RESUMEN
The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty-four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N-TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H-TBW). Patients with higher PBF and rocuronium were dosed based on fat-free mass (H-FFM). A train of four (TOF)-Watch acceleromyography monitor was used to measure the effects of the rocuronium. H-TBW (91.9 ± 28.8 s) had significantly shorter onset time than N-TBW and H-FFM (p = 0.003). H-TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25-0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time.
Asunto(s)
Fármacos Neuromusculares no Despolarizantes , Humanos , Rocuronio , Fármacos Neuromusculares no Despolarizantes/farmacología , Androstanoles/farmacología , China , Obesidad , Tejido AdiposoRESUMEN
BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.
RESUMEN
PURPOSE: The impact of the combination of abdominal peripheral nerve block (PNB) and the depth of neuromuscular blockade on the surgical field were assessed. METHODS: Thirty-eight patients undergoing elective robot-assisted laparoscopic radical prostatectomy (RARP) were randomized into two groups: a PNB group (moderate neuromuscular block [train-of-four 1-3 twitches] with abdominal PNB) and a non-PNB group (deep neuromuscular block [post-tetanic count 0-2 twitches] without abdominal PNB). The primary outcome was the change in the depth of the abdominal cavity relaxation assessed by the change in the distance (Δdistance) between the umbilicus port and peritoneum upon pneumoperitoneal pressure increase from 8 to 12 mmHg. The secondary outcomes were the CO2 usage for the pneumoperitoneal pressure increase and the subjective differences in the Surgical Rating Score (SRS) during surgery. RESULTS: The Δdistance and the CO2 usage from 8 to 12 mmHg did not differ significantly between the non-PNB and PNB groups (1.34 ± 0.65 vs. 1.28 ± 0.61 cm, p = 0.763 and 3.64 ± 1.68 vs. 4.34 ± 1.44 L, p = 0.180, respectively). There was also no significant difference in SRS. Comparisons of the Δdistance values for pressure increases from 6 to 8 mmHg, 6 to 10 mmHg and 6 to 12 mmHg between the non-PNB and PNB groups also showed no between-group differences, despite significant intra-group differences (p < 0.001) by pressure increment. CONCLUSIONS: Our findings indicate that moderate neuromuscular block with abdominal PNB maintained an adequate surgical space for RARP, with no significant difference from the space achieved by deep neuromuscular block.
Asunto(s)
Laparoscopía , Bloqueo Nervioso , Bloqueo Neuromuscular , Prostatectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Bloqueo Neuromuscular/métodos , Masculino , Laparoscopía/métodos , Bloqueo Nervioso/métodos , Prostatectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Neumoperitoneo Artificial/métodos , Dióxido de CarbonoRESUMEN
BACKGROUND: Myasthenia gravis (MG) patients interact unpredictably with anesthetic agents, including neuromuscular blocking agents. Here, we investigate the effectiveness of general anesthesia without muscle relaxants using either propofol via target-controlled infusion systems (TCI) or sevoflurane in MG patients undergoing thoracoscopic thymectomy. METHODS: This prospective, open-label, observational study was conducted in a university hospital. We included 90 myasthenic patients undergoing thoracoscopic thymectomy with general anesthesia. Patients received induction and maintenance anesthesia with propofol TCI (group P, n = 45) or induction with propofol 2-3 mg.kg-1 and maintenance anesthesia with sevoflurane (group S, n = 45). In both groups, the procedure was performed under the guidance of entropy with sufentanil but not a muscle relaxant. Intubation conditions, hemodynamic changes, respiratory function, neuromuscular transmission, arterial blood gas, and complications were evaluated. RESULTS: All patients achieved good intubation conditions. Hemodynamic instability was more frequent in group S than in group P, mostly in the induction stage, and was controllable. The reduction in the intraoperative train-of-four ratio from baseline at 30 min, 60 min, and 90 min in group S was 10.3%, 14.2%, and 14.3%, respectively, significantly higher than that in group P (6.8%, 7.2%, and 8.4%, respectively), which completely recovered at the end of the surgery. All patients were extubated in the operating room without complications. No other significant differences between the groups were observed. CONCLUSIONS: Anesthesia with propofol TCI or sevoflurane without muscle relaxants in MG patients offered safe and effective conditions for thoracoscopic thymectomy. Sevoflurane achieved higher levels of intraoperative muscular relaxation than propofol TCI. Postoperative neuromuscular function was not affected by these anesthetics.
