Effects of mild hypothermia and alkalizing agents on brain injuries in rats with acute subdural hematomas

Brain ischemia is the leading pathopysiological mechanism in the development of secondary brain damage after acute subdural hematoma (SDH). Hypothermia has been employed as an effective cerebroprotective treatment on brain injuries, but the control of the general condition is very difficult under hypothermia, and various severe complications have been reported. Cerebral acidosis in the ischemic area is one of the important factors augmenting the brain edema formation. Tris-(hydroxymethyl)-aminomethane (THAM) has been used as an alkalizing agent for acidosis on brain injury and is reported to be effective. In the present study, we used a rat acute SDH model to assess the effect of mild (35 degrees C) hypothermia and THAM combined treatment on brain water content, brain ischemia, and blood-brain barrier (BBB) permeability at 4 h after hematoma induction. Mild hypothermia did not significantly reduce the brain water content beneath the hematoma (79.5 +/- 0.2%) compared to normothermia (80.2 +/- 0.2%), but mild hypothermia combined to THAM resulted in a significant reduction (78.7 +/- 0.0%; p < 0.01). Combined with mild hypothermia, THAM treatment significantly reduced the Evan's blue extravasation (35 +/- 7 ng/g wet tissue; p < 0.05) compared to normothermia (63 +/- 7 ng/g wet tissue). Furthermore, the volume of infarction at 24 h after the hematoma induction (54 +/- 3 mm(3); p < 0.01) was significantly smaller by the combined treatment compared with normothermia (70 +/- 2 mm(3)). The present findings indicate that mild hypothermia of 35 degrees C combined with THAM presents a potent cerebroprotective strategy. The protection of the BBB is one of the possible cerebroprotective mechanisms in this rat acute SDH model.     

Acute subdural hematoma associated with diffuse brain injury and hypoxemia in the rat: effect of surgical evacuation of the hematoma

The aim of this study was to assess the effect of rapid or delayed surgical evacuation on the physiological consequence and brain edema formation in a rat model of acute subdural hematoma (SDH) coupled with either diffuse brain injury (DBI) or hypoxemia. The SDH was made by an autologous blood injection, while DBI was induced using the impact acceleration model (mild, 450 g/1 m; severe, 450 g/2 m). Physiological parameters measured included intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral blood flow (CBF), and brain tissue water content. At 1 h (rapid evacuation) or 4 h (delayed evacuation) after the SDH induction, surgical evacuation following a craniotomy was performed using saline irrigation and forceps. The study consisted of three different series, including 400 microL of SDH alone (Series 1), SDH400 + mild DBI (Series 2), and SDH300 + severe DBI + 20 min hypoxemia (Series 3). The hypoxemia was added in Group 3 to produce a steadily increasing ICP. In Series 1 and 2, all rats were randomized into the three following groups: non-, rapid, and delayed evacuation; Series 3 had two groups: non- and rapid evacuation. In Series 1, the surgical evacuation showed no beneficial effects on the brain edema formation assessed at 5 h post-injury. In Series 2, the rapid, but not delayed, evacuation significantly reduced both the increased ICP level and brain water content. The additional insult of hypoxemia (Series 3) resulted in a progressive ICP elevation, persistently depressed CBF, and severe brain swelling. Under this situation, the rapid evacuation exacerbated brain edema. These results have clinical implications for the management of severe traumatic SDH, especially its operative indication and timing.     

Continuous nicardipine infusion to control blood pressure after evacuation of acute cerebral hemorrhage

