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Drug designing is high-priced and time taking process with low success rate. To overcome this obligation, computational drug repositioning technique is being promptly used to predict the possible therapeutic effects of FDA approved drugs against multiple diseases. In this computational study, protein modeling, shape-based screening, molecular docking, pharmacogenomics, and molecular dynamic simulation approaches have been utilized to retrieve the FDA approved drugs against AD. The predicted MADD protein structure was designed by homology modeling and characterized through different computational resources. Donepezil and galantamine were implanted as standard drugs and drugs were screened out based on structural similarities. Furthermore, these drugs were evaluated and based on binding energy (Kcal/mol) profiles against MADD through PyRx tool. Moreover, pharmacogenomics analysis showed good possible associations with AD mediated genes and confirmed through detail literature survey. The best 6 drug (darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar) further docked and analyzed their interaction behavior through hydrogen binding. Finally, MD simulation study were carried out on these drugs and evaluated their stability behavior by generating root mean square deviation and fluctuations (RMSD/F), radius of gyration (Rg) and soluble accessible surface area (SASA) graphs. Taken together, darifenacin, astemizole, tubocurarine, elacridar, sertindole and tariquidar displayed good lead like profile as compared with standard and can be used as possible therapeutic agent in the treatment of AD after in-vitro and in-vivo assessment., (© 2023. Springer Nature Limited.)

Background and Purpose: Tubocurarine (d-TC), a non-depolarizing competitive blocker of nicotinic acetylcholine receptors is extensively utilized for the relaxation of skeletal muscles. Drug repositioning is a forthright approach to reduce the cost and speed up drug development process. Herein, we have attempted to evaluate the analgesic and anti-inflammatory activity of d-TC for its possible repurposing in pain and inflammation-related issues., Experimental Approach: We examined the soluble epoxide hydrolase inhibitory (sEHI) activity of d-TC employing in silico high throughput screening protocols, in vitro cell-free sEH inhibitory assay, and in in vivo rodent models for its repositioning in pain and inflammation-related disorders., Key Results: In molecular docking study, d-TC displayed impressive hydrogen bonding interactions within the cavity of sEH enzyme with good docking score. d-TC also exhibited notable sEH inhibitory activity (IC 50 3.72 nm) at the in vitro assay. Oral absorption capability of d-TC (0.1 and 0.2 mg/mL) was determined using an in vitro everted intestinal sac model employing rat ileum tissue that revealed significant oral absorption of d-TC. Besides, in vivo studies revealed that oral administration of d-TC (0.1 and 0.2 mg/kg) in rodents significantly attenuated hyperalgesia (cold plate test, tail immersion test and formalin test) and inflammation (estimation of rectal temperature, acetic acid induced pleurisy test and cotton pellet-induced granuloma test) induced in robust preclinical models. Conclusion and implications These findings are novel and warrant immediate efforts to reposition d-TC as a new therapeutic candidate in the management of hyperalgesia, inflammation, and associated conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Potassium channels are essential for cell survival and regulate the cell membrane potential and electrochemical gradient. During its lifecycle, Plasmodium falciparum parasites must rapidly adapt to dramatically variant ionic conditions within the mosquito mid-gut, the hepatocyte and red blood cell (RBC) cytosols, and the human circulatory system. To probe the participation of K(+) channels in parasite viability, growth response assays were performed in which asexual stage P. falciparum parasites were cultured in the presence of various Ca(2+)-activated K(+) channel blocking compounds. These data describe the novel anti-malarial effects of bicuculline methiodide and tubocurarine chloride and the novel lack of effect of apamine and verruculogen. Taken together, the data herein imply the presence of K(+) channels, or other parasite-specific targets, in P. falciparum-infected RBCs that are sensitive to blockade with Ca(2+)-activated K(+) channel blocking compounds.

