ABSTRACT
OBJECTIVE: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating autoimmune disease of the central nervous system. It is known that the disease, which is manifested by a wide variety of symptoms, may exacerbate after anesthesia and show different responses to muscle relaxants in the normal population. It is planned to measure train-of-four (TOF) values of MS patients to be operated under general anesthesia before sugammadex application. MATERIALS AND METHODS: With the approval of the local ethics committee of the University of Health Sciences Bagcilar Training and Research Hospital and with written consents of participants, we anesthetized ten patients (from April 2014 to March 2017) with MS and ten American Society of Anesthesiologists I-III patients without MS. Neuromuscular conduction was assessed by the acceleromyometric method using a TOF-Guard apparatus (Organon, Holland). The patients were extubated after recovery of TOF higher than 0.9. The primary efficacy variable was the time from the start of administration of sugammadex to recovery of the TOF ratio to 0.9. RESULTS: The demographic characteristics of both groups, the type and duration of surgery and anesthesia applied, and the temperature of the operation room were similar. Similar characteristics of both groups were of concern for postoperative residual paralysis, and therefore we did not notice any difference between time to TOF> 90/s for both groups. CONCLUSION: Sugammadex and TOF patients will increase patient safety in general anesthesia practice.
Subject(s)
Anesthesia, General/methods , Neuromuscular Blockade/methods , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , gamma-Cyclodextrins/pharmacology , Adult , Anesthesia Recovery Period , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Multiple Sclerosis , Neuromuscular Junction/physiology , Neuromuscular Nondepolarizing Agents/adverse effects , Prospective Studies , Sugammadex , gamma-Cyclodextrins/adverse effectsABSTRACT
BACKGROUND: Rocuronium-induced neuromuscular block that spontaneously recovered to a train-of-four count of four can be reversed with sugammadex 0.5 or 1.0 mg/kg. We investigated whether these doses of sugammadex can also reverse vecuronium at a similar level of block. METHODS: Sixty-five patients were randomly assigned, and 64 were analyzed in this controlled, superiority study. Participants received general anesthesia with propofol, sevoflurane, fentanyl, and vecuronium. Measurement of neuromuscular function was performed with acceleromyography (TOF-Watch-SX, Organon Teknika B.V., The Netherlands ). Once the block recovered spontaneously to four twitches in response to train-of-four stimulation, patients were randomly assigned to receive sugammadex 0.5, 1.0, or 2.0 mg/kg; neostigmine 0.05 mg/kg; or placebo. Time from study drug injection to normalized train-of-four ratio 0.9 and the incidence of incomplete reversal within 30 min were the primary outcome variables. Secondary outcome was the incidence of reparalysis (normalized train-of-four ratio less than 0.9). RESULTS: Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed a threshold train-of-four count of four to normalized train-of-four ratio of 0.9 or higher in all patients in 4.4 ± 2.3 min (mean ± SD) and 2.6 ± 1.6 min, respectively. Sugammadex 0.5 mg/kg reversed the block in 6.8 ± 4.1 min in 70% of patients (P < 0.0001 vs. 1.0 and 2.0 mg/kg), whereas neostigmine produced reversal in 11.3 ± 9.7 min in 77% of patients (P > 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group. CONCLUSIONS: Sugammadex 1.0 mg/kg, unlike 0.5 mg/kg, properly reversed a threshold train-of-four count of four vecuronium-induced block but did not prevent reparalysis.
