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OBJECTIVE To evaluate effects of 2 levels of partial neuromuscular block on the ventilatory response to a hypercapnic challenge in anesthetized dogs and to evaluate effects of edrophonium for reversing partial neuromuscular block. ANIMALS 6 healthy adult Beagles. PROCEDURES Each dog was anesthetized twice with propofol and dexmedetomidine. End-tidal partial pressure of CO 2 (Petco 2 ), tidal volume (Vt), and peak inspiratory flow (PIF) were measured during breathing at rest. Maximal Vt and PIF (Vt MAX and PIF MAX , respectively) in response to a hypercapnic challenge consisting of 10% CO 2 inhaled for 1 minute were measured. Variables were measured before administration of atracurium (baseline), during moderate (train-of-four [TOF] ratio, 0.3 to 0.5) and mild (TOF ratio, 0.6 to 0.8) atracurium-induced neuromuscular block, and after neuromuscular block recovery (TOF ratio, ≥ 0.9) following administration of edrophonium or saline (0.9% NaCl) solution. Dogs for which any variable returned to < 80% of the baseline value were identified. RESULTS Partial neuromuscular block increased Petco 2 ; it impaired Vt at rest and Vt MAX but not PIF at rest and PIF MAX . All variables except Petco 2 returned to baseline values when the TOF returned to ≥ 0.9. After recovery from neuromuscular block, significantly more dogs had a Vt MAX < 80% of the baseline value when edrophonium was not administered. CONCLUSIONS AND CLINICAL RELEVANCE Partial neuromuscular block in anesthetized Beagles decreased spontaneous ventilation at rest and impaired the response to a hypercapnic challenge. Response to hypercapnic challenge might remain partially impaired after recovery of the TOF ratio to ≥ 0.9.

A case of laryngeal myasthenia gravis in a 65-year-old woman presenting with hoarseness as the sole symptom is reported. Voice spectrography was performed before and after injection of intravenous edrophonium. There was a marked improvement in the patient's voice after the administration of edrophonium, which was confirmed by the changes seen on the sound spectrogram. This was the only objective indication of a diagnosis of myasthenia gravis. No thymoma was seen on chest X-ray and the patient was negative for anti-acetylcholine receptor antibodies. Treatment for laryngeal myasthenia gravis was initiated and the patient's vocal problems resolved. This case emphasizes the need to consider systemic diseases in the differential diagnosis of hoarseness and demonstrates the need for careful follow-up in such patients.

Objective: To review the evidence regarding the reversal of neuromuscular block (NMB) in companion animals with emphasis on the development and use of newer agents., Database Used: Data sources include scientific reviews and original research publications in both human and veterinary literature using Pubmed and Scopus as search data bases. Unpublished and locally published data on reversal of NMB are presented., Conclusions: Residual NMB has been shown to increase morbidity and mortality in humans and needs to be avoided. It can be detected only by adequate neuromuscular monitoring. The proper use of reversal agents avoids residual NMB and recurarization should not occur. Anticholinesterase inhibitors, such as edrophonium and neostigmine have been used to reverse NMB when the need for this has been established. Reversal is influenced by several factors and a number of undesirable side- effects of these drugs have been reported. Sugammadex, a γ-cyclodextrin, which was designed specifically to encapsulate rocuronium, is more rapid in its actions, has fewer side effects and can reverse profound NMB induced by aminosteroidal muscle relaxants., (© 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

'Dropped head syndrome' (DHS) may be associated with a variety of neurological diseases. The absence of neurological clues to the underlying cause of DHS can make management particularly challenging. We review six patients who presented with only DHS, responded to intravenous edrophonium and turned out to have myasthenia gravis (MG) including similar patients who were previously documented. Six patients presented with neck weakness and three had bulbar symptoms. Acetylcholine receptor (AchR) was positive in four patients. One patient had thymoma. The interval from the onset of DH to the presentation of typical MG features was shorter in patients who tested positive for anti-Ach antibody (1-2 months) than in patients who tested negative for anti-AchR antibody (13 months, 4 years). Our results suggest that patients with DHS responding to intravenous edrophonium might turn out to have MG and such patients might respond to a combination of anticholinesterase agents and steroids.

A case of prolonged muscle relaxation after vecuronium in an anesthetized dog is presented. After using peripheral nerve stimulation to confirm partial recovery of neuromuscular transmission, administration of 0.5 mg/kg IV of intravenous edrophonium failed to complete the reversal process. Subsequent administration of neostigmine resulted in complete recovery from blockade. Without monitoring neuromuscular function with a peripheral nerve stimulator until reversal was complete, it was very likely this patient would have been extubated with incomplete neuromuscular transmission. Several factors affecting the duration of neuromuscular blockade and its reversal are addressed.

Background: The ultra-short-acting neuromuscular blocker gantacurium is chemically degraded in vitro by rapid adduction of L-cysteine to its central olefinic double bond. Preliminary data have suggested that exogenous (intravenous) L-cysteine abolishes gantacurium blockade. Two new analogues of gantacurium (CW 002 and CW 011) have been synthesized to undergo slower L-cysteine adduction, yielding intermediate duration. L-cysteine adduction to and antagonism of these novel agents is further defined herein., Methods: Comparative reaction half-time for L-cysteine adduction in vitro of the three compounds was determined by high-performance liquid chromatography. ED95 for twitch inhibition in monkeys under isoflurane was calculated, and duration at approximately 4-5x ED95 was correlated with reaction half-time for adduction. Speed of L-cysteine antagonism was contrasted with anticholinesterase reversal. Potencies of CW 002 and its adduction product were compared to provide a basis for L-cysteine antagonism., Results: Rate of L-cysteine adduction in vitro (reaction half-time) was 11.4 and 13.7 min for CW 002 and CW 011 versus 0.2 min for gantacurium, and was inversely related to duration of block (P < 0.0001). CW 002 and CW 011 were 3x longer acting than gantacurium (28.1 and 33.3 min vs. 10.4 min), but only half the duration of cisatracurium. The adduct of CW 002 was approximately 70x less potent than CW 002. L-cysteine (10-50 mg/kg intravenously) given 1 min after approximately 4-5x ED95 doses of all the three compounds abolished block within 2-3 min., Conclusions: L-cysteine adduction occurs at different rates by design in olefinic isoquinolinium diester neuromuscular blockers, yielding corresponding durations of action. Antagonism by exogenous L-cysteine is superior to anticholinesterases, inducing inactivation of the active molecules to restore function rapidly at any time.

