Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942010000300002
Brazilian Journal of Anesthesiology
Scientific Article

Avaliação da influência do polimorfismo do códon 16 do receptor beta-2 adrenérgico na incidência de hipotensão arterial e uso de efedrina em grávidas submetidas à anestesia subaracnoidea

Evaluation of the influence of the codon 16 polymorphism of the beta-2 adrenergic receptor gene on the incidence of arterial hypotension and ephedrine use in pregnant patients submitted to subarachnoid anesthesia

Edno Magalhães; Maurício Daher Andrade Gomes; Gustavo Barcelos Barra; Cátia Sousa Govêia; Luis Cláudio Araújo Ladeira

http://dx.doi.org/10.1590/S0034-70942010000300002 Braz J Anesthesiol, vol.60, n3, p.228-236, 2010
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Resumo

JUSTIFICATIVA E OBJETIVOS: O gene do receptor beta-2 adrenérgico possui diversos polimorfismos. Estudos recentes vêm demonstrando sua importância clínica. O objetivo deste trabalho foi avaliar a influência do polimorfismo Arg16Gli na incidência de hipotensão arterial e uso de efedrina em parturientes submetidas ao bloqueio subaracnoideo para cesariana. MÉTODO: Parturientes hígidas (ASA I e II) foram submetidas à anestesia raquidiana para realização de cesariana eletiva (n = 50). Efedrina foi administrada nos casos de hipotensão arterial. A incidência de hipotensão arterial e a dose requerida de efedrina para correção da pressão arterial foram comparadas entre os diferentes genótipos encontrados. RESULTADOS: O genótipo mais prevalente foi o Arg16Gli (60%, n = 30) seguido pelo Gli16Gli (26%, n = 13) e Arg16Arg (14%, n = 7). Não foram observadas diferenças entre as características básicas dos genótipos. Com relação ao genótipo Arg16Arg, o Gli16Gli apresentou aumento da razão de risco de hipotensão arterial (hazard ratio) de 3,95 vezes (IC 95% 0,86-18,11; p = 0,076), enquanto o Arg16Gli apresentou aumento de 4,83 vezes (IC 95% 1,13-20,50; p = 0,033). As parturientes com Arg16Arg precisaram, em média, de 6,4 ± 8,5 mg de efedrina para correção de hipotensão arterial, enquanto as do Arg16Gli precisaram de 19,5 ± 15,9 mg (p = 0,0445; IC 95% 0,3325-25,78) e as do tipo Gli16Gli, 19,2 ± 14,3 (p = 0,0445, IC 95% 0,3476-25,26). CONCLUSÕES: Os resultados mostraram que a variante genética Arg16Arg apresenta menor incidência de hipotensão arterial e que menores doses de efedrina foram necessárias para restabelecimento de normotensão arterial nas pacientes com esse perfil genético. Concluímos que o genótipo Arg16Arg confere maior estabilidade pressórica às parturientes submetidas à anestesia raquidiana para cesariana.

Palavras-chave

ANESTESIA, ANESTESIA, COMPLICAÇÕES, DROGAS, TÉCNICAS ANESTÉSICAS, TÉCNICAS ANESTÉSICAS

Abstract

BACKGROUND AND OBJECTIVES: The beta-2 adrenergic receptor gene has several polymorphisms. Recent studies have demonstrated the clinical importance of the latter. The objective of the present study was to evaluate the influence of the Arg16Gli polymorphism on the incidence of arterial hypotension and ephedrine use in pregnant patients submitted to subarachnoid block for Cesarean section. METHOD: Healthy parturients (ASA I and II) were submitted to subarachnoid anesthesia for elective Cesarean section (n = 50). Ephedrine was administered in cases of arterial hypotension. The incidence of arterial hypotension and the required dose of ephedrine to correct the arterial pressure were compared between the different genotypes identified. RESULTS: The most prevalent genotype was Arg16Gli (60%, n = 30) followed by Gli16Gli (26%, n = 13) and Arg16Arg (14%, n = 7). No differences were observed regarding the basic characteristics of the genotypes. In comparison to the Arg16Arg genotype, the Gli16Gli presented a 3.95-fold increase in the hazard ratio of arterial hypotension (95%CI 0.86-18.11; p = 0.076), whereas the Arg16Gli presented a 4.83-fold increase (95%CI 1.13-20.50; p = 0.033). The parturients with the Arg16Arg needed, on average, 6.4 ± 8.5 mg of ephedrine to correct the arterial hypotension, whereas those with the Arg16Gli needed 19.5 ± 15.9 mg (p = 0.0445; 95%CI 0.3325-25.78) and the ones with the Gli16Gli genotype, 19.2 ± 14.3 (p = 0.0445, 95%CI 0.3476-25.26). CONCLUSIONS: The results show that the genetic variant Arg16Arg presents a lower incidence of arterial hypertension and that lower doses of ephedrine were necessary to reestablish normal arterial pressure in the patients with this genetic profile. We conclude that the Arg16Arg genotype confers better pressure stability to the parturients submitted to subarachnoid anesthesia for Cesarean section.