Subject(s)
Neuromuscular Blockade , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Vecuronium Bromide/antagonists & inhibitors , gamma-Cyclodextrins/pharmacology , Adult , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , SugammadexABSTRACT
BACKGROUND: Electronic neuromuscular monitoring is not widely used to determine either the reversal requirements for neuromuscular block before extubation of the trachea, or to determine if there is any subsequent postoperative residual neuromuscular block (PORNB). OBJECTIVES: To investigate the incidence of PORNB using acceleromyography after spontaneous recovery of rocuronium-induced block and to compare this with the administration of sugammadex, neostigmine or a placebo. DESIGN: Partially randomised, partially randomised, placebo-controlled, double-blind, four-group parallel-arm study. SETTING: Single-centre study performed between October 2013 and December 2015 in a university hospital. PATIENTS: Of the 134 eligible patients, 128 gave their consent and 125 of these completed the study. INTERVENTIONS: Patients received general anaesthesia with propofol, sevoflurane, fentanyl and rocuronium. Neuromuscular transmission was measured by acceleromyography (TOF-Watch-SX; Organon Teknika B.V., Boxtel, the Netherlands) but the anaesthetist was blind to the results. If the anaesthetist deemed pharmacological reversal to be necessary before extubation of the trachea then patients were assigned randomly to receive either sugammadex (2.0âmg kg), neostigmine (0.05âmg kg) or a placebo. In the postanaesthesia care unit, an independent anaesthetist, unaware of the treatment given, assessed the neuromuscular function using acceleromyography. MAIN OUTCOME MEASURES: The incidence of a normalised train-of-four ratio less than 0.9 on arrival in the recovery room. RESULTS: In total, 125 patients were recruited. Neuromuscular block was allowed to recover spontaneously in 50 patients, whereas the remainder received either sugammadex (27), neostigmine (26) or placebo (22). The number of cases with PORNB were one (3.7%), four (15%), 13 (26%) and 10 (45%) after sugammadex, neostigmine, spontaneous recovery and placebo, respectively. Sugammadex and neostigmine were more effective than placebo [odds ratio (OR): 0.05, 95% confidence interval (CI): 0.005 to 0.403, Pâ=â0.005; OR: 0.22, 95% CI: 0.056 to 0.85, Pâ=â0.028, respectively]. Sugammadex performed better than spontaneous recovery (OR: 0.11, 95% CI: 0.014 to 0.89, Pâ=â0.039) unlike neostigmine (OR: 0.52, 95% CI: 0.15 to 1.79, Pâ=â0.297). Yet, antagonism (pooled data) was more effective than spontaneous recovery (OR: 0.3, 95% CI: 0.1 to 0.9, Pâ=â0.03). CONCLUSION: Although pharmacological reversal based on clinical signs was superior to spontaneous recovery it did not prevent PORNB, irrespective of the reversal agent. TRIAL REGISTRATION: The study is registered under EUDRACT number 2013-001965-17.
Subject(s)
Androstanols/adverse effects , Delayed Emergence from Anesthesia/chemically induced , Muscle Relaxation/drug effects , Neuromuscular Blockade/adverse effects , Neuromuscular Monitoring , Neuromuscular Nondepolarizing Agents/adverse effects , Adult , Delayed Emergence from Anesthesia/diagnosis , Delayed Emergence from Anesthesia/epidemiology , Double-Blind Method , Female , Humans , Incidence , Male , Middle Aged , Muscle Relaxation/physiology , Neuromuscular Blockade/methods , Prospective Studies , RocuroniumSubject(s)
Anesthesiologists , Capital Punishment/methods , Ethics, Medical , Physician's Role , American Medical Association , Anesthetics, Intravenous/supply & distribution , Capital Punishment/legislation & jurisprudence , Certification , Drug Industry , Humans , Jurisprudence , Neuromuscular Nondepolarizing Agents , Pancuronium , Potassium Chloride , Societies, Medical , Suicide, Assisted/ethics , Thiopental/supply & distribution , United StatesABSTRACT
BACKGROUND: Surgical closure of patent ductus arteriosus (PDA) is associated with adverse outcomes. Surgical exposure requires retraction of the lung, resulting in decreased aeration and compliance. Optimal respiratory support for PDA surgery is unknown. Experience with volume guarantee (VG) ventilation at our institution led us to hypothesize that surgery would be better tolerated with automatic adjustment of pressure by VG to maintain tidal volume (VT) during retraction. OBJECTIVE: The objective of this study was to describe ventilator support, VT, and oxygenation of infants supported with VG during PDA surgery. DESIGN/METHODS: Ventilator variables, oxygen saturation, and heart rate were recorded during PDA surgery in a convenience sample of infants during PDA closure on VG. Pressure limit increased 11% and set VT was 26% lower during lung retraction. Fentanyl and pancuronium/vecuronium were used for anesthesia/muscle relaxation. Longitudinal data were analyzed by analysis of variance for repeated measures. RESULTS: Seven infants, 25.4 ± 1.5 weeks and 723 ± 141 g, underwent closure of PDA on VG at a mean age 29.9 days. No air leak, bradycardia, or death occurred. Target VT was maintained with a modest increase in inflation pressure. Oxygenation remained adequate. CONCLUSIONS: VG avoided hypoxemia and maintained adequate VT with only a modest increase in peak inflation pressure and thus may be a useful mode during PDA surgery.
