Dosagem da heparina em cirurgia cardíaca com circulação extracorpórea

Moraes, Fernando; Helena, Nader; Carlos P, Dietrich; Ênio, Buffolo

doi:10.1590/S0102-76381996000300010

Resumos

Com o objetivo de quantificar o nível sérico de heparina, sua atenuação em função do tempo e o valor residual após a neutralização com sulfato de protamina, foram coletadas amostras de sangue em tempos pré-estabelecidos em 27 pacientes submetidos a revascularização do miocárdio com circulação extracorpórea. Após a heparinização (400 Ul/kg) as amostras de sangue foram coletadas nos tempos de 5, 10,30 e 60 minutos e subseqüentemente a cada 30 minutos, dependendo do tempo da circulação extracorpórea. A cada hora, após a heparinização, administrava-se nova dose de heparina (200 Ul/kg). As amostras eram armazenadas à temperatura de 4ºC antes do processo de extração da heparina que foi realizado por métodos físico-químicos. As dosagens mostraram que 5 minutos após a heparinização os pacientes apresentaram concentração sangüínea máxima de heparina e, ao tempo de 60 minutos, a sua concentração é de aproximadamente 68% da encontrada aos 5 minutos. Ao tempo de 90 minutos, ou seja, após a reheparinização a concentração de heparina é 96% da evidenciada aos cinco minutos e, após a neutralização com sulfato de protamina (1,5:1), ainda se encontra um valor residual de heparina que corresponde a 4% do observado inicialmente. Observou-se que os pacientes mais idosos têm uma tendência a manter um nível sérico mais prolongado e através da equação (Cone. de heparina = 104,7 + (- 12,85 x minutos (In)) + 0,25 x idade) podemos estimar a concentração de heparina em determinado tempo.

Heparina; Circulação extracorpórea; Revascularização do miocárdio; Heparina

In order to quantify seric levels of heparin, its attenuation as a time function and its residual value after neutralization with protamine sulfate, blood samples were collected, at pre-set intervals, from 27 patients undergoing myocardial revascularization surgery under extracorporeal circulation. After heparinization (400 Ul/Kg), blood samples were collected at 5, 10, 30 and 60 minutes and subsequently every 30 minutes depending upon the extracorporeal circulation lenght. At each hour after heparinization, a new heparin dose (200 Ul/Kg) was administered. The samples were kept at 4ºC prior to the heparin extract process, which was performed by physical/chemical method. The dosages showed that 5 minutes after heparinization the patients show maximal blood concentration of heparin and after 60 minutes it is aproximately 68% of the concentration at 5 minutes. At 90 minutes time, that is, after re-heparinization, the concentration of heparin is 96% of the one showed on the fifth minute and after the protamine sulfate neutralization (1.5:1), a residual value corresponding to 4% of the one initially observed is still found. It was observed that older patients have a tendency to keep longer seric heparin level, and heparin concentration at a given time could be estimated by the Equation Heparin - Concentration = 104.7 + (-12.85 x minutes (In) + 0.25 x age).

Heparin; Myocardial revascularization; Extracorporeal circulation

ARTIGOS ORIGINAIS

Dosagem da heparina em cirurgia cardíaca com circulação extracorpórea

Measurement of heparin in cardiac surgery wilh extracorporea circulation

Fernando Moraes; Helena Nader; Carlos P. Dietrich; Ênio Buffolo

Da Escola Paulista de Medicina

^{Endereço para correspondência} Endereço para correspondência: Fernando Moraes Av. Bernardo Vieira de Melo, 4405/401. Piedade Jaboatão, PE. CEP: 54450-020

