Antivenom therapy: efficacy of premedication for the prevention of adverse reactions

Antivenoms or antitoxins have been effectively used for more than a century. During this time, these products have always proven to be highly effective in the treatment of infections and envenomations. However, antivenoms did not exhibit good safety results in their initial applications. After many improvements, antivenoms have substantially better safety profiles but still have some side effects. Due to the occurrence of adverse reactions, the practice of using premedication with the intent to decrease side effects has become accepted or mandatory in many countries. The drugs used for premedication belong to the histamine H1 antagonist, glucocorticoid and catecholamine groups. Currently, this practice is being questioned due to low or controversial efficacies in clinical assays. In this article, we discuss the causes of adverse reactions, the mechanisms of drugs that block the undesired effects and the results obtained in clinical trials. Although these three families of drugs could have positive effects on reducing adverse reactions, only adrenaline has demonstrated positive results in clinical assays.(AU)

Antivenom therapy: efficacy of premedication for the prevention of adverse reactions

Antivenoms or antitoxins have been effectively used for more than a century. During this time, these products have always proven to be highly effective in the treatment of infections and envenomations. However, antivenoms did not exhibit good safety results in their initial applications. After many improvements, antivenoms have substantially better safety profiles but still have some side effects. Due to the occurrence of adverse reactions, the practice of using premedication with the intent to decrease side effects has become accepted or mandatory in many countries. The drugs used for premedication belong to the histamine H1 antagonist, glucocorticoid and catecholamine groups. Currently, this practice is being questioned due to low or controversial efficacies in clinical assays. In this article, we discuss the causes of adverse reactions, the mechanisms of drugs that block the undesired effects and the results obtained in clinical trials. Although these three families of drugs could have positive effects on reducing adverse reactions, only adrenaline has demonstrated positive results in clinical assays.

Quadro clínico-patológico do envenenamento crotálico experimental em bubalinos comparado com o de bovinos / Comparison between the clinical and pathological picture in the experimental poisoning by crotalic venom

O estudo teve por objetivo verificar a sensibilidade dos bubalinos à peçonha de Crotalus durissus terriiicus, estudar o quadro clínico-patológico e laboratorial nessa espécie e estabelecer comparações com o verificado em bovinos. A inoculação do veneno liofilizado de Crotalus durissus terriiicus, diluído em 1ml de solução fisiológica, foi feita na região da articulação úmero-rádio-ulnar, por via subcutânea, em três bubalinos (doses de 0,015; 0,03; e 0,066mg/kg) e em dois bovinos (doses de 0,03 e 0,066mg/kg). O bubalino que recebeu a dose de 0,03mg/ kg apresentou sinais clínicos graves recuperou-se seis dias após, e o bovino que recebeu a mesma dose morreu com evolução de 22h56min. A dose de 0,066mg/kg causou a morte tanto do bovino quanto do bubalino, com evolução clínica de 4h23min e 8h12min, respectivamente. O bubalino que recebeu a dose de 0,015mg/kg, recuperou-se com evolução de 48 horas. Os sinais clínicos tiveram início dentro de 3h58min no bubalino que morreu, e nos bubalinos que adoeceram mas se recuperaram, dentro de 17h25min e 24h00min após a inoculação do veneno. Nos dois bovinos que morreram (com doses de 0,03 e 0,066mg/kg), os primeiros sinais clínicos foram observados 6h10min e 6h31min após a inoculação do veneno. A inoculação do veneno produziu nos búfalos e bovinos um quadro nervoso de paralisia flácida. Os principais sinais observados tanto nos búfalos quanto nos bovinos, foram discreto aumento de volume no local da inoculação, dificuldade respiratória caracterizada por respiração predominantemente abdominal, apatia, sialorreia, dificuldade para se levantar quando estimulados, evolução para decúbito esternal permanente, seguido de decúbito lateral e movimentos de pedalagem, e diminuição dos reflexos relacionados aos pares de nervos cranianos. Nos bubalinos adicionalmente foi observado aumento da base de sustentação, arrastar das pinças dos membros posteriores, marcha lenta e cambaleante, dificuldade na apreensão dos alimentos; nos bovinos ainda foram observados paralisia do globo ocular, revelada através da não exposição da esclera durante a rotação da cabeça na direção latero-caudal. Tanto nos bovinos quanto nos bubalinos, verificou-se no leucograma, leucocitose por neutrofilia, e na bioquímica sérica, aumento nos níveis de alanina aminotransferase, aspartato aminotransferase, creatinaquinase e dehidrogenase láctica. Não houve alterações na urinálise, nem no tempo de ativação da protrombina e nem no tempo de tromboplastina parcial ativada. À necropsia evidenciou-se apenas discreto edema correspondente ao local da inoculação em um bovino. Os achados histopatológicos observados foram picnose nos núcleos de células epiteliais de alguns túbulos uriníferos no córtex renal (em um búfalo e um bovino) e fígado com leve vacuolização de hepatócitos (em um bovino).

The objective of the study was to verify the sensibility of buffaloes to the poison of Crotalus durissus terriiicus and to study the clinical-pathological picture in buffaloes in comparison with the one in cattle. The subcutaneous inoculation of the liofilized poison of the snake, diluted in 1ml of physiologic solution, was done in the area of the humerus-radio-ulnar joint of three buffaloes at doses of 0.015, 0.03 and 0.066mg/kg, and of two cattle at doses of 0.03 and 0.066mg/kg. The buffalo that received the 0.03mg/kg dose presented severe clinical signs but recovered six days later. The bovine that received the same dose, died after a clinical course of 22h56min. The 0.066mg/kg dose caused death of the bovine as also the buffalo, with a clinical course of 4h23min and 8h12min, respectively. The buffalo that received the 0.015mg/kg dose recovered, after a course of 48 hours. The buffalo that died, showed clinical signs from 3h58min on, and the buffaloes that showed symptoms from 17h25min and 24h00min after inoculation of the venom, but recovered. In the two cattle that died (with doses of 0.03 and 0.066mg/kg), the first clinical signs occurred 6h10min and 6h31min after the inoculation of the venom. The inoculation produced in the buffaloes and cattle nervous symptoms of flaccid paralysis. The main signs observed in the buffaloes as well as the cattle, were slight volume increase at the site of inoculation, respiration difficulties characterized by predominantly abdominal breathing, apathy, sialorreia, difficulty to get up when stimulated, evolution to sternal decubitus followed by lateral decubitus with peddling movements of the legs, and decrease of the reflexes related to the cranial nerves. The buffaloes showed also augmentation of the sustentation base, dragging of the hooves of the hind legs, slow and staggering gait, difficulty in apprehension of the food, The cattle showed additionally paralysis of the eyeballs, revealed through non-exhibition of the sclera during head rotation in latero-caudal direction. Laboratory exams revealed in the cattle and the buffaloes leucocytosis by neutrofilia, and in the biochemistry series, increase in the levels of alanine aminotransferase, aspartato aminotransferase, creatinaquinase and lactic dehydrogenase. There was no alteration in the urinalysis nor in the activation time of protrombine and in the time of partially activated tromboplastin. Necropsy only evidenced slight edema corresponding to the inoculation site in one bovine. Histopathological examination revealed picnosis of the epitelial cell nuclei of some kidney tubules in the cortex (in the buffalo and in one bovine) and slight vacuolation of hepatocites (in one bovine).