In the pathophysiology of sepsis leading to multiple organ dysfunction syndrome (MODS), uncontrolled hyper-inflammatory responses to infected microorganism play a pivotal role. However, the concept that MODS and death from sepsis was attributable to overstimulated immune response, which based on basic studies in which large doses of endotoxin or bacteria were administered and the animal died from “cytokine storm”, and does not reflect the clinical pictures of sepsis. The outcome of sepsis depends mainly on delayed organ failure, which cannot be explained by the concept. We can discuss the pathophysiology of sepsis as mentioned below to comprehend this condition.
1) The duration of overstimulated inflammatory response to infection is short-lasting than it was originally thought to be. Immunosuppression may occur earlier phase of sepsis. Characteristic finding from autopsy of septic patients is apoptotic immune cell death, such as lymphocytes and intestinal epithelial cells, which may contribute to the impaired immune response of sepsis.
2) Organ dysfunction of sepsis cannot be explained by histological evidence of cell death. The concept of sepsis-induced mitochondrial dysfunction is supported as cytopathic hypoxia to understand the pathogenesis of organ dysfunction.
A considerable body of evidence has accumulated the implication of endotoxin in pathophysiology of sepsis. Although 25g of endotoxin is reserved in gut of healthy humans, full clinical manifestations of sepsis can be developed by administration small dose of endotoxin. However, antiendotoxin strategy, such as monoclonal antibody, have not provided survival benefits in clinical trials. EUPHAS trial is a trial to determine whether polymixin B hemoperfusion (PMX-DHP) added to conventional therapy improves outcome, 1) hemodynamic parameters, 2) respiratory parameters, SOFA score, and 28-day mortality compared with conventional therapy. PMX-DHP improved significantly those parameters and mortality. The analysis triggered the stopping rule based on a statistically significant reduction in mortality. We reviewed several points regarding this study.
1) Although circulating endotoxin levels was not determined, does the clinical efficacy of PMX-DHP depend on removal of endotoxin?
2) Severe leukocytopenic/thrombocytopenic patients, those are important target of this treatment, have been excluded.
3) Why did not improve hemodynamic parameters in conventional therapy?
4) Is the 28-day mortality 53% in conventional therapy group too high?
5) Is it important full removal of endotoxin? Does PMX-DHP improve immunosuppressive state of sepsis?
6) Is early termination of the study justified?
This trial realized the importance of PMX-DHP in the management of abdominal sepsis in our country again, and also may provide the influence to the world.

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2-arachidonoyl glycerol (2-AG), an endogenous cannabinoid, has been drawing much attention as an early stage mediator at the onset of sepsis. In the present study, we investigated weather rimonabant, one of the CB1 antagonists, alleviated the medical conditions during endotoxemia and measured the level of prostaglandin E metabolite (PGEM). A cylindrical electric transmitter was connected to the transducer via a cable embedded beneath the animal's dorsal skin and sutured in place. Signals from the transmitter were detected by a receiver placed directly beneath the cage via telemetry. We monitored arterial pressure via catheter in the carotid artery and administrated drugs via catheter in jugular vein. We separated animals into three groups. The control group received lipopolysaccharide (LPS, 0.3 mg/kg, i.v.) and vehicle i.v. Experimental animals received LPS and rimonabant (1, 3 mg/kg/h) i.v. Ten minutes after the injection of the vehicle or rimonabant, LPS (0.3 mg/kg, i.v.) was administered. The prostaglandin E metabolites (PGEM) levels were measured by EIASA. In the control group, LPS induced intestinal paralysis and the decline in blood pressure peaked 1-3h after administration of LPS. In rimonabant-treated group, rimonabant inhibited LPS-induced intestinal paralysis and hypotension. Levels of PGEM in guinea pig was increased by LPS-administrate, rimonabant inhibits PGEM increase. The results suggest that rimonabant was effective against LPS-induced endotoxemia in guinea pigs.

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Percutaneous dilatational tracheostomy (PDT) is a simple and rapid method of tracheostomy. However, a number of complications, such as subcutaneous emphysema, mediastinal emphysema, and pneumothorax, have been reported. We report a case of massive subcutaneous emphysema, mediastinal emphysema, and pneumothorax after PDT with the Blue Rhino method (BR), and discuss preventive measures against these complications. A 56-year-old woman with cerebral contusion, acute subdural hematoma, and lung contusion was weaned from ventilatory support but extubation with an orotracheal tube failed due to dyspnea. The following day, PDT with BR was performed, but the orotracheal tube was extubated prior to insertion of a tracheostomy tube. Massive subcutaneous emphysema, mediastinal emphysema, and right pneumothorax were confirmed immediately after PDT, suggesting that obstruction of the skin incision during insertion of the tracheostomy tube and proximal tracheal obstruction after extubation of the orotracheal tube during PDT with BR blocked evacuation of the high intratracheal pressure caused by coughing, and high-pressure air from the tracheostomy caused emphysema. PDT with BR may cause elevation of intratracheal pressure during insertion of the dilator and tube, and control of the pressure with airway management during PDT with BR is important for prevention of emphysema.

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We report a case of refractory gastric tube ulcer perforating the right atrium. A 72-year-old man with a history of esophageal cancer and subtotal esophagectomy with posterior mediastinal gastric tube reconstruction was diagnosed with a gastric tube ulcer 6 months previously. He developed fever and hemoptysis, was admitted to our department for the treatment of pneumonia, and was then followed-up with antibiotic therapy. However, there was sudden onset of septic shock and bleeding from the gastric tube, and he was transferred to the ICU. The administration of blood transfusion and a vasopressor was not effective, and the patient died of hemorrhagic shock on the fifth day after ICU admission. Autopsy revealed gastric tube ulcer perforation of the right atrium. Gastric tube ulcer perforation has been recognized a fatal postoperative complication. Some patients with such a complication remain asymptomatic until their condition worsens or changes suddenly. To improve the prognosis of patients with gastric tube ulcer through early diagnosis and treatment, it is important to pay attention to symptoms other than gastrointestinal ones.

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A 67-year-old woman was admitted with cardiopulmonary arrest to our hospital's emergency and critical care medical center. The patient's heartbeat was restarted with cardiopulmonary resuscitation. Reintubation with an endotracheal tube was performed, but it was difficult to insert it more than 18 cm because of the circumferential hypertrophy of the tracheal wall demonstrated by computed tomography. We later obtained clinical records showing that she had been extubated about 4 weeks previously after artificial ventilation with intubation for the treatment of acute pneumonia for 13 days in another hospital. Although the patient was slightly hoarse after extubation, stridor was not heard. She had been diagnosed as having sleep apnea syndrome 2 weeks after extubation. Although dyspnea at rest appeared approximately 3 weeks after extubation, she was diagnosed as having asthma. She subsequently exhibited stridor, paradoxical respiration, and chest-wall retraction prior to cardiopulmonary arrest. Histological findings revealed that the hypertrophy of the tracheal wall was due to granulation tissue proliferation. These results indicate that it is necessary to take postintubation tracheal stenosis into consideration with early confirmation of the intubation record in the clinical process.

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