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1.
J Perianesth Nurs ; 37(3): 326-332, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35153119

RESUMEN

PURPOSE: The use of sugammadex at a lower dose after a routine reversal dose of neostigmine may prevent residual neuromuscular blockade (rNMB). Our goal was to investigate the effects of the use of half-dose sugammadex for reversing rNMB after administration of neostigmine, and compare these effects to a routine full-dose of neostigmine. DESIGN: Prospective, single-blinded, randomized trial. METHODS: Ninety-eight patients having lower abdominal tumor resection surgery under general anesthesia were randomized into two groups. Group N (Neostigmine) (n = 48) patients received standard reversal dose of intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg before extubationl Group N + S (Neostigmine + Sugammadex) (n = 50) patients received 1 mg/kg of intravenous sugammadex three minutes after a standard neostigmine reversal dose. The primary end-point was the incidence of a train-of-four (TOF) ratio less than 0.9 at tracheal extubation. Secondary end-points were periods between the start of administration of reversal agents and extubation or operating room discharge in minutes to achieve recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9. FINDINGS: The demographic data were not different between the two groups (P > .005). The incidence of rNMB presented as TOF ratio < 0.9 to 0.7 was present in 52% of Group N patients compared to 8% in Group N + S patients (P < .0001). The time to recovery between administering reversal and extubation as well as operating room discharge in Group N were; 18.52 ± 6.34 minutes and 23.27 ± 6.95 minutes, respectively, whereas; in Group N + S, they were; 12.86 ± 5.05 and 17.82 ± 4.99 minutes, respectively. (P < .0001, P < .0001, respectively). Adverse events were similar between groups (P > .05). CONCLUSIONS: A half-dose sugammadex (1 mg/kg) after full-dose reversal of neostigmine provides a lower incidence of rNMB and shorter recovery times as compared to full-dose neostigmine reversal agent. This practice is safe and effective in case of rNMB.


Asunto(s)
Retraso en el Despertar Posanestésico , Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes , gamma-Ciclodextrinas , Inhibidores de la Colinesterasa/efectos adversos , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Retraso en el Despertar Posanestésico/etiología , Retraso en el Despertar Posanestésico/prevención & control , Humanos , Neostigmina/farmacología , Neostigmina/uso terapéutico , Bloqueo Neuromuscular/efectos adversos , Fármacos Neuromusculares no Despolarizantes/efectos adversos , Proyectos Piloto , Estudios Prospectivos , Sugammadex
2.
Clin Transl Sci ; 15(1): 234-243, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34435439

RESUMEN

Residual shallow neuromuscular block (NMB) is potentially harmful and contributes to critical respiratory events. Evidence for the optimal dose of sugammadex required to reverse vecuronium-induced shallow NMB is scarce. The aims of the present study were to find suitable doses of sugammadex and neostigmine to reverse a residual vecuronium-induced NMB from a time of flight (TOF) ratio of 0.3-0.9 and evaluate their safety and efficacy. In total, 121 patients aged 18-65 years were randomly assigned to 11 groups to receive placebo, sugammadex (doses of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg), or neostigmine (doses of 10, 25, 40, 55, or 70 µg/kg). The reversal time of sugammadex and neostigmine to antagonize a vecuronium-induced shallow residual NMB (i.e., TOF ratio of 0.3) and related adverse reactions were recorded. Several statistical models were tested to find an appropriate statistical model to explore the suitable doses of sugammadex and neostigmine required to reverse a residual vecuronium-induced NMB. Based on a monoexponential model with the response variable on a logarithmic scale, sugammadex 0.56 mg/kg may be sufficient to reverse vecuronium-induced shallow residual NMB at a TOF ratio of 0.3 under anesthesia maintained with propofol. Neostigmine may not provide prompt and satisfactory antagonism as sugammadex, even in shallow NMB.


