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1.
Expert Opin Drug Saf ; 23(7): 845-853, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38938223

RESUMO

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.


Assuntos
Relação Dose-Resposta a Droga , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Sugammadex , Humanos , Sugammadex/administração & dosagem , Sugammadex/efeitos adversos , Sugammadex/farmacologia , Lactente , Bloqueio Neuromuscular/métodos , Bloqueio Neuromuscular/efeitos adversos , Recém-Nascido , Fatores Etários , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Complicações Pós-Operatórias/prevenção & controle , Neostigmina/administração & dosagem , Neostigmina/efeitos adversos , Assistência Perioperatória/métodos
2.
Dan Med J ; 71(6)2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38847412

RESUMO

INTRODUCTION: The effect of neuromuscular blocking agents may be reversed by administration of neostigmine, when two twitches are present using train-of-four (TOF) stimulation. However, in elderly patients, limited data are available about when to administer neostigmine. We hypothesised that time to two twitches after TOF (TOF-2) was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg. Also, we hypothesised that time to TOF-2 would be shorter after rocuronium 0.3 mg/kg than after rocuronium 0.6 mg/kg. METHODS: This was a secondary analysis of 50 elderly patients > 80 years; 16 patients received rocuronium 0.6 mg/kg, another 16 patients received rocuronium 0.9 mg/kg; and, finally, 18 patients received rocuronium 0.3 mg/kg. Patients received total intravenous anaesthesia, and neuromuscular block was monitored with acceleromyography. RESULTS: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg: 37 min. versus 59 min. (difference: 22 min. (95% confidence intervals (CI): 10 to 33 min.), p = 0.0007). Time to TOF-2 after rocuronium 0.3 mg/kg was shorter than after rocuronium 0.6 mg/kg: 19 min. versus 37 min. (difference: 18 min. (95% CI: 11 to 25 min.), p = 0.00006). However, only 33% of the patients receiving 0.3 mg/kg obtained full effect i.e. TOF-0. CONCLUSION: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after 0.9 mg/kg and shorter after rocuronium 0.3 mg/kg than after 0.6 mg/kg. FUNDING: This work was supported by departmental sources. TRIAL REGISTRATION: This study was a secondary analysis of two clinical trials. CLINICALTRIALS: gov (NCT04512313), (NCT03857750).


Assuntos
Período de Recuperação da Anestesia , Neostigmina , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Rocurônio , Humanos , Rocurônio/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Idoso de 80 Anos ou mais , Feminino , Masculino , Bloqueio Neuromuscular/métodos , Neostigmina/administração & dosagem , Fatores de Tempo , Monitoração Neuromuscular/métodos , Relação Dose-Resposta a Droga , Androstanóis/administração & dosagem
3.
Med Sci Monit ; 30: e942773, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38689479

RESUMO

BACKGROUND While many studies have been conducted on sugammadex sodium and neostigmine in patients undergoing general anesthesia, few have explored their effects in patients with interstitial lung diseases (ILDs). MATERIAL AND METHODS Sixty-three patients who underwent transbronchial cryobiopsy under general anesthesia were enrolled in a prospective randomized study. The patients were randomly divided into 2 groups: neostigmine combined with atropine group (group C, n=32) and sugammadex group (group S, n=31). Induction and maintenance of anesthesia were the same in both groups. Patients received rocuronium during anesthesia. At the end of the procedure, when the T2 of the train-of-four stimulation technique (TOF) monitoring appeared, neostigmine 0.04 mg/kg combined with atropine 0.02 mg/kg was injected intravenously in group C, and sodium sugammadex 2 mg/kg was injected intravenously in group S. Time from administration of muscle relaxant antagonist to recovery of TOF ratio (TOFr) to 0.9 and extubation time were recorded. The residual rate of neuromuscular blockade at 1, 3, 5, 7, and 10 min after extubation was calculated. RESULTS Compared to group C, group S had a significantly shorter recovery time of TOFr to 0.9 (4.0[2.0] min vs 14.0[11.0] min, P<0.001) and extubation time (4.0[3.0] min vs 11.0[7.0] min, P<0.001). The residual rate of neuromuscular blockade was remarkably lower in group S than in group C at 3, 5, and 7 min after extubation (3.2% vs 31%, 0% vs 25%, 0% vs 6%, P<0.05). CONCLUSIONS Sugammadex is more effective than neostigmine in reversing the muscle-relaxant effect of rocuronium bromide in patients with ILDs.