Asunto(s)
Éteres Metílicos , Miastenia Gravis , Propofol , Humanos , Propofol/farmacología , Sevoflurano , Timectomía/métodos , Estudios Prospectivos , Miastenia Gravis/cirugía , Anestesia General , Músculos , Anestésicos IntravenososRESUMEN
The neuromuscular blocking potency of rocuronium varies with respiratory pH changes, increasing at lower pH and decreasing at higher pH; thus, hyperventilation-induced respiratory alkalosis is expected to decrease the potency of rocuronium. We report a case of anesthetic management of modified electroconvulsive therapy (m-ECT) for a patient monitored with electromyography-based neuromuscular monitoring during two patterns of ventilation to elucidate their relationship and propose the possible mechanisms underlying the effects by computational simulations. Case presentation: The patient was a 25-year-old man with schizophrenia. In m-ECT, hyperventilation may be used to produce longer seizures. We compared the neuromuscular monitoring data recorded during hyperventilation and during normal ventilation while receiving the same dose of rocuronium. Despite receiving the same dose of rocuronium, the time required for the first twitch to decrease to 80% of the control value was delayed in hyperventilation compared to normal ventilation. Conclusions: This case report and computational simulation suggest that respiratory alkalosis might delay the action of rocuronium. It is necessary to consider the delayed action of rocuronium when hyperventilation is performed.
Asunto(s)
Alcalosis Respiratoria , Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes , Masculino , Humanos , Adulto , Rocuronio , Androstanoles , HiperventilaciónRESUMEN
INTRODUCTION/AIMS: The muscle relaxant methocarbamol and the antimyotonic drug mexiletine are widely used for the treatment of muscle spasms, myotonia, and pain syndromes. To determine whether these drugs affect muscle spindle function, we studied their effect on the resting discharge and on stretch-induced action potential frequencies of proprioceptive afferent neurons. METHODS: Single unit action potential frequencies of proprioceptive afferents from muscle spindles in the murine extensor digitorum longus muscle of adult C57BL/6J mice were recorded under resting conditions and during ramp-and-hold stretches. Maximal tetanic force of the same muscle after direct stimulation was determined. High-resolution confocal microscopy analysis was performed to determine the distribution of Nav 1.4 channels, a potential target for both drugs. RESULTS: Methocarbamol and mexiletine inhibited the muscle spindle resting discharge in a dose-dependent manner with IC50 values around 300 µM and 6 µM, respectively. With increasing concentrations of both drugs, the response to stretch was also affected, with the static sensitivity first followed by the dynamic sensitivity. At high concentrations, both drugs completely blocked muscle spindle afferent output. Both drugs also reversibly reduced the specific force of the extensor digitorum longus muscle after tetanic stimulation. Finally, we present evidence for the presence and specific localization of the voltage-gated sodium channel Nav 1.4 in intrafusal fibers. DISCUSSION: In this study we demonstrate that both muscle relaxants affect muscle spindle function, suggesting impaired proprioception as a potential side effect of both drugs. Moreover, our results provide additional evidence of a peripheral activity of methocarbamol and mexiletine.
Asunto(s)
Metocarbamol , Husos Musculares , Animales , Mexiletine/farmacología , Ratones , Ratones Endogámicos C57BL , Husos Musculares/fisiología , Músculo Esquelético/fisiología , Neuronas Aferentes/fisiologíaRESUMEN
AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.
