RESUMO
RATIONALE: We present the first case of a patient with severe aortic stenosis who developed anaphylactic shock and was successfully treated with adrenaline and landiolol, a highly selective ß1-receptor blocker, to prevent disruption of the myocardial oxygen supply-demand balance caused by tachycardia. PATIENT CONCERNS: An 86-year-old woman was scheduled for simultaneous anterior-posterior fixation for a burst fracture of the 12th thoracic vertebra; 200âmg sugammadex, a neuromuscular blocking agent antagonist, was administered postoperatively, and she was extubated without complications. However, 6âmin after extubation, her blood pressure decreased abruptly to 55/29âmm Hg, and her heart rate increased to 78âbpm. Then, we intervened with fluid loading, an increased dose of noradrenaline, and phenylephrine administration. However, her blood pressure did not increase. DIAGNOSES: A general observation revealed urticaria on the lower leg; thus, we suspected anaphylactic shock due to sugammadex administration. INTERVENTIONS: We carefully administered 2 doses of 0.05âmg adrenaline and simultaneously administered landiolol at 60âµg/kg/min to suppress adrenaline-induced tachycardia. Adrenaline administration resulted in a rapid increase in blood pressure to 103/66âmm Hg and a maximum heart rate of 100âbpm, suppressing excessive tachycardia. OUTCOMES: The patient's general condition was stable after the intervention, and circulatory agonists could be discontinued the following day. She was discharged from the intensive care unit on the fourth postoperative day. LESSONS: Landiolol may help control the heart rate of patients with aortic stenosis and anaphylactic shock. The combined use of landiolol and adrenaline may improve patient outcomes; however, their efficacy and risks must be evaluated by studying additional cases.
Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Anafilaxia/induzido quimicamente , Epinefrina/uso terapêutico , Morfolinas/uso terapêutico , Sugammadex/efeitos adversos , Ureia/análogos & derivados , Idoso de 80 Anos ou mais , Anafilaxia/tratamento farmacológico , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/tratamento farmacológico , Rocurônio/antagonistas & inibidores , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/cirurgia , Ureia/uso terapêuticoRESUMO
High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients' outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.
Assuntos
Laparoscopia/métodos , Bloqueio Neuromuscular/métodos , Sugammadex/administração & dosagem , Humanos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Fármacos Neuromusculares não Despolarizantes/farmacologia , Procedimentos Cirúrgicos Robóticos/métodos , Rocurônio/antagonistas & inibidores , Rocurônio/farmacologia , Sugammadex/farmacologia , Brometo de Vecurônio/antagonistas & inibidores , Brometo de Vecurônio/farmacologiaRESUMO
INTRODUCTION AND OBJECTIVES: There are a few reports in the literature about the successful use of sugammadex in the treatment of hypersensitivity reactions caused by rocuronium; however, the pathophysiological mechanism is still unknown. This study aims to investigate the changes caused by rocuronium in the lung and the effect of sugammadex on these changes with biochemical, light microscopic and immunohistochemical parameters on a rat model. MATERIALS AND METHODS: For the study, 28-male Sprague-Dawley rats were randomly divided, seven of each, into four groups. Group C (control) received only 0. 9 % NaCl without any drug. Group R received rocuronium alone 1mg/kg. Group S received sugammadex alone 96 mg/kg. Group RS received rocuronium 1mg/kg and sugammadex 96 mg/kg. After 24 h later, the animals were sacrificed and their tissues were removed. Biochemical (IgE/CRP), light microscopic and immunohistochemical findings were recorded. RESULTS: Immunoglobulin E and CRP levels, peribronchial, alveolar septal lymphocytic infiltration, thickening of the alveolar membranes and bleeding sites in Group R were significantly higher than all the other groups. In Group RS, while these parameters were significantly lower than that of Group R and Group S, it was significantly higher than that of Group C. Total mast cells and tryptase-positive mast cells counts were significantly higher in Group R than in all other groups. In Group RS, these parameters were statistically lower than that of Group R and Group S, but higher than that of Group C. CONCLUSIONS: This study shows that allergic inflammatory changes due to rocuronium in the lungs of rats are reduced with sugammadex. These results support cases of anaphylaxis due to rocuronium which improved with sugammadex.
