beta2-adrenoceptor genotype affects vasopressor requirements during spinal anesthesia for cesarean delivery.
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.
Article: Zaugg M, Bestmann L, Wacker J, Lucchinetti E, Boltres A, Schulz C, Hersberger M, Kalin G, Furrer L, Hofer C, Blumenthal S, Muller A, Zollinger A, Spahn DR, Borgeat A. Adrenergic receptor genotype but not peri-operative bisoprolol therapy may determine cardiovascular outcome in at-risk patients undergoing surgery with spinal block: the Swiss Beta Blocker in Spinal Anesthesia (BBSA) study: a double-blinded, placebo-controlled, multicenter trial with 1-year follow-up[Show abstract] [Hide abstract]
ABSTRACT: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block. The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined. A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the beta1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04). Perioperative bisoprolol therapy did not affect cardiovascular outcome in these elderly at-risk patients undergoing surgery with spinal block.Anesthesiology 08/2007; 107(1):33-44. DOI:10.1097/01.anes.0000267530.62344.a4 · 5.88 Impact Factor
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ABSTRACT: The optimum intrathecal dose of hyperbaric levobupivacaine for spinal anaesthesia during elective caesarean section has not yet been investigated. A total of 30 parturients undergoing elective caesarean section were included in this prospective, randomised, double-blind study. Parturients received either 7.5, 10 or 12.5 mg hyperbaric 0.5% levobupivacaine intrathecally. Analgesic, sensory and motor block characteristics as well as maternal and fetal levobupivacaine plasma concentrations were determined. Of the parturients receiving 7.5 mg levobupivacaine 40% required supplementary intravenous opioid analgesics intraoperatively and none achieved complete motor block. Compared to 7.5 mg levobupivacaine, 10 and 12.5 mg significantly prolonged duration of effective analgesia postoperatively (median: 45 vs. 81 and 96 min, respectively). Both maternal and fetal levobupivacaine plasma concentrations were low, with dose-dependent, statistically significant differences in maternal plasma concentrations. Levobupivacaine 7.5 mg did not provide satisfactory intraoperative analgesia in all parturients. There were no statistically significant differences between 10 and 12.5 mg levobupivacaine with respect to analgesic, sensory and motor block characteristics. Therefore, based on these data, 10 mg levobupivacaine is recommended for parturients undergoing elective caesarean section with spinal anaesthesia.Der Anaesthesist 09/2007; 56(8):772-9. · 0.76 Impact Factor
Article: Vasopressors in Obstetrics[Show abstract] [Hide abstract]
ABSTRACT: Hypotension is a common, treatable side effect of neuraxial anesthesia, which has significant side effects for the mother and demonstrable biochemical effects in the fetus. It is clear that a shift in management of hypotension in the obstetric population is in order, but we can only speculate on the benefits for the compromised fetus due to the lack of available information in that patient population.Anesthesiology Clinics 04/2008; 26(1):75-88, vi-vii. DOI:10.1016/j.anclin.2007.11.005