RESUMO

Com o objetivo de quantificar o nível sérico de heparina, sua atenuação em função do tempo e o valor residual após a neutralização com sulfato de protamina, foram coletadas amostras de sangue em tempos pré-estabelecidos em 27 pacientes submetidos a revascularização do miocárdio com circulação extracorpórea. Após a heparinização (400 Ul/kg) as amostras de sangue foram coletadas nos tempos de 5, 10,30 e 60 minutos e subseqüentemente a cada 30 minutos, dependendo do tempo da circulação extracorpórea. A cada hora, após a heparinização, administrava-se nova dose de heparina (200 Ul/kg). As amostras eram armazenadas à temperatura de 4ºC antes do processo de extração da heparina que foi realizado por métodos físico-químicos. As dosagens mostraram que 5 minutos após a heparinização os pacientes apresentaram concentração sangüínea máxima de heparina e, ao tempo de 60 minutos, a sua concentração é de aproximadamente 68% da encontrada aos 5 minutos. Ao tempo de 90 minutos, ou seja, após a reheparinização a concentração de heparina é 96% da evidenciada aos cinco minutos e, após a neutralização com sulfato de protamina (1,5:1), ainda se encontra um valor residual de heparina que corresponde a 4% do observado inicialmente. Observou-se que os pacientes mais idosos têm uma tendência a manter um nível sérico mais prolongado e através da equação (Cone. de heparina = 104,7 + (- 12,85 x minutos (In)) + 0,25 x idade) podemos estimar a concentração de heparina em determinado tempo.

Descritores: Heparina, sangue. Circulação extracorpórea. Revascularização do miocárdio. Heparina, cirurgia cardíaca.

ABSTRACT

In order to quantify seric levels of heparin, its attenuation as a time function and its residual value after neutralization with protamine sulfate, blood samples were collected, at pre-set intervals, from 27 patients undergoing myocardial revascularization surgery under extracorporeal circulation. After heparinization (400 Ul/Kg), blood samples were collected at 5, 10, 30 and 60 minutes and subsequently every 30 minutes depending upon the extracorporeal circulation lenght. At each hour after heparinization, a new heparin dose (200 Ul/Kg) was administered. The samples were kept at 4ºC prior to the heparin extract process, which was performed by physical/chemical method. The dosages showed that 5 minutes after heparinization the patients show maximal blood concentration of heparin and after 60 minutes it is aproximately 68% of the concentration at 5 minutes. At 90 minutes time, that is, after re-heparinization, the concentration of heparin is 96% of the one showed on the fifth minute and after the protamine sulfate neutralization (1.5:1), a residual value corresponding to 4% of the one initially observed is still found. It was observed that older patients have a tendency to keep longer seric heparin level, and heparin concentration at a given time could be estimated by the Equation Heparin - Concentration = 104.7 + (-12.85 x minutes (In) + 0.25 x age).

Descriptors: Heparin, blood. Myocardial revascularization. Extracorporeal circulation.

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Trabalho realizado na Disciplina de Cirurgia Cardiovascular do Departamento de Cirurgia e Departamento de Bioquímica da Escola Paulista de Medicina da Universidade Federal de São Paulo, SP, Brasil

Apresentado ao 23º Congresso Nacional de Cirurgia Cardíaca. Recife, PE, 20 a 23 de março, 1996.