Assuntos
Doenças Pulmonares Intersticiais , Neostigmina , Bloqueio Neuromuscular , Sugammadex , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período de Recuperação da Anestesia , Biópsia/métodos , Broncoscopia/métodos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Neostigmina/uso terapêutico , Bloqueio Neuromuscular/métodos , Período Pós-Operatório , Estudos Prospectivos , Rocurônio , Sugammadex/uso terapêutico
4.
Br J Clin Pharmacol ; 90(7): 1667-1676, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38583490

RESUMO

AIMS: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. METHODS: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. RESULTS: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011. CONCLUSION: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated.


Assuntos
Pneumopatias , Neostigmina , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Complicações Pós-Operatórias , Rocurônio , Sugammadex , Humanos , Neostigmina/efeitos adversos , Neostigmina/administração & dosagem , Sugammadex/efeitos adversos , Sugammadex/administração & dosagem , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Bloqueio Neuromuscular/efeitos adversos , Bloqueio Neuromuscular/métodos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Rocurônio/administração & dosagem , Rocurônio/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Pneumopatias/prevenção & controle , Adulto , Respiração Artificial/efeitos adversos , Anestesia Geral/efeitos adversos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38615713

RESUMO

INTRODUCTION AND OBJECTIVES: Some studies investigating the effect of calcium on neostigmine-induced recovery of neuromuscular blockade have shown that this combination promotes neuromuscular recovery, but does not significantly affect the incidence of postoperative residual curarization and time to extubation. This study aimed to evaluate the effects of 10 mg/kg calcium chloride co-administered with neostigmine on early recovery and time to extubation. PATIENTS AND METHODS: This prospective, randomized, double-blinded, placebo-controlled study included 88 ASA I-II patients aged between 18 and 65 years who were scheduled for elective surgery lasting at least 1 h under general anaesthesia in which 10 mg/kg of calcium chloride or the same volume of normal saline was co-administered with 5 µg/kg of neostigmine at the end of surgery. Time to extubation (time from neostigmine administration to extubation), time from neostigmine administration to TOF ratio (TOFr) 0.9 (neuromuscular recovery), and the incidence of residual neuromuscular blockade (RNMB) and other adverse effects were recorded. RESULTS: Median (Q1, Q3) extubation time was significantly shorter in the calcium group vs. the placebo group (6.5 min [5.52-7.43] vs. 9.78 min [8.35-11]), P < .001. Median neuromuscular recovery time in the calcium group was 5 min vs. 7.1 min in the placebo group, P < .001. Patients in the calcium group had significantly higher TOFr and lower incidence of RNMB at 5 and 10 min vs. the placebo group, and no significant side effects. CONCLUSION: Calcium chloride at a dose of 10 mg/kg co-administered with neostigmine promotes early neuromuscular recovery and reduces time to extubation by about 32%.


Assuntos
Extubação , Período de Recuperação da Anestesia , Cloreto de Cálcio , Neostigmina , Bloqueio Neuromuscular , Neostigmina/administração & dosagem , Neostigmina/farmacologia , Humanos , Método Duplo-Cego , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Estudos Prospectivos , Cloreto de Cálcio/administração & dosagem , Cloreto de Cálcio/farmacologia , Fatores de Tempo , Adulto Jovem , Adolescente , Idoso , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/farmacologia
6.
BMC Anesthesiol ; 24(1): 123, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561654

RESUMO

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.