Asunto(s)
Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes , gamma-Ciclodextrinas , Adolescente , Adulto , Androstanoles/efectos adversos , Humanos , Persona de Mediana Edad , Bloqueo Neuromuscular/efectos adversos , Fármacos Neuromusculares no Despolarizantes/efectos adversos , Rocuronio , Sugammadex/farmacología , Adulto Joven , gamma-Ciclodextrinas/farmacología , gamma-Ciclodextrinas/uso terapéuticoRESUMEN
PURPOSE: Stiff person syndrome (SPS), an autoimmune disease that manifests with episodic muscle rigidity and spasms, has anesthetic considerations because postoperative hypotonia may occur. This hypotonia has been linked to muscle relaxants and volatile anesthetics and may persist in spite of neostigmine administration and train-of-four (TOF) monitoring suggesting full reversal. We present a patient with SPS who experienced hypotonia following total intravenous anesthesia (TIVA), which was promptly reversed with sugammadex. These observations are considered in light of the relevant medical literature. CLINICAL FEATURES: A 46-yr-old female patient with SPS underwent breast lumpectomy and sentinel node biopsy. Anesthesia consisted of TIVA (propofol/remifentanil) with adjunctive administration of rocuronium 20 mg to obtain adequate intubating conditions. Despite return of the TOF ratio to 100% within 30 min, hypotonia was clinically evident at conclusion of surgery two hours later. Sugammadex 250 mg reversed residual muscle relaxation permitting uneventful extubation. A literature review identified six instances of postoperative hypotonia (TIVA, n = 3; volatile anesthetics, n = 3) in spite of neostigmine administration (n = 2) and TOF monitoring suggesting full reversal (n = 4). CONCLUSIONS: Patients with SPS may show hypotonia regardless of general anesthetic technique (TIVA vs inhalational anesthesia), which can persist despite recovery of the TOF ratio and may be more effectively reversed by a chelating agent than with an anticholinesterase. If general anesthesia is required, we suggest a cautious approach to administering muscle relaxants including using the smallest dose necessary, considering the importance of clinical assessment of muscle strength recovery in addition to TOF monitoring, and discussing postoperative ventilation risk with the patient prior to surgery.
RéSUMé: OBJECTIF: Le syndrome de la personne raide (SPR), une maladie auto-immune qui se manifeste par une rigidité musculaire et des spasmes épisodiques, requiert certaines considérations anesthésiques en raison du risque d'hypotonie postopératoire. Cette hypotonie a été liée à des myorelaxants et à des anesthésiques volatils et peut persister malgré l'administration de néostigmine et un monitorage du train-de-quatre (TDQ) suggérant une neutralisation complète. Nous présentons le cas d'une patiente atteinte de SPR qui a souffert d'hypotonie après une anesthésie intraveineuse totale (TIVA), laquelle a été rapidement neutralisée à l'aide de sugammadex. Ces observations sont examinées à la lumière de la littérature médicale pertinente. CARACTéRISTIQUES CLINIQUES: Une patiente de 46 ans atteinte de SPR a bénéficié d'une tumorectomie mammaire et d'une biopsie du ganglion sentinelle. L'anesthésie consistait en une TIVA (propofol/rémifentanil) avec administration d'appoint de 20 mg de rocuronium pour atteindre des conditions d'intubation adéquates. Malgré le retour du ratio de TdQ à 100 % dans les 30 minutes, l'hypotonie était cliniquement évidente à la fin de la chirurgie deux heures plus tard. L'administration de 250 mg de sugammadex a neutralisé la relaxation musculaire résiduelle, permettant une extubation sans incident. Une revue de la littérature a identifié six cas d'hypotonie postopératoire (TIVA, n = 3; anesthésiques volatils, n = 3) malgré l'administration de néostigmine (n = 2) et le monitorage du TdQ suggérant une neutralisation complète (n = 4). CONCLUSION: Les patients atteints de SPR peuvent présenter une hypotonie quelle que soit la technique d'anesthésie générale utilisée (TIVA vs anesthésie par inhalation), laquelle peut persister malgré la récupération du rapport de TdQ; cette hypotonie peut être plus efficacement neutralisée par un agent chélateur qu'avec un anticholinestérasique. Si une anesthésie générale est nécessaire, nous suggérons une approche prudente pour l'administration de myorelaxants, y compris l'utilisation de la plus petite dose nécessaire, la prise en compte de l'importance de l'évaluation clinique de la récupération de la force musculaire en plus du monitorage du TdQ, et la communication du risque de ventilation postopératoire au patient avant la chirurgie.