1 Bull B S, Korpan R A, Huse W M, Briggs B D - Heparin therapy during extracorporeal circulation: I. Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg 1975; 69: 674-84.
2 Abildgaard U - Highly purified antithrombin III with heparin cofator activity prepared by disc electrophoresis. Scand J Clin Lab 1968; 21: 89-91.
3 Hattersley P G - Activated coagulation time of whole blood. JAMA 1966; 196: 436-40.
4 Olsson P, Lagergren H, Stig E K - The elimination from plasma of intravenous heparin: an experimental study on dogs and humans. Acta Med Scand 1963; 173: 619-30.
5 Horkay F, Martin P, Rajah M, Walker D - Response to heparinization in adults and childern undergoing cardiac operations. Ann Thorac Surg 1922; 53: 822-6.
6 Dietrich C P & Dietrich S M C - Electrophoretic behavior of acidic mucopolysaccharides in diamine buffers. An Biochem 1976; 70: 645-7.
7 Dietrich C P, McDuffie N M, Sampaio L O - Identification of acidic mucopolysaccharides by agarose gel electrophoresis. J Chromatogr 1977; 130: 299-304.
8 Dietrich C P, Tersariol I L S, Silva R G, Bianchini P, Nader H B - Dependence of the C-6 sulfate of the glucosamine moiety and 1-4 glycosydic linkage of heparin disaccharides for production of hemorrhage: reversal of the antihemostatic activity of heparin and their fragments by adenosin triphosphate and myosin. Semin Thromb Hemost 1991; 17: 65-73.
9 Cassaro C M F & Dietrich C P - The distribution of sulfated mucopolysaccharides in invertebrates. J Biol Chem 1977; 252: 2254-61.
10 Jaques L B, Ballieux R E, Dietrich C P, Kavanagh L W - A microeletrophoresis method for heparin. Can J Physiol Pharmacol 1968; 46: 351-60.
11 Bounameaux H, Marbet G A, Lammle B, Eichlisberger R, Duckert F - Monitoring of heparin treatment: comparison of thrombin time, activated partial thromboplastin time, and plasma heparin concentration, and analysis of the behaviour of antithrombin III. Am J Clin Pathol 1980; 74: 68-73.
12 Garcia H V, Buffolo E, Nader H B, Dietrich C P - ATP reduces blood loss produced by heparin in cardiopulmonary bypass operations. Ann Thorac Surg 1994; 57: 956-9.
13 Jaberi M, Bel W R, Benson D W - Control of heparin therapy in open-heart surgery. J Cardiovasc Surg 1974; 67: 133-41.
14 Kaul T K, Crow M J, Rajah S M, Deverall P B, Watson D A - Heparin administration during extracorporeal circulation: heparin rebound and postoperative bleeding. J Thorac Cardiovasc Surg 1979; 78:95-102.
15 Effeney D J, Goldstone J, Chin U, Krupski W C, Ellis R J - Intraoperative anticoagulation in cardiovascular surgery. Surgery 1981; 90: 1068-74.
16 Estes J W & Poulin P F - Pharmacokinetics of heparin. Thrombos Diathes Haemorrh (Stuttgard) 1974; 33: 26-37.
17 Bârzu T, Molho P, Tobelem G, Petitou M, Caen J P - Binding of heparin and low molecular weight heparin fragments to human vascular endothelial cells in culture. Nouv Rev Fr Hematol 1984; 26: 243-7.
18 Swart C A M, Nijmeyer B, Roelofs J M M, Sixma J J - Kinetics of intravenously administered heparin in normal humans. Blood 1962; 60: 1251 -8.
19 Boldt J, Zickmann B, Herold C, Scholz S, Dapper F, Hempelmann G - Heparin management during cardiac surgery with respect to various blood-conservation techniques. Surgery 1992; 111: 260-5.
20 Nader H B, Dietrich C P, Strauss A H, Takahashi H K - Características físico-químicas da heparina relacionadas com a açâo anticoagulante e anti-hemostática. Rev Bras Biol 1979; 39: 793-816.

Endereço para correspondência:

Fernando Moraes

Av. Bernardo Vieira de Melo, 4405/401. Piedade

Jaboatão, PE. CEP: 54450-020

Datas de Publicação

Publicação nesta coleção
07 Dez 2010
Data do Fascículo
Set 1996

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

[1] 1 Bull B S, Korpan R A, Huse W M, Briggs B D - Heparin therapy during extracorporeal circulation: I. Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg 1975; 69: 674-84.

[2] 2 Abildgaard U - Highly purified antithrombin III with heparin cofator activity prepared by disc electrophoresis. Scand J Clin Lab 1968; 21: 89-91.