Keywords

ANESTHESIA, ANESTHESIA, ANESTHETIC TECHNIQUES, ANESTHETIC TECHNIQUES, COMPLICATION, DRUGS

References

Kharasch ED. Special issue on pharmacogenomics and anesthesia: work presented at the 2004 journal symposium. Anesthesiology. 2005;102:493-494.

Iohom G, Fitzgerald D, Cunningham AJ. Principles of pharmacogenetics: implications for the anaesthetist. Br J Anaesth. 2004;93:440-450.

Cheung VG, Spielman RS, Ewens KG. Mapping determinants of human gene expression by regional and genome-wide association. Nature. 2005;437:1365-1369.

Mayeux R, Saunders AM, Shea S. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer's disease: Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimer's Disease. N Engl J Med. 1998;338:506-511.

Evans WE, McLeod HL. Pharmacogenomics: drug disposition, drug targets, and side effects. N Engl J Med. 2003;348:538-549.

Shastry BS. Pharmacogenetics and the concept of individualized medicine. Pharmacogenomics J. 2006;6:16-21.

Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003;348:529-537.

Bond C, LaForge KS, Tian M. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998;95:9608-9613.

Gerdes LU, Gerdes C, Kervinen K. The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction: a substudy of the Scandinavian simvastatin survival study. Circulation. 2000;101:1366-1371.

Israel E, Chinchilli VM, Ford JG. Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. 2004;364:1505-1512.

Kalow W. Familial incidence of low pseudocholinesterase level. Lancet. 1956;268:576-577.

Sweeney BP. Do genes influence outcome from anaesthesia?. Br J Anaesth. 2003;90:725-727.

Jensen FS, Schwartz M, Viby-Mogensen J. Identification of human plasma cholinesterase variants using molecular biological techniques. Acta Anaesthesiol Scand. 1995;39:142-149.

Lieber CS. Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev. 1997;77:517-544.

Kundra P, Khanna S, Habeebullah S. Manual displacement of the uterus during Caesarean section. Anaesthesia. 2007;62:460-465.

Chan WS, Irwin MG, Tong WN. Prevention of hypotension during spinal anaesthesia for caesarean section: ephedrine infusion versus fluid preload. Anaesthesia. 1997;52:908-913.

Lee A, Ngan Kee WD, Gin T. Prophylactic ephedrine prevents hypotension during spinal anesthesia for Cesarean delivery but does not improve neonatal outcome: a quantitative systematic review. Can J Anaesth. 2002;49:588-599.

Zaugg M, Schaub MC. Genetic modulation of adrenergic activity in the heart and vasculature: implications for perioperative medicine. Anesthesiology. 2005;102:429-446.

Dishy V, Sofowora GG, Xie HG. The effect of common polymorphisms of the beta2-adrenergic receptor on agonist-mediated vascular desensitization. N Engl J Med. 2001;345:1030-1035.

Gratze G, Fortin J, Labugger R. beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians. Hypertension. 1999;33:1425-1430.

Castellano M, Rossi F, Giacche M. Beta(2)-adrenergic receptor gene polymorphism, age, and cardiovascular phenotypes. Hypertension. 2003;41:361-367.

Smiley RM, Blouin JL, Negron M. beta2-adrenoceptor genotype affects vasopressor requirements during spinal anesthesia for cesarean delivery. Anesthesiology. 2006;104:644-650.

Walsh PS, Metzger DA, Higuchi R. Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques. 1991;10:506-513.

Hall PA, Bennett A, Wilkes MP. Spinal anaesthesia for Caesarean section: comparison of infusions of phenylephrine and ephedrine. Br J Anaesth. 1994;73:471-474.

Magalhães E, Goveia CS, Ladeira LCA. Efedrina versus fenilefrina: prevenção de hipotensão arterial durante anestesia raquidea para cesariana e efeitos sobre o feto. Rev Bras Anestesiol. 2009;59:11-20.

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