Optimal chest compression for cardiac arrest until the establishment of ECPR: Secondary analysis of the SAVE-J II study.

INTRODUCTION: The widespread incorporation of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest requires the delivery of effective and high-quality chest compressions prior to the initiation of ECPR. The aim of this study was to evaluate and compare the effectiveness of mechanical and manual chest compressions until the initiation of ECPR. METHODS: This study was a secondary analysis of the Japanese retrospective multicenter registry "Study of Advanced Life Support for Ventricular Fibrillation by Extracorporeal Circulation II (SAVE-J II)". Patients were divided into two groups, one receiving mechanical chest compressions and the other receiving manual chest compressions. The primary outcome measure was mortality at hospital discharge, while the secondary outcome was the cerebral performance category (CPC) score at discharge. RESULTS: Of the 2157 patients enrolled in the SAVE-J II trial, 453 patients (329 in the manual compression group and 124 in the mechanical compression group) were included in the final analysis. Univariate analysis showed a significantly higher mortality rate at hospital discharge in the mechanical compression group compared to the manual compression group (odds ratio [95% CI] = 2.32 [1.34-4.02], p = 0.0026). Multivariate analysis showed that mechanical chest compressions were an independent factor associated with increased mortality at hospital discharge (adjusted odds ratio [95% CI] = 2.00 [1.11-3.58], p = 0.02). There was no statistically significant difference in CPC between the two groups. CONCLUSION: For patients with out-of-hospital cardiopulmonary arrest who require ECPR, extreme caution should be used when performing mechanical chest compressions.

Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes. RESULTS: A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0-40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively). CONCLUSIONS: The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.

Influence of hyperbaric oxygen therapy on thrombus formation ability in humans.

Background: Hyperbaric oxygen (HBO2) therapy was introduced nearly 300 years ago. However, its effect on thrombus formation is unclear. This may be because platelet and coagulation functions are unstable, yielding variable results; hence, accurate measurement is difficult. Our study aimed to analyze changes in thrombus formation before and after HBO2 therapy by using a total thrombus formation analysis system (TTAS). Methods: Six patients were prescribed HBO2 therapy for skin and soft tissue ulcers, and necrotic fasciitis. Blood samples were collected immediately before and after treatment. Then samples were put into a reservoir that connected to AR-chip to assess changes in the thrombus formation ability of both platelets and coagulation factors. We examined the differences in the thrombus formation ability using T-TAS. Time until the onset of white thrombus formation (T10) and complete occlusion of the capillary (T80) were analyzed by a two-way repeated measure analysis of variance (ANOVA). Results: The duration to pressure increase of samples after HBO2 therapy was longer than the duration before HBO2 therapy (p<0.05). This suggests decreased clot adhesiveness to the inner surface of the simulated blood vessel and reduced clot formation ability. Conclusions: The results for T10 and T80 suggest that HBO2 therapy reduced thrombus formation ability in the enrolled patients. We believe that T-TAS is a promising method to predict the efficacy of HBO2 therapy.

Effects of hyperbaric exposure on thrombus formation.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has a long history of use. However, its effect on thrombus formation is unclear. Many reports have indicated that it accelerates platelet aggregation, which suggests that it may increase thrombotic events. However, clinical trial results are inconsistent, and no previous reports have demonstrated that HBO2therapy does in fact increase thrombotic events. Here, we used a total thrombus formation analysis system (T-TAS) to analyze changes in thrombus formation in a specimen group exposed to constant hyperbaric pressure in vitro, and a control group. METHODS: Blood samples were collected from two sets of 10 healthy volunteers (mean age, 28.8 years) with no underlying disease. In the pressurized group, a constant pressure was applied to specimens in temperature-controlled test tubes; the non-pressurized group served as the control. Thrombus formation in samples from both the pressurized and control groups were measured using the T-TAS immediately, 20 minutes, and 40 minutes after pressurization. RESULTS: In the pressurized group, the onset of thrombus formation was significantly delayed, confirming a reduction in thrombus formation ability. However, the reduced ability for thrombus formation in the pressurized group recovered to the level of the control group. That is, the change in thrombus formation ability caused by pressure was proven to be reversible. CONCLUSIONS: We are the first to ascertain a decrease in the thrombus formation ability in specimens exposed to hyperbaric pressure using a T-TAS, which is capable of measuring thrombus formation in an environment similar to that in vivo.

