Sugammadex 16 mg kg−1 can be used for the immediate reversal of neuromuscular block 3 min after administration of rocuronium and could be used in place of succinylcholine for emergency intubation. We have systematically reviewed the efficacy and cost-effectiveness and made an economic assessment of sugammadex for immediate reversal. The economic assessment investigated whether sugammadex appears cost-effective under various assumptions about the value of any reduction in recovery time with sugammadex, the likelihood of a ‘can't intubate, can't ventilate’ (CICV) event, the age of the patient, and the length of the procedure. Three trials were included in the efficacy review. Sugammadex administered 3 or 5 min after rocuronium produced markedly faster recovery than placebo or spontaneous recovery from succinylcholine-induced block. No published economic evaluations were found. Our economic analyses showed that sugammadex appears more cost-effective, where the value of any reduction in recovery time is greater, where the reduction in mortality compared with succinylcholine is greater, and where the patient is younger, for lower probabilities of a CICV event and for long procedures which do not require profound block throughout. Because of the lack of evidence, the value of some parameters remains unknown, which makes it difficult to provide a definitive assessment of the cost-effectiveness of sugammadex in practice. The use of sugammadex in combination with high-dose rocuronium is efficacious. Further research is needed to clarify key parameters in the analysis and to allow a fuller economic assessment.
complications, intubation tracheal; neuromuscular block, recovery; neuromuscular block, rocuronium; neuromuscular block, succinylcholine
Acetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia.
Patients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events.
Eighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group.
Recovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694).
This survey aimed to assess the extent of practice of the Middle Eastern anesthesiologists in the use of neuromuscular blocking agents (NMB) in 2012.
We distributed an electronic survey among 577 members of the Triple-M Middle Eastern Yahoo anesthesia group, enquiring about their practice in the use of neuromuscular blocking agents. Questions concerned the routine first choice use of NMB, choice for tracheal intubation, the use of neuromuscular monitoring (NMT), type of NMB used in difficult airway, frequency of using suxamethonium, cisatracurium, rocuronium and sugammadex, observed side effects of rocuronium, residual curarization, and the reversal of residual curarization of rocuronium.
A total of 71 responses from 22 Middle Eastern institutions were collected. Most of the Middle Eastern anesthesiologists were using cisatracurium and rocuronium frequently for tracheal intubation (39% and 35%, respectively). From the respondents, 2/3 were using suxamethonium for tracheal intubation in difficult airway, 1/3 were using rocuronium routinely and 17% have observed hypersensitivity reactions to rocuronium, 54% reported residual curarization from rocuronium, 78% were routinely using neostigmine to reverse the rocuronium, 21% used sugammadex occasionally, and 35% were using NMT routinely during the use of NMB.
We believe that more could be done to increase the awareness of the Middle Eastern anesthesiologists about the high incidence of PROC (>20%) and the need for routine monitoring of neuromuscular function. This could be accomplished with by developing formal training programs and providing official guidelines.
Middle East; neuromuscular blockers; residual curarization; survey
Sugammadex, a γ-cyclodextrin that encapsulates selectively steroidal neuromuscular blocking agents, such as rocuronium or vecuronium, has changed the face of clinical neuromuscular pharmacology. Sugammadex allows a rapid reversal of muscle paralysis. Sugammadex appears to be safe and well tolerated. Its blood-brain barrier penetration is poor (< 3% in rats), and thus no relevant central nervous toxicity is expected. However the blood brain barrier permeability can be altered under different conditions (i.e. neurodegenerative diseases, trauma, ischemia, infections, or immature nervous system).
Using MTT, confocal microscopy, caspase-3 activity, cholesterol quantification and Western-blot we determine toxicity of Sugammadex in neurons in primary culture. Here we show that clinically relevant sugammadex concentrations cause apoptotic/necrosis neuron death in primary cultures. Studies on the underlying mechanism revealed that sugammadex-induced activation of mitochondria-dependent apoptosis associates with depletion of neuronal cholesterol levels. Furthermore SUG increase CytC, AIF, Smac/Diablo and CASP-3 protein expression in cells in culture. Potential association of SUG-induced alteration in cholesterol homeostasis with oxidative stress and apoptosis activation occurs. Furthermore, resistance/sensitivity to oxidative stress differs between neuronal cell types.
