Emprego da nimodipina (oxigen) como protetor cerebral na cirurgia de revascularização do miocárdio com circulação extracorpórea em pacientes idosos

Manrique, Ricardo; Pavanello, Ricardo; Magalhães, Hélio M. de

doi:10.1590/S0102-76381996000400005

Resumos

Aproximadamente 5% dos pacientes submetidos a cirurgia cardíaca com auxílio da circulação extracorpórea apresentaram problemas neurológicos. Avaliando funções neuropsíquicas, as alterações atingem de 50% a 70% dos casos. Os idosos são mais vulneráveis; nestes, a freqüência de acidente vascular cerebral (AVC) aproxima-se dos 9%. Considerando que a população envelhece a um ritmo acelerado e que 0 coronariopata freqüentemente passa dos 65 anos de idade, é fundamental pesquisar meios profiláticos para diminuir esta incidência. Este é um estudo piloto, duplo cego, randomizado e controlado com 64 pacientes, 30 no Grupo nimodipina e 34 no Grupo placebo. As variáveis demográficas e diagnosticas pré-operatórias foram homogêneas, com exceção da incidência de isquemia cerebral transitória. O Grupo nimodipina, mesmo com programação cirúrgica e evolução intra e pós-operatória mais complicadas, apresentou menor número de casos neurológicos. No Grupo nimodipina foram constatados 3 casos de confusão mental e, no Grupo placebo, além de 3 casos de confusão mental, foram diagnosticados mais 2 casos de sonolência e 1 AVC isquêmico com seqüela. No total, foram 3 (10%) casos em 30 pacientes no Grupo nimodipina, e 6 (17,64%) em 34 pacientes no Grupo placebo, caracterizando uma redução de 76,4%. LEGAULT et al. (15) relatam uma elevada mortalidade de pacientes em uso de nimodipina, quando operados para troca valvar, causada, principalmente, por hemorragia. Nós não encontramos esta correlação. A mortalidade hospitalar é similar em ambos os grupos (1 paciente em cada) e o sangramento não é estatisticamente diferente (1 caso de hemorragia importante no Grupo nimodipina). No seguimento até 41 meses, a mortalidade no Grupo placebo foi maior (4 pacientes) que no Grupo nimodipina (1 paciente).

Revascularização miocárdica; Isquemia cerebral; Confusão; Nimodipina; Nimodipina; Revascularização miocárdica; Circulação extracorpórea; Método duplo-cego

Around 5 percent of the patients submitted to heart surgery with extracorporeal circulation present neurological problems. In relation to neuropsicological functions the alteration rate achieve 50 to 70%. An independent variable to stroke is age, the frequency in patients older then 75 years is close to 9%. Taking in account that rate of the elderly population grows very fast and that the coronary patient are frequently older than 65 years, we found very important to search for prophylactic ways to reduce this incidence. New drugs promise to achieve the goal of a prophylaxis of the cerebral injury induced by extracorporeal circulation and nimodipine, a neurovascular specific calcium channel blocker, seems to be a great promise for the prevention of cerebral damage. This is a pilot, double blind, randomized and controlling study with 64 patients, 30 in the nimodipine group and 34 in the placebo branch. Demographics and preoperative data were similar, without any significative difference but the incidence of previous transitory ischaemic attack. The nimodipine group shows a reduction in the number of neurological events in comparation with the placebo group, although a most complicated surgical procedure and inter and post-operative evolution. In the nimodipine group 3 patients presented mental confusion but in the placebo branch we found also 3 cases of mental confusion plus 2 cases of drowsy and one ischaemic stroke with sequels. In summary in the nimodipine group were 3 cases in 30 patients (10%) against 6 in 34 patients (17.64%) in one placebo group. It means a neurological events reduction of 76.4%. Legault reported high mortality in patients using nimodipine in cardiac valve replacement surgery, mainly related to bleeding. We don't found such correlation. The hospital - mortality was similiar in both groups (1 patient in each group) and non statistically significant difference in bleeding (1 severe case in the nimodipine group). In the follow up till 41 months there was a higher mortality in the placebo (4 patients) than in the nimodipine group (1 case).