Asunto(s)
Retraso en el Despertar Posanestésico/inducido químicamente , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Neostigmina/administración & dosificación , Neostigmina/farmacología , Sugammadex/administración & dosificación , Sugammadex/farmacología , Bromuro de Vecuronio/farmacología , Humanos
3.
Sci Rep ; 10(1): 5265, 2020 03 24.
Artículo en Inglés | MEDLINE | ID: mdl-32210319

RESUMEN

Anesthetics are used to produce hypnosis and analgesic effects during surgery, but anesthesia for a long time after the operation is not conducive to the recovery of animals or patients. Therefore, finding appropriate treatments to counter the effects of anesthetics could enhance postoperative recovery. In the current study, we discovered the novel role of a GluN2A-selective positive allosteric modulator (PAM) in ketamine-induced anesthesia and investigated the effects of the PAM combined with nalmefene and flumazenil (PNF) in reversing the actions of an anesthetic combination (ketamine-fentanyl-dexmedetomidine, KFD). PAM treatment dose-dependently decreased the duration of the ketamine-induced loss of righting reflex (LORR). Compared with those in the KFD group, the duration of LORR and the analgesic effect of the KFD + PNF group were obviously decreased. Meanwhile, successive administration of PNF and KFD had no adverse effects on the cardiovascular and respiratory systems. Both the KFD group and the KFD + PNF group showed no changes in hepatic and renal function or cognitive function in rats. Moreover, the recovery of motor coordination of the KFD + PNF group was faster than that of the KFD group. In summary, our results suggest the potential application of the PNF combination as an antagonistic treatment strategy for anesthesia.


Asunto(s)
Analgesia , Anestesia , Dexmedetomidina/antagonistas & inhibidores , Fentanilo/antagonistas & inhibidores , Flumazenil/farmacología , Antagonistas de Receptores de GABA-A/farmacología , Ketamina/antagonistas & inhibidores , Naltrexona/análogos & derivados , Antagonistas de Narcóticos/farmacología , Receptores de N-Metil-D-Aspartato/agonistas , Adyuvantes Anestésicos , Regulación Alostérica , Animales , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Femenino , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Naltrexona/farmacología , Nocicepción/efectos de los fármacos , Dimensión del Dolor , Ratas , Reflejo de Enderezamiento/efectos de los fármacos , Prueba de Desempeño de Rotación con Aceleración Constante
4.
Eur J Anaesthesiol ; 37(1): 44-51, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31356374

RESUMEN

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 30 min 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 (TEI - TEE/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 30 min 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 30 min 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 0 min (SUG vs. NEO, P < 0.05). Concerning ΔTF, at 30 min more patients in the SUG group returned to baseline than those in the NEO group (P < 0.001), after adjusting for side (P = 0.52), baseline thickening fractioning (P < 0.0001) and time of measurement (P < 0.01). CONCLUSION: We found an early (0 min) but not long-lasting (30 min) 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.


Asunto(s)
Retraso en el Despertar Posanestésico/tratamiento farmacológico , Neostigmina/administración & dosificación , Bloqueo Neuromuscular/efectos adversos , Rocuronio/antagonistas & inhibidores , Sugammadex/administración & dosificación , Adulto , Anciano , Retraso en el Despertar Posanestésico/diagnóstico , Retraso en el Despertar Posanestésico/etiología , Diafragma/diagnóstico por imagen , Método Doble Ciego , Femenino , Humanos , Laringe/cirugía , Masculino , Microcirugia/efectos adversos , Persona de Mediana Edad , Procedimientos Quirúrgicos Otorrinolaringológicos/efectos adversos , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Rocuronio/administración & dosificación , Resultado del Tratamiento , Ultrasonografía
5.
BMC Anesthesiol ; 19(1): 143, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31390986

