Moderate Hypothermia for 48 Hours After Temporary Epidural Brain Compression Injury in a Canine Outcome Model

Abstract

In a previous study with this dog model, post-insult hypothermia of 31 degrees C for 5 h prevented secondary intraventricular pressure (IVP) rise, but during 35 degrees C or 38 degrees C, one-half of the dogs developed delayed IVP rise to brain death. We hypothesized that 31 degrees C extended to 48 h would prevent brain herniation. Using epidural balloon inflation, we increased contralateral IVP to 62 mm Hg for 90 min. Controlled ventilation was to 72 h and intensive care to 96 h. Group 1 dogs (n = 10) were normothermic controls (37.5 degrees C). Group 2 dogs (n = 10) were surface-cooled from 15 to 45 min of balloon inflation and maintained at moderate hypothermia (31 degrees C) to 48 h. Rewarming was from 48 to 72 h. Four additional dogs of hypothermia Group 2 had to be excluded from analysis for pneumonia and/or bleeding diathesis. After balloon deflation, IVP increased to 20 mm Hg or greater at 154 +/- 215 (range 15-720) min following the insult in Group 1 and at 1394 +/- 1191 (range 210-3420) min in Group 2 (p = 0.004), still during 31 degrees C but without further increase during hypothermia. Further IVP rise led to brain death in Group 1 in 6 of 10 dogs at 44 +/- 18 (range 21-72) h (all during controlled ventilation); and in Group 2, in 6 of 10 dogs at 87 +/- 11 (range 72-96) h (p = 0.001), all after rewarming, during spontaneous breathing. Survival to 96 h was achieved by 4 of 10 dogs in Group 1, and by 7 of 10 dogs in Group 2 (NS). Three of the six brain deaths in Group 2 occurred at 96 h. The macroscopically damaged brain volume was only numerically smaller in Group 2. The vermis downward shift was 6.8 +/- 3.5 mm in Group 1, versus 4.7 +/- 2.2 mm in Group 2 (p = 0.05). In an adjunctive study, in 4 additional normothermic dogs, hemispheric cerebral blood flow showed post-insult hypoperfusion bilaterally but no evidence of hyperemia preceding IVP rise to brain death. In conclusion, in this model, moderate hypothermia during and for 48 h after temporary epidural brain compression can maintain a low IVP during hypothermia but cannot prevent lethal brain swelling after rewarming and may cause coagulopathy and pulmonary complications.

Novel Resuscitation from Lethal Hemorrhage - Suspended Animation for Delayed Resuscitation

“…Elective therapeutic hypothermia has been shown to protect the brain and whole organism in animals or patients for up to 15 min CA at brain temperature of about 35'C (mild hypothermia) (16,17), for up to 20 min CA at about 30"C (moderate hypothermia) (18), for up to 30 min CA at about 20'C (deep hypothermia) (19), for up to 60 -150 min CA at 5 -10°C (profound hypothermia) (20)(21)(22)(23)(24)(25)(26)(27), and perhaps even for longer CA with ultraprofound hypothermia (28)(29)(30). The normal brain is not damaged by temperatures lowered to 5-10'C (31), but can be damaged by temperatures below 5'C (32,33).…”

“…None of the 22 necropsies revealed macroscopically necrotic ileum, as is often seen after severe shock states. 18 …”

“…Hypothermia exerts its beneficial effects not merely by a reduction of 02 requirement (uptake) (18,45), but through the synergism of multiple mechanisms, such as preservation of ATP; and reduction of excitotoxicity (47), edema (48), free radical reactions (49), and inflammation (50,51). Protective-preservative profound or ultra-profound hypothermia during CA 60 -180 min, induced with CPB before the insult, in animals, has been reported previously by us (20)(21)(22) and others (23)(24)(25)(26)(27)(28)(29)(30).…”

“…In study III of SA year 4 (18,19), we used a different model in dogs --namely normovolemic ventricular fibrillation cardiac arrest, simulating temporarily unresuscitable hearts --a major civilian public health problem. We are seeking the best bridging method to maintain viability of the organism, starting with the beginning of arrest to about 1 hour later, when in civilian practice sudden cardiac death patients can be rushed to hospital emergency rooms for (portable emergency) cardiopulmonary bypass; this can be prolonged until the heart recovers from stunning, is repaired or replaced, or the brain declared "dead" for organ donation.…”

“…The objectives of suspended animation include: amygdala in the 40C group: all values are 0). 1) helping to save victims of temporarily uncontrollable (internal) traumatic exsanguination (combat casualties 18 and civilian trauma victims'") At necropsy, all the animals in the 400 flush without severe brain trauma, by enabling evacuagroup 2 were macroscopically normal, except one tion and resuscitative surgery during circulatory dog, which had areas of mild hemorrhage in the to b e folwery delaye citaton2 gut ucoa. n te 24 flsh rou 1, ll ogshadarrest, to be followed by delayed resuscitation; 2) gut mucosa.…”