Myocardial revascularization; Cerebral ischemia; Confusion; Nimodipine; Nimodipine; Myocardial revacularizatton; Extracorporeal circulation; Double-blind method

ARTIGOS ORIGINAIS

Emprego da nimodipina (oxigen) como protetor cerebral na cirurgia de revascularização do miocárdio com circulação extracorpórea em pacientes idosos

Use of nimodipine for cerebral injury prophylaxis in surgical myocardial revascularization with extracorporeal circulation in elderly patients

Ricardo Manrique; Ricardo Pavanello; Hélio M. de Magalhães

Do Hospital do Coração da Associação Sírio e do Instituto Dante Pazzanese de Cardiologia

^{Endereço para correspondência} Endereço para correspondência: Rua Desembargador Eliseu Guilherme, 123 São Paulo, SP, Brasil. CEP: 04004-030 Tel: (011) 887-6611

RESUMO

Aproximadamente 5% dos pacientes submetidos a cirurgia cardíaca com auxílio da circulação extracorpórea apresentaram problemas neurológicos. Avaliando funções neuropsíquicas, as alterações atingem de 50% a 70% dos casos. Os idosos são mais vulneráveis; nestes, a freqüência de acidente vascular cerebral (AVC) aproxima-se dos 9%. Considerando que a população envelhece a um ritmo acelerado e que 0 coronariopata freqüentemente passa dos 65 anos de idade, é fundamental pesquisar meios profiláticos para diminuir esta incidência. Este é um estudo piloto, duplo cego, randomizado e controlado com 64 pacientes, 30 no Grupo nimodipina e 34 no Grupo placebo. As variáveis demográficas e diagnosticas pré-operatórias foram homogêneas, com exceção da incidência de isquemia cerebral transitória. O Grupo nimodipina, mesmo com programação cirúrgica e evolução intra e pós-operatória mais complicadas, apresentou menor número de casos neurológicos. No Grupo nimodipina foram constatados 3 casos de confusão mental e, no Grupo placebo, além de 3 casos de confusão mental, foram diagnosticados mais 2 casos de sonolência e 1 AVC isquêmico com seqüela. No total, foram 3 (10%) casos em 30 pacientes no Grupo nimodipina, e 6 (17,64%) em 34 pacientes no Grupo placebo, caracterizando uma redução de 76,4%. LEGAULT et al. ⁽¹⁵) relatam uma elevada mortalidade de pacientes em uso de nimodipina, quando operados para troca valvar, causada, principalmente, por hemorragia. Nós não encontramos esta correlação. A mortalidade hospitalar é similar em ambos os grupos (1 paciente em cada) e o sangramento não é estatisticamente diferente (1 caso de hemorragia importante no Grupo nimodipina). No seguimento até 41 meses, a mortalidade no Grupo placebo foi maior (4 pacientes) que no Grupo nimodipina (1 paciente).

Descritores: Revascularização miocárdica. Isquemia cerebral, prevenção e controle. Confusão, prevenção e controle. Nimodipina, uso terapêutico. Nimodipina administração e dosagem. Revascularização miocárdica, mortalidade. Circulação extracorpórea, efeitos adversos. Método duplo-cego.

