dogs administered sugammadex and 10 dogs recovering spontaneously from rocuronium-induced NMB. METHODS: Files of dogs administered rocuronium between March and August 2023 were inspected. The train-of-four (TOF) count at the time of sugammadex administration and the time between administration and TOF ratio >90% (recovery time) were recorded. The recovery time for those not administered reversal agents was considered from the first TOF value >0 until TOF ratio >90%. The dose of sugammadex and the cumulative dose of rocuronium were recorded. Rocuronium doses and recovery times were compared using Mann-Whitney tests. The coefficient of determination (R2) between the cumulative rocuronium dose and sugammadex dose and the recovery time were calculated. RESULTS: Dogs in the sugammadex and spontaneous recovery groups were administered intravenously (IV) 0.76 (0.4-2.6) and 0.61 (0.3-2.9) mg kg-1 of rocuronium, respectively (p = 0.325). Recovery time after 3.9 (2.9-5.5) mg kg-1 of sugammadex IV was 1 (1-3) minutes and was 20 (10-35) min for spontaneous recovery (p < 0.0001). The R2 for rocuronium and sugammadex doses and recovery times were 0.19 (p = 0.2) and 0.012 (p = 0.758). CONCLUSIONS AND CLINICAL RELEVANCE: Sugammadex 2.9-5.5 mg kg-1 reversed moderate (TOF count 1-3) or deep (TOF count 0) rocuronium-induced NMB within 3 minutes, substantially faster than spontaneous recovery.

Effect of sugammadex on processed EEG parameters in patients undergoing robot-assisted radical prostatectomy.

BACKGROUND: Sugammadex has been associated with increases in the bispectral index (BIS). We evaluated the effects of sugammadex administration on quantitative electroencephalographic (EEG) and electromyographic (EMG) measures. METHODS: We performed a prospective observational study of adult male patients undergoing robot-assisted radical prostatectomy. All patients received a sevoflurane-based general anaesthetic and a continuous infusion of rocuronium, which was reversed with 2 mg kg-1 of sugammadex i.v. BIS, EEG, and EMG measures were captured with the BIS Vista™ monitor. RESULTS: Twenty-five patients were included in this study. Compared with baseline, BIS increased at 4-6 min (ß coefficient: 3.63; 95% confidence interval [CI]: 2.22-5.04; P<0.001), spectral edge frequency 95 (SEF95) increased at 2-4 min (ß coefficient: 0.29; 95% CI: 0.05-0.52; P=0.016) and 4-6 min (ß coefficient: 0.71; 95% CI: 0.47-0.94; P<0.001), and EMG increased at 4-6 min (ß coefficient: 1.91; 95% CI: 1.00-2.81; P<0.001) after sugammadex administration. Compared with baseline, increased beta power was observed at 2-4 min (ß coefficient: 93; 95% CI: 1-185; P=0.046) and 4-6 min (ß coefficient: 208; 95% CI: 116-300; P<0.001), and decreased delta power was observed at 4-6 min (ß coefficient: -526.72; 95% CI: -778 to -276; P<0.001) after sugammadex administration. Neither SEF95 nor frequency band data analysis adjusted for EMG showed substantial differences. None of the patients showed clinical signs of awakening. CONCLUSIONS: After neuromuscular block reversal with 2 mg kg-1 sugammadex, BIS, SEF95, EMG, and beta power showed small but statistically significant increases over time, while delta power decreased.

Association of sugammadex reversal of neuromuscular block and postoperative length of stay in the ambulatory care facility: a multicentre hospital registry study.

