Gastric alkalinization, pneumonia, and systemic infections: the controversy

Gastric alkalinization has been suspected as a cause of pneumonia in critically ill patients. Although meta-analysis of the available data confirms an association between the administration of antacids/H2-antagonists and the risk of pneumonia, controversy remains whether stress ulcer prophylaxis with sucralfate reduces the risk of pneumonia. We hypothesized that the conflicting study results may be due to differences in patient population and general treatment regimens.

Microbiological studies have shown that a gastric pH > 4 is crucial for overgrowth of gastric gram-negative but not gram-positive bacteria. Sucralfate mainly influences the growth of gram-negative bacteria. Thus, in patient groups with a high frequency of gram-positive pneumonia, preservation of gastric acidity does not influence the pneumonia rate. Since 40-60% of critically ill patients show gastric pH values > 4 even without administration of acid-neutralizing agents, an increased risk of nosocomial pneumonia with antacids/H2-antagonists can only be expected if these agents substantially increase the frequency of patients with gastric pH > 4. No influence of stress ulcer prophylaxis on the pneumonia rate can be expected in patients on enteral nutrition, especially if administered continuously. In non-ventilated patients or in those with a short duration of ventilation no significant influence of stress ulcer prophylaxis on nosocomial pneumonia rate can be expected. The same is true for patient groups where regurgitation of gastric content is prevented, e.g. head-up position in neurosurgical patients. Furthermore, in patient groups with primary lung injury nosocomial pneumonia occurs due to specific pathomechanisms, e.g. lung contusion or inhalation injury. Based on these factors we have developed a scoring system and have performed a regression analysis between the sum of the risk scores and the odds ratio of nosocomial pneumonia of all available stress ulcer studies dealing with nosocomial pneumonia.

A highly significant correlation (p < 0.0001) could be demonstrated between the sum of the risk score and the odds ratio for pneumonia. An increased risk of nosocomial pneumonia due to stress ulcer prophylaxis with antacids/H2-antagonists occurred in patient groups with a risk score of > or = 2.

This analysis supports the hypothesis that gastric alkalinization significantly increases the risk of nosocomial pneumonia in long-term ventilated patients. However, this analysis also shows that only specific subgroups of patients benefit from acid-independent stress ulcer prophylaxis relative to nosocomial pneumonia. Furthermore, recent experimental and clinical studies support the hypothesis that gastric alkalinization may increase the risk of systemic infections and that sucralfate may have significant protective effects.