RESUMEN

BACKGROUND: Complete avoidance of residual neuromuscular blockade (RNMB) during the postoperative period has not yet been achieved in current anesthesia practice. Evidently, compliance with NMB monitoring is persistently low, and the risk of RNMB during the perioperative period remains underestimated. To our knowledge, no publications have reported the incidence of RNMB in a university hospital where access to quantitative NMB monitoring and sugammadex is unlimited and where NMB management is not protocolised. The primary aim of this study was to estimate the incidence of RNMB in patients managed with or without sugammadex or neostigmine as antagonists and quantitative NMB monitoring in the operating room. The secondary aim was to explore the associations between RNMB and potentially related variables. METHODS: This retrospective observational cohort study was conducted at a tertiary referral university hospital in Buenos Aires, Argentina. Records created between June 2015 and December 2015 were reviewed. In total, 240 consecutive patients who had undergone elective surgical procedures requiring NMB were included. All patients were monitored via acceleromyography at the adductor pollicis muscle within 5 min of arrival in the postanaesthesia care unit (PACU). Scheduled recovery in the intensive care unit was the only exclusion criterion. RESULTS: RNMB was present in 1.6% patients who received intra-operative quantitative NMB monitoring and 32% patients whose NMB was not monitored (P <  0.01). Multivariable analysis revealed that the use of intra-operative quantitative NMB monitoring and sugammadex were associated with a lower incidence of RNMB, with calculated odds ratios of 0.04 (95% confidence interval [CI]: 0.005 to 0.401) and 0.18 (95% CI: 0.046 to 0.727), respectively. CONCLUSIONS: The results of the present study suggest that intra-operative quantitative NMB monitoring and use of sugammadex are associated with a decreased incidence of RNMB in the PACU, reinforcing the contention that the optimal strategy for RNMB avoidance is the use of quantitative NMB monitoring and eventual use of reversal agents, if needed, prior to emergence from anaesthesia.


Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Bloqueo Neuromuscular , Monitoreo Neuromuscular , Retraso en el Despertar Posanestésico/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neostigmina/uso terapéutico , Complicaciones Posoperatorias , Estudios Retrospectivos , Sugammadex/uso terapéutico
7.
A A Pract ; 13(6): 204-205, 2019 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-30985317

RESUMEN

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.


Asunto(s)
Retraso en el Despertar Posanestésico/tratamiento farmacológico , Insuficiencia Respiratoria/tratamiento farmacológico , Rocuronio/antagonistas & inhibidores , Sugammadex/efectos adversos , Sugammadex/uso terapéutico , Retraso en el Despertar Posanestésico/complicaciones , Femenino , Humanos , Lactante , Bloqueo Neuromuscular/métodos , Periodo Posoperatorio , Insuficiencia Respiratoria/complicaciones , Rocuronio/farmacología
8.
JBI Database System Rev Implement Rep ; 16(10): 1922-1928, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30335038
9.
Trials ; 19(1): 135, 2018 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-29467022

RESUMEN

BACKGROUND: The extensive use of neuromuscular blocking agents (NMBAs) during surgical procedures still leads to potential residual paralyzing effects in the postoperative period. Indeed, neuromuscular monitoring in an intra-operative setting is strongly advocated. Acetylcholinesterase inhibitors can reverse muscle block, but their short half-life may lead to residual curarization in the ward, especially when intermediate or long-acting NMBAs have been administered. Sugammadex is the first selective reversal drug for steroidal NMBAs; it has been shown to give full and rapid recovery of muscle strength, thus minimizing the occurrence of residual curarization. Acceleromyography of the adductor pollicis is the gold standard for detecting residual curarization, but it cannot be carried out on conscious patients. Ultrasonography of diaphragm thickness may reveal residual effects of NMBAs in conscious patients. METHODS/DESIGN: This prospective, double-blind, single-center randomized controlled study will enroll patients (of American Society of Anesthesiologists physical status I-II, aged 18-80 years) who will be scheduled to undergo deep neuromuscular block with rocuronium for ear, nose, or throat surgery. The study's primary objective will be to compare the effects of neostigmine and sugammadex on postoperative residual curarization using two different tools: diaphragm ultrasonography and acceleromyography of the adductor pollicis. Patients will be extubated when the train-of-four ratio is > 0.9. Diaphragm ultrasonography will be used to evaluate the thickening fraction, which is the difference between the end expiratory thickness and the end inspiratory thickness, normalized to the end expiratory thickness. Ultrasonography will be performed before the initiation of general anesthesia, before extubation, and 10 and 30 min after discharging patients from the operating room. The secondary objective will be to compare the incidence of postoperative complications due to residual neuromuscular block between patients who receive neostigmine and those who receive sugammadex. DISCUSSION: Postoperative residual curarization is a topic of paramount importance, because its occurrence can cause complications and increase the length of stay in hospital and the related costs. Diaphragm ultrasound assessment may become a bedside integrative tool in the neuromuscular monitoring field to detect concealed residual curarization in surgical patients who have received paralyzing agents. TRIAL REGISTRATION: EudraCT, 2013-004787-62. Registered on 18 June 2014, as "Evaluation of muscle function recovery after deep neuromuscular blockade by acceleromyography of the adductor pollicis or diaphragmatic echography: comparison between sugammadex and neostigmine." ClinicalTrials.gov, NCT02698969 . Registered on 15 February 2016, as "Recovery of Muscle Function After Deep Neuromuscular Block by Means of Diaphragm Ultrasonography and Adductor Pollicis Acceleromyography: Comparison of Neostigmine vs. Sugammadex as Reversal Drugs."


Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Retraso en el Despertar Posanestésico/diagnóstico por imagen , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Diafragma/efectos de los fármacos , Diafragma/diagnóstico por imagen , Miografía/métodos , Neostigmina/uso terapéutico , Bloqueo Neuromuscular/métodos , Sugammadex/uso terapéutico , Ultrasonografía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Colinesterasa/efectos adversos , Retraso en el Despertar Posanestésico/fisiopatología , Método Doble Ciego , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Neostigmina/efectos adversos , Bloqueo Neuromuscular/efectos adversos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Sugammadex/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
10.
BMC Anesthesiol ; 17(1): 140, 2017 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-29041919

RESUMEN

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.


Asunto(s)
Retraso en el Despertar Posanestésico/inducido químicamente , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Bloqueo Neuromuscular/métodos , Fármacos Neuromusculares no Despolarizantes/administración & dosificación , gamma-Ciclodextrinas/administración & dosificación , Animales , Retraso en el Despertar Posanestésico/diagnóstico , Relación Dosis-Respuesta a Droga , Humanos , Bloqueo Neuromuscular/efectos adversos , Fármacos Neuromusculares no Despolarizantes/efectos adversos , Sugammadex , gamma-Ciclodextrinas/efectos adversos
11.
Rev Esp Anestesiol Reanim ; 64(10): 560-567, 2017 Dec.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28662770

RESUMEN

OBJECTIVE: The overall objective of the study is to determine the ability of TOF-Cuff device (blood-pressure modified cuff, including stimulation electrodes) to monitor with the same device the non-invasive blood pressure (NIBP) and the depth of a neuromuscular blockade (NMB) induced pharmacologically, by stimulation of the brachial plexus at the humeral level and recording evoked changes in arterial pressure. MATERIAL AND METHOD: Clinical, single-centre, open-controlled study with 32 adult patients ASA I-III for scheduled elective surgery under general anaesthesia in supine position, for the validation of neuromuscular monitoring, comparing the values obtained from neuromuscular relaxation TOF-Cuff with those obtained by mechanomyography (MMG) (control method) during the recovery phase of NMB, when a TOF ratio>0.7 and>0.9 (primary endpoint) were reached respectively. And an additional consecutive study of 17 patients for validation of NIBP monitoring with TOF-Cuff device vs invasive blood pressure measured by an intra-arterial catheter. All data were analyzed using the Bland-Altman method. RESULTS: Recovery from NMB measured with the TOF-Cuff was earlier compared to MMG. Comparing TOF-ratio>0.9 measured with TOF-Cuff vs TOF-ratio>0.7 with MMG, a specificity of 91% and a positive predictive value of 84% were obtained. In NIBP measurement, the mean error and standard deviation of both systolic blood pressure (1.6±7mmHg) and diastolic blood pressure (-3.4±6.3) were within the European accuracy requirements for medical devices. CONCLUSIONS: The TOF-Cuff device has been shown to be valid and safe in the monitoring of NMB and in the measurement of NIBP, with no patient presenting any adverse events, skin-level lesions or residual pain. It is not interchangeable with MMG, having a TOF-ratio>0.9 quantified by the TOF-Cuff device, a good correlation with a TOF-ratio>0.7 on MMG.