PURPOSE: To explore the long-term effects of the calcium antagonist, nicardipine, on cerebral hemodynamics in patients with acute cerebral hemorrhage, we investigated the effects of nicardipine infusion on intracranial pressure (ICP), middle cerebral arterial blood flow velocity (Vmca) , and computed tomographical (CT) findings of bleeding and edema. METHODS: Twenty-two patients with acute cerebral hemorrhage were infused with nicardipine for > 72 hr to decrease blood pressure. Blood pressure, heart rate, conscious level, Vmca, pulsatility index (PI, using transcranial Doppler), ICP, cerebral perfusion pressure (CPP) and platelet counts were monitored. CT examination was also performed to detect the changes of bleeding (hematoma) and/or brain edema. RESULTS: Blood pressure decreased (20 to 30% from control, P < 0.05) without any changes in heart rate. Platelet count did not change neither did Vmca and PI change on either the intact or injured side. The ICP decreased 24 hr after the end of infusion from 30 +/- 12 mmHg to 20 +/- 9 mmHg (P = 0.036) but was still higher than normal. The CPP decreased at 24 hr (75 +/- 14 mmHg, P = 0.026) and 72 hr (73 +/- 15 mmHg, P = 0.024) from the baseline (99 +/- 17 mmHg). Conscious level improved but not significantly and CT findings did not show any exacerbation in bleeding or edema. CONCLUSION: In patients with acute cerebral hemorrhage, nicardipine infusion to decrease blood pressure by 20 to 30% had no effect on Vmca, ICP, cerebral bleeding and edema, but decreased CPP.     

Propofol versus isoflurane anesthesia under hypothermic conditions: effects on intracranial pressure and local cerebral blood flow after diffuse traumatic brain injury in the rat

BACKGROUND: The aim of this study was to compare the cerebral protective effects of two known protective anesthetics, isoflurane and propofol, when these were used in combination with moderate hypothermia (33-34 degrees C) after diffuse traumatic brain injury (TBI) in the rat. We assessed cerebral protection by measuring local cerebral blood flow (LCBF), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and intracranial pressure (ICP). METHODS: Sixteen female Wistar rats weighing 275 to 350 g were anesthetized and subjected to an accelerated-impact weight-drop model of diffuse TBI. Hypothermia (33-34 degrees C) was induced 45 minutes after TBI (baseline), and was maintained for 180 minutes. The isoflurane group (n = 8) received 70% N(2)O in O(2), and isoflurane at 0.9 +/- 0.04%. The propofol group (n = 8) received 70% N(2)O in O(2) and a propofol infusion (12 mg/kg/hr). LCBF was measured by laser Doppler flowmeter. MABP, ICP, and brain and rectal temperatures were measured every 15 minutes from baseline through 180 minutes. Blood gas and hematocrit testing was also done at baseline and every 60 minutes thereafter to assess the animals' physiological state. RESULTS: In the isoflurane group, MABP and CPP decreased significantly from baseline to 180 minutes (p < 0.05 and p < 0.01, respectively), and MABP was significantly lower than the pressure in the propofol group from 45 minutes through 180 minutes (p < 0.05, p < 0.01). ICP and LCBF remained unchanged in this group. In the propofol group, from baseline to 180 minutes, CPP increased to maximum 120 +/- 8 mmHg at 75 minutes from 98 +/- 5 mmHg (p < 0.05) and ICP fell from 18 +/- 2 mmHg to 7 +/- 1 mmHg (p < 0.01); and the latter was significantly lower than ICP in the isoflurane group (p < 0.05, p < 0.01, p < 0.001). LCBF in this group was significantly higher than LCBF in the isoflurane group in the last 30 minutes of the experiment (p < 0.05). The propofol group showed no change in MABP over the course of the experiment. CONCLUSION: In the clinical setting, propofol anesthesia may be better for use in combination with hypothermia in cases of traumatic brain injury, as it reduces ICP and increases CPP under these conditions.     

Efficacy of moderate hypothermia in patients with severe head injury and intracranial hypertension refractory to mild hypothermia