Subject(s)
Cardiac Surgical Procedures/methods , Ductus Arteriosus, Patent/surgery , Hypoxia/prevention & control , Respiration, Artificial/methods , Anesthesia, General/methods , Anesthetics, Intravenous/therapeutic use , Fentanyl/therapeutic use , Heart Rate , Humans , Infant , Infant, Newborn , Infant, Premature , Neuromuscular Nondepolarizing Agents/therapeutic use , Oximetry , Pancuronium/therapeutic use , Pilot Projects , Tidal Volume , Vecuronium Bromide/therapeutic useABSTRACT
OBJECTIVE: To compare baseline cardiovascular function in anesthetised pigs using either pancuronium or vecuronium as a neuromuscular blocker. STUDY DESIGN: Retrospective, non-randomized comparison. ANIMALS: Norwegian Land Race pigs (Sus scrofa domesticus) weighing mean 42 ± SD 3 kg. METHODS: One hundred and sixteen animals from four different research protocols premedicated with identical doses of ketamine, diazepam, atropine and isoflurane, and anaesthetised with pentobarbital, fentanyl, midazolam and N(2)O were arranged into three uniform groups with respect to neuromuscular blocking agent: pancuronium bolus of 0.063 mg kg(-1) followed by 0.14 mg kg(-1) hour(-1) (n = 54), low-dose vecuronium 0.4 mg kg(-1) /0.2 mg kg(-1) hour(-1) (n = 29) and high-dose vecuronium 0.6 mg kg(-1) /0.3 mg kg(-1) hour(-1) (n = 33). RESULTS: The majority of cardiovascular parameters demonstrated no significant differences between groups. For heart rate, there was an overall group difference, p = 0.036. Dromotropy was low in the pancuronium group, with an increased normalised PR-interval compared to the high-dose vecuronium group, median 0.200 interquartile range (0.190, 0.215) versus 0.182 (0.166, 0.199), p < 0.05. Left ventricular compliance was increased in pancuronium-treated animals, demonstrated as a reduction in the nonlinear end-diastolic pressure volume relationship ß compared to both vecuronium groups, 0.021 (0.016, 0.025) versus 0.031 (0.025, 0.046) and 0.031 (0.022, 0.048), p < 0.05. The linear end-diastolic pressure volume relationship EDPVR(lin) was reduced as well in the pancuronium group, compared to the low-dose vecuronium group, 0.131 (0.116, 0.169) versus 0.181 (0.148, 0.247), p < 0.05. CONCLUSIONS: There are only minor haemodynamic differences when using pancuronium compared to vecuronium in the fentanyl-pentobarbital-midazolam-N(2)O anesthetised domestic pigs. Furthermore, increasing doses of vecuronium have minimal haemodynamic effects. CLINICAL RELEVANCE: Experimental studies in pigs using either pancuronium or vecuronium as a neuromuscular blocking agent are comparable with regard to cardiac and haemodynamic performance.
Subject(s)
Hemodynamics/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Swine/physiology , Vecuronium Bromide/pharmacology , Animals , Dose-Response Relationship, Drug , Neuromuscular Nondepolarizing Agents/administration & dosage , Vecuronium Bromide/administration & dosageABSTRACT
BACKGROUND: Magnesium enhances the effect of rocuronium. Sugammadex reverses rocuronium-induced neuromuscular block. The authors investigated whether magnesium decreased the efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular block. METHODS: Thirty-two male patients were randomized in a double-blinded manner to receive magnesium sulfate (MgSO4) 60 mg/kg or placebo intravenously before induction of anesthesia with propofol, sufentanil, and rocuronium 0.6 mg/kg. Neuromuscular transmission was monitored using TOF-Watch SX acceleromyography (Organon Ltd., Dublin, Ireland). In 16 patients, sugammadex 2 mg/kg was administered intravenously at reappearance of the second twitch of the train-of-four (moderate block). In 16 further patients, sugammadex 4 mg/kg was administered intravenously at posttetanic count 1 to 2 (deep block). Primary endpoint was recovery time from injection of sugammadex to normalized train-of-four ratio 0.9. Secondary endpoint was recovery time to final T1. RESULTS: Average time for reversal of moderate block was 1.69 min (SD, 0.81) in patients pretreated with MgSO4 and 1.76 min (1.13) in those pretreated with placebo (P = 0.897). Average time for reversal of deep block was 1.77 min (0.83) in patients pretreated with MgSO4 and 1.98 min (0.58) in those pretreated with placebo (P = 0.572). Times to final T1 were longer compared with times to normalized train-of-four ratio 0.9, without any difference between patients pretreated with MgSO4 or placebo. CONCLUSION: Pretreatment with a single intravenous dose of MgSO4 60 mg/kg does not decrease the efficacy of recommended doses of sugammadex for the reversal of a moderate and deep neuromuscular block induced by an intubation dose of rocuronium.
