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1.
Toxins (Basel) ; 12(11)2020 10 31.
Article in English | MEDLINE | ID: mdl-33142783

ABSTRACT

Coastal taipan (Oxyuranus scutellatus) envenoming causes life-threatening neuromuscular paralysis in humans. We studied the time period during which antivenom remains effective in preventing and arresting in vitro neuromuscular block caused by taipan venom and taipoxin. Venom showed predominant pre-synaptic neurotoxicity at 3 µg/mL and post-synaptic neurotoxicity at 10 µg/mL. Pre-synaptic neurotoxicity was prevented by addition of Australian polyvalent antivenom before the venom and taipoxin and, reversed when antivenom was added 5 min after venom and taipoxin. Antivenom only partially reversed the neurotoxicity when added 15 min after venom and had no significant effect when added 30 min after venom. In contrast, post-synaptic activity was fully reversed when antivenom was added 30 min after venom. The effect of antivenom on pre-synaptic neuromuscular block was reproduced by washing the bath at similar time intervals for 3 µg/mL, but not for 10 µg/mL. We found an approximate 10-15 min time window in which antivenom can prevent pre-synaptic neuromuscular block. This time window is likely to be longer in envenomed patients due to the delay in venom absorption. Similar effectiveness of antivenom and washing with 3 µg/mL venom suggests that antivenom most likely acts by neutralizing pre-synaptic toxins before they interfere with neurotransmission inside the motor nerve terminals.


Subject(s)
Antivenins/pharmacology , Elapid Venoms/antagonists & inhibitors , Elapidae , Muscle Contraction/drug effects , Neuromuscular Blocking Agents/antagonists & inhibitors , Neuromuscular Junction/drug effects , Snake Bites/drug therapy , Animals , Chickens , Elapid Venoms/metabolism , Neuromuscular Blocking Agents/metabolism , Neuromuscular Junction/metabolism , Neuromuscular Junction/physiopathology , Snake Bites/metabolism , Time Factors
2.
Anesthesiology ; 129(5): 970-988, 2018 11.
Article in English | MEDLINE | ID: mdl-30212413

ABSTRACT

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Structure-activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by L-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. METHODS: Adduction of CW 1759-50 with L-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee-approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by L-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. RESULTS: The half-time of adduction of L-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of L-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. CONCLUSIONS: CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by L-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.


Subject(s)
Cysteine/metabolism , Neuromuscular Blockade/methods , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/pharmacology , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Humans , Macaca mulatta , Male , Models, Animal
3.
Article in English | MEDLINE | ID: mdl-29382576

ABSTRACT

Anuran toxins released from the skin glands are involved in defence against predators and microorganisms. Secretion from parotoid macroglands of bufonid toads is a rich source of bioactive compounds with the cytotoxic, cardiotoxic and hemolytic activity. Bufadienolides are considered the most toxic components of the toad poison, whereas the protein properties are largely unknown. In the present work, we analysed the cardio-, myo-, and neurotropic activity of extract and the selected proteins from Bufo bufo parotoids in in vitro physiological bioassays carried out on two standard model organisms: beetles and frogs. Our results demonstrate a strong cardioactivity of B. bufo gland extract. The toad poison stimulates (by 16%) the contractility of the insect heart and displays the cardioinhibitory effect on the frog heartbeat frequency (a 27% decrease), coupled with an irreversible cardiac arrest. The gland extract also exhibits significant myotropic properties (a 10% decrease in the muscle contraction force), whereas its neuroactivity remains low (a 4% decrease in the nerve conduction velocity). Among identified peptides present in the B. bufo parotoid extract are serine proteases, muscle creatine kinase, phospholipid hydroperoxide glutathione peroxidase, cytotoxic T-lymphocyte protein, etc. Some proteins contribute to the cardioinhibitory effect. Certain compounds display the paralytic (myo- and neurotropic) properties. As the toad gland extract exhibits a strong cardiotoxic activity, we conclude that the poison is a potent agent capable of slaying a predator. Our results also provide the guides for the use of toad poison-peptides in therapeutics and new drug development.


Subject(s)
Amphibian Proteins/toxicity , Amphibian Venoms/toxicity , Bufo bufo/physiology , Cardiotoxins/toxicity , Neuromuscular Blocking Agents/toxicity , Neurotoxins/toxicity , Skin/metabolism , Amphibian Proteins/chemistry , Amphibian Proteins/isolation & purification , Amphibian Proteins/metabolism , Amphibian Venoms/chemistry , Amphibian Venoms/isolation & purification , Amphibian Venoms/metabolism , Animals , Bufo bufo/growth & development , Cardiotoxins/chemistry , Cardiotoxins/isolation & purification , Cardiotoxins/metabolism , Female , Gardens , Heart/drug effects , Heart/physiology , Heart Rate/drug effects , Hindlimb , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiology , Neural Conduction/drug effects , Neuromuscular Blocking Agents/chemistry , Neuromuscular Blocking Agents/isolation & purification , Neuromuscular Blocking Agents/metabolism , Neurotoxins/chemistry , Neurotoxins/isolation & purification , Neurotoxins/metabolism , Parks, Recreational , Poland , Proteomics/methods , Ranidae , Sciatic Nerve/drug effects , Sciatic Nerve/physiology , Tenebrio
4.
Article in English | MEDLINE | ID: mdl-29074260