ABSTRACT

Around 5 percent of the patients submitted to heart surgery with extracorporeal circulation present neurological problems. In relation to neuropsicological functions the alteration rate achieve 50 to 70%. An independent variable to stroke is age, the frequency in patients older then 75 years is close to 9%. Taking in account that rate of the elderly population grows very fast and that the coronary patient are frequently older than 65 years, we found very important to search for prophylactic ways to reduce this incidence. New drugs promise to achieve the goal of a prophylaxis of the cerebral injury induced by extracorporeal circulation and nimodipine, a neurovascular specific calcium channel blocker, seems to be a great promise for the prevention of cerebral damage. This is a pilot, double blind, randomized and controlling study with 64 patients, 30 in the nimodipine group and 34 in the placebo branch. Demographics and preoperative data were similar, without any significative difference but the incidence of previous transitory ischaemic attack. The nimodipine group shows a reduction in the number of neurological events in comparation with the placebo group, although a most complicated surgical procedure and inter and post-operative evolution. In the nimodipine group 3 patients presented mental confusion but in the placebo branch we found also 3 cases of mental confusion plus 2 cases of drowsy and one ischaemic stroke with sequels. In summary in the nimodipine group were 3 cases in 30 patients (10%) against 6 in 34 patients (17.64%) in one placebo group. It means a neurological events reduction of 76.4%. Legault reported high mortality in patients using nimodipine in cardiac valve replacement surgery, mainly related to bleeding. We don't found such correlation. The hospital - mortality was similiar in both groups (1 patient in each group) and non statistically significant difference in bleeding (1 severe case in the nimodipine group). In the follow up till 41 months there was a higher mortality in the placebo (4 patients) than in the nimodipine group (1 case).

Descriptors: Myocardial revascularization. Cerebral ischemia, prevention and control. Confusion, prevention and control. Nimodipine, therapeutic use. Nimodipine, administration and dosage. Myocardial revacularizatton, mortality. Extracorporeal circulation, adverse effects. Double-blind method.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Recebido para publicação em novembro de 1996.

Trabalho realizado no Hospital do Coração da Associação do Sanatório Sírio e no Instituto Dante Pazzanese de Cardiologia. São Paulo, SP, Brasil.

1 Mills S A - Cerebral injury and cardiac surgery. Ann Thorac Surg 1993; 56 (Supl.5): 586-91.
2 Breuer A C, Furlan A J, Hanson M R et al. - Central nervous system complications of coronary bypass graf surgery: prospective analysis of 421 patients. Stroke 1983; 14: 682-7.
3 Shau P J, Bats D, Cartridge N E F et al. - Neurologic and neuropsychologic morbidity following major surgery: comparation of coronary artery bypass and peripheral vascular surgery. Stroke 1987; 32: 700-7.
4 Weintraub W S, Jones E L, Craver J, Guyton R, Cohen C - Determinants of prolonged length of hospital stay after coronary bypass surgery. Circulation 1982; 80: 276-84.
5 Toward R & Kazda S - The cellular mechanism of action of nimodipine. Br J Pharmacol 1979; 67: 409-10.
6 Brand L, Anderson K E, Edvinson L, Ljunggren B - Effects of extracellular calcium and of calcium antagonist on the contractil response of isolated human pial and mesenteric arteries. J Cereb Blood Flow Metab 1981; 1: 339-47.
7 Harper A M - Effects of dihydropyridine - type calcium antagonist on cerebral flow and metabolism. In: Fleckenstein A, Breemen C, Grob R, Hoffmeister F, eds. Cardiovascular effects of dihydropyridine type calcium antagonist and agonist. Berlin-Heidelberg: Sprirger-Verlag, 1985; 353-60.
8 Siesg B K - Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1981; 1:155-61.
9 Steen P A, Newbwerg L A, Milde J H, Michenfelder J D - Nimodipine improve cerebral flow and neurologic recovery after complete cerebral ischaemia in the dog. J Cereb Blood Flow Metab 1983; 3: 38-42.
10 Steen P A, Newbwerg L A, Milde J H, Michenfelder J D - Cerebral flow and neurologic outcome when nimodipine is given after complete cerebral ischaemia in the dog. J Cerebral Blood Flow Metab 1984; 4: 82-5.
11 Steen P A, Gisvold S E, Milde J H et al. - Nimodipine improves outcome when given after complete ischaemia in primates. Anesthesiology 1985; 62: 406-10.
12 Caettaneo A D - Protezione cerebrale. Minerva Anestesiol 1993; 59: 403-17.
13 Forsman M, Olsnes B J, Sem B G, Steen P A - Effects of nimodipine on cerebral blood flow and neuropsychological outcome after cardiac surgery. Br J Anesthesia 1990; 65: 514-20.
14 Furberg C D, Psaty B M, Meyer J V - Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation 1995; 92: 1326-31.
15 Legault C, Furberg C, Wagenknecht L E et al. - Nimodipine neuroprotection in cardiac valve replacement. Stroke 1996; 27: 593-8.
16 Manrique R - Monitoring of platelet function in the cardiovascular surgery patient. In: Pifarré R. Anticoagulation, hemostasis and blood preservation in cardiovascular surgery. St. Louis: Hanley & Belfus Inc., 1993: 201-13.