Open pneumothorax with extensive thoracic defects sustained in a fall: a case report.

BACKGROUND: Open pneumothorax with chest wall deficit is a rare chest trauma that is serious and can lead to severe respiratory failure; however, it is a potentially lifesaving injury if utilized appropriately. CASE PRESENTATION: Herein, we report a case of an open pneumothorax with extensive chest wall deficit due to falling from a height and highlight the importance of appropriate evaluation and intervention. The patient was a Japanese man in his 50 s who fell from the 6th floor to the 3rd floor while working at a height. The left chest wall was punctured due to injury, the thoracic cavity was open as if a left anterolateral thoracotomy had been performed, and the left lung had prolapsed from the thoracic cavity to the outside. In our emergency department, tracheal intubation with a double lumen tube for differential positive pressure ventilation and a right thoracic drain were inserted, and an emergency operation was started immediately. A pulmonary suture for lung injury and closure of the left thorax were performed during the surgery. The defect was closed with the remaining tissue, but the anterior thoracic skin with poor blood flow was necrotic, so debridement was undertaken. After his general condition was improved, pedicled latissimus dorsi myocutaneous flap was implanted. He was discharged home on the 63rd hospital day. CONCLUSIONS: Although open pneumothorax is rare and sometimes presents lurid findings, we highlighted that it is important to quickly assess the life-threatening organ injury, perform positive pressure ventilation by tracheal intubation, thoracic drainage, and wound closure simultaneously respond calmly as a team.

[Hybrid repair of thoracoabdominal aortic aneurysm in high-risk patients using a quadrifurcated graft].

Surgical treatment for thoracoabdominal aortic aneurysm is still challenging and is associated with a high risk of paraplegia. Hybrid repair with stent graft insertion for the thoracoabdominal aorta excluding the branches of the lumbar and visceral arteries and bypass grafting to the visceral branches has been introduced as a less invasive treatment that reduces the risk of paraplegia. For hybrid repair, it is important to have appropriate management of the revascularized grafts to the 4 visceral arteries with sufficient inflow. We have recently adopted a knitted quadrifurcated graft applied inversely from the abdominal aorta or the iliac artery to the 4 visceral arteries; the celiac, superior mesenteric, and bilateral renal arteries. To date, we have used the graft in hybrid repair of thoracoabdominal aortic aneurysm in 2 high-risk elder patients who had disseminated intravascular coagulopathy and severe renal failure, respectively. We found that a knitted quadrifurcated graft was easy to handle and useful for reducing the number of anastomoses, which were expected to shorten the operation time. Postoperative courses were uneventful without paraplegia in either patient. Postoperative computed tomography showed excellent patency of the inversely applied quadrifurcated graft without any endoleak or migration in the thoracoabdominal stent. In conclusion, revascularization of 4 visceral arteries using a quadrifurcated graft should be considered a preferable option in hybrid treatment for thoracoabdominal aortic aneurysm.

Efficacy of damage control surgery and staged endoscopic pancreatic ductal double stenting therapy for severe pancreatic head injury: a case report.

BACKGROUND: A high-grade pancreatic injury is a life-threatening injury that is associated with high mortality and morbidity. It is currently unclear which treatment strategy results in good clinical outcomes. CASE PRESENTATION: A 23-year-old Japanese woman sustained severe injury in a motor vehicle accident. Abdominal computed tomography revealed severe pancreatic head injury with extravasation of contrast media. Since it was not possible to insert an endoscopic pancreatic stenting tube into the main pancreatic duct, damage control surgery was performed. On day 3, we could insert the endoscopic pancreatic stenting tube from the ampulla of Vater and an endoscopic nasopancreatic drainage tube in the distal pancreatic duct from the accessory ampulla before the second operation. Drainage tubes were placed around the pancreatic head in the second operation. The endoscopic nasopancreatic drainage tube tube was converted to endoscopic pancreatic stenting tube on day 9. On day 51, the patient was discharged on foot from our hospital without serious complications. CONCLUSION: Early and effective hemostasis, staged pancreatic duct drainage with stenting, and surgical external drainage around the pancreas in combination with an endoscopic procedure and damage control surgery were considered appropriate therapeutic strategy for high-grade pancreatic injury.