ABSTRACT

While some US populations of the Mohave rattlesnake (Crotalus scutulatus scutulatus) are infamous for being potently neurotoxic, the Mexican subspecies C. s. salvini (Huamantlan rattlesnake) has been largely unstudied beyond crude lethality testing upon mice. In this study we show that at least some populations of this snake are as potently neurotoxic as its northern cousin. Testing of the Mexican antivenom Antivipmyn showed a complete lack of neutralisation for the neurotoxic effects of C. s. salvini venom, while the neurotoxic effects of the US subspecies C. s. scutulatus were time-delayed but ultimately not eliminated. These results document unrecognised potent neurological effects of a Mexican snake and highlight the medical importance of this subspecies, a finding augmented by the ineffectiveness of the Antivipmyn antivenom. These results also influence our understanding of the venom evolution of Crotalus scutulatus, suggesting that neurotoxicity is the ancestral feature of this species, with the US populations which lack neurotoxicity being derived states.


Subject(s)
Crotalid Venoms/metabolism , Crotalus/physiology , Evolution, Molecular , Muscle, Skeletal/drug effects , Neuromuscular Blocking Agents/metabolism , Neurotoxins/metabolism , Reptilian Proteins/metabolism , Animals , Antivenins/pharmacology , Arizona , Chickens , Crotalid Venoms/antagonists & inhibitors , Crotalid Venoms/chemistry , Crotalid Venoms/toxicity , Crotalus/growth & development , Desert Climate , Female , In Vitro Techniques , Lethal Dose 50 , Male , Mexico , Mice, Inbred BALB C , Muscle Contraction/drug effects , Muscle, Skeletal/innervation , Neuromuscular Blocking Agents/antagonists & inhibitors , Neuromuscular Blocking Agents/chemistry , Neuromuscular Blocking Agents/toxicity , Neurotoxins/antagonists & inhibitors , Neurotoxins/chemistry , Neurotoxins/toxicity , Phospholipases A2/chemistry , Phospholipases A2/metabolism , Phospholipases A2/toxicity , Proteomics/methods , Reptilian Proteins/antagonists & inhibitors , Reptilian Proteins/chemistry , Reptilian Proteins/toxicity , Species Specificity , Substrate Specificity , Texas
5.
Anesthesiol Clin ; 35(2): 285-294, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28526149

ABSTRACT

A significant number of commonly administered medications in anesthesia show wide clinical interpatient variability. Some of these include neuromuscular blockers, opioids, local anesthetics, and inhalation anesthetics. Individual genetic makeup may account for and predict cardiovascular outcomes after cardiac surgery. These interactions can manifest at any point in the perioperative period and may also only affect a specific system. A better understanding of pharmacogenomics will allow for more individually tailored anesthetics and may ultimately lead to better outcomes, decreased hospital stays, and improved patient satisfaction.


Subject(s)
Analgesics, Opioid/pharmacology , Anesthesia , Anesthetics, Inhalation/pharmacology , Genomics , Neuromuscular Blocking Agents/pharmacology , Analgesics, Opioid/adverse effects , Analgesics, Opioid/metabolism , Anesthetics, Inhalation/adverse effects , Anesthetics, Inhalation/metabolism , Humans , Malignant Hyperthermia/genetics , Neuromuscular Blocking Agents/adverse effects , Neuromuscular Blocking Agents/metabolism , Perioperative Period , Postoperative Nausea and Vomiting/genetics
6.
Rev. esp. anestesiol. reanim ; 64(2): 105-107, feb. 2017.
Article in Spanish | IBECS | ID: ibc-159440

ABSTRACT

Los neurolépticos son un grupo de medicamentos ampliamente empleados en el tratamiento de cuadros psicóticos, entre sus efectos adversos cabe destacar la posibilidad de desencadenar un síndrome neuroléptico maligno (SNM). El diagnóstico del SNM se determina por exclusión y su manejo terapéutico inicial será la retirada de los neurolépticos junto a la administración de benzodiacepinas y terapia electroconvulsiva (TEC). La TEC representa una efectiva opción terapéutica en estos pacientes así como en aquellos casos que se obtenga una respuesta escasa al manejo con medicamentos antipsicóticos. Revisamos las alternativas terapéuticas y las implicaciones anestésicas que conlleva manejar un paciente programado para TEC, diagnosticado de esquizofrenia paranoide, en el contexto de SNM (AU)


Neuroleptics are a group of drugs widely used in the treatment of psychotic symptoms. Among their adverse effects is the ability to trigger a neuroleptic malignant syndrome (NMS). The diagnosis of NMS is determined by exclusion, and its initial therapeutic management should be the withdrawal of neuroleptics, the administration of benzodiazepines, and electroconvulsive therapy (ECT). ECT is an effective treatment in these patients, and in those cases with a poor response to treatment with antipsychotic drugs. A review is presented on the treatment options and anaesthetic implications of ECT used to handle a patient diagnosed with paranoid schizophrenia in the context of NMS (AU)


Subject(s)
Humans , Male , Middle Aged , Neuroleptic Malignant Syndrome/complications , Neuroleptic Malignant Syndrome/drug therapy , Electroconvulsive Therapy/methods , Electroconvulsive Therapy , Succinylcholine/therapeutic use , Receptors, GABA-A/therapeutic use , Antipsychotic Agents/therapeutic use , Antipyretics/therapeutic use , Electrocardiography , Propofol/therapeutic use , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Nondepolarizing Agents/therapeutic use
7.
Eur J Med Chem ; 126: 15-23, 2017 Jan 27.
Article in English | MEDLINE | ID: mdl-27744183

