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).
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
Rapid and complete reversal of neuromuscular blockade (NMB) is desirable at the end of surgery. Sugammadex reverses rocuronium-induced NMB by encapsulation. It is well tolerated in Caucasian patients, providing rapid reversal of moderate (reappearance of T2) rocuronium-induced NMB. We investigated the efficacy and safety of sugammadex versus neostigmine in Korean patients.
This randomized, safety assessor-blinded trial (NCT01050543) included Korean patients undergoing general anesthesia. Rocuronium 0.6 mg/kg was given prior to intubation with maintenance doses of 0.1-0.2 mg/kg as required. Patients received sugammadex 2.0 mg/kg or neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg to reverse the NMB at the reappearance of T2, after the last rocuronium dose. The primary efficacy endpoint was the time from sugammadex or neostigmine administration to recovery of the train-of-four (TOF) ratio to 0.9. The safety of these medications was also assessed.
Of 128 randomized patients, 118 had evaluable data (n = 59 in each group). The geometric mean (95% confidence interval) time to recovery of the TOF ratio to 0.9 was 1.8 (1.6, 2.0) minutes in the sugammadex group and 14.8 (12.4, 17.6) minutes in the neostigmine group (P < 0.0001). Sugammadex was generally well tolerated, with no evidence of residual or recurrence of NMB; four patients in the neostigmine group reported adverse events possibly indicative of inadequate NMB reversal.
Sugammadex was well tolerated and provided rapid reversal of moderate rocuronium-induced NMB in Korean patients, with a recovery time 8.1 times faster than neostigmine. These results are consistent with those reported for Caucasian patients.
Caucasian; Korean; Neostigmine; Neuromuscular blockade; Rocuronium; Sugammadex
Sugammadex is belonging to a new class of drugs: the selective relaxant binding agents. Sugammadex can reverse residual paralysis by encapsulating free circulating non depolarizing muscle relaxants. The mains advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and the unique ability, for the first time, to reverse rapidly and efficiently deep levels of neuromuscular blockade. However it only works for reversal of rocuronium or vecuronium-induced neuromuscular blockade. When administered 3 min after rocuronium the use of a large dose (16 mg/kg) can even reverse rocuronium significantly faster than the spontaneous recovery after succinylcholine.
Cyclodextrins; Neostigmine; Neuromuscular block; Residual neuromuscular blockade; Rocuronium; Sugammadex
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
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
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.
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
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.
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.
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
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
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
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
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
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
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
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
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.
Non-cardiogenic pulmonary oedema (NCPE) is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, and no evidence of left atrial hypertension/congestive heart failure/fluid overload. The diagnosis of drug-related NCPE relies upon documented exclusion of other causes of NCPE like gastric aspiration, sepsis, trauma, negative pressure pulmonary oedema, etc. We describe two cases (45-year male and 6-year male), who had undergone elective surgery under general anaesthesia. They developed NCPE within 3-5 minutes after administration of ‘neostigmine-glycopyrrolate’ used to reverse residual neuromuscular blockade. Both patients were treated successfully with mechanical ventilatory support, and adjuvant therapy, viz., frusemide, dopamine, steroids. This report emphasizes that this fatal complication may be seen with neostigmine, the pathogenic mechanism remains unknown, and it probably is a drug-related NCPE.
Drug-related NCPE; neostigmine; reversal; non-cardiogenic pulmonary oedema
Neostigmine is commonly used to reverse neuromuscular blockade. A side effect can be parasympathetic stimulation, which may result in heart block. Renal failure can decrease the clearance and increase the half-life of the drug, thus increasing the likelihood of a vagomimetic response. A case is presented where a child with renal failure developed a type I second-degree heart block after neostigmine was given.
Neostigmine is used to antagonize neoromuscluar blocker-induced residual neuromuscular paralysis. Despite a previous meta-analysis, the effect of neostigmine on postoperative nausea and vomiting (PONV) remains unresolved. We reevaluated the effect of neostigmine on PONV while considering the different anticholinergics as potentially confounding factors. We performed a systematic literature search using Medline, Embase, Cochrane library, reference listings, and hand searching with no language restriction through December 2004 and identified 10 clinical, randomized, controlled trials evaluating neostigmine's effect on PONV. Data on nausea or vomiting from 933 patients were extracted for the early (0-6 h), delayed (6-24 h), and overall postoperative periods (0-24 h) and analyzed with RevMan 4.2 (Cochrane Collaboration, Oxford, UK) and multiple logistic regression analysis. The combination of neostigmine with either atropine or glycopyrrolate did not significantly increase the incidence of overall (0-24 h) vomiting (relative risk (RR) 0.91 [0.70-1.18], P=0.48) or nausea (RR 1.24 [95% CI: 0.98-1.59], P=0.08). Multiple logistic regression analysis indicated that that there was not a significant increase in the risk of vomiting with large compared with small doses of neostigmine. In contrast to a previous analysis, we conclude that there is insufficient evidence to conclude that neostigmine increases the risk of PONV.
