Sixty-six male Sprague-Dawley rats were divided into eight groups. Groups A, B, and C were surgically prepared but received no
trauma. Groups D through H received a nonpenetrating impact to the left cranium. Group A (n = 7) received no treatment. Groups B (n = 4) and C (n = 5) received 60 and 120 mg/kg IP
ketamine, respectively. Group D (n = 8) received no treatment. Groups E (n = 8) and F (n = 7) received 120 and 180 mg/kg IP
ketamine, respectively, 1 hour after
head trauma. Groups G (n = 7) and H (n = 9) were treated with 180 mg/kg IP
ketamine 2 and 4 hours after
head trauma, respectively. Neurological severity score (NSS, 0 through 25 from no injury to severe injury) was determined at 1, 24, and 48 hours after
head trauma. After death at 48 hours, cortical slices were taken adjacent to the lesion on the traumatized hemisphere and from comparable sites in the contralateral hemisphere for determination of tissue specific gravity and water content. Brains were then placed in 4%
formaldehyde, and the volume of hemorrhagic
necrosis was measured 4 days later. NSS was compared within and between groups using the Kruskal-Wallis test for repeated measurements and Mann-Whitney U test for post hoc testing. Water content, specific gravity, and hemorrhagic
necrosis were compared within and between groups using two-way ANOVA followed by Fisher's protected least significant difference procedure. A value of P < .05 was considered statistically significant.
RESULTS:
Head trauma alone increased NSS, decreased specific gravity, increased water content, and caused
cerebral infarction in the injured hemisphere.
Ketamine given in two time-dose regimens, 180 mg/kg IP at 2 hours (group G) and 120 mg/kg IP at 1 hour (group F) after
trauma, improved NSS from 11.6 +/- 1.7 and 14.4 +/- 0.8 at 1 hour to 4.4 +/- 1.3 and 8.0 +/- 1.4 (mean +/- SEM) at 48 hours, respectively (P < .03). Compared with the untreated group (group D), 180 mg/kg IP
ketamine given at 2 and 4 hours after
head trauma decreased the volume of hemorrhagic
necrosis from 37.1 +/- 9.5 mm3 to 10.1 +/- 3.8 and 15.3 +/- 3.6 mm3, respectively (P < .05). Brain tissue specific gravity and water content at 48 hours were not significantly different between treated and untreated groups. There was no difference in rectal and temporalis muscle temperature between groups.
CONCLUSIONS: We conclude that 180 mg/kg IP
ketamine was effective in ameliorating neurological dysfunction after
head trauma in rats when the administration time was delayed for 1 hour to 2 hours but not after 4 hours. When given at 1 hour after
head trauma,
ketamine at 120 mg/kg but not 60 mg/kg is effective in reducing neurological damage after
head trauma.