The resolution phase of inflammation was previously considered to be a passive process. However, recent findings indicate that the resolution of inflammation tends toward being an active process that enables inflamed tissues to return to a state of homeostasis. This process is facilitated by pro-resolving lipid mediators, which are mainly derived from ω6-polyunsaturated fatty acids (PUFA), such as arachidonic acid and ω3-PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The bioactive pro-resolving lipid molecules are 1) lipotoxin A and B, derived from arachidonic acids; 2) resolvin D1-D4, derived from DHA; 3) resolvin E1 and E2, derived from EPA; and 4) protectin D1, derived from DHA. The resolution of inflammation requires pro-resolving mediator-activated programs that stop neutrophil infiltration to inflamed tissues, promote the uptake and clearance of apoptotic inflammatory cells, and stimulate the antimicrobial activities of mucosal epithelial cells. Acetylsalicylic acid (aspirin) promotes the pro-resolving process by facilitating the production of lipoxin, resolvin, and protectin through the acetylation of cyclooxygenase (COX)-2, while selective COX-2 inhibitors block the production of prostaglandins as well as that of pro-resolving molecules. These findings suggest new possibilities in the development of novel prophylactics, nutritional approaches and pharmaceutical therapeutics for the treatment of inflammatory diseases in critical care.

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Pulmonary artery catheterization has been widely used for cardiac output and hemodynamic monitoring. However, the clinical usefulness of pulmonary artery catheterization has been questioned because its use does not necessarily improve prognosis. Fortunately, alternatives to pulmonary artery catheterization have emerged. The pulse contour method monitors the beat-by-beat stroke volume based on an analysis of the arterial pressure waveform, while the partial carbon dioxide rebreathing technique monitors cardiac output by applying the indirect Fick method to carbon dioxide. The esophageal Doppler method approximates cardiac output based on the descending aortic blood flow. Echocardiography and transpulmonary thermodilution not only measure cardiac output, they also provide additional information regarding its determinants. Pulse pressure variation and stroke volume variation are capable of predicting the hemodynamic effects of volume loading. Central venous oxygen saturation, an indicator of the imbalance between oxygen supply and demand, can be monitored continuously using a specific central venous catheter. Here, we address the clinical potentials and limitations of these technologies.

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There are several reports on non-traumatic Clostridium perfringens (C. perfringens) infection rapidly progressing to intravascular hemolysis and metabolic acidosis and eventually death, within a few hours after admission. In such cases, α toxin of C. perfringens is responsible for causing intravascular hemolysis followed by severe anemia, acute renal failure, disseminated intravascular coagulopathy, and multiple organ failure. Surgical debridement is the treatment of choice. High dose of penicillin, hyperbaric oxygen treatment, continuous hemodiafiltration, polymyxin B-immobilized fiber direct hemoperfusion, and plasma exchange are also considered as promising treatment options. However, the optimal therapeutic strategy has not been established thus far. Antitoxin against the α toxin of C. perfringens has been used as a treatment for C. perfringens infection for a long time. However, medical doctors of the current generation are not familiar with this therapeutic option, because it has not been introduced as a treatment of choice in medical papers or congresses. Therefore, in this paper, we introduce the use of antitoxin against the alpha toxin of C. perfringens as the optimal therapy.

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Objectives: To investigate the annual trend in the clinical outcomes observed in a pediatric ICU (PICU) at Osaka Medical Center and Research Institute for Maternal and Child Health. Methods and Patients: The pediatric index of mortality (PIM) score was collected for each patient admitted to our PICU between 2003 and 2006. The patients were categorized into 4 groups according to the respective managing departments; cardiovascular surgery, other surgeries, cardiology and other pediatrics. The predicted number of deaths was obtained by summing the probability of death (PIM score) for every patient in each group. The ratio of the observed to the predicted deaths (O/P ratio) was then calculated. Results: The O/P ratio in total patients decreased from 0.61 in 2003 to 0.30 in 2006. The O/P ratio in the cardiovascular surgery and cardiology also decreased, while that in the other surgeries and other pediatrics did not decrease. The predicted mortality in other pediatrics was high and the O/P ratio remained high for 4 years. Conclusions: Because of the improving the O/P ratio in cardiovascular surgery and cardiology, the total O/P ratio in our PICU improved during the 4-year study period.

