Effects of sucralfate vs antacids on gastric pathogens: results of a double-blind clinical trial.

BACKGROUND: Unblinded studies suggested that sucralfate prophylaxis for stress ulcers is associated with a lower rate of nosocomial pneumonia than acid-reducing approaches. We performed a randomized, double-blind, double-sham clinical trial comparing the exact microbial effects of each treatment. METHODS: One hundred forty patients entered this study before major elective surgery, allowing baseline cultures of gastric and pulmonary secretions to be obtained intraoperatively. Postoperatively, the patients were treated with standard doses of either sucralfate or antacids, plus a sham of the other drug. Cultures were repeated twice daily for 3 days. Molecular epidemiological typing was used to track the appearance of specific microbes and their transmission from site to site, and clinical end points were compared. The number of patients chosen was for sufficient statistical power to detect differences in the microbial measures, as detecting differences in clinical measures would have required increasing the sample size by an order of magnitude. RESULTS: Gastric pH was affected by the form of stress ulcer prophylaxis throughout the study, and this pH effect affected the number of new gastric organisms appearing in the 2 different groups. Colonization of the airway with new gastric organisms occurred more frequently in the antacid than in the sucralfate group, and colonization of the airway with organisms of gastric origin was associated with occurrence of postoperative pneumonia. CONCLUSIONS: Both sucralfate and antacids offered safe and effective stress ulcer prophylaxis in this double-blind clinical trial of postoperative patients in an intensive care unit. In association with the drug's effects on gastric pH, more new pathogens appeared in the gastric contents of antacid-treated than sucralfate-treated patients.

Gastric contractions, secretions and injury in cold restraint.

The clinical syndrome of stress ulceration has been studied for years using rodent cold restraint stress models, although the pathogenesis of the characteristic focal gastric mucosal lesions produced in these models has been controversial. We used gastric strain gauges to characterize fully the gastric motility effects of a 4-h cold restraint protocol, and we determined the relationship of variations in gastric contents and in gastric contractions to the amount of gastric mucosal injury. Additionally, we examined rat stomachs histologically, and determined the location of focal haemorrhagic mucosal lesions on the mucosal rugae. We found a consistent relationship between force of gastric contractions and gastric mucosal injury, and also a relationship between the initial duration of contractions during restraint and ultimate mucosal injury. Volume, acidity and mucus in the gastric contents were unrelated to mucosal injury. The majority (91%) of the mucosal lesions had some relationship to a rugal fold, with 59% of all lesions at the base of a rugal fold. Thus, the mechanical forces of gastric hypercontractility may contribute to the gastric mucosal injury of rodent cold restraint models.

Molecular epidemiology of gastric colonization by Enterococcus faecalis in a surgical intensive care unit.

We applied restriction endonuclease analysis of genomic DNA using pulsed field gel electrophoresis (PFGE) to study gastric colonization with Enterococcus faecalis among patients hospitalized in the surgical intensive care unit (SICU). Isolates were obtained by culturing prospectively the gastric contents of 140 patients in the SICU. In addition, cultures of respiratory specimens were obtained daily and cultures of blood, normally sterile body fluids, wounds, and urine were obtained when indicated clinically. A total of 177 isolates were obtained from 45 patients. Concentrations of E. faecalis in gastric fluid ranged from 1 x 10(2) colony forming units (CFU)/ml to greater than 5 x 10(7) CFU/ml (mean 8.0 x 10(6) CFU/ml). Overall, 33 different DNA types were identified by PEGE. In examining strain variation among isolates obtained from multiple anatomic sites over time, we found that the same DNA type was recovered from gastric aspirates, sputum, and wounds in a given patient and that these strains were carried over time. In general, given individuals were colonized with their own unique DNA type; however, one DNA type (type C) was shared by 11 different patients, and seven DNA types were shared by two individuals each. These results demonstrate the potential importance of gastric colonization as a reservoir for nosocomial strains of E. faecalis in an SICU setting.

Effects of resuscitation on acute gastric mucosal injury: reperfusion injury versus rapid mucosal restitution.