OBJECT: This study was performed to determine whether moderate hypothermia (31 degrees C) improves clinical outcome in severely head injured patients whose intracranial hypertension cannot be controlled using mild hypothermia (34 degrees C). METHODS: Twenty-two consecutive severely head injured patients who fulfilled the following criteria were included in this study: an intracranial pressure (ICP) that remained higher than 40 mm Hg despite the use of mild hypothermia combined with conventional therapies; and a Glasgow Coma Scale score of 8 or less on admission. After the failure of mild hypothermia in combination with conventional therapies; patients were exposed to moderate hypothermia as quickly as possible. As brain temperature was reduced from 34 to 31 degrees C, the volume of intravenous fluid infusion was increased significantly from 1.9 +/- 0.9 to 2.6 +/- 1.2 mg/kg/hr (p < 0.01), and the dose of dopamine infusion increased significantly from 4.3 +/- 3.1 to 8.2 +/- 4.4 microg/kg/min (p < 0.01). Nevertheless, mean arterial blood pressure and heart rate decreased significantly from 97.1 +/- 13.1 to 85.1 +/- 10.5 mm Hg (p < 0.01) and from 92.2 +/- 13.8 to 72.2 +/- 14.3 beats/minute at (p < 0.01) at 34 and 31 degrees C, respectively. Arterial base excess was significantly aggravated from -3.3 +/- 4 at 34 degrees C to -5.6 +/- 5.4 mEq/L (at 31 degrees C; p < 0.05). Likewise, serum potassium concentration, white blood cell counts, and platelet counts at 31 degrees C decreased significantly compared with those at 34 degrees C (p < 0.01). In 19 (86%) of 22 patients, elevation of ICP could not be prevented using moderate hypothermia. In the remaining three patients. ICP was maintained below 40 mm Hg by inducing moderate hypothermia; however, these three patients died of multiple organ failure. These results clearly indicate that moderate hypothermia induces complications more severe than those induced by mild hypothermia without improving outcomes. CONCLUSIONS: The authors concluded that moderate hypothermia is not effective in improving clinical outcomes in severely head injured patients whose ICP remains higher than 40 mm Hg after treatment with mild hypothermia combined with conventional therapies.     

Effect of intracerebral and subdural hematomas on energy-dependent transport across the blood-brain barrier

Although both intracerebral and subdural hematomas induce brain edema, previous studies have indicated that they may have different cerebrovascular effects. Our own investigations have demonstrated that while subdural hematomas (SDH) are associated with ischemia this is not the case following intracerebral hematomas (ICH). Previous studies have demonstrated a decrease in energy-dependent transport of glutamine across the blood-brain barrier (BBB) following focal cerebral ischemia. The present study investigates this further by examining the effects of SDH, ICH, and intracerebral thrombin injections, an agent involved in ICH-induced injury, on blood to brain glutamine transport. The injection of 200 microL of blood into the subdural space induced a marked reduction in glutamine transport (Ki, influx rate constant) into the cerebral cortex at 4 and 24 h following SDH (sham, 105+/-4% of contralateral cortex; SDH 4 h, 63+/-5%, p<0.01; SDH 24 h, 47+/-12%, p<0.05). There were no significant changes in glutamine Ki in subcortical areas following SDH. Following ICH (200-microL clot); however, there were only modest decreases in glutamine Ki in subcortical areas (sham, 98+/-2% of right cortex; ICH 4 h, 91+/-5%, p<0.01; ICH 24 h, 91+/-2%, p<0.05). Intracerebral injection of thrombin (5U) had minimal effect on glutamine Ki, in subcortical areas, at 4 h and induced a modest decrease in transport at 24 h (sham, 98+/-2% of right cortex; thrombin 4 h, 98+/-2%; thrombin 24 h, 86+/-2%, p<0.05). The present studies demonstrate marked differences in the effects of ICH and SDH on BBB function.     

Local saline infusion into ischemic territory induces regional brain cooling and neuroprotection in rats with transient middle cerebral artery occlusion

OBJECTIVE: The neuroprotective effect of hypothermia has long been recognized. Use of hypothermia for stroke therapy, which is currently being induced by whole-body surface cooling, has been limited primarily because of management problems and severe side effects (e.g., pneumonia). The goal of this study was to determine whether local infusion of saline into ischemic territory could induce regional brain cooling and neuroprotection. METHODS: A novel procedure was used to block the middle cerebral artery of rats for 3 hours with a hollow filament and locally infuse the middle cerebral artery-supplied territory with 6 ml cold saline (20 degrees C) for 10 minutes before reperfusion. RESULTS: The cold saline infusion rapidly and significantly reduced temperature in cerebral cortex from 37.2 +/- 0.1 to 33.4 +/- 0.4 degrees C and in striatum from 37.5 +/- 0.2 to 33.9 +/- 0.4 degrees C. The significant hypothermia remained for up to 60 minutes after reperfusion. Significant (P < 0.01) reductions in infarct volume (approximately 90%) were evident after 48 hours of reperfusion. In ischemic rats that received the same amount of cold saline systemically through a femoral artery, a mild hypothermia was induced only in the cerebral cortex (35.3 +/- 0.2 degrees C) and returned to normal within 5 minutes. No significant reductions in infarct volume were observed in this group or in the ischemic group with local warm saline infusion or without infusion. Furthermore, brain-cooling infusion significantly (P < 0.01) improved motor behavior in ischemic rats after 14 days of reperfusion. This improvement continued for up to 28 days after reperfusion. CONCLUSION: Local prereperfusion infusion effectively induced hypothermia and ameliorated brain injury from stroke. Clinically, this procedure could be used in acute stroke treatment, possibly in combination with intra-arterial thrombolysis or mechanical disruption of clot by means of a microcatheter.     