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A 73-year-old male who suffered from massive blood loss of over 39,000 ml due to injury to the azygos and pulmonary veins during elective thoracic surgery was admitted to the ICU. On admission, while his hemodynamics appeared to be almost stable under a low-dose dopamine infusion, blood loss of over 100 ml·hr⁻¹ still persisted through the chest drainage tube. Extensive transfusion therapy, including packed red blood cells, fresh frozen plasma and platelet concentrates, was undertaken during the first 12 hrs, and the laboratory data, including the coagulation profile, almost normalized within the first 24 hrs. However, there was no change in the amount of blood loss, while neither surgical nor intravascular intervention seemed possible. Despite no apparent evidence obtained by thromboelastometry to suggest the occurrence of excessive fibrinolysis, tranexamic acid was injected at a loading dose (10 mg·kg⁻¹), followed by continuous infusion (4 mg·kg⁻¹·hr⁻¹). Obvious reduction of the bleeding was observed within 1 hr of the start of this drug, and the bleeding was almost entirely controlled by 3 hrs after the initiation of tranexamic acid therapy. Tranexamic acid could contribute to hemostasis in cases with intractable bleeding, even in the absence of apparent evidence of excessive fibrinolysis.

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A 53-year-old man without a history of tuberculosis was admitted to our hospital because of disturbances in consciousness. He was diagnosed with meningitis on the basis of the following: fever, nuchal rigidity, and increase in the number of cells in the cerebrospinal fluid. Ceftriaxone was therefore administered. However, his level of consciousness progressively deteriorated, and finally, he became comatose. He was therefore intubated and admitted to the ICU. The ineffectiveness of antibiotic treatment, progressive deterioration of consciousness, development of hydrocephalus and meningeal enhancement primarily around the basilar cisterns —as revealed by gadolinium-enhanced magnetic resonance (MR) images— strongly suggested the presence of tuberculous meningitis. We therefore initiated anti-tuberculous chemotherapy and steroid treatment. The cells in the cerebrospinal fluid were subjected to QuantiFERON^® TB-2G (QFT-2G) test, and positive results were obtained on the 15th day. Mycobacterium tuberculosis was detected in a culture of a cerebrospinal fluid sample on the 51st day. Although anti-tuberculous chemotherapy was continued for 6 months, the patient barely regained consciousness and was severely disabled; therefore, tracheostomy and gastrostomy were required for the management of the patient. The QFT-2G test with cerebrospinal fluid cells is useful for the early diagnosis of tuberculous meningitis.

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We retrospectively investigated the differences in clinical course for 8 patients who developed acute exacerbation of interstitial pneumonia and who were treated in the ICU from December 2005 to May 2008. All patients received high-dose corticosteroid therapy, and four also underwent polymyxin B-immobilized fiber column hemoperfusion (PMX-DHP) treatment, which was initiated as soon as possible after ICU admission and carried out at a flow rate of 80–100 ml·min⁻¹ for 4–6 hours every 2 days. The mean P/F ratio in the 4 patients without PMX-DHP (N group) was 78.8±25.6 (mean±SD) at ICU admission and was 115.7±90.8 at 48 hours post ICU admission. In the patients undergoing PMX-DHP (P group), P/F ratio improved markedly from 87.5±22.7 to 168±64.9 during the identical period. The 1-month and 3-month survival rates in N group were 50 and 25%, while those in P group were 100 and 75%, respectively. All patients in N group were intubated and ventilated mechanically, while only 1 patient in P group required non-invasive positive pressure ventilation for 10 hours. The differences of clinical course between N and P groups suggest that PMX-DHP is effective for acute exacerbation of interstitial pneumonia.

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A 69-year-old man was admitted to our intensive care unit because of a disturbance in consciousness. He had been diagnosed as having type II diabetes at the age of 24 years but had not developed severe liver dysfunction. A plain abdominal CT showed left pyelonephritis and an expanded left renal pelvis as a result of ureteral stones. A laboratory investigation revealed hyperammonemia. A cranial MRI showed edematous changes in bilateral thalamus and bilateral insula, supporting a diagnosis of hyperammonemia. After the placement of a left ureteral stent, the patient's consciousness level reversed and his plasma ammonia level returned to normal. Proteus mirabilis, a urea-metabolizing bacteria, was cultured in blood and urine samples from the patient. The production of urease by bacteria in the urinary tract probably hydrolyzed the urinary urea, producing ammonia. We suspect that the source of the disturbed consciousness in the present patient might have been hyperammonemic encephalopathy caused by the absorption of ammonia produced by bacteria in the retained urine into the systemic circulation.

