Increase and spreading of antibiotic-resistant organisms are widely reported in the world. Especially in respiratory infections, not only community-associated pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae), but also hospital-associated organisms (multiple-drug resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus) and new β-lactamase producing bacteria (extended spectrum β-lactamase, metallo-β-lactamase) are becoming serious problem. Recently, novel type of antibiotic resistant organisms, such as multiple-drug resistant Acinetobacter and New Delhi metallo-β-lactamase-1 producers were focused in Japan. Here, topics of new antibiotic-resistant organisms, and recent trends of antibiotic chemotherapy were reviewed.

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Background: Some patients who are admitted to the ICU die after their discharge from the ICU. The purpose of this study was to investigate the occurrence and cause of death during hospitalization in patients who were discharged from the ICU. Methods: We retrospectively collected data for 570 patients who were admitted to our ICU between 2006 and 2008 and who did not meet the following exclusion criteria: discharge from the ICU within 48 hours; age < 18 years; re-admission to ICU; death during ICU stay; and treatment withhold. Results: 56 patients died during their hospitalization, and a multivariate analysis revealed the presence of 6 independent predictors of death after ICU discharge: admission from the ward [OR (odds ratio) = 2.69], metastatic cancer (OR = 41.0), hematologic malignancy (OR = 9.71), Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR = 1.11 per point), re-intubation (OR = 5.59) and ICU discharge with mechanical ventilation (OR = 3.19). The major causes of death after ICU discharge were infection, progression of malignancy, and sudden cardiac arrest. Conclusion: About 10% of patients who were discharged from the ICU died during their hospitalization. Further evaluation of risk factors at ICU discharge is needed.

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Obscure gastrointestinal bleeding (OGIB) is defined as bleeding from the gastrointestinal tract, wherein the focus of bleeding cannot be clearly identified after upper and lower endoscopic examination. We report a case of OGIB for which the focus of bleeding was detected by capsule and double-balloon endoscopic examination. A 72-year-old man, who had regularly taken aspirin, was admitted to our hospital with severe melena. A routine upper and lower endoscopic examination could not detect the focus of bleeding. We discontinued aspirin treatment after admission because of the continuous melena. Further examination using capsule endoscopy (CE) on the 18th hospital day showed multiple ulcerations in the small intestine. The small bowel was emergently resected because progression of the ulcerations was observed by double-balloon endoscopy (DBE). The specimen showed multiple mesenteric arteriole infarctions. Because the discontinuation of anticoagulant agents increases the thrombotic risk, early examination using CE and/or DBE should be performed for OGIB.

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Ornithine transcarbamylase (OTC) deficiency is a urea cycle disorder that causes recurrent hyperammonemia from neonatal period. Reducing serum ammonia (NH₃) level by renal replacement therapy and nutritional management for correcting the amino acid imbalance are important for treatment in the acute phase of the disease. Here, we report a case of severe hyperammonemia caused by OTC deficiency, for which high-flow continuous hemodiafiltration (high-flow CHDF) was effective although all the conventional treatments, including renal replacement therapy, had failed. The patient was a twenties-year-old man with OTC deficiency who was diagnosed with recurrent hyperammonemia at one year of age. He lost consciousness with no known trigger and was admitted to another hospital with a diagnosis of hyperammonemia attack. Serum NH₃ level remained extremely high after all the conventional treatments, including protein restriction and renal replacement therapy. He was transferred to our hospital on the 10^th day. high-flow CHDF (dialysis flow rate 9 l/hr) was initiated 2 days after the admission. Serum NH₃ level decreased soon, and he regained consciousness. Renal replacement therapy was discontinued on the 32^nd day, and orthotopic liver transplantation was successfully performed on the 67^th day.

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In recent years, the drug abuse among young people has become a serious social problem. In drug abuse, intravenous drug user (IDU) is high risk population of infective endocarditis (IE). Many cases of IE happened after surgical intervention like dental procedures in the patients with cardiac valvular or congenital heart disease. However, in the IDU, IE could happen even in normal valves. Intravenous drug use must be considered in young patients who show the sign of IE. We report a case of IE that occurred in an IDU. A 20-year-old female with a history of intravenous drug abuse was transferred to our department with generalized pain and restlessness. Vegetation on the mitral valve was detected by cardiac ultrasonography, and methicillin-sensitive Staphylococcus aureus was positive on blood culture. In addition, cerebral infarctions associated with micro-bleedings were also found on MRI. We diagnosed IE due to intravenous drug abuse, and antibiotic administration was started. However, 14 days after admission, she developed decompensated heart failure due to advanced mitral regurgitation (MR), resulting in the endotracheal intubation and placed on ventilator assistance. Then, mitral valve replacement (bioprosthesis) and tricuspid valvuloplasty were performed 17 days after admission. The patient’s postoperative course was uneventful, and she discharged on postoperative day 49. The patient currently remains under regular follow-up by both the departments of cardiovascular surgery and psychiatry 6 months after surgery, and the recurrence of IE is not observed.

