There is no doubt that the basic goal in the treatment of sepsis is to regulate the source of infection, including removal of the infectious focus and to maintain the hemodynamics with fluid resuscitation and inotropic drugs. While hyperdynamic circulatory state is a characteristic profile in sepsis, both functional and structural deteriorations in heart develop even at the early stage. Aggressive fluid resuscitation and inotropic support to meet the increased oxygen demand in vital organs could be harmful to injured myocardium. On the contrary, in patients with chronic heart failure or ischemic heart disease, irrespective of the underlying mechanisms, cardioprotective therapy using β-blockers has been demonstrated to be highly beneficial for improving the outcome. Furthermore, in burn patients who show similar aspects of augmented metabolism and hyperdynamic circulatory state to patients with sepsis also, β-blocker therapy could be effective. In this review, we discuss the necessity of cardioprotective strategy and its possibility of β-blocker in sepsis.

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Objectives: Acute kidney injury (AKI) following cardiovascular surgery is common and is associated with both morbidity and mortality. In this study, we evaluated the effects of atrial natriuretic peptide (ANP, carperitide) on hemodynamics and renal function in patients undergoing cardiovascular surgery. Methods: The PubMed database and the references from identified articles were used to perform a literature search on the cardiovascular and renal effects of ANP in patients undergoing cardiovascular surgery. Results: Eleven randomized controlled studies presented data on ANP infusion in patients undergoing cardiovascular surgery. Most of the studies had a small sample size and were from a single center. ANP infusion increased the urine output and creatinine clearance or the glomerular filtration rate (GFR), reduced the use of diuretics, and reduced the serum creatinine and blood urea nitrogen (BUN) levels, compared with a Control group. Only 3 studies mentioned the incidence of hemodialysis and mortality. This combined data was insufficient to determine the effect of ANP infusion during the perioperative period on long-term outcome in patients undergoing cardiovascular surgery. Conclusions: ANP infusion preserved postoperative renal function in patients undergoing cardiovascular surgery. However, few studies have examined the incidence of hemodialysis, the length of hospital stay, mortality, and the associated medical costs. Therefore, a large, multicenter, randomized controlled study is needed to assess the effect of ANP on renal function, the length of hospital stay, outcomes, and medical costs in these patients.

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Objective: Enteral diets enriched with eicosapentaenoic acid (EPA), γ-linolenic acid (GLA) and antioxidant vitamins have been demonstrated to improve outcomes in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There is ethnic difference in the distribution of genetic polymorphisms, and therefore, the efficacy of nutritional treatment may differ among races. We evaluated the efficacy of the enteral diet enriched with EPA, GLA and antioxidants in a Japanese-descendant population with ARDS secondary to severe sepsis or septic shock through a retrospective assessment of the original database of our previous study. Materials and methods: 18 Japanese-descendant patients were identified from the original study based on the ethnic answer on their clinical research forms. All patients were randomly assigned to two groups either with a diet enriched with EPA, GLA and antioxidant vitamins or with an isonitrogenous and isocaloric control diet, delivered at a constant rate to achieve a minimum of 75% of basal energy expenditure x 1.3 during a minimum of 4 days and monitored for 28-days. Results: Those who received the study diet experienced significant improvements in oxygenation status, more ventilator-free days (12.0±2.6 vs. 4.2±1.7, P = 0.0362) and more ICU-free days (8.9±2.2 vs. 2.6±1.2, P = 0.0348). No significant changes were observed in terms of the development of new organ failures and mortality outcomes. Conclusions: In Japanese-descendant patients with severe sepsis or septic shock and requiring mechanical ventilation and tolerating enteral nutrition, a diet enriched with EPA, GLA and antioxidants contributed to better ICU outcomes.