Muscle relaxing agents are clinically in use for general anaesthesia to optimize the conditions to the endotracheal intubation as well as the surgical conditions. Therefore different musclerelaxants with specific pharmacological characteristics are available. Many factors that depend on the condition of the patient and the used musclerelaxant agent influence the duration of the neuromuscular blockade. Rapid reversal of their effects, particularly in cases of profound blockades, proved to be difficult. In cases of postoperative residual paralysis hypoxic complications because of failure of the ventilation increase the morbidity and mortality of the perioperative period. To avoid these complications in cause of postoperative residual neuromuscular blockade it seems to be necessary to evaluate the status of the muscle function. For the tactile or visual assessment or the objective measurement of stimulation the train-of-four (TOF), double-burst (DBS) or tetanus-stimulation of peripheral nerves like the ulnar nerve may be used. Established methods for the objective monitoring of neuromuscular function is the mechanomyography (MMG), the acceleromyography (AMG), the electromyography (EMG), the kinemyography (KMG) and the phonomyography (PMG). A sufficient recovery of the neuromuscular transmission is reached to a TOF-ratio of 0,9 and should be aimed before the extubation at the end of surgery. No subjective evaluation of the neuromuscular recovery is able to identify residual paralysis above a TOF-ratio of 0,5. Recent studies suggest that objective methods should be used to monitor neuromuscular function to avoid postoperative residual blockades.

In 1958, an 11-year-old girl with status epilepticus was given the current treatments which failed to control the convulsions. In order to stop the fits, protect the airway, prevent hypoxia and hyperpyrexia, intermittent positive pressure ventilation (IPPV) and complete muscle paralysis with d-tubocurarine was used for a total of 6 h. The girl made a complete recovery, the first patient to do so using this plan of action.

Purpose: To compare intubating conditions and postoperative myalgias in outpatients after intubation with propofol/alfentanil compared with propofol/alfentanil/succinylcholine with and without precurarisation with d-tubocurarine., Methods: 144 ASA I-II ambulatory patients for dental extraction under anesthesia were studied. Subjects received either 3 mg d-tubocurarine (Group II) or saline (Groups I, III) i.v. prior to induction of anesthesia with 20 microg x kg(-1) alfentanil and 2.5 mg x kg(-1) propofol followed by 1.5 mg x kg(-1) succinylcholine (II and III) or saline 0.9% (I) for muscle relaxation. The ease of airway management and the postoperative incidence, severity and distribution of muscle pains were examined., Results: Intubation was successful in all patients and there were no differences in jaw mobility, ease of bag-mask ventilation, visualization of the vocal cords or cord position. Limb movement was more common during intubation in Group I (37.5%) than in Group III (8.3%) or Group II (2%), P < 0.05. At home, VAS scores for myalgia were higher in Group III than in Group I and II. Neck myalgia was more common in Group II (72%) than in Groups II (44%) and I (41%), P < 0.05. Myalgias were also more common in Group III patients (P < 0.05)., Conclusion: Acceptable intubating conditions were achieved with propofol and alfentanil alone. Succinylcholine reduced limb movement during intubation but was associated with postoperative myalgias for up to five days. Precurarisation with tubocurarine reduced the severity of succinylcholine myalgia.

Administration of alfentanil followed by propofol intravenously (IV) without neuromuscular blockade for induction of anesthesia provides adequate conditions for tracheal intubation. Other hypnotic drugs have not been thoroughly investigated in this regard. Accordingly, 140 ASA physical status I and II premedicated outpatients were randomly assigned to one of seven groups (n = 20/group). Patients in Groups I-VI received alfentanil 40 microg/kg followed by etomidate 0.3 mg/kg, propofol 2 mg/kg, or thiopental 4 mg/kg. One half of these patients (Groups II, IV, VI) also received lidocaine 1 mg/kg IV prior to the administration of the above drugs. Patients in group VII received d-tubocurarine 3 mg followed by thiopental 4 mg/kg and succinylcholine 1 mg/kg. Ninety seconds after induction, laryngoscopy and endotracheal intubation were attempted and graded. Patients in Group V (alfentanil/thiopental) were significantly (P < 0.05) more likely to have a clinically unacceptable response to intubation (55%) (e.g., vigorous coughing, purposeful movement, or requirement for succinylcholine to complete intubation) compared with patients who received propofol (35%) or etomidate (20%). Alfentanil/etomidate yielded intubation conditions comparable to those achieved with alfentanil/propofol and d-tubocurarine/thiopental/succinylcholine. Lidocaine appeared to improve intubating conditions, although this improvement did not reach statistical significance. The results suggest that healthy, premedicated patients with favorable airway anatomy who have received alfentanil 40 microg/kg can be reliably tracheally intubated 90 s after administration of propofol 2 mg/kg or etomidate 0.3 mg/kg.

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.