Assuntos
Hipersensibilidade/complicações , Inflamação/prevenção & controle , Pulmão/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Rocurônio/efeitos adversos , Sugammadex/farmacologia , Anafilaxia/induzido quimicamente , Anafilaxia/prevenção & controle , Animais , Proteína C-Reativa/análise , Modelos Animais de Doenças , Hemorragia/induzido quimicamente , Imunoglobulina E/análise , Inflamação/induzido quimicamente , Inflamação/imunologia , Linfócitos , Masculino , Mastócitos/citologia , Mastócitos/enzimologia , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Alvéolos Pulmonares/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Rocurônio/antagonistas & inibidores , Triptases/análiseRESUMO
Introduction: Sugammadex has been shown to be associated with prolongation of prothrombin time and activated partial thromboplastin time. However, it is not known whether it could be associated with enhancing postoperative hypocoagulation. The objective of this study was to analyze the effect of 4 mg/kg of sugammadex on thromboelastography (TEG) parameters in surgical patients. Methods: After Institutional Review Board approval, a prospective double-blinded randomized controlled study was conducted between September 2016 and April 2017. Sixty adult patients scheduled for laparoscopic abdominal surgery were randomly allocated to receive either sugammadex 4 mg/kg (sugammadex group) or pyridostigmine 0.15 mg/kg in combination with glycopyrrolate 0.4 mg (control group) to reverse rocuronium-induced neuromuscular blockade at the completion of surgery. Blood samples were collected three time points; After the final suture of surgery (baseline) (T1), and at 10 min (T2) and 1 h (T3) after administration of the study drug. Whole blood was analyzed by TEG using TEG 5000 (Hemonetics Corp, Braintree, MA, USA). The primary endpoints were comparison of coagulation time (K, time to 20 mm clot amplitude), R (reaction time), alpha angle, and maximal amplitude (MA) between two groups. Results: Coagulation time was significantly prolonged in sugammadex group after 10 min of the study drug administration compared to control group (mean value 1.3 ± 0.4 vs. 1.5 ± 0.4, P = 0.03). However, R, alpha angle and MA value were not different between two groups. Conclusions: Sugammadex 4 mg/kg showed an increase in coagulation time in surgical patients. Physician should aware the potential enhancement of hypocoagulation by sugammadex in the setting of high risk of postoperative bleeding.
Assuntos
Laparoscopia/métodos , Bloqueio Neuromuscular/métodos , Hemorragia Pós-Operatória/prevenção & controle , Rocurônio/antagonistas & inibidores , Sugammadex/administração & dosagem , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Glicopirrolato/administração & dosagem , Glicopirrolato/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/diagnóstico , Estudos Prospectivos , Tempo de Protrombina , Brometo de Piridostigmina/administração & dosagem , Brometo de Piridostigmina/efeitos adversos , Rocurônio/administração & dosagem , Sugammadex/efeitos adversos , Tromboelastografia , Adulto JovemRESUMO
This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for reversal of moderate or deep neuromuscular block (M-NMB or D-NMB) in adults with morbid obesity. Adults with body mass index ≥ 40 kg/m2 , ABW ≥ 100 kg, and American Society of Anesthesiologists (ASA) Class 3 were stratified by NMB agent (rocuronium or vecuronium) and randomized 1:1:1:1:1 to (i) M-NMB, sugammadex 2 mg/kg ABW; (ii) M-NMB, sugammadex 2 mg/kg IBW; (iii) M-NMB, neostigmine 5 mg + glycopyrrolate 1 mg; (iv) D-NMB, sugammadex 4 mg/kg ABW; and (v) D-NMB, sugammadex 4 mg/kg IBW. Plasma samples for sugammadex quantification were collected predose, 2, 5, 15, 60, and 120 minutes, and 4, 6 hours postdose. Natural log PK parameters were analyzed using linear fixed effect model with treatment, mode (ABW and IBW), and mode by treatment interaction as fixed terms. The sugammadex PK profile showed rapid distribution followed by monophasic decline consistent with a two-compartment model examined by dose and mode. Absolute sugammadex exposures were ~ 50% higher in the ABW vs. IBW group; dose-independent parameters (clearance and volume of distribution) and terminal half-life remained constant. Sugammadex PK parameter values increased in dose-dependent, linear manner following dosing by ABW or IBW, such that PK continues to be predictive across the clinical dose range. In conjunction with previously published results showing faster recovery with ABW vs. IBW dosing across NMB agent and depth of NMB, these PK findings continue to support dosing by ABW in patients with morbid obesity irrespective of depth of NMB.