Assuntos
Sistema Cardiovascular , Recuperação Demorada da Anestesia , Bloqueio Neuromuscular , Idoso , Humanos , Neostigmina/farmacologia , Glicopirrolato , Atropina/farmacologia
8.
Neurol India ; 72(1): 148-150, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38443018

RESUMO

ABSTRACT: Infection is an important trigger of myasthenic crisis (MC), and those infections manifest with pneumonia and muscle involvement may result in more frequent MC. We report two myasthenia gravis (MG) patients with H1N1 infection, and highlight the reasons for deterioration. Two patients with MG had H1N1 infection. The diagnosis of MG was confirmed by neostigmine, repetitive nerve stimulation, and anti-acetylcholine receptor antibody tests. H1N1 was confirmed by nucleic acid detection study, and myositis by creatinine kinase. The patient with pneumonia and myositis had MC needing mechanical ventilation for 10 days, and the other patient without myositis did not have MC. They were treated with oseltamivir 75 mg twice daily for 5 days, and the patients with MC received ceftriaxone intravenously. Both the patients were on prednisolone and azathioprine, and none received prior H1N1 vaccination. The lady with MC with myositis was discharged on day 27 in wheelchair bound state, and the other one patient without myositis or MC was discharged on 6th day with full recovery. These patients highlight the need for evaluation for myositis along with pneumonia in the MG patients with H1N1 infection. Vaccination in MG patients on immunosuppression may be useful.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Miastenia Gravis , Miosite , Pneumonia , Humanos , Miastenia Gravis/complicações , Miosite/diagnóstico , Neostigmina
9.
Eur J Anaesthesiol ; 41(5): 374-380, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38497249

RESUMO

BACKGROUND: Residual neuromuscular blockade after surgery remains a major concern given its association with pulmonary complications. However, current clinical practices with and the comparative impact on perioperative risk of various reversal agents remain understudied. OBJECTIVE: We investigated the use of sugammadex and neostigmine in the USA, and their impact on postoperative complications by examining national data. DESIGN: This population-based retrospective study used national Premier Healthcare claims data. SETTING AND PARTICIPANTS: Patients undergoing total hip/knee arthroplasty (THA, TKA), or lumbar spine fusion surgery between 2016 and 2019 in the United States who received neuromuscular blocking agents. INTERVENTION: The effects of sugammadex and neostigmine for pharmacologically enhanced reversal were compared with each other and with controls who received no reversal agent. MAIN OUTCOMES: included pulmonary complications, cardiac complications, and a need for postoperative ventilation. Mixed-effects regression models compared the outcomes between neostigmine, sugammadex, and controls. We report odds ratios (OR) and 95% confidence intervals (CI). Bonferroni-adjusted P values of 0.008 were used to indicate significance. RESULTS: Among 361 553 patients, 74.5% received either sugammadex (20.7%) or neostigmine (53.8%). Sugammadex use increased from 4.4% in 2016 to 35.4% in 2019, whereas neostigmine use decreased from 64.5% in 2016 to 43.4% in 2019. Sugammadex versus neostigmine or controls was associated with significantly reduced odds for cardiac complications (OR 0.86, 95% CI, 0.80 to 0.92 and OR 0.83, 95% CI, 0.78 to 0.89, respectively). Both sugammadex and neostigmine versus controls were associated with reduced odds for pulmonary complications (OR 0.85, 95% CI, 0.77 to 0.94 and OR 0.91, CI 0.85 to 0.98, respectively). A similar pattern of sugammadex and neostigmine was observed for a reduction in severe pulmonary complications, including the requirement of invasive ventilation (OR 0.54, 95% CI, 0.45 to 0.64 and OR 0.53, 95% CI, 0.46 to 0.6, respectively). CONCLUSIONS: Population-based data indicate that sugammadex and neostigmine both appear highly effective in reducing the odds of severe life-threatening pulmonary complications. Sugammadex, especially, was associated with reduced odds of cardiac complications.


