METHODS: The distribution of polymorphic variants in the SLCO1B1 gene at eight loci that spanned approximately 48 kb was investigated in the three different Asian ethnic groups and in 32 non-cancerous liver tissues from Chinese patients.
RESULTS: Of the 26 polymorphisms screened, we found eight polymorphic variants that differed in genotypic and allelic frequencies between the Chinese, Malay and Indian populations. Significant interethnic differences were observed in the genotype frequency distributions across the promoter SNP [g.-11187G>A (P = 0.030)] as well as three coding region SNPs [c.388G>A (P < 0.001); c.571T>C (P < 0.001); c.597C>T (P < 0.001)] in the healthy subjects. Haplotype analysis revealed 12 different haplotypes in both the Chinese and Malay populations and 18 haplotypes in the Indian population. In both the Malay and Indian populations, the htSNPs were c.388A>G, c.571T>C and c.597C>T, whereas in the Chinese population they were g.-11187G>A, c.388A>G and c.597C>T. The c.388A>G and c.597C>T htSNPs accounted for more than 70% of the variations between the three major haplotypes in each Asian ethnic group. In terms of the c.388A>G htSNPs, genotypic-phenotypic association analyses revealed that there was no effect on SLCO1B1 expression in hepatic tissues; in addition, no genotypic-phenotypic associations were evident with regards to the c.597C>T htSNP.
CONCLUSION: Future studies should investigate the phenotypic effects of the c.388A>G htSNP on the disposition of OATP1B1 substrates in Asian populations.
MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled prospective study, we enrolled 40 children undergoing tonsillectomy. Anesthetic care was standardized. Intraoperative analgesia was provided with remifentanil 0.5 microg x kg(-1) followed by an infusion of 0.25 microg x kg(-1) x min(-1). Group I (ketamine, n = 20) received a bolus dose of ketamine 0.5 mg x kg(-1) followed by a continuous infusion of 2 microg x kg(-1) x min(-1) before start of surgery. The infusion was stopped when surgery ended. Group II (placebo, n=20) received normal saline in the same manner. Pain was assessed postoperatively using the Children's Hospital Eastern Ontario Pain Scale (CHEOPS; range of scores 4 13), and total morphine consumption was recorded in the postanesthesia care unit (PACU). Patients were transferred to the ward and morphine was administered via a patient-controlled analgesia (PCA) device and analgesia was recorded using a visual analogue scale (VAS) (0 - 10).
RESULTS: Intraoperative remifentanil consumption was not different between the ketamine group (0.29+/-0.09 microg x kg x min(-1) ) and the control group (0.24+/-0.07 microg x kg x min(-1)). There were no significant differences between CHEOPS scores and VAS score between the two groups. The total mean morphine consumption in the ward was not significantly different between the two groups: 376.5 +/-91.6 microg x kg(-1) with ketamine and 384.4+/-97.3 microg x kg(-1) with placebo. The time-to-first analgesic requirement was also similar in both groups.
CONCLUSIONS: Small-dose ketamine did not decrease postoperative pain after tonsillectomy in children when added to a continuous intraoperative remifentanil infusion.