Hidetaka Onda

Time course of recovery from cerebral vulnerability after severe traumatic brain injury : A microdialysis study

BACKGROUND The aim of this study was to evaluate the time course of recovery from cerebral vulnerability, using microdialysis (MD) technique and cerebral vascular autoregulation measurement, to clarify the appropriate timing of subsequent major surgical procedures, and to minimize the possibility of secondary brain injury in patients with severe traumatic brain injury (STBI). METHODS In 3,470 MD samples of 25 patients with STBI, cerebral extracellular biomarkers (glucose, lactate, pyruvate, glycerol, and glutamate) were measured. In addition, to estimate cerebral vascular autoregulaton, the pressure reactivity index (PRx) was calculated with intracranial pressure (ICP) and mean arterial pressure. The data with ICP, cerebral perfusion pressure (CPP), and PRx were collected hourly for 7 days after injury and they were compared with MD biomarkers daily. RESULTS During the study period, the average ICP and CPP remained stable and were within the threshold of STBI treatment guidelines. After injury, the extracellular glucose concentration decreased, and the levels of glycerol, glutamate, and lactate/pyruvate ratio (LPR), which indicate cerebral ischemia and neural cell damage, increased. On the fourth day after injury, the extracellular glucose concentration improved, and the value of LPR decreased. The average PRx decreased daily and became negative on the fifth day after injury. CONCLUSION Our results indicated that cerebral vascular autoregulation would recover on the fourth day after STBI, and cerebral perfusion might be increased by recovery of autoregulation. Thus, subsequent nonemergent surgery should be performed at least 4 days after STBI to prevent secondary brain injury. In addition, we should keep in mind that the cerebral vulnerability might persist for 4 days after suffering STBI.

Global end-diastolic volume is associated with the occurrence of delayed cerebral ischemia and pulmonary edema after subarachnoid hemorrhage.

Predictive variables of delayed cerebral ischemia (DCI) and pulmonary edema following subarachnoid hemorrhage (SAH) remain unknown. We aimed to determine associations between transpulmonary thermodilution–derived variables and DCI and pulmonary edema occurrence after SAH. We reviewed 34 consecutive SAH patients monitored by the PiCCO system. Six patients developed DCI at 7 days after SAH on average; 28 did not (non-DCI). We compared the variable measures for 1 day before DCI occurred (DCI day −1) in the DCI group and 6 days after SAH (non-DCI day −1) in the non-DCI group for control. The mean value of the global end-diastolic volume index (GEDI) for DCI day −1 was lower than that for non-DCI day −1 (676 ± 65 vs. 872 ± 85 mL/m2, P = 0.04). Central venous pressure (CVP) was not significantly different (7.8 ± 3.1 vs. 9.4 ± 1.9 cm H2O, P = 0.45). At day −1 for both DCI and non-DCI, 11 patients (32%) had pulmonary edema. Global end-diastolic volume index was significantly higher in patients with pulmonary edema than in those without this condition (947 ± 126 vs. 766 ± 81 mL/m2, P = 0.02); CVP was not significantly different (8.7 ± 2.8 vs. 9.2 ± 2.1 cm H2O, P = 0.78). Although significant correlation was found between extravascular lung water (EVLW) measures and GEDI (r = 0.58, P = 0.001), EVLW and CVP were not correlated (r = 0.03, P = 0.88). Thus, GEDI might be associated with DCI occurrence and EVLW accumulation after SAH. ABBREVIATIONS 95% CI — 95% confidence interval AUC — area under the receiver operating characteristic curve CO — cardiac output CVP — central venous pressure DCI — delayed cerebral ischemia EVLW — extravascular lung water EVLWI — extravascular lung water index GEF — global ejection fraction GEDV — global end-diastolic volume GEDI — global end-diastolic volume index ITBV — intrathoracic blood volume ITTV — intrathoracic thermal volume PVPI — pulmonary vascular permeability index SAH — subarachnoid hemorrhage SVRI — systemic vascular resistance index

Outcome and Refractory Factor of Intensive Treatment for Geriatric Traumatic Brain Injury: Analysis of 1165 Cases Registered in the Japan Neurotrauma Data Bank