[3] 3 Hattersley P G - Activated coagulation time of whole blood. JAMA 1966; 196: 436-40.

[4] 4 Olsson P, Lagergren H, Stig E K - The elimination from plasma of intravenous heparin: an experimental study on dogs and humans. Acta Med Scand 1963; 173: 619-30.

[5] 5 Horkay F, Martin P, Rajah M, Walker D - Response to heparinization in adults and childern undergoing cardiac operations. Ann Thorac Surg 1922; 53: 822-6.

[6] 6 Dietrich C P & Dietrich S M C - Electrophoretic behavior of acidic mucopolysaccharides in diamine buffers. An Biochem 1976; 70: 645-7.

[7] 7 Dietrich C P, McDuffie N M, Sampaio L O - Identification of acidic mucopolysaccharides by agarose gel electrophoresis. J Chromatogr 1977; 130: 299-304.

[8] 8 Dietrich C P, Tersariol I L S, Silva R G, Bianchini P, Nader H B - Dependence of the C-6 sulfate of the glucosamine moiety and 1-4 glycosydic linkage of heparin disaccharides for production of hemorrhage: reversal of the antihemostatic activity of heparin and their fragments by adenosin triphosphate and myosin. Semin Thromb Hemost 1991; 17: 65-73.

[9] 9 Cassaro C M F & Dietrich C P - The distribution of sulfated mucopolysaccharides in invertebrates. J Biol Chem 1977; 252: 2254-61.

[10] 10 Jaques L B, Ballieux R E, Dietrich C P, Kavanagh L W - A microeletrophoresis method for heparin. Can J Physiol Pharmacol 1968; 46: 351-60.

[11] 11 Bounameaux H, Marbet G A, Lammle B, Eichlisberger R, Duckert F - Monitoring of heparin treatment: comparison of thrombin time, activated partial thromboplastin time, and plasma heparin concentration, and analysis of the behaviour of antithrombin III. Am J Clin Pathol 1980; 74: 68-73.

[12] 12 Garcia H V, Buffolo E, Nader H B, Dietrich C P - ATP reduces blood loss produced by heparin in cardiopulmonary bypass operations. Ann Thorac Surg 1994; 57: 956-9.

[13] 13 Jaberi M, Bel W R, Benson D W - Control of heparin therapy in open-heart surgery. J Cardiovasc Surg 1974; 67: 133-41.

[14] 14 Kaul T K, Crow M J, Rajah S M, Deverall P B, Watson D A - Heparin administration during extracorporeal circulation: heparin rebound and postoperative bleeding. J Thorac Cardiovasc Surg 1979; 78:95-102.

[15] 15 Effeney D J, Goldstone J, Chin U, Krupski W C, Ellis R J - Intraoperative anticoagulation in cardiovascular surgery. Surgery 1981; 90: 1068-74.

[16] 16 Estes J W & Poulin P F - Pharmacokinetics of heparin. Thrombos Diathes Haemorrh (Stuttgard) 1974; 33: 26-37.

[17] 17 Bârzu T, Molho P, Tobelem G, Petitou M, Caen J P - Binding of heparin and low molecular weight heparin fragments to human vascular endothelial cells in culture. Nouv Rev Fr Hematol 1984; 26: 243-7.

[18] 18 Swart C A M, Nijmeyer B, Roelofs J M M, Sixma J J - Kinetics of intravenously administered heparin in normal humans. Blood 1962; 60: 1251 -8.

[19] 19 Boldt J, Zickmann B, Herold C, Scholz S, Dapper F, Hempelmann G - Heparin management during cardiac surgery with respect to various blood-conservation techniques. Surgery 1992; 111: 260-5.

[20] 20 Nader H B, Dietrich C P, Strauss A H, Takahashi H K - Características físico-químicas da heparina relacionadas com a açâo anticoagulante e anti-hemostática. Rev Bras Biol 1979; 39: 793-816.