ABSTRACT

The synthesis, biological evaluation and molecular modeling study of 6,7-dihydro-[1,3,4] thiadiazolo[3,2-a][1,3]diazepine analogues as new class of neuromuscular blocking agents are described. The new compounds act via competitive mechanism with ACh which could be reversed by the anticholinesterase - Physostigmine. Compounds GS-53 (30) and AAH1 (33) induced dose-dependent neuromuscular blockade with onset time of 3 and 10 min, ED50 0.15 and 0.36 mmol/kg i.p., respectively, in rats. Compound 30 proved to be as twice as potent as 33 with rapid onset and shorter duration (P < 0.05). Docking profile of 30 and 33 closely resembles HIE-124 (3), in α7ß2 nAChR receptor. Molecular modeling analysis indicated that hydrogen bonding to Thr120 and Thr124 beside hydrophobic interactions play effective role incorporating the active ligands to nAChR. The obtained model could be useful for further development of new skeletal muscle relaxants.


Subject(s)
Drug Design , Molecular Docking Simulation , Neuromuscular Blocking Agents/chemical synthesis , Neuromuscular Blocking Agents/pharmacology , Thiadiazoles/chemical synthesis , Thiadiazoles/pharmacology , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Animals , Chemistry Techniques, Synthetic , Chickens , Male , Neuromuscular Blocking Agents/chemistry , Neuromuscular Blocking Agents/metabolism , Protein Conformation , Rats , Thiadiazoles/chemistry , Thiadiazoles/metabolism
9.
Rev. esp. anestesiol. reanim ; 61(10): 565-570, dic. 2014.
Article in English | IBECS | ID: ibc-129799

ABSTRACT

Purpose. Bariatric surgery patients are at high risk of perioperative respiratory adverse events. We hypothesized that the use of sugammadex to reverse neuromuscular blockade could improve postoperative respiratory outcomes. Methods. Prospective observational series of consecutive patients scheduled for laparoscopic bariatric surgery in whom neuromuscular blockade was reverted with sugammadex were compared with a historical matched cohort of patients reverted with neostigmines. The necessity of postoperative mechanical ventilation or pathological changes in postoperative chest X-ray were two of the comparisons done. Results. We enrolled 160 patients in each group (Sugammadex - SG and Historical - HG). Two patients (mean, CI 95%), (1.25, 0.34-4.4) in the SG and five patients in the HG (mean, CI 95%), (3.13, 1.34-7.11) required mechanical ventilation immediately after surgery (p = 0.38, chi-square test). Significantly less chest X-ray postoperative changes were observed in the SG: 11 patients (6.9%) versus 26 patients (16.3%) in the HG (Odds ratio OR, CI 95%) (0.36, 0.18-0.8). Conclusion. Requirement of mechanical ventilation is not associated to the reversal agent employed. Less pathological postoperative chest X-ray changes were found in the group of patients whose neuromuscular blockade was reverted with sugammadex (AU)


Objetivos. Los pacientes candidatos a cirugía bariátrica presentan mayor riesgo de eventos respiratorios adversos. Nuestra hipótesis fue que la utilización de sugammadex para revertir el bloqueo neuromuscular podría mejorar los resultados postoperatorios desde el punto de vista respiratorio. Métodos. Se comparó una serie prospectiva de pacientes sometidos a cirugía bariátrica laparoscópica revertidos con sugammadex con una cohorte histórica cotejada de pacientes sometidos a la misma cirugía revertidos con neostigmina. Se compararon, entre otros datos, la necesidad de ventilación mecánica postoperatoria y la aparición de cambios radiológicos patológicos tras la operación. Resultados. Se incluyeron 160 pacientes en cada grupo (Sugammadex [SG] e Histórico HG). Dos pacientes (media 1,25%, IC 95% 0,34-4,4) en el SG y 5 en el HG (media 3,13%, IC 95% 1,34-7,11) precisaron ventilación mecánica inmediatamente después de la cirugía (p = 0,38 test chi-cuadrado). Se observaron significativamente menos cambios en la radiografía posoperatoria de tórax en el grupo SG que en el HG: 11 pacientes (6,9%) frente a 26 (16,3%) (odds ratio 0,36, IC 95% 0,18-0,8). Conclusión. Las necesidades de ventilación mecánica no se asocian al agente reversor empleado. Se observaron menos cambios patológicos en la radiografía postoperatoria de tórax en el grupo de pacientes cuyo bloqueo neuromuscular fue revertido con sugammadex (AU)


Subject(s)
Humans , Male , Female , Bariatric Surgery/methods , Laparoscopy/methods , Laparoscopy/trends , Laparoscopy , Neuromuscular Agents/metabolism , Neuromuscular Agents/therapeutic use , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/therapeutic use , Neostigmine , Prospective Studies , Obesity, Morbid/drug therapy , Obesity, Morbid/surgery , Breath Tests , Respiration Disorders/complications , Respiration Disorders/drug therapy , Respiration Disorders/prevention & control
10.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 58(1): 11-18, ene.-feb. 2014.
Article in Spanish | IBECS | ID: ibc-118585

