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1.
Chem Commun (Camb) ; 60(32): 4350-4353, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38546190

RESUMO

The binding affinity of pillar[6]MaxQ toward a panel of neuromuscular blockers and neurotransmitters was measured in phosphate buffered saline by isothermal titration calorimetry and 1H NMR spectroscopy. In vivo efficacy studies showed that P6MQ sequesters rocuronium and vecuronium and reverses their influence on the recovery of the train-of-four (TOF) ratio.


Assuntos
Fármacos Neuromusculares não Despolarizantes , Brometo de Vecurônio , Brometo de Vecurônio/farmacologia , Rocurônio/farmacologia , Androstanóis/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Calorimetria
2.
Clin Exp Pharmacol Physiol ; 51(3): e13836, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38302078

RESUMO

The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty-four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N-TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H-TBW). Patients with higher PBF and rocuronium were dosed based on fat-free mass (H-FFM). A train of four (TOF)-Watch acceleromyography monitor was used to measure the effects of the rocuronium. H-TBW (91.9 ± 28.8 s) had significantly shorter onset time than N-TBW and H-FFM (p = 0.003). H-TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25-0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time.


Assuntos
Fármacos Neuromusculares não Despolarizantes , Humanos , Rocurônio , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , China , Obesidade , Tecido Adiposo
3.
Vet Anaesth Analg ; 51(1): 60-63, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38072747

RESUMO

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.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Cães , Animais , Sugammadex/farmacologia , Rocurônio , gama-Ciclodextrinas/farmacologia , Estudos Retrospectivos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Fatores de Tempo , Bloqueio Neuromuscular/veterinária
4.
Magnes Res ; 36(2): 31-39, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37897256

RESUMO

Magnesium enhances the effects of neuromuscular blocking agents. However, there is a paucity of evidence demonstrating possible effects of magnesium on neostigmine-induced recovery from neuromuscular blockade with rocuronium. This study compared the profiles of recovery from neuromuscular blockade between groups treated with magnesium (Group M) and placebo controls (Group C). Sixty-four patients were randomly allocated to Group M or Group C. Patients in Group M received a loading dose of 50 mg/kg magnesium and continuous infusion of 15 mg/kg/hr. Patients in Group C received a comparable amount of saline. Rocuronium at 0.6 mg/kg was used for tracheal intubation and 0.1 mg/kg of rocuronium was additionally administered to maintain train-of-four (TOF) status of 2-3 during surgery. At the end of surgery, neostigmine (50 µg/kg) plus glycopyrrolate (10 µg/kg) were administered, and the recovery time for TOF ratios of 0.7, 0.8, and 0.9 was measured. The primary outcome was the time from neostigmine administration to recovery with a TOF ratio of 0.9. In addition, rocuronium onset time (time from administration of rocuronium to 95% suppression of the first TOF twitch response), additional requirements for rocuronium and spontaneous recovery period (the time from administration of rocuronium to reappearance of the first TOF twitch response) were also measured. Neostigmine-induced recovery time was comparable between Group M and Group C (10.6 ± 4.3 vs. 9.1 ± 5.0 min, respectively, p = 0.22). The rocuronium onset time was shorter in Group M, and the spontaneous recovery period was longer in Group M. The amount of additional rocuronium administered was 27% lower in Group M, but this difference was not significant. Magnesium was not shown to prolong neostigmine-induced recovery time from neuromuscular blockade with rocuronium, however, it enhanced the clinical effects of rocuronium.


Assuntos
Anestésicos , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Humanos , Rocurônio , Neostigmina/farmacologia , Neostigmina/uso terapêutico , Bloqueio Neuromuscular/efeitos adversos , Sulfato de Magnésio/farmacologia , Sulfato de Magnésio/uso terapêutico , Fármacos Neuromusculares não Despolarizantes/farmacologia , Magnésio , Androstanóis/farmacologia
5.
Vet Anaesth Analg ; 50(6): 485-491, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37648629

RESUMO

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.