Assuntos
Bloqueio Neuromuscular , Procedimentos Ortopédicos , Humanos , Neostigmina/efeitos adversos , Sugammadex , Estudos Retrospectivos , Bloqueio Neuromuscular/efeitos adversos , Inibidores da Colinesterase/efeitos adversos
10.
J Chin Med Assoc ; 87(4): 448-452, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38391199

RESUMO

BACKGROUND: This study compared sugammadex and neostigmine as agents for routine neuromuscular blockade reversal in video-assisted thoracoscopic surgery (VATS) to determine the optimal choice that achieves a shorter operation time and improved turnover efficiency while enhancing postoperative outcomes and ensuring patient safety during thoracic surgery. METHODS: This prospective study, conducted from July 2022 to March 2023, compared the effect of sugammadex and neostigmine on operation time and turnover efficiency in VATS, involving 60 participants randomly assigned to either group, with the primary objective of identifying the optimal anesthesia reversal choice for improved outcomes and patient safety during thoracic surgery. RESULTS: In the study, the sugammadex group showed a significantly shorter total operation room occupancy time (130 ± 7 vs 157 ± 7 minutes; p = 0.009) than the neostigmine group. Patients in the neostigmine group had higher mean pulse rates when leaving the operation room (85 ± 3 vs 73 ± 3 beats/min; p = 0.002) and 120 minutes later in the postanesthesia care unit (76 ± 2 vs 68 ± 2; p = 0.016). CONCLUSION: This study's findings suggest that sugammadex may enhance total operating room occupancy time, operation turnover efficacy, and respiratory recovery outcomes in VATS, potentially improving patient care and anesthesia management.


Assuntos
Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , Neostigmina , Estudos Prospectivos , Sugammadex , Cirurgia Torácica Vídeoassistida
11.
PLoS One ; 19(2): e0291543, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38354108

RESUMO

Our previous work demonstrated that the anisodamine (ANI) and neostigmine (NEO) combination produced an antiseptic shock effect and rescued acute lethal crush syndrome by activating the α7 nicotinic acetylcholine receptor (α7nAChR). This study documents the therapeutic effect and underlying mechanisms of the ANI/NEO combination in dextran sulfate sodium (DSS)-induced colitis. Treating mice with ANI and NEO at a ratio of 500:1 alleviated the DSS-induced colitis symptoms, reduced body weight loss, improved the disease activity index, enhanced colon length, and alleviated colon inflammation. The combination treatment also enhanced autophagy in the colon of mice with DSS-induced colitis and lipopolysaccharide/DSS-stimulated Caco-2 cells. Besides, the ANI/NEO treatment significantly reduced INF-γ, TNF-α, IL-6, and IL-22 expression in colon tissues and decreased TNF-α, IL-1ß, and IL-6 mRNA levels in Caco-2 cells. Meanwhile, the autophagy inhibitor 3-methyladenine and ATG5 siRNA attenuated these effects. Furthermore, 3-methyladenine (3-MA) and the α7nAChR antagonist methyllycaconitine (MLA) weakened the ANI/NEO-induced protection on DSS-induced colitis in mice. Overall, these results indicate that the ANI/NEO combination exerts therapeutic effects through autophagy and α7nAChR in a DSS-induced colitis mouse model.