The importance of brain temperature in patients after severe head injury: relationship to intracranial pressure,cerebral perfusion pressure,cerebral blood flow,and outcome

Brain temperature was continuously measured in 58 patients after severe head injury and compared to rectal temperature, intracranial pressure, cerebral blood flow, and outcome after 3 months. The temperature difference between brain and rectal temperature was also calculated. Mild hypothermia (34-36 degrees C) was also used to treat uncontrollable intracranial pressure (ICP) above 20 mm Hg when other methods failed. Brain and rectal temperature were strongly correlated (r = 0.866; p < 0.001). Four groups were identified. The mean brain temperature ranged from 36.9 +/- 0.4 degrees C in the normothermic group to 38.2 +/- 0.5 degrees C in the hyperthermic group, 35.3 +/- 0.5 degrees C in the mild therapeutic hypothermia group, and 34.3 +/- 1.5 degrees C in the hypothermia group without active cooling. The mean DeltaT(br-rect) was positive for patients with a T(br) above 36.0 degrees C (0.0 +/- 0.5 degrees C) and negative for patients during mild therapeutic hypothermia (-0.2 +/- 0.6 degrees C) and also in those with a brain temperature below 36 degrees C without active cooling (0.8 +/- -1.4 degrees C) - the spontaneous hypothermic group. The cerebral perfusion pressure (CPP) was increased significantly by active cooling compared to the normothermic and hyperthermic groups. The mean cerebral blood flow (CBF) in patients with a brain temperature between 36.0 degrees C and 37.5 degrees C was 37.8 +/- 14.0 mL/100 g/min. The lowest CBF was measured in patients with a brain temperature <36.0 degrees C and a negative brain-rectal temperature difference (17.1 +/- 14.0 mL/100 g/min). A positive trend for improved outcome was seen in patients with mild hypothermia. Simultaneous monitoring of brain and rectal temperature provides important diagnostic and prognostic information to guide the treatment of patients after severe head injury (SHI) and the wide differentials that can develop between the brain and core temperature, especially during rapid cooling, strongly supports the use of brain temperature measurement if therapeutic hypothermia is considered for head injury care.     

Hypothermic protection following middle cerebral artery occlusion in the rat

The effects of deep hypothermia on ischemic neuronal injury were examined using a permanent middle cerebral artery occlusion model in the rat. Animals were maintained at temporalis temperatures of either 24 degrees C or 36 degrees C and killed 6 hours after arterial occlusion. Normothermic rats displayed an average infarct volume of 25.1% +/- 1.6% of the right hemisphere, whereas hypothermic rats had an average infarct volume of 4.1% +/- 1.3% (p less than 0.001). The right/left hemispheric ratio was 1.05 +/- 0.02 in the normothermic group and 1.00 +/- 0.02 in the hypothermic group (p less than 0.05). These results suggest that hypothermia to 24 degrees C may reduce cerebral infarction and edema formation following middle cerebral artery occlusion in the rat.     

Ubiquitin reduces contusion volume after controlled cortical impact injury in rats

