Effects of two levels of partial neuromuscular block with atracurium on the ventilatory response to hypercapnia in anesthetized Beagles.

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 CO2 (Petco2), tidal volume (Vt), and peak inspiratory flow (PIF) were measured during breathing at rest. Maximal Vt and PIF (VtMAX and PIFMAX, respectively) in response to a hypercapnic challenge consisting of 10% CO2 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 Petco2; it impaired Vt at rest and VtMAX but not PIF at rest and PIFMAX. All variables except Petco2 returned to baseline values when the TOF returned to ≥ 0.9. After recovery from neuromuscular block, significantly more dogs had a VtMAX < 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.

Detectable voice change with the edrophonium test in laryngeal myasthenia gravis.

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.

Reversal of neuromuscular block in companion animals.

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.

Dropped head with positive intravenous edrophonium, progressing to myasthenia gravis.

'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.

Failure to reverse prolonged vecuronium-induced neuromuscular blockade with edrophonium in an anesthetized dog.

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.

Rapid chemical antagonism of neuromuscular blockade by L-cysteine adduction to and inactivation of the olefinic (double-bonded) isoquinolinium diester compounds gantacurium (AV430A), CW 002, and CW 011.

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.

Cardiovascular and autonomic nervous effects of edrophonium and atropine combinations during neuromuscular blockade antagonism in sheep.

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.

Diverse inhibitory actions of quaternary ammonium cholinesterase inhibitors on Torpedo nicotinic ACh receptors transplanted to Xenopus oocytes.

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.

Sugammadex reversal of rocuronium-induced neuromuscular blockade: a comparison with neostigmine-glycopyrrolate and edrophonium-atropine.

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.

Edrophonium provocative testing for the evaluation of upper gastrointestinal hypersensitivity in patients with nonulcer dyspepsia.

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.

Simplified tilt table test protocol with continuous upright position during medication administration and no hydration.

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.

Development of generalized disease at 2 years in patients with ocular myasthenia gravis.

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.

Edrophonium antagonism of cisatracurium-induced neuromuscular block: dose requirements in children and adults.

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.

[Edrophonium chloride (Tensilon) test: a safe method in diagnosing myasthenia gravis]. / Der Edrophonium-Chlorid (Tensilon)-Test: Ein sichere Methode in der Diagnostik der Myasthenia gravis.

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.

[Heart rate reduction using edrophonium during coronary artery bypass grafting without cardiopulmonary bypass].

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.

The antiallodynic effects of intrathecal cholinesterase inhibitors in a rat model of neuropathic pain.

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.

Isolated inferior rectus palsy caused by a metastasis to the oculomotor nucleus.

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.

The effect of edrophonium chloride on muscle balance in normal subjects and those with nonmyasthenic strabismus.

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.