BACKGROUND: Encapsulation of rocuronium or vecuronium with sugammadex can reverse neuromuscular block faster than neostigmine reversal. This pharmacodynamic profile might facilitate patient discharge after ambulatory surgery. METHODS: We included patients who underwent ambulatory surgery with general anaesthesia and neuromuscular block between 2016 and 2021 from hospital registries at two large academic healthcare networks in the USA. The primary outcome was postoperative length of stay in the ambulatory care facility (PLOS-ACF). We examined post hoc whether the type of reversal affects postoperative nausea and vomiting and direct hospital costs. RESULTS: Among the 29 316 patients included, 8945 (30.5%) received sugammadex and 20 371 (69.5%) received neostigmine for reversal. PLOS-ACF and costs were lower in patients who received sugammadex vs neostigmine (adjusted difference in PLOS-ACF: -9.5 min; 95% confidence interval [95% CI], -10.5 to -8.5 min; adjusted difference in direct hospital costs: -US$77; 95% CI, -$88 to -$66; respectively; P<0.001). The association was magnified in patients over age 65 yr, with ASA physical status >2 undergoing short procedures (<2 h) (adjusted difference in PLOS-ACF: -18.2 min; 95% CI, -23.8 to -12.4 min; adjusted difference in direct hospital costs: -$176; 95% CI, -$220 to -$128; P<0.001). Sugammadex use was associated with reduced postoperative nausea and vomiting (17.2% vs 19.6%, P<0.001), which mediated its effects on length of stay. CONCLUSIONS: Reversal with sugammadex compared with neostigmine was associated with a small decrease in postoperative length of stay in the ambulatory care unit. The effect was magnified in older and high-risk patients, and can be explained by reduced postoperative nausea and vomiting. Sugammadex reversal in ambulatory surgery may also help reduce cost of care.

A prospective observational study of the effects of sugammadex on peri-operative oestrogen and progesterone levels in women who take hormonal contraception.

Pharmacokinetic modelling suggests that sugammadex may interact with endogenous progesterone and reduce levels by 34% in patients taking hormonal contraception. Due to this potential interaction that may be equivalent to missing one dose of an oral contraceptive pill, both the manufacturer and professional anaesthesia organisations recommend counselling patients to use additional non-hormonal contraception after administration of sugammadex. We performed a prospective observational study examining the changes in serum oestrogen and progesterone concentrations in premenopausal adult women undergoing an operative procedure. Sixty participants who were on hormonal contraception received sugammadex. Two additional control groups were recruited, consisting of 30 participants who were not on hormonal contraception and did not receive sugammadex, and 32 who were not on hormonal contraception and did receive sugammadex. Three blood samples were taken: before sugammadex; 15 min post-sugammadex; and 240 min post-sugammadex or end of operating theatre time. Median oestrogen levels decreased from baseline by around 40% at 240 min in all three groups (p ≤ 0.001). Progesterone levels rose significantly at 15 min (p = 0.002) in patients on contraception then decreased non-significantly to 20% below baseline at 240 min. The decrease in oestrogen and the rise in progesterone could both act to minimise the risk of ovulation and thus protect contraception in this population. We found no evidence of a change in hormone levels that might threaten contraceptive efficacy in women on hormonal contraception receiving sugammadex.

Effect of intraoperative muscle relaxation reversal on the success rate of motor evoked potential recording in patients undergoing spinal surgery: a randomized controlled trial.

BACKGROUND: Partial neuromuscular blockade (NMB) has been applied for some surgeries to reduce bleeding and prevent patient movement for spinal surgery. Sugammadex selectively binds to rocuronium in the plasma and consequently lowers the rocuronium concentration at the neuromuscular junction. In this study, we aimed to observe whether the success rate of transcranial motor-evoked potential (TceMEP) can be increased by sugammadex compared with partial NMB during spinal surgery. METHODS: Patients who underwent elective spinal surgery with TceMEP monitoring were randomly assigned to the sugammadex group and control group. Rocuronium was continuously infused to maintain the train of four counts (TOFc) = 2. The sugammadex group discontinued rocuronium infusion at the time of TceMEP monitoring and was infused with 2 mg/kg sugammadex; the control group was infused with the same dose of saline. RESULTS: A total of 171 patients were included. The success rate of TceMEP monitoring in the sugammadex group was significantly higher than that in the control group. TceMEP amplitudes were greater in the sugammadex group than in the control group at 5 min, 10 min, and 20 min after the start of motor-evoked potential monitoring. The latencies of upper extremity TceMEPs monitoring showed no difference between groups. TOF ratios were greater in the sugammadex group at 5 min, 10 min, and 20 min after the start of motor-evoked potential monitoring. There were no adverse effects caused by sugammadex. CONCLUSIONS: Sugammadex can improve the success rate of motor-evoked potential monitoring compared with moderate neuromuscular blockade induced by continuous infusion of rocuronium in spinal surgery. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov.cn on 29/10/2020 (trial registration number: NCT04608682).