Sugammadex; apoptosis; CytC; AIF; Smac/Diablo and CASP-3.
Sugammadex is a modified gamma-cyclodextrin which is showing favorable outcomes regarding reversal of neuromuscular blockade, especially by rocuronium. It is designed to encapsulate rocuronium and being considered a new class of drugs as selective relaxant binding agents. It has given countless benefits to the patients at risk of incomplete or delayed recovery after neuromuscular block and has renown for another milestone in anesthesia practice. Recurrence of neuromuscular block has not been reported to be associated with the provided doses of sugammadex that are adequate for selected for reversal. Acceptable profiles are brought to light telling safety of sugammadex. However, some questions related to the twitch characteristics those resembled succinylcholine when reversal, the application for rocuronium anaphylaxis, and the hypersensitivity or anaphylaxis to sugammadex remain and are need of further investigation. It is imperative that potential problems that we need attention may include the patient's history of pulmonary disease and allergic disease for using sugammadex.
Allergy; Hypersensitivity; Neuromuscular blockade; Patient safety; Sugammadex
Sugammadex is the first clinical representative of a new class of drugs called selective relaxant binding agents. It has revolutionized the way anesthesiologists think about drug reversal. Sugammadex selectively binds rocuronium or vecuronium, thereby reversing their neuromuscular blocking action. Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any depth of neuromuscular block. So far, it has been approved for use in adult patients and for pediatric patients over 2 years. Since its approval in Europe, Japan, and Australia, further insight on its use in special patient populations and specific diseases have become available. Due to its pharmacodynamic profile, sugammadex, in combination with rocuronium, may have the potential to displace succinylcholine as the “gold standard” muscle relaxant for rapid sequence induction. The use of rocuronium or vecuronium, with the potential of reverse of their action with sugammadex, seems to be safe in patients with impaired neuromuscular transmission, ie, neuromuscular diseases, including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence suggesting an economic advantage of using sugammadex and justifying its relatively high cost for an anesthesia-related drug, is missing.
reversal agent; cyclodextrin; PORC; SRBAs
Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.
neuromuscular block; rocuronium; neuromuscular blocking agent; sugammadex; reversal agent
We report a patient with myotonic dystrophy who showed prolonged rocuronium-induced neuromuscular blockade, although with a fast recovery with sugammadex. During general anesthesia with propofol and remifentanil, the times to spontaneous recovery of the first twitch (T1) of train of four to 10% of control values after an intubating dose of rocuronium 1 mg/kg and an additional dose of 0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively antagonized rocuronium-induced neuromuscular block in 90 s.
Neuromuscular blockade, induced by neuromuscular blocking agents, has allowed prescribed immobility, improved surgical exposure, optimal airway management conditions, and facilitated mechanical ventilation. However, termination of the effects of neuromuscular blocking agents has, until now, remained limited. A novel cyclodextrin encapsulation process offers improved termination of the paralytic effects of aminosteroidal non-depolarizing neuromuscular blocking agents. Sugammadex sodium is the first in a new class of drug called selective relaxant binding agents. Currently, in clinical trials, sugammadex, a modified gamma cyclodextrin, has shown consistent and rapid termination of neuromuscular blockade with few side effects. The pharmacology of cyclodextrins in general and sugammadex in particular, together with the results of current clinical research are reviewed. The ability of sugammadex to terminate the action of neuromuscular blocking agents by direct encapsulation is compared to the indirect competitive antagonism of their effects by cholinesterase inhibitors. Also discussed are the clinical implications that extend beyond fast, effective reversal, including numerous potential perioperative benefits.