Asunto(s)
Anestésicos por Inhalación , Bloqueo Neuromuscular , Propofol , Síndrome de la Persona Rígida , Humanos , Femenino , Rocuronio , Sugammadex , Neostigmina , Síndrome de la Persona Rígida/complicaciones , Inhibidores de la Colinesterasa , Remifentanilo , Hipotonía Muscular , Anestésicos por Inhalación/efectos adversos , Quelantes , Bloqueo Neuromuscular/métodosRESUMEN
Micromeria biflora, a traditional medicinal plant, is extensively used for treating various painful conditions, such as nose bleeds, wounds, and sinusitis. A phytochemical investigation of the chloroform fraction of Micromeria biflora led to the isolation of salicylalazine. Salicylalazine was assessed in vivo for analgesia, muscle relaxation, sedative, and anti-inflammatory properties, as well as in vitro for COX-1/2 inhibition activities. It was assessed against a hot plate-induced model at different doses. The muscle relaxant potential of salicylalazine was evaluated in traction and inclined screening models, while sedative properties were determined using an open-field model. The anti-inflammatory potential of salicylalazine was assessed in histamine and carrageenan-induced paw edema screening models. Salicylalazine exhibited significant analgesic potential in a dose-dependent manner. In both screening models, an excellent time-dependent muscle-relaxation effect was observed. Salicylalazine demonstrated excellent sedation at high doses. Its anti-inflammatory activity was determined through the initial and late phases of edema. It exhibited anticancer potential against NCI-H226, HepG2, A498, and MDR2780AD cell lines. In vitro, salicylalazine showed preferential COX-2 inhibition (over COX-1) with an SI value of 4.85. It was less effective in the initial phase, while, in the later phase, it demonstrated significant effects at 15 and 20 mg/kg doses compared with the negative control. Salicylalazine did not exhibit cytotoxicity in the MTT assay, preliminarily indicating its safety.
Asunto(s)
Lamiaceae , Extractos Vegetales , Analgésicos/uso terapéutico , Antiinflamatorios/química , Carragenina/efectos adversos , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo , Humanos , Hipnóticos y Sedantes/uso terapéutico , Simulación del Acoplamiento Molecular , Extractos Vegetales/químicaRESUMEN
The accelerometry(AMG) muscle relaxant monitor is the most widely used quantitative muscle relaxant monitor to assess the degree of neuromuscular at present. In this study, the ulnar nerve was stimulated by using train of four stimulation(TOF) mode of the AMG muscle relaxant monitor, and the movement of the adductor pollicis muscle was monitored. In this way, the distribution range of key parameters (acceleration peak value, response time, and TOF ratio) of the adductor pollicis muscle during the use of muscle relaxant in clinical practice is analyzed and will provide a practical basis for the development and improvement of the muscle relaxant monitor.
Asunto(s)
Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes , Estimulación Eléctrica , Músculo Esquelético , Nervio Cubital/fisiologíaRESUMEN
BACKGROUND: The muscle relaxant methocarbamol is widely used for the treatment of muscle spasms and pain syndromes. To elucidate molecular mechanisms of its action, we studied its influence on neuromuscular transmission, on isometric muscle force, and on voltage-gated Na+ channels. METHODS: Neuromuscular transmission was investigated in murine diaphragm-phrenic nerve preparations and muscle force studied on mouse soleus muscles. Nav 1.4 channels and Nav 1.7 channels were functionally expressed in eukaryotic cell lines. RESULTS: Methocarbamol, at 2 mM, decreased the decay of endplate currents, slowed the decay of endplate potentials and reduced tetanic force of soleus muscles. The drug reversibly inhibited current flow through muscular Nav 1.4 channels, while neuronal Nav 1.7 channels were unaffected. CONCLUSIONS: The study provides evidence for peripheral actions of methocarbamol on skeletal muscle. Muscular Na+ channels are a molecular target of methocarbamol. Since Nav 1.7 currents were unaffected, methocarbamol is unlikely to exert its analgesic effect by directly blocking Nav 1.7 channels.