Subject(s)
Androstanols/antagonists & inhibitors , Magnesium Sulfate/pharmacology , Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , gamma-Cyclodextrins/pharmacology , Adolescent , Adult , Androstanols/adverse effects , Anesthesia Recovery Period , Double-Blind Method , Endpoint Determination , Female , Humans , Injections, Intravenous , Magnesium Sulfate/administration & dosage , Magnesium Sulfate/adverse effects , Male , Middle Aged , Monitoring, Intraoperative , Neuromuscular Blockade/adverse effects , Neuromuscular Nondepolarizing Agents/adverse effects , Preanesthetic Medication , Rocuronium , Sugammadex , Young Adult , gamma-Cyclodextrins/adverse effectsABSTRACT
OBJECTIVES: The benefits of spontaneous breathing over muscle paralysis have been proven mainly in mild lung injury; no one has yet evaluated the effects of spontaneous breathing in severe lung injury. We investigated the effects of spontaneous breathing in two different severities of lung injury compared with muscle paralysis. DESIGN: Prospective, randomized, animal study. SETTING: University animal research laboratory. SUBJECTS: Twenty-eight New Zealand white rabbits. INTERVENTIONS: Rabbits were randomly divided into the mild lung injury (surfactant depletion) group or severe lung injury (surfactant depletion followed by injurious mechanical ventilation) group and ventilated with 4-hr low tidal volume ventilation with spontaneous breathing or without spontaneous breathing (prevented by a neuromuscular blocking agent). Inspiratory pressure was adjusted to control tidal volume to 5-7 mL/kg, maintaining a plateau pressure less than 30 cm H2O. Dynamic CT was used to evaluate changes in lung aeration and the regional distribution of tidal volume. MEASUREMENTS AND RESULTS: In mild lung injury, spontaneous breathing improved oxygenation and lung aeration by redistribution of tidal volume to dependent lung regions. However, in severe lung injury, spontaneous breathing caused a significant increase in atelectasis with cyclic collapse. Because of the severity of lung injury, this group had higher plateau pressure and more excessive spontaneous breathing effort, resulting in the highest transpulmonary pressure and the highest driving pressure. Although no improvements in lung aeration were observed, muscle paralysis with severe lung injury resulted in better oxygenation, more even tidal ventilation, and less histological lung injury. CONCLUSIONS: In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.
Subject(s)
Acute Lung Injury/therapy , Respiratory Paralysis/chemically induced , Respiratory Physiological Phenomena , Severity of Illness Index , Acute Lung Injury/pathology , Acute Lung Injury/physiopathology , Acute-Phase Proteins/metabolism , Animals , Bronchoalveolar Lavage , Bronchoalveolar Lavage Fluid/cytology , Disease Models, Animal , Doxapram/pharmacology , Neuromuscular Nondepolarizing Agents/pharmacology , Neutrophils/metabolism , Pancuronium/pharmacology , Positive-Pressure Respiration , Prospective Studies , Pulmonary Atelectasis/pathology , Pulmonary Gas Exchange/physiology , Pulmonary Surfactants/metabolism , Rabbits , Random Allocation , Respiration, Artificial/adverse effects , Respiratory Mechanics/physiology , Respiratory System Agents/pharmacology , Tidal Volume/physiology , Tomography, X-Ray Computed , Ventilator-Induced Lung Injury/etiologyABSTRACT
BACKGROUND: Intravenous lidocaine is increasingly used in surgical patients. As it has neuromuscular blocking effects, we tested the impact of an intravenous lidocaine infusion on the time course of a rocuronium-induced neuromuscular block. METHODS: Fifty-two adults undergoing surgery were randomly allocated to intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of 2 mg/kg/h or physiological saline (control) throughout surgery. Anaesthesia was induced and maintained with a target-controlled propofol infusion and sufentanil. After loss of consciousness, rocuronium 0.6 mg/kg was given. Neuromuscular transmission was measured using train-of-four (TOF)-watch SX (Organon, Swords Co., Dublin, Ireland) acceleromyography. RESULTS: Onset time (to 95% depression of first twitch) was on average 113.9 s (standard deviation 35.3) with lidocaine and 119.5 s (44.9) with saline (P = 0.618). Total recovery time (TOF ratio 0.9) was on average 58.1 min (15.1) with lidocaine and 54.3 min (16.9) with saline (P = 0.394). Clinical duration (until first twitch has recovered to 25%) was on average 33.3 min (7.2) with lidocaine and 30.6 min (8.1) with saline (P = 0.21). Recovery index (time between 25% and 75% recovery of the first twitch) was on average 11.5 min (5.0) with lidocaine and 10.6 min (4.1) with saline (P = 0.458). Recovery time (between 25% recovery of the first twitch and TOF ratio 0.9) was on average 24.8 min (9.3) with lidocaine and 23.2 min (9.2) with saline (P = 0.541). CONCLUSION: A continuous intravenous infusion of lidocaine has no impact on the time course of the neuromuscular blockade induced by a standard intubation dose of rocuronium.
