Preoperative clear fluid fasting and endoscopy-measured gastric fluid volume in children.

BACKGROUND: In light of new recommendations to shorten clear fluid fasting time before anesthesia, our study aimed at exploring residual fluid volume in the stomach after different fasting times. We intended to perform direct endoscopic aspiration of stomach contents under vision, as part of routine gastroscopy assessment. Hereby we would be able to quantify true residual gastric fluid volume and acidity in children and measure their correlation with fasting times. METHODS: The study was performed as a single-center, prospective study in pediatric perioperative day care at a university-affiliated tertiary care center. Aspiration of gastric fluid contents was performed in anesthetized children aged 1-18 years undergoing an elective gastroscopy. Recorded data included patient fast time, last meal content, last clear fluid content, and aspirated gastric volume and pH, as well as patient characteristics. RESULTS: We included 253 gastroscopies, performed in 245 children. Mean fasting time for clear fluids was 6.9 h (range 1 h 40 min - 18 h 35 min) (SD 4.5). Mean age was 9.8 years (SD 5.1) and mean body weight was 33.2 kg (SD 18.7). Mean residual gastric volume was 12 mL (0-90) (SD 13.5) or 0.34 mL/kg (SD 0.37) and mean pH was 1.5 (SD 0.9). No significant correlation was observed between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight (r = -.103, p = .1), nor between clear fluid fasting time and the pH of the residual gastric fluid (r = -.07, p = .3). In more than half of the patients the residual gastric volume was less than 10 mL, unrelated to fasting time. CONCLUSIONS: In children undergoing gastroscopy, we could not demonstrate any association between clear fluid fasting time and the child's residual gastric fluid volume per kg body weight. Since we did not see a clinically relevant association between clear fluids fasting time and gastric residual volume, this study may support the recommendation to shorten clear fluids fasting time.

An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.

We are developing an orally available small-molecule, allosteric TSH receptor (TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was, therefore, predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen(®)). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer.