During the spring of 2009, a pandemic influenza A (H1N1) virus emerged and spread globally. Preliminary comparisons with seasonal influenza suggest that pandemic 2009 influenza A (H1N1) disproportionately affects individuals of younger ages and causes a generally mild disease. However, based on clinical studies in Mexico, North America, and the southern hemisphere, the virus has caused an epidemic of critical illness, with some patients developing severe acute respiratory distress syndrome (ARDS). A proportion of these patients with ARDS have even been treated using extracorporeal membrane oxygenation (ECMO). Since the fall of 2009, the number of critically ill patients has been increasing in Japan, although the number is much lower than in foreign countries. In this article, we focus on the characteristics of the novel 2009 influenza A (H1N1) virus and the clinical features of patients infected with this virus. Also, we refer to the recent knowledge describing the molecular mechanisms by which the influenza virus can cause critical illnesses, such as ARDS, in humans.

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Objectives: The Surviving Sepsis Campaign guidelines 2008 indicate red cell transfusion to target a hemoglobin of 7–9 g·dl⁻¹ in adults when hemoglobin decreases to < 7 g·dl⁻¹. To evaluate the validity of this recommendation, we systematically reviewed the literature regarding red cell transfusion strategies for the critically ill. Methods: We searched PubMed from January 1966 to May 2008 using the key words, “preoperative, postoperative, perioperative or surgery”, or “intensive care or critical care”, and “hemoglobin and transfusion”, then limited the search to English or Japanese references, and randomized controlled trial (RCT). This strategy resulted in 395 articles. Results: Seven articles were aimed at comparing restrictive and liberal transfusion strategies. Four of the 7 studies were subgroup analyses based on a previous report. All of them found that the restrictive transfusion strategy (for example, Hb 7–9 g·dl⁻¹) was equal to or better than the liberal transfusion strategy (for example, Hb 10–12 g·dl⁻¹) with respect to mortality and morbidity among the critically ill. Conclusions: A restrictive strategy of red cell transfusion is at least as effective as, and possibly superior to a liberal transfusion strategy for the critically ill.

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Objective: Vasopressin has been reported to increase blood pressure in patients with septic shock. However vasopressin has an intense vasoconstriction effect that may decrease the splanchnic blood flow. There is no report of the effect of vasopressin on the splanchnic blood flow. Methods: We administered vasopressin of 0.016 U·min⁻¹ in 10 patients with norepinephrine-resistant septic shock. We measured the blood flows of liver and kidney by Duplex Doppler Examination before and during a continuous infusion of vasopressin. Results: The peak velocities of the portal vein, the hepatic artery and the interlobar arteries of the kidney with vasopressin changed 105±48% (mean±SD), 101±24% and 114±43%, respectively, compared with those without vasopressin. The resistive index of the hepatic artery and the interlobar arteries of the kidney changed 98±10% and 100±5%, respectively. Conclusions: Hepatic and renal blood flows were maintained during a continuous infusion of a small amount of vasopressin in patients with septic shock.

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Objectives: To evaluate the clinical usefulness and appropriate indications of the β-D-glucan assay for the diagnosis of deep-seated mycoses. Methods: The microbiologic database of a university hospital for the years 1998–2005 was analyzed to assess the clinical usefulness of the β-D-glucan assay for the diagnosis of culture-proven fungemia or deep-seated mycoses. The reasons for initiation of antifungal therapy were surveyed and the drug costs associated with antifungal therapy were calculated using the pharmacy database for the year 2005. Results: 1) Based on the results of receiver operating characteristic curve analysis, the cutoff value of the β-D-glucan assay for the diagnosis of fungemia was determined to be 11 pg·ml⁻¹. 2) The sensitivity and specificity of the β-D-glucan assay using this cutoff value were 76.1% and 78.7%, respectively, and the negative predictive value was 99.7%. 3) Serodiagnosis, including the β-D-glucan assay, was the second most frequent reason (24.4%) for the initiation of antifungal therapy. No microbiologic examination was performed or no fungi were detected in 81.8% of the cases treated with antifungal agents. 4) The drug cost of antifungal therapy was similar to that of broad-spectrum antibiotic therapy. Conclusions: The β-D-glucan assay, with its high negative predictive value, can be used as a screening test to exclude the possibility of deep-seated mycoses. β-D-glucan assay should be prudently conducted and its efficacy should be further investigated taking into consideration the risk factors or colonization index, in order to minimize overtreatment and the associated costs.