The effects of sugammadex on gastric ischemia-reperfusion injury in rats: Biochemical and histopathological evaluation.

The primary sources of reactive oxygen species (ROS) that cause ischemia-reperfusion (I/R) injuries are enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in the literature, whereby one of the main ROS producing cells via NOX activity are polymophonuclear leukocytes (PNL). Sugammadex, the effect of which we plan to research against gastric I/R damage, is a modified gamma-cyclodextrin that antagonizes the action of steroidal neuromuscular blocking drugs. Previous studies have reported that sugammadex inhibits PNL infiltration. However, it is unknown whether an inhibitory effect on XO is present. We aimed to biochemically and histopathologically investigate the effects of sugammadex on I/R-induced stomach damage in rats. The animals were divided into groups that underwent gastric ischemia-reperfusion (GIR), 4 mg/kg sugammadex + gastric ischemia-reperfusion (SGIR), and a sham operation group (SG). The effect of sugammadex was evaluated by measuring oxidant-antioxidant and PNL parameters. There was no significant difference in XO levels between the SGIR and GIR groups. In the SGIR group, sugammadex inhibited the increase in myeloperoxidase (MPO) and malondialdehyde (MDA) levels (p < 0.001). The amount of MDA and MPO in the SGIR group was similar as in the SG group. Sugammadex significantly suppressed the decrease in tGSH levels in the SGIR group (p < 0.001). The difference between tGSH levels in the SG and SGIR groups was slight. In the SGIR group, sugammadex significantly suppressed the increase in tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL1-ß) levels compared to the GIR group (p < 0.001). Additionally, sugammadex corrected histopathological modifications as much as sham group. In conclusion, sugammadex may be beneficial in preventing oxidative stress.

Sugammadex for reversal of rocuronium-induced neuromuscular blockade during alfaxalone anesthesia in dogs.

OBJECTIVE: To investigate the reversal effect of sugammadex on neuromuscular blockade induced by a single bolus of rocuronium in dogs under alfaxalone anesthesia. STUDY DESIGN: Randomized, prospective, crossover experimental study. ANIMALS: A group of six adult Beagle dogs (three females and three males), weighing 11.3-15.8 kg and aged 6-8 years, were used. METHODS: Dogs were anesthetized twice with a 1.25 times minimum infusion rate of alfaxalone, with a washout period of at least 14 days between experiments. Neuromuscular function was monitored using acceleromyography with train-of-four (TOF) stimulation of the peroneal nerve. After recording the control TOF ratio (TOFRC), rocuronium (0.5 mg kg-1) was administered intravenously. Subsequently, sugammadex (4 mg kg-1) or an equal volume of saline (control treatment) was administered intravenously when the TOF count returned from 0 to 1 after neuromuscular blockade. Time from rocuronium injection to TOF count = 0 (onset time), time from TOF count = 0 to TOF count = 1 (maximum blockade period), time of first twitch amplitude recovery from 0.25 to 0.75 (recovery index), and time from sugammadex or saline administration to TOF ratio/TOFRC ≥ 0.9 (recovery time) were recorded. RESULTS: The onset time and maximum blockade duration did not differ between sugammadex treatment [1.2 (0.7-1.5) minutes and 9.9 (6.3-10.5) minutes, respectively] and control treatment [median (range); 1.0 (0.7-1.1) minutes and 9.9 (8.8-11.5) minutes, respectively] (p = 0.219 and 0.844, respectively). Recovery index was 0.5 (0.3-0.7) minutes in sugammadex treatment, which was shorter than that in control treatment [4.5 (3.7-4.9) minutes] (p = 0.031). Recovery time was 0.8 (0.5-2.8) minutes in sugammadex treatment, which was shorter than that in control treatment [10.5 (6.8-14.3) minutes] (p = 0.031). CONCLUSIONS AND CLINICAL RELEVANCE: Rocuronium-induced neuromuscular blockade was effectively reversed by sugammadex in dogs anesthetized with alfaxalone.