ABSTRACT

Objetivo. El uso del cemento óseo esta muy extendido en COT, existiendo multitud de estudios experimentales que lo avalan. La mayoría de los ensayos mecánicos están realizados en seco, lo que cuestiona la extrapolación de los resultados a la clínica. El objetivo de este estudio es evaluar si las propiedades mecánicas del polimetilmetacrilato (PMMA) obtenidas en series previas en seco, se mantienen en un medio fisiológico. Material y método. Se ha diseñado un estudio experimental para evaluar este aspecto, utilizando PMMA con antibiótico (vancomicina). Cuatro grupos fueron definidos en función del medio estudiado (seco o líquido) y de la realización de un acondicionamiento previo en suero fisiológico (una semana o un mes). Se hicieron estudios de desgaste y resistencia a flexión según las normativas ISO y ASTM, valorando el desgaste, el coeficiente de fricción, la resistencia a la rotura y el modulo de Young. Las muestras fueron analizadas mediante microscopía electrónica. Resultados. Las muestras ensayadas en medio líquido presentaron menores valores de desgaste, así como menor resistencia a flexión, obteniéndose significación en el desgaste. El tipo de desgaste se modificó de un desgaste abrasivo a uno adhesivo en aquellas muestras estudiadas en medio líquido. El tiempo de acondicionamiento proporcionó menores valores de desgaste (p < 0,05). Conclusiones. Se recomienda precaución a la hora de extrapolar los resultados de los estudios sobre PMMA en seco dado el diferente comportamiento mecánico del cemento en un medio líquido mucho más cercano a la situación clínica real, como es el suero fisiológico (AU)


Purpose. The use of bone cement is widespread in orthopaedic surgery. Most of the mechanical tests are performed in dry medium, making it difficult to extrapolate the results. The objective of this study is to assess if the mechanical properties of polymethylmethacrylate (PMMA), obtained in previous reports, are still present in a liquid medium. Material and method. An experimental study was designed with antibiotic (vancomycin) loaded PMMA. Four groups were defined according to the medium (dry or liquid) and the pre-conditioning in liquid medium (one week or one month). Wear and flexural strength tests were performed according to ASTM and ISO standards. Volumetric wear, friction coefficient, tensile strength, and Young's modulus were analyzed. All samples were examined by scanning electron microscopy (AU)


Subject(s)
Humans , Male , Female , Joint Instability/diagnosis , Joint Instability/therapy , Implants, Experimental/standards , Implants, Experimental , Proprioception , Proprioception/physiology , Proprioception/radiation effects , Biomechanical Phenomena , Biomechanical Phenomena/physiology , Biomechanical Phenomena/radiation effects , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/pharmacokinetics , Neuromuscular Diseases/complications , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/therapy
11.
Rev. esp. anestesiol. reanim ; 60(8): 434-439, oct. 2013.
Article in Spanish | IBECS | ID: ibc-115547

ABSTRACT

Objetivos. Determinar la incidencia de dificultad de intubación traqueal (DIT) en pacientes obesos operados de cirugía bariátrica y valorar los factores predictivos. El objetivo secundario fue determinar los factores que influyeron en la elección del bloqueante neuromuscular (succinilcolina o rocuronio). Métodos. Estudio observacional, prospectivo en pacientes consecutivos de cirugía bariátrica. Se efectuó la intubación traqueal mediante laringoscopia directa con un tubo traqueal con fiador. Se consideró DIT cuando se observó un grado en la clasificación de Cormack-Lehane III - IV o fue necesario aplicar el algoritmo para DIT (laringoscopia con guía Frova y, en caso de no poder intubar, videolaringoscopio Airtraq). Si con estas medidas no era posible la intubación traqueal, se administró sugammadex en aquellos pacientes con rocuronio y posteriormente se realizó la intubación traqueal con anestesia local y fibroscopio. Resultados. Se incluyó a a 166 pacientes. En un caso se realizó la intubación con fibroscopio. De los 165 pacientes restantes, en 14 pacientes se utilizó la succinilcolina y en 151, el rocuronio. Quince pacientes presentaron DIT (9%): en 4 fue necesario el Airtraq; de ellos, uno requirió sugammadex y fue posteriormente intubado con fibroscopio. La incidencia de intubación con fibroscopio fue del 1,2% (IC 95%; 0,3-4%). La DIT se asoció a los grados de Mallampati 3-4 (odds ratio: 3 [IC 95%; 1,37-6,8], sensibilidad 33%, especificidad 91%) y a la distancia tiromentoniana < 6 cm (odds ratio: 4,8 [IC 95%; 1,45-16]; sensibilidad 53%; especificidad 79%). Conclusión. El protocolo de rescate de DIT con Frova y Airtraq evitó el rescate con sugammadex excepto en un caso (AU)


Subject(s)
Humans , Male , Female , Intubation, Intratracheal , Nerve Block/instrumentation , Nerve Block/methods , Nerve Block , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/pharmacokinetics , Neuromuscular Blocking Agents/therapeutic use , Anesthesia, Local/instrumentation , Anesthesia, Local/methods , Nerve Block/trends , Obesity, Morbid/drug therapy , Obesity, Morbid/surgery , Bariatric Surgery/methods , Bariatric Surgery , Succinylcholine/therapeutic use , Prospective Studies , Odds Ratio
12.
Rev. esp. anestesiol. reanim ; 60(8): 465-468, oct. 2013.
Article in English | IBECS | ID: ibc-115551