Assuntos
Colite , Neostigmina , Alcaloides de Solanáceas , Camundongos , Animais , Humanos , Neostigmina/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Interleucina-6/metabolismo , Células CACO-2 , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Autofagia , Sulfato de Dextrana/toxicidade , Colo/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
12.
Anesth Analg ; 138(5): 1043-1051, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190344

RESUMO

BACKGROUND: Sugammadex is not advised for patients with severe renal impairment, but has been shown in a variety of other populations to be superior to neostigmine for reversal of neuromuscular blockade. The objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus reversal of cisatracurium-induced neuromuscular blockade with neostigmine results in a faster return to a train-of-four ratio (TOFR) ≥90% in patients with severe renal impairment. METHODS: We conducted a prospective, randomized, blinded, controlled trial at a large county hospital. A total of 49 patients were enrolled. Inclusion criteria included patients age ≥18, American Society of Anesthesiologists (ASA) physical status III and IV, with a creatinine clearance <30 mL/min, undergoing general anesthesia with expected surgical duration ≥2 hours and necessitating neuromuscular blockade. Subjects received either cisatracurium 0.2 mg/kg or rocuronium 0.6 mg/kg for induction of anesthesia to facilitate tracheal intubation. Subjects were kept at moderate neuromuscular blockade during surgery and received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 10 µg/kg glycopyrrolate for reversal of neuromuscular blockade. Neuromuscular monitoring was performed with electromyography (TwitchView), and the TOFR was recorded every minute after administration of the reversal agent. The time from administration of neuromuscular reversal until the patient reached a TOFR ≥90% was recorded as the primary outcome. RESULTS: The mean time to recovery of TOFR ≥90% was significantly faster with sugammadex at 3.5 (±1.6) min compared with neostigmine at 14.8 (±6.1) min ( P < .0001; mean difference, 11.3 minutes; 95% confidence interval [CI], 9.0-13.5 minutes). There were no major adverse events in either group. CONCLUSIONS: In patients with severe renal impairment, neuromuscular blockade with rocuronium followed by reversal with sugammadex provides a significantly faster return of neuromuscular function compared to cisatracurium and neostigmine, without any major adverse effects.


Assuntos
Anestésicos , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Humanos , Inibidores da Colinesterase/efeitos adversos , Neostigmina/efeitos adversos , Bloqueio Neuromuscular/efeitos adversos , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Estudos Prospectivos , Rocurônio , Sugammadex , Adulto
13.
Biomol Biomed ; 24(2): 395-400, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-37715536

RESUMO

Postoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed. The cohort was dichotomized into two groups by reversal agent: 1) sugammadex and 2) neostigmine with glycopyrrolate. The primary outcome, POUR, was defined as unplanned postoperative bladder recatheterization. A propensity-adjusted analysis was performed to investigate the association between POUR and reversal agent by using inverse probability of treatment weighting to adjust for potential confounders. We identified 1,974 patients, of whom 1,586 (80.3%) received neostigmine-glycopyrrolate and 388 (19.7%) received sugammadex for reversal of neuromuscular blockade. The frequency of POUR was 24.8% (393/1,586) after reversal with neostigmine-glycopyrrolate and 18.3% (71/388) with sugammadex. Results from the propensity-adjusted analysis showed that sugammadex was associated with a lower POUR risk than neostigmine-glycopyrrolate (odds ratio 0.53, 95% confidence interval [CI] 0.37 - 0.76, P < 0.001). A post hoc analysis of sugammadex recipients who received glycopyrrolate for another indication showed a higher POUR risk than among those who did not receive glycopyrrolate (odds ratio 1.86, 95% CI 1.07 - 3.22, P = 0.03). Use of sugammadex to reverse aminosteroid neuromuscular blocking agents is associated with decreased risk of POUR after hysterectomy. A potential mechanism is the omission of glycopyrrolate, which is coadministered with neostigmine to mitigate unwanted cholinergic effects.


