Purification and partial characterization of a novel neurotoxic protein from eggs of black widow spiders (Latrodectus tredecimguttatus).

Up to now, there have been a few reports on the toxic components purified from black widow spider (Latrodectus tredecimguttatus) eggs. In the present study, a novel neurotoxic protein was purified from the eggs by gel filtration combined with ion-exchange chromatography. Its molecular weight was 23.752 kDa determined by electrospray mass spectrometry. The protein could block the neuromuscular transmission in mouse-isolated phrenic nerve-hemidiaphragm preparations completely in a reversible manner and activate tetrodotoxin-sensitive sodium current in rat dorsal root ganglion cells. The N-terminal sequence of the protein was identified by the Edman degradation to be N-S-I-A-D-D-R-Y-R-W-P-G-Y-P-G-A-G-L-I-P-Y-I-I-D-S-. When the sequence was used to search against protein database with a sequence query in Mascot engine there was no matched sequence or protein whereas the Basic Local Alignment Search Tool (BLAST) analysis indicated that no significant similarity was found. These results demonstrated that the protein (named Latroeggtoxin-I) is a novel neurotoxic protein purified from the eggs of black widow spiders.

Prolonged paralysis and apnea after receiving a neuromuscular blocking agent: what nurses should know.

After receiving mivacurium, a short-acting neuromuscular blocking agent used for intubation before surgery, a patient experienced prolonged paralysis and prolonged apnea that required ventilator support. Although this complication is rare, all critical care nurses should be aware of it so they can be competent in managing and providing holistic and comprehensive nursing care to the patient and the patient's family. Although this complication has been documented in the anesthesia literature, it has received little mention in critical care nursing journals.

Skin reactions to intradermal neuromuscular blocking agent injections: a randomized multicenter trial in healthy volunteers.

BACKGROUND: Numerous reports confirm the performance of intradermal tests for the diagnosis of anaphylaxis during anesthesia; however, there is controversy over their diagnostic value regarding the newer neuromuscular blocking agents (NMBAs). METHODS: One hundred eleven healthy volunteers were randomly assigned to receive intradermal injections of two NMBAs, at five increasing concentrations. A concentration was considered as a reactive concentration when it led to a positive reaction in more than 5% of the subjects. These concentrations were compared with the maximal concentration recommended for the diagnosis of sensitization to NMBAs. RESULTS: The maximal nonreactive concentrations were 10 m for suxamethonium; 10 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10 m for atracurium and mivacurium. Except for mivacurium, these nonreactive concentrations were close to the maximal concentrations used for the diagnosis of sensitization against NMBAs. For mivacurium, the nonreactive concentrations were higher than the maximal concentration currently recommended in clinical practice. CONCLUSION: The aminosteroidal NMBAs pancuronium, vecuronium, and rocuronium and the benzylisoquinoline cisatracurium have a similar potency to induce a nonspecific skin reactivity. If the criteria for positivity and the maximal concentrations of the commercially available compounds recommended by French practice guidelines are used, the risk of false-positive results is limited, and only minor modifications of these recommendations could be suggested. A slight reduction in the maximal concentration used for rocuronium from 1:100 to 1:200 and an increase from 1:1,000 to 1:200 for mivacurium can be proposed.

[Effects of priming technique on onset profile of cisatracurium]. / Auswirkung der Priming-Technik auf die Anschlagszeit von Cisatracurium.

