Adult respiratory distress syndrome associated with epidural fentanyl infusion.

OBJECTIVE: To determine the cause of unexplained postoperative adult respiratory distress syndrome (ARDS). DESIGN: Case-control study of postoperative ARDS. SETTING: Intensive care unit (ICU) of a Veterans Affairs hospital. PATIENTS: Six postoperative patients recovering from uncomplicated vascular or cardiothoracic surgery developed unexplained ARDS. Controls were 17 patients having similar procedures without the development of ARDS. INTERVENTION: Infusion of fentanyl with a tamper-proof device. MEASUREMENTS AND MAIN RESULTS: Development of ARDS. ARDS began 1 to 4 days after surgery, was characterized by maximum alveolar-arterial oxygen gradient that ranged from 232 to 544 torr (30.9 to 72.5 kPa), and was associated with death of two patients. We observed no association with patient location before ARDS onset, nonanalgesic medication administered, staff assignment, or mode of respiratory therapy. All six patients who developed unexplained ARDS had received epidural fentanyl compared with none of 17 control patients without ARDS (p = .0002). We instituted a tamper-proof mode of parenteral fentanyl administration, and subsequently observed one case of ARDS in 26 consecutive surgical patients (p = .000014). CONCLUSIONS: Based on these findings, as well as a prior history of fentanyl theft at our institution, we conclude that tampering with fentanyl infusate was responsible for the ARDS epidemic that we observed.

Inhibition of lymphoproliferation by middle ear effusion in experimental otitis media.

In this study, experimental otitis media was created in the chinchilla by direct middle ear challenge with Escherichia coli endotoxin, Streptococcus pneumoniae, Haemophilus influenzae, or Pseudomonas aeruginosa. The effusions recovered from the chinchillas in all four challenge groups were shown to inhibit the lymphoproliferative response of chinchilla peripheral blood lymphocytes to stimulation with phytohemagglutinin. The effect was dose dependent, and for effusions of infectious origin, the degree of inhibition was directly related to the duration of infection. Presence of the inhibitor in plasma was undocumented, suggesting a local production within the middle ear. Lymphocytes from middle ears infected with bacteria but not middle ears challenged with endotoxin were hyporesponsive or nonresponsive to stimulation with phytohemagglutinin. These results confirm the presence of an inhibitor of the lymphoproliferative response in experimental otitis media of different etiologies.

Purification and properties of Streptococcus pneumoniae neuraminidase.

Considerable amounts (200 units/ml) of neuraminidase activity were detected in middle ear effusion of children (age 1 month-10 years) and its presence was highly correlated with the presence of Streptococcus pneumoniae. When isolates of this organism are cultured, neuraminidase activity appears in the growth medium during the exponential phase of growth. In order to study the role of this enzyme in the pathology of otitis media we have developed a method for its purification. The enzyme was purified over 5,800-fold by removing the organism and passing the culture broth through a series of affinity and ion-exchange columns. The overall yield was 2 mg enzyme protein and the final specific activity was 1.8 X 10(6) units/mg protein. A molecular weight of 65,000 was estimated by SDS-PAGE and gel filtration chromatography. The Stokes radius of neuraminidase was calculated to be 32 A, its isoelectric point was 7.2, and its pH optimum was 6.0. In terms of specificity, the enzyme catalyzed the hydrolysis of sialic acid linkages in mucin, glycoproteins, and gangliosides: bovine submaxillary mucin supported the highest catalytic efficiency, and alpha-1-antitrypsin the lowest. Neuraminidase acted on at least three linkage classes of substrates, alpha-2,6 and alpha-2,3 linkages of N-acetylneuraminic acid to galactose, and alpha-2,6 linkages to N-acetyl-galactosamine.