Am. J. Respir. Crit. Care Med.,
Volume 165, Number 4, February 2002, 514-520
Particulate Matter Contamination of Intravenous
Antibiotics Aggravates Loss of Functional Capillary
Density in Postischemic Striated Muscle
HANS-ANTON
LEHR,
JOACHIM
BRUNNER,
RAMZAN
RANGOONWALA,
and
C.
JAMES KIRKPATRICK
Institute of Pathology, University of Mainz, Mainz, Germany; and University of Frankfurt, Frankfurt, Germany
Through the increased use of less expensive and counterfeit medicines, the contamination of parenteral fluids and drugs by particulate matter poses an increasing health hazard worldwide. However, the mechanism of action of such contamination has never been conclusively demonstrated. We have systemically injected the particles contained in three different 1-g preparations of the
antibiotic cefotaxime into hamsters and visualized the functional capillary density in striated skin muscle, using intravital fluorescence microscopy. Injection of particles from either of the three preparations did not affect capillary perfusion in normal muscle (n = 3 hamsters, each). However, injection of particles from two generic
drug preparations, but not the original preparation or the saline
control, significantly reduced capillary perfusion in muscle tissue that
had previously been exposed to 4 h of pressure-induced ischemia and
2 h of reperfusion (n = 9 hamsters per group). Histological sections
demonstrated birefringent particles mechanically obliterating the
microcirculation of the striated muscle. The loss of capillary perfusion
due to particle injection or injection of standardized microspheres
was dependent on the extent of ischemia/reperfusion-induced muscle injury, with more capillaries lost in the more severely compromised muscle areas. These findings suggest that particle contaminants may not pose a major threat in intact tissue, but may severely compromise tissue perfusion in patients with prior microvascular compromise of vital organs (i.e., after trauma, major surgery, or
sepsis) and thus predispose to complications such as acute respiratory distress syndrome or multiple organ failure.