Assuntos
Bloqueio Neuromuscular , Rocurônio , Sugammadex , Animais , Cães , Feminino , Masculino , Anestesia/veterinária , Anestésicos , Bloqueio Neuromuscular/veterinária , Fármacos Neuromusculares não Despolarizantes/farmacologia , Estudos Prospectivos , Rocurônio/farmacologia , Sugammadex/farmacologia , Estudos Cross-Over
6.
Vet Anaesth Analg ; 50(3): 204-210, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36967325

RESUMO

OBJECTIVE: To determine the median effective dose (ED50) and effective dose required to depress the twitch value by 95% (ED95) of rocuronium during alfaxalone anesthesia in dogs. STUDY DESIGN: A randomized, prospective, crossover experimental study. ANIMALS: A total of eight adult Beagle dogs (four female, four male), weighing 10.3-14.6 kg and aged 6-8 years. METHODS: The dogs were anesthetized three times with 1.25-fold the individual minimum infusion rate of alfaxalone at intervals of ≥ 14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC) and first twitch of TOF (T1C), a single bolus dose of rocuronium 100, 175 or 250 µg kg-1 (treatments R100, R175 or R250) was administered intravenously. The maximum suppression of the first twitch of TOF (T1) was recorded and calibrated with T1C to construct the dose-response curve, from which ED50 and ED95 were calculated. Time from rocuronium administration to TOF ratio/TOFRC > 0.9 (duration TOFR0.9) was recorded. RESULTS: ED50 and ED95 of rocuronium during alfaxalone anesthesia were 175 and 232 µg kg-1, respectively. The median (range) duration TOFR0.9 was longer in treatment R250 [10.1 (9.2-10.9) minutes] than in treatments R100 [3.1 (2.9-4.4) minutes; p < 0.0001] and R175 [7.7 (6.9-8.1) minutes; p < 0.0001]; and longer in treatment R175 than in treatment R100 (p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: The duration of TOFR0.9 correlated positively with the dosage of rocuronium, indicating that recovery time of rocuronium was also dose-dependent in dogs anesthetized with alfaxalone. The duration TOFR0.9 of rocuronium 250 µg kg-1 was 10 minutes during alfaxalone anesthesia in dogs.


Assuntos
Anestesia , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Cães , Masculino , Animais , Feminino , Rocurônio/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Estudos Prospectivos , Anestesia/veterinária , Bloqueio Neuromuscular/veterinária
7.
Vet Ophthalmol ; 26(5): 407-413, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36799561

RESUMO

OBJECTIVE: To compare the variability in the duration of action of a single dose of rocuronium or cisatracurium, and duration of subsequent top-up doses in anesthetized dogs. ANIMALS: Thirty dogs requiring ophthalmic surgery with neuromuscular block. PROCEDURES: Neuromuscular function was monitored with train-of-four (TOF) and acceleromyography. Dogs received an initial dose of rocuronium 0.6 mg/kg, or cisatracurium 0.15 mg/kg IV, which produced complete neuromuscular block. Upon return of the first response (T1) of TOF, a third of the initial dose was repeated. The duration of the initial dose and its variability were compared between agents. Duration of subsequent top-up doses was assessed with mixed effect models. Spontaneous (from last return of T1) or neostigmine-enhanced (from administration to complete recovery) recovery times were measured for each agent. RESULTS: Duration of action of the initial dose was [median (range)] 25 (10-60) min with rocuronium and 35 (15-45) min with cisatracurium (p = .231). The variability of rocuronium was 3.25 times larger than cisatracurium (p = .034). Duration of top-up doses did not vary for either agent. Spontaneous recovery was shorter for rocuronium [15 (10-20) min] than cisatracurium [25 (15-45) min] (p = .02). Neostigmine-enhanced recovery times were 5 (5-25) for rocuronium and 10 (5-10) for cisatracurium (p = .491). CONCLUSIONS: Duration of action for a single dose is significantly more variable with rocuronium than cisatracurium. Time to spontaneous recovery was longer for cisatracurium, and cases of unexpectedly long recovery times were observed with both agents. Objective monitoring is recommended.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Cães , Animais , Rocurônio/farmacologia , Bloqueio Neuromuscular/veterinária , Fármacos Neuromusculares não Despolarizantes/farmacologia , Neostigmina , Androstanóis/farmacologia , Atracúrio/farmacologia
8.
J Neurosurg Anesthesiol ; 35(2): 224-231, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34839318

RESUMO

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.


