Pepsin as a Marker for Pulmonary Aspiration

Pulmonary aspiration of gastric contents is the most serious complication of tube feeding. However, little consensus exists on how frequently it occurs in patients receiving mechanical ventilation because researchers who studied this problem used widely varied definitions of aspiration and methods for its detection. A well-controlled study by Torres et al1 suggested that aspiration occurs in 32% of patients receiving mechanical ventilation when the patients are semirecumbent and in 68% when they are supine. Aspiration of gastric contents has numerous deleterious consequences, including transient hypoxemia, chemical pneumonitis, and potentially life-threatening nosocomial pneumonia. Aspiration of gastric contents is one cause of ventilator-associated pneumonia, a condition that increases duration of mechanical ventilation, length of hospital stays, and use of medical resources. In a study2 of 120 critically ill patients receiving mechanical ventilation, patients with ventilator-associated pneumonia had a 16-day greater length of stay and almost a $30000 greater cost per case than did patients without pneumonia. Although observed single aspirations of a large volume of gastric contents sometimes occur, most tube-fed patients experience repeated unobserved aspirations of small volumes of gastric contents that can ultimately lead to pneumonia.3 Clinicians try to detect aspiration early so that interventions can be implemented to prevent further aspiration events and poor outcomes. In clinical settings, methods used to detect aspiration of tube feedings include (1) adding food dye to the enteral formula and then observing for dye-stained tracheal secretions and (2) using glucose oxidase reagent strips to test tracheal secretions for the presence of glucose-rich formula. Unfortunately, neither method is wholly satisfactory.4 For example, the sensitivity and safety of the dye method5-7 and the specificity of the glucose method8,9 have been questioned. Therefore, the search for effective, yet harmless, clinical methods to detect aspiration of gastric contents should continue. Because pepsin is plentiful in gastric juice, but not in tracheal secretions, several groups of investigators have suggested that pepsin would be a good marker or indicator for the aspiration of gastric juice.10,11 To test this hypothesis, Ufberg et al11 used unspecified methods to detect pepsin in specimens of gastric fluid and tracheal secretions obtained from 10 fasting preoperative patients. All 10 of the gastric specimens tested positive for pepsin, and all 10 of the tracheal specimens were negative. Ufberg et al concluded that a pepsin assay is a promising tool for the diagnosis of occult pulmonary aspiration of gastric contents. Using a pepsin assay developed by Anson12 (a method in which proteolytically active pepsin is allowed to digest a known quantity of hemoglobin), Badellino et al10 tested the same hypothesis in an animal model. Human gastric juice (2 mL/kg) was instilled intratracheally into 24 rabbits; similar volumes of isotonic sodium chloride solution were instilled intratracheally in 10 control rabbits. Bronchoalveolar lavage was performed 15 minutes, 30 minutes, or 60 minutes after the instillation of fluid. In the rabbits given human gastric juice, peptic activity was detected in the lavage fluid in 8 of 8 animals at 15 minutes, 6 of 8 at 30 minutes, and 5 of 8 at 60 minutes. Because the Anson method relies on the presence of proteolytically active pepsin to digest a hemoglobin substrate, it cannot be used to detect pepsin that has been degraded in the alkaline environment of the lung. This factor explains why fewer specimens tested positive for pepsin at the 30- and 60-minute times. No peptic activity was present in lavage fluid from control animals at any time. In another study,13 the Anson method was used to assay for pepsin in 102 specimens of tracheal secretions collected from acutely ill human subjects. Only 2 of the 102 specimens contained sizeable amounts of pepsin (66.2 and 83.1 μg/mL). Because a variety of other proteins in addition to pepsin are detected with the Anson method, these values may be overestimations of the actual amount of pepsin in the 2 samples.