Compared to atracurium, cisatracurium releases less laudanosine and histamine, but it has a longer onset time. The primary objective of this study was a blinded, randomized comparison of intubation scores and onset times of a threefold ED 95 of cisatracurium using the priming technique with two priming substances cisatracurium itself and pancuronium. To test the effect of priming with cisatracurium or pancuronium on the onset of cisatracurium, 45 patients were anaesthetised with 0.15-0.25 mg/kg alfentanil, 0.25-0.3 mg/kg edomidate i.v. and O2/N2O, and were randomisely divided into one of three groups. After induction, 15 patients were primed with sodium chloride and thereafter received 0.15 mg/kg cisatracurium, 15 patients were primed with 0.01 mg/kg cisatracurium, another 15 patients were primed with 0.015 mg/kg pancuronium and the last two groups received 0.14 mg/kg cisatracurium three minutes later. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG) by stimulating in a TOF pattern. Times for T1 reduction to 75%, 50%, 25% and 0% and T1 recovery to 25% were taken. Intubation was performed 120 seconds after the main relaxant dose and scored in four grades. The two priming groups showed a significantly faster onset of neuromuscular blockade than the control group (cisatracurium priming group: T1 = 0: 178.4 +/- 16.3 sec., pancuronium priming group 171.2 +/- 15.3 sec. vs. control group: T1 = 0: 205.5 +/- 18.9 sec.). Both primed groups showed no significantly better intubation scores, compared with the control group. Using the priming principle, cisatracurium will give good intubation scores 120 seconds after injection with a clinical duration profile comparable to an equipotent dose of atracurium.

Clinical pharmacology of neuromuscular blocking agents.

The clinical pharmacology of neuromuscular blocking agents is described. During neuromuscular blockade, succinylcholine attaches to receptors in the motor end plate and depolarizes the neuromuscular junction, making the end plate refractory to acetylcholine. The nondepolarizing relaxants have a structure similar to that of succinylcholine and bind to the same receptors. Instead of depolarizing the junction, they block acetylcholine from binding to the receptor and cause channel blockade. As the concentration of nondepolarizing relaxant increases relative to acetylcholine, neuromuscular transmission is compromised. This relationship is used clinically to facilitate recovery from nondepolarizing agents. Succinylcholine is popular because its onset is faster than that of the nondepolarizing relaxants and metabolism by pseudocholinesterase clears it quickly. It is commonly given as an i.v. bolus to facilitate tracheal intubation. The onset of these agents varies widely and is dose dependent. Large doses are usually given to hasten the onset of paralysis; subsequent doses are adjusted according to response. The nondepolarizing agents interact with inhaled anesthetics, magnesium, and many antimicrobials. Drugs like neostigmine, edrophonium, and pyridostigmine antagonize neuromuscular blockade; an anticholinergic drug is typically administered to counteract the cardiovascular effects. The most serious adverse effects of succinylcholine are malignant hyperthermia syndrome, masseter muscle rigidity, and bradycardia. Some nondepolarizing relaxants (atracurium, mivacurium, and pancuronium) are associated with histamine release, occasionally causing serious hypotension and tachycardia. Neuromuscular blocking agents are essential to anesthesia. Older compounds produce greater toxicity than newer compounds, and several of these older compounds therefore are no longer in clinical use.

Myopathy following mechanical ventilation for acute severe asthma: the role of muscle relaxants and corticosteroids.

BACKGROUND: Acute myopathy following mechanical ventilation for near-fatal asthma (NFA) has been described recently, and some researchers have suggested that this complication is related to the use of neuromuscular blocking agents (NMBAs) and corticosteroids (CSs). OBJECTIVES: To determine the incidence of acute myopathy in a group of patients and to examine the most important predictors of its development. DESIGN AND METHODS: A retrospective cohort study over a 10-year period (1985 to 1995) of all asthma patients who received mechanical ventilation at two centers in Vancouver (designated center 1 and center 2). RESULTS: In center 1, there were 58 patients who had 64 episodes of NFA, and in center 2, there were 28 patients who had 30 episodes. NMBAs were used in 30 of 86 admissions for acute severe asthma (35%). The mean (+/- SD) duration of muscle paralysis was 3.1+/-2.3 days. A total of 9 patients (10.4%) developed significant myopathy. The incidence of myopathy was 9 of 30 (30%) among patients who received NMBAs. In a multiple logistic regression model, the development of myopathy was only significantly associated with the duration of muscle relaxation. The odds ratio for the development of myopathy increased by 2.1 (95% confidence interval, 1.4 to 3.2) with each additional day of muscle relaxation. The dose and the type of the CS were not significantly associated with the myopathy in the multiple logistic regression analysis. CONCLUSION: Our study showed that there is a high incidence of acute myopathy when NMBAs are used for NFA. The incidence of myopathy increases with each additional day of muscle relaxation.

