Temporal Trends in Outcomes after Out-of-Hospital Cardiac Arrests Witnessed by Emergency Medical Services in Japan: A Population-Based Study.

OBJECTIVE: Survival after out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical service (EMS) personnel has been insufficiently understood. The aim of this study was to evaluate temporal trends in survival after EMS-witnessed OHCAs in Japan. METHODS: A nationwide, population-based, observational cohort study of consecutive adult OHCA patients with emergency responder resuscitation attempts from January 2005 to December 2012 in Japan. We assessed the trends in annual incidence, characteristics, and outcomes of OHCA patients witnessed by EMS personnel. Multiple logistic regression analysis was used to assess factors that were potentially associated with neurologically favorable outcome defined as cerebral performance category scale 1or 2. RESULTS: During the study period, a total of 66,760 EMS-witnessed OHCAs were documented. The annual incidence rates per 100,000 persons of EMS-witnessed OHCA patients increased from 4.6 (n = 7219) in 2005 to 4.9 (n = 9256) in 2012 (p for trend = 0.035). The proportion of one-month survival with neurologically favorable outcome improved from 5.9% in 2005 to 8.6% in 2012 (p for trend < 0.001), and the proportion increased from 22.1% in 2005 to 30.2% in 2012 in cases with shockable rhythm (p for trend < 0.001). In a multivariate analysis, adults, male gender, shockable rhythm, presumed cardiac origin, and year were associated with a better neurological outcome. CONCLUSIONS: In this population, the proportion of one-month survival with neurologically favorable outcome among OHCA patients witnessed by EMS personnel significantly improved during the study period.

A Phase II study of polyclonal anti-TNF-α (AZD9773) in Japanese patients with severe sepsis and/or septic shock.

Because tumor necrosis factor-alpha (TNF-α) induces many of the pathophysiological signs and symptoms observed in sepsis, it is a potential therapeutic target for treatment. The primary objective of this study was to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple intravenous (i.v.) infusions of two doses of AZD9773 in Japanese patients with severe sepsis and/or septic shock. In this Phase II, double-blind, placebo-controlled, dose-escalation study (ClinicalTrials.gov Identifier: NCT01144624), Japanese patients were randomized to two successive treatment cohorts (cohort 1, loading/maintenance doses of 250/50 U/kg or placebo; cohort 2, loading/maintenance doses of 500/100 U/kg or placebo) for a 5-day treatment period, then a follow-up period to day 29. Twenty patients were enrolled (AZD9773 cohort 1, n = 7; AZD9773 cohort 2, n = 7; placebo, n = 6), and all completed the study. Most treatment-emergent adverse events (TEAEs) were mild or moderate and none led to discontinuation. The most common TEAEs in the AZD9773 cohorts were pleural effusion (64.3%) and peripheral edema (28.6%). Pharmacokinetic data demonstrated an approximately proportional increase in concentration with increasing dose. Treatment with AZD9773 led to a decrease in TNF-α concentrations, which was more discernible in the AZD9773 cohort 2; TNF-α concentrations generally decreased with time in patients receiving placebo. A similar pattern of response was observed with interleukin-6 (IL-6) and IL-8. AZD9773 was generally well tolerated with dose-proportional pharmacokinetics in Japanese patients with severe sepsis/septic shock.

The relationship between cerebral regional oxygen saturation during extracorporeal cardiopulmonary resuscitation and the neurological outcome in a retrospective analysis of 16 cases.