Assuntos
Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Sugammadex/farmacologia , Rocurônio , gama-Ciclodextrinas/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Potencial Evocado Motor , Androstanóis
9.
Eur J Drug Metab Pharmacokinet ; 48(1): 101-114, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36477706

RESUMO

BACKGROUND AND OBJECTIVES: Probability of target attainment (PTA) curves are commonly used to support dose recommendations of antibiotics for different patient groups. In this study we propose PTA analysis to optimize sugammadex dosing in children. METHODS: This study involved data from an observational cohort study of 30 American Society of Anesthesiologists (ASA) Physical Status I and II children undergoing surgery requiring muscle relaxation. All patients received 0.6 mg/kg rocuronium, with sugammadex administered at the end of surgery in three different doses (0.5, 1.0, and 2.0 mg/kg) to reverse the neuromuscular blockade. RESULTS: The data were analyzed using a population Bayesian-based approach. The developed model was used to simulate pharmacokinetic-pharmacodynamic profiles for different patient groups and dosing regimens before the PTA analysis was performed to translate these simulations into a clinically useful measure. The target was defined as neuromuscular blockade reversal measured by Train-of-Four (TOF ratio > 90%) at 1.5, 3, and 5 min post sugammadex dose. The sugammadex doses leading to 90% PTA were determined for different patients' body weights, rocuronium doses, and time gaps between rocuronium and sugammadex administration assuming the model, priors, and gathered data. For comparison, PTA curves for a range of clinical scenarios are provided to illustrate the usefulness of PTA analysis in selecting the appropriate dose for a given patient. CONCLUSIONS: The proposed PTA analysis is useful to support the sugammadex dose selection in different clinical scenarios. TRIAL REGISTRATION: The study was registered by ClinicalTrials.gov under number NCT04851574 on 21 April 2021.


Assuntos
Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Criança , Sugammadex , Rocurônio , gama-Ciclodextrinas/farmacologia , Teorema de Bayes , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Probabilidade
10.
Anaesth Intensive Care ; 51(1): 38-42, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36524300

RESUMO

Rocuronium bromide is a neuromuscular blocker in widespread use in anaesthesia, emergency and intensive care. Reports of reduced efficacy of a new different formulation of rocuronium bromide were submitted to Medsafe, the New Zealand Medicines and Medical Devices Safety Authority, in 2020. Given the requirement for rapid and predictable paralysis for patient safety the efficacy of the two available formulations of rocuronium bromide was investigated in an animal model. After ethics committee approval, 19 rats were anaesthetised and paralysis, defined as loss of tibialis anterior flexion on direct electrical stimulation of the sciatic nerve, was assessed by mechanomyography in response to ED90 doses of rocuronium.Paralysis was observed at a median of 12 seconds for the new different formulation: A, Hameln Pharma (interquartile range (IQR) 6-106 seconds) and 28 seconds for formulation B: Pfizer (IQR 12-68 seconds) P = 0.48. Offset of paralysis was observed after 293 seconds for formulation A (IQR 250-372 seconds) and 241 seconds for formulation B (IQR 220-263 seconds). While the differences observed were substantial, they were not statistically significant. Moreover, the direction of observed difference was towards a shorter median onset and longer offset for the newer formulation, a finding in the opposite direction to the initial clinical concern.Relevance to the clinical situation is indeterminate given the study was stopped at low numbers for futility and limitations around the clinical applicability of animal pharmacokinetics and dynamics. Nevertheless our findings provide some reassurance that the newly available different formulation of this critical use medication does not exhibit a substantial increase in time to onset.


Assuntos
Fármacos Neuromusculares não Despolarizantes , Animais , Ratos , Rocurônio , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Androstanóis/uso terapêutico , Fatores de Tempo , Paralisia/tratamento farmacológico , Modelos Animais
11.
Acta Vet Scand ; 64(1): 38, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36522634