Objective: To study heart rate (HR), arterial blood pressure (BP) and autonomic nervous (AN) effects of edrophonium-atropine combinations during neuromuscular blockade (NMB) antagonism in sheep., Experimental Design: Randomized, prospective and experimental study., Animals: Seventy-eight Scottish blackface ewes; mean age: 4.5 years; mean body mass: 54 kg., Methods: After induction with IV etomidate (0.5 mg kg(-1)) and midazolam (0.5 mg kg(-1)), anaesthesia was maintained with halothane and NMB produced with atracurium or mivacurium. In the first study (n = 53), the electrocardiographic (ECG), HR, BP and AN effects of low (40 microg kg(-1)) and high (80 microg kg(-1)) atropine doses combined with either of two edrophonium doses (0.5 or 1.0 mg kg(-1)) were investigated. These variables were also measured in a second study when edrophonium (1.0 mg kg(-1)) was administered 5 minutes before atropine (80 microg kg(-1)) and vice versa. Data were analysed using one-way within-subjects and repeated measures anova., Results: In the first study, all combinations reversed NMB but significantly (p < 0.001) increased HR and BP within 2 minutes without arrhythmias. In the second study, edrophonium (1.0 mg kg(-1)) significantly increased HR and BP, saliva flow (n = 1) and lung sounds (n = 3) and caused ECG changes (n = 1). Cardiovascular changes were partially reversed by atropine (80 microg kg(-1)) administered 5 minutes later. Administered first, atropine (80 microg kg(-1)) significantly decreased HR and BP effects which were fully (HR) and partially (BP) reversed by edrophonium (1 mg kg(-1)) administered 5 minutes later., Conclusion and Clinical Relevance: The cardiovascular effects of edrophonium and atropine were opposite to those reported in humans and dogs. Edrophonium (0.5 mg kg(-1)) and atropine (80 microg kg(-1)) caused the mildest HR changes without ECG and noncardiac AN disturbances, and is recommended for the antagonism of NMB in sheep.

Background and Purpose: This work was aimed at comparing and analysing the effects and mechanisms of action of the quaternary ammonium cholinesterase inhibitors (QChEIs) BW284c51, decamethonium and edrophonium, on nicotinic ACh receptor (nAChR) function., Experimental Approach: nAChRs purified from Torpedo electroplax were transplanted to oocytes and currents elicited by ACh (I(ACh)) either alone or in presence of these QChEIs were recorded., Key Results: None of the QChEIs, by itself, elicited changes in membrane conductance; however, when co-applied with ACh, all of them decreased I(ACh) in a concentration-dependent way. The mechanisms of nAChR inhibition were different for these QChEIs. BW284c51 blockade was non-competitive and voltage-dependent, although it also affected the n(H) of the dose-response curve. By contrast, decamethonium and edrophonium inhibition, at -60 mV, was apparently competitive and did not modify either desensitisation or n(H). Decamethonium effects were voltage-independent and washed out slowly after its removal; by contrast, edrophonium blockade had strong voltage dependence and its effects disappeared quickly after its withdrawal. Analysis of the voltage-dependent blockade indicated that BW284c51 bound to a shallow site into the channel pore, whereas edrophonium bound to a deeper locus. Accordingly, additive inhibitory effects on I(ACh) were found among any pairs of these QChEIs., Conclusions and Implications: The tested QChEIs bound to the nAChR at several and different loci, which might account for their complex inhibitory behaviour, acting both as allosteric effectors and, in the case of BW284c51 and edrophonium, as open channel blockers.

Background: Sugammadex is a modified [gamma] cyclodextrin compound, which encapsulates rocuronium to provide for a rapid reversal of residual neuromuscular blockade. We tested the hypothesis that sugammadex would provide for a more rapid reversal of a moderately profound residual rocuronium-induced blockade than the commonly used cholinesterase inhibitors, edrophonium and neostigmine., Methods: Sixty patients undergoing elective surgery procedures with a standardized desflurane-remifentanil-rocuronium anesthetic technique received either sugammadex, 4 mg/kg IV (n = 20), edrophonium, 1 mg/kg IV and atropine, 10 microg/kg IV (n = 20), or neostigmine, 70 microg/kg IV and glycopyrrolate, 14 microg/kg IV (n = 20) for reversal of neuromuscular blockade at 15 min or longer after the last dose of rocuronium using acceleromyography to record the train-of-four (TOF) responses. Mean arterial blood pressure and heart rate values were recorded immediately before and for 30 min after reversal drug administration. Side effects were noted at discharge from the postanesthesia care unit., Results: The three groups were similar with respect to their demographic characteristics and total dosages of rocuronium prior to administering the study medication. Although the initial twitch heights (T1) at the time of reversal were similar in all three groups, the time to achieve TOF ratios of 0.7 and 0.9 were significantly shorter with sugammadex (71 +/- 25 and 107 +/- 61 s) than edrophonium (202 +/- 171 and 331 +/- 27 s) or neostigmine (625 +/- 341 and 1044 +/- 590 s). All patients in the sugammadex group achieved a TOF ratio of 0.9 < or =5 min after reversal administration compared with none and 5% in the edrophonium and neostigmine groups, respectively. Heart rate values at 2 and 5 min after reversal were significantly higher in the neostigmine-glycopyrrolate group compared with that in sugammadex. Finally, the incidence of dry mouth was significantly reduced in the sugammadex group (5% vs 85% and 95% in the neostigmine and edrophonium groups, respectively)., Conclusion: Sugammadex, 4 mg/kg IV, more rapidly and effectively reversed residual neuromuscular blockade when compared with neostigmine (70 microg/kg IV) and edrophonium (1 mg/kg IV). Use of sugammadex was associated with less frequent dry mouth than that with the currently used reversal drug combinations.

The aim of this study was to examine if edrophonium provocative testing is useful for evaluating upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia (NUD). A questionnaire rating dyspeptic symptoms was done for 58 patients with NUD. The patients were then given an intravenous infusion of saline followed by 5 mg of edrophonium. Baseline esophageal manometry was also done. Patients whose usual symptoms were reproduced (48.3%) had significantly higher symptom scores (13.0 [8.5, 17.0] vs. 8.5 [6.0, 11.0]; P = 0.015) and a significantly higher number of symptoms (4.0 [2.5, 6.0] vs. 3.0 [1.0, 4.0]; P = 0.010) than patients whose usual symptoms were not reproduced. The presence of an esophageal motility disorder was not significantly different between the two groups. These findings suggest upper gastrointestinal hypersensitivity in the patients whose symptoms were reproduced. Edrophonium provocative testing might be useful for evaluating upper gastrointestinal hypersensitivity in patients with NUD.

