The role of intragastric acidity and stress ulcus prophylaxis on colonization and infection in mechanically ventilated ICU patients. A stratified, randomized, double-blind study of sucralfate versus antacids.

UNLABELLED: This study evaluates the effects of sucralfate and antacids on intragastric acidity, colonization of stomach, oropharynx and trachea, and the incidence of ventilator-associated pneumonia (VAP) in mechanically ventilated patients in intensive care units. We conducted a prospective randomized double-blind trial in which patients were stratified on initial gastric pH. Intragastric acidity was measured with computerized, continuous intragastric monitoring. The diagnosis of VAP was established with protected specimen brush and/or bronchoalveolar lavage. The study included consecutive eligible patients with mechanical ventilation and nasogastric tube. INTERVENTIONS: After stratification on initial intragastric pH into two groups, patients from both groups were randomly assigned to receive either antacids (a suspension of aluminum hydroxide and magnesium hydroxide), 30 mL every 4 h, or sucralfate, 1 g every 4 h. Continuous intragastric pH monitoring was performed in 112 patients (58 antacids, 54 sucralfate). Using predetermined criteria, colonization of stomach, oropharynx, and trachea, and the incidence of VAP were assessed. Altogether, 141 patients were included (74 receiving antacids, 67 sucralfate) and continuous intragastric pH monitoring was performed in 112 patients, with a mean of 75 h per patient. The median pH and the percentage of time with a pH < 4.0 were calculated from each measurement. No significant differences in median pH values (4.7 +/- 2.2 and 4.5 +/- 2.0 for antacids and sucralfate, respectively) were observed. Median pH values were higher in patients with gastric bacterial colonization than in noncolonized patients (5.5 +/- 2.1 and 3.3 +/- 2.0, p < 0.01), but colonization of oropharynx and trachea was not related to intragastric acidity. Thirty-one patients (22%) developed VAP, with a similar incidence in both treatment groups. In addition, antibiotic use, duration of hospitalization, and mortality rates were similar in both groups. Enteral feeding did not change intragastric acidity significantly but increased gastric colonization with Enterobacteriaceae, without influencing oropharyngeal and tracheal colonization. Antacids and sucralfate had a similar effect on intragastric acidity, colonization rates, and incidence of VAP. Intragastric acidity influenced gastric colonization but not colonization of the upper respiratory tract or the incidence of VAP. Therefore, it is unlikely that the gastropulmonary route is important for the development of VAP.

Colonization in patients receiving and not receiving topical antimicrobial prophylaxis.

The influence of topical antimicrobial prophylaxis (TAP) on colonization of oropharynx and trachea was studied in patients receiving and not receiving prophylaxis. Twenty-two patients in Intensive Care Unit (ICU) I (Group 1) received TAP (tobramycin, colistin, and amphotericine B in oropharynx and stomach). Simultaneous to Group 1, 21 patients (Group 2) not receiving TAP were studied in ICU I. A control group of patients admitted to another, identical, ICU (ICU II), where no TAP was administered, were studied simultaneously (Group 3a, n = 23). A second control group (Group 3b, n = 31), was formed by collecting data from patients admitted to ICU I in Period II. Patients receiving TAP were less frequently colonized than patients not receiving prophylaxis. Moreover, of the patients not receiving TAP, those staying in the ICU where TAP was administered (Group 2) were less frequently colonized than patients in another ICU (Group 3). Of the patients not colonized on admission, those staying in the ICU where TAP was administered remained free of colonization for a longer time. In the ICU where no TAP was administered, more patients were colonized simultaneously and cross-acquisition occurred more frequently. TAP significantly influenced colonization of oropharynx and trachea in patients receiving and not receiving prophylaxis within the same ICU as compared with patients not receiving prophylaxis in another identical ICU.

The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients.

STUDY OBJECTIVE: To study sequences of colonization of different species of microorganisms and to determine the importance of gastric colonization for the development of nosocomial pneumonia. DESIGN: A prospective study. SETTING: Two identical ICUs of a university hospital. PATIENTS: Sixty-four patients admitted to ICU for at least 5 days; 59 were intubated. INTERVENTIONS: Microbiologic cultures of serially taken samples of gastric aspirates, oropharyngeal swabs, and tracheal aspirates were performed at the time of ICU admission and subsequently twice a week. Diagnosis of pneumonia was based on quantitative cultures from bronchoalveolar lavage (BAL) and protected specimen brush (PSB). Sequences of colonization were examined by comparing isolates of the same species, with concordance of minimum inhibitory concentration values to six antibiotics. MEASUREMENTS AND RESULTS: Eleven patients developed 14 episodes of nosocomial pneumonia, yielding 20 species of microorganisms. Seventeen of 20 species (85 percent), associated with pneumonia, were cultured, previous to or on the day of diagnosis, from tracheal aspirates, and 6 of 20 (30 percent) species were cultured from gastric samples. A sequence of colonization from the stomach to the upper respiratory tract eventually leading to pneumonia was not observed in any of the six species. Initial colonization with Pseudomonas aeruginosa and Enterobacter species was more often demonstrated in the trachea (16/24 and 13/25 cases) as compared with the stomach (1/24 and 6/25 cases; p < 0.0001 and p = 0.02 respectively). In contrast, initial colonization with Klebsiella species and Enterococcus faecalis was more frequently demonstrated in the stomach (13/28 and 8/15 cases) as compared with the trachea (6/28 and 0/15 cases; p = 0.02 and p < 0.0001, respectively). CONCLUSIONS: Based on studying sequences of colonization in ICU patients, we concluded that the stomach is unlikely to be an important source of pathogens leading to nosocomial pneumonia as diagnosed by BAL/PSB. Furthermore, the initial site and route of colonization might not be the same for all microorganisms.

Topical antimicrobial prophylaxis of nosocomial pneumonia in mechanically ventilated patients. Microbiological observations.

Generally, reduction of colonization and infection with potentially pathogenic microorganisms in intensive care units (ICU) is attempted by a combination of antimicrobial agents administered topically in the digestive tract and systematically. We tested the efficacy of topical antimicrobial prophylaxis of the oropharynx and stomach administered in combination with sucralfate without systemic prophylaxis in 25 mechanically ventilated ICU patients. The regimen successfully reduced colonization with potentially pathogenic microorganisms in the oropharynx and trachea without modifying the intestinal flora. However, colonization and infections with gram-positive cocci and gram-negative rods other than Enterobacteriaceae and Pseudomonadaceae and resistant to one or both the antimicrobial agents used were observed.

Urinary catecholamines in iron-deficient rats at rest and following surgical stress.

The purpose of this study was to determine catecholamine concentrations both at rest and in response to a surgical stress in iron-deficient and control rats. Twenty-one-day-old rats were randomized to one of two groups which received a diet containing either 6 or 50 mg iron/kg. Three to five days later, when anemia was first detectable, urinary norepinephrine (NE) concentrations were already significantly elevated in the iron-deficient compared to control rats. In contrast, urinary dopamine (DA) became depressed after 10 days of the iron-deficient regimen. At 38 days of age, both groups were subjected to a surgical stress. NE and DA became elevated over baseline values in both diet groups during the 24-h period following surgery; NE remained significantly higher and DA significantly lower in the iron-deficient than in the control group. We conclude that changes in urine catecholamine concentration occur early in the development of iron deficiency and that they are characteristic of both baseline and stress conditions.