ABSTRACT

We report two cases in which moderate and intense rocuronium-induced neuromuscular block was reversed intraoperatively with low sugammadex doses in order to facilitate electromyographic evaluation of facial nerve function during surgery of the parotid gland and the middle ear. Acceleromyography was used to assess reversal of neuromuscular block before starting electromyography monitoring. Rocuronium-induced neuromuscular block was reversed with sugammadex 0.22mgkg−1 when the TOF ratio was 0.14 in the first patient, and with sugammadex 2mgkg−1 during intense block (PTC 0) in the second patient. In each case, appropriate neuromuscular function (TOF ratio ≥ 0.9) was established soon after sugammadex administration, and electromyographic evaluation of facial nerve was successfully conducted. The use of rocuronium and sugammadex, coupled with objective neuromuscular monitoring with acceleromyography, assured complete restoration of neuromuscular function and created the optimal conditions for the surgical team


Presentamos 2 casos con bloqueo neuromuscular superficial e intenso inducidos por rocuronio y revertidos intraoperatoriamente con dosis bajas de sugammadex para facilitar la evaluación de la función del nervio facial mediante electromiografía durante la cirugía de la glándula parótida y oído. La aceleromiografía se utilizó para poder valorar el grado de bloqueo neuromuscular antes del comienzo de la electromiografía y para titular la dosis baja apropiada del antagonista. El bloqueo neuromuscular se revirtió con sugammadex 0,22 mgkg−1 para un ratio del tren de 4 (TOFr) de 0,14 en el primer paciente y con sugammadex 2 mgkg−1 durante un bloqueo intenso (PTC 0) en el segundo paciente. La recuperación completa de la función neuromuscular (TOFr ≥ 0,9) se alcanzó después de la administración de sugammadex en ambos casos. La evaluación mediante electromiografía del nervio facial se realizó con éxito después de la reversión con sugammadex. El uso de rocuronio y de sugammadex a dosis bajas, asociado con monitorización objetiva por medio de aceleromiografía, aseguró el restablecimiento completo de la función neuromuscular y permitió condiciones óptimas de trabajo para el equipo quirúrgico


Subject(s)
Humans , Male , Female , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/therapeutic use , Neuromuscular Blockade/instrumentation , Neuromuscular Blockade/methods , Neuromuscular Blockade , Facial Nerve/metabolism , Facial Nerve , Monitoring, Physiologic/methods , Neuromuscular Blockade/trends
14.
Actual. anestesiol. reanim ; 22(2): 2-8[2], abr.-jun. 2012.
Article in Spanish | IBECS | ID: ibc-101633

ABSTRACT

El uso del sugammadex en la práctica clínica ha producido una revolución en el campo de la reversión del bloqueo neuromuscular no despolarizante (BNMND) del grupo de los aminoesteroideos, especialmente rocuronio y vecuronio. Se exponen las últimas novedades en el uso clínico del sugammadex en las poblaciones y patologías especiales, junto con las últimas publicaciones de ensayos clínicos y nuestra experiencia como centro de referencia en la monitorización del bloqueo neuromuscular, así como las nuevas posibilidades terapéuticas del fármaco y las situaciones clínicas con las que el anestesiólogo puede encontrarse en su práctica clínica. Se precisan todavía estudios para poder conocer todas las posibilidades de los usos clínicos del sugammadex en la práctica anestésica. Igualmente, hay un amplio margen para la investigación y el desarrollo de nuevas publicaciones de un fármaco que podría reducir a cero los problemas de la curarización residual, siendo su principal inconveniente su elevado precio(AU)


The use of sugammadex in clinical practice has been a revolution in the field of neuromuscular blockade reversal of no depolarizing (BNMND) group of the aminosteroid, especially rocuronium and vecuronium. We describe the latest developments in clinical use of sugammadex in special populations and conditions, the latest publications of clinical trials and our experience as a reference center for monitoring of neuromuscular blockade, and moreover new therapeutic possibilities of the drug for different clinical situations that the anaesthesiologist can be found in their clinical practice. Studies are required to know all possibilities of clinical use of sugammadex in anaesthetic practice. Furthermore, there are great possibilities for research and development of new publications of a drug that could reduce to zero problems of residual curarization. However, the high price it is the main disadvantage(AU)


Subject(s)
Humans , Male , Female , Clinical Clerkship/methods , Clinical Clerkship/trends , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/therapeutic use , Neuromuscular Blocking Agents/administration & dosage , Neuromuscular Blocking Agents/therapeutic use , Vecuronium Bromide/therapeutic use , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Blocking Agents/pharmacokinetics
15.
Actual. anestesiol. reanim ; 22(2): 9-12[2], abr.-jun. 2012.
Article in Spanish | IBECS | ID: ibc-101634

ABSTRACT

Desde la introducción del curare en la anestesia clínica en 1942, la utilidad de los bloqueantes neuromusculares se ha descrito ampliamente en la literatura. Pero a pesar de sus beneficios, siguen teniendo una serie de limitaciones importantes. La dosis del bloqueante neuromuscular durante la intubación orotraqueal continúa siendo un problema debido a la duración clínica de su efecto en cirugías de corta o mediana duración. También estamos muy limitados ante la necesidad urgente de una reversión inmediata en una situación "no intubable no ventilable". Además en cirugía mayor ambulatoria, se continúa pagando el precio de una duración larga del bloqueante neuromuscular al no tener una reversión rápida y predecible del mismo. Por otra parte, también estamos muy limitados para conseguir unas condiciones quirúrgicas óptimas con un bloqueo profundo hasta el final de cirugías exigentes que lo precisan, debido al problema de la curarización residual. Por todo esto, se analiza el impacto clínico del sugammadex desde su introducción hace cuatro años y cómo nos está ayudando a salvar todas estas limitaciones, abriéndonos puertas a nuevos escenarios en nuestra práctica clínica(AU)