Background: Generalized myasthenia gravis will develop in more than 50% of patients who present with ocular myasthenia gravis, typically within 2 years. The optimal treatment of ocular myasthenia gravis, including the use of corticosteroids, remains controversial. In addition, the prevalence of thymoma and the optimal performance of the edrophonium chloride test for ocular myasthenia remain unknown., Objective: To assess the effect of oral corticosteroid therapy on the frequency of development of generalized myasthenia gravis within 2 years, the incidence of thymoma, and the amount of edrophonium needed for a positive test result in patients with ocular myasthenia gravis., Methods: We reviewed an ocular myasthenia gravis database of 147 patients. Patients underwent measurement of acetylcholine receptor (AChR) antibody levels and chest computed tomography. Unless contraindicated, patients with diplopia were recommended for therapy with prednisone, up to 40 to 60 mg/d, with the dosage tapered for 5 to 6 weeks. Most continued to receive daily or alternate-day doses of 2.5 to 10 mg to prevent diplopia. Patients not given prednisone (untreated group) received pyridostigmine bromide or no medication. After the diagnosis, we documented the signs and symptoms of ocular and generalized myasthenia gravis and performed 2-year follow-up in 94 patients., Results: The mean dose of edrophonium chloride to give a positive response was 3.3 mg (SD, 1.6 mg) for ptosis and 2.6 mg (SD, 1.1 mg) for ocular motor dysfunction. Thymoma occurred in 1 patient (0.7%). Generalized myasthenia gravis developed within 2 years in 4 of 58 treated and 13 of 36 untreated patients. The odds ratio (OR) for development of generalized disease in the treated group was 0.13 (95% confidence interval [CI], 0.04-0.45) compared with the untreated group. The AChR antibody level was not predictive of development of generalized myasthenia gravis at 2 years, but the risk was greater in patients with abnormal AChR antibody levels (OR, 6.33; 95% CI, 1.71-23.42). Logistic regression that included age, abnormal AChR antibody level, and prednisone therapy yielded significance only for abnormal AChR antibody level (OR, 7.03; 95% CI, 1.35-36.64) and treatment (OR, 0.06; 95% CI, 0.01-0.30)., Conclusions: At 2 years, prednisone treatment appears to reduce the incidence of generalized myasthenia gravis to 7% in contrast to 36% of patients who did not receive prednisone. Thymoma, although uncommon, occurs in ocular myasthenia gravis. Only small amounts of edrophonium are needed to diagnose ocular myasthenia gravis.

Recommendations for head-up tilt testing (HUT) often include the prolonged abstaining from food and water consumption (nothing by mouth [NPO]) and intravenous fluids administration before HUT. After the baseline test, supine equilibration periods are recommended before and between each dose of medication. The aim of this study was to determine if similar results are obtainable with a simpler protocol. After 2-3 hours NPO, 1,540 HUTs were performed at 70 degrees for 30 minutes unless predetermined endpoints were reached. Then, with the patient remaining in the tilted position, isoproterenol (ISO) (1 microgram/min), titrated every 3 minutes to a maximum of 5 micrograms/min (n = 803 patients), sublingual nitroglycerin (NTG) (300-400 micrograms) (n = 143 patients), or edrophonium (EDP) (5 mg) repeated once after 3 minutes (n = 46 patients) were administered. No aspiration or other adverse effects attributable to the abbreviated fasting period were observed. ISO was well tolerated as doses were increased. Vasovagal manifestations developed in 31% of ISO tests, in 11% with EDP, and in 50% with NTG (P < 0.001). Time consumed with rehydration before and postural changes during HUTs may be avoided when ISO is administered. With NTG the response may be excessive.

This randomized, controlled study compared edrophonium dose requirements to antagonize cisatracurium-induced neuromuscular block in children and adults. Sixty children, aged two to 10 years, and 60 adults aged 20 to 60 years, all subjects ASA physical status 1 or 2, having propofol, fentanyl and isoflurane-N2O anaesthesia, were studied. Cisatracurium 0.1 mg x kg(-1) was given for muscle relaxation. Neuromuscular block was monitored with accelerometry. Edrophonium 0.1, 0.2, 0.4 or 1 mg x kg(-1) or no anticholinesterase (controls) was given by random allocation to antagonize 90% neuromuscular block in each of the study groups (n=12). Atropine 5 to 10 microg x kg(-1) was given according to edrophonium dose. Onset time of cisatracurium-induced block in children was mean (SD) 2.4 (0.8) versus 4.1 (2.3) minutes in adults, P<0.01. The times to 10% spontaneous recovery of the first twitch (T1) were respectively, 28.4 (5.2) and 41.8 (6.1) minutes in children and adults, P<0.01. Spontaneous and antagonist assisted neuromuscular recovery was more rapid in children. Adequate neuromuscular recovery (train of four (TOF) ratio 80%) was achieved in children at 3 and 10 minutes after edrophonium 1.0 mg kg(-1) and 0.4 mg x kg(-1), respectively. A TOF ratio of 80% was not achieved, within 10 minutes, with any of the four dose levels of edrophonium in adults. The dose of edrophonium to achieve a TOF ratio of 80% (ED(TOF-80)) after 5 and 10 minutes in children were, respectively, mean (SD) 0.85 (0.38) and 0.38 (0.19) mg x kg(-1). The equivalent ED(TOF-80) in adults was outside the edrophonium dose range studied.

Objective: To evaluate the safety of edrophonium chloride in the course of the Tensilon test by measurement of hemodynamic and ECG parameters and the observation of adverse events., Methods: 25 patients with known or suspected myasthenia gravis were included in an open, prospective study concerning the performance of the Tensilon test. Blood pressure, heart rate, continuous ECG and adverse events were recorded 10 minutes following intravenous application of Tensilon., Results: Blood pressure and heart rate did not change significantly during the observation period. One patient on beta-blockers developed a grade I AV block. Self-limiting adverse events of short duration were observed in 11 patients. Serious adverse events such as syncope or hemodynamic deterioration did not occur., Conclusion: The Tensilon test appears to be a safe procedure. A detailed clinical cardiac history, the history of medication and twelve lead ECG recordings should be documented in all patients undergoing the Tensilon test. Patients with a history of dysrhythmia receiving digitalis, beta-blocking agents or Ca antagonist therapy should be managed with special care, as Tensilon enhances vagal effects.

Coronary artery bypass grafting without the use of cardiopulmonary bypass (CPB) is performed with increasing frequency. Performing revascularization on a beating heart is technically more demanding than performing revascularization on the arrested heart, especially in high-risk patients. beta-Blockers and calcium-channel antagonists have been used for the reduction of heart rate (HR) for the local immobilization of the anastomotic site. However, their negative inotropic actions often lead to serious hypotension. Therefore, we investigated the effect of edrophonium on HR reduction in high-risk patients undergoing CABG without CPB. Ten high-risk patients undergoing CABG without CPB were selected. To reduce HR during anastomosis, edrophonium was administered during the procedure. Systemic blood pressure (sBP), HR, and cardiac index (CI) were measured from the induction of anesthesia to the end of surgery. All surgeries were successfully performed without serious complications. To keep the rate under 60 bpm, edrophonium was administered at the time of anastomosis and this decreased the cardiac index from 2.19 to 1.95, while the sPB was maintained easily over 90 mmHg with the infusion of methoxamine. Edrophonium may be useful for the reduction of HR during coronary anastomosis in high-risk patients undergoing CABG without CPB.