Asunto(s)
Determinación de la Presión Sanguínea/métodos , Monitores de Presión Sanguínea , Monitorización Neurofisiológica Intraoperatoria/instrumentación , Bloqueo Neuromuscular , Adulto , Anestesia General , Presión Sanguínea/efectos de los fármacos , Plexo Braquial/fisiología , Cateterismo Periférico , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Retraso en el Despertar Posanestésico/fisiopatología , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neostigmina/farmacología , Neostigmina/uso terapéutico , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Sugammadex , gamma-Ciclodextrinas/farmacología , gamma-Ciclodextrinas/uso terapéutico
12.
Sci Rep ; 7(1): 5724, 2017 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-28720838

RESUMEN

The aim of this study is to evaluate the efficacy and safety of sugammadex for reversing neuromuscular blockade in pediatric patients. MEDLINE and other three Databases were searched. Randomized clinical trials were included if they compared sugammadex with neostigmine or placebo in pediatric patients undergoing surgery involving the use of rocuronium or vecuronium. The primary outcome was the time interval from administration of reversal agents to train-of-four ratio (TOFr, T4/T1) > 0.9. Incidences of any drug-related adverse events were secondary outcomes. Trial inclusion, data extraction, and risk of bias assessment were performed independently. Mean difference and relative risk were used as summary statistics with random effects models. Statistical heterogeneity was assessed by the I2 statistic. Funnel plot was used to detect publication bias. Ten studies with 580 participants were included. Although considerable heterogeneity (I2 = 98.5%) was detected in primary outcome, the results suggested that, compared with placebo or neostigmine, sugammadex can reverse rocuronium-induced neuromuscular blockade more rapidly with lower incidence of bradycardia. No significant differences were found in the incidences of other adverse events. Compared with neostigmine or placebo, sugammadex may reverse rocuronium-induced neuromuscular blockade in pediatric patients rapidly and safely.


Asunto(s)
Retraso en el Despertar Posanestésico/tratamiento farmacológico , Sugammadex/administración & dosificación , Sugammadex/efectos adversos , Adolescente , Niño , Preescolar , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Humanos , Incidencia , Lactante , Recién Nacido , Neostigmina/administración & dosificación , Neostigmina/efectos adversos , Placebos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Resultado del Tratamiento
13.
J Neurophysiol ; 118(3): 1591-1597, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28659466

RESUMEN

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP]i)-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A2A receptor blockade and [cAMP]i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP]i and adenosine receptor blockade play a role in this response.NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia.


Asunto(s)
Antagonistas del Receptor de Adenosina A2/farmacología , Anestesia General/métodos , Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Retraso en el Despertar Posanestésico/prevención & control , Antagonistas del Receptor de Adenosina A2/administración & dosificación , Antagonistas del Receptor de Adenosina A2/uso terapéutico , Anestésicos Generales/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Cafeína/administración & dosificación , Cafeína/uso terapéutico , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/uso terapéutico , Colforsina/farmacología , AMP Cíclico/metabolismo , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Isoflurano/farmacología , Pirimidinas/farmacología , Ratas , Ratas Sprague-Dawley , Triazoles/farmacología
14.
MedEdPORTAL ; 13: 10628, 2017 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-30800829

