Intestinal elimination of hydroxyethyl starch?

OBJECTIVE: Hydroxyethyl starch (HES) is mainly eliminated via the kidneys. Any information about extrarenal elimination obtained so far has been either incomplete or contradictory. The objective of this study was to quantify the intestinal excretion of infused HES with a mean molecular weight of 200,000 and a molar substitution of 0.5 (HES 200/0.5) and to compare the reappearance/recovery rate in urine and plasma. DESIGN: Prospective clinical study without control group. SETTING: The study was conducted at the Institute of Hypertension of the Society of Clinical Pharmacology, Vienna, Austria, which is an establishment for research in volunteers. PARTICIPANTS: The results of six out of seven healthy male volunteers were appropriate for analysis. One trial subject had to be excluded from the study because of severe protocol violation (mixing of stool and urine samples). INTERVENTIONS AND METHODS: Each volunteer was administered 500 ml of 10% HES 200/0.5 in a 0.9% NaCl solution intravenously within 1 h. A gut lavage with 6 l of a polysaccharide free solution was continuously administered from 3 h prior to until 2 h after the HES infusion to facilitate the collection of the samples and to exclude any source of error at analysis. HES was quantified with the hexokinase method. MEASUREMENTS AND RESULTS: Right from the beginning of the infusion until 10 h after its completion, the cumulative HES excretion with feces (principle parameter) and urine as well as selective plasma volume and HES plasma level were measured. Six and 14 h after the infusion had been completed, the recovery rates of HES in urine were about 30% and 40%, respectively, and in plasma about 23% and 8%, respectively. By contrast, not more than a kind of "background noise amount" of HES (about 0.2 %) could be recovered in feces ( mean value in % of the infused amount of the substance). Six and 14 h after the infusion had been completed, the total recovery rates of HES were 53% and 49%, respectively. CONCLUSION: In a physiologically unimpaired gut HES 200/0.5 is not, or only to an infinitesimal extent, eliminated via the intestine. The question if there is any alternative path to renal excretion for HES still remains to be answered. As the calculated reappearance/recovery rate of HES is only about 50 % of the administered dose, further investigations as to the final fate of HES appear necessary.

Conjugated bile acid replacement therapy for short-bowel syndrome.

BACKGROUND & AIMS: Although fat malabsorption in the short-bowel syndrome is caused in part by decreased bile acid secretion, bile acid replacement therapy is not used because of the belief that ingested bile acids would worsen diarrhea, outweighing the benefits of improved fat absorption. This study compared the effect of a natural conjugated bile acid mixture from ox bile with that of cholylsarcosine, a synthetic conjugated bile acid, on fat absorption and diarrhea in a patient with the short-bowel syndrome. Cholylsarcosine is resistant to bacterial metabolism and has no cathartic activity. METHODS: Metabolic balance studies and a clinical trial were performed in an emaciated patient with the short-bowel syndrome and ileostomy in whom parenteral nutrition could not be used. RESULTS: In balance studies, conjugated bile acid replacement therapy with either preparation caused fat absorption to increase by approximately 40 g/day. Calcium absorption also increased. Neither bile acid product caused a clinically significant increase in ileostomy water output. During a 4-month outpatient trial, while the patient ingested 2 g/meal natural bile acids, her weight increased from 80 to 98 lb, without side effects. CONCLUSIONS: Conjugated bile acid replacement therapy should be part of the armamentarium for the treatment of selected patients with the short-bowel syndrome.

Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease.

Hyperkalemia in patients with renal failure is frequently treated with a cation exchange resin (sodium polystyrene sulfonate, hereafter referred to as resin) in combination with a cathartic, but the effect of such therapy on serum potassium concentration has not been established. This study evaluates the effect of four single-dose resin-cathartic regimens and placebo on 5 different test days in six patients with chronic renal failure. Dietary intake was controlled. Fecal potassium output and serum potassium concentration were measured for 12 h. Phenolphthalein alone caused an average fecal potassium output of 54 mEq. The addition of resin caused an increase in insoluble potassium output but a decrease in soluble potassium output; therefore, there was no significant effect of resin on total potassium output. Sorbitol plus resin caused less potassium output than phenolphthalein plus resin. On placebo therapy, the average serum potassium concentration increased slightly (0.4 mEq/L) during the 12-h experiment. This rise was apparently abrogated by some of the regimens that included resin; this may have been due in part to extracellular volume expansion caused by absorption of sodium released from resin. Phenolphthalein regimens were associated with a slight rise in serum potassium concentrations (similar to placebo); this may have been due to extracellular volume contraction produced by high volume and sodium-rich diarrhea and acidosis secondary to bicarbonate losses. None of the regimens reduced serum potassium concentrations, compared with baseline levels. Because single-dose resin-cathartic therapy produces no or only trivial reductions in serum potassium concentration, and because this therapy is unpleasant and occasionally is associated with serious complications, this study questions the wisdom of its use in the management of acute hyperkalemic episodes.

[Intestinal lavage solution for orthograde intestinal irrigation]. / Darmspüllösung zur orthograden Darmspülung.

Gut lavage by ingestion of large volumes of electrolyte solutions has been shown to be an effective method of cleansing the colon before colonoscopy, barium enema or surgery. Absorption of water and electrolytes, which might be hazardous to patients who are unable to readily excrete an additional sodium and/or water load, is prevented by addition of non-absorbable substances to the solutions, but systematic studies are lacking. We have evaluated the influence of three solutions for gut lavage with different electrolyte composition (sodium concentration 67 mmol/l and 125 mmol/l) and addition of different non-absorbable substances (mannitol and polyethylene glycol [PEG]) on water and electrolyte homeostasis and subjective tolerance, both in healthy volunteers and in patients before endoscopy of the colon. In a randomized, blind study 6 liters of the three solutions were administered via a nasogastric tube to 6 healthy volunteers during 4 hours (i.e. 1.5 l/h). Body weight, serum concentrations of sodium, potassium and of phosphate were measured before infusion of the solution and after the last rhythmic rectal effluent. No significant changes were observed in any of the studied parameters and the incidence of side effects (nausea, abdominal cramps) was comparable. In an additional clinical double blind study, 26 patients before diagnostic colonoscopy were asked to drink 4 liters of the gut lavage solutions as quickly as possible in order to clean out the colon. The time for drinking was significantly shorter in patients using the mannitol and low sodium solution (204 +/- 70 minutes) than in patients drinking the solution with polyethylene glycol and a high sodium concentration (387 +/- 137 minutes). There was a tendency to a longer drinking period in patients ingesting the solution with polyethylene glycol and low sodium (306 +/- 106 minutes). Thus, the acceptance for solutions containing polyethylenglycol and high sodium concentration is reduced because of low palatibility. Again no influence on serum electrolyte concentrations or body weight could be observed in any patient, the spectrum of side effects was similar and the cleansing effect of all three solutions was adequate. In conclusion solutions for gut lavage containing a balanced electrolyte concentration and nonresorbable substances such as mannitol or polythylenglycol are equivalent. However, solutions containing mannitol and a low sodium concentration are better tolerated by the patients but the use of mannitol is limited because of the risk of releasing explosive gases during interventional endoscopy. To enhance the acceptance and palatibility of solutions for gut lavage containing polethylenglycol the addition of flavoured substances is recommended.