RESUMO

BACKGROUND: Neuromuscular blocking agents are frequently administered to pigs used for research. In humans, administration of the drugs is not without risk and may result in accidental awareness under general anaesthesia and postoperative residual neuromuscular blockade that can lead to serious respiratory complications. Despite the extensive administration, the pharmacodynamics of neuromuscular blocking agents are not thoroughly studied in pigs. Therefore, this study investigates the neuromuscular response of two infusion rates of rocuronium, a commonly used non-depolarizing neuromuscular blocking agent. A group of 14 female Danish Landrace-Yorkshire-Duroc pigs used for supervised surgical training, weighing 40.3 ± 2.1 kg (mean ± SD), were included in the study. They received a loading dose of 0.85 mg/kg rocuronium intravenously followed by infusion of either 2.5 mg/kg/hour (L, low dose) or 5 mg/kg/hour (H, high dose) rocuronium for 30 min. Neuromuscular monitoring was performed with acceleromyography using train-of-four (TOF) stimulation. Onset time, time to reappearance of T1, T4, TOF ratio 90% and 100% were recorded. RESULTS: All pigs in group H experienced loss of T1 throughout rocuronium infusion, whereas six out of seven pigs in group L had reappearance of T1 during rocuronium infusion, with additional reappearance of T4 in three of these pigs. The time to recovery of TOF ratio 90% was 14.0 ± 5.4 (L) and 21.7 ± 6.1 (H) minutes and recovery to TOF ratio 100% was 18.7 ± 6.5 (L) and 27.9 ± 9.2 min (H) (mean ± SD). Substantial inter-animal variation in neuromuscular recovery time was observed. CONCLUSION: The large inter-animal variation in pharmacodynamic profiles emphasizes that individual neuromuscular monitoring and titration to effect should be used routinely in research protocols that include rocuronium. In addition to other important measures, these actions are key in order to avoid overdosing and limit the risk of residual neuromuscular blockade.


Assuntos
Recuperação Demorada da Anestesia , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Doenças dos Suínos , Feminino , Humanos , Suínos , Animais , Rocurônio , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Bloqueio Neuromuscular/veterinária , Bloqueio Neuromuscular/métodos , Recuperação Demorada da Anestesia/veterinária
12.
Int J Clin Pract ; 2022: 6840960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263238

RESUMO

Methods: This is a prospective, observational study. Patients between the ages of 18 and 65 with BMI of 18.5-34.9, who are expected to be under general anesthesia for less than 6 hours, were divided into 3 groups according to their BMI (Group 1 BMI = 18.5-24.9, Group 2 BMI = 25-29.9, Group 3 BMI = 30-34.9). These groups were randomly divided into 2 subgroups: Groups LBW; 1 LBW, 2 LBW, and 3 LBW were given rocuronium intubation dosages based on their LBW while control groups; 1K, 2K, and 3K were given 0.6 mg/kg rocuronium according to their total body weight. The data on the duration of action of rocuronium and its effects on the endotracheal intubation conditions were evaluated. Results: In Group 1, T1 time was found to be significantly longer (p=0.001). Intubation score and the use of additional rocuronium dose were found to be significantly higher in Group 1 LBW than in Group 1K (p=0.001). In Group 1, an additional rocuronium dose was needed to achieve optimal intubation conditions for subgroup 1 LBW. Rocuronium duration of action was found to be significantly longer in control groups 2 and 3, that received TBW-based dosage. Conclusion: In adult patients with a BMI of 18.5 and 24.9 BMI, we report optimal intubation conditions with the LBW-adjusted rocuronium dosage. This trial is registered with NCT05476952.


Assuntos
Androstanóis , Fármacos Neuromusculares não Despolarizantes , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Rocurônio , Androstanóis/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Intubação Intratraqueal , Peso Corporal
13.
Front Endocrinol (Lausanne) ; 13: 875597, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36004347