modified cyclodextrin; selective relaxant binding agent (SRBA); sugammadex; encapsulation; muscle relaxants; neuromuscular blockade reversal
Background. The obese patients have differences in body composition, drug distribution, and metabolism. Sugammadex at T2 recovery in a dose of 2 mg kg−1 of real body weight (RBW) can completely reverse the NMB block; in our study we investigated the safety and efficacy of Sugammadex dose based on their ideal body weight (IBW). Methods. 40 patients of both sexes undergoing laparoscopic bariatric surgery were enrolled divided into 2 groups according to the dose of Sugammadex: the first received a dose of 2 mg kg−1 of IBW and the second received a dose of 2 mg kg−1 of RBW. Both were anesthetized with doses calculated according to the IBW: fentanyl 2 μg kg−1, propofol 3 mg kg−1, rocuronium 0,6 mg kg−1, oxygen, air, and desflurane (6–8%). Maintenance doses of rocuronium were 1/4 of the intubation dose. Sugammadex was administrated at T2 recovery. Results. The durations of intubation and maintenance doses of rocuronium were similar in both groups. In IBW group, the T4/T1 value of 0.9 was reached in 151 ± 44 seconds and in 121 ± 55 seconds in RBW group (P = 0.07). Discussion. Recovery times to T4/T1 of 0.9 are surprisingly similar in both groups without observing any postoperative residual curarization. Conclusion. Sugammadex doses calculated according to the IBW are certainly safe for a rapid recovery and absence of PORC.
The aim of this prospective audit was to investigate clinical practice related to muscle relaxant reversal and the impact made by the recent introduction of sugammadex on patient outcome at a tertiary teaching hospital.
Data from all patients intubated at our institution during two epochs of seven consecutive days each was collected prospectively. Directly prior to extubation, the train-of-four (TOF) ratio was assessed quantitatively by an independent observer. Postoperative outcome parameters were complications in the recovery room and radiological diagnosed atelectasis or pneumonia within 30 days.
Data from 146 patients were analysed. Three reversal strategies were used: no reversal, neostigmine or sugammadex. The TOF ratio was less than 0.7 in 17 patients (nine no reversal, eight neostigmine) and less than 0.9 in 47 patients (24 no reversal, 19 neostigmine, four sugammadex). Those reversed with sugammadex showed fewer episodes of postoperative oxygen desaturation (15% vs. 33%; P<0.05). TOF ratios of less than 0.7 (P<0.05) and also <0.9 (P<0.01) were more likely associated with X-ray results consistent with postoperative atelectasis or pneumonia.
Our results suggest a significant impact of residual paralysis on patient outcome. The use of sugammadex resulted in the lowest incidence of residual paralysis.
Neostigmine; residual paralysis; sugammadex
Surgical conditions in laparoscopic surgery are largely determined by the depth of neuromuscular relaxation. Especially in procedures that are confined to a narrow working field, such as retroperitoneal laparoscopic surgery, deep neuromuscular relaxation may be beneficial. Until recently, though, deep neuromuscular block (NMB) came at the expense of a variety of issues that conflicted with its use. However, with the introduction of sugammadex, rapid reversal of a deep NMB is feasible. In the current protocol, the association between the depth of NMB and rating of surgical conditions by the surgeon and anesthesiologist is studied.
This is a single-center, prospective, randomized, blinded, parallel group and controlled trial. Eligible patients are randomly assigned to one of two groups: (1) deep NMB (post-tetanic count, one or two twitches; n = 12) and (2) moderate NMB (train-of-four, 1 to 2 twitches, n = 12) by administration of high-dose rocuronium in Group 1 and a combination of atracurium and mivacurium in Group 2. The NMB in Group 1 is reversed by 4 mg/kg sugammadex; the NMB in Group 2 by 1 mg neostigmine and 0.5 mg atropine. Patients are eligible if they are over 18 years, willing to sign the informed consent form, and are scheduled to undergo an elective laparoscopic renal procedure or laparoscopic prostatectomy. A single surgeon performs the surgeries and rates the surgical conditions on a five-point surgical rating scale (SRS) ranging from 1 (poor surgical conditions) to 5 (excellent surgical conditions). The intra-abdominal part of the surgeries is captured on video and a group of five anesthesiologists and ten surgical experts will rate the videos using the same SRS. The primary analysis will be an intention-to-treat analysis. Evaluation will include the association between the level of NMB and SRS, as obtained by the surgeon performing the procedure and the agreement between the scoring of the images by anesthesiologists and surgeons.
