Efeitos da dexmedetomidina sobre a coagulação sangüínea avaliada através do método da tromboelastografia

César Romão Martins; Maria Angela Tardelli; José Luiz Gomes do Amaral

doi:10.1590/S0034-70942003000600002

Scientific Article

Efeitos da dexmedetomidina sobre a coagulação sangüínea avaliada através do método da tromboelastografia

Effects of dexmedetomidine on blood coagulation evaluated by thromboelastography

César Romão Martins; Maria Angela Tardelli; José Luiz Gomes do Amaral

http://dx.doi.org/10.1590/S0034-70942003000600002 Braz J Anesthesiol, vol.53, n6, p.705-719, 2003

PDF

Downloads: 0

Resumo

JUSTIFICATIVA E OBJETIVOS: A dexmedetomidina é um agente agonista dos receptores adrenérgicos alfa2 altamente seletivo, usado em anestesia por seus efeitos hipnoanalgésicos e pela estabilidade cardiovascular. O estímulo dos receptores adrenérgicos alfa2 pode apresentar efeitos pró e antiagregantes plaquetários, por mecanismos diretos e indiretos. No presente estudo, avaliaram-se os efeitos da dexmedetomidina sobre a coagulação através do método da tromboelastografia. MÉTODO: Vinte e quatro pacientes foram aleatoriamente divididos em três grupos. Os pacientes do grupo 1 receberam infusão de solução fisiológica (controle), os do grupo 2 receberam dexmedetomidina na dose de 1 µg.kg-1 em 10 minutos, seguida da infusão de 0,4 µg.kg-1.h-1 por 20 minutos e os do grupo 3 receberam midazolam na dose de 0,05 mg.kg-1. Os pacientes sedados mantiveram índices 3 ou 4 na escala da sedação de Ramsay. Foram coletadas amostras de sangue e obtidos traçados de tromboelastografia previamente e após 30 minutos do tratamento. RESULTADOS: A dexmedetomidina, de forma estatisticamente significativa, aumentou o tempo de reação (parâmetro R) e diminuiu o índice de coagulação nos traçados finais em relação aos iniciais. No entanto, os valores permaneceram dentro dos intervalos considerados normais. Este fenômeno não foi observado nos demais grupos. CONCLUSÕES: A interação dos mecanismos pró e antiagregantes da dexmedetomidina leva à discreta hipocoagulação; porém, mantém a coagulação dentro de parâmetros considerados normais. Os efeitos da dexmedetomidina sobre a coagulação provavelmente não ocorrem pela ansiólise, uma vez que a sedação foi igual ao grupo que recebeu midazolam.

Palavras-chave

DROGAS, DROGAS, EXAMES LABORATORIAIS, SANGUE

Abstract

BACKGROUND AND OBJECTIVES: Dexmedetomidine is a highly selective alpha2-adrenoceptor agonist used in anesthesia for its hypnoanalgesic and cardiovascular effects. Stimulation of alpha2-adrenoceptors may determine pro and anti-platelet aggregation effects through direct and indirect mechanisms. This study aimed at determining the effects of dexmedetomidine on coagulation evaluated by thromboelastography. METHODS: Twenty four patients were randomly distributed in 3 groups: Group 1 patients received saline solution (control group), Group 2 patients received 1 µg.kg-1 dexmedetomidine in 10 minutes, followed by 0.4 µg.kg-1.h-1 infusion for 20 minutes and Group 3 patients received 0.05 mg.kg-1 midazolam. Sedated patients maintained scores 3 or 4 in Ramsays sedation scale. Blood samples were collected before and 30 minutes after the treatment for thromboelastography. RESULTS: Dexmedetomidine has significantly increased reaction time (parameter R) and decreased coagulation index in final curves as compared to initial ones. Values, however, have remained within ranges accepted as normal. This phenomenon was not observed in remaining groups. CONCLUSIONS: Dexmedetomidine pro and anti-platelet aggregation mechanisms interaction determines mild hypocoagulation, however maintaining coagulation within normal ranges. Dexmedetomidine effects on coagulation are probably not mediated by anxiolysis, since sedation was equivalent to the midazolam group.

Keywords

BLOOD, DRUGS, DRUGS, LABORATIAL TESTS

Referencias

Hayashi Y, Maze M. Alpha2-adrenoceptor agonists and anesthesia. Br J Anaesth. 1993;71:108-118.

Tonner PH, Schlolz J. Clinical perspectives of alpha2-adrenoceptor agonists. Curr Opin Anaesth. 1996;9:471-480.

Aantaa R, Scheinin M. Alpha2-adrenergic agents in anesthesia. Acta Anaesthesiol Scand. 1993;37:433-448.

Khan ZP, Ferguson CN, Jones RM. Alpha2 and imidazoline receptor agonists, their pharmacology and therapeutic role. Anaesthesia. 1999;54:146-165.

MacDonald E, Scheinin M. Distribution and pharmacology of alpha2-adrenoceptors in the central nervous system. J Physiol Pharmacol. 1995;46:241-258.

Bachand R, Scholz J, Pinaud M et al. The effects of dexmedetomidina in patients in the intensive care setting. Intensive Care Med. 1999;25(^s1).