A prospective, randomised trial was undertaken in 60 healthy adults to determine the efficacy of intravenously administered phenytoin in doses of 5 mg.kg-1 for the prevention of suxamethonium-induced fasciculations, a rise in serum K+ and myalgia. This was compared with tubocurarine pretreatment and no pretreatment (control group). Phenytoin pretreatment significantly reduced myalgia from 45% (nine patients) in the control group to 10% (two patients) (p less than 0.05). It also decreased the duration and mean intensity of fasciculations. Incidentally, phenytoin was also found to decrease significantly mean serum Na+ levels (p less than 0.001) both at 5 and 20 min after administration. Tubocurarine pretreatment (3 mg) resulted in a significant decrease in fasciculations, but myalgia, which occurred in five patients, remained the same. No significant correlation was found between muscle fasciculations, postoperative myalgia and K+ changes, but patients with myalgia had a significant decrease in mean serum Na+ levels at 5 and 20 min after suxamethonium (p less than 0.01).

The incidence of muscle pains and changes in serum concentrations of potassium, calcium and creatine kinase following suxamethonium were investigated after no pretreatment or pretreatment with intravenous tubocurarine 0.05 mg.kg-1, intravenous chlorpromazine 0.1 mg.kg-1, alphatocopherol (vitamin E) 600 mg in three divided doses orally, aspirin 600 mg orally or intravenous calcium chloride 5 mg.kg-1 in groups of 20 patients each. The incidence of myalgia was reduced significantly by tubocurarine, chlorpromazine and alphatocopherol. However, the increase in creatine kinase was attenuated only in the groups of patients who received tubocurarine and chlorpromazine. The changes in serum potassium and calcium concentrations were within acceptable limits. The intubating conditions were not as good in the patients who received tubocurarine as in the other groups. Effectiveness of chlorpromazine in preventing both the myalgia and the biochemical changes suggests the involvement of phospholipases in the pathogenesis of suxamethonium-induced muscle damage.

Forty-four patients, ASA physical status I or II, undergoing thiamylal, fentanyl, N2O/O2 anaesthesia were studied to determine the dose-response to succinylcholine (Sch) without prior defasciculation (24 pt - Group 1), or three minutes following d-tubocurarine (dTC), 0.043 mg.kg-1 (20 pt - Group 2). The individual log dose-logit response curve for each patient was determined using a cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle. The mean (+/- SEM) ED50, ED90 and ED95 values for Sch in Group 1 were 0.13 +/- 0.01, 0.19 +/- 0.01 and 0.22 +- 0.01 mg.kg-1, and in Group 2 were 0.16 +/- 0.01, 0.25 +/- 0.01 and 0.29 +/- 0.02 mg.kg-1, respectively. The mean ED values in Group 2 were significantly greater than the equivalent values in Group 1 (P less than 0.05). Compared with values in Group 1, ED values in Group 2 represented mean increases of 23, 32, and 32 per cent, respectively. These pharmacodynamic data indicate that the dose of Sch needs to be increased by 32 per cent following a defasciculating dose of dTC 3 mg.70 kg-1 (0.043 mg.kg-1).

Two hundred and fifty women undergoing termination of pregnancy during the first trimester under general anaesthesia were studied to determine the effects of precurarisation on suxamethonium-induced postoperative myalgia and on the need for postoperative analgesics after suxamethonium. Either alcuronium (0.03 mg/kg), atracurium (0.04 mg/kg), tubocurarine (0.05 mg/kg), vecuronium (0.01 mg/kg) or saline was administered in a double-blind manner 4 min before giving suxamethonium. An additional 50 patients were studied who received isoflurane rather than precurarisation and suxamethonium. Every pretreatment prevented fasciculations better than did saline (P less than 0.001). In the saline group, 92% of patients had fasciculations and in the other groups this ranged from 8 to 32%, respectively. On the first postoperative day, 76% of the patients in the saline group had myalgia while myalgia was manifested in 28, 54 and 34% of patients given alcuronium, tubocurarine or vecuronium, respectively (P less than 0.05). Atracurium failed in this effect with 62% having myalgia. In the isoflurane group, none of the patients complained of myalgia on the first postoperative morning. The need for analgesics was less (P less than 0.005) in the isoflurane group (8%) and in the pretreatment groups (18-27%) than in the saline group (42%). It is concluded that precurarisation with tubocurarine, vecuronium or, most effectively, with alcuronium but not with atracurium decreases suxamethonium-induced postoperative myalgia and seems to be necessary also during the first trimester of pregnancy.