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We report on a case of thrombotic thrombocytopenic purpura (TTP) that developed during pregnancy. A 37-year-old woman at 23 weeks of gestation was admitted to our hospital with disturbance of consciousness, severe anemia, and thrombocytopenia. A disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) activity was less than 3% and specific antibodies to ADAMTS13 were detected, and therefore plasma exchange was performed six times. Steroid pulse and antiplatelet therapy were also started. The platelet count immediately increased after the start of these therapies, and the ADAMTS13 activity recovered and the antibodies could no longer be detected. The ADAMTS13 activities were measured periodically and they were stable with no findings indicating recurrence. Periodic measurements of ADAMTS13 activity were useful for management of TTP and to decide on the indication of plasma exchange.

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A 73-year-old woman was admitted to our hospital because of genital bleeding, high fever and severe hypotension. Urine samples were bloody, and urinalysis revealed occult blood. Hemolysis was suspected, because her total bilirubin (T-Bil), AST and LDH levels rose to 7.6 mg/dl, 77 IU/l and 589 IU/l, respectively. When we examined the patient, there was purulent discharge flowing out from the vagina. The Gram stain of the discharge revealed a large number of Gram-positive rods. Abdominal CT showed a large quantity of gas in the uterus. We made the diagnosis of septic shock associated with uterine gas gangrene caused by Clostridium species. We immediately started treatment for the shock, and hysterectomy was performed for source control. We treated the patient intensively with multidisciplinary approaches, including administration of vasopressin and hydrocortisone, as well as mechanical ventilation and renal replacement therapy. Her T-Bil, AST and LDH were elevated to 30.9 mg/dl, 2,751 IU/l and 5,898 IU/l, respectively, by intravascular hemolysis on hospital day 3. In spite of massive intravascular hemolysis, the patient gradually improved and was discharged from the ICU. A final culture of blood and secretion of the uterus revealed C. perfringens. Massive intravascular hemolysis is a classic complication of C. perfringens septicemia and usually fatal. Early recognition and intensive therapy are needed to save patients' lives.

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A 54-year-old man was admitted to our intensive care unit because of disturbed consciousness. He had been given a diagnosis of type 1 diabetes and was receiving long-term peritoneal dialysis. The blood sodium and glucose levels were 107 mmol/l and 1,452 mg/dl, respectively. Laboratory tests revealed infection and metabolic acidosis. Diabetic ketoacidosis (DKA) due to infection was diagnosed, but conventional fluid loading therapy for DKA could not be administered because of anuria. We initiated treatment with a continuous intravenous infusion of regular insulin and maintenance dosage of fluid. The blood glucose level was controlled by frequently adjusting the dose of insulin. Blood glucose levels and electrolyte levels were measured every hour to avoid overcorrection of hyperglycemia and hyponatremia. After blood glucose and electrolyte levels returned to the normal ranges, the patient regained consciousness. The findings suggested that a subcutaneous abscess was the focus of the infection, and therefore, we administered antibiotic therapy. The patient was successfully discharged from our hospital without neurologic complications by means of careful and mild corrections of electrolyte and glucose levels.

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We report a case of a 66-year-old woman who had metformin-associated lactic acidosis after overdosing of zolpidem tartrate. She displayed restlessness on admission to our emergency room. Blood gas analysis showed severe lactic acidosis and she was admitted to the ICU. After 9 hours, she complained of chest pain. Apical ballooning was observed on echocardiography, and Takotsubo cardiomyopathy was suspected. Her condition resolved, and on the 9th hospital day, she was discharged from the ICU. Lactic acidosis is a rare but sometimes fatal adverse effect of metformin. In this case, respiratory failure as a result of zolpidem tartrate overdose may have induced severe lactic acidosis, which is associated with metformin. The physical stress of lactic acidosis and the psychic stress which caused suicide attempt might eventually result in Takotsubo cardiomyopathy.