OBJECTIVE With the increase in the aged population, geriatric traumatic brain injury (gTBI) is also rapidly increasing in Japan. There is thus a need to review the effect of intensive treatments for gTBIs. The aim of this study was 1) to assess how intensive treatments influenced patient outcome and 2) to identify the refractory factor against these intensive treatments in gTBI, from the Japan Neurotrauma Data Bank (JNTDB). METHODS Of all 3194 patients in the JNTDB, 1165 (≥ 65 years old) with severe gTBIs were enrolled in this study. The clinical features and their outcomes based on the Glasgow Outcome Scale on discharge and 6 months after injury were compared. RESULTS Intensive treatments were administered to 71.4% of all patients with severe gTBI showing a significant increase over 15 years. Accordingly, mortality decreased significantly (from 62.7% to 51.1%, P = 0.001). On the other hand, severely disabled dependent survivors, who need daily help from others for living, increased accordingly (from 63.2% to 68.4%). The existence of intraventricular hemorrhage (IVH) rather than the patients age was identified as the strongest refractory factor (odds ratio, 5.762; 95% confidence interval, 1.317-25.216) against intensive treatment. CONCLUSIONS This study clarified that 1) intensive treatments are associated with higher survival rates (however, they also increase the incidence of severely disabled survivors) and 2) the strongest refractory factor for intensive treatment in cases of severe gTBI was not age but the existence of IVH. These results warrant further establishment of a seamless strategy for both the acute and the chronic phase of gTBI.

Quantitative pupillometry and neuron-specific enolase independently predict return of spontaneous circulation following cardiogenic out-of-hospital cardiac arrest: a prospective pilot study

This study aimed to identify neurological and pathophysiological factors that predicted return of spontaneous circulation (ROSC) among patients with out-of-hospital cardiac arrest (OHCA). This prospective 1-year observational study evaluated patients with cardiogenic OHCA who were admitted to a tertiary medical center, Nippon Medical School Hospital. Physiological and neurological examinations were performed at admission for quantitative infrared pupillometry (measured with NPi-200, NeurOptics, CA, USA), arterial blood gas, and blood chemistry. Simultaneous blood samples were also collected to determine levels of neuron-specific enolase (NSE), S-100b, phosphorylated neurofilament heavy subunit, and interleukin-6. In-hospital standard advanced cardiac life support was performed for 30 minutes.The ROSC (n = 26) and non-ROSC (n = 26) groups were compared, which a revealed significantly higher pupillary light reflex ratio, which was defined as the percent change between maximum pupil diameter before light stimuli and minimum pupil diameter after light stimuli, in the ROSC group (median: 1.3% [interquartile range (IQR): 0.0–2.0%] vs. non-ROSC: (median: 0%), (Cut-off: 0.63%). Furthermore, NSE provided the great sensitivity and specificity for predicting ROSC, with an area under the receiver operating characteristic curve of 0.86, which was created by plotting sensitivity and 1-specificity. Multivariable logistic regression analyses revealed that the independent predictors of ROSC were maximum pupillary diameter (odds ratio: 0.25, 95% confidence interval: 0.07–0.94, P = 0.04) and NSE at admission (odds ratio: 0.96, 95% confidence interval: 0.93–0.99, P = 0.04). Pupillary diameter was also significantly correlated with NSE concentrations (r = 0.31, P = 0.027). Conclusively, the strongest predictors of ROSC among patients with OHCA were accurate pupillary diameter and a neuronal biomarker, NSE. Quantitative pupillometry may help guide the decision to terminate resuscitation in emergency departments using a neuropathological rationale. Further large-scale studies are needed.

536: SERIAL MEASUREMENTS OF AUDITORY BRAINSTEM RESPONSE CAN PREDICT PATIENT OUTCOMES WITH MORE PRECISION

effect of rAIH on neuroinflammation in non-spinal CNS regions is not known, nor is its effect on microglia, CNS immune cells that mediate inflammatory responses to CIH. We hypothesized that rAIH would down-regulate microglial inflammatory gene expression in a CNS region-dependent manner. Methods: Using real time PCR, we measured mRNA levels of inflammatory factors following rAIH treatment in 8 healthy adult Sprague-Dawley rats. A comparison group of 8 control rats were subjected to identical exposure conditions but received room air in place of episodic 10.5% O2. We compared the cellular sources of gene expression in immunomagnetically-isolated microglia and CNS tissue homogenates from the frontal cortex, brainstem, and upper and lower cervical spinal cord. Results: We found that rAIH did not elicit increases in the relative expression of the inflammatory genes COX-2, IL-1beta, IL-6, or TNF-alpha in either microglia or homogenate samples in any CNS region evaluated, compared with controls (all p>0.05 vs. normoxia). Conclusions: These data indicate that while rAIH is not anti-inflammatory in this rat strain, it does not appear to promote neuroinflammation in either microglia or tissue homogenates in any of the CNS regions studied here. These results have important implications for the safety of rAIH as a potential therapy to enhance neuroplasticity and motor function in patients with spinal injury or other neurologic disorders.