Antagonism of pancuronium and tubocurarine blocks by edrophonium or neostigmine: a comparative study.

Edrophonium 0.5 and neostigmine 0.05 mg kg-1 were compared as antagonists of pancuronium and tubocurarine-induced neuromuscular blocks, at varying degrees of recovery, in groups of 20 patients each. Adequate antagonism was defined as attaining a sustained train-of-four (TOF) ratio of 0.7 or more. Administration of edrophonium was associated with a more rapid onset of action (17 s with both relaxants with edrophonium, and 31 s and 29 s with neostigmine with pancuronium and tubocurarine, respectively), and a shorter time to attain a TOF ratio of 0.7 (74 s and 48 s with edrophonium and 230 s and 293 s with neostigmine for pancuronium and tubocurarine blocks, respectively). However, whereas neostigmine administration provided adequate antagonism in all 20 patients given pancuronium and in 19 out of 20 patients given tubocurarine, edrophonium failed to achieve adequate antagonism in six patients after pancuronium and eight patients after tubocurarine. The majority of these patients had shown three or less responses to a TOF stimulation prior to antagonism. Two separate groups of 10 patients each with relatively deeper pancuronium or tubocurarine blocks (three or less responses to TOF stimulation) were given edrophonium in a dose of 1.0 mg kg-1. However, adequate antagonism even with this dose of edrophonium was attained in only two out of 10 patients given pancuronium and in five out of 10 patients given tubocurarine. It is concluded that edrophonium is unreliable for antagonism of relatively deep blocks by pancuronium or tubocurarine and that neostigmine is the preferred and more reliable antagonist.

Intensive anti-oxidant pretreatment retards motor nerve degeneration.

Intensive pretreatment of cats with a combination of the antioxidants D-alpha-tocopherol (200 IU) and selenium (50 micrograms) once daily for 5 days (p.o.) was found to significantly preserve the functional capacity of degenerating soleus motor nerve terminals (measured at 48 h after axon section at the hip) in the in vivo soleus nerve-muscle preparation. The preservation of function was apparent in terms of: a greater soleus contractile response to nerve stimulation at low frequencies, a more rapid recovery from D-tubocurarine-induced neuromuscular block, and a better maintenance of tetanic contractile tension during high-frequency nerve stimulation. The ability of antioxidants to retard the anterograde axonal degeneration (i.e. 'Wallerian') process suggests that lipid peroxidation may be a fundamental mechanism of neuronal degeneration.

Dose-response curves for edrophonium, neostigmine, and pyridostigmine after pancuronium and d-tubocurarine.

To determine the potencies of neostigmine, pyridostigmine, and edrophonium in reversing pancuronium and d-tubocurarine blockade, dose-response curves were established for first twitch height recovery and train-of-four ratio. One hundred and twenty ASA physical status I or II patients scheduled for elective surgery received either 0.06 mg/kg pancuronium or 0.36 mg/kg d-tubocurarine during a thiopental-nitrous oxide-enflurane anesthetic. Train-of-four stimulation was applied every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When first twitch height had recovered spontaneously to 10% of its initial value, neostigmine (0.005, 0.01, 0.02 or 0.05 mg/kg), pyridostigmine (0.02, 0.04, 0.1, or 0.2 mg/kg), or edrophonium (0.1, 0.2, 0.4 or 1 mg/kg) was injected by random allocation. Recovery was measured 10 min after the injection of the antagonist. First twitch ED50's were 0.013, 0.085, and 0.17 mg/kg after pancuronium, and 0.017, 0.11, and 0.27 mg/kg after d-tubocurarine, for neostigmine, pyridostigmine, and edrophonium, respectively. The ED50 for pyridostigmine and edrophonium obtained after d-tubocurarine was significantly larger (P less than 0.05) than that after pancuronium. The train-of-four dose-response curves were significantly flatter for edrophonium than for the other two agents, indicating a greater ability of edrophonium to antagonize fade at low doses. It is concluded that the potency of reversal agents may be different for different relaxants, and that potency ratios might depend upon the end-point chosen as full neuromuscular recovery.

[Tetanus-Myomechanographic measurement of receptor liberation by pyridostigmine in neuromuscular block produced by d-tubocurarine, gallamine, pancuronium or alcuronium (author's transl)]. / Tetanusmyomechanographische Bestimmung der Rezeptorbefreiung durch Pyridostigmin bei neuromuskulärer Blockade mit d-Tubocurarin, Gallamin, Pancuronium oder Alcuronium.