Subject(s)
Androstanols/pharmacology , Anesthetics, Local/pharmacology , Lidocaine/pharmacology , Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents/pharmacology , Adult , Female , Humans , Injections, Intravenous , Male , Middle Aged , RocuroniumABSTRACT
OBJECTIVE: To quantify the dose of pancuronium required to obtain moderate neuromuscular blockade as monitored by acceleromyography (NMB(mod) : train-of-four count of ≤2) as a part of a balanced anaesthetic protocol in pigs used in cardiovascular research. STUDY DESIGN: Prospective cross-sectional study. ANIMALS: Five pigs (median body weight: 60 (range 60-63) kg). METHODS: Anaesthesia was induced with xylazine, ketamine, atropine and midazolam and maintained with isoflurane in O(2) :air and fentanyl. Pigs received 0.1 mg kg(-1) pancuronium initial bolus to reach NMB(mod) followed by 0.1 mg kg(-1) hour(-1) constant rate infusion (CRI). During anaesthesia a twitch count of 3 or measureable T4/T1 ratio indicated unsatisfactory NMB. In this case additional 0.4 mg boluses of pancuronium were administered IV to effect in addition to the CRI. Descriptive statistical analysis was performed to express the median and range of the bolus and CRI dose of pancuronium in pigs. Cardiovascular parameters were analyzed at selected time points with Friedman Repeated Measures Analysis on Ranks. Spearman Rank test was used to evaluate correlation between parameters. RESULTS: Acceleromyographic monitoring of NMB is feasible in anaesthetized pigs. The median initial dose and rate of pancuronium required to achieve NMB(mod) were 0.10 (range 0.10-0.13) mg kg(-1) and 0.11 (range 0.10-0.21) mg kg(-1) hour(-1) , respectively. The administration rate showed considerable individual variation. CONCLUSIONS AND CLINICAL RELEVANCE: These pancuronium doses can be used as a guideline to achieve NMB(mod) in pigs as part of a balanced anaesthetic protocol. Instrumental NMB monitoring is essential because of individual kinetic variations and compliance to monitoring guidelines.
Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/administration & dosage , Pancuronium/pharmacology , Swine , Animals , Cardiovascular Physiological Phenomena/drug effects , Dose-Response Relationship, DrugABSTRACT
Several studies from our laboratory show that axial stretch of the lower esophageal sphincter (LES) in an oral direction causes neurally mediated LES relaxation. Under physiological conditions, axial stretch of the LES is caused by longitudinal muscle contraction (LMC) of the esophagus. Because longitudinal muscle is composed of skeletal muscle in mice, vagal-induced LMC and LES relaxation are both blocked by pancuronium. We conducted studies in rats (thought to have skeletal muscle esophagus) to determine if vagus nerve-mediated LES relaxation is also blocked by pancuronium. LMC-mediated axial stretch on the LES was monitored using piezoelectric crystals. LES and esophageal pressures were monitored with a 2.5-Fr solid-state pressure transducer catheter. Following bilateral cervical vagotomy, the vagus nerve was stimulated electrically. LES, along with the esophagus, was harvested after in vivo experiments and immunostained for smooth muscle (smooth muscle α-actin) and skeletal muscle (fast myosin heavy chain). Vagus nerve-stimulated LES relaxation and esophageal LMC were reduced in a dose-dependent fashion and completely abolished by pancuronium (96 µg/kg) in six rats (group 1). On the other hand, in seven rats, LES relaxation and LMC were only blocked completely by a combination of pancuronium (group 2) and hexamethonium. Immunostaining revealed that the longitudinal muscle layer was composed of predominantly skeletal muscle in the group 1 rats. On the other hand, the longitudinal muscle layer of group 2 rats contained a significant amount of smooth muscle (P < 0.05). Our study shows tight coupling between axial stretch on the LES and relaxation of the LES, which suggests a cause and effect relationship between the two. We propose that the vagus nerve fibers that cause LMC induce LES relaxation through the stretch-sensitive activation of inhibitory motor neurons.
Subject(s)
Esophageal Sphincter, Lower/innervation , Esophageal Sphincter, Lower/physiology , Muscle Relaxation/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Vagus Nerve/physiology , Animals , Ganglionic Blockers/pharmacology , Hexamethonium/pharmacology , Male , Mechanoreceptors/physiology , Motor Neurons/drug effects , Motor Neurons/physiology , Muscle Relaxation/drug effects , Muscle, Smooth/innervation , Muscle, Smooth/physiology , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Rats , Rats, Sprague-Dawley , Vagus Nerve/drug effectsABSTRACT
A novel capillary electrophoretic method for the separation of pancuronium (PM) and vecuronium (VM) ions utilizing capacitively coupled contactless conductivity detection was devised and validated. The separation was carried out in bare fused-silica capillaries (50 µm id, 75/45 cm) at 25°C. Optimal BGE was 50 mM borate buffer of pH 9.5 containing 12.5 mg/mL of (2-hydoxypropyl)-γ-CD. The samples were injected hydrodynamically at 1000 mbar for 3 s. Separation was performed at +30 kV. Under such conditions the PM and VM were base-line resolved and the separation took < 4 min. For quantification phenyltrimethylammonium iodide was used as internal standard. Calibration curves were linear for both pancuronium bromide (PMB) and vecuronium bromide (VMB) in the range 25-250 µg/mL with r> 0.9968. The limits of detection were 7 and 6 µg/mL for PMB and VMB, respectively. The accuracy tested by recovery experiment at three concentration levels of added PMB and VMB was satisfactory (95.7-102.7%, n =3, with RSD < 2.61%). The method was successfully applied to the assay of PMB and VMB in commercial injection solutions.