Assuntos
Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Obesidade Mórbida/cirurgia , Sugammadex/farmacocinética , Adulto , Índice de Massa Corporal , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Peso Corporal Ideal , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Obesidade Mórbida/metabolismo , Rocurônio/administração & dosagem , Rocurônio/antagonistas & inibidores , Sugammadex/administração & dosagem , Brometo de Vecurônio/administração & dosagem , Brometo de Vecurônio/antagonistas & inibidoresRESUMO
BACKGROUND: Early extubation can reduce pulmonary complications in children undergoing cardiac surgery. The aim of this study is to evaluate the effects of sugammadex for postoperative respiratory management in children with congenital heart disease. METHODS: Sixty children with congenital heart disease undergoing elective cardiac surgery were divided into group S and group C (30 children in each group). When post tetanic twitches count (PTC)â¯=â¯1-2 and train-of-four (TOF)â¯=â¯0, the children in group S received sugammadex4â¯mg/kg for reversal of neuromuscular block at the end of surgery, and the children in group C received the same volume of normal saline. The recovery time to TOF of 0.9, the mechanical ventilation and extubation times were recorded. On the other side, the hemodynamic parameters before and 5â¯min after administration, and side effects were also recorded. The levels of C-reactive protein (CRP) and procalcitonin (PCT) before and 24â¯h after surgery were measured. RESULTS: The recovery time to TOF of 0.9 and extubation time were significantly shorter in the group S than in the group C (4.2⯱â¯1.4 vs 108.2⯱â¯26.7â¯min, 66.3⯱â¯6.5 vs 171.6⯱â¯23.1â¯min, respectively, Pâ¯<⯠0.01). The CRP and PCT levels were found to be increased in both groups at postoperative 24â¯h than before surgery. Further, the levels of PCT and CRP at postoperative 24â¯h were lower in group S when compared to group C (median, 7 vs 17.5â¯mg/ml, 1.76 vs 5.22â¯ng/ml, respectively, Pâ¯<⯠0.05). There were no statistical differences observed between the two groups (P> 0.05) with respect to side effects. CONCLUSION: Sugammadex is rapid and effective in reversing rocuronium-induced neuromuscular block, and significantly reduces the extubation time and the release of postoperative CRP and PCT in children with congenital heart diseases.
Assuntos
Cardiopatias Congênitas/cirurgia , Bloqueio Neuromuscular/métodos , Rocurônio/administração & dosagem , Sugammadex/administração & dosagem , Período de Recuperação da Anestesia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Monitoração Neuromuscular , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Rocurônio/antagonistas & inibidores , Sugammadex/farmacologia , Fatores de TempoRESUMO
BACKGROUND: Residual neuromuscular block has been associated with postoperative pulmonary complications. We hypothesised that sugammadex reduces postoperative pulmonary complications in patients aged ≥70 yr having surgery ≥3 h, compared with neostigmine. METHODS: Patients were enrolled in an open-label, assessor-blinded, randomised, controlled trial. At surgical closure, subjects were equally randomised to receive sugammadex 2 mg kg-1 or neostigmine 0.07 mg kg-1 (maximum 5 mg) for rocuronium reversal. The primary endpoint was incidence of postoperative pulmonary complications. Secondary endpoints included residual paralysis (train-of-four ratio <0.9 in the PACU) and Phase 1 recovery (time to attain pain control and stable respiratory, haemodynamic, and neurological status). The analysis was by intention-to-treat. RESULTS: Of the 200 subjects randomised, 98 received sugammadex and 99 received neostigmine. There was no significant difference in the primary endpoint of postoperative pulmonary complications despite a signal towards reduced incidence for sugammadex (33% vs 40%; odds ratio [OR]=0.74; 95% confidence interval [CI]=[0.40, 1.37]; P=0.30) compared with neostigmine. Sugammadex decreased residual neuromuscular block (10% vs 49%; OR=0.11, 95% CI=[0.04, 0.25]; P<0.001). Phase 1 recovery time was comparable between sugammadex (97.3 min [standard deviation, sd=54.3]) and neostigmine (110.0 min [sd=62.0]), difference -12.7 min (95% CI, [-29.2, 3.9], P=0.13). In an exploratory analysis, there were fewer 30 day hospital readmissions in the sugammadex group compared with the neostigmine group (5% vs 15%; OR=0.30, 95% CI=[0.08, 0.91]; P=0.03). CONCLUSIONS: In older adults undergoing prolonged surgery, sugammadex was associated with a 40% reduction in residual neuromuscular block, a 10% reduction in 30 day hospital readmission rate, but no difference in the occurrence of postoperative pulmonary complications. Based on this exploratory study, larger studies should determine whether sugammadex may reduce postoperative pulmonary complications and 30 day hospital readmissions. CLINICAL TRIAL REGISTRATION: NCT02861131.