Intraoperative hypothermia has become a common occurrence. Postoperative rewarming often is accompanied by shivering and results in increased metabolic and circulatory demands. We examined the metabolic, hemodynamic, and biochemical variables in 2 groups of hypothermic (greater than 35.8 degrees C) patients requiring mechanical ventilation after a major operation. One was observed during routine medical management whereas the other group received 40 mg of metocurine iodide and then observed during routine medical management. All patients were allowed to rewarm passively. O2 consumption (VO2, ml/min, STPD), CO2 production (VCO2, ml/min, STPD) and respiratory quotient (RQ) measurements were made every 15 min using a Beckman Metabolic Measurement Cart. Esophageal temperature, arterial blood pressure, heart rate (HR), rate pressure product, CVP, arterial blood gases, serum lactate concentration, and duration of shivering also were recorded. Suppression of the shivering by metocurine increased rewarming time significantly and decreased VCO2, VO2, HR, rate pressure product, mean arterial pressure (MAP), and the O2 cost of rewarming. Thus, the elimination of shivering during postoperative rewarming is associated with a decrease in caloric, metabolic demands and myocardial work (as assessed by the rate pressure product) while rewarming time is prolonged. In the postoperative, hypothermic, critically ill patient, suppression of the shivering response in selected patients may be indicated.

Intermittent positive-pressure ventilation and muscle relaxants were first used in Cape Town in 1958 in an attempt to reduce the mortality from tetanus neonatorum, which was then over 90%. Problems of effective ventilation, of tracheostomy, and of infection in the neonate were gradually overcome so that between 1967 and 1972 the mortality in 186 cases was 21%. In a consecutive series of 97 cases the mortality was 10%.

The effect of pretreatment with d-tubocurarine on the incidences of succinylcholine-induced fasciculations and post-operative muscle pain, and the time to onset of and 50% recovery from neuromuscular blockade were studied in 75 obstetric patients. Thirty women with term pregnancies undergoing general anesthesia for elective cesarean section or cesarean section indicated by cephalopelvic disproportion were randomly assigned to two groups. Group C-1 patients received 0.05 mg/kg of d-tubocurarine followed by 1.5 mg/kg of succinylcholine, and group C-2 patients received 1.5 mg/kg of succinylcholine, and group C-2 patients received 1 ml of normal saline followed by 1 mg/kg of succinylcholine. An investigator, unaware of the relaxant regimen used, judged severity of fasciculations and postoperative muscle pain and measured times to onset of and 50% recovery from neuromuscular blockade. This same study design was followed in a group of 30 women undergoing tubal ligation 1 day after vaginal delivery (groups T-1 and T-2). The incidence of both fasciculations and postoperative muscle pain was low and was not significantly different between pretreated and nonpretreated groups. Time to 100% twitch depression was also not significantly different between pretreated and nonpretreated groups. Time to 50% recovery from neuromuscular blockade was significantly longer in both nonpretreated groups (C-2 and T-2). An additional group of 15 patients undergoing general anesthesia for cesarean section using 0.7 mg/kg of succinylcholine without d-tubocurarine pretreatment was studied (group C-3). This smaller dose of succinylcholine produced onset and 50% recovery times similar to the group pretreated with d-tubocurarine (group C-1).(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective study is described of peri-operative dreaming in 144 paediatric patients aged 5-14 years who received suxamethonium for day case surgery. No case of awareness was elicited. One group received pretreatment with 80 micrograms/kg [corrected] tubocurarine. The incidence of dreaming in the 72 patients who were not pretreated was 16.7% compared with 2.8% in the patients pretreated with tubocurarine. This difference is statistically significant. The use of an intermittent suxamethonium technique gives a high incidence of dreaming which may be caused by muscle spindle discharge that produces cerebral arousal. Pretreatment with a non-depolarizing agent decreases this risk of dreaming.

A patient with continuous muscle fiber activity is described. From our search of the literature, we believe this is the oldest patient with a reported case of this disorder, and the symptoms and treatment varied from previously reported cases in these respects: symptoms remained confined to the lower extremities after 18 months had elapsed, there was no response to phenytoin sodium or carbamazepine, and the patient required a full dose of tubocurarine chloride to stop the abnormal myoelectric potentials. A site of dysfunction in the unbranched motor axon is suggested as the locus of generation of the stimulus for the abnormal myoelectric activity.