Adamgammadex in patients to reverse a moderate rocuronium-induced neuromuscular block.

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.

A comparison between the adductor pollicis muscle and the abductor digiti minimi muscle using electromyography AF-201P in rocuronium-induced neuromuscular block: a prospective comparative study.

BACKGROUND: The AF-201P, a new electromyography (EMG)-based neuromuscular monitor has been developed recently. The aim of this clinical study was to compare two ulnar nerve innervated muscles: the adductor pollicis (AP) muscle and the abductor digiti minimi (ADM) muscle during the recovery from rocuronium-induced neuromuscular block by using EMG AF-201P. METHODS: Twenty patients undergoing surgery with general anesthesia were enrolled in the study. During total intravenous general anesthesia, train-of-four (TOF) and post-tetanic counts (PTC) responses following 0.9 mg/kg rocuronium administration were concurrently monitored at the AP and the ADM muscles with EMG AF-201P on the opposite arms. At the end of the surgery, sugammadex 2 mg/kg was administered when TOF counts of 2 (TOFC2) was observed at both muscles. The primary outcome of the study was time from administration of rocuronium to first appearance of PTC response (first PTC). The secondary outcomes of the study were time from administration of rocuronium to TOF count of 1 (TOFC1), time from first PTC to TOFC1 (PTC-TOF time), time to TOFC2, and time from administration of sugammadex to TOF ratio ≥ 0.9. Agreement between the two muscles was assessed using the Bland-Altman analysis. Data are expressed as mean ± standard deviation. RESULTS: Nineteen patients were included in the analysis. Time to first PTC was significantly faster at the ADM muscle than the AP muscle (24.4 ± 11.4 min vs 32.4 ± 13.1 min, p = 0.006). PTC-TOF time was significantly longer with the ADM muscle than the AP muscle (19.4 ± 7.3 min vs 12.4 ± 10.6 min, p = 0.019). There were no significant differences in time to TOFC2 and sugammadex-facilitated recovery between the two muscles. Bland-Altman analyses showed acceptable ranges of bias and limits of agreement of the two muscles. CONCLUSIONS: The ADM muscle showed a good agreement with the AP muscle during rocuronium-induced neuromuscular block but faster recovery of PTC response when using EMG. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000044904 ). Registered 19 July 2021 -Retrospectively registered, https://center6.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000051290 .

Sugammadex reversal of muscle relaxant blockade provided less Post-Anesthesia Care Unit adverse effects than neostigmine/glycopyrrolate.

Sugammadex is a direct reversal agent of aminosteroid muscle relaxants, particularly rocuronium, with promptly and completely reverse of deep neuromuscular block (NMB), which allows better surgical conditions. Sugammadex exhibits advantages over indirect reversal agent acetylcholinesterase inhibitor neostigmine with less adverse effects. In this retrospective review, we compared the incidence of postoperative vomiting (POV), postoperative urinary retention (POUR), and hemodynamic changes between sugammadex and neostigmine/glycopyrrolate in reversal of muscular blockade. Sugammadex showed superior in all three aspects. The heart rate was 7.253 lower (P < 0.0001) and mean arterial pressure was 5.213 lower (P < 0.0001) in sugammadex group. The POV of neostigmine/glycopyrrolate group was 3.16 times more than sugammadex group (OR = 3.16, p < 0.0001), and POUR of neostigmine/glycopyrrolate group was 4.291 times more than sugammadex group (OR = 4.291, p < 0.0001). Sugammadex showed better hemodynamic stability, and lower incidence of POV and POUR than neostigmine/glycopyrrolate.

