One of the main goals of recent intensive care medicine is to overcome sepsis; however, no clinical trials about sepsis have proved the effectiveness of treatments. The cause seems to be due to the entry criteria of clinical studies about sepsis. Sepsis is defined as systemic inflammatory response syndrome (SIRS) caused by infection, but SIRS criteria is not specific and does not reflect severity and the pathophysiology of patients. Therefore, the PIRO score has been propounded, similar to the TNM classification in oncology. The four components of the PIRO score are predisposition, insult/infection, response, organ dysfunction and each category is scored to stratify the severity of sepsis. Staging contents of each category in the PIRO score have been proposed for severe sepsis, community acquired pneumonia, and nosocomial pneumonia. The PIRO score accurately predicted the prognosis of patients. A clinical study using this PIRO score as a precise characterization tool and staging system of patients is expected.

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Fluid therapy using massive crystalloids started in the 1960's for the purpose of resuscitation for acute hemorrhagic shock. Although the concept was “fluid resuscitation”, its concept was converted to the fluid regimen for surgery. The exsistence of non-functional extracellular volume (nfECV) developed the concept of “third space”, and it also facilitated the massive crystalloid use during surgery. Although the leaders of this “fluid resuscitation”, Shires and Moore warned potential users about the adverse effect of massive infusion, this concept of massive crystalloid infusion has prevailed, and has been still a recognized procedure up to the present. Recently, it has been confirmed that massive crystalloid infusion is significantly related to postoperative complications through weight gain. The concept of third space was re-evaluated, and the existence of nfECV is now being denied. It has been shown that postoperative ECV depends on the in-out balance of crystalloids. The concept of “edema steals water” may be wrong, and “crystalloid makes edema” may be justified. We should try to reduce postoperative edema to avoid massive crystalloid load. We should be particularly aware of sodium overload, since intraoperatively-administered sodium remains several days postoperatively.

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A recombinant human activated protein C had been used for the treatment of severe sepsis and septic shock but was withdrawn from the global market because no survival benefit has been shown according to the findings of a recent randomized controlled trial following a decade of extensive controversy concerning its safety and effectiveness. The original large phase III trial published in 2001 was funded by Eli Lilly and Company, the manufacturer of the drug, and was criticized for a problematic protocol amendment, an early termination for benefit and interpretation of abundant subgroup analyses. The company also financially supported the Surviving Sepsis Campaign and caused those conflict-of-interest issues. Controversy remains over the successful administration in critical care in Japan and it is important to learn how to practice the evidence-based medicine from the failure of this drug.

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Evidence-based practice (EBP) aims to effectively provide high-quality care that provides good cost-benefit results to patients, care providers, and healthcare institutions, and also meets individual patient's needs. A review of English literature on critical care nursing reported in the past 5 years showed the following findings. The number of EBP models described in critical care nursing journals was 13 in 21 papers, and the number of papers using EBP models for research was 4. The most commonly used model was the IOWA model, and EBP efficacy had been studied using this model. The EBP processes used for EBP models often described in the journals of critical care nursing involved search and collection of evidence resolving clinical questions, evaluation of evidence, evidence integration considering clinical experiences, patients' value judgments and situations of healthcare institutions, and evaluation of EBP and its efficacy.

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Objectives: The purpose of the study was to investigate the clinical and prognostic effects of recombinant thrombomodulin (rTM) for sepsis-induced disseminated intravascular coagulation (DIC), compared with danaparoid sodium (DS). Methods: A single center retrospective observational study of 73 patients with sepsis-induced DIC was performed from January 2006 to December 2010. Results: The patients were classified into rTM (n = 33), and DS (n = 40) groups. Patients in the rTM group had a DIC score ≥5 or a DIC score of 4 and a platelet score of 3, and were treated with rTM. Those in the DS group met the same criteria and were treated with DS. In the rTM group, platelet count showed a significant increase after Day 4. The antithrombin (AT) values significantly increased in the rTM and DS groups in Day 4 compared with Day 1. The D-dimer values did not change significantly in any of the groups. The rTM group had significantly better long-term outcome than the DS group. However, after adjusting for Sequential Organ Failure Assessment score without Glasgow coma scale(SOFA–CNS), intra abdominal sites, pneumonia, rTM did not significantly affect the 28-day mortality. Conclusions: These results show that rTM is effective for treatment of septic DIC, with good recovery of the platelet count and good long-term prognosis (P < 0.01). However, rTM did not significantly affect the 28-day mortality.