Recent data suggest that ubiquitin has anti-inflammatory properties and therapeutic potential after severe trauma and brain injuries. However, direct evidence for its neuroprotective effects has not yet been provided. We hypothesized that ubiquitin treatment is neuroprotective, and thus reduces brain edema formation and cortical contusion volume after closed traumatic brain injuries. To test this hypothesis, a focal cortical contusion was induced using a controlled cortical impact (CCI) model in Sprague-Dawley rats. Animals (n = 27) were randomized to either 1.5 mg/kg ubiquitin or vehicle (placebo) intravenously within 5 min after CCI. Blood pressure, arterial blood gases (ABG) and intracranial pressure (ICP) were monitored. Ubiquitin serum and cerebrospinal fluid levels were measured by ELISA. Brain water content was quantified gravimetrically after 24 h and cerebral contusion volume was determined in triphenyltetrazolium-chloride stained brains after 7 days. All animals recovered to normal activity. ICP and cerebral perfusion pressures were normal at the end of the observation period. Ubiquitin serum and CSF levels at 24 h and 7 days after CCI were similar in both groups. With ubiquitin brain water content of the injured hemisphere was slightly lower (n = 6/group; 79.97 +/- 0.29% vs. 81.11 +/- 0.52%; p = 0.08). Cortical contusion volume was significantly lower with ubiquitin (n = 7-8/group; 32.88 +/- 2.1 mm(3) vs. 43.96 +/- 4.56 mm(3); p = 0.025). This study shows that ubiquitin treatment after brain injury has direct neuroprotective effects, as demonstrated by improved brain morphology 7 days after brain injury. In connection with its beneficial effects in our previous studies, these data suggest ubiquitin as a promising candidate protein therapeutic for the treatment of brain injuries.     

Is cerebral perfusion pressure a major determinant of cerebral blood flow during head elevation in comatose patients with severe intracranial lesions?

OBJECT: Head elevation as a treatment for lower intracranial pressure (ICP) in patients with intracranial hypertension has been challenged in recent years. Therefore, the authors studied the effect of head position on cerebral hemodynamics in patients with severe head injury. METHODS: The effect of 0 degrees, 15 degrees, 30 degrees, and 45 degrees head elevation on ICP, cerebral blood flow (CBF), systemic arterial (PsaMonro) and jugular bulb (Pj) pressures calibrated to the level of the foramen of Monro, cerebral perfusion pressure (CPP), and the arteriovenous pressure gradient (PsaMonro - Pj) was studied in 37 patients who were comatose due to severe intracranial lesions. The CBF decreased gradually with head elevation from 0 to 45 degrees, from 46.3+/-4.8 to 28.7+/-2.3 ml x min(-1) x 100 g(-1) (mean +/- standard error, p<0.01), and the PsaMonro - Pj from 80+/-3 to 73+/-3 mm Hg (p< 0.01). The CPP remained stable between 0 degrees and 30 degrees of head elevation, at 62+/-3 mm Hg, and decreased from 62+/-3 to 57+/-4 mm Hg between 30 degrees and 45 degrees (p<0.05). A simulation showed that the 38% decrease in CBF between 0 degrees and 45 degrees resulted from PsaMonro - Pj changes for 19% of the decrease, from a diversion of the venous drainage from the internal jugular veins to vertebral venous plexus for 15%, and from CPP changes for 4%. CONCLUSIONS: During head elevation the arteriovenous pressure gradient is the major determinant of CBF. The influence of CPP on CBF decreases from 0 to 45 degrees of head elevation.     

Effect of mild hypothermia on brain dialysate lactate after fluid percussion brain injury in rodents

OBJECTIVE: To investigate the effects of mild hypothermia on brain microdialysate lactate after fluid percussion traumatic brain injury (TBI) in rats. METHODS: Brain dialysate lactate before and after fluid percussion brain injury (2.1 +/- 0.2 atm) was measured in rats with preinjury mild hypothermia (32 degrees C), postinjury mild hypothermia (32 degrees C), injury normothermia (37 degrees C), and the sham control group. Mild hypothermia (32 degrees C) was induced by partial immersion in a water bath (0 degrees C) under general anesthesia and maintained for 2 hours. RESULTS: In the normothermia TBI group, brain extracellular fluid lactate increased from 0.311 +/- 0.03 to 1.275 +/- 0.08 mmol/L within 30 minutes after TBI (P < 0.01) and remained at a high level (0.546 +/- 0.05 mmol/L) (P < 0.01) at 2 hours after injury. In the postinjury mild hypothermic group, brain extracellular fluid lactate increased from 0.303 +/- 0.03 to 0.875 +/- 0.05 mmol/L at 15 minutes after TBI (P < 0.01) and then gradually decreased to 0.316 +/- 0.04 mmol/L at 2 hours after TBI (P > 0.05). In the preinjury mild hypothermic group, brain extracellular fluid lactate remained at normal levels after injury (P > 0.05). CONCLUSION: The cerebral extracellular fluid lactate level increases significantly after fluid percussion brain injury. Preinjury mild hypothermia completely inhibits the cerebral lactate accumulation, and early postinjury mild hypothermia significantly blunts the increase of cerebral lactate level after fluid percussion injury.     