Evaluation of Neuroprotective Effects of Sugammadex Following a Head Trauma in an Experimental Study.

ABSTRACT: To compare the efficacy of mannitol, the first choice of treatment in daily clinical practice for head trauma, and sugammadex, a frequently used neuroanesthesia in recent years. A total of 35 male rats were randomly selected and were divided into 5 groups, each comprising 7 rats. The groups were divided into Group I, sham (n = 7); Group II, control (head trauma, n = 7); Group III, treated with mannitol (head trauma, mannitol 20% 1 g/kg, n = 7); Group IV, treated with sugammadex (head trauma, sugammadex 100 mg/ kg, n = 7); and Group V, treated with mannitol and sugammadex (head trauma, mannitol 20% 1 g/kg and sugammadex 100 mg/kg, n = 7). After the sacrification, histological examination and immu-nohistochemical staining were performed in the brain of all subjects. Mann-Whitney U test was used to evaluate the significance between neuronal density, neuronal nuclei, and activated caspase-3 immunohistochemistry results measured from the prefrontal cortex. Neuronal density showing neuronal viability was observed to significantly increase in Group III compared to Group IV. However, neuronal nuclei immunohistochemistry showing apoptotic neurons also significantly increased. The present study has shown that sugammadex, an agent reversing the effects of neuromuscular blocking agents, has neuroprotective effects and is as effective as mannitol.

MRGPRX2 activation in mast cells by neuromuscular blocking agents and other agonists: Modulation by sugammadex.

BACKGROUND: Neuromuscular-blocking agents (NMBAs) can cause both IgE-dependent and IgE-independent anaphylactic reactions, with activation of the mast cell receptor MRGPRX2 being important to the latter. Sugammadex, a reversal agent for certain aminosteroid NMBAs, has been proposed as an antidote for these anaphylactic events with conflicting outcomes. OBJECTIVE: We further characterize the involvement of MRGPRX2 in NMBA-induced mast cell activation and determine how this is influenced by sugammadex. We then apply these in vitro results to infer the possible utility of sugammadex in the acute management of non-IgE-dependent anaphylaxis. METHODS: The LAD2 human mast cell line and a MRGPRX2 knock-down derivative were used to validate the involvement of MRGPRX2 and to test the effect of sugammadex on mast cell activation by NMBAs and other MRGPRX2 agonists. RESULTS: All MRGPRX2 agonists tested were shown to induce MRGPRX2-dependent LAD2 mast cell calcium mobilization and cytokine release and all, apart from rocuronium, induced degranulation. Co-treatment of mast cells with sugammadex and some MRGPRX2 agonists significantly reduced cell activation, but if sugammadex was administered a few minutes following stimulation, degranulation was not attenuated. However, addition of sugammadex up to 180 min following LAD2 MRGPRX2 stimulation, significantly reduced CCL2 mRNA and protein induction. CONCLUSIONS AND CLINICAL RELEVANCE: We show that sugammadex, known to reverse muscle blockade by certain NMBAs, is also able to reduce MRGPRX2 activation by NMBAs and other, but not all, MRGPRX2 agonists. As sugammadex was ineffective in attenuating mast cell degranulation when added rapidly post MRGPRX2 activation, this suggests against the agent having efficacy in controlling acute symptoms of anaphylaxis to NMBAs caused by MRGPRX2 activation. Interestingly, however, sugammadex did impair MRGPRX2-induced CCL2 release, suggesting that it may have some benefit in perhaps dampening less well-defined adverse effects of MRGPRX2-dependent anaphylaxis associated with the more slowly elaborated mast cell mediators.