Asunto(s)
Metocarbamol/farmacología , Músculos/efectos de los fármacos , Nervio Frénico/efectos de los fármacos , Canales de Sodio Activados por Voltaje/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Masculino , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacosRESUMEN
Neuropeptides in the SALMFamide family serve as muscle relaxants in echinoderms and may affect locomotion, as the motor behavior in sea cucumbers involves alternating contraction and extension of the body wall, which is under the control of longitudinal muscle. We evaluated the effect of an L-type SALMFamide neuropeptide (LSA) on locomotory performance of Apostichopus japonicus. We also investigated the metabolites of longitudinal muscle tissue using ultra performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to assess the potential physiological mechanisms underlying the effect of LSA. The hourly distance, cumulative duration and number of steps moved significantly increased in sea cucumbers in the fourth hour after injection with LSA. Also, the treatment enhanced the mean and maximum velocity by 9.8% and 17.8%, respectively, and increased the average stride by 12.4%. Levels of 27 metabolites in longitudinal muscle changed after LSA administration, and the increased concentration of pantothenic acid, arachidonic acid and lysophosphatidylethanolamine, and the altered phosphatidylethanolamine/phosphatidylcholine ratio are potential physiological mechanisms that could explain the observed effect of LSA on locomotor behavior in A. japonicus.
Asunto(s)
Neuropéptidos , Pepinos de Mar , Stichopus , Secuencia de Aminoácidos , Animales , Locomoción , MúsculosRESUMEN
The recovery time of the motor evoked potential (MEP) amplitude following a neuromuscular blockade (NMB) during surgery is useful for interpreting low-amplitude waveforms or selecting the baseline waveform. In this study, the MEP data of 195 orthopedic cases who received a bolus dose of rocuronium at the beginning of surgery, between June 2009 and January 2016 were used. A non-linear regression analysis was applied to MEP amplitude data of multiple patients. The time taken for 90% of the maximum-amplitude recovery was estimated from the identified time series model. The 90% amplitude recovery time was 88.6 min in the pharmacological model and 89.4 min in the logistic model. These results were included in the 95% confidence interval of the previous studies. Although MEP amplitude is relatively unstable because of anesthesia, the averaged time series model of MEP amplitude can be estimated by using a large number of data.
Asunto(s)
Anestésicos , Bloqueo Neuromuscular , Anestésicos/farmacología , Potenciales Evocados Motores , Humanos , Análisis de Regresión , Rocuronio/farmacologíaRESUMEN
BACKGROUND & AIMS: Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). Little is known about the combined effects of sublingual nitrate and NSAIDs. We performed a randomized trial to assess whether the combination of NSAIDs and sublingual nitrate is more effective than NSAIDs alone in preventing PEP. METHODS: In a prospective superiority trial, eligible patients underwent ERCP at 12 endoscopic units in Japan, from March 2015 through May 2018. Patients were randomly assigned to groups given diclofenac suppositories (50 mg) within 15 minutes after the endoscopic procedure alone (diclofenac-alone group, n = 442) or in combination with sublingual isosorbide dinitrate (5 mg) 5 minutes before the endoscopic procedure (combination group, n = 444). The primary endpoint was the occurrence of PEP. RESULTS: PEP developed in 25 patients in the combination group (5.6%), and in 42 patients in the diclofenac-alone group (9.5%) (relative risk 0.59; 95% confidence interval 0.37-0.95; P = .03). Moderate to severe pancreatitis developed in 4 patients (0.9%) in the combination group, and 10 patients (2.3%) in the diclofenac-alone group (relative risk 0.12; 95% confidence interval 0.13-1.26; P = .12). There was no serious adverse event related to the additional administration of sublingual nitrate. CONCLUSIONS: In a randomized controlled trial, we found that prophylaxis with rectal diclofenac and sublingual nitrate significantly reduces the overall incidence of PEP compared with diclofenac suppository alone. ClinicalTrials.gov, no: UMIN 000016274.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Diclofenaco/uso terapéutico , Dinitrato de Isosorbide/uso terapéutico , Donantes de Óxido Nítrico/uso terapéutico , Pancreatitis/prevención & control , Administración Sublingual , Anciano , Quimioterapia Combinada , Femenino , Humanos , Dinitrato de Isosorbide/administración & dosificación , Masculino , Persona de Mediana Edad , Donantes de Óxido Nítrico/administración & dosificación , Pancreatitis/etiología , Estudios ProspectivosRESUMEN
Dantrolene, the only therapeutic agent for malignant hyperthermia, is known to have not only a muscle relaxant effect, but also a neuroprotective effect and Alzheimer's disease improving effect. Recently, it has been reported that dantrolene has a weak inhibitory effect on acetylcholinesterase (AChE), which is a therapeutic drug target for Alzheimer's disease. Thus, we focused on developing of AChE inhibitors with benzylpiperidine/piperazine moieties that are based on the dantrolene skeleton. Several derivatives showed an inhibitory activity. Among them, ortho-nitro derivative 8c showed the most potent inhibitory activity with the IC50 value of 34.2 nM. Furthermore, Lineweaver-Burk plot analysis indicated that 8c is AChE-selective inhibitor, which shows only a weak inhibitory effect on butyrylcholinesterase (BuChE) and a non-competitive inhibition.