Assuntos
Recuperação Demorada da Anestesia/prevenção & controle , Pneumopatias/prevenção & controle , Neostigmina/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Sugammadex/farmacologia , Idoso , Idoso de 80 Anos ou mais , Inibidores da Colinesterase/farmacologia , Método Duplo-Cego , Feminino , Humanos , Período Intraoperatório , Pneumopatias/etiologia , Masculino , Bloqueio Neuromuscular , Junção Neuromuscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Readmissão do Paciente/estatística & dados numéricos , Rocurônio/antagonistas & inibidoresRESUMO
BACKGROUND: Sugammadex reverses rocuronium-induced neuromuscular blockade quickly and effectively. This study compared efficacy of sugammadex and pyridostigmine for reversal of rocuronium-induced light block or minimal block in children scheduled for elective entropion surgery. METHODS: A prospective randomized study was conducted on 60 pediatric patients aged 1 to 11 years and scheduled for entropion surgery under sevoflurane anesthesia. Neuromuscular blockade was achieved by administration of 0.6âmg/kg rocuronium and assessed using train-of-four (TOF) ulnar nerve stimulation. Patients were randomly assigned to 2 groups receiving sugammadex 2âmg/kg or pyridostigmine 0.2âmg/kg plus glycopyrrolate 0.01âmg/kg. Primary outcomes were time from reversal agents administration to TOF ratio 0.9 and time from reversal agent administration to TOF ratio 1.0. Time from TOF ratio 0.9 to extubation, time from TOF ratio 1.0 to extubation, and postoperative adverse events were also recorded. RESULTS: There were no substantial differences in demographic variables. Time from reversal agents administration to TOF ratio 0.9 and time from reversal agents to TOF ratio 1.0 were significantly faster in sugammadex group: 1.30â±â0.84 versus 3.53â±â2.73âminutes (Pâ<â.001) and 2.75â±â1.00 versus 5.73â±â2.83âminutes (Pâ<â.001). Extubation time was shorter in sugammadex group. Incidence of skin rash, nausea, vomiting, and postoperative residual neuromuscular blockade (airway obstruction) was not statistically different between groups. Incidence of patients agitation in recovery room was lower in sugammadex group. CONCLUSION: Sugammadex provided more rapid reversal of rocuronium-induced neuromuscular blockade in pediatric patients undergoing surgery lasting 30 to 60âminutes than did pyridostigmine plus glycopyrrolate, with no differences in incidence of adverse events between groups.
Assuntos
Inibidores da Colinesterase/administração & dosagem , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Brometo de Piridostigmina/administração & dosagem , Rocurônio/antagonistas & inibidores , Sugammadex/administração & dosagem , Criança , Pré-Escolar , Inibidores da Colinesterase/farmacologia , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Brometo de Piridostigmina/farmacologia , Distribuição Aleatória , Método Simples-Cego , Sugammadex/farmacologia , Fatores de TempoRESUMO
BACKGROUND: Reversing a neuromuscular blockade agent with sugammadex is known to lessen postoperative complications by reducing postoperative residual curarization. However, its effects on 90-day mortality are unknown. Therefore, this study aimed to compare the effects of sugammadex and neostigmine in terms of 90-day mortality after non-cardiac surgery. METHODS: This retrospective cohort study analyzed the medical records of adult patients aged 18 years or older who underwent non-cardiac surgery at a single tertiary care hospital between 2011 and 2016. Propensity score matching and Cox regression analysis were used to investigate the effectiveness of sugammadex and neostigmine in lowering 90-day mortality after non-cardiac surgery. RESULTS: A total of 65,702 patients were included in the analysis (mean age: 52.3 years, standard deviation: 15.7), and 23,532 of these patients (35.8%) received general surgery. After propensity score matching, 14,179 patients (3906 patients from the sugammadex group and 10,273 patients from the neostigmine group) were included in the final analysis. Cox regression analysis in the propensity score-matched cohort showed that the risk of 90-day mortality was 40% lower in the sugammadex group than in the neostigmine group (hazard ratio: 0.60, 95% confidence interval: 0.37, 0.98; P = 0.042). These results were similar in the multivariable Cox regression analysis of the entire cohort (hazard ratio: 0.62, 95% confidence interval: 0.39, 0.96; P = 0.036). CONCLUSIONS: This retrospective cohort study suggested that reversing rocuronium with sugammadex might be associated with lower 90-day mortality after non-cardiac surgery compared to neostigmine. However, since this study did not evaluate quantitative neuromuscular function in the postoperative period due to its retrospective design, the results should be interpreted carefully. Future prospective studies with quantitative neuromuscular monitoring in the postoperative period should be performed to confirm these results.