Assuntos
Fármacos Neuromusculares não Despolarizantes , Retenção Urinária , Adulto , Humanos , Feminino , Sugammadex/uso terapêutico , Neostigmina/efeitos adversos , Glicopirrolato/farmacologia , Estudos de Coortes , Retenção Urinária/induzido quimicamente , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Histerectomia
14.
J Chromatogr Sci ; 62(3): 213-221, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37207317

RESUMO

A stability indicating RP-HPLC method is suggested for determination of Glycopyrrolate-Neostigmine (GLY/NEO) in bulk drugs and injection formulation. GLY/NEO were eluted from a Chromolith High Resolution RP-18e (100 mm×4.6 mm) with buffer solution (pH 3.0) as mobile phase A and a mixture of HPLC grade acetonitrile and water mixture (90:10) as mobile phase B. The gradient was optimized with a flowrate of 0.5 mL/min and wavelength of 222 nm. A complete analytical method validation was effectively carried out as per ICH Q2 (R1) guidelines. Recovery studies were performed at 50-150% level of working concentrations, and results were in the range of 99-101%. The linearity was detected in the range of LOQ to 200% of the specification limits i.e., 0.5% each for NEO and GLY, 0.01% for NEO Impurity B and 1.0% for rest of the impurities with respect to the test concentration of the respective components. For stability study, various stress conditions such as acid, base, oxidation and thermal as per ICH guidelines were studied. The high recovery and low relative standard deviation confirm the suitability of proposed method that can be employed for the routine analysis in bulk and pharmaceutical formulation.


Assuntos
Glicopirrolato , Neostigmina , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos
15.
J Clin Anesth ; 93: 111344, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38007845

RESUMO

STUDY OBJECTIVE: Perioperative neuromuscular blocking agents are pharmacologically reversed to minimize complications associated with residual neuromuscular block. Neuromuscular block reversal with anticholinesterases (e.g., neostigmine) require coadministration of an anticholinergic agent (e.g., glycopyrrolate) to mitigate muscarinic activity; however, sugammadex, devoid of cholinergic activity, does not require anticholinergic coadministration. Single-institution studies have found decreased incidence of post-operative urinary retention associated with sugammadex reversal. This study used a multicenter database to better understand the association between neuromuscular block reversal technique and post-operative urinary retention. DESIGN: Retrospective cohort study utilizing large healthcare database. SETTING: Non-profit, non-governmental and community and teaching hospitals and health systems from rural and urban areas. PATIENTS: 61,898 matched adult inpatients and 95,500 matched adult outpatients. INTERVENTIONS: Neuromuscular block reversal with sugammadex or neostigmine plus glycopyrrolate. MEASUREMENTS: Incidence of post-operative urinary retention by neuromuscular block reversal agent and the independent association of neuromuscular block reversal technique and risk of post-operative urinary retention. MAIN RESULTS: The incidence of post-operative urinary retention was 2-fold greater among neostigmine with glycopyrrolate compared to sugammadex patients (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients; both p < 0.0001). Multivariable logistic regression identified reversal with neostigmine to be independently associated with greater risk of post-operative urinary retention (inpatients: odds ratio, 2.20; 95% confidence interval, 2.00 to 2.41; p < 0.001; outpatients: odds ratio, 2.57; 95% confidence interval, 2.13 to 3.10; p < 0.001). Post-operative urinary retention-related visits within 2 days following discharge were five-fold higher among those reversed with neostigmine than sugammadex among inpatients (0.05% vs. 0.01%, respectively; p = 0.018) and outpatients (0.5% vs. 0.1%; p < 0.0001). CONCLUSION: Though this study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk, additional studies are needed to fully understand the association.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Retenção Urinária , Adulto , Humanos , Neostigmina/efeitos adversos , Sugammadex/efeitos adversos , Bloqueio Neuromuscular/efeitos adversos , Bloqueio Neuromuscular/métodos , Retenção Urinária/induzido quimicamente , Retenção Urinária/epidemiologia , Glicopirrolato , Estudos Retrospectivos , Inibidores da Colinesterase/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Hospitais
17.
Br J Anaesth ; 132(1): 107-115, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38036323