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Objective: The administration of sivelestat for acute lung injury (ALI) was observed to be associated with a deterioration in the long-term prognosis based on a multicenter trial, and its usage was therefore cancelled in our ICU since 2007. In this study, we compared the prognosis of sepsis-induced ALI before and after changing the therapeutic strategy. Method: The subjects consisted of adult sepsis-induced ALI cases that were admitted to the ICU within 21 months before and after January 2007, and required mechanical ventilation within 24 hours. These patients were divided into 64 cases for the early group and 36 cases for the latter group, and they were compared with each other. Result: There was no difference between the two groups regarding patient background. Sivelestat was used in 54 cases (84.4%) in the early group and 4 cases (11.1%) in the later group. There was no significant difference in the 28-ventilator free days (VFD), the length of ICU stay, the length of hospital stay, or in-hospital mortality, but the mechanical ventilation time was significantly shorter in the latter group. Based on a multivariate analysis for in-hospital mortality, the odds ratio of the latter group was lower compared to the early group, at 0.269 (P = 0.028), while according to a multivariate analysis for in-hospital mortality and 28-VFD including the use of sivelestat, no prognosis-improving tendency due to sivelestat was observed. Conclusion: The prognosis of sepsis-induced ALI was not found to deteriorate after cancelling the administration of sivelestat.

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Purpose: To elucidate factors responsible for delayed rehabilitation in the perioperative period of cardiac surgery. Methods: A total of 55 patients scheduled for cardiac surgery were classified into two groups: those in the successful group could walk before day 4 postoperatively, while those in the delayed group could not walk until at least day 5 postoperatively. The two groups were compared with regard to various factors, including age, preoperative body mass index, histories of smoking and cardiac surgery, preoperative complications, preoperative New York Heart Association (NYHA) class, left ventricular ejection fraction, postoperative pulmonary complications, postoperative using or without norepinephrine, period of postoperative intubation, cardiopulmonary bypass (CPB) time, postoperative pain, postoperative interleukin (IL)-6 production, retinol-binding protein, and prealbumin level. Results and Conclusion: The results of the present study indicated significant differences between the successful group and delayed group in preoperative NYHA class, postoperative using or without norepinephrine, CPB time, period of postoperative intubation, IL-6, and prealbumin level. IL-6 level, period of postoperative intubation, and CPB time were detected as factors correlated with delayed rehabilitation by multivariate logistic regression analysis. Summary: NYHA class, Postoperative circulation unstable, period of postoperative intubation, and CPB time were correlated with delayed rehabilitation following cardiac surgery. These effects were suggested to be related to inflammation accompanying surgical invasion.

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We report a case of severe Churg-Strauss syndrome (CSS) complicated with diffuse alveolar hemorrhage. A 47-year-old female patient complicated with diffuse alveolar hemorrhage, disseminated intravascular coagulation and intracerebral hemorrhage was admitted to our ICU due to acute respiratory failure. As a result of several examinations, the patient was first diagnosed as having CSS. After treatment with high-dose steroid under mechanical ventilation, acute respiratory failure with diffuse alveolar hemorrhage was improved. However, when the steroid dose was reduced, diffuse alveolar hemorrhage recurred. Therefore, plasma exchange therapy was performed and resulted in dramatic improvement of recurrent diffuse alveolar hemorrhage, and the patient was weaned from mechanical ventilation and survived. Generally, immunosupressant agents are recommended for treatment of CSS when there is no response to steroid therapy. However, it has been demonstrated that the main cause of death in CSS patients with diffuse alveolar hemorrhage is sepsis. Therefore, plasma exchange rather than immunosuppressant therapy is a useful option for treatment of severe CSS to prevent complication with severe infection.

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The patient was a 67-year-old male who required emergency transport due to a traffic injury. Intra-abdominal hemorrhage was diagnosed and emergency surgery was performed. On day 9 after surgery, his respiratory condition aggravated and bilateral pulmonary arterial embolism and inferior vena cava thrombosis at the level from the upper to lower region of the renal vein developed concomitantly. Since the patient was under treatment with unfractionated heparin to prevent atrial fibrillation, which he had developed in the past, and was positive for antibodies against heparin-platelet factor-4 (PF4) complex, we concluded that the thrombi were formed by heparin-induced thrombocytopenia (HIT). Sepsis also developed concomitantly and methicillin-resistant Staphylococcus aureus (MRSA) was detected in blood culture. No apparent source of infection was observed on imaging, which suggested that the thrombi may have been infected through a catheter, leading to suppurative thrombophlebitis. This case serves as a reminder that heparin administration may cause thrombosis and induce suppurative thrombophlebitis.

