Yoshikatsu Kawamura

Xanthine oxidase is one of the major sources of superoxide anion radicals in blood after reperfusion in rats with forebrain ischemia/reperfusion

We recently reported that excessive superoxide anion radical (O(2)(-)) was generated in the jugular vein during reperfusion in rats with forebrain ischemia/reperfusion using a novel electrochemical sensor and excessive O(2)(-) generation was associated with oxidative stress, early inflammation, and endothelial injury. However, the source of O(2)(-) was still unclear. Therefore, we used allopurinol, a potent inhibitor of xanthine oxidase (XO), to clarify the source of O(2)(-) generated in rats with forebrain ischemia/reperfusion. The increased O(2)(-) current and the quantified partial value of electricity (Q), which was calculated by the integration of the current, were significantly attenuated after reperfusion by pretreatment with allopurinol. Malondialdehyde (MDA) in the brain and plasma, high-mobility group box 1 (HMGB1) in plasma, and intercellular adhesion molecule-1 (ICAM-1) in the brain and plasma were significantly attenuated in rats pretreated with allopurinol with dose-dependency in comparison to those in control rats. There were significant correlations between total Q and MDA, HMGB, or ICAM-1 in the brain and plasma. Allopurinol pretreatment suppressed O(2)(-) generation in the brain-perfused blood in the jugular vein, and oxidative stress, early inflammation, and endothelial injury in the acute phase of forebrain ischemia/reperfusion. Thus, XO is one of the major sources of O(2)(-)- in blood after reperfusion in rats with forebrain ischemia/reperfusion.

Peak value of blood myoglobin predicts acute renal failure induced by rhabdomyolysis

PURPOSE Acute renal failure (ARF) is the most important complication of rhabdomyolysis. Serial measurements of blood myoglobin might be useful for predicting rhabdomyolysis-induced ARF. METHODS Thirty patients with rhabdomyolysis were examined. The causes of rhabdomyolysis were trauma, burns, and ischemia, among others. Serial blood myoglobin levels were measured by immunochromatography, and the peak value was determined. The relationship between blood myoglobin levels and the incidence of ARF was evaluated. RESULTS The median peak blood myoglobin level was 3335 ng/mL. Acute renal failure occurred in 12 patients (40%). Nine patients (30%) underwent renal replacement therapy. Peak creatine kinase and peak blood myoglobin levels in the ARF group were significantly higher than those in the non-ARF group. Three patients in the ARF group were treated with renal replacement therapy before occurrence of uremia because of extremely high levels of blood myoglobin (>10,000 ng/mL). Receiver operating characteristic analysis showed that the area under the curve for blood myoglobin that predicted ARF was 0.88, and the best cutoff value for blood myoglobin was 3865 ng/mL. CONCLUSIONS The peak value for blood myoglobin might be a good predictor of rhabdomyolysis-induced ARF. Early renal protective therapies should be considered for patients with rhabdomyolysis at high risk of ARF.

Real-time monitoring of heart rate variability in critically ill patients

PURPOSE Heart rate variability (HRV) is widely used to evaluate autonomic nervous function; however, real-time monitoring of HRV has rarely been attempted in the intensive care unit (ICU). We report our experience in performing real-time monitoring of HRV in our ICU. METHODS We investigated 10 critically ill patients on total ventilatory support. Heart rate variability analysis was performed using the MemCalc system, which is a noninvasive, real-time analysis system. The low-frequency (LF) component of HRV reflects sympathetic and parasympathetic modulation, whereas the high-frequency (HF) component mainly reflects parasympathetic modulation. The LF/HF ratio represents a measure of sympathetic/parasympathetic balance. RESULTS The HRV parameters for patients breathing spontaneously after extubation were significantly higher than those for patients on total ventilatory support. These findings suggest that mechanical ventilation under sedation may reduce autonomic nervous function in critically ill patients. In a representative case with septic shock, systolic blood pressure and LF/HF ratio showed a significant increase after intravenous infusion of epinephrine and then the HF component showed a significant increase due to vagal reflex. CONCLUSIONS The MemCalc system is practicable for real-time monitoring of HRV in the ICU. Heart rate variability parameters may offer useful information in the management of critically ill patients.