RESUMO

BACKGROUND: Residual neuromuscular block is associated with increased patient morbidity. Therefore prevention of residual neuromuscular block is an important component of general anaesthesia where neuromuscular blocking agents are used. Whereas sugammadex improves reversal based on neuromuscular twitch monitoring parameters, there have been no prospective, adequately powered definitive studies demonstrating that sugammadex is also associated with less patient morbidity. METHODS: We performed a systematic review of randomised trials comparing sugammadex with anticholinesterase-based reversal or placebo reversal that reported important patient outcomes beyond the postanaesthesia care unit. RESULTS: We identified 43 articles, including 5839 trial participants. Only one trial reported days alive and out of hospital to 30 days (DAOH-30), which showed that the number of DAOH-30 was similar in those allocated to sugammadex compared with neostigmine-based reversal (25 days [19-27] vs 24 days [21-27], median difference 0.00 [-2.15 to 2.15]). Pooled analyses of data from 16 trials showed an estimated odds ratio (OR) for postoperative pulmonary complications of 0.67 (95% confidence interval 0.47-0.95) with sugammadex use. Pooled analysis showed that pneumonia (eight trials OR 0.51 [0.24-1.01] with sugammadex use), hospital length of stay (23 trials, mean difference -0.31 [-0.84 to 0.22] with sugammadex use), and patient-reported quality of recovery (11 trials, varied depending on metric used) are similar in those allocated to sugammadex vs control. The difference seen in mortality (11 trials, OR 0.39 [0.15-1.01] with sugammadex use) would be considered to be clinically significant and warrants further investigation, however, the rarity of these events precludes drawing definitive conclusions. CONCLUSION: Although few trials reported on DAOH-30 or important patient outcomes, sugammadex is associated with a reduction in postoperative pulmonary complications, however, this might not translate to a difference in hospital length of stay, patient-reported quality of recovery, or mortality. CLINICAL TRIAL REGISTRATION: PROSPERO database (CRD42022325858).


Assuntos
Recuperação Demorada da Anestesia , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Humanos , Sugammadex , Recuperação Demorada da Anestesia/prevenção & controle , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Neostigmina/uso terapêutico , Inibidores da Colinesterase , Complicações Pós-Operatórias/prevenção & controle , Anestesia Geral/efeitos adversos , Morbidade
18.
Brain Res ; 1825: 148713, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38097126

RESUMO

The presence of the cholinergic system in the brain areas implicated in the precipitation of obsessive-compulsive behavior (OCB) has been reported but the exact role of the central cholinergic system therein is still unexplored. Therefore, the current study assessed the effect of cholinergic analogs on central administration on the marble-burying behavior (MBB) of mice, a behavior correlated with OCB. The result reveals that the enhancement of central cholinergic transmission in mice achieved by intracerebroventricular (i.c.v.) injection of acetylcholine (0.01 µg) (Subeffective: 0.1 and 0.5 µg), cholinesterase inhibitor, neostigmine (0.1, 0.3, 0.5 µg/mouse) and neuronal nicotinic acetylcholine receptor agonist, nicotine (0.1, 2 µg/mouse) significantly attenuated the number of marbles buried by mice in MBB test without affecting basal locomotor activity. Similarly, central injection of mAChR antagonist, atropine (0.1, 0.5, 5 µg/mouse), nAChR antagonist, mecamylamine (0.1, 0.5, 3 µg/mouse) per se also reduced the MBB in mice, indicative of anti-OCB like effect of all the tested cholinergic mAChR or nAChR agonist and antagonist. Surprisingly, i.c.v. injection of acetylcholine (0.01 µg), and neostigmine (0.1 µg) failed to elicit an anti-OCB-like effect in mice pre-treated (i.c.v.) with atropine (0.1 µg), or mecamylamine (0.1 µg). Thus, the findings of the present investigationdelineate the role of central cholinergic transmission in the compulsive-like behavior of mice probably via mAChR or nAChR stimulation.