Background: This study determined the effect of intrathecally administered cholinesterase inhibitors, edrophonium and neostigmine, on nerve injury-induced, touch-evoked allodynia and identified the pharmacologic characteristics of this action., Methods: Rats were prepared with tight ligation of the left L5 and L6 spinal nerves and with lumbar intrathecal catheters fitted for long-term monitoring. Edrophonium (3, 10, 30, or 100 microg) or neostigmine (0.3, 1, 3, or 10 microg) was administered intrathecally. Tactile allodynia and motor weakness were assessed. To evaluate the pharmacologic characteristics of the activity, a muscarinic receptor antagonist or a nicotinic receptor antagonist was administered intrathecally before edrophonium or neostigmine was injected. To compare the action of subtype antagonists, the M1 muscarinic receptor antagonist pirenzepine, the M2 antagonist methoctramine, the M3 antagonist 4-DAMP (diphenylacetoxy-N-methypiperidine), and the M4 antagonist tropicamide were administered intrathecally before cholinesterase inhibitors were injected., Results: Intrathecal edrophonium or neostigmine produced a dose-dependent antagonism of the touch-evoked allodynia. Neostigmine resulted in a moderate effect on motor weakness at doses of 3 and 10 microg. Pretreatment with intrathecal atropine but not mecamylamine yielded a complete antagonism of the effects of the cholinesterase inhibitors. In addition, antiallodynia produced by edrophonium (100 microg) was reversed by pretreatment with methoctramine, 4-DAMP, tropicamide, and pirenzepine. In the neostigmine (10 microg) group, only the M1 antagonist pirenzepine had a moderate effect on reversal of increased allodynic threshold., Conclusions: These experiments suggest that intrathecal edrophonium or neostigmine produces an antagonism on touch-evoked allodynia at the spinal level in a rat model of neuropathic pain and that the antiallodynic action of cholinesterase inhibitors is probably mediated by a spinal muscarinic system, especially at the M1 receptor subtype.

Purpose: To report a case of isolated inferior rectus palsy secondary to a metastasis to the oculomotor nucleus., Methods: Case report. A 41-year-old woman with a history of breast cancer presented with acute onset of left hypotropia and exotropia., Results: Forced generation testing confirmed weakness of the right inferior rectus muscle that was not reversed by intravenous edrophonium infusion. Magnetic resonance imaging disclosed numerous metastatic lesions to the cerebral hemispheres and brainstem. One lesion in the right midbrain was adjacent to the cerebral aqueduct in the right oculomotor nucleus., Conclusion: Metastasis to the oculomotor nucleus is a rare cause of isolated inferior rectus palsy; however, this entity should be considered in the differential diagnosis of an isolated inferior rectus palsy because of the life-threatening consequences of a brainstem lesion.

Because the Lancaster red-green test and the Hess screen are not widely used by most ophthalmologists, we used the alternate prism-cover test to study the effect of intravenous edrophonium chloride (Tensilon) on the ocular alignment of 30 normal subjects and 14 individuals with nonmyasthenic strabismus. After measurement of their baseline phorias and tropias, patients received an intravenous injection of Tensilon via the incremental dose technique until autonomic effects of the drug were noted or until 10 mg was administered. Another set of measurements of muscle balance was taken immediately postinjection and 2 and 5 min later. Apart from a small increase (mean, 2 prism dipoters; p = 0.004) in their exophoria at near, normal subjects exhibited no significant change in their phorias after Tensilon injection. One third to one half of the nonmyasthenic strabismics, however, showed a change in their vertical deviation after Tensilon (46% at distance and 38% at near), with the majority of them increasing their angle of squint. These changes were small (mean, 1.7 prism diopters; maximum, 5 prism diopters). In only one case did reversal of the direction of deviation occur. Tensilon produces a statistically significant increase in near exophorias of normal subjects and in vertical distance deviations of nonmyasthenic strabismics. These changes, however, are clinically insignificant and should not be considered to constitute a positive Tensilon test.

Background: It is not known to what extent patients with non-cardiac chest pain have esophageal ischemia or motor dysfunction. The aim of this study was to investigate whether chest pain provoked by intravenous edrophonium chloride could be due to esophageal ischemia or to muscular spasm., Methods: Sixteen patients with a history of non-cardiac chest pain took part. Ten patients (32-69 years old) who did not develop chest pain with intravenous edrophonium chloride were compared with six patients (50-71 years old) who did develop edrophonium-provoked chest pain. Esophageal motility was monitored manometrically. Changes in esophageal blood flow, assessed as the rewarming time after esophageal cooling, was measured with a thermistor technique., Results: The esophageal rewarming time after cooling was the same before and during the edrophonium test in both groups. The esophageal contraction amplitudes and contraction duration were significantly increased only in patients with edrophonium-provoked chest pain., Conclusion: Strong esophageal contractions and not a decreased blood flow in the esophageal wall seem to be the cause of chest pain provoked by intravenous edrophonium chloride.

This study compared spontaneous with edrophonium-induced recovery of neuromuscular transmission (NMT) after mivacurium infusion. During nitrous oxide-narcotic-propofol anesthesia, the electromyogram (EMG) of the adductor pollicis (AP) was recorded and the movement of the first toe in response to stimulation of the posterior tibial nerve was noted. Mivacurium infusion was titrated to produce posttetanic count of 1-5 at the toe and absence of NMT at the AP. Thirty children were assigned to three groups on the basis of age. Edrophonium, 1 mg/kg, with atropine 10 micrograms/kg, was given after the mivacurium infusion when NMT of the AP was 1% or 10% of baseline. In the third group, spontaneous recovery was observed. Edrophonium given when NMT was 11% +/- 1% SEM produced the most rapid recovery, 7.5 +/- 0.6 min to a train-of-four (TOF) ratio (T4/T1) of 0.9 and the shortest interval from T4/T1 of 0.4-0.9, when residual block was likely to be underestimated, 4.8 +/- 0.6 min. Edrophonium given when block was greater produced recovery of the T4/T1 to 0.4 in 2.8 +/- 0.7 min, but the time from then to T4/T1 = 0.9 was 7.9 +/- 1.1 min, as long as during spontaneous recovery. Spontaneous recovery to T4/T1 = 0.9 occurred 12.9 +/- 0.7 min after the first measurable AP EMG. There was no significant relationship between duration of infusion, which ranged from 16 to 135 min, and time to appearance of AP EMG after the infusion, which averaged 3.1 +/- 0.5 min. We recommend that administration of edrophonium to induce reversal of mivacurium be delayed until two responses to a TOF stimuli are observed because this will produce the most rapid recovery and decrease the interval in which residual block may be underestimated.