Eighty-four fit, unpremedicated patients who presented for routine surgery and received a standard anaesthetic technique were allocated randomly to three equal groups. Group 1 received tubocurarine 0.05 mg/kg before induction of anaesthesia. Group 2 received soluble aspirin 600 mg orally one hour before surgery, while Group 3 received no pretreatment. Aspirin prophylaxis produced a significant reduction in the incidence of subsequent suxamethonium-induced myalgia and the improvement was similar to that achieved with tubocurarine pretreatment. Pre-operative oral administration of aspirin effectively reduces muscle pains and avoids many of the complications associated with pretreatment with non-depolarising agents.

Acute administration of phospholine [diethyl-S-(2-dimethyl aminoethyl)phosphorothioate] at 0.2 mg/kg sc produces a myopathy characterized by initial focal changes in the subsynaptic area of the skeletal muscle. The onset of the myopathy is associated with fasciculations of high frequency. Agents that either prevent or reduce the fasciculations, such as d-tubocurarine, atropine sulfate, and diazepam, were effective in reducing the number of muscle lesions. These agents may reduce spontaneous muscle activity by blocking the postsynaptic receptor, by modifying the ionic-channel characteristics, by reducing presynaptic acetylcholine (ACh) release, or by a combination of any of these mechanisms. Creatine phosphate (CP) does not reduce fasciculations, but it is effective in reducing the number of necrotic fibers, probably by stimulating and sustaining the mechanism of Ca2+ uptake into the sarcoplasmic reticulum. It is postulated that an increase in the sarcoplasmic Ca2+ concentration triggers the events that lead to muscle necrosis.

The quantitative and qualitative aspects of the phenomenon of resistance to competitive (non-depolarizing) neuromuscular blocking agents in burn patients are described. The correlates and temporal features of this resistance are discussed, in addition to therapeutic approaches and the possible mechanisms underlying the resistance.

The role of d-tubocurarine in blocking the hypertensive tachycardiac response following laryngoscopy and endotracheal intubation was evaluated in 45 female patients aged 20-40 yr. The patients belonging to grade I (of American Society of Anaesthesiologists) and undergoing elective surgical procedures under general anaesthesia were allocated in 3 equal groups. Patients in the 3 groups received 1.5 mg/kg succinylcholine, 0.6 mg/kg d-tubocurarine and 0.12 mg/kg pancuronium bromide, respectively for intubation. There were no dysrhythmias in any of the groups following endotracheal intubation. There was significant (P less than 0.01) fall in blood pressure following induction prior to intubation in all the three groups. Maximum fall was noted in group II (23.53 +/- 7.21 mmHg in mean arterial pressure). Following endotracheal intubation, blood pressure and heart rate increased significantly (P less than 0.01) in all 3 groups. Maximum increase was observed in group I (26.4 +/- 4.95 mmHg in mean arterial pressure and 19.07 +/- 6.54 beats/min in heart rate). Blood pressure and heart rate increases in groups II and III were comparable. Our findings indicate that hypotension produced by d-tubocurarine through ganglion blockade is not effective in attenuating the cardiovascular responses following endotracheal intubation. It is also possible that increased cardiovascular response following endotracheal intubation may not be due to sympathetic ganglion stimulation.

The pharmacodynamics and pharmacokinetics of metocurine were studied in five neurosurgical patients with normal renal function, and in five anephric patients during and following a renal transplant. Following a single intravenous dose of metocurine (0.3 mg/kg), measurements of serum levels and urinary excretion were made using a specific radioimmunoassay for metocurine. Evoked compound electromyographic (ECEMG) response of the thumb adductor to supramaximal stimulation of the ulnar nerve was also studied. In the patients for renal transplant, plasma clearance of metocurine was significantly reduced (0.38 vs. 1.2 ml . kg-1 . min-1, P less than 0.01) and the elimination half-life was significantly prolonged (11.4 vs. 6.0 h, P less than 0.01). The higher serum concentration of metocurine in patients for renal transplant was accounted for by the absence of renal excretion and a reduced total volume of distribution (0.353 vs. 0.472 l/kg, P less than 0.05). The mean serum metocurine concentration necessary for 90 per cent inhibition of the ECEMG was 2.3 times greater in patients undergoing renal transplant than in patients undergoing craniotomy, 1.05 vs. 0.46 microgram/ml (P less than 0.01). Although serum metocurine concentrations were still high at the end of the renal transplants, reversal of the neuromuscular blockade was possible. Metocurine appears to be an acceptable neuromuscular blocking agent for patients in renal failure although no major advantage over d-tubocurarine and pancuronium could be found.