A patient with severe polytrauma with massive pulmonary contusion and hemorrhage successfully treated with multiple treatment modalities: a case report.

BACKGROUND: The mortality rate is very high for patients with severe multiple trauma with massive pulmonary contusion containing intrapulmonary hemorrhage. Multiple treatment modalities are needed not only for a prevention of cardiac arrest and quick hemostasis against multiple injuries, but also for recovery of oxygenation to save the patient's life. CASE PRESENTATION: A 48-year-old Japanese woman fell down stairs that had a height of approximately 4 m. An X-ray showed pneumothorax, pulmonary contusion in her right lung, and an unstable pelvic fracture. A chest drain was inserted and preperitoneal pelvic packing was performed to control bleeding, performing resuscitative endovascular balloon occlusion of the aorta. A computed tomography scan revealed massive lung contusion in the lower lobe of her right lung, pelvic fractures, and multiple fractures and hematoma in other areas. An emergency thoracotomy was performed, and then we performed wide wedge resection of the injured lung, clamping proximal to suture lines with two Satinsky blood vessel clamps. The vessel clamps were left in the right thoracic cavity. The other hemorrhagic areas were embolized by transcatheter arterial embolization. However, since her respiratory functions deteriorated in the intensive care unit, veno-venous extracorporeal membrane oxygenation was used for lung assist. Planned reoperation under veno-venous extracorporeal membrane oxygenation was performed on day 2. Since her respiratory condition improved gradually, the veno-venous extracorporeal membrane oxygenation circuit was withdrawn on day 7. She was transferred to the psychiatric ward of our hospital on day 75. CONCLUSION: Utilizing multiple treatment modalities such as resuscitative endovascular balloon occlusion of the aorta, damage control surgery, transcatheter arterial embolization, and veno-venous extracorporeal membrane oxygenation with appropriate timing saves a patient with severe polytrauma with massive pulmonary contusion including intrapulmonary hemorrhage.

High-dose Factor XIII administration induces effective hemostasis for trauma-associated coagulopathy (TAC) both in vitro and in rat hemorrhagic shock in vivo models.

BACKGROUND: Trauma-associated coagulopathy (TAC) is an early and primary complication in severe trauma patients. Factor XIII (FXIII) is reported to stabilize a clot in the late phase of the coagulation cascade. The goal of this study was to investigate whether the administration of FXIII improves the condition of TAC both in vitro and in vivo. METHODS: We evaluated the effects of different doses, including a very high dose of FXIII (3.6-32.4 IU/mL) on tissue-plasminogen activator-induced hyperfibrinolysis and the combined condition of dilutional coagulopathy and tissue-plasminogen activator-induced hyperfibrinolysis in vitro. The coagulation status was analyzed by rotational thromboelastometry (ROTEM) and Sonoclot. Then, we evaluated the effect of high-dose FXIII (300 IU/kg) for severe coagulopathy in vivo using a rat liver trauma model in which coagulopathy similar to TAC was observed. Survival time and the amount of intra-abdominal bleeding of rats were measured, and a coagulation test was also performed. Histologic evaluations of rats' lung and kidney after FXIII administration were completed. RESULTS: High-dose FXIII significantly improved clot strength as well as increased resistance to hyperfibrinolysis in vitro which was confirmed by ROTEM. Platelet function on Sonoclot was significantly increased by FXIII in a dose-dependent manner. Factor XIII significantly decreased the total amount of bleeding and prolonged the survival time compared to control (control vs FXIII: 108.9 ± 11.4 vs 32.6 ± 5.5 mL/kg; p < 0.001; 26.0 ± 8.8 vs 120 minutes, p < 0.001) in a rat model. Rotational thromboelastometry parameters and platelet function on Sonoclot were significantly improved in the FXIII (+) group compared to control. No adverse effects of FXIII were detected histologically. CONCLUSION: Factor XIII not only generated stable clot resistance to hyperfibrinolysis but also enhanced platelet function by facilitating clot retraction. High-dose FXIII administration therapy has significant clinical impact for severe trauma accompanied with TAC. STUDY TYPE: Human in vitro and rat in vivo experimental study.