Assuntos
Neostigmina/farmacologia , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Complicações Pós-Operatórias/mortalidade , Rocurônio/antagonistas & inibidores , Sugammadex/farmacologia , Inibidores da Colinesterase/farmacologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Bloqueio Neuromuscular , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios , TempoRESUMO
BACKGROUND: Postoperative residual curarisation (PORC) is a risk directly related to the use of neuromuscular blocking agents during surgical procedures. Acceleromyography is distressing for conscious patients when assessing PORC. Diaphragm ultrasonography could be a valid alternative. OBJECTIVES: The primary objective was to achieve a 28% lower incidence of PORC in patients who, after rocuronium administration, received neostigmine or sugammadex at 30âmin after surgery. To assess PORC, diaphragm ultrasonography was used, and thickening fractioning [the difference of thickness at the end of inspiration (TEI) and at the end of expiration (TEE), normalised for TEE (TEIâ-âTEE/TEE)] was measured. PORC was defined as thickening fractioning of 0.36 or less. The secondary object was the comparison, in the two treatment groups, of the return to baseline thickening fractioning at 30âmin after surgery (ΔTF30). DESIGN: Randomised, double-blind, single-centre study. SETTING: University Hospital Careggi, Florence, Italy. PATIENTS: Patients of American Society Anesthesiologists' physical status 1 or 2, 18 to 80 years, receiving rocuronium during microlaryngeal surgery. INTERVENTIONS: At the end of surgery participants were randomised to receive neostigmine (NEO group) or sugammadex (SUG group) as the reversal drug. Thickening fractioning and ΔTF30 were evaluated at baseline and at 0, 10 and 30âmin after surgery. MAIN OUTCOME MEASURES: TEE and TEI at each time point. RESULTS: A total of 59 patients with similar demographic characteristics were enrolled. An association between lack of recovery (thickening fractioning ≤0.36) and drug treatment was only observed at 0âmin (SUG vs. NEO, Pâ<â0.05). Concerning ΔTF, at 30âmin more patients in the SUG group returned to baseline than those in the NEO group (Pâ<â0.001), after adjusting for side (Pâ=â0.52), baseline thickening fractioning (Pâ<â0.0001) and time of measurement (Pâ<â0.01). CONCLUSION: We found an early (0âmin) but not long-lasting (30âmin) association between diaphragm failure and treatment allocation; a full recovery in baseline diaphragm function was observed only in patients receiving sugammadex. We cannot exclude that further differences have not been found due to interpatients variability in assessing diaphragm contractility by ultrasonography. TRIAL REGISTRATION: EudraCT Identifier: 2013-004787-62, Clinicaltrials.gov Identifier: NCT02698969.
Assuntos
Recuperação Demorada da Anestesia/tratamento farmacológico , Neostigmina/administração & dosagem , Bloqueio Neuromuscular/efeitos adversos , Rocurônio/antagonistas & inibidores , Sugammadex/administração & dosagem , Adulto , Idoso , Recuperação Demorada da Anestesia/diagnóstico , Recuperação Demorada da Anestesia/etiologia , Diafragma/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Laringe/cirurgia , Masculino , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Rocurônio/administração & dosagem , Resultado do Tratamento , UltrassonografiaRESUMO
Since its clinical introduction in 2008, sugammadex has demonstrated a high degree of safety and superior effectiveness compared to neostigmine when used to antagonize muscle relaxation produced by steroid nondepolarizing neuromuscular blockers. This includes its use in special populations, such as the elderly, children over 2 years old, and patients with renal, hepatic, or lung disease. In contrast, clinical evidence guiding its use during pregnancy, in women of childbearing potential, and in lactating women, is sparse. An exception is administration at the end of surgery in parturients undergoing cesarean delivery (CD) with general anesthesia (GA), for whom effectiveness and safety evidence is rapidly accumulating. We review evidence regarding sugammadex rescue reversal shortly after high-dose rocuronium in cases of cannot intubate/cannot ventilate (CICV), the extent of placental transfer of maternally administered sugammadex, adverse fetal effects of sugammadex exposure, potential effects on maintenance of early pregnancy, and the extent of transfer to breast milk. Finally, many anesthesiologists appear to heed the manufacturer's warning regarding informing women of childbearing potential regarding the risk of hormone contraceptive failure after sugammadex exposure. We provide a medical ethics analysis of the ex post facto counseling commonly reported after sugammadex administration, which favors either preoperative discussion and shared decision making, or the decision by the physician to use neostigmine. This review highlights the disparity in evidence regarding sugammadex use in various contexts of female reproductive health, including current research gaps that prevent this population from sharing in the benefits of sugammadex enjoyed by most perioperative patients.