Five patients suffering from progressive Reye's syndrome were aggressively treated in our ICU. Our protocol consisted of endotracheal intubation, curarization, mechanical ventilation, hypothermia to 31 degrees C, and fluid restriction. Intracranial pressure (ICP) was monitored and remained below 10-20 torr in all patients except one in whom ICP rose only once (for a few minutes) to 27 torr. Pulmonary artery wedge pressure was monitored in 4 patients and was maintained at 4-5 torr. Duration of active intervention as outlined above was 3-4 days. All 5 patients started with clinical stage IV and EEG grade IV or worse. Four patients had complete recovery and one died. In this group of patients, high ICP was not a feature of the disease. We recommend that use of mannitol for active dehydration be reserved for cases with proven rise in ICP, in which case hemodynamics should be carefully monitored.

The effect of tubocurarine and pancuronium on the initiation or prevention of porcine malignant hyperthermia (MH) was investigated in Pietrain pigs. Tubocurarine 0.6 mg/kg body weight inhibited a suxamethonium-induced response in three pigs, but failed to prevent a fatal halothane-induced response in a further four pigs. Pancuronium 0.2 mg/kg body weight was given to six pigs before a halothane challenge. Three animals developed MH and died; the remainder succembed only after reversal of the neuromuscular blockade. The partial protection afforded by large doses of pancuronium is discussed in relation to the ability of previous muscle activity to influence the sensitivity to halothane.

Postoperative respiratory function was evaluated in 94 patients with myasthenia gravis after thymectomy. Preoperative clinical and pulmonary function data were submitted to statistical analyses. The duration of respiratory support and intratracheal intubation time were significantly correlated to % vital capacity, the clinical stage of myasthenia gravis, and the clinical stage of thymoma. Statistical analyses proved that anticholinesterase drugs taken in immediate postoperative period contributed to the improvement of postoperative respiratory function, and non-depolarizing muscle relaxants, i.e. d-tubocurarine which had been considered to be contraindicated in myasthenia gravis was found to be beneficial immediately after the operation in patients with severely deteriorated respiratory function preoperatively.

The occurrence of postoperative deep vein thrombosis (DVT) was studied in 209 elective surgery patients aged 40 years or over. Most of the operations were cholecystectomies or other major abdominal operations. In the detection of thrombosis the 125I-fibrinogen method was used. Of 209 patients, 51 (24.4%) developed postoperative DVT and of these 10 developed thrombosis in both legs. In 36% of the DVT cases the process started during the operation or on the first postoperative day. Clinical signs of DVT did not agree with the 125I-fibrinogen test very well, whereas the correlation of the 125I-fibrinogen test with phlebography was good: of the 17 patients with a postive 125I-fibrinogen test in whom a phlebography was done, the latter method revealed thrombosis in 14 patients (82.4%). The main purpose of the study was to determine whether the mode of mechanical ventilation used during anaesthesia has any effect on the occurrence of postoperative DVT. One hundred and nine patients received intermittent positive pressure ventilation (IPPV), whereas in 100 patients the intrathoracic pressure was decreased by applying intermittent positive-negative (--5 cmH2O) pressure ventilation (IPNPV). Ventilation was standardized in both groups by keeping the end-tidal CO2% at a constant level. Inspired oxygen concentration was the same in every patient. The decreasing effect of IPNPV on intrathoracic pressure and central venous pressure as compared with IPPV was confirmed in preliminary studies.

The frequency of post-suxamethonium pain after pretreatment with small doses of non-depolarizing neuromuscular blocking agents was studied in 299 patients. Gallamine 10 and 20 mg, tubocurarine 5 mg and pancuronium 1 mg were equally effective when a 2-min interval was allowed between their injection and suxamethonium administration. Fazadinium was ineffective and caused difficulty with intubation. No evidence supporting the concept that dosage should be related to patient's weight was found. Inpatients suffered from post-suxamethonium pain as much as did outpatients.