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We report a case of rapidly progressing septic shock in a previously healthy infant, who was suspected to have Waterhouse-Friderichsen syndrome (WFS) on the basis of a CT scan. A comatose 6-month-old infant was brought to our hospital after losing consciousness. We first diagnosed him with hypoxic brain damage from the clinical course and radiographic evidences, and started treatment of therapeutic hypothermia despite metabolic acidosis. However, the patient's condition, including his hemodynamic status and laboratory data, worsened 8 hours after admission. We then diagnosed him with disseminated intravascular coagulation and severe sepsis, stopped hypothermic management and administered antibiotics. A re-evaluation by contrast enhanced whole body CT was performed to determine the etiology, which revealed hemorrhage from bilateral adrenal glands. We suspected WFS and provided multidisciplinary intensive care including steroids. He died 29 hours after ICU admission due to multiple organ dysfunction syndrome despite intensive treatment against septic shock and adrenal insufficiency. This case underscores the importance of clinical diagnosis of infection in infants. This case also highlights the importance of judicial consideration of the application of therapeutic hypothermia. We should first suspect severe infectious disease from the evidence of metabolic acidosis of unknown cause and reconsider indications for therapeutic hypothermia.

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To date, no cases of acquired non-malignant tracheoesophageal fistula (TEF) have been reported in patients with anorexia nervosa (AN). We describe a case of a 28-year-old woman with AN (body mass index=9.6) complicated by cuffed tracheal tube-induced TEF during mechanical ventilation. After emergent surgery for pan-peritonitis, she developed multiple organ dysfunction syndrome (MODS), possibly due to refeeding syndrome and/or severe sepsis. She was orally intubated and received prolonged mechanical ventilation, during which a cuffed tracheal tube-induced TEF formed. We therefore performed high-frequency positive pressure ventilation under massive air leakage permission, and she gradually recovered from aspiration pneumonia and MODS without exacerbation of TEF. Subsequently, she underwent tracheostomy and her trachea was successfully isolated from TEF using a variable-length tracheostomy tube by placing the tip of the tube just upon the carina. This airway isolation was continued for nearly 3 years until her nutritional status improved by enteral nutrition via gastrostomy, and then she underwent surgical closure of TEF and was discharged. Considering the difficulties of the management of TEF with AN under mechanical ventilation, precise control of tracheal cuff pressure and prevention of several risk factors to prolong mechanical ventilation, especially refeeding syndrome, seem to be important.

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A 70-year-old male was admitted to our hospital with gastric ulcers. We treated this patient conservatively and he showed improvement of the gastric ulcers. The night after starting enteral feeding, he complained of fever, bloody diarrhea with mucus and a decreased urine volume. A non-contrast abdominal CT image showed hepatic portal venous gas (HPVG) the next day. There were no signs of peritonitis on physical examination. Therefore, conservative treatment was provided. A contrast abdominal CT was repeated 6 hours later and showed nearly complete disappearance of HPVG. In addition, no definite evidence of bowel necrosis or ischemia was seen. We monitored the patient closely with a reduced threshold for surgical correction under appropriate conditions in the ICU, and conservative management was continued. Subsequently, his general condition improved, and he was transferred back to the ward on the 4th ICU day. On admission, blood cultures revealed Acinetobacter baumannii. There was no culture revealed A. baumannii without blood. The final diagnosis was bacterial translocation (BT). HPVG had complicated with BT in this case.

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Three post-cardiac arrest survivors exhibited marked hemoconcentration during therapeutic hypothermia. Case 1: A 31-year-old man suffered from cardiopulmonary arrest (CPA) due to Brugada syndrome. When the body temperature was reduced to 33.8°C from 36.9°C, the blood hemoglobin level increased from 16.3 g/dl to 20.7 g/dl. Case 2: An 86-year-old man suffered from CPA due to the airway obstruction after surgery for gum cancer. When the body temperature was reduced to 30.7°Cfrom 37.3°C , the blood hemoglobin level increased to 12.8 g/dl from 10.3 g/dl. In both cases, the blood hemoglobin level returned to the baseline after rewarming. Case 3: A 3-month-old girl suffered from CPA at home. On admission, her body temperature was 33.6°C. As the body was rewarmed, the blood hemoglobin level decreased to 9.8 g/dl from 12.2 g/dl. Therapeutic hypothermia prevents or mitigates neurologic injury. However, it also has potential adverse effects. Hypovolemia is one of the most important adverse effects, due to cold diuresis and extravasation. We should bear in mind the possible risk of increase in blood viscosity.