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Objectives: To investigate the incidence of central venous catheter-related thrombosis (CRT), risk factors, complication and convalescence in critically ill patients. Methods: This observational study comprised patients with central venous catheters (CVCs) from November 2009 to November 2010 in ICU of Saga University Hospital. We used ultrasonography to detect CRT. Results: The incidence of CRT was 107/205 cases of CVCs (52%) in 67/100 patients. The incidence of CRT at internal jugular vein was higher than the incidence at femoral vein (63% vs 28%, P < 0.001). Patients with CRT often complicated any infection in comparison with patients without CRT (67% vs 45%, P = 0.04). Rates of central line-associated bloodstream infection were higher among CVCs with CRT than CVCs without CRT (9% vs 1%, P = 0.008). Length of ICU stay for patients with CRT was prolonged in comparison with patients without CRT, whereas mortality rate was comparable between patients with CRT and patients without CRT. Conclusions: CRT occurred in 52% of 205 CVCs and might be related with infection.

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While surgical intervention is recommended for fulminant Clostridium difficile infection (CDI), the indications, timing, and technique of surgical intervention remain controversial because of the high postoperative mortality. We herein report a fatal case of fulminant CDI complicated with a toxic megacolon that required a colectomy. A 69-year-old male suffered from CDI complicated with septic shock and high intra-abdominal pressure, and he soon developed multiple organ failure. He first underwent a colostomy in order to reduce his intra-abdominal pressure. After the colostomy, his lactate concentration value was temporary improved to below 5 mmol/l. However, the level soon increased to above 5 mmol/l, and he therefore underwent a second-look operation, and received a right-side colectomy and a massive small bowel resection. After the second-look surgery, he suffered from severe sepsis which was probably caused by the residual CDI and/or a bacterial translocation, and/or other health-care associated infections. The patient was also complicated with a short-bowel syndrome-related hepatic failure. On postoperative day 45, he developed multiple organ failure and died. To ensure that surgical benefit can be derived from intervention for fulminant CDI, physicians therefore have to timely perform subtotal colectomies when deemed appropriate.

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Scrub typhus is tick-borne rickettsial infection and is known to become severe in rare cases. The case of a 64-year-old woman is presented. The patient presented with headache and fever higher than 39 degrees Celsius after mushroom hunting 9 days prior to admission. Then, she developed impaired consciousness and respiratory failure and was transferred from another hospital to our hospital. She developed multiorgan failure associated with septic shock, disseminated intravascular coagulation and acute respiratory distress syndrome and was admitted to the ICU. Hemorrhagic shock requiring emergency endoscopic hemostasis occurred twice from a hemorrhagic gastric ulcer during her illness. Scrub typhus was suspected because of the medical history and characteristic skin rash, therefore, treatment with minocycline was administered, which resulted in improvement of the systemic symptoms. After day 10, the cognitive decline and character change were still present with new appearance of hyperalbuminorrhachia. Consequently, the patient was diagnosed as having encephalitis caused by scrub typhus. The encephalitis was improved and the patient was discharged on day 27. The principal symptom of scrub typhus is considered to be vasculitis due to vascular endothelial cell disorder. The vasculitis may be associated with not only multiorgan failure, but also multiple gastric mucosal injury and encephalitis in this case.

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Proteus syndrome is a rare disorder of patchy or mosaic postnatal overgrowth, with only about 100 cases having been reported to date. We describe a case of progressive tracheobronchial stenosis induced by thoracic deformity and scoliosis which were caused by progressive overgrowth of vertebrae and back muscles with Proteus syndrome. An 11-year-old boy suddenly developed severe dyspnea during hospitalization for treatment for asthma, then he was intubated and on mechanical ventilation. Chest CT revealed severe stenosis of trachea and bilateral bronchi. Despite medical treatment he could not be weaned from ventilator. He underwent tracheotomy and additional intervention to the thoracic deformity, the Nuss procedure, to push the sternum ante-ward with a curved steel bar, and episternectomy. Although he could not be taken off the ventilator postoperatively, reduced support was feasible and he was transferred to the pediatric ward. Chest CT showed amelioration of the tracheobronchial compression. Approximately 2 months later, however, the thoracic deformity worsened and the bronchi became stenotic again. He ultimately died of pneumonia. Although tracheobronchial stenosis was improved by the surgical intervention, its effect did not last long.

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Intravascular lymphoma (IVL) is a rare subtype of malignant lymphoma characterized by the proliferation of lymphoma cells in the lumina of small vessels of various organs. IVL is a rapidly progressive disease with a poor prognosis and is often difficult to diagnose because of its heterogeneous and non-specific symptoms. We herein report the rescued case of a 79-year-old male patient with IVL presenting with refractory circulatory shock. He initially complained of fever and appetite loss, and later developed circulatory shock and severe abdominal pain; he was diagnosed as having septic shock as a result of perforative peritonitis. He underwent an exploratory laparotomy, but no obvious abnormal findings were pointed out. He was transferred to the ICU postoperatively and presented with persistent circulatory shock and hyperlactacidemia refractory to fluid and catecholamine administration. His peripheral smear showed blast forms, so we performed bone marrow aspiration and random skin biopsies on ICU day 2 and 9, respectively, and the diagnosis of IVL with hemophagocytic syndrome was confirmed. Following a high-dose of methylprednisolone, antineoplastic agents were administered. He recovered from shock and was discharged to the general ward on ICU day 19.