Sphingosine-1-Phosphate (S1P) Is a Feasible Biomarker in Predicting the Efficacy of Polymyxin B-Immobilized Fiber Direct Hemoperfusion (PMX-DHP) in Patients with Septic Shock.

PURPOSE: The aim of this study was to identify a useful biomarker to predict the efficacy of polymyxin B-immobilized fiber direct hemoperfusion (PMX-DHP) in patients with septic shock. METHODS: The 44 patients included in this study were divided into two groups. Group A had an increase in systolic blood pressure (SBP) over 30 mmHg after PMX-DHP treatment. Group B had an increase in SBP less than 30 mmHg after PMX-DHP treatment. We evaluated the clinical characteristics and demographics of both groups. We also assessed whether the cause of sepsis affected the efficacy of PMX-DHP and compared the prognosis of both groups. Finally, we investigated whether there were any significant differences in the levels of sepsis-related biomarkers, including sphingosine-1-phosphate (S1P), between both groups before PMX-DHP in an effort to identify a biomarker that could predict the efficacy of PMX-DHP. RESULTS: PMX-DHP significantly increased SBP regardless of the cause of sepsis. Although there was some tendency, PMX-DHP did not significantly improve the prognosis of effective cases in comparison with non-effective cases, probably because of the limited number of patients included. Among the sepsis-related biomarkers, only S1P values were significantly different between the two groups before PMX-DHP, and S1P levels were significantly increased after treatment in the effective cases. CONCLUSION: S1P levels prior to PMX-DHP can be used to predict its efficacy. In addition, continuous monitoring of S1P levels can indicate the effectiveness of PMX-DHP in patients with septic shock.

The efficacy and associated bleeding complications of recombinant antithrombin supplementation among intensive care unit patients.

INTRODUCTION: The aim of this study was to evaluate the efficacy and complications of recombinant antithrombin (rAT) supplementation for adult patients with disseminated intravascular coagulation (DIC) compared with conventional plasma derived AT (pAT) treatment in the intensive care unit. MATERIALS AND METHODS: This study was performed in a single national university hospital in Japan. Adult patients from April 2015 to March 2016 with DIC were divided into two groups based on the type of AT agent used: the pAT group (n=24) and the rAT group (n=21). Patient demographics, medical history, diagnosis, blood tests, various clinical scores, AT activity, complications, and clinical outcome were collected and analyzed retrospectively. RESULTS: Significantly higher SIRS and APACHEII scores were confirmed in the rAT group than the pAT group. The initial dose of AT was significantly higher in the rAT group than in the pAT group. ATIII values before and after initial supplementation and during their ten-day clinical course were statistically similar between two groups. During the same period, 10 bleeding adverse events were found and there was no significant difference between both groups. Significantly more cases of the rAT group were administered with recombinant thrombomodulin concomitantly than those of the pAT group. Despite significantly more severe patients in rAT group, the clinical outcomes were the same in each group. CONCLUSIONS: Compared with pAT, the supplementation of rAT indicates clinical effectiveness without increasing the risk of bleeding complications in adult DIC patients with low AT activity.

Thromboelastometric analysis of the risk factors for return of spontaneous circulation in adult patients with out-of-hospital cardiac arrest.