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Perinatal fulminant group A streptococcal infections are associated with a particularly dramatic course and often results in a loss of both the patient as well as her conceptus. Such a case in an early stage of pregnancy is reported herein in which treatment was successful. The patient, a 34-year-old woman, was referred from another institution with major complaints of vomiting and a pain in the lower abdomen. Shortly after admission and while urinating, she delivered a fetus with an approximate gestational age of 15 weeks. Immediately, the uterine contents were evacuated but within several hours, she developed septic shock and multiple organ failure, which necessitated the start of intensive care. A vaginal culture yielded group A Streptococcus, leading to a diagnosis of perinatal fulminant group A streptococcal infection. The patient was treated with ampicillin and clindamycin. On day 38 of the infection, she was released without complications. Many reported cases of this infection occur in the late stages of pregnancy and few were successfully rescued. Success in the present case may be explained by the early stage of pregnancy that enabled rapid and complete removal of the uterine contents that constituted the infectious foci and early and immediate administration of intensive care. The possibility of a perinatal fulminant group A streptococcal infection should be considered when one faces septicemia in the field of gynecology and obstetrics.

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We herein report a case of a 17-day-old neonate with fulminant hepatic failure (FHF) who underwent living donor liver transplantation (LDLT) donated by her father. At present, this is the youngest and smallest case of successful LDLT in Japan. She was diagnosed with FHF at the 8th day after her birth. She received repeated plasma exchange (PE) and continuous hemodiafiltration (CHDF) thereafter. She was transferred to our hospital by helicopter at the 16th day after her birth. We performed PE and CHDF again on ICU admission day, and operation was performed on the following day. After the operation, she received continuous hemodialysis for 63 hours due to oliguria. She was then successfully weaned from mechanical ventilation on the 4th post-operative day. Fresh frozen plasma was administered continuously, and for the prevention of the hepatic arterial thrombosis, anticoagulant therapy using mainly nafamostat mesilate was performed. She showed no sign of acute phase rejection and discharged to general ward on the 10th day after admission to ICU.

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There are accumulating data which demonstrate the usefulness of brain hypothermia for the treatment of severe traumatic brain injury and hypoxic encephalopathy in children and neonates. We herein report the successful treatment of postresuscitative encephalopathy in a 57-day-old male with mild brain hypothermia. The patient was admitted to our pediatric ICU (PICU) after resuscitation due to out-of-hospital cardiopulmonary arrest. He had a flat electroencepharography (EEG), no light reflex, and no spontaneous respiration on admission. Head cooling was immediately initiated and his esophageal temperature was maintained at 34°C for 72 hours. After this cooling period, he was then slowly rewarmed at a rate of 1°C·day⁻¹. His light reflex emerged on the next day after resuscitation, EEG became normal on hospital day 8, the trachea was extubated on day 14, and he was discharged from the PICU on day 16 and from the hospital on day 43. He became possible to sit almost alone at 9 months of age. No serious adverse effects were observed during mild brain hypothermia. Mild hypothermia is therefore considered to be a safe treatment strategy and modality, and it might have contributed to the favorable neurological outcome of this patient.

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A 25-year-old man who had undergone lung transplantation from a living donor for the treatment of primary pulmonary hypertension was transferred to the ICU with percutaneous cardiopulmonary support (PCPS), because of depressed cardiac function due to the relatively small size of the transplanted lung. He was weaned from the PCPS on post operative day 2, however, mechanical ventilation was continued on account of poor dynamic lung compliance. On post operative day 9, the pulmonary arterial pressure rose, with an increase in the pulmonary/systemic arterial pressure ratio and an unfavorable ventilatory status. As the patient developed pulmonary edema possibly attributable to graft rejection, the PCPS was reinstituted. The elevation in the pulmonary arterial pressure subsided in response to correction of water balance and reduction of cardiac output, and the patient was weaned from the PCPS and mechanical ventilation. A patient with a small-sized lung graft is prone to developing pulmonary edema due to the relatively small size of pulmonary vascular bed. In the case reported herein, the time-course of changes of the pulmonary/systemic blood pressure ratio appeared to reflect the status of the transplanted lung.