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A 39-year-old man accidentally ingested a cleaning solution containing 1.3% hydrofluoric acid and 10% ammonium fluoride. He was brought to our hospital within half an hour of this episode. He was fed milk via a nasogastric tube and admitted to the ICU. As a treatment for prolonged hypocalcemia, calcium gluconate was administered. Continuous hemodialysis (CHD) was performed because of rapidly progressive hyperkalemia. Within 4 hrs of hospitalization, his blood potassium level increased rapidly. Torsades de pointes (TdP) developed suddenly 7 hrs after his admission to the hospital; 2 g of magnesium sulfate was administered immediately and the cardiac rhythm was restored. At the time of TdP, his blood K level was found to be 3.97 mEq·l⁻¹. During CHD and after Ca administration, his blood Ca level was found to be 7.68 mg·dl⁻¹. However, the Mg level was as low as 0.8 mg·dl⁻¹, and this was suspected to be the cause of TdP. The Mg concentration of the fluid used for CHD has been adjusted to 1.2 mg·dl⁻¹, which is the concentration used for patients with chronic renal failure. Therefore, this concentration was not appropriate for our patient with hypomagnesemia.

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A 61-year-old man developed atrial fibrillation 20 days after repair of a left ventricular rupture caused by acute myocardial infarction. Sinus rhythm was restored by cardioversion and maintained with pilsicainide (150 mg·day⁻¹). Hyperkalemia appeared on postoperative day 47 and thus hemodialysis was scheduled. However, the patient was immediately transferred to the ICU for continuous hemodiafiltration (CHDF) before starting hemodialysis due to the development of ventricular tachycardia (VT). It could not be denied that the hyperkalemia might be related to the VT, but polymorphic VT persisted when the serum potassium concentration reached the normal range 12 hours after starting CHDF. These findings indicated that the proarrhythmic effect of pilsicainide was responsible for the sustained VT, which was accompanied by pilsicainide toxicity. The sinus rhythm was restored 36 hours after CHDF, when the serum pilsicainide concentration was 3.36 μg·ml⁻¹, which was still substantially higher than the therapeutic range of 0.2–0.9 μg·ml⁻¹. Despite the limited ability of hemodialysis to remove pilsicainide, CHDF clearly contributed to reducing the serum pilsicainide concentration, which apparently restored the sinus rhythm. These findings suggest that CHDF can help to treat arrhythmia caused by pilsicainide toxicity.

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Acquired hemophilia A is a rare, but refractory and life-threatening hemorrhagic disease, caused by an autoantibody to coagulation factor VIII. We report the case of an 80-year-old female without any history of abnormal bleeding who underwent esophagectomy for esophageal carcinoma. Two months after the operation she experienced the sudden onset of dyspnea associated with a right extrapleural hematoma and was transferred to our hospital. Her activated partial thromboplastin time was extremely prolonged, and there was continuous oozing from the venipuncture sites. Fresh-frozen plasma infusion was ineffective, and she was later diagnosed with acquired hemophilia A based on a positive test for autoantibody to factor VIII (36.0 Bethesda U·ml⁻¹). We started treatment with prednisolone and recombinant activated factor VII, and the factor VIII autoantibody titer decreased to 1.2 Bethesda U·ml⁻¹ by 70 days after admission. The patient experienced repeated nasal and digestive tract bleeding, but the bleeding and the size of extrapleural hematoma gradually decreased. The patient was discharged from the hospital 78 days after admission. The early diagnosis and rapid treatment would have contributed to her good outcome.

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Procalcitonin (PCT) is a useful biomarker for bacterial infection. However, several cases of an elevated PCT level in patients without infection have been reported. A 66-year-old man with Goodpasture's syndrome was found to have a high anti-glomerular basement membrane antibody (anti-GBM antibody) level (111 EU) and was transferred to our ICU because of acute respiratory failure due to pulmonary alveolar hemorrhage. Even after steroid pulse therapy and plasma exchange (PE), the patient's renal function remained aggravated. Hemodialysis (HD) had already been started prior to ICU admission. On the 30th hospital day, an elevated serum PCT level of 50.32 ng·ml⁻¹ was noted, although no other evidence of infection was seen. Steroid pulse therapy and PE were continued, and the patient's serum PCT level decreased to 3.72 ng·ml⁻¹ and his anti-GBM antibody titer became negative. On the 40th hospital day, he developed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and his PCT level once again increased (22.5 ng·dl⁻¹). However, his anti-GBM antibody titer remained negative. His clinical conditions improved, and he returned to the general ward on the 75th hospital day. In the present case, the PCT level might have reflected tissue damage of the lungs and kidneys caused by the anti-GBM antibody and the presence of Goodpasture's syndrome. Therefore, in cases with Goodpasture's syndrome and a high PCT level, the possibility of not only bacterial infection, but also lung and/or renal injury caused by the anti-GBM antibody should be considered.

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