In a randomised double-blind trial carried out on fit, unpremedicated patients undergoing standard minor operations with early postoperative mobility, using a standard form of anaesthesia, pretreatment with diazepam 0.15 mg/kg or midazolam 0.1 mg/kg failed to reduce significantly the incidence of postoperative muscle pains following suxamethonium 1 mg/kg. By contrast, tubocurarine 0.05 mg/kg proved to be effective as a pretreatment. Neither benzodiazepine influenced the incidence or severity of fasciculations seen with suxamethonium or the duration of neuromuscular block. Tubocurarine virtually abolished visible fasciculation and, in the dose used, reduced the intensity and duration of the neuromuscular block. There were no clinically significant changes in serum potassium, creatinine phosphokinase or aldolase after suxamethonium, although 5 out of 47 showed an atypical rise in creatinine phosphokinase.

Neuromuscular, circulatory, and adverse effects of intravenous succinylcholine (SCh), mg/kg, were compared in 3 groups of 40 patients each. Group I served as control; group II received diazepam, 0.05 mg/kg, 5 min before SCh; and group III was given d-tubocurarine (d-Tc), 0.05 mg/kg, for pretreatment. Diazepam pretreatment prevented muscle fasciculations, increases in serum potassium (K+) and creatinine phosphokinase (CPK) levels, increased heart rate and arterial pressure, and postoperative myalgia associated with SCh administration. The neuromuscular blocking action of SCh was not affected. Pretreatment with d-Tc did not abolish increases in serum K+ and CPK levels, was associated with a higher incidence of postoperative myalgia, and decreased the onset and magnitude of SCh-induced muscle paralysis. Our data demonstrate that diazepam, a predominant centrally acting muscle relaxant, is more effective than d-Tc in preventing the adverse effects of SCh, a peripherally acting muscle relaxant.

To determine the effectiveness of diazepam pretreatment in preventing succinylcholine-induced fasciculations, 61 surgical patients were randomly allocated into three groups receiving either diazepam (0.05 mg/kg), d-tubocurarine (0.05 mg/kg) or saline in a double-blind fashion. Following the induction of anesthesia with fentanyl and thiopental, a bolus dose of succinylcholine (1 mg/kg was injected 5 minutes after the pretreatment drugs. Resulting fasciculations were then graded visually. Responses to electrical simulation of the ulnar nerve, somatic motor responses to laryngoscopy and endotracheal intubation, and changes in serum levels of potassium were also evaluated. Diazepam had no effect on frequency or intensity of succinylcholine fasciculations. Fasciculations were observed in 90% of the patients given placebo injections and in 95% of those given diazepam, but in only 16% of those given tubocurarine. Tubocurarine prolonged the onset and shortened the duration of the succinylcholine block and thus made intubation more difficult. Diazepam accelerated onset, but had no effect on duration of succinylcholine block. The twitch response following ulnar nerve stimulation disappeared after 84 seconds (p < 0.01 vs placebo) in patients given diazepam after 115 seconds in patients given tubocurarine, and after 106 seconds in those given placebo injections. The increase in serum potassium after succinylcholine was prevented by pretreatment with d-tubocurarine but not by diazepam.

To determine the effectiveness of diazepam pretreatment in preventing succinylcholine (SCh)-induced fasciculations and body pains, 587 patients were randomly allocated to six groups. Patients in Group I received no pretreatment and served as controls. Patients in Groups II and III were pretreated with 0.05 mg/kg of diazepam either 4-5 min (Group II) or 8-10 min (Group III) prior to SCh administration. Patients in Groups IV and V received 0.1 mg/kg of diazepam either 4-5 min (Group IV) or 8-10 min (Group V) prior to SCh administration, while patients in Group VI were pretreated with 0.05 mg/kg of d-tubocurarine (dTc) 4-5 min prior to SCh. The succinylcholine dosage was 1.0 mg/kg in Groups I through V and 1.5 mg/kg in Group VI. Fasciculations, intubation conditions and postoperative body pains were evaluated in all groups. Fasciculations were seen in 90% of patients in the control group and 15% in the dTc pretreatment group, while diazepam was ineffective in altering the frequency or intensity of fasciculations. Conditions for intubation were judged to be clinically adequate in all groups. Body pains were seen in 33% of patients in the control group and 28-36% in diazepam-pretreated groups and in only 8% of patients in the dTc pretreatment group. There was no statistically significant difference in the incidence of body pains by virtue of site of operation, age, sex, and inpatient/outpatient status. It is concluded that the problem of postoperative myalgia is significant and that dTc pretreatment is the effective method for prevention of fasciculations and postoperative myalgia. Diazepam pretreatment was ineffective for the prevention of fasciculations and myalgia.