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The patient was a 2-year-old boy, who had fever and pharyngeal pain from 9 days before admission and developed vomiting and diarrhea from a day before admission. He had a depressed level of consciousness, and developed cardiac arrest while being transferred to a neighborhood clinic by his family. After advanced cardiac life support was performed at this clinic, he regained heartbeat and respiration, but did not regain consciousness, and thus was referred to our hospital. Since hemolytic uremic syndrome was suspected at first, intensive care, including continuous hemodiafiltration and brain hypothermia, was started. On admission, fecal cultures revealed Escherichia coli O-1, but no verotoxin. The platelet count did not improve despite frequent platelet transfusions. Therefore, TTP was suspected, and thus plasma exchange was performed on the 11th and 12th ICU days. On the 15th ICU day, TTP was diagnosed by markedly decreased activity of a disintegrin and metalloproteinase with thrombospondin type 1 motif, number 13 and by the presence of antibody to this protease. Subsequently, the patient's general condition improved, and he was discharged from the ICU on the 20th ICU day.

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Ventilator-associated pneumonia (VAP) is the most serious but preventable infectious complication in intensive care unit. Ventilator care bundle has been proposed as a possible tool in preventing VAP. Scarce data, however, have been reported regarding the bundle, and no studies exist specifically in Japanese practice. We conducted a 2-year prospective survey to elucidate the adherence rate and efficacy of ventilator bundle in a single-institute. We investigated the adherence rate of the 4 components of ventilator bundle and incidence of VAP in 109 intensive care patients receiving mechanical ventilation >48 hours on daily basis for 7 days starting the initiation of mechanical ventilation. The 4 components of the bundle included: 1) head of bed (HOB) elevation, 2) sedation vacation (daily discontinuation of sedatives), 3) peptic ulcer prophylaxis, and 4) deep venous thrombosis prophylaxis. The adherence rates of deep vein thrombosis prophylaxis (P = 0.02), and all of the 4 components (P = 0.04) were increased significantly in year 2007 compared with those of year 2006. When evaluating the adherence in the first 48 hours, the rate of HOB elevation improved significantly in year 2007 compared with that of year 2006 (P = 0.02). The adherence rates of HOB elevation and sedation vacation component were relatively lower than the other two components. The incidence of VAP per 1,000 ventilator days decreased from 12.7 in year 2006 to 5.2 in year 2007. Improvement in the adherence rate, specifically focusing on HOB elevation and sedation vacation components, should further be directed by using educational approach for healthcare personnel and application of protocolized care.

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Objectives: In response to an outbreak of H1N1 influenza (A/H1N1 pdm) in Japan in 2009, The Japanese Society of Intensive Care Medicine-Pediatric Intensive Care Unit (JSICM-PICU) network, a task-force of the Neonatal and Pediatric Intensive Care Committee in The Japanese Society of Intensive Care Medicine evaluated a group of critically ill children with A/H1N1 pdm. Methods: The characteristics, treatment and outcomes of A/H1N1 pdm cases of children under 15 years old identified in August to October 2009 were surveyed by the network. Results: Nine patients, with a median age of 5 years and 3 months, received mechanical ventilation in ICU due to confirmed infection of A/H1N1 pdm. Although the average predicted mortality by the Pediatric Index of Mortality-2 (PIM-2) was 15.4%, none of these children died. Indications for initiation of mechanical ventilation were acute respiratory failure due to asthma, bronchitis or pneumonia in 5 cases, decreased level of consciousness due to enchepharopathy in 3 cases and circulatory failure due to myocarditis in 1 case. Two patients required extracorporeal membrane oxygenation for severe cardio-respiratory failure. All patients received oseltamivir, an antiviral agent for treatment of the A/H1N1 pdm, with the median time from onset of symptoms of influenza to initiation of oseltamivir 1 day. Conclusions: Information regarding a larger number of cases is necessary to develop optimal diagnostic and therapeutic strategies for severe A/H1N1 pdm infection in children.

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