Tracheal intubating conditions and neuromuscular effects of succinylcholine, rocuronium, and mivacurium were studied in 100 healthy women undergoing outpatient laparoscopic surgery. After a standardized fentanyl-thiopental induction, tracheal intubation was facilitated with succinylcholine 1 mg/kg in Groups I (n = 23) and II (n = 25), rocuronium 0.6 mg/kg in Group III (n = 27), or mivacurium 0.2 mg/kg in Group IV (n = 25). If clinically indicated, bolus doses of rocuronium 5-10 mg (Groups I and III) or mivacurium 2-4 mg (Groups II and IV) were administered during the maintenance period. Anesthesia was maintained with desflurane and nitrous oxide 60% in oxygen. At the end of the surgery, residual neuromuscular block was reversed with edrophonium 0.5 mg/kg and atropine 10 micrograms/kg, if needed. The neuromuscular function was assessed using electromyography with a train-of-four mode of stimulation every 10 s at the wrist. Intubating conditions 90 s after succinylcholine and rocuronium were significantly better than after mivacurium. The onset time (from the end of injection until 95% suppression of the first twitch [T1]) for succinylcholine (63 +/- 21 s and 62 +/- 17 s in Groups I and II, respectively) were significantly shorter than for rocuronium (158 +/- 76 s) or mivacurium (210 +/- 93 s). Moreover, the onset times for rocuronium were significantly shorter than mivacurium. The recovery times (of T1 to 25% of the control value) were significantly shorter with succinylcholine and mivacurium than rocuronium. Significantly fewer patients needed reversal of residual neuromuscular blockade after mivacurium compared to rocuronium. One patient in Group I and six patients in Group IV displayed erythema on the upper body. Postoperative myalgia were experienced by 16% of the patients in Groups I and II compared to none in Groups III and IV. There was on difference in the incidence of postoperative nausea and vomiting among the four groups. In conclusion, rocuronium appears to be an acceptable alternative to succinylcholine for tracheal intubation. However, rocuronium's longer duration of action increases the need for reversal drugs. When rapid tracheal intubation is unnecessary, mivacurium is also an acceptable alternative to succinylcholine and is associated with a more rapid spontaneous recovery than rocuronium.

Background: The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit., Methods: In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode., Results: Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05)., Conclusions: This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

Background: Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children., Methods: Fifty-four adults, aged 40.1 +/- 10.9 yr, and 54 children, aged 4.9 +/- 0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg x kg(-1) intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micrograms x kg(-1)) or edrophonium (100, 200, 400, and 1,000 micrograms x kg(-1)) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min., Results: Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97 +/- 2% (SD) in children compared with 69 +/- 11% in adults and train-of-four to 84 +/- 5% versus 30 +/- 13% (P<0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children., Conclusions: Spontaneous recovery from mivacurium- induced neuromuscular block is more rapid in children than in adults. Ten minutes after attempted reversal, recovery is accelerated by edrophonium and usually by neostigmine in adults but not in children. Thus, when reversal is required, edrophonium may be preferred to neostigmine.

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans and trans-trans) undergo rapid metabolism by plasma cholinesterase (t1/2 beta < 2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5-10% of control T1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg.kg-1 (Group EDR-1), 0.25 mg.kg-1 (Group EDR-2), or 0.50 mg.kg-1 (Group EDR-3), in addition to a corresponding dose of atropine. Spontaneous recovery, from a T1 response of < 10% to a TOF ratio > or = 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison, patients in the EDR-1 group required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of > or = 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an EUEA genotype, whereas the two patients with delayed recovery in the EDR-1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg.kg-1) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg.kg-1 provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.

Background: The most common form of idiopathic ventricular tachycardia (VT) is repetitive monomorphic VT (RMVT), which is characterized by frequent ventricular ectopy and salvos of nonsustained VT with intervening sinus rhythm. Unlike most other forms of idiopathic VT, this tachycardia typically occurs at rest and is nonsustained. The mechanism of RMVT is undefined. Because of a common site of origin, the right ventricular outflow tract (RVOT), we hypothesized that RMVT is mechanistically related to paroxysmal sustained, exercise-induced VT, which has been shown to be consistent with cAMP-mediated triggered activity. Therefore, in this study, we sought to identify (1) the mechanism of RMVT at the cellular level by using electropharmacological probes known to activate either stimulatory or inhibitory G proteins and thereby modify intracellular cAMP levels, (2) potential autonomic triggers of RMVT through analysis of heart rate variability, and (3) whether well-characterized somatic activating mutations in the stimulatory G protein, G alpha s, underlie RMVT., Methods and Results: Twelve patients with RMVT underwent electrophysiological study. Sustained monomorphic VT was reproducibly initiated and terminated with programmed stimulation and/or isoproterenol infusion in 11 of the 12 patients (the other patient had incessant RMVT). Induction of VT demonstrated cycle length dependence and was facilitated by rapid atrial or ventricular pacing. Termination of VT occurred in response to interventions that either lowered stimulated levels of intracellular cAMP (and thus decreased intracellular Ca2+)--ie, adenosine (12 of 12), vagal maneuvers or edrophonium (8 of 9), and beta-blockade (3 of 5)--or directly decreased the slow-inward calcium current--ie, verapamil (10 of 12). Analysis of heart rate variability during 24-hour ambulatory monitoring in 7 patients showed that the sinus heart rate is increased and accelerates before nonsustained VT (P < .05), whereas high-frequency heart rate variability is unchanged. These findings are consistent with transient increases in sympathetic tone preceding nonsustained VT. Finally, myocardial biopsy samples were obtained from the site of origin of the VT (typically the RVOT) and from the right ventricular apex from 9 patients. Genomic DNA was extracted from each biopsy sample, and three exons of G alpha s in which activating mutations have previously been described were amplified by polymerase chain reaction. All sequences from these regions were found to be identical to that of control., Conclusions: Although the arrhythmia occurs at rest, the constellation of findings in idiopathic VT that is characterized by RMVT is consistent with the mechanism of cAMP-mediated triggered activity. Therefore, the spectrum of VT resulting from this mechanism includes not only paroxysmal exercise-induced VT but also RMVT.

The dose-response relationship for edrophonium during antagonism of vecuronium-induced neuromuscular blockade was studied in two groups of adult patients of mean (SD) age 35 (10.0) years (n = 42) and 77 (5.4) years (n = 42) respectively. Neuromuscular block was monitored by recording the force of contraction of the adductor pollicis muscle following train-of-four stimulation. Six patients in each age group received 0.1, 0.3, 0.5, 0.7, 1.0, or 1.5 mg.kg-1 of edrophonium, or normal saline at 10% recovery of T1 (first response in the train-of-four) after a single dose of vecuronium 0.08 mg.kg-1. The train-of-four ratios were recorded continuously over the next 10 min and the values at 1 min intervals from 5 min onwards were used to construct the dose-response curves. The dose-response curves showed no significant difference between the two age groups except at 10 min. The estimated dose of edrophonium required for attaining a train-of-four ratio of 0.7 at 10 min was 0.9 and 1.3 mg.kg-1 in the younger and older groups, respectively (p < 0.05).

We report a 43-year-old man suffering from myasthenia gravis with invasive thymoma accompanied with alopecia areata and dry mouth. These complications are extremely rare and the pathogenetic etiology of these complications was thought to depend on a generalized immunological disturbance.