We aim to show that under the right conditions the perceived opposing goals of surgeons and anesthesiologists (optimal surgical conditions vs. optimal postoperative conditions) may be met without compromise to either.
ClinicalTrials.gov identifier NCT01631149.
Anesthesia; Neuromuscular block; Surgical rating scale
Sugammadex is a new drug used for the reversal of neuromuscular blockade by rocuronium or vecuronium, a muscle relaxant used as fast acting.
We performed a review of a case of a patient scheduled for osteosynthesis of the ankle with a history of bronchial asthma and sensitization to Dermatophagoides pteronyssinus. After the surgery the patient suffered anaphylaxis, a minute after the use of sugammadex.
We evaluated the drugs used during anesthesia Prick and intradermal, and we obtained positive results with Sugammadex at 1 month, 3 and 6 months. We performed the basophil activation test giving a positive result. Tests show IgE-mediated sensitization with positive skin tests and basophil activation test.
It is believed that prior sensitization may have occurred due to ingestion of cyclodextrins which is present in many foods. The atopic status of this patient may have had some awareness of cyclodextrins. This case has been published as the first documented case of anaphylaxis by sugammadex with normal doses. Our case raises clear that the underlying mechanism of this reaction was an IgE-mediated sensitization.
Neostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuronium-induced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB.
Forty-one left phrenic nerve-hemidiaphragms (from male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Three consecutive single twitches (ST, 0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained for each increase in concentration of rocuronium or clindamycin. The concentrations of rocuronium were cumulatively increased until an 80% to 90% reduction in ST was attained in the Krebs solutions pre-treated with 0 (n = 5), 0.1 (n = 1), 0.25 (n = 1), 0.5 (n = 4), or 1.0 (n = 1) mM clindamycin or with 0 (n = 4), 0.1 (n = 1), 0.5 (n = 5), 1.0 (n = 5), or 2.0 (n = 4) mM clindamycin in combination with 250 nM neostigmine, and so were the concentrations of clindamycin in the Krebs solutions pre-treated with 0 (n = 6) or 250 nM (n = 6) neostigmine.
Clindamycin increased the potency of rocuronium for ST and tetanic fade, irrespective of the presence of neostigmine. Neostigmine shifted the concentration-response curve of rocuronium to the right in the presence or absence of clindamycin. The interaction between rocuronium and clindamycin was synergistic when clindamycin concentrations were in excess of 0.5 mM, irrespective of the presence of neostigmine.
Neostigmine may partially antagonize the neuromuscular block that is induced by a combination of clindamycin and rocuronium. Clinicians are advised to be aware that clindamycin synergistically increases the degree of rocuronium-induced neuromuscular block, even when neostigmine is present.
Clindamycin; Neostigmine; Neuromuscular block; Reversal; Rocuronium; Synergy
We report a case of a patient with tumor of the caecum with coexistent myasthenia gravis (a form according to Osserman II A), requiring general anesthesia for abdominal surgery. To reverse the neuromuscular block induced by vecuronium was used sugammadex.
sugammadex; myasthenia gravis; neuromuscular monitoring; vecuronium
Several neuromuscular blocking (NMB) agents are available for clinical use in anesthesia. The present study was performed in order to identify preferences and behaviors of anesthesiologists for using vecuronium, rocuronium or other NMB agents in their clinical practice.
Material and methods
The cross-sectional survey was applied at the Updated Course of the Colegio Mexicano de Anestesiología performed last year. Of 989, 282 (28.5%) surveys were returned.