Assuntos
Neostigmina/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Complicações na Gravidez/prevenção & controle , Rocurônio/antagonistas & inibidores , Sugammadex/administração & dosagem , Adulto , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Anestesia Obstétrica , Cesárea , Inibidores da Colinesterase/administração & dosagem , Feminino , Humanos , Intubação , Lactação , Bloqueio Neuromuscular/efeitos adversos , Junção Neuromuscular/efeitos dos fármacos , Placenta/fisiologia , Período Pós-Parto , Gravidez , Sugammadex/efeitos adversos , Brometo de Vecurônio/antagonistas & inibidoresRESUMO
Studies have reported that protracted dexamethasone treatment induces resistance to nondepolarizing neuromuscular blocking agents (NMBAs) and the association with nicotinic acetylcholine receptors in the diaphragm of rats. Here, we investigated the effect of protracted dexamethasone administration on the sensitivity to rocuronium and the recovery profile when reversed by sugammadex; additionally, we observed the recovery period of pharmacodynamic change after withdrawal. Sprague-Dawley rats received daily intraperitoneal injections of dexamethasone or saline for 14 days. On days 1, 3, and 7 after the last dexamethasone treatment (Dexa1, Dexa3, and Dexa7, respectively) or 1 day after saline (control group), the phrenic nerve-hemidiaphragm preparation was dissected for assay. The dose-response curve of rocuronium in Dexa1 was shifted to the right compared to controls, but curves in Dexa3 and Dexa7 were not significantly different. Groups were not significantly different in attaining the train-of-four ratio ≥ 0.9, but the recovery index in Dexa7 was shorter than that in control and Dexa1. Recovery profiles (period of sugammadex reversal) were not correlated with resistance properties but rather with total administered drugs (binding capacity of NMBAs and sugammadex). Protracted dexamethasone exposure induced resistance to rocuronium but seemed to have no effect on sugammadex reversal in the rat diaphragm.
Assuntos
Dexametasona/administração & dosagem , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Rocurônio/antagonistas & inibidores , Sugammadex/farmacologia , Período de Recuperação da Anestesia , Animais , Diafragma/inervação , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Injeções Intraperitoneais , Masculino , Modelos Animais , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Nervo Frênico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Rocurônio/administração & dosagemAssuntos
Bloqueio Neuromuscular/métodos , Doença de Parkinson/fisiopatologia , Sugammadex/farmacologia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Junção Neuromuscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Rocurônio/antagonistas & inibidores , Fatores de TempoRESUMO
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The ventilatory response to hypoxia is a critical reflex that is impaired by neuromuscular blocking drugs. However, the degree to which this reflex is restored after reversal of blockade is unknown. WHAT THIS ARTICLE TELLS US THAT IS NEW: Despite full reversal of neuromuscular blockade at the thumb using different drug classes, this hypoxic chemoreflex is not fully restored. BACKGROUND: The ventilatory response to hypoxia is a life-saving chemoreflex originating at the carotid bodies that is impaired by nondepolarizing neuromuscular blocking agents. This study evaluated the effect of three strategies for reversal of a partial neuromuscular block on ventilatory control in 34 healthy male volunteers on the chemoreflex. The hypothesis was that the hypoxic ventilatory response is fully restored following the return to a train-of-four ratio of 1. METHODS: In this single-center, experimental, randomized, controlled trial, ventilatory responses to 5-min hypoxia (oxygen saturation, 80 ± 2%) and ventilation at hyperoxic isohypercapnia (end-tidal carbon dioxide concentration, 55 mmHg) were obtained at baseline, during rocuronium-induced partial neuromuscular block (train-of-four ratio of 0.7 measured at the adductor pollicis muscle by electromyography), and following reversal until the train-of-four ratio reached unity with placebo (n = 12), 1 mg neostigmine/0.5 mg atropine (n = 11), or 2 mg/kg sugammadex (n = 11). RESULTS: This study confirmed that low-dose rocuronium reduced the ventilatory response to hypoxia from 0.55 ± 0.22 (baseline) to 0.31 ± 0.21 l · min · % (train-of-four ratio, 0.7; P < 0.001). Following full reversal as measured at the thumb, there was persistent residual blunting of the hypoxic ventilatory response (0.45 ± 0.16 l · min · %; train-of-four ratio, 1.0; P < 0.001). Treatment effect was not significant (analysis of covariance, P = 0.299) with chemoreflex impairment in 5 (45%) subjects following sugammadex reversal, in 7 subjects (64%) following neostigmine reversal, and in 10 subjects (83%) after spontaneous reversal to a train-of-four ratio of 1. CONCLUSIONS: Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at train-of-four ratios greater than 0.9 following reversal with neostigmine and sugammadex or spontaneous recovery of the neuromuscular block.
