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1.
Br J Anaesth ; 133(1): 16-18, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38879265

ABSTRACT

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.


Subject(s)
Intubation, Intratracheal , Neuromuscular Nondepolarizing Agents , Rocuronium , Sugammadex , Humans , Intubation, Intratracheal/methods , Rocuronium/administration & dosage , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Sugammadex/pharmacology , Androstanols/antagonists & inhibitors , Benzodiazepines/pharmacology , Fentanyl , Analgesics, Opioid , Naloxone , Rapid Sequence Induction and Intubation/methods
2.
Expert Opin Drug Saf ; 23(7): 845-853, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38938223

ABSTRACT

INTRODUCTION: Sugammadex, a novel selective antagonist of non-depolarizing neuromuscular blocking agents, has been shown to rapidly and effectively reverse moderate and deep paralysis in adults and pediatric patients over age 2, improving patient recovery and reducing the risk of postoperative complications. AREAS COVERED: Since the use of sugammadex in patients under age 2 is not widely studied, we aim to provide an overview on the drug's application and potential use in infants and neonates. There is a limited but growing body of evidence for the safe, efficacious use of sugammadex in children under age 2. Relevant studies were identified from the most updated data including case reports, clinical trials, systematic reviews, and meta analyses. EXPERT OPINION: The results suggest that at a dose of 2 to 4 mg/kg of sugammadex can be safely used to rapidly and effectively reverse neuromuscular blockade in neonates and infants; it is non-inferior based on incidence of adverse events compared to neostigmine. Additionally, sugammadex doses between 8 and 16 mg/kg may be used as a rescue agent for infants during 'can't intubate, can't ventilate' crisis. Overall, sugammadex offers new value in the perioperative care of patients under age 2, with further studies warranted to better understand its application and full effect in the pediatric population.


Subject(s)
Dose-Response Relationship, Drug , Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , Sugammadex , Humans , Sugammadex/administration & dosage , Sugammadex/adverse effects , Sugammadex/pharmacology , Infant , Neuromuscular Blockade/methods , Neuromuscular Blockade/adverse effects , Infant, Newborn , Age Factors , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/adverse effects , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Postoperative Complications/prevention & control , Neostigmine/administration & dosage , Neostigmine/adverse effects , Perioperative Care/methods
3.
J Med Chem ; 67(3): 2176-2187, 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38284525

ABSTRACT

Long-acting neuromuscular blocks followed by rapid reversal may provide prolonged surgeries with improved conditions by omitting repetitive or continuous administration of the neuromuscular blocking agent (NMBA), eliminating residual neuromuscular block and minimizing postoperative recovery, which, however, is not clinically available. Here, we demonstrate that imidazolium-based macrocycles (IMCs) and acyclic cucurbit[n]urils (ACBs) can form such partners by functioning as long-acting NMBAs and rapid reversal agents through a pseudo[2]catenation mechanism based on stable complexation with Ka values of over 109 M-1. In vivo experiments with rats reveal that, at the dose of 2- and 3-fold ED90, one IMC attains a duration of action corresponding to 158 or 442 min for human adults, covering most of prolonged surgeries. The block can be reversed by one ACB with recovery time significantly shorter than that achieved by sugammadex for reversing the block of rocuronium, the clinically most widely used intermediate-acting NMBA.


Subject(s)
Catenanes , Neuromuscular Blockade , gamma-Cyclodextrins , Adult , Humans , Animals , Rats , Sugammadex/pharmacology , Rocuronium
6.
Vet Anaesth Analg ; 51(1): 60-63, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38072747

ABSTRACT

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.


Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , gamma-Cyclodextrins , Dogs , Animals , Sugammadex/pharmacology , Rocuronium , gamma-Cyclodextrins/pharmacology , Retrospective Studies , Neuromuscular Nondepolarizing Agents/pharmacology , Androstanols/pharmacology , Time Factors , Neuromuscular Blockade/veterinary
7.
Microsc Res Tech ; 87(3): 506-515, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37933747

ABSTRACT

Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. The aim of this study is to investigate the teratogenic effects of sugammadex on neural tube and embryonic development in early chick embryos. In this study, 50 0-day fertile specific non-pathogenic (SPF) eggs were used. Fifty eggs were divided into 5 different groups, each consisting of 10 pieces. While no substance was given to the control group at the 28th hour of the study, 4 different doses of sugammadex were administered to the experimental groups, respectively 2, 4, 8, 16 mg/kg. Cranio-caudal lengths of embryos, somite numbers, average number of argyrophilic nucleolar regulatory regions (AgNOR) per nucleus, total AgNOR area/total nuclear area (TAA/NA) ratios, Caspase-3 H-Score results, and presence of neural tube defect were compared among the groups. While the mean cranio-caudal lengths, somite counts, TAA/NA ratios and AgNOR counts of the embryos were found to be statistically significantly lower than the control group, Caspase-3 H-Score mean results were found to be significantly higher (p < .05). In addition, it was observed that there was an increase in neural tube patency and developmental delay. As a result, sugammadex crossing the placenta was revealed to increase the release of proapopitotic molecules and disrupt the developmental stages of embryos. Thus, it was determined that sugammadex in increased developmental delay and incidence of neural tube defects in early chick embryos with increased dose dependent. Despite these results, the effects of sugammadex on fetal development in in vivo and in vitro environments should be studied with further studies. RESEARCH HIGHLIGHTS: Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. It has been observed that different doses of sugammadex increase the risk of neural tube defect development on chick embryos and slow the embryo development in a dose-dependent manner.


Subject(s)
Neural Tube Defects , Neural Tube , Animals , Chick Embryo , Neural Tube/pathology , Caspase 3 , Sugammadex/pharmacology , Neural Tube Defects/chemically induced , Neural Tube Defects/pathology , Embryonic Development
8.
Ann Ital Chir ; 94: 612-616, 2023.
Article in English | MEDLINE | ID: mdl-38131376

ABSTRACT

AIM: Neuromuscular muscle relaxants are still indispensable for surgical procedures requiring general anesthesia, and the use of these agents may result in postoperative residual curarization. Sugammadex may offer a distinct advantage to pediatric patients where residual neuromuscular blockade may be poorly tolerated. Sugammadex is approved for use in adults and children over two years. This is the main reason why large-scale studies could not be conducted in the group of patients younger than two years old. This study aimed to evaluate the efficacy and safety of sugammadex for reversing deep rocuronium-induced neuromuscular blockade in children under two years of age. METHODS: Pediatric patients younger than two years of age who underwent neurosurgery under sevoflurane anesthesia were included in the study. Neuromuscular block was achieved by the administration of rocuronium. It was antagonized by the administration of 5 mg/kg sugammadex and evaluated using train-of-four (TOF). Primary outcome measure was the time from sugammadex administration to return of the TOF ratio to 0,9. Postoperative adverse events were also recorded. RESULTS: Two hundred eighty patients (10 day-24 months of age; 3-18 kg) were included in this study. Reversal of deep rocuronium-induced neuromuscular block with sugammadex was rapid in all patients. No residual curarization or recurarization was observed. No adverse events or hypersensitivity reactions were observed after administration of sugammadex. CONCLUSION: Reversal of rocuronium-induced deep neuromuscular block in infants was rapid and safe. Sugammadex provided safe extubation in patients younger than two years of age who had undergone neurosurgery. Research Fund. KEY WORDS: Neuromuscular blockade, Neuromuscular monitoring, Pediatrics, Sugammadex.


Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , gamma-Cyclodextrins , Adult , Infant , Humans , Child , Child, Preschool , Rocuronium , Sugammadex/pharmacology , Neuromuscular Blockade/adverse effects , Neuromuscular Blockade/methods , gamma-Cyclodextrins/adverse effects , Neuromuscular Nondepolarizing Agents/adverse effects , Androstanols/adverse effects , Anesthesia, General , Anesthesia Recovery Period
9.
Sci Rep ; 13(1): 20776, 2023 11 27.
Article in English | MEDLINE | ID: mdl-38012277

ABSTRACT

Sugammadex reverses neuromuscular blockade by encapsulating steroidal neuromuscular blockers; therefore, it does not pharmacologically affect sedation levels. However, some clinicians avoid using it because of sudden unwanted acting out or patient arousal. Previous studies suggested sugammadex-induced awakening, but frontal muscle contraction after sugammadex administration compromised reliability of results obtained from EEG-based anesthesia depth monitoring tools like bispectral index (BIS). We hypothesized that sugammadex would affect patients' arousal depending on their baseline levels of sedation. We evaluated arousal signs after sugammadex administration with BIS between 25 - 35 and 45 - 55 under steady-state propofol-remifentanil anesthesia at the end of a surgery (n = 33 in each group). After sugammadex administration, twelve patients with a BIS of 45 - 55 showed clinical signs of awakening but none with a BIS of 25 - 35 (36.4% vs. 0%, P = 0.001). The distribution of the modified observer's assessment of alertness/sedation scale scores was also significantly different between the two groups (P < 0.001). Changes in the BIS were significantly greater in the BIS 45 - 55 than in the 25 - 35 group (median difference, 7; 95% CI 2 - 19, P = 0.002). Arousal after sugammadex was affected by patient sedation levels, and clinical signs of awakening appeared only in those with BIS 45 - 55. Unwanted arousal of the patient should be considered when using sugammadex under shallow anesthesia.Clinical trial registry number: Clinical Trial Registry of Korea ( https://cris.nih.go.kr ; Principal investigator: Jieae Kim; Registration number: KCT0006248; Date of first registration: 11/06/2021).


Subject(s)
Anesthesia , Neuromuscular Blockade , Propofol , Humans , Sugammadex/pharmacology , Propofol/pharmacology , Neuromuscular Blockade/methods , Remifentanil/pharmacology , Reproducibility of Results , Anesthesia/methods , Anesthetics, Intravenous , Arousal
10.
BMC Anesthesiol ; 23(1): 290, 2023 08 25.
Article in English | MEDLINE | ID: mdl-37626303

ABSTRACT

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).


Subject(s)
Evoked Potentials, Motor , Neuromuscular Diseases , Humans , Rocuronium , Sugammadex/pharmacology , Muscle Relaxation
11.
Vet Anaesth Analg ; 50(6): 485-491, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37648629

ABSTRACT

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.


Subject(s)
Neuromuscular Blockade , Rocuronium , Sugammadex , Animals , Dogs , Female , Male , Anesthesia/veterinary , Anesthetics , Neuromuscular Blockade/veterinary , Neuromuscular Nondepolarizing Agents/pharmacology , Prospective Studies , Rocuronium/pharmacology , Sugammadex/pharmacology , Cross-Over Studies
12.
Br J Anaesth ; 131(3): 523-530, 2023 09.
Article in English | MEDLINE | ID: mdl-37422414

ABSTRACT

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.


Subject(s)
Neuromuscular Blockade , Robotics , Adult , Humans , Male , Sugammadex/pharmacology , Prostatectomy , Electroencephalography , Androstanols
13.
Am J Vet Res ; 84(7)2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37253449

ABSTRACT

OBJECTIVE: To evaluate the effects of rocuronium and sugammadex on the patient state index (PSI) in dogs anesthetized with propofol. ANIMALS: 6 intact healthy male Beagles. PROCEDURES: Anesthesia was induced with and maintained on a propofol infusion. The estimated plasma propofol concentration (ePC) was recorded. Baseline PSI and train-of-four ratio (TOFR) readings were collected for 2 minutes in stable general anesthesia. Neuromuscular blockade (NMB) was induced with 0.6 mg/kg, IV, rocuronium, and full NMB was confirmed with a TOFR of 0. After 5 minutes, the neuromuscular function was restored with 4 mg/kg sugammadex, IV (reversal), and monitored for 5 minutes. Throughout the data collection, ePC, PSI, and TOFR were recorded every 15 seconds and compared with mixed-effect ANOVA. RESULTS: Baseline ePC, PSI, and TOFR were 3.63 ± 0.38, 41 ± 6, and 0.97 ± 0.08 µg/mL, respectively. There was no difference between the baseline of ePC and PSI from NMB or reversal. Compared to the baseline, the TOFR decreased to 0 with NMB (P < .001) and returned to 0.96 ± 0.08 (P = .721) on reversal. After 5 minutes, sugammadex fully reversed 5 out of 6 dogs to TOFR > 0.90 and partially reversed 1 animal to TOFR = 0.80. CLINICAL RELEVANCE: There was no evidence that NMB with rocuronium and sugammadex-induced reversal interfered with PSI readings under steady-state total intravenous anesthesia with propofol. Further evaluation of PSI is warranted to assess its utility in a clinical population to detect changes in levels of consciousness during NMB.