RESUMEN

Introduction: Delayed emergence is failure to regain consciousness following general anesthesia. It commonly involves altered mental status and respiratory compromise leading to increased morbidity, operating room delays, and increased cost. Causes include residual anesthetics, pharmacologic actions, surgical complications, neurologic events, endocrine disturbances, and patient-related factors. Pseudocholinesterase deficiency is an important consideration in delayed emergence. These patients are unable to effectively metabolize the muscle relaxants succinylcholine and mivacurium, leading to prolonged paralysis following administration. Methods: This simulation exercise is designed for medical students, student nurse anesthetists, and resident physicians. It is a 1-hour small-group learning activity centered upon a single patient encounter. We employ this exercise using an anesthesiology resident physician to proctor, a simulation technician to program and run, and a faculty anesthesiologist to mentor each session. It is intended to reinforce required reading assignments and improve the approach to delayed emergence from anesthesia. The debriefing includes discussion of risk-reduction strategies for incorporation in clinical practice. This exercise is easily reproduced using modern simulation mannequins without specialized programming. Results: Learners provided evaluations of their experience participating in the exercise, and resident physicians evaluated their experience proctoring the sessions. Responses were positive, and constructive criticism led to modifications to the exercise after development. Discussion: We use this exercise as an educational opportunity for medical students rotating clinically in our department. Medical students are paired with resident physicians for scenario development and work with faculty to produce valuable educational activities that benefit the entire department.


Asunto(s)
Anestesiología/educación , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Entrenamiento Simulado/métodos , Adulto , Retraso en el Despertar Posanestésico/diagnóstico , Retraso en el Despertar Posanestésico/etiología , Educación de Postgrado en Medicina/métodos , Femenino , Humanos , Masculino , Quirófanos/organización & administración , Entrenamiento Simulado/normas , Estudiantes de Medicina/estadística & datos numéricos
15.
Curr Opin Anaesthesiol ; 29(6): 662-667, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27755128

RESUMEN

PURPOSE OF REVIEW: To revise the current literature on concepts for neuromuscular block management. Moreover, consequences of incomplete neuromuscular recovery on patients' postoperative pulmonary outcome are evaluated as well. RECENT FINDINGS: The incidence of residual paralysis may be as high as 70% and even small degrees of residual paralysis may have clinical consequences. Neostigmine should not be given before return of the fourth response of the train-of-four-stimulation and no more than 40-50 µg/kg should be given. Sugammadex acts more rapidly and more predictably than neostigmine. Finally, there is convincing evidence in the literature that incomplete neuromuscular recovery may lead to a poor postoperative pulmonary outcome. SUMMARY: New evidence has emerged about the pathophysiological implications of incomplete neuromuscular recovery. Not only are the pulmonary muscles functionally impaired, but respiratory control is also affected. Residual paralysis endangers the coordination of the pharyngeal muscles and the integrity of the upper airway. However, neuromuscular monitoring and whenever needed pharmacological reversal prevent residual paralysis.


Asunto(s)
Obstrucción de las Vías Aéreas/etiología , Inhibidores de la Colinesterasa/uso terapéutico , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Neostigmina/uso terapéutico , Bloqueo Neuromuscular/efectos adversos , Respiración/efectos de los fármacos , Obstrucción de las Vías Aéreas/epidemiología , Periodo de Recuperación de la Anestesia , Inhibidores de la Colinesterasa/administración & dosificación , Inhibidores de la Colinesterasa/efectos adversos , Retraso en el Despertar Posanestésico/complicaciones , Retraso en el Despertar Posanestésico/epidemiología , Retraso en el Despertar Posanestésico/fisiopatología , Humanos , Incidencia , Neostigmina/administración & dosificación , Neostigmina/efectos adversos , Monitoreo Neuromuscular/instrumentación , Músculos Respiratorios/efectos de los fármacos , Sugammadex , Resultado del Tratamiento , gamma-Ciclodextrinas/efectos adversos , gamma-Ciclodextrinas/uso terapéutico
16.
Expert Opin Pharmacother ; 17(6): 819-33, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26799963

