Plasma platelet-activating factor acetylhydrolase activity in critically ill patients.

OBJECTIVE: Platelet-activating factor (PAF) is a potent proinflammatory mediator in systemic inflammation and sepsis and is inactivated by the enzyme PAF-acetylhydrolase (PAF-AH). Recently, a large phase III clinical trial using recombinant PAF-AH to treat patients with severe sepsis was performed but failed to reduce 28-day mortality rate. To get more information on the activity of PAF-AH in sepsis, we repeatedly measured its activity in plasma in critically ill patients compared with healthy controls. DESIGN: Retrospective cohort study. SETTING: Intensive care unit. PATIENTS: Two hundred thirty-one patients who were admitted to an operative intensive care unit within 1 yr were enrolled and evaluated daily for American College of Chest Physicians/Society of Critical Care Medicine criteria. PAF-AH activity was measured as the release of [H]-acetate from [H]-acetyl-PAF. INTERVENTIONS: Analysis of plasma samples. MEASUREMENTS AND MAIN RESULTS: At the day of admission, PAF-AH activity of patients was below controls but markedly increased over time. Higher activities were seen in patients with severe sepsis or septic shock compared with those without organ failure. With respect to the clinical outcome, lower values were found in nonsurvivors only as long as they had not developed organ failure. In severe sepsis/septic shock, values of nonsurvivors exceeded those of survivors. PAF-AH activity was positively correlated with plasma levels of inflammatory mediators such as neopterine and tumor necrosis factor-alpha but not with acute phase reactants such as C-reactive protein, interleukin-6, or PCT. In addition, parenteral nutrition with lipid emulsions was seemingly associated with low PAF-AH activity compared with enteral nutrition. CONCLUSION: The data indicate severity- and time-dependent changes in PAF-AH activity and may help to explain the failure of recombinant PAF-AH treatment strategies that were not based on activity measurements.

Enteral naloxone reduces gastric tube reflux and frequency of pneumonia in critical care patients during opioid analgesia.

OBJECTIVE: Opioid analgesia impairs gastrointestinal motility. Enteral administration of naloxone theoretically allows selective blocking of intestinal opioid receptors caused by extensive presystemic metabolism. Therefore, we studied the effect of enteral naloxone on the amount of gastric tube reflux, the frequency of pneumonia, and the time until first defecation in mechanically ventilated patients with fentanyl analgesia. DESIGN: Prospective, randomized, double-blinded study. SETTING: University hospital intensive care unit. PATIENTS: Eighty-four mechanically ventilated, fentanyl-treated patients without gastrointestinal surgery or diseases. INTERVENTIONS: Patients were assigned to receive 8 mg naloxone or placebo four times daily via a gastric tube during fentanyl administration. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients received naloxone and 43 placebo; three patients were excluded because of protocol violation. Median gastric tube reflux volume (54 vs. 129 mL, p =.03) and frequency of pneumonia (34% vs. 56%, p =.04) were significantly lower in the naloxone group. In both groups, time until first defecation, ventilation time, and length of intensive care unit stay did not differ. There was no difference in fentanyl requirements between the naloxone and the placebo group (7 vs. 6.5 microg/kg/hr, p =.15). CONCLUSIONS: Our results provide evidence that the administration of enteral opioid antagonists in ventilated patients with opioid analgesia might be a simple-and possibly preventive-treatment of increased gastric tube reflux and reduces frequency of pneumonia.