beta2-adrenoceptor genotype affects vasopressor requirements during spinal anesthesia for cesarean delivery.

Clinical Anesthesiology, Department of Anesthesiology, Columbia University, New York, New York, USA.
Anesthesiology (Impact Factor: 6.17). 05/2006; 104(4):644-50.
Source: PubMed

ABSTRACT Maternal hypotension is common after spinal anesthesia for cesarean delivery. There is wide variability in the incidence and severity of hypotension and in the response to treatment. The beta2 adrenoceptor (beta2AR) possesses several polymorphic sites. Codons 16 (Arg16Gly) and 27 (Glu27Gln) have been shown to affect desensitization of the receptor. The goal of this study was to determine whether genetic variants of the beta2AR alter incidence of hypotension or the amount of vasopressor treatment required during spinal anesthesia for cesarean delivery.
One hundred seventy healthy women undergoing elective cesarean delivery were studied. Spinal anesthesia was performed with 12 mg hyperbaric bupivacaine, 25 microg fentanyl, and 200 microg morphine. Hypotension was treated with ephedrine and/or phenylephrine intravenously, and beta2AR genotype at codons 16 and 27 was determined. Analysis of variance was used to compare variables between genotypes, with data expressed as mean +/- SD.
Ephedrine or phenylephrine was used in more than 90% of patients, with no difference in the incidence of hypotension between beta2AR genotypes. However, there was a significant effect of genotype on the amount of vasopressor required. Gly16 homozygotes received significantly less ephedrine (18 +/- 14 mg) than Arg16 homozygotes (28 +/- 13 mg) and Arg16Gly heterozygotes (30 +/- 20 mg; P = 0.0005). Glu27 homozygotes required significantly less ephedrine than Gln 27 homozygotes (14 +/- 13 vs. 30 +/- 19 mg; P = 0.002). Gln27Glu heterozygotes received less ephedrine than Gln27 homozygotes (23 +/- 16 vs. 30 +/- 19 mg; P = 0.03).
Glycine at position 16 and/or glutamate at position 27 of the beta2AR leads to lower vasopressor use for treatment of hypotension during spinal anesthesia.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: during the scheduled cesarean section, the main side effect of the spinal anesthesia is the spinal anesthesia-induced hypotension (SAIH). Objective: to identify the course of action with regard to the use of fluids and vasopressors for the prevention and management of the SAIH during the cesarean section in healthy women. Methods: a survey by means of e-mail address was carried out to the members of the Sociedad Colombiana de Anestesiología y Reanimación (SCARE) in April in 2012, with the objective to determine their strategies for the prevention and management of the SIAH with regard to the use of fluids and vasopressors. This survey was created by the authors and without the validation process. Results: of 2113 anesthesiologists, just 491 (23.2%) answered the survey. 61.7% of the participants used fluids as prevention strategies of the SAIH. Of them, 60% administered it only as precharge and the other ones as adjuvant. 10.2% of all the participants combined intravenous fluids and vasopressors. 3.7% used only vasopressors and the 24.4% did not use any of those measures as prevention of the SAIH. The crystalloids were used by more than 99% of the survey respondents that administer fluids in a routine way, being the doses of preference between 500 and 1000 cc. Just the 14% of the survey respondents use vasopressors in a prophylactic way, from which the 53% uses etilefrine, the majority in intravenous bolus. The majority of the survey respondent use vasopressors just in a therapeutic way, being preferred by 65% the etilefrine, followed by the ephedrine, both administered mainly in intravenous bolus. Conclusions: the etilefrine is the most used agent by a group of Colombian anesthesiologists belong to the SCARE, mainly in intravenous bolus, as prophylactic and therapeutic measure for the SAIH in cesarean section. Rev.cienc.biomed. 2014;5(2):263-271. KEYWORDS Hypotension; Obstetrical anesthesia; Spinal anesthesia; Vasoconstrictor agents.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs.
    Pharmacogenomics 01/2014; 15(1):69-78. DOI:10.2217/pgs.13.228 · 3.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: /st>While the β2-adrenoceptor pathway is essential for cardiovascular regulation, the impact of ADRB2 gene variations on circulatory responses is unclear, possibly due to neural compensatory mechanisms. We tested the hypotheses that (i) sympathetic block by thoracic epidural anaesthesia (TEA) unmasks the influence on arterial pressure of genetic variations and (ii) vasopressor requirements during TEA depend on ADRB2 gene variation. /st>Ninety-three elective patients undergoing abdominal surgery were included prospectively. After epidural bupivacaine 0.5% (15 mg test dose+50 mg), arterial pressure, heart rate, and progression of sensory block were measured for 20 min in the supine awake state and for 20 min after standardized anaesthetic induction of general anaesthesia. The primary endpoint was cumulative dose of the α-adrenoreceptor agonist phenylephrine administered to sustain a mean arterial pressure >70 mm Hg. The ADRB2 polymorphisms Arg16Gly and Gln27Glu were genotyped using Slowdown-PCR. /st>After TEA, 86 (93%) patients required phenylephrine. The mean dosages (sd) were significantly different between the ADRB2 genotypes [Arg16Arg 357 µg (326), Arg16Gly 776 µg (449), Gly16Gly 600 µg (443), P=0.036; Gln27Gln 356 µg (254), Gln27Glu 639 µg (354), Glu27Glu 577 µg (388), P=0.007]. Multiple linear regression analysis revealed that age, male gender, rostral extent of sensory block, lower arterial pressure before TEA, and ADRB2 Glu27 allele together explained 37% of phenylephrine dosage variation, with genetic variants being the second most important predictor (10%; P<0.001). /st>The ADRB2 Glu27 allele is an independent predictor of arterial hypotension and vasopressor requirements after TEA. Neural block can unmask genetic influences on neurohumoral regulation.Clinical trial registrationDRKS00005260.
    BJA British Journal of Anaesthesia 12/2013; 112(3). DOI:10.1093/bja/aet404 · 4.35 Impact Factor