RESUMEN

INTRODUCTION: Acetylcholinesterase inhibitors (neostigmine, edrophonium) and encapsulating agents (sugammadex and calabadion) can be used to reverse residual neuromuscular blockade (NMB). AREAS COVERED: This review provides information about efficacy, effectiveness, and side effects of drugs (acetylcholinesterase inhibitors and encapsulating agents) used to reverse neuromuscular blocking agents (NMBAs). EXPERT OPINION: The therapeutic range of acetylcholinesterase-inhibitors is narrow and effectiveness studies demonstrate clinicians don't use these unspecific reversal agents effectively to increase postoperative respiratory safety. The encapsulating drugs sugammadex and calabadion reverse all levels of NMB, and complete recovery of muscle strength can be achieved almost immediately after administration. For this reason encapsulating agents can be used as a solution for "cannot intubate cannot ventilate"- situations. Poor binding selectivity of encapsulating agents carries the risk of displacement of the NMBA by a competitively binding drug, which may lead to recurarization. In order to avoid side-effects, related to unspecific binding of endogenous proteins and drugs administered perioperatively it is prudent to titrate the dose of reversal agents to the minimal effective dose, depending on the depth of neuromuscular transmission block identified by neuromuscular transmission monitoring. Calabadions provide a diversified (increased binding selectivity) and expanded (reversal of benzylisoquinolines) spectrum of possible indications.


Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Bloqueo Neuromuscular , Ácidos Sulfónicos/uso terapéutico , gamma-Ciclodextrinas/uso terapéutico , Periodo de Recuperación de la Anestesia , Anestesia General , Edrofonio/uso terapéutico , Humanos , Neostigmina/uso terapéutico , Fármacos Neuromusculares no Despolarizantes , Sugammadex
17.
Minerva Anestesiol ; 82(7): 735-42, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26472231

RESUMEN

BACKGROUND: Postoperative residual curarization (PORC) is an important complication of neuromuscular blocking drug (NMBD) use. This study evaluates the incidence of PORC in the Postanesthesia Care Unit (PACU), its relation to the type of muscle relaxant and reversal agent used, and its implication in the development of postoperative respiratory complications. METHODS: A prospective observational study of cohorts was made with 558 patients operated under general anesthesia. Data regarding patient history, muscle relaxation (train-of-four [TOF]) monitoring, type of relaxants and reversal agents used, and TOF upon admission to the PACU was collected. Four groups were established: cisatracurium, cisatracurium-neostigmine, rocuronium, and rocuronium-sugammadex. An evaluation was made on the incidence of PORC (TOF ratio [TOFr] <0.9) in PACU, and its relation to the relaxants and reversal agents used and to the development of postoperative respiratory complications - minor and major (pneumonia, atelectasis). RESULTS: From a total of 558 patients, 27.9% presented with PORC. According to the NMBD used and the administration or not of a reversal agent, the incidence of PORC in the four groups was: cisatracurium 34%, cisatracurium-neostigmine 28.6%, rocuronium 34%, and rocuronium-sugammadex 1.15%. The global incidence of minor critical respiratory events (CREs) was 14.5%: cisatracurium 27.5%, cisatracurium-neostigmine 17.4%, rocuronium 10.5%, and rocuronium-sugammadex 2.3%, with statistically significant differences. The global incidence of major CREs was 7.5%, and was significantly higher in patients with TOFr<0.9 upon admission to the PACU. CONCLUSIONS: PORC in the PACU is associated to a greater incidence of major and minor respiratory complications. The use of rocuronium-sugammadex significantly reduces the incidence of PORC in the PACU.


Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Retraso en el Despertar Posanestésico/epidemiología , Neostigmina/uso terapéutico , Bloqueo Neuromuscular/efectos adversos , Trastornos Respiratorios/inducido químicamente , gamma-Ciclodextrinas/uso terapéutico , Periodo de Recuperación de la Anestesia , Atracurio/análogos & derivados , Atracurio/uso terapéutico , Humanos , Monitoreo Neuromuscular , Fármacos Neuromusculares no Despolarizantes/uso terapéutico , Estudios Prospectivos , Trastornos Respiratorios/tratamiento farmacológico , Trastornos Respiratorios/epidemiología , Sugammadex
18.
Vet Anaesth Analg ; 42(5): 455-71, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26058553