Gastric mucosal injury after hemorrhagic shock may be a consequence of both ischemia and reperfusion, as toxic oxygen-derived compounds are generated when ischemic tissues are reperfused. The present study was designed to estimate the magnitude of the reperfusion component of gastric mucosal injury, in comparison with the known capacity of the gastric mucosal surface to rapidly restore or restitute its surface after removal of various insults. Twelve dogs were subjected to 2 hr of hemorrhagic shock, with intragastric acid infused to produce gastric mucosal injury. Half were sacrificed 15 min after return of shed blood, while half were fully resuscitated with additional crystalloids and sacrificed 2 hr later. Gross and microscopic injury to the gastric mucosal surface were not increased by resuscitation. Particularly in the antrum, the resuscitated animals had significantly less gastric mucosal injury than unresuscitated animals. The amount of gastric mucosal injury was strongly inversely related to the success of resuscitation after 2 hr, specifically correlating with left ventricular pressure, cardiac index, mean arterial pressure, and systemic pH. Our data suggest that gastric mucosal restitution rather than reperfusion injury may predominant within a few hours of hemorrhagic shock and show that the degree of shock-induced gastric mucosal injury is inversely related to hemodynamic performance after resuscitation.

Postoperative pneumonia: a prospective study of risk factors and morbidity.

BACKGROUND: Postoperative pneumonia (PP) is a major complication that has been linked to microaspiration of pathogens originating in the gastrointestinal tract. This prospective study was performed to define the role of gastric bacterial aspiration in the development of PP. METHODS: Informed consent was obtained before operations from 140 veterans scheduled for major elective procedures requiring nasogastric tubes, and cultures were obtained of the gastric contents and sputum twice daily after operation. RESULTS: PP developed in 26 (18.6%) of 140 patients. The patients who had PP did not differ from those with no pneumonia after operation except for a history of chronic obstructive pulmonary disease, which was found in 38.5% of those with PP compared with 20% of patients with no pneumonia (p < 0.05). Morbidity was increased in association with PP, because length of stay in the surgical intensive care unit (6.2 vs 2.6 days), days intubated (2.7 vs 0.6), total postoperative days (15.3 vs 8.4), and mortality rates (19.2% vs 1.7%) were greater than in patients with no pneumonia. Gastric pathogens were present on entry in 38% of patients, and 32% of these had PP compared with 13% whose initial gastric cultures were sterile (p = 0.01). Colonization of sputum for greater than 24 hours with gastric pathogens occurred in 28% of patients. These patients had a 40% incidence of PP compared with 12% in patients without such evidence of microaspiration (p < 0.01). CONCLUSIONS: PP is a morbid postoperative complication associated with not only chronic obstructive pulmonary disease but also the presence of gastric bacteria during operation and transmission of gastric bacteria to the pulmonary tree after operation.

Liver dysfunction and energy source: results of a randomized clinical trial.

Controversy still exists regarding the role of the carbohydrate:fat ratio on liver function abnormalities associated with the administration of total parenteral nutrition (TPN). We designed a prospective clinical trail comparing standard carbohydrate-based TPN (8.5% amino acids, 50% dextrose, 7.5% of total calories from lipids) with an isocaloric lipid-based TPN (8.5% amino acids, 30% dextrose, 40% of total calories from lipids) in 43 patients exclusively receiving TPN > or = 2 weeks. Energy needs were calculated as basal energy expenditure x 1.5. The mean daily calorie intake for patients who obtained carbohydrate-based TPN (CHO) was 2227 kcal, whereas the lipid-based TPN (LIP-CHO) group achieved a mean of 2310 kcal. Patients with preexisting liver disease were excluded. There was no significant difference in age or diagnosis between the groups. We monitored total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyl transferase, lactic dehydrogenase, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase. Initial liver-associated tests did not vary significantly between groups. Group mean values after 2 weeks of TPN were significantly different for total bilirubin (1.5 mg/dL in the CHO group compared with 0.7 in the LIP-CHO group, p < .05) and direct bilirubin (0.8 mg/dL in the CHO group compared with 0.3 mg/dL in the mixed substrate group, p < .05). Differences in mean values between groups were also noted for serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and lactic dehydrogenase. In conclusion, this prospective trial reveals that the use of a balanced energy source TPN solution prevents the abnormalities in liver-associated tests commonly associated with TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intragastric and intravenous glucose on restraint model of stress ulceration.

Intragastric glucose prevents acute stress-induced gastric mucosal injury in the restrained rat. Because increased gastric contractions contribute to mucosal injury in this model and because parenteral glucose infusions have been shown to suppress gastric contractility, we hypothesized that centrally mediated responses to hyperglycemia might contribute to the cytoprotective effect of intragastric glucose. We compared intragastric and intravenous 25% glucose with saline infusions during cold restraint and measured their impact on gastric lesions, serum glucose levels, gastric residual volume (an indirect indicator of net gastric contractility), acidity, and mucin concentration. We found that both intravenous and intragastric glucose infusions increased serum glucose to over 500 mg/dl after 4 hr of stress. Intragastric glucose increased residual volume and gastric pH, as well as decreased gastric mucosal injury, but intravenous glucose had no effects on gastric function. We found that none of the potentially protective effects of intragastric glucose are mediated by central responses to hyperglycemia, and likewise that intravenous glucose has no effect on gastric mucosal injury.