BACKGROUND: In recent years, the measurement of cerebral regional oxygen saturation (rSO2) during resuscitation has attracted attention. The objective of this study was to clarify the relationship between the serial changes in the cerebral rSO2 values during extracorporeal cardiopulmonary resuscitation (ECPR) and the neurological outcome. METHODS: We measured the serial changes in the cerebral rSO2 values of patients with out-of-hospital cardiac arrest before and after ECPR in Osaka National Hospital. RESULTS: From January 2013 through March 2015, the serial changes in the cerebral rSO2 values were evaluated in 16 patients. Their outcomes, as measured by the Glasgow Outcome Scale (GOS) score at discharge, included good recovery (GR) (n = 4), vegetative state (VS) (n = 2), and death (D) (n = 10). In the poor neurological group (VS and D: n = 12; age, 52.8 ± 4.0 years), the cerebral rSO2 values showed a significant increase during ECPR (5 min before ECPR: 52.0 ± 1.8%; 2 min before ECPR: 56.1 ± 2.3%; 2 min after ECPR: 63.5 ± 2.2%; 5 min after ECPR: 66.4 ± 2.2%; 10 min after ECPR: 67.6 ± 2.3% [P < 0.01]). In contrast, in the good neurological group (GR: n = 4; age, 53.8 ± 6.9 years), the cerebral rSO2 values did not increase to a significant extent during ECPR (5 min before ECPR: 61.9 ± 3.1%; 2 min before ECPR: 57.1 ± 4.0%; 2 min after ECPR: 59.6 ± 3.8%; 5 min after ECPR: 61.0 ± 3.7%; 10 min after ECPR: 62.0 ± 3.8% [P = 0.88]). Our study suggested that the patients whose cerebral rSO2 values showed no significant improvement after ECPR might have had a good neurological prognosis. CONCLUSIONS: The serial changes in the cerebral rSO2 values during ECPR may predict a patient's neurological outcome. The further evaluation of the validity of rSO2 monitoring during ECPR may lead to a new resuscitation strategy.

Emergency room thoracotomy for acute traumatic cardiac tamponade caused by a blunt cardiac injury: A case report.

INTRODUCTION: Traumatic blunt cardiac injuries have a high mortality rate, and prompt diagnosis and treatment can be lifesaving in cardiac tamponade. PRESENTATION OF CASE: A 62-year-old man was transferred to the emergency department after a motor vehicle accident. He was hemodynamically unstable. A focused assessment with sonography in trauma (FAST) showed pericardial fluid with right ventricular collapse consistent with cardiac tamponade in the subxiphoid view. He collapsed despite a subxiphoid pericardiotomy. Owing to the ongoing hemodynamic instability, we performed a left anterolateral thoracotomy. Direct incision of the pericardium showed blood and clots within the pericardial space, indicating hemopericardium. The heart stroke and hemodynamic status recovered on removing the clot. DISCUSSION: Although the physical findings of cardiac tamponade are not always apparent in life-threatening acute cardiac tamponade after blunt trauma, FAST is a reliable tool for diagnosing and following cardiac tamponade. A median sternotomy is a standard approach for evaluating cardiac injury in hemodynamically stable patients with or without cardiopulmonary bypass. However, a left anterior thoracotomy was the fastest, simplest life-saving procedure considering the need for open-chest cardiac massage given our patient's life-threatening condition. CONCLUSION: A prompt diagnosis using FAST and treatment can be lifesaving in traumatic acute cardiac tamponade. A pericardiotomy via a thoracotomy is mandatory for lifesaving cardiac decompression in acute traumatic cardiac tamponade in cases of ineffective drainage due to clot formation within the pericardial space.

Spontaneous Escherichia coli bacterial meningitis mimicking heatstroke in an adult.

Bacterial meningitis can be difficult to recognize: the meningeal triad symptoms are not always present and the alteration in mental status can mimic heatstroke. Escherichia coli meningitis is a serious disease whose early diagnosis, appropriate antibiotic treatment, and hemodynamic management are essential.

Temporal intrailiac balloon occlusion for the treatment of intractable pelvic fracture hemorrhage.

Case: A 48-year-old schizophrenic man sustained multiple injuries following a fall. Unstable pelvic fractures were diagnosed in the emergency department. The patient's hemodynamic status was stabilized following bilateral internal iliac artery embolization using a gelatin sponge. However, recurrent bleeding and an expanding retroperitoneal hemorrhage occurred 1 h after transcatheter arterial embolization. Outcome: Using temporal intrailiac balloon occlusion, with preperitoneal gauze packing, the patient's hemodynamic status was stabilized in the intensive care unit. No complications were observed following transcatheter arterial embolization and balloon occlusion. Conclusions: Temporary intrailiac balloon occlusion is a rapid and safe treatment for refractory pelvic hemorrhage, which can be administered simultaneously with other treatments including preperitoneal gauze packing and external fixation.