Assuntos
Acetilcolina , Receptores Nicotínicos , Camundongos , Animais , Mecamilamina/farmacologia , Acetilcolina/farmacologia , Neostigmina/farmacologia , Inibidores da Colinesterase/farmacologia , Agonistas Nicotínicos/farmacologia , Atropina/farmacologia , Receptores Nicotínicos/fisiologia , Comportamento Animal
19.
Anesth Analg ; 138(3): 589-597, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100389

RESUMO

BACKGROUND: The goal of this study was to investigate the efficacy of neostigmine on postoperative cognitive dysfunction (POCD) and determine its effect on systematic markers of oxidative stress in older patients. METHODS: This double-blind placebo-controlled trial enrolled 118 elderly patients (≥65 years) undergoing noncardiac surgeries who were allocated to a neostigmine treatment group (0.04 mg/kg) or a placebo control group (normal saline) postoperatively. POCD was diagnosed if the Z -scores for the mini-mental state examination and the Montreal Cognitive Assessment were both ≤-1.96. Postoperative serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were also compared. Multivariable regression analysis with dose adjustment of atropine was used to demonstrate the influence of neostigmine on the incidence of POCD. RESULTS: Patients receiving neostigmine had a significantly reduced incidence of POCD compared to patients who were treated with placebo on the first day after surgery (-22%, 95% confidence interval [CI], -37 to -7), but not on the third (8%, 95% CI, -4 to 20) or seventh day after surgery (3%, 95% CI, -7 to 13). Postoperative plasma MDA levels were significantly lower ( P = .016), but SOD and BDNF levels were increased ( P = .036 and .013, respectively) in the neostigmine group compared to the control group on the first day after surgery. CONCLUSIONS: Neostigmine reduced POCD on the first day after noncardiac surgery in older patients. Neostigmine treatment inhibited oxidative stress and increased serum BDNF levels. There was no significant influence of neostigmine on POCD on the third or seventh day after surgery. The clinical influence of neostigmine on POCD should be further investigated.


Assuntos
Disfunção Cognitiva , Complicações Cognitivas Pós-Operatórias , Idoso , Humanos , Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva/complicações , Neostigmina/efeitos adversos , Complicações Cognitivas Pós-Operatórias/induzido quimicamente , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Superóxido Dismutase , Método Duplo-Cego
20.
Front Immunol ; 14: 1256089, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106406

RESUMO

Objective: To explore the clinical manifestations of glutamic acid decarboxylase 65 (GAD65) antibody-positive patients with extraocular symptoms and the possible mechanism. Method: Assays for the presence of GAD65 antibodies were performed on patients' serum and cerebral spinal fluid (CSF). The brain and ocular structures involved in eye movement were assessed via magnetic resonance imaging (MRI). Tests such as electromyography (EMG), particularly repetitive nerve stimulation (RNS), and neostigmine tests were utilized for differential diagnosis. Additionally, the interaction of GAD65 antibodies with muscle tissue was confirmed using immunofluorescence techniques. Result: Each patient exhibited symptoms akin to extraocular myasthenia gravis (MG), with two individuals reporting diplopia and two experiencing ptosis. GAD65 antibodies were detected in either the serum or CSF, which were shown to bind with monkey cerebellum slides and mouse muscle slides. Neuroimaging of the brain and extraocular muscles via MRI showed no abnormalities, and all patients tested negative for the neostigmine test, RNS via EMG, and the presence of MG antibodies. However, thyroid-related antibodies were found to be abnormal in four of the patients. Conclusion: Our results showed that GAD65 antibodies are not only associated with encephalitis, cerebellum ataxia or stiff-person syndrome caused by the decrease of GABAergic transmission but also diplopia and ptosis. Therefore, we should pay more attention to extraocular muscle paralysis patients without pathogenic antibodies directed against the components of neuromuscular junctions.


Assuntos
Miastenia Gravis , Músculos Oculomotores , Animais , Camundongos , Humanos , Diplopia , Neostigmina , Anticorpos , Miastenia Gravis/diagnóstico , Paralisia
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