Reversal of residual neuromuscular block with neostigmine or sugammadex and postoperative pulmonary complications: a prospective, randomised, double-blind trial in high-risk older patients.

BACKGROUND: Residual neuromuscular block is associated with an increased risk of postoperative pulmonary complications in retrospective studies. The aim of our study was to investigate prospectively the incidence of postoperative pulmonary complications after reversal with either sugammadex (SUG) or neostigmine (NEO) in high-risk older patients. METHODS: We randomly allocated 180 older patients with significant morbidity (ASA physical status 3) ≥75 yr old to reversal of rocuronium with either SUG or NEO. Adverse events in the recovery room and pulmonary complications (defined by a 5-point [0-4; 0=best to 4=worst] outcome score) on postoperative Days 1, 3, and 7 were compared between groups. RESULTS: Data from 168 patients aged 80 (4) yr were analysed; SUG vs NEO resulted in a reduced probability (0.052 vs 0.122) of increased pulmonary outcome score (impaired outcome) on postoperative Day 7, but not on Days 1 and 3. More patients in the NEO group were diagnosed with radiographically confirmed pneumonia (9.6% vs 2.4%; P=0.046). The NEO group showed a non-significant trend towards longer hospital length of stay across all individual centres (combined 9 vs 7.5 days), with a significant difference in Malaysia (6 vs 4 days; P=0.011). CONCLUSIONS: Reversal of rocuronium neuromuscular block with SUG resulted in a small, but possibly clinically relevant improvement in pulmonary outcome in a select cohort of high-risk older patients. CLINICAL TRIAL REGISTRATION: ACTRN12614000108617.

The mode of action of sugammadex on coagulation.

OBJECTIVE: To explore the mode of action (MoA) by which sugammadex interferes with coagulation. MATERIALS AND METHODS: The effect of sugammadex on various steps in the coagulation cascade including thrombin generation, factor Xa activity, and factor Xa generation was explored in human plasma. RESULTS: Sugammadex did not affect a conventional thrombin generation test (TGT), while it prolongs activated partial thromboplastin time (APTT) and prothrombin time (PT). However, a customized TGT with PT reagent revealed sugammadex effects. In addition, sugammadex prolonged a one-step prothrombinase-induced clotting time (PiCT) using human factor Xa. Furthermore, sugammadex interfered with factor Xa generation induced by an intrinsic and not by an extrinsic activator, nor by Russell's viper venom factor X (RVV-X). CONCLUSION: Adapted, rather than standard, experiments show that sugammadex is likely to decrease factor Xa activity in the common pathway and activation of factor X specifically in the intrinsic pathway.

Economic impact of improving patient safety using Sugammadex for routine reversal of neuromuscular blockade in Spain.