Prevalence and associated factors for delirium in critically ill patients at a Japanese intensive care unit

OBJECTIVE To investigate the prevalence and associated factors of delirium in critically ill patients during an intensive care unit (ICU) stay. METHODS We investigated 103 of 172 patients admitted consecutively to a university-based 20-bed ICU in a 3-month period. Six ICU physicians, who were familiar with the Confusion Assessment Method for the ICU (CAM-ICU), assessed patient delirium daily. Patient demographics, diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mechanical ventilation and maximum serum C-reactive protein (max-CRP) level during the ICU stay (max-CRP) were compared between patients who developed delirium and those who did not. RESULTS Twenty-one (20%) of 103 patients and 13 (76%) of 17 mechanically ventilated patients developed delirium. APACHE II scores and max-CRP were significantly higher in patients who experienced delirium than in those who did not (P<.001). Use of a mechanical ventilator (P=.002), max-CRP (P=.032) and length of ICU stay (P=.043) were identified as independent associations for delirium development. CONCLUSIONS The prevalence of delirium was 20% in ICU patients and 80% in ventilated patients in a Japanese ICU.

Prognostic value of biochemical markers of brain damage and oxidative stress in post-surgical aneurysmal subarachnoid hemorrhage patients

The aim of this study is to determine effective biochemical markers and optimal sampling timing for prediction of neurological prognosis in post-surgical aneurysmal subarachnoid hemorrhage (SAH) patients. Subjects were a sequential group of SAH patients admitted to our centre who underwent aneurysm clipping before Day 3 and who received a cerebrospinal fluid (CSF) drain. CSF samples from 32 patients were collected on Days 3, 7, and 14. Neurological outcome was assessed by neurosurgeons using the Glasgow outcome scale (GOS) at 6 months after onset. CSF levels of neuron-specific enolase (NSE), S100B, and glial fibrillary acidic protein (GFAP) were determined using enzyme-linked immunosorbent assay, and the CSF concentrations of malondialdehyde (MDA) were determined using spectrophotometric assay. In univariate analysis, S100B on Days 3 and 14, GFAP on Days 3 and 7, and MDA on Day 14 were significantly higher in the poor outcome group (GOS 1-4) than in the good outcome group (GOS 5). In multivariate analysis, only MDA on Day 14 was identified as a significant predictor of poor neurological outcome at 6 months after onset. The area under the receiver-operating characteristic (ROC) curve for MDA on Day 14 was 0.841. For a threshold of 0.3 microM, sensitivity and specificity were 0.875 and 0.750, respectively. Our findings suggest that these biochemical markers, especially MDA, show significant promise as predictors of neurological outcome in clinical practice.

Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims: A pilot study

OBJECTIVES To investigate whether high mobility group box 1 (HMGB1) and S100B in cerebrospinal fluid (CSF) and the serum predict the neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS This study was designed as a prospective observational study. Twenty-five patients, who received standard cardiopulmonary resuscitation and post-resuscitation intensive care, were enrolled in this study. The patients were divided into two groups according to Glasgow-Pittsburgh Cerebral Performance categories (CPCs) at 6 months after return of spontaneous circulation (ROSC), Group G (n = 7, CPC 1 or 2) and Group P (n = 18, CPC ≥ 3). Their blood samples were taken at 6, 24, and 48h after ROSC. The patients, whose CSF was sampled at 48h, were also divided into either sub-Group G (n = 6) or sub-Group P (n = 8) at 6 months after ROSC. RESULTS HMGB1 and S100B in CSF in sub-Group P were significantly higher than those in sub-Group G (HMGB1, <1.0 vs. 12.4 ng/ml, P = 0.009; S100B, 2.68 vs. 84.2 ng/ml, P = 0.007, respectively). HMGB1 in CSF was strongly correlated with S100B (σ = 0.81, P = 0.001). HMGB1 was elevated in serum at 6h and normalized within 48 h after ROSC without any significant differences between the two groups. Serum S100B in Group P was significantly higher than that in Group G at each time point. CONCLUSIONS The significant elevations of HMGB1 and S100B in CSF, and S100B in serum are associated with the neurologically poor outcome in OHCA patients.

Effects of mechanical chest compression device with a load-distributing band on post-resuscitation injuries identified by post-mortem computed tomography.