Since the introduction of curare in clinical anesthesia in 1942, the utility of neuromuscular blocking agents has been widely described in literature. But despite its benefits, are still a number of important limitations. The dose of neuromuscular blocker during tracheal intubation remains a problem due to the clinical duration of effect in surgery for short or medium term. We are also limited to the urgent need for an immediate reversal in a "cannot intubate cannot ventilate” situation. Also in ambulatory surgery, continue paying the price for a long duration of neuromuscular blocking by not having a predictable and rapid reversal of it. Moreover we are bound to get optimal surgical conditions with a profound block to the end of demanding surgeries that require it due to the problem of residual curarization. For all this, we analyze the clinical impact of sugammadex since its introduction four years ago and how is helping to save all these limitations, opening doors to new scenarios in our clinical practice(AU)


Subject(s)
Humans , Male , Female , Anesthesia/methods , Anesthesia/trends , Neuromuscular Blocking Agents/administration & dosage , Neuromuscular Blocking Agents/therapeutic use , Intubation/instrumentation , Intubation/methods , Clinical Clerkship/methods , Clinical Clerkship/trends , Anesthesiology/methods , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Blocking Agents/pharmacokinetics , Clinical Clerkship/organization & administration , Clinical Clerkship/standards
16.
Rev. esp. anestesiol. reanim ; 59(4): 187-196, abr. 2012.
Article in Spanish | IBECS | ID: ibc-100368

ABSTRACT

Introducción. Nuestro objetivo fue comprobar si distintas intensidades de neuroestimulación con el catéter estimulador a nivel del nervio femoral, influyen en la adecuación de la analgesia postoperatoria durante las primeras 48h del postoperatorio tras prótesis total de rodilla. Los catéteres estimuladores permiten posicionar la punta del catéter en la proximidad del nervio y, por tanto, reducir la cantidad de anestésico local necesaria para un bloqueo con éxito. En la actualidad, está debatida cuál es la intensidad de estimulación a la que se deben colocar para proporcionar analgesia adecuada, aunque parece ser que si se obtiene con 1mAmp o menos, el bloqueo es más efectivo. Material y métodos. Estudio comparativo, prospectivo y aleatorizado en pacientes intervenidos de prótesis total de rodilla. Tras la cirugía con anestesia subaracnoidea, se realizó un bloqueo femoral continuo con un catéter estimulador a una intensidad de neuroestimulación de entre 0,2 y 0,5mAmp en el grupo 1, entre 0,6 y 1mAmp en el grupo 2, igual o superior a 1,1mAmp en el grupo 3, y en el grupo 4 se introdujo el catéter entre 3-5cm sin buscar respuesta motora. Se administró a través del catéter ropivacaína 0,2% 0,4mL/kg y perfusión a 5mL/h, con bolos de 10mL/30min. En todos los pacientes se efectuó también un bloqueo del nervio ciático con 20ml de ropivacaína 0,5%. Se registraron los datos demográficos de los pacientes, características de la analgesia postoperatoria, bloqueo sensitivo y motor en cada territorio, bolos solicitados y administrados, analgesia de rescate y efectos indeseables a las 8, 16, 24, 36 y 48h. Resultados. Se incluyó a 124 pacientes, 32 en grupo 1 (25,8%), 21 en grupo 2 (16,9%), 31 en grupo 3 (25%) y 40 en grupo 4 (32,3%). Los 4 grupos fueron homogéneos respecto a edad, talla, peso y ASA. En el dolor postoperatorio no se encontraron diferencias estadísticamente significativas, excepto durante el movimiento a las 36h en el territorio femoral (p=0,032). También se encontraron diferencias estadísticamente significativas en el bloqueo sensitivo en territorio femoral a las 48h (p=0,019) y en el femorocutáneo a las 8 (p=0,049) y a las 24h (p=0,045). Con relación al bloqueo motor, tan solo se encontraron diferencias en el nervio obturador a las 24h (p=0,016). No hubo diferencias en la analgesia de rescate, bolos PCA solicitados y administrados, excepto en el número de bolos solicitados a las 16h, que fueron menores en el grupo 3 (p= 0,049). Tampoco hubo diferencias significativas en los efectos indeseables ni en el grado de satisfacción de los pacientes entre los 4 grupos. Conclusiones. En nuestro estudio, no se ha encontrado influencia de la intensidad de neuroestimulación a la que responde el sistema neuromuscular implicado cuando se coloca un catéter estimulador a nivel femoral sobre la analgesia que proporciona tras la cirugía protésica de rodilla(AU)