Pre-hospital portable monitoring of cerebral regional oxygen saturation (rSO2) in seven patients with out-of-hospital cardiac arrest.

BACKGROUND: In recent years, measurement of cerebral regional oxygen saturation (rSO2) has attracted attention during resuscitation. However, serial changes of cerebral rSO2 in pre-hospital settings are unclear. The objective of this study was to clarify serial changes in cerebral rSO2 of patients with out-of-hospital cardiac arrest (OHCA) in the pre-hospital setting. METHODS: We recently developed a portable rSO2 monitor that is small (170 × 100 × 50 mm in size and 600 g in weight) enough to carry in pre-hospital settings. The sensor is attached to the patient's forehead by the ELT (Emergency Life-saving Technician), and it monitors rSO2 continuously. RESULTS: From June 2013 through August 2014, serial changes in cerebral rSO2 in seven patients were evaluated. According to the results of the serial changes in rSO2, four patterns of rSO2 change were found, as follows. Type 1: High rSO2 (around about 60 %) type (n = 1). Initial electrocardiogram was ventricular fibrillation and ROSC (return of spontaneous circulation) could be diagnosed in pre-hospital setting. Her outcome at discharge was Good Recovery (GR). Type 2: Low rSO2 (around about 45-50 %) type (n = 3). They did not get ROSC even once. Type 3: Gradually decreasing rSO2 type (n = 2): ROSC could be diagnosed in hospital, but not in pre-hospital setting. Their outcomes at discharge were not GR. Type 4: other type (n = 1). In this patient with ROSC when ELT started cerebral rSO2 measurement, cerebral rSO2 was 67.3 % at measurement start, it dropped gradually to 54.5 %, and then rose to 74.3 %. The cerebral oxygenation was impaired due to possible cardiac arrest again, and after that, ROSC led to the recovery of cerebral blood flow. CONCLUSION: We could measure serial changes in cerebral rSO2 in seven patients with OHCA in the pre-hospital setting. Our data suggest that pre-hospital monitoring of cerebral rSO2 might lead to a new resuscitation strategy.

Negative pressure wound therapy-assisted dermatotraction for the closure of large open wounds in a patient with non-clostridial gas gangrene.

Case: A 53-year-old woman developed septic shock associated with non-clostridial gas gangrene. She presented to the emergency department with two large open wounds on both thighs and in her sacral region. Non-enhanced computed tomography showed air density in contact with the right iliopsoas, which extended to the posterior compartment of the thigh. We made repeated efforts at surgical debridement of the wound with resection of necrotic tissues. Outcome: Using negative pressure wound therapy-assisted dermatotraction, the pus pockets and the wound dehiscence decreased in size. Using this method we were successful in achieving delayed closure without skin grafts. Conclusion: Negative pressure wound therapy can be an effective treatment for large and infected open contoured wounds. Negative pressure wound therapy-assisted dermatotraction might be beneficial for poorly healing, large, open wounds in patients in poor condition and with insufficient reserve to tolerate reconstructive surgery.

Safe tracheostomy: blunt puncture and dilation after minimal surgical exposure of the trachea (BPAD tracheostomy).

A number of complications can occur following both surgical tracheostomy (ST) and percutaneous tracheostomy (PT). A flexible new tracheostomy insertion technique with the advantages of both ST and PT is proposed to reduce these complications. Our blunt puncture and dilation technique (BPAD tracheostomy) appears to be technically safe and feasible to perform.

Venovenous Extracorporeal Membrane Oxygenation for Negative Pressure Pulmonary Hemorrhage in an Elderly Patient.

The patient in this case report was an 88-year-old male. Acute upper airway obstruction by food led to transient cardiac arrest, and negative pressure pulmonary hemorrhage (NPPH) occurred 1 hour after the foreign body obstruction. Using venovenous extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome resulting from NPPH, his respiratory state was recovered and hemoptysis stopped. NPPH is a life-threatening disease, the rapid recognition of which is required to initiate appropriate therapy. Although active hemorrhage might be a contraindication for ECMO, our experience showed this to be an effective treatment option. Moreover, our experience suggests that the application of ECMO to elderly patients should be considered on a case-by-case basis.