Most anesthesiologists were working at both public and private hospitals, performed anesthetic procedures for hospitalized and ambulatory patients, and anesthetized children as well as adults. Respondents did not consider mechanomyography as the gold standard method for neuromuscular monitoring. The T25 was not recognized as a pharmacodynamic parameter that represents the clinical duration of the neuromuscular block. Most answered that vecuronium induces less histamine release than rocuronium, had never used any neuromuscular monitor, did not know the cost of vecuronium and rocuronium, and preferred rocuronium in multiple-sampling vials and vecuronium in either a vial for single or multiple sampling. Rocuronium was preferred for emergency surgery in patients with full stomach only. Almost all of anesthesiologists that conserve the unused drug did it without refrigeration and more than 30% conserve the unused drug in one syringe for further use.
Vecuronium was preferred for most clinical situations, and the decision for this choice was not based on costs. Storage of unused drugs without refrigeration in a single syringe for purpose of future use in several patients represented a dangerous common practice.
It is standard practice to administer a cholinesterase inhibitor (e.g., neostigmine) at the end of a surgical case to reverse suspected effects of neuromuscular blocking agents regardless of whether such residual effects are present. The authors hypothesized that cholinesterase inhibition when given the in absence of neuromuscular blockade (NB) would decrease upper airway dilatory muscle activity and consequently upper airway volume.
The authors measured genioglossus and diaphragm electromyograms during spontaneous ventilation in anesthetized, tracheostomized rats before and after administration of neostigmine (0.03, 0.06, or 0.12 mg/kg), after recovery of the train-of-four ratio (quadriceps femoris muscle) to unity after NB (n = 18). For comparison, the authors made the same measurements in rats that had no previous NB (n = 27). In intact anesthetized rats, the authors measured upper airway volume and end-expiratory lung volume by magnetic resonance imaging before and after 0.12 mg/kg neostigmine (n = 9).
Neostigmine treatment in rats that had fully recovered from NB based on the train-of-four ratio caused dose-dependent decreases in genioglossus electromyogram (to 70.3 = 7.6, 49.2 = 3.2, and 39.7 = 2.3% of control, respectively), decreases in diaphragm electromyogram (to 103.1 ± 6.5, 83.1 ± 4.7, and 68.7 ± 7.3% of control), and decreases in minute ventilation to a nadir value of 79.6 ± 6% of preneostigmine baseline. Genioglossus electromyogram effects were the same when neostigmine was given with no previous NB. Neostigmine caused a decrease in upper airway volume to 83 ± 3% of control, whereas end-expiratory lung volume remained constant.
The cholinesterase inhibitor neostigmine markedly impairs upper airway dilator volume, genioglossus muscle function, diaphragmatic function, and breathing when given after recovery from vecuronium-induced neuromuscular block.
Despite the significant improvements in the pharmacology of muscle relaxants in the past six decades, the search for the ideal muscle relaxant continues, mainly because of the incomplete efficacy and persistent side effects associated with their antagonism. Clinical concerns remain about the residual paralysis and hemodynamic side effects associated with the classic pharmacologic reversal agents, the acetylcholinesterase inhibitors. Although the development of the “ideal muscle relaxant” remains illusory, pharmacologic advancements hold promise for improved clinical care and patient safety. Recent clinical advances include the development of short-acting nondepolarizing muscle relaxant agents that have fast onset and a very rapid metabolism that allows reliable and complete recovery; and the development of selective, “designer” reversal agents that are specific for a single drug or class of drugs. This article reviews recent developments in the pharmacology of these selective reversal agents: plasma cholinesterases, cysteine, and sugammadex. Although each of the selective reversal agents is specific in its substrate, the clinical use of the combination of muscle relaxant with its specific reversal agent will allow much greater intraoperative titrating ability, decreased side effect profile, and may result in a decreased incidence of postoperative residual paralysis and improved patient safety.