Clindamycin-induced neuromuscular blockade.

The purpose of this article is to report the case of a patient who developed prolonged neuromuscular block after a large dose of clindamycin (2400 mg). A 58-yr-old, 65 kg woman with severe rheumatoid arthritis was admitted for wrist arthrodesis. After d-tubocurarine (3 mg) and fentanyl (1.5 micrograms.kg-1), anaesthesia was induced with thiopentone (4 mg.kg-1) followed by succinylcholine (1.5 mg.kg-1) and was maintained with N2O in O2 and isoflurane (0.75-1.0% end tidal) and ventilation was controlled. No further neuromuscular relaxants were given although full return of neuromuscular activity in response to train-of-four and 100 Hz tetanic stimulation was observed after succinylcholine. An overdose of clindamycin (2400 mg, instead of the intended 600 mg) was given i.v. soon after the start of surgery. At the end of surgery, 75 min later, the patient made no attempt at spontaneous ventilation, was unresponsive to painful stimuli and naloxone (0.2 mg i.v.) was ineffective. Controlled ventilation was continued in the Recovery Room where neuromuscular testing showed a train-of-four ratio of 0.27 which improved to only 0.47 five minutes after calcium chloride (1.5 mg.kg-1 i.v.), and to 0.62 after edrophonium (20 mg) and neostigmine (2 mg). Nine hours later the patient began to cough, the TOF had returned to 1.0 and two hours later the trachea was extubated and spontaneous ventilation was resumed. Large doses of clindamycin can induce profound, long-lasting neuromuscular blockade in the absence of non-depolarizing relaxants and after full recovery from succinylcholine has been demonstrated.

The use of fetal neuromuscular blockade during intrauterine procedures.

Advances in fetal therapy have led to the utilization of such techniques as intravascular transfusion of the Rh-affected fetus, bladder shunt placement in the fetus with obstructive uropathy, and percutaneous umbilical blood sampling. Fetal movement makes these procedures technically more difficult while increasing the risk of fetal injury. However, maternal sedation rarely results in adequate suppression of fetal activity. Thus we tested the sedative effects of intramuscular d-tubocurarine (3 or 1.5 mg/kg) or pancuronium bromide (0.3 mg/kg) injected into the fetal gluteal region under ultrasound guidance in conjunction with 70 invasive in utero procedures. Short-term paralysis of the fetus was induced in all cases. No deleterious effects of this technique were noted on initial examination of the neonates. Neuromuscular blockade was found to be a very useful adjunct to both diagnostic and therapeutic procedures involving the fetus.

[Pharmacodynamics of vecuronium. A clinical study]. / Pharmakodynamische Untersuchungen mit Vecuronium. Eine klinische Studie.

54 Patients (ASA I + II) were paralysed with different doses of vecuronium during neuroleptanesthesia. Time course of action was registered by means of mechanical twitch response. ED 95 as calculated by linear regression amounted to 63 micrograms/kg (ED 50: 27 micrograms/kg). After administration of ED 95 about 3/4 of the patients are completely paralysed. After administration of 70 micrograms/kg 9/10 of the patients are completely paralysed. Mean duration of action of these two doses is 28 and 35 min respectively. Vecuronium doses from 60 micrograms/kg on are suitable for orotracheal intubation. However onset time of action is 3-4 min. Circulatory side effects after administration of vecuronium were not observed.

Precurarization--a hazard to the patient?

Four case histories are presented illustrating the unpleasant and serious reactions that may follow precurarization with small doses of non-depolarizing muscle relaxants. The importance of preoperative information, the necessity of relating the dose of the precurarizing drug to the weight of the patient and the possibility of hypersensitivity to this drug are emphasized.