Endereço para correspondência:

Rua Desembargador Eliseu Guilherme, 123

São Paulo, SP, Brasil. CEP: 04004-030

Tel: (011) 887-6611

Datas de Publicação

Publicação nesta coleção
16 Dez 2010
Data do Fascículo
Dez 1996

Histórico

Recebido
Nov 1996

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1 Mills S A - Cerebral injury and cardiac surgery. Ann Thorac Surg 1993; 56 (Supl.5): 586-91.

[2] 2 Breuer A C, Furlan A J, Hanson M R et al. - Central nervous system complications of coronary bypass graf surgery: prospective analysis of 421 patients. Stroke 1983; 14: 682-7.

[3] 3 Shau P J, Bats D, Cartridge N E F et al. - Neurologic and neuropsychologic morbidity following major surgery: comparation of coronary artery bypass and peripheral vascular surgery. Stroke 1987; 32: 700-7.

[4] 4 Weintraub W S, Jones E L, Craver J, Guyton R, Cohen C - Determinants of prolonged length of hospital stay after coronary bypass surgery. Circulation 1982; 80: 276-84.

[5] 5 Toward R & Kazda S - The cellular mechanism of action of nimodipine. Br J Pharmacol 1979; 67: 409-10.

[6] 6 Brand L, Anderson K E, Edvinson L, Ljunggren B - Effects of extracellular calcium and of calcium antagonist on the contractil response of isolated human pial and mesenteric arteries. J Cereb Blood Flow Metab 1981; 1: 339-47.

[7] 7 Harper A M - Effects of dihydropyridine - type calcium antagonist on cerebral flow and metabolism. In: Fleckenstein A, Breemen C, Grob R, Hoffmeister F, eds. Cardiovascular effects of dihydropyridine type calcium antagonist and agonist. Berlin-Heidelberg: Sprirger-Verlag, 1985; 353-60.

[8] 8 Siesg B K - Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1981; 1:155-61.

[9] 9 Steen P A, Newbwerg L A, Milde J H, Michenfelder J D - Nimodipine improve cerebral flow and neurologic recovery after complete cerebral ischaemia in the dog. J Cereb Blood Flow Metab 1983; 3: 38-42.

[10] 10 Steen P A, Newbwerg L A, Milde J H, Michenfelder J D - Cerebral flow and neurologic outcome when nimodipine is given after complete cerebral ischaemia in the dog. J Cerebral Blood Flow Metab 1984; 4: 82-5.

[11] 11 Steen P A, Gisvold S E, Milde J H et al. - Nimodipine improves outcome when given after complete ischaemia in primates. Anesthesiology 1985; 62: 406-10.

[12] 12 Caettaneo A D - Protezione cerebrale. Minerva Anestesiol 1993; 59: 403-17.

[13] 13 Forsman M, Olsnes B J, Sem B G, Steen P A - Effects of nimodipine on cerebral blood flow and neuropsychological outcome after cardiac surgery. Br J Anesthesia 1990; 65: 514-20.

[14] 14 Furberg C D, Psaty B M, Meyer J V - Nifedipine: dose-related increase in mortality in patients with coronary heart disease. Circulation 1995; 92: 1326-31.

[15] 15 Legault C, Furberg C, Wagenknecht L E et al. - Nimodipine neuroprotection in cardiac valve replacement. Stroke 1996; 27: 593-8.

[16] 16 Manrique R - Monitoring of platelet function in the cardiovascular surgery patient. In: Pifarré R. Anticoagulation, hemostasis and blood preservation in cardiovascular surgery. St. Louis: Hanley & Belfus Inc., 1993: 201-13.