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Postoperative atrial fibrillation (PAF) is a common complication after esophagectomy that is associated with prolonged ICU and hospital stays as well as increased costs. Therefore, various types of prophylaxis and treatments for PAF have been investigated. We retrospectively evaluated hemodynamic effects of short-acting β₁ selective blocker, landiolol, on persistent PAF in 7 patients after esophagectomy. All patients were males aged 51–87 years. They were refractory to conventional antiarrhythmic therapies. Landiolol was thus infused at rates ranging from 4.3μg/kg/min to 33.5μg/kg/min. Average heart rate (HR) was significantly decreased 1 hour later from 153 [140, 167] [95% confidence intervals] /min to 101 [88, 116] /min (P < 0.0001). Mean arterial pressure remained stable throughout the infusion (88 [78, 94] mmHg to 82 [74, 89] mmHg; P = 0.37) and none of the patients developed hypotension that was severe enough to stop the landiolol infusion. The PAF was converted to sinus rhythm within 24 hours after landiolol administration in 6 patients. Even at low infused doses, landiolol effectively controlled HR in patients with persistent PAF after esophagectomy without severe hypotension.

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We report a case of acute respiratory distress syndrome (ARDS) associated with tricyclic antidepressant (TCA) overdose. A 34-year-old woman taking clomipramine hydrochloride for depression was admitted to the emergency department of our hospital after ingesting 3.5 g (70 mg/kg) of clomipramine hydrochloride 4 hr prior to arrival. On arrival, her vital signs were normal, and the Glasgow coma scale (GCS) score was E1V1M2. She was admitted to the department of internal medicine. Eleven hours after dose, the GCS score was E3V5M6. Her SpO₂ was measured to be 94% when oxygen was supplied through a face mask at 6 l/min. A chest radiograph revealed a bilateral infiltration shadow. Twenty hours after dose, she entered a state of shock. She was transferred to the intensive care unit. We presumed that the cause of ARDS was pneumonia. Although the inflammatory response was improved on antibiotics administration, but the respiratory condition did not. After the administration of the methylpredonizorone on the 12th day, the respiratory condition gradually improved. On the 14th day, she was weaned from mechanical ventilation, and on the 22nd day, she was discharged. Cases of ARDS associated with TCA overdose have been reported from abroad. The lung injury caused by TCA overdose has also been reported in experimented conducted on animals. Physicians should include the possibility of developing ARDS when encountering a patient of TCA overdose.

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A fetal case of chronic distigmine bromide intoxication in a 72 year old woman is presented. She had had a history of chronic renal dysfunction and liver cirrhosis for approximately 20 years. She initially presented with dysuria, and was place placed on 10 mg/day of oral distigmine bromide. After 9 months, she developed intractable diarrhea, vomiting, and finally cardiopulmonary arrest. She was resuscitated, but was finally pronounced dead despite the treatment. Her serum concentration of distigmine bromide found to be 69.9 ng/dl. Her serum cholinesterase was low. Bases on the aforementioned data, a diagnosis of distigmine bromide intoxication were confirmed. She had a background of chronic renal failure and liver cirrhosis as well as a chronically low level of cholinesterase, and it therefore took a long time to reach a diagnosis of distigmine bromide intoxication. When the residual ratio of serum cholinesterase was calculated, it had been at an abnormally low level since approximately 7 months before, and based on this and the time at which the intractable digestive symptoms began to occur, we therefore diagnosed chronic intoxication. When elderly patients on distigmine bromide developed intractable digestive symptoms, intoxication caused by this drug must be included in one of the differential diagnosis and should be candidate for intensive care.

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Since the report of Dalmau et al. in 2007, anti-N-methyl-D-aspartate (NMDA) receptor encephalitis has received an increasing amount of attention. This condition accounts for some cases of limbic encephalitis and is often paraneoplastic. Here, we report a patient with non paraneoplastic anti-NMDA receptor encephalitis. A 29-year-old woman was admitted to our intensive care unit because of aspiration pneumonia and intractable convulsions. After experiencing common cold symptoms, the patient developed psychiatric symptoms, such as hallucinations and delusions, and persistent limbic convulsions in spite of the administration of several anticonvulsants prior to admission. Her laboratory studies and electroencephalographic examinations were not significant, and no tumor was found. However, a spinal fluid examination revealed a mild elevation in mononuclear cells and protein and the existence of anti-glutamate receptor antibodies, indicating that the limbic encephalitis might have been caused by autologous antibodies. The patient quickly recovered from the pneumonia in response to appropriate antibiotics and respiratory management, and her convulsions (and psychiatric symptoms) were ameliorated with steroid therapy. Limbic encephalitis, including anti-NMDA receptor encephalitis, remains unfamiliar to many physicians, but awareness of this condition is important as anti-NMDA receptor encephalitis accounts for a relevant proportion of unexplained, new-onset convulsions and psychiatric symptoms and is responsive to several therapies, with a favorable prognosis.

