ABSTRACT
BACKGROUND: In patients homozygous for atypical plasma cholinesterase, mivacurium causes a long-lasting neuromuscular block, but injection of human cholinesterase has been proven effective in antagonizing the block. The purpose of this study was to evaluate the pharmacodynamics and pharmacokinetics of mivacurium in such patients, as well as the effect of cholinesterase injected early or late after mivacurium. METHODS: Eleven patients phenotypically homozygous for the atypical variant received 0.075 mg/kg (1 patient) or 0.15 mg/kg (10 patients) mivacurium. The neuromuscular block was monitored using train-of-four nerve stimulation and mechanomyography. Cholinesterase, 2.8-10.0 mg/kg, was administered approximately 30 or 120 min after mivacurium. The times to different levels of neuromuscular recovery and the venous concentrations of the isomers of mivacurium were measured. RESULTS: Injection of cholinesterase increased plasma cholinesterase activity to normal and the clearances of the active isomers and the elimination rate constants by a factor of 10-15. The first response was seen in 13.5 min (3.7-44.2 min). Time to a train-of-four ratio of 0.8 ranged from 30 to 60 min (n = 6). Neostigmine injected after cholinesterase shortened recovery further, and a train-of-four ratio of 0.8 was reached in 10-30 min. CONCLUSION: As expected, the duration of action of mivacurium is markedly prolonged in homozygous atypical patients. Injection of cholinesterase significantly increases the metabolism of mivacurium, leading to a shorter duration of action. Injection of neostigmine after the administration of cholinesterase speeds up recovery.
Subject(s)
Cholinesterases/administration & dosage , Cholinesterases/genetics , Genetic Variation/genetics , Homozygote , Isoquinolines/blood , Phenotype , Adolescent , Adult , Cholinesterases/blood , Female , Humans , Isoquinolines/pharmacokinetics , Isoquinolines/pharmacology , Male , Middle Aged , MivacuriumABSTRACT
En el presente trabajo se pretende estudiar la estabilidad de la actividad colinesterasa en muestras de sangre entera de diferentes especies animales, y determinar aquellas condiciones de almacenamiento que permitan conservar la actividad de la enzima durante el mayor tiempo posible. Muestras de sangre entera de las especies canina, equina y ovina fueron almacenadas, sin diluir o diluidas al 1:50 en agua destilada, a tres temperaturas diferentes: 25º, 4º y -20º C. La actividad colinesterasa se determinó el día de obtención de las muestras y después de 1 día, 3 días, 1 semana, 2 semanas, 1 mes, 3 meses y 6 meses de almacenamiento, utilizando una adaptación del método de Ellman para el espectrofotómetro automático Coulter Profile Analyzer. Simultáneamente, muestras de sangre entera canina fueron congeladas y descongeladas una vez al día durante cinco días seguidos, con el fin de evaluar su efecto sobre la colinesterasa. La máxima estabilidad de la colinesterasa se observó al conservar la sangre a 20º C en el caso de las especies canina y ovina, y a 4º C en la especie equina. La dilución de las muestras provocó una rápida pérdida de actividad si el almacenamiento se producía a 25º ó 4º C; a -20º C la dilución de la sangre proporcionó mayor estabilidad en la especie ovina, menor en la equina, y similar a la sangre no diluida en la especie canina. Las sucesivas congelaciones y descongelaciones de las muestras de sangre no afectaron de forma significativa a la actividad de la enzima. (AU)
Subject(s)
Animals , Dogs , Cholinesterase Inhibitors/administration & dosage , Cholinesterases/administration & dosage , Enzyme Stability , Enzyme Stability/physiology , Sheep/blood , Spectrophotometry , Spectrophotometry/veterinary , Horses/bloodABSTRACT
The competitive action of acetil-salicylic acid with respect to colinesterasi is demonstrated. The A. proposes a routine dose of this enzyme in the preparation for surgery with a high haemorrhage risk, such as tonsillectomy.
Subject(s)
Aspirin/pharmacology , Blood Coagulation/drug effects , Cholinesterases/deficiency , Hemorrhage/prevention & control , Aspirin/adverse effects , Cholinesterases/administration & dosage , Hepatitis/enzymology , Humans , Liver Cirrhosis/enzymology , Preoperative CareABSTRACT
A case of prolonged suxamethonium apnoea successfully terminated by the infusion of a commercial preparation of serumcholinesterase is reported. The patient appeared to be homozygous for the dibucaine resistant gene, having only 15% of normal activity in his serum. His dibucaine number was 21, and the Michaelis constant was 5.5 times that of normal sera. One and a half hours after receiving 110 mg suxamethonium for oesophagoscopy, the patient was still apnoeic with no response to ulnar nerve stimulation. Intravenous administration of 90 mg commercial serumcholinesterase, the equivalent to 1000 ml fresh human plasma, restored twitch and tetanic responses and the patient could lift his head 15 min after the beginning of the enzyme injection. The serumcholinesterase activity of the patient's serum increased by 55% (from 15% to 70%) following the injection. This rise was halved over the next 8 days.