Introduction. Stimulating catheters allow the catheter point to be positioned near the nerve, thus reducing the amount of local anaesthetic required for a successful block. There is currently a debate on what is the stimulation intensity required to provide adequate analgesia, although it does seem that if it is obtained with 1mAmp or less the block is more effective. The objective of the study was to demonstrate whether different neurostimulation intensities with the stimulating catheter at femoral nerve level, had an influence on the adequacy of post-surgical analgesia during the 48h after total knee arthroplasty. Material and methods. A comparative, prospective and randomised study was conducted on patients subjected to total knee replacement. After surgery with subarachnoid anaesthesia, a continuous femoral block was performed with a stimulating catheter at a neurostimulation intensity 0.2 and 0.5mAmp in Group 1, between 0.6 and 1mAmp in Group 2, equal or higher than 1.1mAmp in Group 3, and in Group 4 the catheter was introduced between 3-5cm without looking for a motor response. A dose of 0.2% ropivacaine 0.4mL/kg and an infusion at 5mL/h, with boluses of 10mL/30min, was administered via the catheter. Sciatic nerve block was also performed on all patients with 20ml of 0.5% ropivacaine. The patient demographics were recorded, as well as, post-surgical analgesia details, sensory and motor block in each area, boluses requested, rescue analgesia, and undesirable effects at 8, 16, 24, 36 and 48h. Results. A total of 124 patients were included, 32 in Group 1 (25.8%), 21 in Group 2 (16.9%), 31 in Group 3 (25%), and 40 in group 4 (32.3%). The 4 groups were homogeneous as regards age, height, weight and ASA. There were no statistically significant differences found in the post-operative pain, except during movement in the femoral area at 36hours (p=.032). There were also no statistically significant differences found in the sensory block in the femoral area at 48hours (p=.019) and in the femoral cutaneous nerve block at 8hours (p=.049) or at 24hours (p=.045). As regards motor block, differences were only found in the obturator nerve at 24hours (p=.016). There were no differences in rescue analgesia, patient controlled analgesia (PCA) boluses requested or administered, except that the number of boluses requested at 16hours was less in Group 3 (p=.049). There were also no significant differences in undesirable effects or in the level of satisfaction of the patients between the four groups. Conclusions. In our study, no influence was found on the level of analgesia provided after knee replacement surgery with the neurostimulation intensity to which the neuromuscular system involved responded when a stimulating catheter is inserted at femoral level(AU)


Subject(s)
Humans , Male , Female , Implantable Neurostimulators/trends , Implantable Neurostimulators , Catheters , Analgesia , Knee Prosthesis/trends , Knee Prosthesis , /methods , Analgesia/instrumentation , Analgesia/methods , Postoperative Care , Prospective Studies , Neuromuscular Agents/therapeutic use , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/therapeutic use
17.
Rev. esp. anestesiol. reanim ; 58(10): 578-582, dic. 2011. tab
Article in Spanish | IBECS | ID: ibc-138754

ABSTRACT

Introducción y objetivos: La miastenia gravis es una enfermedad autoinmune que cursa con títulos elevados de anticuerpos del tipo de IgG. Estos anticuerpos, aceleran la destrucción de los receptores colinérgicos e interfieren el mecanismo de la transmisión neuromuscular. El objetivo de este estudio fue identificar si existen diferencias en la respuesta a la monitorización de la función neuromuscular entre rocuronio y vecuronio en pacintes miasténicos, así como identificar las condiciones de extubación en el quirófano o en la sala de cuidados intensivos. Material y métdos: Se realizó un ensayo clínico en una serie de pacientes miasténicos tipo II a y II b, según la clasificación de Osserman, aleatorizado, simple ciego, subdivididos en: grupo VEC (vecuronio) y grupo ROC (rocuronio). Como parámetros se registraron oximetría, capnografía, frecuencia cardiaca, presión arterial no invasiva, electrocardiograma y función neuromuscular. Ésta se monitorizó con un acelerómetro. Se administró 25% de la dosis del bloqueante neuromuscular intraoperatoriamente. El mantenimiento se realizó con infusión continua de propofol y fentalino. Todos los pacientes se extubaron por criterios clínicos y se corroboró con el cociente T4/T1. Resultados: El tiempo de recuperación del 25% (T-25), fue de 53,1 +- 1,9 min en el grupo ROC frente a 65,2 +- 0,8 min en el grupo VEC (p=0,01) y el tiempo total de bloqueo (T-90) fue 71,3+- 2,7 min en el grupo ROC frente a 96,3+- 1,2 min. en el grupo VEC (P=0,001). De los 30 pacientes del Grupo ROC se extubaron 28 (93,3 %), con una recuperación de la altura del twitch de 89,1 +- 0,5 % y un cociente T4/T1 de 0,83. La diferencia fue estadísticamente significativa (p=0,001). No se administraron dosis de mantenimiento ni se empleó reversión en ningún paciente. Conclusiones: El rocuronio resultó con mejor perfil frente a vecuronio, con lo cual se evita la depresión respiratoria con sus consecuencias inmediatas, principal motivo de búsqueda de un fármaco cuyas características se aproximen a las necesidades clínicas de estos pacientes (AU)


BACKGROUND AND OBJECTIVES: Myasthenia gravis is an autoimmune disease marked by high titers of immunoglobulin G antibodies, which accelerate destruction of cholinergic receptors and interfere with neuromuscular transmission. This study aimed to determine whether neuromuscular function under a rocuronium block is different from function under a vecuronium block patients with myasthenia gravis and to describe extubation conditions in the operating room or the intensive care unit. MATERIAL AND METHODS: Randomized, single-blind clinical trial enrolling patients with myasthenia gravis type IIa and IIb according to the classification of Osserman. The patients were randomized to groups receiving a vecuronium or rocuronium block. We recorded arterial oxygen saturation, capnogram, heart rate, noninvasive blood pressure, electrocardiogram, and neuromuscular function by accelerometry. During surgery 25% of the total dose of the neuromuscular blocking agent was administered. Maintenance was with a continuous infusion of propofol and fentanyl. All patients were extubated according to clinical criteria, confirmed by train-of-four ratio (T4/T1). RESULTS: The mean (SD) time elapsed before recovery of 25% of neuromuscular function was 53.1 (1.9) min in the rocuronium group and 56.2 (0.8) min in the vecuronium group (P = .01). Time elapsed before recovery of 90% of function was 71.3 (2.7) min in the rocuronium group and 96.3 (1.2) min in the vecuronium group (P = .001). Twenty-eight of the 30 patients in the rocuronium group (93.3%) were extubated with recovery of 89.1% (0.5%) of twitch response and a T4/T1 ratio of 0.83. The difference between groups was statistically significant (P = .01). In no case was it necessary to administer a maintenance dose or reverse the block. CONCLUSIONS: The rocuronium block had a better profile than the vecuronium block in this study. With this blocking agent we were able to circumvent respiratory depression, with its immediate consequences, and thus meet the main clinical criterion when anesthetizing patients with myasthenia gravis (AU)