selective reversal agents; cysteine; plasma cholinesterases; sugammadex
Rocuronium and vecuronium, two non-depolarizing neuromuscular blockers, have been widely used in surgery procedures. However, their electrophysiological properties need to be more widely explored. We examined the effects of rocuronium and vecuronium on initial rundown of endplate potential amplitudes in the non-uniform stretched muscle preparation of the rat isolated phrenic nerve diaphragm. More specifically, the endplate potentials were recorded with one microelectrode from a single endplate. The effects of rocuronium or vecuronium each at 4 concentrations (0.5 ×, l ×, 2 ×, 4 × EC95; EC95 = concentration of the drug required to produce the inhibitory effect by 95%) on the amplitude of endplate potentials and its rundown were observed. Treatment of the isolated rat phrenic nerve-diaphragm preparation with rocuronium (2.5–20 μg/ml) or vecuronium (0.5–4 μg/ml) decreased the amplitude of endplate potentials and inhibited its rundown in a concentration-dependent manner. At the concentration (2.5 μg/ml for rocuronium and 0.5 μg/ml for vecuronium) that did not alter the endplate potential amplitude, the onset of reduced endplate potential rundown was 3 and 5 min after administration of rocuronium or vecuronium, respectively. The results suggest that rocuronium and vecuronium block the neuromuscular junction presynaptically and that rocuronium does it faster than vecuronium.
Rocuronium; Vecuronium; Motor endplate; Neuromuscular junction; Diaphragm
Duchenne muscular dystrophy is a hereditary disorder characterized by progressive muscle weakness and contracture, and special care during anesthesia is needed in these patients. Because inhalational anesthetics and succinylcholine can cause fatal results, intravenous anesthetics are commonly used. However, monitorings for the pediatric population are not otherwise specified. We report our experience of a 6 year-old boy that underwent muscle biopsy suspicious of muscle dystrophy under general anesthesia. The patient received midazolam, fentanyl, propofol and a small dose of rocuronium. He was monitored with bispectral index (BIS), acceleromyography (TOF). At the end of surgery, recovery of TOF ratio to 90% was evaluated, followed by injection of pyridostigmine and glycopyrrolate. When reversal of neuromuscular block was confirmed quantitatively and clinically, the patient was extubated and he experienced no complication.
Anesthesia; Bispectral index; Monitoring; Muscular dystrophy
To study the effect of pantoprazole on neuromuscular transmission and its interactions with vecuronium at the neuromuscular junction (NMJ).
Materials and Methods:
Effect of pantoprazole on neuromuscular transmission (2 μM – 16 mM) and reversal of neuromuscular blockade by pantoprazole and vecuronium with neostigmine (3.3 μM), 3,4-diaminopyridine (0.25 mM), KCl (6 mM), and CaCl2 (10 mM) were studied by the indirect and direct stimulated preparation of rat phrenic nerve hemidiaphragm. Cumulative reponse curves (CRC) of vecuronium (1 μM to 32 μM) were studied in the absence and presence of 32 μM, 64 μM, and 128 μM pantoprazole. Time for head drop by vecuronium infusion was recorded in the absence and presence of acute and chronic administration of pantoprazole (1.9 mg/kg) in rabbits.
Pantoprazole potentiated the basal contractile twitch responses at a lower concentration followed by neuromuscular blockade at a higher concentration. The neuromuscular blockade was not reversed by neostigmine (3.3 μM), 3,4-diaminopyridine (0.25 mM), KCl (6 mM), and CaCl2 (10 mM). Pantoprazole potentiated the vecuronium-induced neuromuscular blockade. It decreased the total time for complete blockade in rat phrenic nerve hemidiaphragm preparation (P < 0.05) and decreased the time for the head drop in rabbits with vecuronium infusion (P < 0.0001).
Pantoprazole has a direct neuromuscular blocking action. It has the potential to interact with vecuronium.
Drug interaction; neuromuscular junction; pantoprazole; vecuronium
The antimuscarinic effects of atropine were studied in 46 patients to whom neostigmine had been given after operation to reverse the action of a muscle relaxant. Neostigmine was given to alternate patients three minutes after, or together with, atropine, and the effects of the two procedures were compared by measuring the secretions which collected in the buccal and oropharyngeal cavities and observing the heart rate.