Subject(s)
Electrophoresis, Capillary/methods , Neuromuscular Nondepolarizing Agents/analysis , Pancuronium/analysis , Vecuronium Bromide/analysis , Electric Conductivity , Linear Models , Pharmaceutical Solutions/chemistry , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
The role of 5-hydroxytryptamine (5-HT) 1A (5-HT1A) receptors in lower urinary tract function was examined in urethane-anesthetized female Sprague-Dawley rats. Bladder pressure and the external urethral sphincter electromyogram (EUS EMG) activity were recorded during continuous-infusion transvesical cystometrograms (TV-CMGs) to allow voiding and during transurethral-CMGs (TU-CMGs) which prevented voiding and allowed recording of isovolumetric bladder contractions. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, decreased volume threshold (VT) for initiating voiding and increased contraction amplitude (CA) during TU-CMGs but decreased CA during TV-CMGs. 8-OH-DPAT prolonged EUS bursting as well as the intrabursting silent periods (SP) during voiding. N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamine trihydrochloride (WAY-100635), a 5-HT1A antagonist, increased VT, increased residual volume, markedly decreased voiding efficiency, decreased the amplitude of micturition contractions recorded under isovolumetric conditions, and decreased the SP of EUS bursting. These results indicate that activation of 5-HT1A receptors by endogenous 5-HT lowers the threshold for initiating reflex voiding and promotes voiding function by enhancing the duration of EUS relaxation, which should reduce urethral outlet resistance.
Subject(s)
Anesthesia, General , Muscle Contraction , Receptor, Serotonin, 5-HT1A/metabolism , Serotonin/metabolism , Urinary Bladder/metabolism , Urination , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Animals , Electromyography , Female , Muscle Contraction/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Piperazines/pharmacology , Pressure , Pyridines/pharmacology , Rats , Rats, Sprague-Dawley , Reflex , Serotonin 5-HT1 Receptor Agonists , Serotonin 5-HT1 Receptor Antagonists , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Time Factors , Urinary Bladder/drug effects , Urinary Bladder/innervation , Urination/drug effectsABSTRACT
BACKGROUND: Present practice guidelines recommend sedative-analgesic and neuromuscular blocking administration during therapeutic hypothermia in comatose patients after cardiac arrest. However, none suggests the best administration protocol. In this study, we evaluated intensivists' preferences regarding administration. METHODS: A systematic literature review was conducted to identify clinical studies published between 1997 and July 2009. Selected articles had to meet the following criteria: use of hypothermia to improve neurologic outcome after cardiac arrest, and specific mention of the sedative protocol used. We checked drugs and dose used, the reason for their administration, and the specific type of neurologic and neuromuscular monitoring used. RESULTS: We identified 44 studies reporting protocols used in 68 intensive care units (ICUs) from various countries. Midazolam, the sedative used most often, was used in 39 ICUs at doses between 5 mg/h and 0.3 mg/kg/h. Propofol was used in 13 ICUs at doses up to 6 mg/kg/h. Eighteen ICUs (26%) did not report using any analgesic. Fentanyl was the analgesic used the most, in 33 ICUs, at doses between 0.5 and 10 microg/kg/h, followed by morphine in 4 ICUs. Neuromuscular blocking drugs were routinely used to prevent shivering in 54 ICUs and to treat shivering in 8; in 1 ICU, their use was discouraged. Pancuronium was used the most, in 24 ICUs, followed by cisatracurium in 14. Four ICUs used neuromuscular blocking drug administration guided by train-of-four monitoring and 3 ICUs used continuous monitoring of cerebral activity. CONCLUSIONS: There is great variability in the protocols used for anesthesia and analgesia during therapeutic hypothermia. Very often, the drug and the dose used do not seem the most appropriate. Only 3 ICUs routinely used electroencephalographic monitoring during paralysis. It is necessary to reach a consensus on how to treat this critical care population.
Subject(s)
Analgesia , Anesthesia , Heart Arrest/therapy , Hypothermia, Induced/methods , Analgesics, Opioid , Clinical Protocols , Critical Care , Humans , Hypnotics and Sedatives , Nervous System Diseases/etiology , Nervous System Diseases/prevention & control , Neuromuscular Blocking Agents , Neuromuscular Nondepolarizing Agents , Pancuronium , Practice Guidelines as Topic , Shivering , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
Curare and pancuronium have multiple effects on previously undepressed rat diaphragm; these include depression of transmitter output and prolongation of the refractory period of prejunctional structures. The effect of curare on motor nerve terminals is greater than that of pancuronium. Both drugs depress postjunctional receptors; but curare, in addition, raises the threshold for the generation of muscle action potentials. In addition, these results raise questions about the validity of statistical methods used to calculate transmitter output.