BACKGROUND: Neuromuscular blocking (NMB) agents are often administered to facilitate tracheal intubation and prevent patient movement during surgical procedures requiring the use of general anesthetics. Incomplete reversal of NMB, can lead to residual NMB, which can increase the risk of post-operative pulmonary complications. Sugammadex is indicated to reverse neuromuscular blockade induced by rocuronium or vecuronium in adults. The aim of this study is to estimate the clinical and economic impact of introducing sugammadex to routine reversal of neuromuscular blockade (NMB) with rocuronium in Spain. METHODS: A decision analytic model was constructed reflecting a set of procedures using rocuronium that resulted in moderate or deep NMB at the end of the procedure. Two scenarios were considered for 537,931 procedures using NMB agents in Spain in 2015: a scenario without sugammadex versus a scenario with sugammadex. Comparators included neostigmine (plus glycopyrrolate) and no reversal agent. The total costs for the healthcare system were estimated from the net of costs of reversal agents and overall cost offsets via reduction in postoperative pneumonias and atelectasis for which incidence rates were based on a Spanish real-world evidence (RWE) study. The model time horizon was assumed to be one year. Costs were expressed in 2019 euros (€) and estimated from the perspective of a healthcare system. One-way sensitivity analysis was carried out by varying each parameter included in the model within a range of +/- 50%. RESULTS: The estimated budget impact of the introduction of sugammadex to the routine reversal of neuromuscular blockade in Spanish hospitals was a net saving of €57.1 million annually. An increase in drug acquisition costs was offset by savings in post-operative pulmonary events, including 4806 post-operative pneumonias and 13,996 cases of atelectasis. The total cost of complications avoided was €70.4 million. All parameters included in the model were tested in sensitivity analysis and were favorable to the scenario with sugammadex. CONCLUSIONS: This economic analysis shows that sugammadex can potentially lead to cost savings for the reversal of rocuronium-induced moderate or profound NMB compared to no reversal and reversal with neostigmine in the Spanish health care setting. The economic model was based on data obtained from Spain and from assumptions from clinical practice and may not be valid for other countries.

Does Sugammadex Suppress Allergic Inflammation Due to Rocuronium in Animal Model of Rat?

INTRODUCTION AND OBJECTIVES: There are a few reports in the literature about the successful use of sugammadex in the treatment of hypersensitivity reactions caused by rocuronium; however, the pathophysiological mechanism is still unknown. This study aims to investigate the changes caused by rocuronium in the lung and the effect of sugammadex on these changes with biochemical, light microscopic and immunohistochemical parameters on a rat model. MATERIALS AND METHODS: For the study, 28-male Sprague-Dawley rats were randomly divided, seven of each, into four groups. Group C (control) received only 0. 9 % NaCl without any drug. Group R received rocuronium alone 1mg/kg. Group S received sugammadex alone 96 mg/kg. Group RS received rocuronium 1mg/kg and sugammadex 96 mg/kg. After 24 h later, the animals were sacrificed and their tissues were removed. Biochemical (IgE/CRP), light microscopic and immunohistochemical findings were recorded. RESULTS: Immunoglobulin E and CRP levels, peribronchial, alveolar septal lymphocytic infiltration, thickening of the alveolar membranes and bleeding sites in Group R were significantly higher than all the other groups. In Group RS, while these parameters were significantly lower than that of Group R and Group S, it was significantly higher than that of Group C. Total mast cells and tryptase-positive mast cells counts were significantly higher in Group R than in all other groups. In Group RS, these parameters were statistically lower than that of Group R and Group S, but higher than that of Group C. CONCLUSIONS: This study shows that allergic inflammatory changes due to rocuronium in the lungs of rats are reduced with sugammadex. These results support cases of anaphylaxis due to rocuronium which improved with sugammadex.

Sugammadex Reduces PACU Recovery Time after Abdominal Surgery Compared with Neostigmine.

OBJECTIVE: This study blindly evaluated sugammadex compared with neostigmine on length of stay in the postanesthesia care unit (PACU). METHODS: Fifty patients undergoing elective laparoscopic cholecystectomy or abdominal wall hernia repair consented to receive either sugammadex (2 mg/kg) or neostigmine (0.07 mg/kg) for the reversal of rocuronium neuromuscular blockade. Reversal agents were administered during surgical closing, and the train of four was measured until a twitch ratio of T4:T1 ≥ 0.9 was obtained to signify a robust reversal. Postreversal outcomes also were measured during PACU stay. Aldrete scores, pain visual analog scale score, and nausea were measured during the PACU stay. RESULTS: Patients receiving sugammadex experienced a shorter PACU stay at the time of discharge than patients receiving neostigmine, by an average of 12 minutes (P < 0.05). CONCLUSIONS: Sugammadex patients had a significantly shorter PACU stay.