Subject(s)
Female , Humans , Male , Myasthenia Gravis/drug therapy , Receptors, Cholinergic/therapeutic use , Neuromuscular Agents/therapeutic use , Neuromuscular Blocking Agents/metabolism , Neuromuscular Blocking Agents/therapeutic use , Neuromuscular Nondepolarizing Agents/metabolism , Neuromuscular Nondepolarizing Agents/pharmacokinetics , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Heart Rate , Propofol/therapeutic use , Fentanyl/therapeutic use
18.
Rev. esp. anestesiol. reanim ; 58(10): 614-617, dic. 2011. ilus
Article in Spanish | IBECS | ID: ibc-138759

ABSTRACT

La distrofia muscular de Becker es una enfermedad que afecta, sobre todo, al músculo esquelético y se caracteriza por necrosis de las fibras musculares y debilidad progresiva. Presentamos el caso de una paciente de 61 años, diagnosticada de esta enfermedad 45 años antes, que iba a ser intervenida de una neoplasia de mama derecha. Se le realizó una anestesia general con propofol, fentanilo y un bloqueante neuromuscular no despolarizante (rocuronio). Se empleó un monitor TOF Watch SX para evaluar continuamente la función neuromuscular por aceleromiografía, y se revirtió el bloqueo neuromuscular con sugammadex. Tras preoxigenación e inducción con fentanilo y propofol, se calibró el acelerómetro y se registró el cociente del tren de cuatro estímulos (TOFr) basal. Se inyectó rocuronio 1 mg/kg, y se evaluaron las respuestas del TOF cada 15 segundos. El máximo descenso del TOF (O) fue de 52 segundos. Se intubó la tráquea sin incidencias. Se mantuvo la anestesia intravenosa y la cirugía duró 74 min. El segundo componente del TOF (T2) reapareció a los 86 min de la dosis inicial. Se administró sugammadex 2 mg/kg. El tiempo desde la inyección de sugammadex hasta TOFr 0,7 fue de 79 seg, hasta TOFr 0,9 de 108 seg y TOFr 1,0 de 152 seg. No se observaron alteraciones electrocardiográficas ni hemodinámicas durante su administración y no hubo signos de bloqueo neuromuscular residual en el despertar ni acontecimientos adversos en las 24 horas posteriores (AU)


Becker muscular dystrophy affects mainly the musculoskeletal system, causing muscle wasting and progressive weakness. A 61-year-old woman with breast cancer, who had been diagnosed with Becker muscular dystrophy 45 years earlier, was scheduled for right mastectomy. We induced general anesthesia with propofol, fentanyl, and a nondepolarizing muscle blocker (rocuronium). Neuromuscular function was monitored continuously by acceleromyographic train-of-four ratio (TOFr) (Watch-SX monitor). The block was reversed with sugammadex. After preoxygenation with fentanyl and propofol, the device was calibrated and the baseline TOFr was recorded. We injected 1 mg/kg of rocuronium and assessed TOF responses every 15 seconds. The maximum decrease in TOF response (to 0 twitches) was at 52 seconds. Tracheal intubation was uneventful. Anesthesia was maintained by intravenous infusion. The operation lasted 74 minutes. The second TOF twitch (T2) reappeared 86 minutes after the initial dose. After we injected 2 mg/kg of sugammadex, a TOFr of 0.7 was reached at 79 seconds; a TOFr of 0.9 was reached at 108 seconds and a TOFr of 1.0 at 152 seconds. No electrocardiographic or hemodynamic abnormalities occurred during sugammadex administration and there were no signs of residual neuromuscular blockade on awakening or adverse events in the following 24 hours (AU)


Subject(s)
Adult , Female , Humans , Middle Aged , Muscular Dystrophies/complications , Muscular Dystrophies/drug therapy , Muscle, Skeletal , Anesthesia, General/methods , Anesthesia, General , Propofol/therapeutic use , Fentanyl/therapeutic use , Muscular Dystrophy, Duchenne/drug therapy , Neuromuscular Blocking Agents/pharmacokinetics , Neuromuscular Blocking Agents/therapeutic use , Anesthesia, General/instrumentation , Anesthesia, General/trends , Neuromuscular Blocking Agents/pharmacology , Neuromuscular Depolarizing Agents/pharmacokinetics , Neuromuscular Depolarizing Agents/therapeutic use , Muscular Dystrophy, Duchenne , Neuromuscular Blocking Agents/metabolism , Muscular Dystrophy, Duchenne/surgery , Muscular Dystrophy, Duchenne/diagnosis
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