A new rat model of diffuse brain injury associated with acute subdural hematoma: assessment of varying hematoma volume,insult severity,and the presence of hypoxemia

The aim of this study was to develop a new rat model of diffuse brain injury (DBI) associated with acute subdural hemorrhage (SDH). In order to make this model more clinically relevant, we determined whether the varying hematoma volume, severity of DBI, or the presence of hypoxemia could influence the physiological consequence. SDH was made by an autologous blood injection, while DBI was induced using the impact acceleration model (mild, 450 g/1 m, severe, 450 g/2 m). Physiological parameters measured included intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral blood flow (CBF), and brain tissue water content. In the first series, 23 rats were randomized into the five following groups: Group 1, sham; Group 2, 400 (microL SDH; Group 3, SDH400 + mild DBI; Group 4, SDH400 + severe DBI; and Group 5, SDH300 + severe DBI. Results suggested that SDH300 + severe DBI (Group 5) may be the most suitable model, in which the MABP and CBF temporarily decreased during the SDH induction, but thereafter recovered to the baseline. Conversely, ICP was persistently elevated throughout the experiment. The water content was also significantly higher in both hemispheres compared to that of sham. In the second series, the animal was exposed to a hypoxemic insult (10 or 30 min) in addition to SDH300 + severe DBI (Group 6). The prolonged hypoxemia caused both a severe CBF reduction without recovery and a bilateral brain swelling, whereas the brief hypoxemia showed a gradual CBF recovery from the transient reduction and an increased water content only in the SDH side. These results suggest that these models may be potentially useful to study the combination of DBI and SDH with or without hypoxemia.     

High intracranial pressure effects on cerebral cortical microvascular flow in rats

To manage patients with high intracranial pressure (ICP), clinicians need to know the critical cerebral perfusion pressure (CPP) required to maintain cerebral blood flow (CBF). Historically, the critical CPP obtained by decreasing mean arterial pressure (MAP) to lower CPP was 60?mm Hg, which fell to 30?mm Hg when CPP was reduced by increasing ICP. We examined whether this decrease in critical CPP was due to a pathological shift from capillary (CAP) to high-velocity microvessel flow or thoroughfare channel (TFC) shunt flow. Cortical microvessel red blood cell velocity and NADH fluorescence were measured by in vivo two-photon laser scanning microscopy in rats at CPP of 70, 50, and 30?mm Hg by increasing ICP or decreasing MAP. Water content was measured by wet/dry weight, and cortical perfusion by laser Doppler flux. Reduction of CPP by raising ICP increased TFC shunt flow from 30.4±2.3% to 51.2±5.2% (mean±SEM, p<0.001), NADH increased by 20.3±6.8% and 58.1±8.2% (p<0.01), and brain water content from 72.9±0.47% to 77.8±2.42% (p<0.01). Decreasing CPP by MAP decreased TFC shunt flow with a smaller rise in NADH and no edema. Doppler flux decreased less with increasing ICP than decreasing MAP. The decrease seen in the critical CPP with increased ICP is likely due to a redistribution of microvascular flow from capillary to microvascular shunt flow or TFC shunt flow, resulting in a pathologically elevated CBF associated with tissue hypoxia and brain edema, characteristic of non-nutritive shunt flow.     

Early effects of acid-base management during hypothermia on cerebral infarct volume,edema, and cerebral blood flow in acute focal cerebral ischemia in rats

BACKGROUND: Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and alpha-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats. METHODS: Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33 degrees C). Animals were artificially ventilated with either alpha- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[(14)C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS). RESULTS: Compared with the alpha-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm(3) vs. 53.6 +/- 21.6 mm(3); P > or = 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0% vs. 3.1 +/- 2.4%; P > or = 0.05). Global CBF during pH-stat management exceeded that of alpha-stat animals (69.5 +/- 12.3 ml x 100 g(-1) x min(-1) vs. 54.7 +/- 13.3 ml x 100 g(-1) x min; P > or = 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml x 100 g(-1) x min(-1) in the pH-stat group versus 48.2 +/- 7.2 ml x 100 g(-1) x min(-1) in the alpha-stat group ( P> or = 0.05). CONCLUSIONS: In the very early reperfusion period (5 h), pH-stat management significantly decreases cerebral infarct volume and edema as compared with alpha-stat during moderate hypothermia, probably by increasing CBF.     

Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury.

OBJECT: Progressive intracranial hemorrhage after head injury is often observed on serial computerized tomography (CT) scans but its significance is uncertain. In this study, patients in whom two CT scans were obtained within 24 hours of injury were analyzed to determine the incidence, risk factors, and clinical significance of progressive hemorrhagic injury (PHI). METHODS: The diagnosis of PHI was determined by comparing the first and second CT scans and was categorized as epidural hematoma (EDH), subdural hematoma (SDH), intraparenchymal contusion or hematoma (IPCH), or subarachnoid hemorrhage (SAH). Potential risk factors, the daily mean intracranial pressure (ICP), and cerebral perfusion pressure were analyzed. In a cohort of 142 patients (mean age 34 +/- 14 years; median Glasgow Coma Scale score of 8, range 3-15; male/female ratio 4.3: 1), the mean time from injury to first CT scan was 2 +/- 1.6 hours and between first and second CT scans was 6.9 +/- 3.6 hours. A PHI was found in 42.3% of patients overall and in 48.6% of patients who underwent scanning within 2 hours of injury. Of the 60 patients with PHI, 87% underwent their first CT scan within 2 hours of injury and in only one with PHI was the first CT scan obtained more than 6 hours postinjury. The likelihood of PHI for a given lesion was 51% for IPCH, 22% for EDH, 17% for SAH, and 11% for SDH. Of the 46 patients who underwent craniotomy for hematoma evacuation, 24% did so after the second CT scan because of findings of PHI. Logistic regression was used to identify male sex (p = 0.01), older age (p = 0.01), time from injury to first CT scan (p = 0.02), and initial partial thromboplastin time (PTT) (p = 0.02) as the best predictors of PHI. The percentage of patients with mean daily ICP greater than 20 mm Hg was higher in those with PHI compared with those without PHI. The 6-month postinjury outcome was similar in the two patient groups. CONCLUSIONS: Early progressive hemorrhage occurs in almost 50% of head-injured patients who undergo CT scanning within 2 hours of injury, it occurs most frequently in cerebral contusions, and it is associated with ICP elevations. Male sex, older age, time from injury to first CT scan, and PTT appear to be key determinants of PHI. Early repeated CT scanning is indicated in patients with nonsurgically treated hemorrhage revealed on the first CT scan.     

Acute cerebral ischemia after intracranial bleeding in unilateral moyamoya disease: case report

A 31-year-old male presenting with intracranial hemorrhage manifesting as deep coma and anisocoria underwent immediate emergency surgery. Three-dimensional computed tomography (CT) angiography revealed stenosis of the right middle cerebral artery (MCA) and perfusion CT immediately after the surgery suggested severe hypoperfusion in the right MCA territory. Postoperative angiography demonstrated right unilateral moyamoya disease. We predicted that brain edema and intracranial pressure (ICP) elevation occurring after the hemorrhage might result in cerebral infarction. Hyperosmotic drugs were contraindicated by dehydration. Therefore, therapeutic hypothermia was induced that controlled the ICP. We considered that the increased ICP, dehydration, vasospasm, and shrinkage of the ruptured vessel comprised the pathogenesis of acute cerebral ischemia after intracranial bleeding. Cerebral hemodynamics should be evaluated during the acute phase of cerebral hemorrhage to prevent subsequent cerebral infarction.     