RESUMEN

OBJECTIVE: To review the evidence regarding the reversal of neuromuscular block (NMB) in companion animals with emphasis on the development and use of newer agents. DATABASE USED: Data sources include scientific reviews and original research publications in both human and veterinary literature using Pubmed and Scopus as search data bases. Unpublished and locally published data on reversal of NMB are presented. CONCLUSIONS: Residual NMB has been shown to increase morbidity and mortality in humans and needs to be avoided. It can be detected only by adequate neuromuscular monitoring. The proper use of reversal agents avoids residual NMB and recurarization should not occur. Anticholinesterase inhibitors, such as edrophonium and neostigmine have been used to reverse NMB when the need for this has been established. Reversal is influenced by several factors and a number of undesirable side- effects of these drugs have been reported. Sugammadex, a γ-cyclodextrin, which was designed specifically to encapsulate rocuronium, is more rapid in its actions, has fewer side effects and can reverse profound NMB induced by aminosteroidal muscle relaxants.


Asunto(s)
Antídotos/administración & dosificación , Inhibidores de la Colinesterasa/administración & dosificación , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Bloqueo Neuromuscular/veterinaria , Fármacos Neuromusculares no Despolarizantes/antagonistas & inhibidores , Mascotas/fisiología , Anestesia Intravenosa/veterinaria , Anestésicos Intravenosos/administración & dosificación , Animales , Edrofonio/administración & dosificación , Datos de Secuencia Molecular , Neostigmina/administración & dosificación , Sugammadex , gamma-Ciclodextrinas/administración & dosificación
19.
Am J Ther ; 22(4): 288-97, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25299637

RESUMEN

Muscle relaxants are used in the perioperative period to aid in endotracheal intubation, facilitate surgical exposure, and in the critical care setting for prolonged relaxation. Until now, the only mechanism to reverse their effect is acetylcholinesterase inhibitors that result in excess parasympathetic activity and require the second drug to prevent this side effect. Additionally, the onset and degree of neuromuscular antagonism are often unpredictable and unreliable. Sugammadex is the first of the cyclodextrins to be used as a therapeutic agent. It quickly, effectively, and safely reverses steroidal neuromuscular blockers by encapsulating the muscle relaxant and rendering it inactive. Sugammadex may be considered the ideal reversal agent and the first drug in its class, which will likely change the practice of anesthesia and clinical neuromuscular pharmacology.


Asunto(s)
Anestesia/métodos , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Relajación Muscular/efectos de los fármacos , gamma-Ciclodextrinas/farmacología , gamma-Ciclodextrinas/uso terapéutico , Humanos , Sugammadex , Resultado del Tratamiento
20.
Am J Ther ; 22(4): 298-317, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25299638

RESUMEN

Although neuromuscular block (NMB) allows immobility for airway management and surgical exposure, termination of its effect is limited by and associated with side effects of acetylcholinesterase inhibitors. Sugammadex is a selective relaxant binding agent that has been shown to reverse deep NMB, even when administered 3 minutes following a 1.2 mg/kg dose of rocuronium. This novel drug is a modified gamma cyclodextrin, that through encapsulation process terminates the effects of rocuronium and vecuronium (aminosteroid muscle relaxants), and enables the anesthesiologists rapidly to reverse profound NMB induced by rocuronium or vecuronium, in a "can't ventilate, can't intubate" crisis. In this review, data from published phase 1, 2, and 3 clinical trials are reviewed and presented. In addition, clinical trials on special patient populations (patients with pulmonary disease and renal insufficiency) are evaluated. Each article reviewed will conclude with a discussion of relevance, focus on adverse event profile, and clinical usefulness.


Asunto(s)
Anestesia/métodos , Retraso en el Despertar Posanestésico/tratamiento farmacológico , Relajación Muscular/efectos de los fármacos , gamma-Ciclodextrinas/farmacología , gamma-Ciclodextrinas/uso terapéutico , Humanos , Sugammadex , Resultado del Tratamiento
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