Assuntos
Hipóxia/fisiopatologia , Neostigmina/farmacologia , Bloqueio Neuromuscular/métodos , Respiração/efeitos dos fármacos , Rocurônio/antagonistas & inibidores , Sugammadex/farmacologia , Adolescente , Adulto , Período de Recuperação da Anestesia , Inibidores da Colinesterase/farmacologia , Método Duplo-Cego , Eletromiografia , Voluntários Saudáveis , Humanos , Masculino , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Adulto JovemAssuntos
Dor Abdominal/etiologia , Anafilaxia/induzido quimicamente , Hipersensibilidade a Drogas/etiologia , Rocurônio/antagonistas & inibidores , Sugammadex/efeitos adversos , Dor Abdominal/diagnóstico , Dor Abdominal/tratamento farmacológico , Adolescente , Anafilaxia/complicações , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Anestesia Dentária/métodos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Efedrina/administração & dosagem , Epinefrina/administração & dosagem , Feminino , Humanos , Dente Serotino/cirurgia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Período Pós-Operatório , Rocurônio/administração & dosagem , Índice de Gravidade de Doença , Extração Dentária/efeitos adversosRESUMO
STUDY OBJECTIVE: To evaluate the influence of reversal of neuromuscular blockade with sugammadex or neostigmine on postoperative quality of recovery following a single bolus dose of rocuronium after pars plana vitrectomy (PPV) under general anesthesia. DESIGN: Prospective, double-blind, randomized controlled trial. SETTING: This study was conducted in a University Teaching Hospital from February to July 2017. PATIENTS: A total of 84 patients with an American Society of Anesthesiologists physical status of I or II who were scheduled to undergo PPV under general anesthesia. INTERVENTIONS: The patients were randomly assigned to the neostigmine (Group N, nâ¯=â¯44) or sugammadex (Group S, nâ¯=â¯40) groups; 3â¯ml of study drug was prepared for the patients. For patients in Group N, a solution of neostigmine methylsulfate (1â¯mg) and glycopyrrolate (0.2â¯mg) was prepared, while a solution of sugammadex sodium (2â¯mg/kg) and normal saline was prepared for patients in Group S. MEASUREMENTS: The primary endpoint was the effect of sugammadex, compared with neostigmine, on the recovery rate in the physiological domain in patients who underwent PPV with general anesthesia. The quality of recovery was assessed using the Postoperative Quality Recovery Scale at 15â¯min and 40â¯min after surgery, and on postoperative day 1. MAIN RESULTS: The recovery rate in the physiological domain was higher in Group S at 15â¯min after surgery (Pâ¯=â¯0.020). Though there were no significant differences in the overall cognitive recovery domain, patients in Group S could recall more numbers in reverse order. However, there were no significant differences between the groups in the other domains of the scale. CONCLUSIONS: The use of sugammadex may increase the quality of physiological recovery at early postoperative periods, compared with that of neostigmine, following a single bolus dose of rocuronium in patients undergoing PPV with general anesthesia. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03108989). Registration number: NCT03108989.
Assuntos
Período de Recuperação da Anestesia , Anestesia Geral/métodos , Neostigmina/administração & dosagem , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Sugammadex/administração & dosagem , Idoso , Anestesia Geral/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neostigmina/efeitos adversos , Bloqueio Neuromuscular/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Complicações Cognitivas Pós-Operatórias/diagnóstico , Complicações Cognitivas Pós-Operatórias/etiologia , Estudos Prospectivos , Rocurônio/administração & dosagem , Rocurônio/antagonistas & inibidores , Sugammadex/efeitos adversos , Vitrectomia/efeitos adversosRESUMO
We present a case of a pediatric patient who developed recurarization after a cardiac catheterization procedure. Intraoperative neuromuscular blockade was achieved with 2 doses of rocuronium, and the blockade was reversed with a bolus dose of sugammadex at the end of the procedure. While recovering in the pediatric cardiac intensive care unit, the patient developed respiratory failure and a decline in the train-of-four response. The patient fully recovered after receiving a second dose of sugammadex.
