Pyrogenic reactions and hemorrhage associated with intrinsic exposure to endotoxin-contaminated intravenous solutions.

OBJECTIVE: An epidemiological investigation was conducted to determine risk factors for adverse reactions among patients in hospitals and the possibility of extrinsic or intrinsic contamination of intravenous solutions. DESIGN: A retrospective cohort study was conducted to identify solutions associated with adverse reactions. Implicated lots were cultured for bacteria, and endotoxin concentrations were measured. SETTING: Five hospitals in the state of Pernambuco, Brazil, were investigated from February through March 2002. PATIENTS: Surgical inpatients or outpatients receiving intravenous solutions during the study period. RESULTS: Of 355 surgical patients or outpatients treated at hospitals, 28 (8%) developed illness within a mean of 2.5 hours after exposure to intravenous solutions implicated in adverse reactions; 5 (17.9%) of the case patients died. Laboratory testing of bottles from the lots of Ringer's lactate solution implicated in deaths demonstrated a high mean endotoxin concentration of 88.3 endotoxin units (EU)/mL (range, 9.7-298.0 EU/mL), compared with the permitted limit in Brazil of <0.5 EU/mL. Testing of metronidazole implicated in adverse reactions at another hospital and produced by the same company that manufactured the lots Ringer's lactate solution also showed high endotoxin concentrations (mean level, 8.3 EU/mL [range, 5.0-58.3 EU/mL]). The outbreak was controlled after a national recall of the implicated brand of intravenous solutions. CONCLUSIONS: Case patient status was associated with use of Ringer's lactate solution and metronidazole from large bottles, both of which were produced by the same company. High endotoxin concentrations were demonstrated in unopened bottles of implicated products, which is consistent with intrinsic contamination. The high mortality rate may have been compounded by the fact that clinicians administered additional volumes of contaminated 0.9% isotonic sodium chloride solution in response to hypotension or bleeding to some surgical patients. No additional case patients were identified after a national recall of products, inspection, closure of the implicated company's manufacturing facility, and establishment of random quality-control testing of intravenous solutions.