The routine use of cholinesterase inhibitors to antagonize residual neuromuscular block may be associated with increased postoperative emesis. Rapid spontaneous recovery from mivacurium may obviate the need for these drugs. In this randomized, double-blind, placebo-controlled study of 113 healthy children who had received mivacurium as part of a standardized anesthetic regimen, we compared the incidence of postoperative complications after spontaneous recovery and after the use of neostigmine-glycopyrrolate or edrophonium-atropine. The anesthetic regimen consisted of halothane, nitrous oxide, fentanyl, 2 micrograms/kg intravenous (i.v.), mivacurium in an initial dose of 0.2 mg/kg, followed by an infusion, adjusted to maintain > or = 1 evoked contraction response to a supramaximum train-of-four stimulus. At the end of the procedure, patients received by random assignment one of three drug combinations: 1) neostigmine 70 micrograms/kg + glycopyrrolate 10 micrograms/kg, i.v., 2) edrophonium 1 mg/kg + atropine 10 micrograms/kg, i.v., and 3) saline. The trachea was extubated when evoked responses to peripheral nerve stimulation and clinical signs of adequate neuromuscular recovery were present. Postoperative pain was treated with morphine and emesis with metoclopramide. There were no significant differences between the three groups with respect to age, surgery, intraoperative fentanyl, and mivacurium use, time from the end of surgery to tracheal extubation, postanesthesia care unit (PACU) arrival and discharge, or in postoperative oxygen saturation values and analgesic requirements. Compared to the placebo group, emesis occurred more often in the PACU in patients receiving the neostigmine-glycopyrrolate combination, but not after edrophonium-atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

The time course of recovery after early administration of anticholinesterases during intense mivacurium-induced block was evaluated by recording the mechanomyographic response of the adductor pollicis to post-tetanic count (PTC) and train-of-four (TOF) ulnar nerve stimulation. Seventy-two adult patients receiving thiopentone, fentanyl, nitrous oxide, isoflurane anaesthesia and mivacurium 0.15 mg kg-1 were allocated randomly to one of six equal groups according to the type of anticholinesterase and intensity of block at which antagonism was attempted. Groups 1, 3 and 5 received neostigmine 0.07 mg kg-1, while groups 2, 4 and 6 received edrophonium 1 mg kg-1. At the time of administration of antagonist there was no response to PTC in groups 1 and 2, a PTC of 1 or more was detectable in groups 3 and 4 and the first twitch of the TOF (T1) had recovered to 10% in the conventional antagonism groups (5 and 6). The longest clinical duration (CD) values (time from administration of mivacurium to T1 25%) were encountered in groups 1, 5 and 6 and were 17.4 (7.9), 19.7 (3.4) and 21.4 (4.8) min, respectively. CD was reduced significantly in groups 2, 3 and 4 and values were 13.9 (3.5), 13.7 (3.5) and 13.8 (3.3) min, respectively. Recovery indices (RI) (time interval between T1 25% and 75%) were 13.8 (7.3), 6.3 (1.4), 4.6 (1.8), 6.0 (2.1), 3.7 (2.2) and 4.8 (3.1) min in groups 1-6, respectively and was prolonged with neostigmine antagonism at PTC 0 (group 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery from the effects of muscle relaxants can occur either spontaneously by their metabolism in the body or by elimination via the normal excretion pathways, or by the administration of pharmacologic antagonists. The decision as to whether spontaneous recovery should be allowed to take place or pharmacologic reversal should be induced depends upon several factors, principal among them being the duration of action of the muscle relaxant used, its dose, and the time that is available. The recovery times of most relaxants, including atracurium and vecuronium, are such as to require antagonism if adequate recovery is to be attained quickly. An agent such as mivacurium may, however, allow complete spontaneous recovery to take place without the use of antagonists.

Mivacurium, a new benzylisoquinoline muscle relaxant, appears to be close to the ideal for short to intermediate surgical procedures. Ideal properties of such an agent are discussed, in addition to indications for muscle relaxation in such procedures. Two studies are presented, showing the onset and offset times of mivacurium and its cardiovascular stability in both young and elderly patients. It is concluded that it is a well-tolerated and appropriate agent for use in short to intermediate surgical procedures in those patients with normal plasma cholinesterase function, despite a slight prolongation of action in the elderly.

Many patients with end-stage renal disease (ESRD) have signs and symptoms of easy fatigability, fluctuating weakness, apathy, dry mouth, and blurring of vision. These symptoms can be confused with disorders of neuromuscular transmission. When present, the physician may want to determine whether the patient has myasthenia gravis--the commonest of all neuromuscular disorders--and administer the edrophonium (Tensilon) test. An unequivocally positive response to the test must be interpreted with caution in ESRD. However, the exact mechanism of a positive response is unclear but may be explained by metabolic abnormalities related to end-stage renal disease, i.e., uremic toxins, disordered calcium metabolism, abnormal neuromuscular mechanism, associated neurological disorders, or myopathic processes in uremia, all of which can affect neuromuscular transmission.

Neuromuscular, electrocardiographic and autonomic nervous changes were studied when edrophonium and four combinations of edrophonium and atropine were used to antagonise vecuronium-induced neuromuscular blockade in 87 dogs anaesthetised with halothane. Edrophonium (500 micrograms/kg body-weight) was given alone, or with atropine (40 micrograms/kg) or one minute after a dose of 600 micrograms of atropine, and a lower dose of edrophonium (250 micrograms/kg) was used with high (40 micrograms/kg) and low (20 micrograms/kg) doses of atropine. The neuromuscular blockade was antagonised when some recovery was present. The reversal was rapid and complete in 75 cases, but the remaining 12 dogs which received the low dose of edrophonium required a second injection. Trials with the high dose of edrophonium alone were discontinued because cardiac arrest occurred in one dog and bronchosecretion with profuse salivation in another. The heart rate increased with the low dose of edrophonium and the high dose of atropine, and increased and then decreased when edrophonium was followed by 600 micrograms of atropine. The heart rate was stable when the high and low doses of atropine and edrophonium were matched. All the treatments caused atrioventricular blockade. Non-cardiac autonomic changes (salivation and bronchosecretion) occurred in only two of the 87 dogs.

Background: Spinal cholinergic receptors have been shown to have a potent antinociceptive action, an effect that can be mimicked by spinal cholinesterase inhibitors. We (1) characterized the cholinergic receptor system through which intrathecally applied cholinesterase inhibitors produce their antinociceptive effect and (2) examined their interaction with spinal mu opioid and alpha 2-adrenergic receptors., Methods: Rats were prepared with chronic intrathecal catheters and the nociceptive threshold was assessed by the use of the radiant heat-evoked hind paw withdrawal., Results: Spinal administration of neostigmine, edrophonium, carbachol, clonidine, and morphine produced a dose-dependent increase on the thermally evoked hind paw withdrawal latency. The order of potency (dose producing a 50% effect, in nanomoles) was morphine (1.1) = neostigmine (1.2) > clonidine (4.4) > carbachol (15) >> edrophonium (112). Spinal pretreatment with atropine (35 nmol) attenuated the antinociceptive effect of intrathecal carbachol (55 nmol), neostigmine (15 nmol), and edrophonium (500 nmol) but did not affect the potency of intrathecal morphine (15 nmol) or clonidine (435 nmol). In addition, intrathecal pretreatment with naloxone (31 nmol) and yohimbine (28 nmol) attenuated the effects of intrathecally administered morphine and clonidine, respectively, but did not significantly affect the potency of carbachol, neostigmine, or edrophonium. The nicotinic receptor antagonist mecamylamine (60 nmol) did not affect thermal nociception. Isobolographic analysis revealed a synergistic interaction after the coadministration of neostigmine-clonidine (P < 0.001), edrophonium-clonidine (P < 0.0001), and edrophonium-morphine (P < 0.01) mixtures. Neostigmine-morphine exhibited simple additivity., Conclusions: These data indicate that analgesia after spinal cholinesterase inhibition is mediated through muscarinic, but not nicotinic cholinergic, opioid, or alpha 2-adrenergic receptor systems, and that these spinal effects of cholinesterase inhibition interact synergistically with the antinociceptive effects of intrathecal mu and alpha 2 agonists.