Muscular relaxation with atracurium, vecuronium and duador under balanced anaesthesia.

The neuromuscular effects of three new nondepolarizing neuromuscular blocking drugs, atracurium, vecuronium and Duador, were investigated in surgical patients under balanced anaesthesia. (The numbers of patients in each study are given in the tables.) There were no significant differences in the neuromuscular effects of the three agents. None showed any cumulation after repeated administration of maintenance doses. Muscular relaxation for upper abdominal surgery was adequate as long as the isometric twitch tension (P) was no more than 25% of control. Conditions for tracheal intubation were satisfactory within less than 3 min after the start of injection. Spontaneous recovery of P to 90-95% of control, after the last dose of neuromuscular blocker was the fastest with vecuronium (35.8 +/- 2.4 min) and about the same with atracurium (54.3 +/- 2.4 min) and Duador (54.2 +/- 4.7 min). The T4/T1 ratio at the time of greater than 90% recovery of P was 0.44, 0.52 and 0.56 with vecuronium, Duador and atracurium, respectively, indicating the need for the reversal of the residual neuromuscular block. This could be accomplished within 2 min by the i.v. injection of edrophonium 0.5 mg kg-1, preceded by atropine 0.01 mg kg-1. No side-effects were observed with vecuronium. Atracurium caused mild to moderate histamine release in four of 50 patients included in this study, all of whom received an initial dose of 0.5 mg kg-1. The initial dose of Duador caused a 16.7% increase in heart rate. The findings indicate that the three new muscle relaxants merit further clinical trial. In our opinion, until the results of such studies become available, atracurium should not be used in patients with a history of allergic diathesis and Duador in those in whom increased heart rate may be harmful.

Hazards of succinylcholine administration during electrotherapy.

We describe prolonged apnea following electrotherapy in a patient who was also being treated with a topical organophosphate anticholinesterase, ecothiophate iodide (phospholine iodide), for glaucoma. The increased duration of action of succinylcholine resulted from low levels of serum cholinesterase that had been caused by the organophosphate. Attention is called to other drugs that directly or indirectly (by lowering serum cholinesterase) interact with succinylcholine chloride resulting in prolonged apnea. Other potential hazards of succinylcholine administration, such as hyperkalemia and cardiac arrhythmias, are also discussed.

Carcinoid syndrome: its relevance to the anaesthetist.

This paper presents the pathology, pharmacophysiology and therapy of the carcinoid syndrome. Forty reports from the literature are reviewed and the anaesthetic management of the patients is discussed. The carcinoid syndrome is a rare multihumoral endocrine disease. Secretions may be stimulated by certain anaesthetic and surgical manoeuvres and produce undesirable, and occasionally fatal, cardiovascular and respiratory complications. A radical surgical approach to the disease is current. Anaesthetists may therefore be involved in the management of these patients more frequently than before. The implication of both serotonin and bradykinin in the pharmacophysiology of this disease allows a more rational approach to the treatment of complications occurring during anaesthesia. However, other, as yet undiscovered vasoactive substances, may be involved.

Effects on non-depolarizing neuromuscular blocking agents on peripheral autonomic mechanisms in cats.

Intravenous dose-response relationships were used to correlate neuromuscular paralysis with effects on autonomic mechanisms in anaesthetized cats. Whereas autonomic blockade with tubocurarine occurred at parasympathetic and sympathetic ganglia, neuromuscular paralysing doses of gallamine, alcuronium, pancuronium and fazadinium caused blockade at vagal postganglionic sites in the heart. The vagolytic (atropinic) activity of these compounds in cats relative to their neuromuscular blocking activity appeared to correlate well with their known liability to cause undesirable hypertension and tachycardia in man. The absence of cardiovascular effects after the administration of neuromuscular blocking doses of dimethyl tubocurarine would support its more extensive clinical use, but the need remains for a short-acting muscle relaxant with properties similar to those of dimethyl tubocurarine.