PFPC Daily - April 16, 2005

NOTE: Some might remember the stories in 2001 surrounding the deaths
of over 50 people in Croatia, Spain, and elsewhere, linked to the
Althane Dialyzers, made by Baxter in the US. At first the filters
were blamed, others said the causes of death were not related to the
dialyzers. Baxter then acknowledged that perhaps a 'processing fluid
used in routine testing of blood filter products made at its
manufacturing plant in Ronneby, Sweden,' was partly responsible.

The culprit has been enlarved as PF-5070...


Canaud B, Aljama P, Tielemans C, Gasparovic V, Gutierrez A, Locatelli
F - "Pathochemical Toxicity of Perfluorocarbon-5070, a Liquid Test
Performance Fluid Previously Used in Dialyzer Manufacturing,
Confirmed in Animal Experiment" J Am Soc Nephrol. 2005 Apr 13; [Epub
ahead of print]

In the light of clustered deaths in late 2001 associated with
hemodialysis (HD), this article analyzes the pathochemical toxicity
of the perfluorocarbon-5070 (PF-5070), a liquid used as test
performance fluid for detecting capillary leaks during dialyzer
manufacturing. Residual PF-5070 in some Athane dialyzers of the
involved brands was infused in the injured patients during
hemodialysis. The clinical presentation was in contrast with other
previously described severe reactions to HD. Foam material was
discovered in the right ventricle and caval vein of the patients who
underwent postmortem examination. Deaths were attributed to gas
embolism without the external causes identified. To explore the
pathochemical toxicity of the inert liquid PF-5070, an animal model
was developed. In a rabbit model, single slug intravenous injections
as bolus of increasing doses of PF-5070 were performed. In a first
set of experiments, three groups of three rabbits were administered
increasing doses of PF-5070 at 4, 40, or 160 microl/kg. After
intravenous injection, the animals were observed for clinical signs
of adverse effects and underwent autopsy after death. Doses were
normalized to animal body weight to allow comparison with supposed
patient exposure. Five of nine rabbits died soon after PF-5070
dosing: One rabbit died within 4 h in the 4 microl/kg group, one
rabbit died within 30 min in the 40 microl/kg group, and three
rabbits died within 30 min in the 160 microl/kg group. In a second
set of experiments, six rabbits were injected with a lethal dose of
PF-5070 to analyze clinical symptoms and pathophysiology. All rabbits
died on the day of dosing and displayed neurologic disorders
(paralysis, nystagmus, rigidity, convulsions), then breathing
abnormalities (rapid breathing, salivation, dark mucous membrane),
and fatal collapse. Autopsy of rabbits showed evidence of gas
retention in the lung tissue and gas bubbles in the right cardiac
cavities. Histologic findings included alveolar hemorrhage with
pulmonary edema, cerebellum, and cortex patchy areas of infarction.
Single-dose intravenous administration of PF-5070 reproduced in a
rabbit model the pathophysiologic effects observed in the
hemodialysis patients. Severity of the symptoms observed in the
animals was dose-dependent. Clinical and pathologic findings can be
explained by the capacity of perfluorocarbon to emulsify blood at body
temperature, to increase partial pressure in the pulmonary capillary
bed, and to form bubbles in the pulmonary capillary circulation, thus
blocking lung and visceral perfusion. Such experimental findings
indicate the toxicity of PF-5070 administered intravenously and make
the pathochemical toxicity link with the hemodialysis-related deaths
caused by the presence of residues of PF-5070 in the Althane
dialyzers. We conclude, in light of this outbreak and the subsequent
investigations, that liquid PF-5070 is a highly toxic compound when
administered intravenously because of its emulsifying properties. The
use of PF-5070 or any liquid fluorocarbon compounds in medical
devices with blood contact and particularly in the dialyzer
manufacturing should be considered with caution.

PMID: 15829702