Asunto(s)
Acetilcolinesterasa/química , Inhibidores de la Colinesterasa/química , Dantroleno/química , Relajantes Musculares Centrales/química , Acetilcolinesterasa/metabolismo , Butirilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/síntesis química , Inhibidores de la Colinesterasa/metabolismo , Dantroleno/síntesis química , Dantroleno/metabolismo , Diseño de Fármacos , Humanos , Concentración 50 Inhibidora , Cinética , Piperazina/química , Piperidinas/química , Relación Estructura-ActividadRESUMEN
Ammi visnaga L. (Visnaga daucoides Gaertn., Family Apiaceae), also known as Khella Baldi or toothpick weed, is an annual or biennial herb indigenous to the Mediterranean region of North Africa, Asia, and Europe. The plant is known to have been used in traditional medicine a long time ago. Nowadays, it is used in modern medicine to treat many aliments such as renal colic and coronary insufficiency, and is used as an antioxidant, antifungal, and antibacterial, with a larvicidal effect on mosquito larvae. Peer-reviewed studies show that these pharmacological activities are due its valuable chemical constituents that include mainly essential oil, polyphenolic compounds including flavonoids, as well as γ-pyrones, represented mainly by khellin and visnagin. Its essential oil is reported to have antiviral, antibacterial, and larvicidal effects, while its flavonoid content is responsible for its antioxidant activity. Its γ-pyrone content has a powerful effect on facilitating the passage of kidney stones and relieving renal colic, in addition to having a relaxant effect on smooth muscle including that of the coronary arteries. The current review represents the progress in research on A. visnaga in terms of either its chemistry or biological activities. This review represents scientific support material for the use of the plant by the pharmaceutical industry.
Asunto(s)
Ammi/química , Antibacterianos/química , Antifúngicos/química , Antioxidantes/química , Flavonoides/química , Fármacos Neuromusculares/química , Aceites Volátiles/química , Polifenoles/química , Animales , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Enfermedad Coronaria/tratamiento farmacológico , Enfermedad Coronaria/fisiopatología , Culicidae/efectos de los fármacos , Culicidae/fisiología , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Humanos , Insecticidas/química , Insecticidas/aislamiento & purificación , Insecticidas/farmacología , Larva/efectos de los fármacos , Larva/fisiología , Fármacos Neuromusculares/aislamiento & purificación , Fármacos Neuromusculares/farmacología , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/farmacología , Extractos Vegetales/química , Plantas Medicinales , Polifenoles/aislamiento & purificación , Polifenoles/farmacología , Cólico Renal/tratamiento farmacológico , Cólico Renal/fisiopatologíaRESUMEN
PURPOSE: The aim of this study was to compare tracheal intubation conditions after induction of anesthesia with a bolus of propofol-sufentanil or propofol-remifentanil and a rapid induction technique. MATERIAL AND METHODS: A total of 70 patients (American Society of Anesthesiologists (ASA) classification III) undergoing outpatient surgery under general anesthesia with intubation for tooth extraction were randomly assigned to two groups in this double-blind study. Patients received either a bolus of remifentanil (3⯵g/kg) or sufentanil (0.3⯵g/kg) together with 2.5â¯mg/kg propofol for intubation. The primary outcome was the percentage of excellent intubation conditions and the secondary outcomes were the percentage of patients with a decrease of over 20% in mean arterial pressure (MAP) or heart rate (HR), time to achieve spontaneous respiration, time between the end of surgery and extubation and time to achieve an Aldrete score of 10. VAS pain score was >3 or having laryngeal pain 15â¯min after arriving in the postanesthesia care unit (PACU) were also analyzed. RESULTS: Intubating conditions (perfectâ¯+ good conditions) were significantly better with remifentanil than with sufentanil (88.5% vs. 68.6%; pâ¯= 0.01). When using remifentanil, the hemodynamic conditions were good. Using remifentanil did not significantly increase the pain score or the laryngeal pain in the recovery room. This was confirmed by no significant differences between the groups for morphine consumption. Remifentanil significantly decreased the time to achieve an Aldrete score of 10. CONCLUSION: When intubation without muscle relaxants is required, intubating conditions are much better when a remifentanil bolus is used compared to a sufentanil bolus. The remifentanil/propofol rapid induction technique is a valuable technique to quickly intubate and achieve good conditions.