Jalonen J, Markku H. Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology. 1997;86:331-345.

Hynynen M, Jalonen J. Dexmedetomidine infusion improves perioperative adrenergic stability during coronary artery bypass grafting. J Cardiothorac Vasc Surg. 1994;8(^s3):56-62.

Fragen RJ, Fitzgerald P, Paul C. The effect of dexmedetomidine on the minimum alveolar concentration (MAC) of sevoflurane in adults age 55 to 70 years to prevent response to skin incision. Anesthesiology. 1998;89((3AS):134-140.

Nunes RR, Cavalcante SL. Influência da dexmedetomidina na concentração expirada do sevoflurano: Avaliação pelo índice bispectral, taxa de supressão e análise espectral da potência do eletroencefalograma. Rev Bras Anestesiol. 2002;52:133-145.

Curtis FG, Castiglia YMM, Stolf AA et al. Dexmedetomidina e sufentanil como analgésicos per-operatórios: Estudo comparativo. Rev Bras Anestesiol. 2002;52:525-534.

Bagatini A, Gomes CR, Masella MZ. Dexmedetomidina: farmacologia e uso clínico. Rev Bras Anestesiol. 2002;52:606-617.

Grant JA, Scrutton MC. Interaction of selective alpha-adrenoceptor agonists and antagonists with human and rabbit blood platelets. Br J Pharmacol. 1980;71:121-134.

Cohen J, Eckstein L, Gutman Y. The mechanism of alpha-adrenergic inhibition of catecholamine realize. Br J Pharmacol. 1980;71:135-142.

Misioäek H, Wojcieszek E, Dyakzy A. Comparison of influence of thiopentone, propofol and midazolam on blood serum concentration of noradrenaline and cortisol in patients undergoing non-toxic struma operation. Med Sci Monit. 2000;6:319-324.

Mallett SV, Cox DJA. Thromboelastography. Br J Anaesth. 1992;69:307-313.

Gilman AG. G protein: transducers of receptor-generated signal. Ann Rev Biochem. 1987;56:615-649.

Birnbaumer L, Abramowitz J, Brown AM. Receptor-effectors coupling by G proteins. Biochemical et Biophysical Acta. 1990;1031:163-224.

Codina J. The subunit of the GTP binding protein Gk pens atrial potassium channels. Science. 1987;236:442-445.

Aghajanian GK, VanderMaelen CP. Alpha2 adrenoceptor-mediated hyperpolarization of locus coeruleus neurons: intracellular studies in vivo. Science. 1982;215:1394-1396.

Herscheler H. The GTP-binding protein, G0, regulates neuronal calcium channels. Nature. 1987;325:445-447.

Isom LL, Cragoe Jr EJ, Limbird LE. Alpha2 adrenergic receptors accelerate Na+/H+ exchange in neuroblastoma x glioma cells. J Biol Chem. 1987;262:6720-6787.

Bylund DB. Heterogeneity of alpha2 adrenergic receptors. Pharmacol, Biochem Behavior. 1985;22:835-843.

Lidbrink P. The effect of lesion of ascending noradrenergic pathways on sleeping and awaking in rats. Brain Research. 1974;74:19-40.

Belleville JP, Wards DS, Bloor BC et al. Effects of intravenous dexmedetomidine in humans: I Sedation, ventilation, and metabolic rate. Anesthesiology. 1992;77:1125-1133.

Bloor BC, Wards DS, Belleville JP et al. Effects of intravenous dexmedetomidine in humans: II Hemodynamic changes. Anesthesiology. 1992;77:1134-1142.

Dyck JB, Shafer SL. Dexmedetomidine pharmacokinetics and pharmacodynamics. Anaesth Pharm Review. 1993;1:238-245.

Clare KA, Scrutton MC, Thompson NT. Effects of alpha2-adrenoceptor agonists and of related compounds on aggregation of, and on adenylate cyclase activity in, human platelets. Br J Pharmacol. 1984;82:467-476.

Almeida TV. Hemostasia. Fisiologia. 1991;1:94-108.

Clare KA, Scrutton MC. Interactions of human platelets with plasma adrenoceptor agonists. Br J Pharmacol. 1984;78:158-166.

Radomsky MW, Palmer RMJ, Moncada S. The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol. 1987;92:639-646.

Azuma H, Ishikawa M, Sekizaki S. Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol. 1990;88:411-415.

Kubota T, Hirota K, Yoshida S. Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats. Psychopharmacol. 1999;148:335-338.

Kobayashi Y, Muldoon SM, Kiyose M. Inhibition by midazolam of the adrenergic function in the isolated canine mesenteric vein. Acta Anaesthesiol Scand. 1998;42:1157-1163.

Kohro S, Yamakage M, Omote T. In vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastography technique. Acta Anaesthesiol Scand. 1999;43:217-219.

Efeitos da dexmedetomidina sobre a coagulação sangüínea avaliada através do método da tromboelastografia

Effects of dexmedetomidine on blood coagulation evaluated by thromboelastography

César Romão Martins; Maria Angela Tardelli; José Luiz Gomes do Amaral

Resumo

Palavras-chave

Abstract

Keywords

Referencias

Links

compartir

Braz J Anesthesiol