Focal
cerebral contusions can be dynamic and expansive, leading to delayed neurological deterioration. Due to the high mortality associated with such
cerebral contusions, our standard practice had evolved into evacuating
contusions in patients who had a deterioration in level of consciousness, lesions > 30 cc and CT suggestion of raised ICP. Experimental
brain edema studies have implicated
kinins in causing 2 degrees
brain swelling.
CP-0127 (Bradycor), a specific
bradykinin antagonist, has been found to reduce
cerebral edema in a cold lesion model in rats. In a randomized, single blind pilot study,
a 7 day infusion of
CP-0127 (3.0 micrograms/kg/min) was compared to placebo in patients with focal
cerebral contusions presenting within 24-96 hours of
closed head injury with an initial GCS 9-14. The ICP, GCS, and vital signs were monitored hourly. The total lesion burden (TLB) was measured on serial CT scans. There were no differences in age, baseline GCS, TLB, initial ICP, or laboratory findings between the two groups (n = 20). The mean (+/- s.d.) rise in peak ICP from baseline was greater in the placebo group than with
CP-0127 (21.9 +/- 4.7 vs 9.5 +/- 2.0, P = 0.018). In addition, the mean reduction in GCS in the placebo group was significantly greater than in the
CP-0127 group (4 +/- 1.0 vs 0.6 +/- 0.4, P = 0.002). Significantly raised ICP and clinically significant neurological deterioration occurred in 7/9 patients on placebo (77%) and only in 1 patient (9%; n = 11) on
CP-0127, mandating surgery (P = 0.005). There were no
adverse drug reactions, significant changes in vital signs or variations in the laboratory values. The cerebral perfusion pressure was adequately maintained in all patients irrespective of
therapy. These preliminary results with
CP-0127 provide supporting evidence that the
kinin-
kallikrein system could be involved in
cerebral edema. In this study, treatment with
CP-0127 appeared to alter the natural history of traumatic
brain contusions by preventing the 2 degrees
brain swelling. In addition,
CP-0127 obviated the need for surgery in the majority of treated patients.
CP-0127 could act on the cerebral vasculature to limit dys-autoregulation and
brain swelling or on the blood brain barrier to reduce
cerebral edema.