Asunto(s)
Anestesia Intravenosa/métodos , Anestésicos Intravenosos , Intubación Intratraqueal/métodos , Propofol , Remifentanilo , Sufentanilo , Extracción Dental/métodos , Adolescente , Adulto , Anestesia General , Anestésicos Intravenosos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/epidemiología , Faringitis/etiología , Faringitis/terapia , Propofol/administración & dosificación , Estudios Prospectivos , Remifentanilo/administración & dosificación , Mecánica Respiratoria/efectos de los fármacos , Sufentanilo/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the effect of different anesthesia management on clinical outcomes in former prematurely born infants undergoing surgeries for retinopathy of prematurity (ROP). METHODS: In this retrospective study, electronic medical record database was searched for all former prematurely born infants (gestational age < 37 weeks and post conceptual age < 60 weeks) who received ROP surgery under inhalational general anesthesia between November 2016 and October 2018. The patients were divided into two groups based on anesthesia management: laryngeal mask airway (LMA) insertion without intravenous muscle relaxant injection and with pressure support ventilation (LMA group) or airway secured with endotracheal tube (ETT) with intravenous muscle relaxant injection and pressure controlled ventilation (ETT group). Primary outcomes included perioperative adverse events and complications. Extubation time and length of stay after surgery were also recorded. RESULTS: Sixty eight preterm infants in the LMA group and 100 preterm infants in the ETT group were included. The incidence of adverse events during surgery (including airway management change and desaturation) was similar in LMA group and ETT group (4.4% vs. 1.0%, P =0.364). During the early recovery period after surgery, the incidence of difficult extubation (extubation time >30 min) was significantly lower in LMA group compared with ETT group (4.4% vs.15.0%, RR=0.262, 95%CI:0.073ï¼0.942, P=0.029). The incidence of respiratory events was similar between the two groups (20.6% vs. 27.0%, P =0.342). However, the incidence of apnea was significantly lower in the LMA group than in the ETT group (5.9% vs.19.0%, RR=0.266, 95%CI: 0.086ï¼0.822, P =0.015). No significant difference was observed between the LMA group and ETT group in incidences of cardiovascular events (0% vs. 1.0%, P =1.000) and unplanned admission to neonatal intensive care unit (5.9% vs. 7.0%, P=0.774). No airway spasm, re-intubation, aspiration or regurgitation was observed during early recovery. During late recovery after returning to ward, the incidence of adverse events was also similar between the two groups (0% vs. 2.0%, P =0.241). The median (IQR) extubation time was 6 (5, 10) min in LMA group and 10 (6, 19) min in ETT group (P < 0.001). The median length of stay after surgery was significantly shortened in LMA group compared with ETT group [20 (17, 22) hours vs. 22 (17, 68) hours, P =0.002]. CONCLUSION: Compared with endotracheal intubation with intravenous muscle relaxant injection, laryngeal mask airway insertion without muscle relaxant could achieve an early extubation, and reduce the incidence of apnea during early recovery period in former prematurely born infants undergoing ROP surgery.