Edrophonium (EDR) has the advantages of a quick onset of action and reduced cholinergic effects compared to neostigmine (NST) when they are used to antagonize neuromuscular block (NMB). There are few studies about antagonism of very weak residual NMB. Therefore we compared hemodynamic stability, train-of-four (TOF) characteristics and reversal time (time from administration of antagonists to train-of-four-ratio (TR) at least 0.70) of EDR 0.5 mg kg-1 + atropine (ATR) 0.007 mg kg-1 to NST 0.04 mg kg-1 + glycopyrrolate (GLY) 0.008 mg kg-1 when they were used to antagonize a residual vecuronium (VEC)-induced NMB (T1 25-75%). The NMB was monitored in 64 patients using the evoked electromyogram of the hypothenar muscle of the hand. An adequate antagonism was defined as a TR of 0.70 or higher. Heart rate was significantly higher in NST+GLY group 2 min after administration of the antagonists in comparison with the EDR+ATR group. The advantages of EDR (higher T1, TR and percentage of patients with an adequate recovery) were obvious during the first 5 min of reversal time. Therefore we conclude, that under the conditions described in the present study, EDR antagonizes residual VEC induced NMB faster than NST.

The purpose of this study was to find an antidote against death adder envenomation that can be used in cases of emergency, when antivenoms are not readily available (Papua New Guinea and the Australian outback). Such an antidote should allow bite victims to survive until established treatment is possible. Death adder venom is thought to act postsynaptically at the neuromuscular junction to reduce responses to acetylcholine. This causes severe flaccid paralysis and finally death, which is usually a consequence of respiratory failure. Albino Wistar rats were injected with a lethal dose of crude death adder venom. At the onset of severe envenomation symptoms, anticholinesterases (neostigmine and edrophonium) in conjunction with atropine sulfate were administered. At the minimum lethal dose (0.15 mg/kg) all animals survived as a result of the anticholinesterase treatment. The expected survival time of animals subjected to higher venom doses was significantly extended. These results indicate that death adder bite victims may gain valuable time, if anticholinesterases can be administered during the initial critical stage of envenomation.

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T4/T1 > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-of-four (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg.kg-1, during thiopentone-N2O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg.kg-1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg.kg-1, was given. Two minutes later, edrophonium, 0.1 mg.kg-1, was given if T4/T1 did not reach 0.7. After another two minutes, edrophonium, 0.2 mg.kg-1, was given if T4/T1 did not reach 0.7 or more. Finally, if T4/T1 was still < 0.7, a dose of 0.4 mg.kg-1 was given. Seventeen patients (42.5%) required 0.1 mg.kg-1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg.kg-1 and six patients (15%) required 0.4 mg.kg-1. Only one patient received 0.8 mg.kg-1. There was a good correlation between T4/T1 two minutes after the first dose of edrophonium and pre-reversal T4/T1 (r = 0.6; P = 0.00014). All patients with pre-reversal T4/T1 > 0.23 required at most 0.2 mg.kg-1 of edrophonium for successful reversal.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the effects of different types of anticholinesterase on the incidence of the postoperative nausea and vomiting, 100 ASA class I-II adult premenopausal female patients undergoing elective lower abdominal surgery were randomized into two groups. In both groups, anesthesia was induced with thiopental and fentanyl and 50% nitrous oxide and 0.5-1.5% of isoflurane were used for anesthetic maintenance with succinylcholine 1 approximately 1.5 mg/kg for intubation and atracurium 0.3 mg/kg/hr for maintenance of muscle relaxation. Patients received reversal agents for neuromuscular blockade after operation when the evoked train-of-four (TOF) count returned to four visual responses. A mixture of atropine 8 micrograms/kg and edrophonium 0.75 mg/kg was given to the first group of patients while atropine 15 micrograms/kg and neostigmine 40 micrograms/kg was given to another group of patients. All the patients were observed for the occurrence of nausea or vomiting for 2 hours after the operation in the recovery room. The incidence of nausea was not statistically significantly different in both groups (20% in neostigmine group and 26% in edrophonium group). The occurrence of vomiting was also similar in both groups (8% in neostigmine group and 6% in edrophonium group). We concluded that there were no difference in the incidence of postoperative nausea or vomiting with the use of either neostigmine or edrophonium with atropine for antagonizing neuromuscular blockade after the lower abdominal surgery.

A case of bilateral blepharospasm who registered the efficacy of edrophonium was reported. The case is a 49-year-old female. She had been in good health until January, 1991 when she complained of difficulty in opening her eyes while driving. Thereafter the condition progressed to such a degree that she was unable to experience a comfortable life. Her blinking rate did not changed. The symptoms were triggered by stress or some physical action, such as walking or driving. They were attenuated by taking a bath, sleep or sedation. The severity of the symptoms varied during the day and from day to day. Neurological examination revealed bilateral spasms of the orbicular oculi muscles, and occasionally of the orbicular oris muscles, sternocleidmastoid muscles and the perinasal regions. Neither orolingual dyskinesia nor other involuntary movements were detected. Surface electromyography (EMG) disclosed tonic discharges mainly from the orbicular oculi muscles. The abnormal spasm disappeared with the injection of edrophonium chloride. The test for the serum antiacetylcholine receptor antibody was negative and a repetitive stimulation EMG showed no waning phenomenon. No thymoma or thymus abnormalities were detected by pneumomediastinography. A needle EMG revealed neurogenic change in the distal portion of the limbs. A single fiber EMG showed elongation of the jitter value and the blocking phenomenon. Although distigmine bromide was ineffective against the spasm, pyridostigmine bromide and the local injection of botulinum toxin were very effective.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to investigate the effect of divided administration of edrophonium on the course of neuromuscular recovery from a pipecuronium neuromuscular blockade. During thiopentone-nitrous oxide-halothane anaesthesia 48 patients were given pipecuronium 70 micrograms.kg-1. Patients were randomly assigned to one of four groups (n = 12 in each) to receive either edrophonium 1 mg.kg-1 (Groups I and II) or edrophonium 0.75 mg.kg-1 (Groups III and IV). In Groups I and III (single-dose groups), edrophonium was administered as a single bolus dose. In Groups II and IV (divided-dose groups) edrophonium was administered as an initial dose of 0.25 mg.kg-1 followed three minutes later by either 0.75 or 0.50 mg.kg-1 respectively. Reversal was attempted at 20% spontaneous recovery of twitch height. Administration of edrophonium in divided doses (Groups II and IV) accelerated the reversal of the pipecuronium neuromuscular blockade. At ten minutes post-reversal, train-of-four (TOF) ratio recovery reached 0.75 or more in 12 (100%) and in ten (83%) patients in Groups II and IV respectively. Similarly, times to attain a TOF of 0.75 (SEM) were shorter in the divided-dose groups than in the single-dose groups (P less than 0.05), being 354.5 (38.7) and 398.3 (49.1) sec in Groups II and IV vs 705.4 (66.6) and 651.2 (54.3) sec in Groups I and III respectively. Time was counted from the first administration of edrophonium. It is concluded that administration of edrophonium in divided doses produced a faster reversal of residual pipecuronium-induced neuromuscular blockade than single bolus administration. Also, administration in divided doses reduced the requirements of edrophonium needed for reversal of pipecuronium neuromuscular blockade.