Corticosteroid therapy for hemolytic anemia and respiratory failure due to Mycoplasma pneumoniae pneumonia.

This is a report of hemolytic anemia and respiratory failure due to Mycopkisma pneumoniae pneumonia. His chest CT scans showed bilateral diffuse thickened bronchovascular bundles and emphysematous changes. The pulmonary function test supported the diagnosis of chronic obstructive pulmonary disease (COPD). He was diagnosed as coldagglunitin-associated hemolytic anemia and M. pneumonzae pneumonia in inapparent COPD. Corticosteroid administration was remarkabily effective for hemolytic anemia and beneficial for acute exacerbation of COPD.

Analysis of magnetic resonance imaging (MRI) morphometry and cerebral blood flow in patients with hypoxic-ischemic encephalopathy.

The aim of this study was to analyze magnetic resonance imaging (MRI) morphometry and cerebral blood flow (CBF) in patients with hypoxic-ischemic encephalopathy, and determine the viability of such measurements for predicting cerebral outcome. The subjects were 26 patients with histories of cardiopulmonary resuscitation who had subsequently developed encephalopathy. We examined the CBF using stable xenon-computed tomography (Xe-CT) and MR images in the subacute period (8-20 days). Three signal-change patterns in the basal ganglia emerged in the MRI study. The first pattern, isointense areas evident in both the T1-weighted image (T1WI) and the T2-weighted image (T2WI), was observed in four patients with favorable outcomes. The second pattern, iso- or hypointense areas evident in the T1WI and hyperintense areas evident in the T2WI, was observed in six patients with favorable outcomes and three patients with poor outcomes. The third pattern, hyperintense areas evident in both the T1WI and T2WI, was observed in 13 patients with poor outcomes. Hemispheric CBFs were 38.9+/-4.6 (mean (SD)) ml/100 g/min in patients with favorable outcomes and 25.3+/-4.3 ml/100 g/min in patients with poor outcomes (p < 0.01). The CBF increase after acetazolamide administration was 13.3+/-3.4 ml/100 g/min in patients with favorable outcomes and 6.8+/-5.6 ml/100 g/min in patients with poor outcomes ( p < 0.05). The presence of hyperintense lesions in the basal ganglia in T1WI, low hemispheric CBF ( < 30 ml/100 g/min), and low acetazolamide reactivity ( < 10 ml/100 g/min) are all factors associated with poor outcome in patients with hypoxic-ischemic encephalopathy.

Prevalence of metabolic syndrome in stroke patients: a prospective multicenter study in Japan.

AIMS: The fact that Metabolic Syndrome (MetS) increases the risk of atherosclerosis has been epidemiologically studied and proven; however, a prospective study on the prevalence of MetS in stroke patients has never been conducted because of the difficulty in diagnosis under critical illness in the acute phase. Therefore, we conducted a prospective multicenter study to investigate the prevalence of MetS in stroke patients with modified diagnostic criteria for MetS. METHODS: Stroke patients admitted in the seven participating Emergency and Critical Care Centers within the two years from April 2007 were registered in this study as a prospective multicenter study. Inclusion criteria were 50 to 89 year-old stroke patients who presented within three days from the onset of symptoms. A total of 992 subjects were classified according to the stroke type and the prevalence of MetS and the associated risk factors were investigated. The participants in a medical checkup without any history of a stroke were enrolled as the control group, and compared between the two groups. RESULTS: The prevalence of MetS as well as hyperglycemia and dyslipidemia in the infarction group was significantly higher than that in the non-stroke group. While the hemorrhage group showed no significant difference in the prevalence of MetS, only hypertension was significantly high. According to a subtype analysis, there is a significant correlation between waist circumference increment of the stroke patients and the prevalence of the risk factors of hypertension, hyperglycemia and dyslipidemia. CONCLUSIONS: Different risk factors are significantly related to the type of stroke.

Feasibility study of immediate pharyngeal cooling initiation in cardiac arrest patients after arrival at the emergency room.