Subject(s)
Anesthetics , Neuromuscular Blockade , Propofol , gamma-Cyclodextrins , Male , Animals , Dogs , Rocuronium/pharmacology , Sugammadex/pharmacology , Neuromuscular Blockade/veterinary , gamma-Cyclodextrins/pharmacology , gamma-Cyclodextrins/therapeutic use , Propofol/pharmacology , Androstanols/pharmacology , Anesthesia, General/veterinary
14.
Fundam Clin Pharmacol ; 37(4): 786-793, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36880372

ABSTRACT

This experiment was intended to evaluate the effect of sugammadex on the cytotoxicity induced by glutamate, involving the nitric oxide and oxidative stress pathways. C6 glioma cells were used in the study. Glutamate was given to cells in the glutamate group for 24 h. Sugammadex at different concentrations was given to cells in the sugammadex group for 24 h. Cells in the sugammadex + glutamate group were pre-treated with sugammadex at various concentrations for 1 h and then exposed to glutamate for 24 h. XTT assay was used to assess cell viability. Levels of nitric oxide (NO), neuronal nitric oxide synthase (nNOS), total antioxidant (TAS), and total oxidant (TOS) in the cells were calculated using commercial kits. Apoptosis was detected by TUNEL assay. Sugammadex at concentrations of 50 and 100 µg/mL significantly enhanced the cell viability in C6 cells after the cytotoxicity induced by glutamate (p < 0.001). Moreover, sugammadex considerably decreased the levels of nNOS NO and TOS and the number of apoptotic cells and increased the level of TAS (p < 0.001). Sugammadex has protective and antioxidant properties on cytotoxicity and could be an effective supplement for neurodegenerative diseases such as Alzheimer and Parkinson if further research in vivo supports this claim.


Subject(s)
Glutamic Acid , Nitric Oxide , Nitric Oxide/metabolism , Glutamic Acid/toxicity , Glutamic Acid/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , Sugammadex/pharmacology , Cell Line , Oxidative Stress
16.
Gen Physiol Biophys ; 42(1): 67-75, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36705306

ABSTRACT

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.


Subject(s)
Reperfusion Injury , Rats , Animals , Sugammadex/pharmacology , Rats, Wistar , Reactive Oxygen Species , Reperfusion Injury/drug therapy , Ischemia , Stomach/pathology , Malondialdehyde , Oxidative Stress
17.
J Neurosurg Anesthesiol ; 35(2): 224-231, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-34839318

