Lung and 'end organ' injury due to mechanical ventilation in animals: comparison between the prone and supine positions.

INTRODUCTION: Use of the prone position in patients with acute lung injury improves their oxygenation. Most of these patients die from multisystem organ failure and not from hypoxia, however. Moreover, there is some evidence that the organ failure is caused by increased cell apoptosis. In the present study we therefore examined whether the position of the patients affects histological changes and apoptosis in the lung and 'end organs', including the brain, heart, diaphragm, liver, kidneys and small intestine. METHODS: Ten mechanically ventilated sheep with a tidal volume of 15 ml/kg body weight were studied for 90 minutes. Five sheep were placed in the supine position and five sheep were placed in the prone position during the experiment. Lung changes were analyzed histologically using a semiquantitative scoring system and the extent of apoptosis was investigated with the TUNEL method. RESULTS: In the supine position intra-alveolar hemorrhage appeared predominantly in the dorsal areas, while the other histopathologic lesions were homogeneously distributed throughout the lungs. In the prone position, all histological changes were homogeneously distributed. A significantly higher score of lung injury was found in the supine position than in the prone position (4.63 +/- 0.58 and 2.17 +/- 0.19, respectively) (P < 0.0001). The histopathologic changes were accompanied by increased apoptosis (TUNEL method). In the supine position, the apoptotic index in the lung and in most of the 'end organs' was significantly higher compared with the prone position (all P < 0.005). Interestingly, the apoptotic index was higher in dorsal areas compared with ventral areas in both the prone and supine positions (P < 0.003 and P < 0.02, respectively). CONCLUSION: Our results suggest that the prone position appears to reduce the severity and the extent of lung injury, and is associated with decreased apoptosis in the lung and 'end organs'.

Phospholipases A2 and platelet-activating-factor acetylhydrolase in patients with acute respiratory distress syndrome.

OBJECTIVE: Phospholipases A2 (PLA2) comprise a family of enzymes probably implicated in the development of acute respiratory distress syndrome (ARDS). The aim was to investigate PLA2 activities and characteristics in bronchoalveolar lavage (BAL) fluid, BAL cells, and plasma from patients with ARDS by a fluorometric method. DESIGN: Prospective, controlled study. SETTING: Fourteen-bed polyvalent intensive care unit in a university hospital. PATIENTS: A total of 31 mechanically ventilated patients, 20 with and 11 without ARDS, were studied. INTERVENTION: BAL was performed by fiberoptic bronchoscopy in mechanically ventilated patients with a controlled mechanical ventilation mode. MEASUREMENTS: PLA2 and platelet-activating-factor acetylhydrolase were determined in BAL fluid, cells, and plasma. For the classification of PLA2-specific inhibitors, Western blot analysis and their biochemical characteristics were used. RESULTS: In ARDS patients, increased PLA2 levels were detected in BAL fluid, BAL cells, and plasma compared with the control patients. PLA2 in BAL fluid was mainly type IIA secretory and cytosolic types. In plasma, type IIA secretory and cytosolic and a Ca-independent PLA2 were found. In BAL cells, a cytosolic form, probably a Ca-independent intracellular form, and a low activity of type IIA secretory PLA2 was also observed. Total PLA2 activity correlated inversely with Pao2/Fio2 ratio and positively with the mortality rate. Patients with direct ARDS exhibited higher PLA2 activity compared with patients with indirect ARDS. Platelet-activating-factor acetylhydrolase activity was higher in BAL fluid and plasma, but it was lower in BAL cells. CONCLUSION: Ca-dependent, secretory, cytosolic, and Ca-independent forms of PLA2 and platelet-activating-factor acetylhydrolase could play important roles in the development or down-regulation of inflammation in ARDS, respectively.

Intrapericardial drug delivery: pharmacologic properties and long-term safety in swine.

BACKGROUND: Intrapericardial drug delivery is a promising new technique, but the pharmacologic properties of various agents delivered via this route are not known. Furthermore, the long-term safety of intrapericardial catheters has not been previously examined. METHODS: Using a pericardial access device, a catheter connected to a drug-delivery system was implanted in five pigs. Plasma levels and electrocardiographic measurements were obtained after intravenous and intrapericardial administration of digoxin and procainamide. Histological examination was performed after the device had been implanted for a total of 6 months. RESULTS: The QTc interval did not change significantly after digoxin or procainamide intravenous administration. QTc decreased by 47+/-23 ms (p=0.046) 8 h after digoxin intrapericardial administration and increased by 128+/-60 ms (p=0.002) 1 h after procainamide intrapericardial administration. The QRS duration did not change significantly after intravenous administration of either agent, but it increased by 17+/-9 ms (p=0.004) 1 h and by 15+/-4 ms (p=0.01) 8 h after procainamide intrapericardial administration. After intravenous procainamide the RR interval decreased, but it did not change significantly after intrapericardial administration of either agent. Histology showed moderate inflammatory infiltration and fibrosis adjacent to the catheter. CONCLUSIONS: Intrapericardial delivery of digitalis and procainamide produces unique electrophysiological properties. In contrast to satisfactory success of the implantation technique, long-term dwell of the catheter in the pericardium induces moderate, albeit probably clinically significant, fibrosis.

Selective decontamination of subglottic area in mechanically ventilated patients with multiple trauma.

OBJECTIVE: To determine whether selective decontamination locally in the subglottic area (SDSA) reduces tracheal colonization and prevents ventilator-associated pneumonia (VAP) in patients with multiple trauma. DESIGN AND SETTING: A prospective randomized, controlled, clinical study in a 14-bed general intensive care unit of a university hospital. PATIENTS: 79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 5 days; 61 patients completed the protocol. INTERVENTION: Patients were randomly assigned to receive SDSA using a continuous infusion of a suspension containing three nonabsorbable antibiotics (polymyxin, tombramycin, and amphotericin B; n=30) or placebo ( n=31). MEASUREMENTS: The incidence of bronchial and gastric colonization and the number of cases of VAP were recorded. Gastric fluid and tracheal secretion cultures were obtained soon after intubation and thereafter every 4 days. Etiological diagnosis of VAP was based on samples taken by a specific protected double catheter set. RESULTS: VAP developed in 5 of 30 (16.6%) patients receiving SDSA and 16 of 31 (51.6%) patients receiving placebo. Negative bronchial secretion cultures were found in 14 of 30 (46.6%) patients in the SDSA group and in only 3 of 31 (9.6%) patients in the control group. No patient with negative bronchial secretion culture developed VAP. No significant differences in outcome were found. CONCLUSIONS: The SDSA is an effective and safe type of chemoprophylaxis against tracheal colonization and can significantly reduce the incidence of VAP in mechanically ventilated patients with multiple trauma.