GLYCOPYRROLATE--NEOSTIGMINE MIXTURE FOR ANTAGONISM OF NEUROMUSCULAR BLOCK: COMPARISON WITH ATROPINE--NEOSTIGMINE MIXTURE

Glycopyrrolate, a new anticholinergic agent, was evaluated andcompared with atropine. Glycopyrrolate 0.2 mg to neostigmine1.0 mg was found to be safe and effective. The heart rates remainedmore stable with glycopyrrolate, and the frequency of arrhythmia,which was both transient and of no consequence, was similarin the two groups. The antisialogogue action of glycopyrrolatewas superior to that of atropine.     

Vecuronium and Atracurium in the Elderly: A Clinical Comparison with Pancuronium

The intubating conditions, time to complete block and duration of clinical relaxation were observed in a group of 101 elderly patients (aged over 65 years) following pancuronium 0.1 mg kg^-1, vecuronium 0.1 mg kg^-1 or atracurium 0.5 mg kg^-1. The intubating conditions in the three groups were similar when assessed at 2 min following relaxant administration. The time to complete block was shortest with vecuronium (4.3 min) in comparison to atracurium (5.0 min) and pancuronium (6.0 min), but the differences were not statistically significant. The duration of clinical relaxation, however, was significantly shorter with vecuronium (37 min) and atracurium (35 min) in comparison to pancuronium (99 min).     

ANTAGONISM OF VERCURONIUM-INDUCED NEUROMUSCULAR BLOCKADE WITH EDROPHONIUM OR NEOSTIGMINE

Antagonism of vecuronium-induced neuromuscular blockade wasattempted, at varying degrees of spontaneous recovery, withedrophonium 0.5 mg kg ^–1 or neostigmine 0.05 mg kg^–1in two groups of 20 patients. Neuromuscular blockade was monitoredusing a train-of-four (TOF) stimulation. Adequate antagonismof neuromuscular blockade, defined as a sustained TOF ratioof 0.7 or more, was attained in all 20 patients given neostigmineand in 13 out of 20 given edrophonium. Five of the remainingseven patients given edrophonium had shown three or less responsesto TOF stimulation before antagonism. While the time to onsetof the action of edrophonium (22 s) was not significantly shorterthan neostigmine (26 s), the time taken to attain a TOF ratioof 0.7 was significantly shorter with edrophonium (67 s comparedwith 194 s with neostigmine). It is concluded that edrophonium0.5 mg kg^–1 does not consistently antagonize vecuronium-inducedneuromusocular blockade, particularly if there are three orless responses to a TOF stimulation present before antagonism.     

COMPARATIVE POTENCY OF PIPECURONIUM BROMIDE AND PANCURONIUM BROMIDE

Cumulative dose-response curves were constructed to determinethe comparative potency of pipecuronium and pancuronium. Fromthese, the ED₅₀ and ED₉₅ values were calculated. These were24.96 g kg^–1 and 44.96 µg kg^–1, respectively,for pipecuronium and 30.42 µg kg^–1 and 61.12 µgkg^–1, respectively, for pancuronium.     

Neuromuscular and haemodynamic effects of mivacurium in elderly and young adult patients

We have studied the neuromuscular effects of mivacurium andchanges in heart rate and arterial pressure in 40 elderly (aged70 yr) and 20 young adult (aged 18–40yr) patients anaesthetizedwith thiopentone, fentanyl, nitrous oxide in oxygen and halothane.Neuromuscular block was monitored by train-of-four (TOF) stimulationof the ulnar nerve and recording of the force of contractionof the adductor pollicis muscle using a force displacement transducerand a neuromuscular function analyser (Myograph 2000, BiometerLtd). Twenty elderly and 10 young adults received single closesof mivacurium 0.15 mg kg^–1 and spontaneous recovery wasrecorded. The other 20 elderly and 10 adults received the samedose but an infusion was started at T1 (first response in TOF)of 10% and the block maintained at this level. Haemodynamiceffects were studied after administration of mivacurium over15 or 5 s in elderly (n=10 each) and over 5 s in adult (n=10)patients. Onset of maximum block occurred at a mean time of122 (sd 32) and 125 (49) s in elderly and young adults, respectively.Recovery of T1 to 25% occurred in 22.0 (5.7) and 17.2 (4.4)min, and T1 to 90% in 32.8 (6.9) and 24.4 (5.8) min in elderlyand adult subjects, respectively. Recovery of the TOF ratioto 0.7 occurred in 32.8 (7.1) and 26.0 (15.0) min in the elderlyand young subjects, respectively (all P<0.05 between youngand elderly). Mean mivacurium requirements by continuous infusionfor maintenance of 90% block were 3.67 and 5.50 ng kg^–1min^–1 in elderly and the young adults, respectively (P< 0.05). In the elderly, neuromuscular effects were prolongedby approximately 30% and infusion requirements reduced by 38%.Residual neuromuscular block was antagonized easily with edrophoniumor neostigmine. Except for small changes in systolic arterialpressure, mivacurium exhibited good haemodynamic stability inboth groups. Cutaneous flushing was observed in six elderly(1 5%) and six young adults (30%).     

Intravenous administration of glycopyrronium

Intravenous administration of glycopyrronium in doses up to 0.2 mg, was associated with minimal changes in cardiac rate and rhythm. Sinus arrhythmia, nodal rhythm and occasional atrial ectopics were the dysrhythmias observed. There were no accompanying changes in blood pressure.     

COMPARISON OF CUMULATIVE AND SINGLE BOLUS DOSE TECHNIQUES FOR DETERMINING THE POTENCY OF VECURONIUM

The potency of vecuronium was determined using single bolusdose administrations of 10–50 µg kg^–1in 28patients anaesthetized with thiopentone, nitrous oxide, oxygenand fentanyl. The results were compared with those previouslyobtained using a cumulative dose technique in a comparable groupof 10 patients. The 50% and 95% blocking doses (ED₅₀and ED₉₅)of vecuronium were found to be 23.1 and 39.6 µg kg^–1,respectively. These were significantly lower than the 30.5 and56.7µg kg^–1 obtained previously using the cumulativedose technique. We recommend the use of single bolus dose methodof determining potency for relatively shorter-acting drugs likevecuronium.     

Muscle pains and biochemical changes following suxamethonium administration after six pretreatment regimens

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.