Assuntos
Recuperação Demorada da Anestesia/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , Rocurônio/antagonistas & inibidores , Sugammadex/efeitos adversos , Sugammadex/uso terapêutico , Recuperação Demorada da Anestesia/complicações , Feminino , Humanos , Lactente , Bloqueio Neuromuscular/métodos , Período Pós-Operatório , Insuficiência Respiratória/complicações , Rocurônio/farmacologiaRESUMO
Abstract Background and objectives: Sugamadex is a modified gamma-cyclodextrin, the first selective agent for reversal of neuromuscular blockade induced by steroidal non-depolarizing muscle relaxants, with greater affinity for rocuronium. In this article we present a case of severe bradycardia and asystole following sugammadex administration. Case report: A 54-year-old male patient, ASA II, with a history of hypertension, dyslipidemia and obesity, who underwent an emergency umbilical herniorrhaphy under balanced general anesthesia. Intraoperative muscle relaxation was maintained with rocuronium. At the end of the surgery, the patient maintained a neuromuscular block with two TOF responses, and sugammadex (200 mg) was administered. About thirty seconds after its administration, the patient developed marked bradycardia (HR 30 bpm) followed by asystole. Conclusions: Documented bradycardia and asystole were attributed to the administration of sugammadex. This case shows that, although rare, cardiac arrest is a possible adverse effect of this drug, and that the knowledge of this situation can be determinant for the patient's evolution.
Resumo Justificativa e objetivos: O sugamadex é uma gama ciclodextrina modificada, o primeiro agente seletivo para reversão do bloqueio neuromuscular induzido pelos relaxantes musculares não despolarizantes do tipo esteroide, com maior afinidade para o rocurônio. Neste artigo apresentamos um caso de bradicardia grave e assistolia após administração de sugamadex. Relato do caso: Doente do sexo masculino, 54 anos, ASA II, com antecedentes pessoais de hipertensão, dislipidemia e obesidade, submetido à herniorrafia umbilical em regime de urgência sob anestesia geral balanceada. O relaxamento muscular intraoperatório foi mantido com rocurônio. No fim da cirurgia o doente mantinha bloqueio neuromuscular com duas respostas no TOF, pelo que foi administrado sugamadex 200 mg. Cerca de trinta segundos após a sua administração, o doente desenvolveu bradicardia acentuada (FC 30 bpm) seguida de período de assistolia. Conclusões: A bradicardia e a assistolia documentadas foram atribuídas à administração do sugamadex. Este caso evidencia que, apesar de rara, a parada cardíaca é um efeito adverso possível desse fármaco e que o conhecimento dessa situação pode ser determinante para a evolução do doente.
Assuntos
Humanos , Masculino , Bradicardia/induzido quimicamente , Sugammadex/efeitos adversos , Parada Cardíaca/induzido quimicamente , Índice de Gravidade de Doença , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Bloqueio Neuromuscular/métodos , Sugammadex/administração & dosagem , Rocurônio/administração & dosagem , Rocurônio/antagonistas & inibidores , Pessoa de Meia-IdadeAssuntos
Colostomia/efeitos adversos , Laringismo/induzido quimicamente , Sugammadex/efeitos adversos , Idoso , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intubação Intratraqueal , Laringismo/diagnóstico , Laringismo/terapia , Masculino , Bloqueio Neuromuscular/métodos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Rocurônio/administração & dosagem , Rocurônio/antagonistas & inibidores , Sugammadex/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Sugamadex is a modified gamma-cyclodextrin, the first selective agent for reversal of neuromuscular blockade induced by steroidal non-depolarizing muscle relaxants, with greater affinity for rocuronium. In this article we present a case of severe bradycardia and asystole following sugammadex administration. CASE REPORT: A 54-year-old male patient, ASA II, with a history of hypertension, dyslipidemia and obesity, who underwent an emergency umbilical herniorrhaphy under balanced general anesthesia. Intraoperative muscle relaxation was maintained with rocuronium. At the end of the surgery, the patient maintained a neuromuscular block with two TOF responses, and sugammadex (200mg) was administered. About thirty seconds after its administration, the patient developed marked bradycardia (HR 30 bpm) followed by asystole. CONCLUSIONS: Documented bradycardia and asystole were attributed to the administration of sugammadex. This case shows that, although rare, cardiac arrest is a possible adverse effect of this drug, and that the knowledge of this situation can be determinant for the patient's evolution.