Vomiting: postoperative, nausea; Statistics: meta analysis; Antagonists (Neuromuscular relaxants): neostigmine; Pharmacology: atropine, glycopyrrolate
The postulated role of the acetylcholine receptor in the formation of neuromuscular synapses during the course of embryonic development was investigated in the superior oblique muscle of white Peking duck embryos. The possibility that the number of receptors could be experimentally lowered by chronic injections of the anticholinesterase agent, neostigmine methylsulfate, was determined using 125I-alpha- bungarotoxin. The total number of acetylcholine receptors on incubation day 12, 2 d subsequent to the onset of treatment, was reducted 45% as compared to saline-treated controls. A similar reduction in total receptor content (49%) was also observed on day 19. Radioautographic preparations showed that clusters of acetylcholine receptors were rare and that the grain density of extrajunctional receptors was also reduced. Hence, chronic treatment with neostigimine during development was observed to exert an effect on both the number and distribution of receptors in the developing superior oblique muscle. These changes occurred in the absence of any apparent effect on muscle differentiation in general. Myoblasts and myotubes were present on day 14 and further differentiated into myofibers by day 18 in both neostigmine and saline-treated muscles. The cytology of the develop;ing muscle cells also appeared normal. This is in contradistinction to the striking morphological changes that take place in adult mammalian and avian muscle after anticholinesterase treatment. More significantly, the decreased total receptor content and sparsity of clusters had no apparent effect on the formation of developing neuromuscular junctions at the electron microscopic level. The frequency of neuromuscular junctions in neostigmine-treated muscles was similar to that of the controls. It is concluded that acetylcholine receptor clusters are not required for the events leading to the morphological formation of neuromuscular junctions during in vivo development.
Neostigmine is a parasympathomimetic drug that acts as a reversible acetylcholinesterase inhibitor. Clinically it is used in patients with acute colonic pseudo-obstruction (ACPO or Ogilvie's syndrome, which is a gastrointestinal motility disorder characterized by marked dilatation of the colon in the absence of mechanical obstruction), postoperative ileus, urinary retention, myasthenia gravis, and in anesthesia to reverse the effects of nondepolarizing muscle relaxants. Both bolus and infusion are noted to be effective and lead to prompt evacuation of flatus or stool with a reduction in abdominal distention on physical examination. Median duration is noted to be 4–30 minutes in some trials. Here we present our experience of using 2 mg of intravenous neostigmine to help relieve the severe abdominal distention and ileus in a patient with severe fecal impaction when all conservative measures had been futile. The most frequent side effect of the drug is abdominal pain/cramping, which was noted in our patient as well. Other complications include bradycardia which is very infrequently symptomatic to require atropine. Overall, the drug is a simple, safe, and effective strategy; and as pointed out in the previous studies, the drug appears to be underused in patients who do not have a true contraindication to its use.
Postoperative residual blockade, longer duration of action for neuromuscular blockade, and slower recovery were relatively common in elderly patients.
We aimed to investigate the safety of train-of-four ratio and clinical tests in the assessment of patient recovery, and to determine the effects of the rocuronium, vecuronium, and cisatracurium on intubation, extubation and recovery times in elderly patients undergoing abdominal surgery.
Patients and Methods
After obtaining institutional approval and informed consent, 60 patients over 60 years old and undergoing elective abdominal operations were included in this double-blind, randomized clinical trial. Following a standard anesthesia induction, 0.6mg kg-1 rocuronium, 0.1mg kg-1 vecuronium, and 0.1mg kg-1 cisatracurium were administered to the patients in Group R, Group V, and Group C, respectively. Train-of-four (TOF) ratios were recorded at 10-minute intervals during and after the operation. Modified Aldrete Score (MAS) and clinical tests were recorded in the recovery room at 10-minute intervals. In addition, intubation and extubation times, duration of recovery room stay, and any complications were recorded.
Intubation time was found to be shorter in Group R than that in Groups V and C (P ˂ 0.001). Times to positive visual disturbances and grip strength tests were shorter in Group C than that in Group V (P = 0.016 and P = 0.011, respectively). In Group R and group C, time to TOF ≥ 0.9 was significantly longer than all positive clinical test times except grip strength (P < 0.05).
We hold the opinion that cisatracurium is safer in elderly patients compared to other drugs. We also concluded that the usage of TOF ratio together with clinical tests is suitable for assessment of neuromuscular recovery in these patients.
Neuromuscular Blockade; Aged; Rocuronium; Cisatracurium; Vecuronium Bromide