Cholecystokinin does not mediate glucose's cytoprotective effects.

Cold restraint stress produces acute gastric mucosal injury in association with altered gastric motility. Enteral nutrients prevent this injury in conjunction with inhibition of gastric emptying. Because cholecystokinin (CCK) is released by nutrients known to be cytoprotective and is thought to inhibit gastric emptying, we performed three experiments to see if CCK contributes to the gastric mucosal protection afforded by enteral nutrients. Our data show that enteral glucose protects the gastric mucosa and increases gastric volume, gastric luminal pH, and gastric mucin. Neither physiologic nor pharmacologic doses of CCK protected the mucosa. None of the other significant effects of glucose on gastric function during cold restraint were affected by exogenous CCK. Furthermore, antagonism of CCK receptors with L-364,718 did not have any independent effects, nor did it diminish the protection associated with enteral glucose. We conclude that enteral glucose protects the gastric mucosa from cold restraint injury in association with a number of potentially beneficial effects on gastric physiology, but none of the effects of glucose in this model appear to be mediated by CCK.

Naloxone and restraint stress: effects on gastric mucosal injury and gastric function.

Contradictory findings have been reported from previous investigations of the effects of opiate receptor blockade on stress-related gastric injury. We performed two studies of the effects of naloxone on gastric mucosal injury and gastric function in cold restraint stress. In the first, naloxone had a linear, dose-dependent effect, reducing mucosal injury both parenterally and enterally. Gastric acidity was not related to the dose of naloxone, or to the amount or extent of mucosal injury. Gastric residual volume, by contrast, was related to both naloxone dose and gastric mucosal injury. In the second study we investigated the effect of gastric distention by enteral vehicle in the restraint model, and the interaction of the vehicle with the effects of naloxone. Periodic distention of the stomach with enteral vehicle did not alter the drug's effects on mucosal injury or on gastric residual volume. Because cold restraint stress produces harmful gastric contractions, naloxone is likely to be protective by altering gastric motility.

Enteral nutrients prevent stress ulceration and increase intragastric volume.

Tube feedings and intragastric glucose prevent stress ulceration by unknown mechanisms. We tested the hypothesis that glucose protects the gastric mucosa by direct repletion of glycogen stores. We compared the effects of enteral glucose with enteral lipids in the rat restraint model. The rats were given equal volumes of 0.9% saline, 20% lipids, or 25% glucose during a 4-h period of restraint stress. The effects of each treatment on gastric residual volume and luminal pH, as well as on stress lesion formation were measured. Both enteral nutrients significantly reduced the number of mucosal lesions compared to saline. In conjunction with their protective effect, both nutrients significantly increased both gastric residual volume and luminal pH. As stress-induced prolonged gastric contractions are related to mucosal injury in this model, the nutrient solutions may have been protective in part because they increased gastric volume and prevented mechanical trauma to the mucosa. We conclude that tube feedings do not prevent stress ulceration by glucose's repletion of local glycogen stores, as lipids and glucose were equally effective. Both increased intragastric volume and increased intraluminal pH associated with administration of enteral nutrients may contribute to their protection of the gastric mucosa from stress ulceration.

Pharmacokinetics of naloxone: an insight into the locus of effect on stress-ulceration.

The purpose of this study was to determine if the beneficial effect of naloxone on formation of acute gastric mucosal lesions was brought about via central or peripheral mechanisms by measuring blood concentrations of naloxone in rats during a 4-hr period of restraint stress. The study involved administration of naloxone to rats at doses of 5, 20 and 40 mg.kg-1.hr by either the intravenous or enteral routes. Blood samples were collected throughout the period of restraint and gastric stress-lesions were counted at the end of the experiments. Both routes of administration were equally effective in preventing stress-ulceration, with only rats receiving drug intravenously showing the presence of naloxone in blood samples. Inverse linear relationships existed between mean trough blood concentrations and lesions (P = .0003), as well as a linear correlation between area under the time-concentration curve and mean trough concentrations (P = .0001). Although our results show tight correlation between blood levels and effect on lesions in the group given drug intravenously, the effect must be on peripheral rather than central opiate receptors as no detectable blood levels were found when naloxone was given enterally.