OBJECTIVE To determine the effects of cardiopulmonary resuscitation (CPR) with AutoPulse™ (LDB-CPR) on post-resuscitation injuries identified by post-mortem computed tomography (PMCT). AutoPulse™ is a novel mechanical chest-compression device with a load-distributing band (LDB) that may affect post-resuscitation injury identified by PMCT. METHODS We conducted a retrospective cohort study of non-traumatic adult out-of-hospital cardiac arrest patients whose death was confirmed in our emergency department between October 2009 and September 2014. Patients were divided according to whether LDB-CPR (LDB-CPR group) or manual CPR only (manual CPR only group) was performed. The background characteristics and post-resuscitation injuries identified by PMCT were compared between both groups. Logistic regression was used to identify risk factors for posterior rib fracture and abdominal injury. RESULTS Overall, 323 patients were evaluated, with 241 (74.6%) in the LDB-CPR group. The total duration of CPR was significantly longer in the LDB-CPR group than in the manual CPR only group. Posterior rib fracture, hemoperitoneum, and retroperitoneal hemorrhage were significantly more frequent in the LDB-CPR group. The frequencies of anterior/lateral rib and sternum fracture were similar in both groups. Pneumothorax tended to be more frequent in the LDB-CPR group, although not significantly. LDB-CPR was an independent risk factor for posterior rib fracture (odds ratio 30.57, 95% confidence interval 4.15-225.49, P=0.001) and abdominal injury (odds ratio 4.93, 95% confidence interval 1.88-12.95, P=0.001). CONCLUSIONS LDB-CPR was associated with higher frequencies of posterior rib fracture and abdominal injury identified by PMCT. PMCT findings should be carefully examined after LDB-CPR.

Extent of pleural effusion on chest radiograph is associated with failure of high-flow nasal cannula oxygen therapy.

PURPOSE The purpose of the study was to determine whether pleural effusion (PE) is associated with a failure of high-flow nasal cannula (HFNC) therapy. MATERIALS AND METHODS We conducted a single-center retrospective study. Seventy-three patients with acute respiratory failure given HFNC therapy between January 2012 and December 2014 were reviewed. HFNC failure was defined as intubation or noninvasive positive pressure ventilation following HFNC therapy. The numbers of quadrants with consolidation or ground glass opacity were counted on chest radiographs performed within 24 hours before starting HFNC therapy, and the PE score was calculated. PE score was the original score, verified by the computed tomographic images of some of the study patients. RESULTS Overall, 29 of 73 experienced HFNC failure. PE score was significantly greater in the HFNC failure group, but the number of quadrants with opacity was not significantly different. Age and Sequential Organ Failure Assessment (SOFA) score were significantly greater in the HFNC failure group. The PE (odds ratio, 1.49; 95% confidence interval, 1.10-2.02; P = .01) and SOFA (odds ratio, 1.33; 95% confidence interval, 1.05-1.68; P = .02) scores were independently associated with HFNC failure in multivariate analysis. CONCLUSIONS The extent of PE on chest radiograph and SOFA score were associated with HFNC failure.

Global end-diastolic volume, serum osmolarity, and albumin are risk factors for increased extravascular lung water

BACKGROUND The transpulmonary thermodilution technique allows the determination of cardiac preload (global end-diastolic volume index) and quantification of pulmonary edema (extravascular lung water index [EVLWI]). Pulmonary edema commonly develops in critically ill patients; however, the underlying pathophysiology, that is, hydrostatic (cardiac) or permeability-induced (noncardiac), often remains unclear. In this study, hemodynamic and serum parameters of osmolarity and oncotic pressure were analyzed to identify risk factors for increased EVLWI. METHODS A retrospective, single-center analysis in an intensive care unit of a university hospital was performed. No interventions were made for the study. Forty-two critically ill patients were included, and 126 simultaneous hemodynamic measurements and serum determinations were analyzed by logistic regression and Spearman rank correlation coefficient analysis. RESULTS Global end-diastolic volume index (P = .001), serum albumin (P = .006), and serum osmolarity (P = .029) were significant factors for increased EVLWI (defined as >10 mL/kg). CONCLUSION Hypervolemia, hypoalbuminemia, and high plasma osmolarity are associated with increased EVLWI.

Development of a prompt model for predicting neurological outcomes in patients with return of spontaneous circulation from out‐of‐hospital cardiac arrest

Early prediction of the neurological outcomes of patients with out‐of‐hospital cardiac arrest is important to select the optimal clinical management. We hypothesized that clinical data recorded at the site of cardiopulmonary resuscitation would be clinically useful.