Asunto(s)
Máscaras Laríngeas , Retinopatía de la Prematuridad , Anestesia General/efectos adversos , Preescolar , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Intubación Intratraqueal/efectos adversos , Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/cirugía , Estudios RetrospectivosRESUMEN
CONTEXT: Crocus sativus L. (Iridaceae), or saffron, has been used as food additives and spices. In the traditional medicine of Iran, C. sativus has been used for the treatment of liver disorders, coughs, and as an anti-inflammatory agent for eyes. OBJECTIVE: The current study reviewed the possible therapeutic effects of C. sativus stigma and its petal flavonoid (kaempferol) on respiratory disorders with several mechanisms such as anti-inflammatory, and smooth muscle relaxant effects. MATERIALS AND METHODS: This review article searched databases including PubMed, Google Scholar, and ScienceDirect, up to November 2019. The keywords including; 'Crocus sativus', 'saffron', 'kaempferol', 'airway inflammation', and 'smooth muscle relaxant' were searched. RESULTS: C. sativus reduced nitric oxide (NO), inducible nitric oxide synthase (iNOS) levels and inflammatory cytokines in the lung tissue. Saffron and kaempferol reduced white blood cells (WBCs) and the percentage of neutrophils and eosinophils in bronchoalveolar lavage fluid. Moreover, saffron reduced tracheal responsiveness to methacholine and ovalbumin on tracheal smooth muscles. In addition, kaempferol reduced the total leukocyte and eosinophil counts similar to the effect of dexamethasone and also showed relaxant effects on smooth muscle. DISCUSSION AND CONCLUSION: Crocus sativus and its petal flavonoid, kaempferol, showed relatively potent therapeutic effects on respiratory disorders by relaxation of tracheal smooth muscles via stimulatory or blocking effects on ß-adrenoceptor and muscarinic receptors, respectively. Saffron and kaempferol also decreased production of NO, inflammatory cytokines and chemokines in respiratory systems.
Asunto(s)
Crocus/química , Flavonoides/uso terapéutico , Flores/química , Quempferoles/uso terapéutico , Neumonía/tratamiento farmacológico , Enfermedades Respiratorias/tratamiento farmacológico , Animales , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Antiinflamatorios no Esteroideos/farmacología , Líquido del Lavado Bronquioalveolar/citología , Citocinas/metabolismo , Humanos , Recuento de Leucocitos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Enfermedades Respiratorias/metabolismoRESUMEN
BACKGROUND AND AIMS: Succinylcholine and high dose rocuronium are neuromuscular blocking agents commonly used for rapid sequence induction of anesthesia. Their usage is limited or contraindicated in some circumstances. The aim of this study is to determine the dosage and efficacy of atracurium without priming for rapid sequence induction of anesthesia. MATERIAL AND METHODS: One hundred fifteen surgical patients under general anesthesia were randomised into three groups. All patients were given 2-3 mg/kg propofol and 1 µg/kg fentanyl intravenously for the induction of anesthesia followed by different doses of atracurium (0.6 mg/kg, 0.75 mg/kg or 1 mg/kg) without a priming dose. Tracheal intubation was performed within one minute after the administration of the study drugs. The intubating conditions, vocal cord movement and diaphragm movement were graded as the primary endpoints. Statistical analysis was done using one-way analysis of variance (ANOVA) and Post Hoc tests. RESULTS: Atracurium doses of 1 mg/kg, 0.75 mg/kg, and 0.6 mg/kg provided 51.4%, 43.6% and 26.3% success rates of intubation without coughing or bucking, respectively (P = 0.03). The intubating conditions were graded as excellent or good in 86.5% of the 1 mg/kg atracurium group patients and in 84.6% of the 0.75 mg/kg group patients (P < 0.05). An atracurium dose of 1 mg/kg facilitated significant differences in vocal cord and diaphragm paralysis compared with the dose of 0.6 mg/kg (P = 0.03). CONCLUSION: The administration of a relatively high dose of atracurium without priming can be used as an alternative neuromuscular blocking agent for rapid sequence induction of anesthesia in some circumstances.