In 48 patients anaesthetized with nitrous oxide-oxygen and hexobarbitone the neuromuscular (n-m) block (greater than or equal to 95% depression) produced by roughly equipotent doses of d-tubocurarine (dTC), gallamine (GALL), pancuronium (PANC) or alcuronium (ALC), respectively, was antagonized by 10 mg of pyridostigmine (P) applied intravenously 35-460 min after the relaxant at variable levels of spontaneous recovery from n-m block. Muscular reactions to tetanic stimulation (30 to 400 Hz, 4-5 s each) of the ulnar nerve transmitted by a force-displacement system served as a measure for calculating the relative amount of n-m receptors liberated from relaxant molecules. Within 3-10 min after its injection P increased the number of relaxant-free n-m receptors by 16 +/- 6% (M +/- SD). Thereafter recovery progressed at similar speed as before. Reinjections of 5-10 mg P were comparably as effective as the first injection. No correlations were to be found between the effectiveness of P and the dose of relaxant applied (r = 0,12 to 0,27), the level of recovery reached before P (r = 0,32), or the time at which P was injected after the relaxant (r = -0,39), respectively. However, the amount of receptors liberated by P decreased with increasing recovery from n-m block and with increasing time interval between the relaxant and the antidote injection. P was significantly more effective (P less than 0,01), when applied within 150 min after the relaxant than at applications after that time. The relative number of receptors liberated by this drug was insignificantly larger in the PANC-and GALL-block than in the ALC-and dTC-block.

[Comparison of 2-aminopyridine, 3-aminopyridine and 4-aminopyridine hydrochlorides and iodomethylates by the degree of decrease in curare toxicity]. / Sravniavane na khidrokhloridite i iodmetilatite na 2-aminopiridina, 3-aminopiridina i 4-aminopiridina po stepenta na ponizhavane na kurarinovata toksichnost.

The authors carried out studies on rats with apnoea, indiced by (+)-tubucurarine and found protective action, due to galantamine, neostigmine, hydrochlorides and jodometilates of 2-aminopyridine, 3-aminopyridine and 4-aminopyridine. Jodmethylates had protective action in larger doses in comparison with the respective hydrochlorides of nonsubstituted pyridilamines. The authors proposed a method for determination and comparison of the effect of compounds, eliminating the action of antidepolarizating myorelaxants, on tubocurarine toxicity.

Bradycardia during antagonism of pancuronium-induced neuromuscular block.

Heart rate was compared in matched patients during antagonism of neuromuscular block induced by tubocurarine, pancuronium or alcuronium with neostigmine 0.03 mg kg-1 preceded by atropine 0.015 mg kg-1. The frequency of bradycardia was greater during antagonism of pancuronium compared with alcuronium. Although there was a difference between the group receiving pancuronium and that receiving tubocurarine, it was not statistically significant. The decrease in heart rate was more rapid and profound in the pancuronium group; seven of the 15 patients who received pancuronium required an additional dose of atropine as compared with only one patient who received tubocurarine. However, the difference in heart rate between those who received pancuronium and those receiving tubocurarine was short-lasting, whereas the heart rate of those who received alcuronium was higher than that in the other groups during the entire 60-min period of observation. The findings with pancuronium may be a result of its inhibitory effect on serum cholinesterase.

Tubocurarine and the neonate.

Tubocurarine, given as a single bolus, may be used safely for neuromuscular blockade in the neonate. The recommended dose is 250 mug/kg at birth, increasing to 500 mug/kg at 28 days of age. This dose should be reduced in the event of prematurity, acidosis or hypothermia, or when certain antibiotics or inhalation anaesthetic agents are present in the tissues. A single dose as described has a duration of approximately 1 h and it is only after this time that satisfactory antagonism can be obtained. The potency of pancuronium when compared with tubocurarine in the study is 6:1, from birth to 28 days.

Pyridostigmine as an antagonist of d-tubocurarine-induced and pancuronium-induced neuromuscular blockade.

In an evaluation of the clinical effectiveness of pyridostigmine as an antagonist of d-tubocurarine-induced and pancuronium-induced neuromuscular blockade in patients anesthetized with a neurolept-nitrous oxide (N2O) technic, 60 adults received either d-tubocurarine (dTc) (N equals 30) or pancuronium (N equals 30). The pancuronium-dTc potency ratio with neurolept-N2O anesthesia is 4.85:1. The mean doses of pyridostigmine necessary for 50 percent recovery of control twitch height and sustained tetanus were 5.72 plus or minus 0.45 (S.E.) mg. and 11.6 plus or minus 0.88 mg., respectively, for dTc, and 4.05 plus or minus 0.24 mg. and 8.27 plus or minus 0.41 mg., respectively, for pancuronium. There was no correlation between the amount of pyridostigmine necessary for relaxant antagonism and the total dose of relaxant used. In 24 patients, neuromuscular blockade was reversed by an intravenous injection of pyridostigmine and either 0.6 mg. or 1 mg. of atropine. Within 2 minutes, patients given 1 mg. of atropine had a significantly faster heart rate than those given 0.6 mg of atropine (p smaller than 0.0001). There was no correlation between control heart rate and maximum changes in heart rate. No cardiac arrhythmia or bronchospasm was observed in patients with either pancuronium or dTc following atropine-pyridostigmine mixtures. The cardiac muscarinic effects of pyridostigmine could be modified by simultaneous administration of 1 mg. of atropine.