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Genetic effects on propofol induced hypotension: 4AP2-6

Chakithandy, S.; Anderson, P. G.; Wouters, K. M.; Arenas, M.; Lewis, C. M.; Morley, A. P.

European Journal of Anaesthesiology: June 2011 - Volume 28 - Issue - p 46
Abstracts and Programme: EUROANAESTHESIA 2011: The European Anaesthesiology Congress: Clinical and Experimental Circulation
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Guy's and St. Thomas' NHS Foundation Trust, Department of Anaesthesiology, London, United Kingdom

Background and Goal of Study: Propofol-induced hypotension (PIH) may affect postoperative outcome.1 Its mechanism is unclear. We previously studied PIH in 262 ASA I-II Caucasian surgical patients aged 18-65 years, excluding diabetics, hypertensives and the obese. PIH was associated with weight and baseline mean arterial pressure (MAP).2-4

In the current study, we aimed to establish the effect of selected genetic polymorphisms on PIH.

Materials and Methods: We recruited 247 more patients using the same criteria. All 509 patients received intravenous propofol for 15 minutes in all, initially at 40mg/kg/h. When electroencephalographic bispectral index decreased to 50, propofol dose (PD) was recorded and infusion rate reduced to 8mg/kg/h. Patients breathed facial oxygen at 4l/min. Non-invasive airway support was applied if needed. MAP was recorded every minute.

For each patient, we calculated the maximum percentage decrease from baseline MAP (max%ΔMAP) and then corrected for PD before testing for genetic association. The 155 patients at the upper (PIH sensitive) and lower (PIH resistant) tails of the distribution were selected for genotyping. DNA was extracted from blood samples.

Genotyping was conducted at the insertion/deletion polymorphism in the angiotensinogen converting enzyme gene (ACE In/Del) and four single nucleotide polymorphisms (genes): rs4961 (α adducin, ADD1), rs699 and rs5051 (angiotensin, AGT) and rs5186 (angiotensin II receptor type1, AGTR1). All have been associated with antihypertensive drug response. At each polymorphism, patient genotypes were coded 0,1 or 2, with 1 representing heterozygosity.

Association of polymorphisms with PIH sensitive and PIH resistant groups was tested with a linear model.

Results and Discussion: Mean (SD) max%ΔMAP was 32.2(3.7)% and 17.4(4.7) % in PIH sensitive and PIH resistant groups respectively. Genotype frequencies did not differ significantly between groups. P values for each polymorphism were: ACE In/Del = 0.27, rs4961 = 0.65, rs699 = 0.37, rs5051 = 0.26, rs5186 = 0.07.

Conclusion: These polymorphisms do not strongly affect PIH. This does not preclude effects of other polymorphisms on PIH in these or other genes.

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References:

(1) Reich DL et al. Anesth Analg 2005;101:622-8
(2) Morley AP et al. Anaesthesia 2008;63:467-73
(3) Morley AP et al. Anesth Analg 2010;111:1373-77
(4) Natarajan A et al. Anaesthesia 2010, Nov 29 epub

Acknowledgements: National Institute of Academic Anaesthesia Small Project Grant, 2008

© 2011 European Society of Anaesthesiology