RESUMO

Background: Inducing and reversing neuromuscular block is essential to a positive outcome of thyroid surgery, with intraoperative neuromonitoring (IONM) being used to decrease recurrent and superior laryngeal nerve injuries and improve vocal outcome. Neostigmine is a non-specific broad-spectrum and inexpensive reversal agent for neuromuscular blocking agents (NMBAs). The aim of this porcine study was to explore the effect of neostigmine on electromyography (EMG) signal recovery profile following the commonly used NMBAs, cisatracurium and rocuronium. Methods: Twelve piglets were allocated into two groups with six piglets in each group. When stable baseline EMG signals were obtained, a neuromuscular block was induced by intravenous cisatracurium 0.2 mg/kg (group C) or rocuronium 0.6 mg/kg (group R) for each piglet. We compared laryngeal EMG tracing with spontaneous recovery (control) and neostigmine (0.04 mg/kg) reversal for each group. The time course of real-time laryngeal EMG signals was observed for 30 min from NMBA injection. Effects of neostigmine on EMG signal were assessed at 50% EMG recovery and by the maximum neuromuscular block recovery degree from the baseline value. Results: Neostigmine shortened the recovery time to 50% EMG amplitude in both group C (16.5 [2.5] vs. 29.0 [2.0] min, P<0.01) and group R (16.5[2.5] vs. 26.5 [1.5] min, P<0.05) compared to spontaneous recovery, respectively. Neostigmine reversal also enhanced the maximum degree of EMG amplitude recovery in both group C (83.6 [5.1] vs. 47.2 [6.1] %, P<0.01) and group R (85.6 [18.2]vs. 57.1 [6.3] %, P<0.05) compared to spontaneous recovery, respectively. The reversal effect of neostigmine did not differ significantly between cisatracurium and rocuronium. Conclusions: This porcine model demonstrated that neostigmine provides an adequate and timely IONM signal suppressed by both cisatracurium and rocuronium. These results can potentially expand the options for precision neuromuscular block management during IONM to improve vocal outcomes in thyroid surgery patients.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Androstanóis/farmacologia , Animais , Atracúrio/análogos & derivados , Eletromiografia , Neostigmina/farmacologia , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Rocurônio , Suínos
14.
BMC Anesthesiol ; 22(1): 117, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35459095

RESUMO

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 .


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Androstanóis/farmacologia , Eletromiografia , Humanos , Músculo Esquelético , Fármacos Neuromusculares não Despolarizantes/farmacologia , Estudos Prospectivos , Rocurônio , Sugammadex/farmacologia
16.
Anaesth Crit Care Pain Med ; 41(1): 101011, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34922064

RESUMO

BACKGROUND: Sickle cell disease is the most widespread genetic disease in the world. The chronic organ damage due to this disease could lead to variability of responses to the anaesthetic drugs. We analysed the pharmacodynamics response of rocuronium to sickle cell patients. METHODS: We observed and compared the onset time and clinical duration (time to recovery first twitch) of 0.6 mg kg-1 of rocuronium using a TOFscan® monitor, as well as the time before the first incremental dose (time to recovery second twitch), in a group of 22 homozygous sickle cell patients and a group of 23 controls, all programmed for laparoscopic surgical procedures. RESULTS: The onset time of rocuronium was longer in sickle cell patients [mean ± SD (extremes)], [6.3 ± 2.1 (1.8-10) min] than in the control group [2.5 ± 0.6 (1.4-3.5) min] (P < 0.01). The clinical duration was shorter in sickle cell patients [19.2 ± 7.1 (13-41) min] when compared to the control group [28.9 ± 6.9 (21-48) min] (P < 0.01). The time before the first incremental dose was shorter in the sickle cell patients group [27.7 ± 7.9 (19-49) min] compared to the control group [39.9 ± 8.7 (30-56) min] (P < 0.01). CONCLUSION: The onset time of rocuronium was significantly longer with a shorter duration of action in patients with sickle cell disease versus the general population.


Assuntos
Anemia Falciforme , Fármacos Neuromusculares não Despolarizantes , Androstanóis/farmacologia , Anemia Falciforme/tratamento farmacológico , Humanos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Rocurônio , Fatores de Tempo
17.
Vet Anaesth Analg ; 49(1): 36-44, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34893432

