Specific risk factors and their potential correction or indications for stoma were identified. An AL severity score is proposed to aid clinical decision-making.
Due to the risk of inducing hyperchloraemic acidosis in routine practice, when crystalloid resuscitation or replacement is indicated, balanced salt solutions, eg Ringer' s lactate/acetate or Hartmann' s solution should replace 0.9% saline, except in cases of hypochloraemia, eg from vomiting or gastric drainage. Evidence level 1b * Recommendation 2Solutions such as 4% dextrose/0.18% saline and 5% dextrose are important sources of free water for maintenance, but should be used with caution as excessive amounts may cause dangerous hyponatraemia, especially in children and the elderly. These solutions are not appropriate for resuscitation or replacement therapy except in conditions of significant free water deficit, eg diabetes insipidus. Evidence level 1b * Recommendation 3To meet maintenance requirements, adult patients should receive sodium 50-100 mmol/day, and potassium 40-80 mmol/day in 1.5-2.5 litres of water by the oral, enteral or parenteral route (or a combination of routes). Additional amounts should only be given to correct deficit or continuing losses. Careful monitoring should be undertaken using clinical examination, fluid balance charts, and regular weighing when possible. Evidence level 5 * Preoperative fluid management Recommendation 4In patients without disorders of gastric emptying undergoing elective surgery, clear non-particulate oral fluids should not be withheld for more than two hours prior to the induction of anaesthesia. Evidence level 1a * Recommendation 5In the absence of disorders of gastric emptying or diabetes, preoperative administration of carbohydrate-rich beverages 2-3 h before induction of anaesthesia may improve patient well being and facilitate recovery from surgery. It should be considered in the routine preoperative preparation for elective surgery. Evidence level 2a * Recommendation 6Routine use of preoperative mechanical bowel preparation is not beneficial and may complicate intra-and post-operative management of fluid and electrolyte balance. Its use should therefore be avoided whenever possible. Evidence level 1a* Recommendation 7Where mechanical bowel preparation is used, fluid and electrolyte derangements commonly occur and should be corrected by simultaneous intravenous fluid therapy with Hartmann' s or Ringer-lactate/acetate type solutions. Evidence level 5 * Recommendation 8Excessive losses from gastric aspiration/vomiting should be treated preoperatively with an appropriate crystalloid solution which includes an appropriate potassium supplement. Hypochloraemia is an indication for the use of 0.9% saline,
The levels of drug-metabolizing enzymes (DMEs) and transporter proteins in the human intestine are pertinent to determine oral drug bioavailability. Despite the paucity of reports on such measurements, it is well recognized that these values are essential for translating in vitro data on drug metabolism and transport to predict drug disposition in gut wall. In the current study, clinically relevant DMEs [cytochrome P450 (P450) and uridine 59-diphospho-glucuronosyltransferase (UGT)] and drug transporters were quantified in total mucosal protein preparations from the human jejunum (n 5 4) and ileum (n 5 12) using quantification concatemer-based targeted proteomics. In contrast to previous reports, UGT2B15 and organic anion-transporting polypeptide 1 (OATP1A2) were quantifiable in all our samples. Overall, no significant disparities in protein expression were observed between jejunum and ileum. Relative mRNA expression for drug transporters did not correlate with the abundance of their cognate protein, except for P-glycoprotein 1 (P-gp) and organic solute transporter subunit alpha (OST-a), highlighting the limitations of RNA as a surrogate for protein expression in dynamic tissues with high turnover. Intercorrelations were found within P450 [2C9-2C19 (P 5 0.002, R 2 5 0.63), 2C9-2J2 (P 5 0.004, R 2 5 0.40), 2D6-2J2 (P 5 0.002, R 2 5 0.50)] and UGT [1A1-2B7 (P 5 0.02, R 2 5 0.87)] family of enzymes. There were also correlations between P-gp and several other proteins [OST-a (P < 0.0001, R 2 5 0.77), UGT1A6 (P 5 0.009, R 2 5 0.38), and CYP3A4 (P 5 0.007, R 2 5 0.30)]. Incorporating such correlations into building virtual populations is crucial for obtaining plausible characteristics of simulated individuals. SIGNIFICANCE STATEMENTA number of drug transporters were quantified for the first time in this study. Several intercorrelations of protein abundance were reported. mRNA expression levels proved to be a poor reflection of differences between individuals regarding the level of protein expression in gut. The reported abundance of drug-metabolizing enzymes and transporters and their intercorrelations will contribute to better predictions of oral drug bioavailability and drug-drug interactions by linking in vitro observations to potential outcomes through physiologically based pharmacokinetic models.
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