Subject(s)
Androstanes/pharmacology , Curare/pharmacology , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Action Potentials/drug effects , Animals , Diaphragm/drug effects , Muscles/physiology , Pancuronium/pharmacology , Rats , Refractory Period, Electrophysiological/drug effects , Synaptic Transmission/drug effectsABSTRACT
BACKGROUND: Sugammadex is the first selective relaxant binding agent that has been studied for reversal of neuromuscular blockade induced by rocuronium and other steroidal non-depolarizing neuromuscular blocking agents (NMBAs). OBJECTIVES: To assess the efficacy and safety of sugammadex in reversing neuromuscular blockade induced by steroidal non-depolarizing NMBAs and in preventing postoperative residual neuromuscular blockade. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August 2008), and EMBASE (1980 to August 2008). In addition, we handsearched reference lists of relevant articles and meeting abstracts. Furthermore, we contacted the medication's manufacturer for more information. SELECTION CRITERIA: All randomized controlled trials (RCTs) on adult patients (>/= 18 years old) in which sugammadex was compared with placebo or other medications, or in which different doses of sugammadex were compared with each other. We excluded non-randomized trials and studies on healthy volunteers. DATA COLLECTION AND ANALYSIS: We independently performed determination of trial inclusion, quality assessment, and data extraction. We applied standard meta-analytic techniques. MAIN RESULTS: We included18 RCTs (n = 1321 patients). Seven trials were published as full-text papers, and 11 trials only as meeting abstracts. All the included trials had adequate methods of randomization and allocation concealment. The results suggest that, compared with placebo or neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular blockade regardless of the depth of the block. We identified 2, 4, and 16 mg/kg of sugammadex for reversal of rocuronium-induced neuromuscular blockade at T(2) reappearance , 1 to 2 post-tetanic counts, and 3 to 5 minutes after rocuronium, respectively. The number of trials are very limited regarding vecuronium and pancuronium. Serious adverse events occurred in < 1% of all patients who received the medication. There was no significant difference between sugammadex and placebo in terms of the prevalence of drug-related adverse events (RR 1.20, 95% CI 0.61 to 2.37; P = 0.59, I(2) = 0%, 5 RCTs). Also, no significant difference was found between sugammadex and neostigmine for adverse events (RR 0.98, 95% CI 0.48 to1.98; P = 0.95, I(2) = 43%, 3 RCTs). AUTHORS' CONCLUSIONS: Sugammadex was shown to be effective in reversing rocuronium-induced neuromuscular blockade. This review has found no evidence of a difference in the instance of unwanted effects between sugammadex, placebo or neostigmine. These results need to be confirmed by future trials on larger patient populations and with more focus on patient-related outcomes.
Subject(s)
Neuromuscular Blockade , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , gamma-Cyclodextrins/pharmacology , Adult , Androstanols/antagonists & inhibitors , Cholinesterase Inhibitors/pharmacology , Humans , Neostigmine/pharmacology , Pancuronium/antagonists & inhibitors , Randomized Controlled Trials as Topic , Rocuronium , Sugammadex , Vecuronium Bromide/antagonists & inhibitorsABSTRACT
PURPOSE: We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade. METHODS: Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 +/- 3.3 Hz; mean +/- SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated. RESULTS: The concentrations required for approximately 25% fade were 413 microM for hexamethonium (26.8 +/- 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 +/- 2.55% fade), 0.32 microM for pancuronium (25.4 +/- 2.2% fade), and 0.32 microM for cisatracurium (24.7 +/- 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 microM, attenuated the fade induced by hexamethonium (to 16.0 +/- 2.5% fade), d-tubocurarine (to 6.0 +/- 1.6 fade), pancuronium (to 8.0 +/- 4.0% fade), and cisatracurium (to 11.0 +/- 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 +/- 0.11% fade) and cisatracurium (to 13.3 +/- 5.3% fade). Cisatracurium (0.32 microM) showed antiacetylcholinesterase activity (in plasma, 14.2 +/- 1.6%; 6%; in erythrocyt 17.2 +/- 2.66%) similar to that of pancuronium (0.32 microM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium. CONCLUSION: The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.