It is well known that coagulopathy is observed in patients with out-of-hospital cardiac arrest (OHCA). Thrombolytic therapy for those patients has been controversial until now. The purpose of this study was to identify a significant predictor for return of spontaneous circulation (ROSC) of OHCA patients in the emergency department (ED) using whole blood viscoelastic testing. Adult non-trauma OHCA patients transported to our hospital that underwent thromboelastometry (ROTEM) during cardiopulmonary resuscitation between January 2013 and December 2015 were enrolled in this study. We divided patients into two groups based on the presence or absence of ROSC, and performed statistical analysis utilizing patient characteristics, prehospital data, laboratory data, and ROTEM data. Seventy-five patients were enrolled. The ROSC group and non-ROSC group included 23 and 52 patients, respectively. The logistic regression analysis, utilizing significant parameters by univariate analysis, demonstrated that lactate level [odds ratio (OR) 0.880, 95% confidence interval (CI) 0.785-0.986, p = 0.028] and A30 of EXTEM test [OR 1.039, 95% CI 1.010-1.070, p = 0.009] were independent risk factors for ROSC. The cut-off values of lactate and A30 in EXTEM were 12.0 mmol/L and A 48.0 mm, respectively. We defined a positive prediction for ROSC if the patient presented lower lactate level (<12.0 mmol/L) and higher A30 of EXTEM (≥48.0 mm) with high specificity (94.7%) and accuracy (75.0%). The present study showed that lactate level and ROTEM parameter of clot firmness were reliable predictors of ROSC in the ED for adult patients with OHCA.

The thromboelastometric discrepancy between septic and trauma induced disseminated intravascular coagulation diagnosed by the scoring system from the Japanese association for acute medicine.

The aim of this study is to evaluate the hematological differences between septic and traumatic disseminated intravascular coagulation (DIC) using the rotational thromboelastometry (ROTEM).This retrospective study includes all sepsis or severe trauma patients transported to our emergency department who underwent ROTEM from 2013 to 2014. All patients were divided into 2 groups based on the presence of DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We statistically analyzed the demographics, clinical characteristics, laboratory data, ROTEM findings (EXTEM and FIBTEM), and outcome.Fifty-seven patients (30 sepsis and 27 severe trauma) were included in primary analysis. Sepsis cases were significantly older and had higher systemic inflammatory response syndrome (SIRS) scores, whereas there were no significant differences in other parameters including Acute Physiology and Chronic Health Evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score. Twenty-six patients (14 sepsis and 12 severe trauma) were diagnosed with DIC. The Septic DIC (S-DIC) group was significantly older and had higher DIC scores than the traumatic DIC (T-DIC) group. Hematologic examination revealed significantly higher CRP, fibrinogen, lower FDP, DD, and higher FDP/DD ratio were found in the S-DIC group in comparison with the T-DIC group. ROTEM findings showed that the A10, A20, and MCF in the FIBTEM test were significantly higher in the S-DIC group. However, no statistical differences were confirmed in the LI30, LI45, and ML in EXTEM test.The plasma fibrinogen level and fibrinogen based clot firmness in whole-blood test revealed statistical significance between septic and traumatic DIC patients.

Utility of Measurement of Serum Lactate in Diagnosis of Coagulopathy Associated with Peripheral Circulatory Insufficiency: Retrospective Evaluation Using Thromboelastometry from a Single Center in Japan.

Recently, serum lactate level rather than systolic blood pressure (sBP) has been widely used to diagnose peripheral circulatory insufficiency, which often leads to coagulopathy with systemic inflammation. However, most of the reported disorders were examined by plasma samples. The aim of this study was to evaluate the utility of serum lactate for detecting coagulopathy with circulatory failure by using thromboelastometry as well as standard coagulation test. 192 adult patients transported to our hospital between January 2013 and September 2014 were enrolled in this retrospective study. The sBP, serum lactate and thromboelastometry (ROTEM(®)) were measured in these patients in the emergency department. All patients were divided into three groups based on serum lactate levels: (1) the severe group (≥4 mmol/L, n=41); (2) the mild group (<4 mmol/L and ≥2 mmol/L, n=59); and (3) the normal group (<2 mmol/L, n=92). Patients in the severe group were of a significantly younger age but had lower pH and poor outcome. SBP was significantly lower and heart rates were higher in the severe group than in the other groups. Prolonged PT-INR and APTT were statistically confirmed in the severe group. ROTEM findings in the severe group revealed significantly lower alpha angle, shortened Lysis Onset Time and significantly more cases exhibited hyperfibrinolysis. The same analysis with the cut-off level of sBP at 90 mmHg showed no significant difference in ROTEM findings between the two groups. Abnormal serum lactate levels (≥4.0 mmol/L) properly reflected peripheral circulatory insufficiency and were more closely associated with coagulopathy such as hyperfibrinolysis and hypocoagulability than sBP.