Antagonism of intense neuromuscular block induced by atracurium 0.5 mg kg-1 was attempted in four groups of six children using one of two doses of neostigmine (0.05 mg kg-1 and 0.1 mg kg-1) or of edrophonium (0.5 mg kg-1 and 1.0 mg kg-1) when the first twitch of the post-tetanic count (PTC1) was 10% of control. For comparison with normal practice, a fifth group received neostigmine 0.05 mg kg-1 when the first twitch of the train-of-four was 10% of control. Total recovery time from PTC1 10% to a train-of-four ratio of 0.8 was not reduced by early administration of the anticholinesterases, compared with conventional administration of neostigmine at T1 10%. However, recovery from intense block was faster after neostigmine than edrophonium (P less than 0.01). Doubling the doses of the anticholinesterases did not reduce the recovery time and had the effect of increasing variability. We conclude that there is no clinical advantage in attempting to antagonize intense neuromuscular block in children using normal or increased doses of neostigmine or edrophonium.

Edrophonium chloride is used frequently as a provocative agent in the assessment of noncardiac chest pain (NCCP). However, the optimum dose and most appropriate method of interpreting test results is controversial. We studied 150 consecutive NCCP patients and 50 age-matched controls who alternately received either 80 micrograms/kg or 10 mg intravenous bolus doses of edrophonium preceded by saline placebo injections. Distal esophageal pressures were measured before and after drug injection in response to ten 5-cc wet swallows. Following 10 mg of edrophonium, 33% of patients and 4% of controls reported chest pain, while 29% of patients and no controls receiving the 80 micrograms/kg dose complained of chest pain. Amplitude changes after either dose were not significantly different for all comparisons, but the duration of response did distinguish the two doses in patients with chest pain. A significantly greater (P = 0.01) increase in distal contraction duration occurred after 10 mg (74 +/- 12%; +/- SE) compared to 80 micrograms/kg dose (43 +/- 6%). However, individual responses to the two doses overlapped considerably. If a positive test is redefined to include both chest pain and manometric changes that are significantly different from controls, the positivity rate changes drastically; 33% to 9% in the 10-mg group and 30% to 3% in the 80-micrograms/kg group. Side effects were similar between doses, but there was a significant (P = 0.02) linear relationship between intensity of side effects and the edrophonium dose per kilogram of body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the influence of enflurane on the ability of edrophonium to antagonize atracurium block, dose-response curves were constructed for edrophonium in the presence of 0%, 1% and 2% enflurane, and for 2% enflurane discontinued at the time of administration of edrophonium. One hundred ASA Physical Status I or II patients (four groups of 25), selected randomly and undergoing elective surgery, received atracurium 0.5 mg kg-1, with thiopentone, nitrous oxide and enflurane. Supplementary doses of fentanyl were given if needed. Train-of-four (TOF) stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height (T1) had recovered spontaneously to 10% of initial value, edrophonium 0.1, 0.2, 0.4 or 1 mg kg-1 was administered by random allocation. Enflurane concentrations remained constant, except that enflurane was discontinued in 50% of the patients who had received 2% enflurane. Monitoring was continued for at least 10 min, at which time T1 and TOF ratio (T4/T1) were measured. The ED80 for T1 recovery depended on the dose of enflurane: 0.08 (SEM 0.03), 0.21 (0.06) and 0.42 (0.18) mg kg-1 for 0%, 1% and 2% enflurane, respectively (P less than 0.005). With enflurane 2% discontinued, the ED80 was 0.095 (0.050) mg kg-1 (P less than 0.02 compared with 2% enflurane).(ABSTRACT TRUNCATED AT 250 WORDS)

Edrophonium administered in divided doses has been reported to accelerate antagonism of neuromuscular blockade, i.e., a "priming" effect. Since measured onset times can be affected by the type of stimulation used, this effect was studied using both train-of-four (TOF) and single twitch (ST) stimulation. During thiopentone-nitrous oxide-enflurane anaesthesia 20 adults were given atracurium 0.5 mg.kg-1. Both ulnar nerves were stimulated with TOF every 12 sec until one per cent recovery of first twitch (T1). At this time, ST stimulation was applied to one arm, selected at random. When the mean value of T1 and ST reached ten per cent of control, edrophonium, 1 mg.kg-1, preceded by atropine was given either as a single dose, or in two doses consisting of 0.2 mg.kg-1 followed by 0.8 mg.kg-1 three minutes later. No statistically significant differences were observed between T1 and ST for the next ten minutes, whether edrophonium had been given in single or divided doses. Giving edrophonium in divided doses did not improve recovery significantly, measured with either T1, ST or train-of-four ratio (T4/T1). Five minutes after the first administration of edrophonium, T1 was (mean +/- SEM) 86 +/- 3 and 86 +/- 2 per cent control in the single and divided dose groups respectively. Corresponding values for ST were 89 +/- 1 and 89 +/- 2 per cent (NS), and for TOF, 49 +/- 3 and 57 +/- 3 per cent (NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The actions of edrophonium on neuromuscular transmission in vivo have been studied using the lateral segmental tail muscles of the rat. The drug produced an increase in amplitude of the miniature endplate potentials (m.e.p.p.s) without an effect on their frequency and increased the amplitude of the end-plate potentials (e.p.p.s) without increasing quantal release of transmitter. It is concluded that the anticholinesterase action of this drug in vivo facilitates neuromuscular transmission, which confirms many of the findings from in vitro studies.

This study was designed to investigate the effect of different priming doses of edrophonium on the relationship between the the recovery of the first twitch of the train-of-four (T1) and train-of-four (TOF) ratio. This relationship was studied after the administration of the full dose of the antagonist in all groups. Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I, controls) or in an initial dose of 0.05, 0.1, 0.15 or 0.2 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to V. Reversal was attempted at the ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Of all the groups studied, Group V had a significantly greater recovery in the TOF ratio at any given T1 value. When first twitch tension (T1) had recovered to 100 per cent of the control, it was found for the same tension that the TOF ratio was greater in Group V, being 0.75 compared to 0.63, 0.65, 0.65 and 0.64 in Groups I to IV respectively. The implication is that this differential ability to reverse fade (or prejunctional activity) may be involved in the acceleration of recovery.