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Prostacyclin reduces elevation of intracranial pressure and plasma volume loss in lipopolysaccharide-induced meningitis in the cat.

BACKGROUND
Severe meningitis may compromise cerebral perfusion through increases in intracranial pressure (ICP) and through hypovolemia caused by a general inflammation with systemic plasma leakage. From its antiaggregative/antiadhesive and permeability-reducing properties, prostacyclin (PGI2) is a potential adjuvant treatment in meningitis, but previously published data have been ambiguous. The objective of this study was to evaluate the effects of PGI2 on meningitis on ICP, plasma volume, blood pressure, and cerebral oxidative metabolism.


METHODS
Meningitis was induced by intrathecal injection of lipopolysaccharide (LPS, 0.8 x 10 units/kg) in cats. Four hours after the injection, the animals were randomized to intravenous treatment with either low-dose PGI2 (1 ng/kg/min) or the vehicle for 6 hours (n = 7 in each group). No LPS and no PGI2 or vehicle was given to three cats (sham group). Effects of treatment on ICP, mean arterial pressure, plasma volume (I-albumin technique), and brain tissue lactate/pyruvate ratio (microdialysis technique) were evaluated.


RESULTS
ICP increased from 10.0 mm Hg +/- 1.3 mm Hg and 10.8 mm Hg +/- 1.7 mm Hg to 19.9 mm Hg +/- 1.7 mm Hg and 19.6 mm Hg +/- 3.3 mm Hg in the PGI2 and the vehicle group, respectively, 4 hours after the LPS injection (not significant). ICP increased further to 21.8 mm Hg +/- 4.5 mm Hg and to 25.8 mm Hg +/- 6.0 mm Hg after treatment for 6 hours with PGI2 or vehicle, respectively (p < 0.05). There was no significant difference in arterial pressure between groups. Plasma volume loss was less in the PGI2 group than in the vehicle group at the end of the experiment and urine production and arterial oxygenation was higher in the PGI2 group. Lactate/pyruvate ratio was within the normal range in all groups.


CONCLUSION
Low-dose PGI2 may be a beneficial adjuvant therapy for meningitis by reducing elevation of ICP and plasma volume loss.