ABSTRACT

INTRODUCTION: Neuromuscular blockade suppresses transcranial electrical motor evoked potential (TceMEP) amplitude and is usually avoided during TceMEP monitoring. In this randomized controlled trial, we investigated whether rocuronium-induced suppression of TceMEP amplitude could be reversed by sugammadex in patients undergoing spine surgery. METHODS: Seventy-six patients undergoing spinal surgery were randomly allocated into sugammadex and control groups. In the sugammadex group, a rocuronium infusion was titrated to maintain moderate neuromuscular blockade (2 twitches on train-of-four) until dural opening when the rocuronium infusion was discontinued and 2 mg/kg sugammadex administered. In the control group, no neuromuscular blockade was administered after induction of anesthesia. The primary outcome was a comparison between sugammadex and control groups of mean TceMEP amplitudes in the abductor pollicis brevis muscles of both upper extremities 5 minutes after dural. Secondary outcomes included TceMEP amplitudes at 10, 20, 30, and 60 minutes after dural opening. RESULTS: Sixty-six patients were included in the analysis. TceMEP amplitudes were significantly greater in the sugammadex group (629 µV, interquartile range: 987 µV) than in the control group (502 µV, interquartile range: 577 µV; P =0.033) at 5 minutes after dural opening. TceMEP amplitudes were also greater in the sugammadex group at 10 minutes ( P =0.0010), 20 minutes ( P =0.003), 30 minutes ( P =0.001), and 60 minutes ( P =0.003) after dural opening. CONCLUSIONS: Moderate neuromuscular blockade induced by continuous infusion of rocuronium was effectively reversed by sugammadex. This suggests that sugammadex could be used to enhance TceMEP waveform monitoring during spine surgery requiring muscle relaxation.


Subject(s)
Neuromuscular Nondepolarizing Agents , gamma-Cyclodextrins , Humans , Sugammadex/pharmacology , Rocuronium , gamma-Cyclodextrins/pharmacology , Neuromuscular Nondepolarizing Agents/pharmacology , Evoked Potentials, Motor , Androstanols
18.
Korean J Anesthesiol ; 76(2): 152-159, 2023 04.
Article in English | MEDLINE | ID: mdl-36377331

ABSTRACT

BACKGROUND: Animal and other experimental studies have demonstrated increased block time and quality when α- and ß-cyclodextrin drugs are combined with local anesthetics. However, to our knowledge, no study has utilized γ-cyclodextrins in such a combination. In the present study, we used an animal model to evaluate the effects of different doses of the combined administration of γ-cyclodextrin (sugammadex) and bupivacaine on the duration of sciatic nerve blocks in rats. METHODS: Sciatic nerve blocks were performed with a 0.20 ml mixture in all groups. For the non-experimental groups, this mixture consisted of 0.2 ml saline (Sham group), 0.2 ml sugammadex (Group S), or 0.16 ml bupivacaine 0.5% and 0.04 ml saline (Group B). For the experimental groups, 0.16 ml bupivacaine 0.5% was administered along with 0.01 ml sugammadex and 0.03 ml saline (Group BS1), 0.02 ml sugammadex and 0.02 ml saline (Group BS2), or 0.04 ml sugammadex (Group BS4). Proprioception, nociception, and motor function were evaluated until the sciatic block was completely reversed. RESULTS: Motor, proprioceptive, and nociceptive blockades occurred within 5 min in all experimental groups. In Group BS4, the duration of the motor, proprioceptive, and nociceptive blockades was significantly increased compared with the other experimental groups. However, in Groups BS1 and BS2, only the duration of the nociceptive blockade was significantly increased. CONCLUSIONS: The combined administration of sugammadex and bupivacaine for sciatic nerve blocks in rats led to a significant increase in the duration of motor, proprioceptive, and nociceptive blockades.


Subject(s)
Bupivacaine , Nerve Block , Animals , Rats , Nociception , Sciatic Nerve/physiology , Sugammadex/pharmacology
19.
Br J Anaesth ; 130(3): 296-304, 2023 03.
Article in English | MEDLINE | ID: mdl-36535827

ABSTRACT

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.


Subject(s)
Neostigmine , Neuromuscular Blockade , Humans , Aged , Sugammadex/pharmacology , Neostigmine/adverse effects , Neuromuscular Blockade/methods , Postoperative Nausea and Vomiting/epidemiology , Postoperative Nausea and Vomiting/prevention & control , Postoperative Nausea and Vomiting/chemically induced , Length of Stay , Anesthesia Recovery Period , Ambulatory Care , Registries , Hospitals , Cholinesterase Inhibitors/pharmacology
20.
Anaesthesia ; 78(2): 180-187, 2023 02.
Article in English | MEDLINE | ID: mdl-36336462

ABSTRACT

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.


Subject(s)
Contraception , Progesterone , Adult , Humans , Female , Sugammadex/pharmacology , Contraception/methods , Estrogens , Prospective Studies
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