Small volume resuscitation with HyperHaes improves pericontusional perfusion and reduces lesion volume following controlled cortical impact injury in rats

The hyperosmolar and hyperoncotic properties of HyperHaes (HHES) might improve impaired posttraumatic cerebral perfusion. Possible beneficial effects on pericontusional perfusion, brain edema, and contusion volume were investigated in rats subjected to controlled cortical impact (CCI). Male Sprague-Dawley rats (n = 60) anesthetized with isoflurane were subjected to a left temporoparietal CCI. Thereafter, rats were randomized to receive HHES (10% hydroxyethylstarch, 7.5% NaCl) or physiological saline solution (4 mL/kg body weight) intravenously. Mean arterial blood pressure (MABP) and intracranial pressure (ICP) were determined before and following CCI, after drug administration and 24 h later. Regional pericontusional cortical perfusion was determined by scanning laser Doppler flowmetry before CCI, and 30 min, 4 and 24 h after injury. At 24 h brain swelling and water content were measured gravimetrically. At 7 days, cortical contusion volume was determined planimetrically. MABP was not influenced by HHES. ICP was significantly decreased immediately after HHES infusion (5.7 +/- 0.4 vs. 7.1 +/- 1.0 mm Hg; p < 0.05). Pericontusional cortical perfusion was significantly decreased by 44% compared to pre-injury levels (p < 0.05). HHES significantly improved cortical perfusion at 4 h after CCI, approaching baseline values (85 +/- 12%). While increased posttraumatic brain edema was not reduced by HHES at 24 h, cortical contusion volume was significantly decreased in the HHES-treated rats at 7 days after CCI (23.4 +/- 3.5 vs. 39.6 +/- 6.2 mm3; p < 0.05). Intravaneous administration of HHES within 15 min after CCI has a neuroprotective potential, as it significantly attenuated impaired pericontusional perfusion and markedly reduced the extent of induced structural damage.     

Study on therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury

BACKGROUND: The therapeutic mechanism and clinical effect of mild hypothermia in patients with severe head injury were studied. METHODS: All 396 patients with severe head injury [Glasgow Coma Scale score (GCS) equal to or less than 8 on admission] were randomly divided into the hypothermic group (198 cases) and the control group (198 cases). Hypothermia was induced within 24 hours of injury. Rewarming began 1 to 7 days (average 62.4 +/- 27.6 h) after the rectal temperature (RT) reached 32.0 to 35.0 degrees C. Meanwhile, the vital signs, intracranial pressure (ICP), blood gas values, blood electrolytes, brain tissue oxygen pressure (P(bt)O2), brain tissue temperature (BT), cerebral blood flow (CBF), and jugular venous oxygen saturation (S(jv)O2) were measured. The rectal temperature of control patients was induced to 36.5 to 37.0 degrees C. According to GOS, the prognosis of the patients was evaluated. RESULTS: In comparison with control group, during mild hypothermia the high level of ICP, hyperglycemia and blood lactic acid significantly decreased (p < 0.05) and cerebral flow improved dominantly. The vital signs, blood gas values, and blood electrolytes did not change significantly. Decreased mortality and good recovery were also found in hypothermia group. CONCLUSIONS: Mild hypothermia is safe and effective for preventing brain damage on patients with severe head injury, as well as reducing mortality and improving the prognosis. It is important to monitor P(bt)O2, BT, CBF, and S(jv)O2 in hypothermic therapy.     

急性重度颅脑外伤伴天幕裂孔疝的手术治疗

目的比较标准外伤大骨瓣开颅血肿清除去大骨瓣减压并天幕裂孔疝复位术与常规大骨瓣开颅血肿清除去大骨瓣减压术对急性重度颅脑损伤伴天幕裂孔疝的治疗效果。方法 40例急性重度颅脑伤伴天幕裂孔疝患者(GCS≤8分)随机分为两组,每组20例。研究组采用标准外伤大骨瓣开颅血肿清除去大骨瓣减压并脑疝腹位术,对照组采用常规大骨瓣开颅血肿清除大骨瓣减压术。术后1 d、3 d、7 d对两组GCS评分、颅内压、脑水肿范围和中线结构移位等指标进行比较。结果术后3 d、7 d研究组较对照组的GCS评分、颅内压、脑水肿范围和中线结构移位等指标有显著改善(P0.01)。术后1年随访,研究组和对照组生存率分别为85%和60%,重残及死亡率分别为25%和50%,组间比较有显著差异(P0.05或P0.01)。结论标准外伤大骨瓣开颅血肿清除去大骨瓣减压并天幕裂孔疝复位术能提高患者生存率,减少死残率,是手术治疗重度颅脑外伤伴天幕裂孔疝的有效方法。