It was found that the glands of the oral cavity were stimulated to a greater extent when neostigmine was given with atropine than after atropine. Any dose of atropine sufficient to inhibit peristaltic movements of the bowel is more than enough to block completely secretion by the salivary glands, and the appearance of some secretion in all cases after the administration of neostigmine suggests that the bowel was at liberty to react to the neostigmine in every case, but perhaps particularly so when atropine and neostigmine were given mixed. The integrity of an anastomosis of the bowel could be endangered by vigorous peristalsis in the early postoperative period.
Electrocardiograms in about half the patients from each group confirmed earlier work that the muscarinic effects of neostigmine on the heart can be prevented by giving the atropine either before or together with the neostigmine.
Regional anesthesia is widely used to perform different surgical procedures including those performed on the extremities. In this study, the anesthetic effects of adding intrathecal neostigmine or magnesium sulphate to bupivacaine in patients under lower extremities surgeries were assessed.
Materials and Methods:
In this double-blind randomized clinical trial, 90 patients, candidate for lower extremities surgeries in a training hospital, were recruited. The patients with ASA class I and II aging from 20 to 65 years between 2009 and 2010 were evaluated. The selected patients were randomly assigned to receive either bupivacaine alone (Group A, n=30), or bupivacaine plus magnesium sulphate 50% (Group B, n=30), or bupivacaine plus neostigmine (Group C, n=30). Then sensory and motor onset and complete block and the time of recovery were measured.
The sensory block onset time were 3.03 ± 0.981 in group A, 3.90 ± 2.71 in group B and 3.7 ± 1.08 in group C and knee flexion time were not significantly different among the three groups (P > 0.05), whereas the time to complete motor block was significantly longer in group C and motor recovery time were significantly different between groups (P=0.001).
According to the obtained results, it may be concluded that magnesium sulphate is a safe and effective adjuvant for increasing the onset time of motor block.
Bupivacaine; magnesium sulphate; motor block; neostigmine; sensory block; spinal anesthesia
We report a case of presumptive neuroleptic malignant syndrome requiring muscle relaxation for electro-convulsive therapy. short acting muscle relaxation without the use of succinylcholine was achieved using rocvronivm reversed with the novel reversal agent sugammadex. We suggest that this combination is a safe and effective alternative to succinylcholine in such cases.
Neuroleptic malignant syndrome; electro convulsive therapy; succinyl choline; rocuronium; sugammadex
Rocuronium produces faster neuromuscular blockade compared with other neuromuscular blocking drugs. It produces comparable intubating conditions to that of succinylcholine, but does not have the short intubation time of the latter. Hence, it may not be preferable for rapid sequence intubation, but rocuronium with priming may produce comparable intubating time and conditions to that of succinylcholine. Rocuronium with priming may be an alternative to succinylcholine in rapid sequence intubation in conditions where succinylcholine is contraindicated. The present study was conducted to compare the intubating conditions and intubation time of rocuronium with and without priming.
Sixty patients of ASA physical status I and II, aged between 18 and 60 years, of both sexes, were divided into priming and control groups of 30 each. Patients in the priming group received 0.06 mg/kg of rocuronium and those in the control group received normal saline. All patients received fentanyl 1 μg/kg, followed by thiopentone 5 mg/kg for induction. Intubating dose of rocuronium 0.54 mg/kg in the priming group and 0.6 mg/kg in the control group were administered 3 min after priming. Onset time of intubation was assessed using a Train of Four stimuli, and the intubating conditions were compared by the Cooper scoring system.
The onset time of intubation was 50.67±7.39 s in the priming group and 94.00±11.62 s in the control group, with excellent intubating conditions in both the groups and without any adverse effects.
Priming with rocuronium provides excellent intubating conditions in less than 60 s with no adverse effects.
Endotracheal intubation; intubating conditions; priming; rocuronium