Subject(s)
Atracurium/analogs & derivatives , Muscle Contraction/drug effects , Neuromuscular Nondepolarizing Agents/pharmacology , Pancuronium/pharmacology , Receptor, Adenosine A1/drug effects , Receptor, Muscarinic M1/drug effects , Receptor, Muscarinic M2/drug effects , Animals , Atracurium/pharmacology , Diamines/pharmacology , Electric Stimulation , Hexamethonium/pharmacology , In Vitro Techniques , Male , Muscarinic Antagonists/pharmacology , Muscle, Skeletal/drug effects , Muscle, Skeletal/innervation , Nicotinic Antagonists/pharmacology , Phrenic Nerve/drug effects , Pirenzepine/pharmacology , Rats , Rats, Wistar , Xanthines/pharmacologyABSTRACT
Sugammadex sodium is the generic drug name for the novel modified gamma cyclodextrin that terminates neuromuscular blockade induced by aminosteroidal neuromuscular blocking agents. Published phase II and phase III clinical data support preclinical and clinical phase I study findings of fast, safe, and efficacious reversal of all levels of neuromuscular blockade induced by rocuronium and vecuronium. Low levels of neuromuscular blockade induced by pancuronium have also been successfully reversed by sugammadex. This agent does not reverse the bis-isoquinoline neuromuscular blocking agents. Special patient populations, including pediatric, elderly, cardiac, and renal-compromised subjects, have been studied in phase III. This update focuses on the most recent findings of phase II and III clinical studies.
Subject(s)
Androstanols/antagonists & inhibitors , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Vecuronium Bromide/antagonists & inhibitors , gamma-Cyclodextrins/therapeutic use , Clinical Trials, Phase II as Topic , Clinical Trials, Phase III as Topic , Dose-Response Relationship, Drug , Humans , Pancuronium/antagonists & inhibitors , Research Design , Rocuronium , Safety , Sugammadex , Time Factors , gamma-Cyclodextrins/adverse effectsABSTRACT
BACKGROUND: Postoperative residual curarisation (PORC) is a serious and underestimated problem and may occur even after relaxation with medium-acting non-depolarising agents. METHODS: One hundred adult patients, scheduled for elective surgical procedures, were enrolled in the study. Atracurium or cis-atracurium was used for relaxation. Neostigmine was administered for reversal at the end of surgery, at the discretion of the attending anaesthesiologist. Neuromuscular transmission was not monitored in the operating room. In the recovery room, the presence of residual block was assessed by a blinded investigator using accelerometry (TOF-Guard, Organon, Holland) immediately after arrival (T-A) and after 45 min (T-B). Those who received neostigmine were allocated to group I (49 patients), and those who did not were allocated to group II (51 patients). RESULTS: The mean duration of anaesthesia was 92 min in group I and 103 min in group II. The respective doses of atracurium were 78.2 and 72.0 mg; and of cis-atracurium--17.6 mg and 18.0 mg. Immediately after arrival, a TOF below 0.7 was detected in 26% of patients, and below 0.9 in 48% of patients. After forty-five minutes the TOF was still below 0.7 in one patient and below 0.9 in seven. The number of patients with residual block (TOF<0.9) did not differ statistically between those who received neostigmine and those who did not (3.92% and 10.2%, respectively). CONCLUSION: The clinical assessment of neuromuscular blockade reversal did not allow for detection of PORC. Neostigmine was not fully effective in reversal.
Subject(s)
Anesthesia Recovery Period , Atracurium/adverse effects , Cholinesterase Inhibitors/therapeutic use , Neostigmine/therapeutic use , Neuromuscular Junction/drug effects , Neuromuscular Nondepolarizing Agents/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Atracurium/antagonists & inhibitors , Elective Surgical Procedures , Electric Stimulation , Female , Humans , Male , Middle Aged , Neuromuscular Junction/physiopathology , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Neurosurgical Procedures , Recovery of Function , Time Factors , Ulnar Nerve , Young AdultABSTRACT
Translational correlates to pain with activities after deep tissue injury have been rarely studied. We hypothesized that deep tissue incision causes greater activation of nociception-transmitting neurons evoked by muscle contraction. In vivo neuronal activity was recorded in 203 dorsal horn neurons (DHNs) from 97 rats after sham, skin-only, or skinâ¯+â¯deep muscle incision. We evaluated DHN responses to static, isometric muscle contractions induced by direct electrical stimulation of the muscle. The effect of pancuronium on DHN response to contractions was also examined. Approximately 50% of DHNs with receptive fields in the hindpaw were excited during muscle contraction. One-second .5- and 1.0-g muscle contractions produced greater DHN activity after skinâ¯+â¯deep muscle incision (median [interquartile range], 32 [5-39] impulses, Pâ¯=â¯.021; and 36 [26-46] impulses, Pâ¯=â¯.006, respectively) than after sham (6 [0-21] and 15 [8-32] impulses, respectively). Neuromuscular blockade with pancuronium inhibited the muscle contractions and DHN activation during electrical stimulation, demonstrating contraction-induced activation. The greater response of spinal DHNs to static muscle contraction after skinâ¯+â¯deep muscle incision may model and inform mechanisms of dynamic pain after surgery. PERSPECTIVE: Completion of various activities is an important milestone for recovery and hospital discharge after surgery. Skinâ¯+â¯deep muscle incision caused greater activation of nociception-transmitting DHNs evoked by muscle contraction compared with skin-only incision. This result suggests an important contribution of deep muscle injury to activity-evoked hyperalgesia after surgery.