AIM: Cooling the pharynx and upper oesophagus would be more advantageous for rapid induction of therapeutic hypothermia since the carotid arteries run in their vicinity. The aim of this study was to determine the effects of pharyngeal cooling on brain temperature and the safety and feasibility for patients under resuscitation. METHODS: Witnessed non-traumatic cardiac arrest patients (n=108) were randomized to receive standard care with (n=53) or without pharyngeal cooling (n=55). In the emergency room, pharyngeal cooling was initiated before or shortly after return of spontaneous circulation by perfusing physiological saline (5 °C) into a pharyngeal cuff for 120 min. RESULTS: There was a significant decrease in tympanic temperature at 40 min after arrival (P=0.02) with a maximum difference between the groups at 120 min (32.9 ± 1.2°C, pharyngeal cooling group vs. 34.1 ± 1.3°C, control group; P<0.001). The return of spontaneous circulation (70% vs. 65%, P=0.63) and rearrest (38% vs. 47%, P=0.45) rates were not significantly different based on the initiation of pharyngeal cooling. No post-treatment mechanical or cold-related injury was observed on the pharyngeal epithelium by macroscopic observation. The thrombocytopaenia incidence was lower in the pharyngeal cooling group (P=0.001) during the 3-day period after arrival. The cumulative survival rate at 1 month was not significantly different between the two groups. CONCLUSIONS: Initiation of pharyngeal cooling before or immediately after the return of spontaneous circulation is safe and feasible. Pharyngeal cooling can rapidly decrease tympanic temperature without adverse effects on circulation or the pharyngeal epithelium.

Systemic inflammatory response syndrome criteria and vancomycin dose requirement in patients with sepsis.

PURPOSE: Vancomycin has been used in patients with sepsis infected by MRSA and shows large interindividual variability in its dosing. In this observational study the potential influence of sepsis status on the vancomycin dose requirement in relation to systemic inflammatory response syndrome (SIRS) criteria was assessed. METHODS: From about 250 patients receiving serum vancomycin monitoring from May 2006 to April 2011 at the Osaka National Hospital, 105 adult patients who had been assessed using the SIRS criteria were identified. Patients on chemotherapy or intermittent positive pressure ventilation in whom the SIRS criteria could not accurately evaluate inflammatory status were excluded. Using two vancomycin serum concentrations at peak and trough, individual pharmacokinetic parameters were calculated by the Bayesian estimation method using a two-compartment model. Creatinine clearance rate was estimated by the Cockcroft-Gault formula (eCcr). RESULTS: Patients with SIRS had a significantly higher vancomycin clearance than those without SIRS, indicating that SIRS patients had a higher elimination capacity. The vancomycin clearance was positively correlated with the SIRS score defined as the number of positive items in the criteria, and negatively with age, except in patients with renal dysfunction. A linear relationship between the vancomycin clearance and eCcr remained even in the supernormal eCcr phase (more than approximately 120 mL/min). CONCLUSIONS: This study provides a new insight into the need for quick prediction of dose requirement. That is, an increased vancomycin dosage would be needed in patients with a higher SIRS score to maintain the therapeutic target concentration, in particular in those with a high eCcr value.

Hypothermia inhibits translocation of CaM kinase II and PKC-alpha, beta, gamma isoforms and fodrin proteolysis in rat brain synaptosome during ischemia-reperfusion.

To clarify the involvement of intracellular signaling pathway and calpain in the brain injury and its protection by mild hypothermia, immunoblotting analyses were performed in the rat brain after global forebrain ischemia and reperfusion. After 30 min of ischemia followed by 60 min of reperfusion, Ca2+/calmodulin-dependent kinase II (CaM kinase II) and protein kinase C (PKC)-alpha, beta, gamma isoforms translocated to the synaptosomal fraction, while mild hypothermia (32 degrees C) inhibited the translocation. The hypothermia also inhibited fodrin proteolysis caused by ischemia-reperfusion, indicating the inhibition of calpain. These effects of hypothermia may explain the mechanism of the protection against brain ischemia-reperfusion injury through modulating synaptosomal function.