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Some injuries are exacerbated during intensive care in multiple trauma cases. Especially, delay of clinical diagnosis of chest and abdomen injury can be fatal. In our hospital, there were 6 cases requiring emergency surgery for chest and abdomen injury diagnosed after admission during a period from April 2009 to September 2010. The average patient age was 54±22 years old. Injury severity score (ISS) was from 19 to 43. Causes of injury included falling from a high place (2 cases) and traffic injuries (4 cases). The details of the delayed injury were 2 cases of intercostal artery injury, 3 cases of diaphragm injury, and 1 case of mesenteric artery injury. Time until deterioration was 5–95 hours. Two cases died. It is important to prevent delayed injury in multiple trauma cases. Delayed injury to the chest and abdominal organs causes exacerbation of the cardiopulmonary state, and intercostal artery injury and diaphragm injury are the main reasons for delayed injury. In the intensive care of multiple traumas, we should not treat only damage diagnosed at first. We need to recognize the risk of delayed injury (for example, multiple rib fractures) and perform intensive care immediately, as well as gain complete understanding of all injuries in an early stage.

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We report a fatal case of severe acute iron poisoning, which is extremely rare in Japan. The patient died due to acute hepatic failure and its complications. The patient was a 23-year-old woman with anemia who was treated with ferrotherapy. She intentionally ingested an over-dose of iron of 2,400 mg. At the time of treatment initiation in our hospital, she only experienced mild drowsiness, stomachache, and vomiting. Therefore at that time, we did not identify the poisoning as severe. Subsequently, her condition progressively worsened, and she experienced disturbed consciousness, and disseminated intravascular coagulation (DIC) was observed. We treated her by intravenous infusion of deferoxamine, transfusion, plasma exchange, and continuous hemodiafiltration. However, she died of hepatic failure and its complications - DIC and brain swelling. Therefore, treatment of severe acute iron poisoning should be initiated before complete hepatic failure. Decontamination treatment and intravenous infusion of deferoxamine should be promptly administered in cases with severe acute iron poisoning. Moreover, a combined therapy involving an intravenous infusion of deferoxamine and acute hemocatharsis may be required.

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Objectives: Pilsicainide, an anti-arrhythmic agent of class Ic of the Vaugham Williams 4-level schema, is reported to be safe and effective in the treatment of perioperative supraventricular arrhythmia. We investigated the effects and pharmacokinetics of intravenous administration of pilsicainide on supraventricular arrhythmias in patients after esophageal cancer surgery. Subjects and methods: After obtaining Institutional Review Board approval and informed consent, 0.75 mg/kg of pilsicainide hydrochloride for injection was administered in 10 minutes to 8 patients who developed supraventricular arrhythmia (2: paroxysmal atrial fibrillation, 2: paroxysmal supraventricular tachycardia, 4: premature atrial contractions≥10/min) after esophageal cancer surgery. Blood samples were collected prior to, and 10, 20, 30, 40, 50, 60, 120, 240, 480 minutes after pilsicainide administration. The plasma pilsicainide concentration was determined by high-performance liquid chromatography. The pharmacokinetic parameters were obtained using a 2-compartment model and compared with those of healthy adults (1). Results: Pilsicainide successfully terminated supraventricular arrhythmia in 6 of 8 patients. No adverse effects, such as hypotension and abnormal ECG pattern, were observed. The maximum plasma concentration (Cmax) of pilsicainide was 2.07±0.59 [mean±SD (standard deviation)] μg/ml, which was significantly higher than that of the healthy adults (1.20±0.16μg/ml). The half-life of α-phase (t1/2α) was significantly prolonged, and the volume of distribution at the steady state (Vdss) and the volume of the peripheral compartment (V2) were significantly decreased. Discussion and Conclusion: Since a single injection of pilsicainide was suggested to be effective for treatment of supraventricular arrhythmia after esophageal cancer surgery, changes in pharmacokinetic parameters warranted the closest attention to avoid relative overdose and adverse effects.

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Severe invasive streptococcal infection is associated with a sudden onset and rapid multiple organ dysfunction syndrome. We report a case of severe invasive streptococcal infection and acute empyema that developed in a patient with pneumonia caused by Streptococcal pyogenes infection. A 27-year-old healthy woman experienced symptoms of a common cold several days before the onset of the symptom. Acute pharyngitis was diagnosed during the day, and the patient was unexpectedly hospitalized for acute pneumonia in the evening of the same day. On the next day, she was referred to our critical care center because of rapid multiple organ dysfunction syndrome. Clinical manifestations and examination indicated severe invasive streptococcal infection, and treatment was administered. Thereafter, the patient's general condition improved, but she showed marked pleural effusion due to acute empyema. Although the pleural space was drained, acute empyema did not improve. Therefore, we performed thoracoscopic surgery on day 19. Postoperatively, the lung function remained below the normal limits because of pleural thickening, but gradually improved. The patient was discharged on day 35. It is necessary to consider the early treatment of acute empyema.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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