Tomoya Miyagi

Optimal temperature for the management of severe traumatic brain injury: effect of hypothermia on intracranial pressure, systemic and intracranial hemodynamics, and metabolism.

OBJECTIVEWe studied the effect of hypothermia on intracranial pressure, systemic and intracranial hemodynamics, and metabolism in patients with severe traumatic brain injury to clarify the optimal temperature for hypothermia, with a view toward establishing the proper management techniques for such patients. METHODSThe study was performed in 31 patients with severe head injury (Glasgow Coma Scale score as high as 5). All patients were sedated, paralyzed, ventilated, and cooled to 33°C. Brain temperature, core temperature, intracranial pressure, cerebral perfusion pressure, jugular venous oxygen saturation, mixed venous oxygen saturation, cardiac output, oxygen delivery, oxygen consumption, and resting energy expenditure were monitored continuously. RESULTSIntracranial pressure decreased significantly at brain temperatures below 37°C and decreased more sharply at temperatures 35 to 36°C, but no differences were observed at temperatures below 35°C. Cerebral perfusion pressure peaked at 35.0 to 35.9°C and decreased with further decreases in temperature. Jugular venous oxygen saturation and mixed venous oxygen saturation remained in the normal range during hypothermia. Resting energy expenditure and cardiac output decreased progressively with hypothermia. Oxygen delivery and oxygen consumption decreased to abnormally low levels at rectal temperatures below 35°C, and the correlation between them became less significant at less than 35°C than that when temperatures were 35°C or higher. Brain temperature was consistently higher than rectal temperature by 0.5 ± 0.3°C. CONCLUSIONThese results suggest that, after traumatic brain injury, decreasing body temperature to 35 to 35.5°C can reduce intracranial hypertension while maintaining sufficient cerebral perfusion pressure without cardiac dysfunction or oxygen debt. Thus, 35 to 35.5°C seems to be the optimal temperature at which to treat patients with severe traumatic brain injury.

Effect of 35°C Hypothermia on Intracranial Pressure and Clinical Outcome in Patients With Severe Traumatic Brain Injury

BACKGROUND From 1994, we have used therapeutic hypothermia in patients with severe traumatic brain injury (Glasgow Coma Scale scores of 5 or less). In 2000, we altered the target temperature to 35 degrees C from the former 33 degrees C, as our findings suggested that cooling to 35 degrees C is sufficient to control intracranial hypertension, and that hypothermia below 35 degrees C may predispose patients to persistent cumulative oxygen debt. We attempted to clarify whether 35 degrees C hypothermia has the same effect as 33 degrees C hypothermia in reducing intracranial hypertension and whether it is associated with fewer complications and improved outcomes. METHODS We compared intracranial pressure (ICP) and biochemical parameters in the 30 patients treated with 35 degrees C hypothermia (January 2000 to June 2005) with those in the 31 patients treated with 33 degrees C hypothermia (July 1994 to December 1999). RESULTS Patient characteristics were similar in the two groups. The mean temperature during hypothermia was 35.1 +/- 0.7 degrees C in the 35 degrees C hypothermia group and 33.4 +/- 0.8 degrees C in the 33 degrees C hypothermia group. Mean ICP was controlled under 20 mm Hg during hypothermia in both the 35 degrees C hypothermia and 33 degrees C hypothermia groups. The incidence of intracranial hypertension and low cerebral perfusion pressure did not differ between the two groups. The 35 degrees C hypothermic patients exhibited a significant improvement in the decline of serum potassium concentrations during hypothermia and in the increment of C-reactive protein after rewarming. The mortality rate and the incidence of systemic complications tended to be lower in the 35 degrees C group. CONCLUSIONS Cooling patients to 35 degrees C is safe and the ICP reduction effects of 35 degrees C hypothermia are similar to those of 33 degrees C hypothermia.