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Acute necrotizing encephalopathy is a relatively rare condition in adults. We encountered an adult case of severe acute necrotizing encephalopathy that rapidly progressed to multiple organ failure and disseminated intravascular coagulation (DIC). A 24 year-old man had been treated for a sternal fracture and injuries to both knees, sustained during a motor vehicle accident. He did not have any significant medical history. He lost consciouness and his vital signs indicated shock after he had been running a temperature of 39°C and was transferred to another hospital. Soon after his arrival at the second hospital, the patient experienced convulsions, and was transferred to our institute under intubation, for more detailed evaluation and treatment. On admission, brain CT and cerebrospinal fluid examination yielded normal results. Initially, we suspected septic shock of unknown origin, and initiated treatment in the ICU. Lactic acidosis and hyperkalemia were noted, and continuous renal replacement therapy (CRRT) was initiated. The liver enzyme levels were drastically elevated, and the DIC worsened. On the second day after admission, brain herniation occurred. At this time, brain CT showed severe brain edema and bilaterally symmetrical low-density areas in the thalamus, brain stem, and cerebellum. We induced mild brain hypothermia (34°C) and administered 1 g of methylprednisolone and 180 g of mannitol for 3 days. However, on the fourth day, an electroencephalogram showed flat lines. On the 14th day after admission, the patient died of ventricular arrhythmia caused by hyperkalemia. In conclusion, clinicians should be alert to the possibility of acute necrotizing enchephalopathy, which causes impairment of consciousness, liver damage, and DIC, even in adults. The treatment of brain edema should never be delayed.

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A 34-year-old man with an implantable cardioverter-defibrillator (ICD) to control ventricular tachyarrhythmias arising from a cardiac lipoma developed a ventricular tachycardia (VT) storm. He was deeply sedated and treated with the intravenous administrations of amiodarone, nifekalant, lidocaine, propranolol, and landiolol. Concurrently, he was treated with antitachycardia pacing and direct current cardioversion, but the VT storm continued. Thoracic epidural anesthesia was performed to reduce the sympathetic output to the heart, and the VT storm was completely suppressed. This case suggests that thoracic epidural anesthesia is effective for the treatment of VT storms refractory to medications and catheter ablation.

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A 63-year-old man with chronic myelomonocytic leukemia and chronic renal failure received red cell concentrates (RCC) perioperatively during inguinal hernia repair. Irregular antibodies measured before the operation were negative, but on the 7th postoperative day, anti-E antibody was positive, and E antigen of the transfused RCC was also positive. There was no evidence of hemolysis, but if a delayed hemolytic transfusion reaction (DHTR) were to occur, the patient was not expected to survive. Therefore, RBC exchange was performed to remove E antigen-positive RBCs using plasmapheresis with the blood purification system for continuous hemodiafiltration (CHDF) and a blood plasma separation membrane. Native plasma was returned to the patient, the red blood cells were removed, and replaced with E-antigen negative RCC, albumin and saline. After RBC exchange, the percentage of E antigen-positive RBCs were decreased, and no transfusion reaction occurred. When patients with chronic renal failure have a risk of DHTR, RBC exchange may prevent DHTR.

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We report a patient who suddenly developed pulmonary embolism, respiratory arrest and circulatory collapse because of megacolon. A 67-year-old woman who had abdominal bloating six months before, and had general fatigue from one week before admission, suddenly became respiratory arrest and circulatory collapse on the way to doctor visit. She was transported to our hospital after return of spontaneous circulation in response to the resuscitative maneuver. Although consciousness was recovered on arrival at hospital, significant abdominal bloating and lower-limb edema was observed. Chest X-rays showed that patient's heart was extremely pressed to the right side of thorax by a enlarged colon filled with gas. Blood clots were recognized at bilateral lower pulmonary artery by thorax and the abdominal enhanced CT. Gut distention was relieved by colon fiberscopy. We started thrombolytic treatment. The pulmonary artery thrombus was diminished on the 4th day and she was discharged from hospital on the 19th day. She underwent elective total colectomy and made unevenful recovery. More than 90% of the thrombi that induce pulmonary embolism are produced in pelvic vein. In this case, we considered that dehydration and increased intra-abdominal pressure because of megacolon caused venous stagnation, which developed pulmonary embolism.

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