RESUMO

OBJECTIVE: To compare the effects of sevoflurane, propofol and alfaxalone on the neuromuscular blockade induced by a single intravenous bolus of rocuronium in dogs. STUDY DESIGN: A randomized, prospective, crossover experimental study. ANIMALS: A total of eight adult Beagle dogs (four female, four male), weighing 8.9-15.3 kg and aged 5-7 years. METHODS: The dogs were anesthetized three times with 1.25× minimum alveolar concentration of sevoflurane (SEVO treatment) and 1.25× minimum infusion rate of propofol (PROP treatment) or alfaxalone (ALFX treatment) at intervals of ≥14 days. Neuromuscular function was monitored with train-of-four (TOF) stimulation of the peroneal nerve by acceleromyography. After recording the control TOF ratio (TOFRC), a single bolus dose of rocuronium (1 mg kg-1) was administered intravenously. The times from rocuronium administration to achieving TOF count 0 (onset time), from achieving TOF count 0 to the reappearance of TOF count 4 (clinical blockade period), from 25% to 75% of TOFRC (recovery index) and from achieving TOF count 0 to TOF ratio/TOFRC >0.9 (total neuromuscular blockade duration) were recorded. RESULTS: The onset time and recovery index did not differ among the treatments. The median clinical blockade period was longer in the SEVO treatment [27.3 (26.0-30.3) minutes] than in PROP [16.6 (15.4-18.0) minutes; p = 0.002] and ALFX [22.4 (18.6-23.1) minutes; p = 0.017] treatments; and longer in the ALFX treatment than in the PROP treatment (p = 0.020). The mean total neuromuscular blockade duration was longer in the SEVO treatment (43.7 ± 9.9 minutes) than in PROP (25.1 ± 2.7 minutes; p < 0.001) and ALFX (32.5 ± 8.4 minutes; p = 0.036) treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with alfaxalone and propofol, sevoflurane prolonged rocuronium-induced neuromuscular blockade by a significantly greater extent in dogs.


Assuntos
Anestésicos Inalatórios , Éteres Metílicos , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Propofol , Androstanóis , Anestésicos Intravenosos , Animais , Cães , Feminino , Masculino , Bloqueio Neuromuscular/veterinária , Fármacos Neuromusculares não Despolarizantes/farmacologia , Pregnanodionas , Propofol/farmacologia , Estudos Prospectivos , Rocurônio , Sevoflurano
18.
Basic Clin Pharmacol Toxicol ; 130(1): 141-150, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34734679

RESUMO

Rocuronium is widely utilized in clinical general anaesthesia, and individual differences in pharmacology and clearance have been observed. Two hundred thirty-six Chinese patients undergoing selective thyroid/breast mass resection were studied. Total intravenous anaesthesia was induced with a single dose of propofol (2 mg·kg-1 ), sufentanil (0.5 µg·kg-1 ), and rocuronium (0.6 mg·kg-1 ) and maintained with propofol (3-5 mg·kg-1 ·h-1 ) and remifentanil (0.2-0.4 µg·kg-1 ·min-1 ). Intubation conditions and a train-of-four index of patients were utilized to assess the effects and duration of rocuronium. The data from 228 patients were analysed and reported. Genotypes NR1I2 rs2472677 C > T, NR1I2 rs6785049 G > A, SLCO1B1 rs4363657 T > C, SLCO1A2 rs4762699 T > C, and UGT1A1 rs4148323 G > A contributed to individual variation in rocuronium. Of the clinical variables tested, age, BMI, total dose of propofol, NR1I2 rs2472677, and SLCO1A2 rs4762699 correlated significantly (P < 0.05 for all) with the clinical duration or total clinical action time of rocuronium in a multiple linear regression model. No significant interactions were observed in intubation conditions. Genetic variations in NR1I2 rs2472677, NR1I2 rs6785049, SLCO1B1 rs4363657, SLCO1A2 rs4762699, and UGT1A1 rs4148323 were related to extensive interindividual variability in the clinical duration and total clinical action time of rocuronium.


Assuntos
Anestesia Geral/métodos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Rocurônio/farmacologia , Adulto , Povo Asiático , Doenças Mamárias/cirurgia , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Polimorfismo de Nucleotídeo Único , Propofol/administração & dosagem , Remifentanil/administração & dosagem , Rocurônio/administração & dosagem , Sufentanil/administração & dosagem , Doenças da Glândula Tireoide/cirurgia , Fatores de Tempo
20.
J Clin Monit Comput ; 36(2): 587-592, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33745069

RESUMO

The duration of action of extravasated rocuronium varies depending on the patient's comorbidities. In patients who receive high doses of non-depolarizing neuromuscular blocking agents subcutaneously, anesthesiologists should be aware of unexpected prolongation of the progress and recovery of neuromuscular block. In such cases, the depth and recovery of neuromuscular block should be objectively monitored to avoid residual neuromuscular block and recurarization.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Androstanóis , Humanos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Rocurônio , Sugammadex
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