Age-Associated Increases in Poor Outcomes after Traumatic Brain Injury: A Report from the Japan Neurotrauma Data Bank

Age is an important factor influencing outcome after severe traumatic brain injury (TBI). In general, the older the victim, the higher the probability of a poor outcome. To investigate the mechanism underlying the link between age and outcome, the data for 797 patients enrolled in the Japan Neurotrauma Data Bank (JNTDB), aged 6 years or older, with Glasgow Coma Scale (GCS) scores of 8 or less on admission or deterioration to that level within 48 h of impact were analyzed. Thirty-eight percent of the patients were between the ages of 40 and 69 years, and 24% of the patients were older than 69 years. Older patients had higher rates of mortality and lower rates of favorable outcome. The frequency of mass lesions which were associated with poorer outcomes significantly increased with age, but regardless of the intracranial lesion type, older patients had poorer outcomes. The GCS score and the occurrence of systemic complications did not differ significantly according to age. Multiple systemic injury was less frequent in older patients. The varied occurrence of intracranial lesion types according to age is likely caused by the disparity between the young and aged brain in the progression of secondary brain injury. Alteration in the pathophysiological response, which is related to the development of secondary brain injury in the aging brain, probably contributes to more severe and irreversible brain damage in older patients, and is thus associated with poor outcomes.

Effect of hypothermia on serum electrolyte, inflammation, coagulation, and nutritional parameters in patients with severe traumatic brain injury.

Introduction: We evaluated the effect of induced hypothermia on biochemical parameters in patients with severe traumatic brain injury.Methods: We obtained hemoglobin, hematocrit, white blood count, lymphocyte count, platelet count, and serum concentrations of sodium, potassium, glucose, albumin, and C-reactive protein, and prothrombin time, hepaplastin test, activated partial thromboplastin time, antithrombin-III, α2PI, and nitrogen excretion on the day of admission, and on days 1, 3, 5, 7, 14, and 21 after the injury in 31 patients with severe head injury who were treated with hypothermia of 33°ranging from 48 to 72 hours. We selected 33 normothermic patients as a control group; these patients were selected from patients who had been treated before hypothermia was used as a treatment modality, by the same criteria for hypothermia therapy. We compared the biochemical markers and rectal temperature and intracranial pressure in the hypothermia group with those in the normothermia group. Outcome was assessed using the Glasgow Outcome Scale at 6 months after injury.Results: The demographic characteristics, severity, and outcome were similar in the hypothermia and normothermia group. Intracranial pressure was significantly decreased by hypothermia. Serum potassium concentration decreased significantly during hypothermia. White blood cell counts and C-reactive protein levels were higher after rewarming in the hypothermia group, and these were also higher in the patients with infectious complications, although the incidence of infectious complications did not differ between the hypothermia and normothermia groups. There were no statistically significant prolongations of activated partial thromboplastin time and no decline in prothrombin time with hypothermia. Platelet count, antithrombin-III, and α2PI did not differ significantly between the two groups.Conclusion: Hypothermia of 33° for 48–72 hours does not appear to increase the risk for coagulopathy and infections, although hypothermic patients exhibited significant increments in inflammatory markers such as C-reactive protein and white blood counts after rewarming.

Neurochemical monitoring in the management of severe head-injured patients with hypothermia

Abstract The neuroprotective action and effect of hypothermia on the neurochemical system is not well understood. The present study was performed using six patients with GCS scores of 5 or less to clarify the relationship between monitored brain temperature, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and oxygen saturation of the jugular venous blood (SjO2). Changes in concentration of excitatory amino acids, glutamate (CLU) and aspartate (ASP), and NO2 were studied using intracerebral microdialysis as well as in jugular venous blood and cerebrospinal fluid (CSF). Changes in brain temperature, CPP and SjO2 resulting from hypothermia and brain death associated with markedly higher concentrations of and fluctuations in the concentrations of CLU, ASP and NO2 were observed in the dfalysate than in the jugular venous blood or CSF. Hypothermic treatment significantly reduces excitatory amino acid and NO2 concentrations, a finding which was associated with an improvement in CPP and SjO2. Measurement of CLU and ASP using intracerebral microdialysis is a clinically useful method for clarifying abnormal neurochemical events associated with severe head injury and for evaluating the effects of hypothermia. [Neurol Res 2000; 22: 657-664]

Posttraumatic Edema in the Corpus Callosum Shown by MRI

MRI was performed on 120 patients who sustained closed head injury of varying severity. Patients ranged in age from 4 to 87 years (average, 32 years). All patients had an initial MRI within 28 days (median 12 days) of injury. MRI disclosed areas of abnormal signals in the corpus callosum of 21 (18%) of the 120 patients; 1 (2%) of the 44 patients who sustained mild injuries (GCS > or = 13), 3 (10%) of the 31 moderate injuries (GCS 9-12), and 17 (38%) of the 45 severe injuries (GCS < or = 8) (p < 0.0001). All but 2 of the 21 patients with corpus callosum lesions had other parenchymal lesions that were visualized by MRI. Of these 21 patients, MRI was repeated in 19. In 13 of the 19 patients, repeat MRI scans at 25 to 42 days after injury showed the disappearance of lesions that had on the first MRI shown a high signal on T2-weighted and FLAIR images and a normal signal on T1-weighted images. The MRI findings and time source of the disappearance of the corpus callosum lesions mirrored those of paracontusional edema in the subcortical white matter. Patients in whom the corpus callosum lesion disappeared had a better outcome than those in whom the lesion remained (good recovery/moderate disability; 92% vs 63%). The present MRI results suggest that some lesions in the corpus callosum following closed head injury are reversible, thus resembling edema that may be produced by a relatively mild shear strain force to the corpus callosum.

Production of platelet-activating factor by neuronal cells in the rat brain with cold injury

Abstract The production and localization of platelet-activating factor (PAF) in the brain following focal brain injury were examined. Immunofluorescent staining was used to detect PAF in the rat brain with cold-induced local brain injury. After cold injury, immediate-early PAF staining was observed within the cold lesion followed later by immunoreactivity in the ipsilateral white matter. PAF immunoreactivity was also clearly seen both in cortical neurons adjacent to the cold lesion and in the ipsilateral hippocampus which showed delayed neuronal degeneration. The data suggest that PAF synthesis occurs in the neuronal cells in the perilesional area and hippocampus as well as within the cold lesion site during the early stages of cold-induced brain injury. PAF expression may contribute to the onset and progression of further brain damage, such as delayed axotomy and delayed neuronal loss. [Neurol Res 2001; 23: 605-611]

35??C Hypothermia Can Reduce Increased Intracranial Pressure as Well as 33??C Hypothermia in Patients with Severe Traumatic Brain Injury: 845

INTRODUCTION: For many years, we have used therapeutic hypothermia (48–72 hr) in patients with severe traumatic brain injury (Glasgow Coma Scale scores of 5 or less). In 2000, we altered the target temperature to 35°C from the former 33°C, as our findings suggested that cooling to 35°C is sufficient to control intracranial hypertension and that hypothermia below 35°C may predispose patients to persistent cumulative oxygen debt, which may be associated with an increased risk of complications. In this study, we attempted to clarify whether 35°C hypothermia has the same effect as 33°C hypothermia in reducing intracranial hypertension and whether it is associated with fewer complications and improved outcomes. METHODS: We compared intracranial pressure and biochemical parameters of the 30 patients treated with 35°C hypothermia (January 2000–June 2005) with those of the 31 patients treated with 33°C hypothermia (July 1994–December 1999). RESULTS: Patient characteristics were similar in the two groups. The mean intracranial pressure on Days 1 to 7 after injury were 15.3 9.6 to 20.1 9.0 mmHg in the 35°C hypothermia group and 14.9 10.2 to 20.7 12.7 mmHg in the 33°C hypothermia group (P 0.0669 to 0.9903). The incidence of intracranial hypertension ( 20 mmHg) on Days 1 to 7 was 18 to 39% and 18 to 37% of measurements in the 35°C and 33°C groups, respectively (P 0.1444–0.9930). Furthermore, our 35°C hypothermic patients exhibited a significant improvement in the decline of systemic oxygen consumption and serum potassium concentrations during hypothermia, and in the increment of C-reactive protein after rewarming. Although the mortality rate tended to be lower in the 35°C group (27 versus 48%, P 0.0801), there were no statistically significant differences in the incidence of systemic complications. CONCLUSION: The effects of 35°C hypothermia on intracranial hypertension are similar to those of 33°C hypothermia.