Recent Development of Rigors during Infusion of Urokinase: Is it Related to an Endotoxin?

This study was undertaken to determine the prevalence of rigors associated with the use of urokinase (UK) and to assay for the presence of an endotoxin in the UK solution. Records of 75 patients who underwent 86 UK infusions between January 1988 and July 1992 were reviewed to evaluate for the development of UK-associated rigors. A modified chromogenic limulus amebocyte lysate (LAL) test was performed to determine the presence of endotoxin in four samples of UK from lots associated with rigors, one sample of UK not associated with rigors, sterile water, nonionic contrast medium, and ionic contrast medium. Between January 1, 1988, and July 10, 1990, 43 patients underwent 46 UK treatments (group 1) with no documented rigors (0% prevalence). In 45 of these 46 treatments, a standard, non-pulse-spray bolus of 75,000–500,000 IU of UK (mean dose, 182,222 IU) was used. Between July 11, 1990, and July 6, 1992, 38 patients underwent 40 UK treatments (group 2). In 33 of these 40 treatments, a standard bolus was given. Five patients received a pulse-spray bolus. The mean bolus was 213,768 IU (range, 100,000–500,000 IU). Eleven group 2 patients developed rigors (28% prevalence; P = .0005 vs group 1). The chromogenic LAL tests demonstrated no endotoxin in sterile water, nonionic contrast media, or ionic contrast media. Endotoxin was detected in small concentrations in the four samples of UK associated with rigors and in the UK sample not associated with rigors. The increase in the prevalence of rigors associated with the use of UK does not appear to be related to an endotoxin in UK, since the concentration of endotoxin detected is well below the threshold pyrogenic dose in humans.