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We report a neonate with severe digoxin intoxication. The patient was a 23-day-old girl. Two days after birth, she was diagnosed with ventricular septal defect (VSD), patent ductus arterious (PDA), and atrial septal defect (ASD). Treatment with furosemide, spironolactone, digoxin, and enalapril maleate was started. After she was discharged from the previous hospital, vomiting was noted. She was referred and admitted to our hospital 23 days after birth. On admission, she demonstrated hypovolemic shock judging from weight loss, an anterior fontanel excavation, oliguria, and marked peripheral coldness. Blood drug concentration measurement and blood chemistry showed increases in the serum digoxin, blood urea nitrogen (BUN), creatinine (Cre), and potassium ion (K⁺) levels. These findings suggested severe digoxin intoxication with hyperpotassiumemia and acute renal failure. The oral agents were discontinued, and transfusion loading and glucose-insulin (GI) therapy were performed, leading to a favorable outcome. In Japan, no specific antibody against digoxin has become commercially available. Furthermore, digoxin has large volume of distribution; it cannot be removed by hemocatharsis therapy. Therefore, it is important to prevent serious complications by continuing the correction of serum electrolytes and symptomatic therapy for arrhythmia until digoxin is excreted.

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An 80-year-old woman developed acute respiratory distress syndrome from severe community-acquired pneumonia. Intermittent mandatory ventilation was initiated in association with administration of meropenem and sivelestat sodium hydrate. Since the P/F ratio decreased to 87 mmHg, the ventilation mode was changed to airway pressure release ventilation (APRV) with a continuous positive airway pressure (CPAP) phase of 27 cmH₂O. While the P/F ratio increased to 230 mmHg 12 hours later, circulatory failure occurred, and the level of CPAP phase was lowered to 22 cmH₂O. The patient developed disseminated intravascular coagulation on the 2nd disease day, and anticoagulant therapy with antithrombin and thrombomodulin was started. Thereafter, the P/F ratio was maintained at around 200 mmHg. Streptococcus pneumoniae fully sensitive to meropenem was indicated from a sputum culture sampled on admission. Inflammation and coagulopathy gradually improved. On the 7th disease day, the P/F ratio increased to more than 300 mmHg, and the patient was weaned from mechanical ventilation. APRV improved the pulmonary oxygenation to a certain degree but disturbed the circulation.

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Previous reports have indicated that intravenous immunoglobulin (IVIG) preparation reduces some types of inflammatory cytokines. In the present study, we investigated the short-term and direct effects of IVIG in 16 patients with sepsis. Following the administration of 5 g of IVIG for 1 hour, we took blood samples immediately following IVIG treatment and at 1 hour after IVIG treatment. Blood samples taken at 1 hour and just prior to IVIG administration were used as controls. While there was no difference between 1 hour before and just prior to IVIG treatment, statistically significant decreases were observed in the levels of interleukin-6 (IL-6) after the administration of IVIG. No significant changes were observed in the plasma levels of tumor necrosis factor-α and high mobility group box 1. We confirmed the results of previous animal studies. While we reported that the administration of IVIG directly reduces the plasma levels of IL-6 in patients with sepsis, a further prospective study of the anti-cytokine effects following IVIG treatment will be conducted in the near future.

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Objective: Pulmonary edema is divided into cardiogenic and permeability types. There are no quantitative diagnostic criteria for differentiating between the pathologic mechanisms. The purpose of this study is to establish quantitative differential criteria for cardiogenic pulmonary edema and acute lung injury/acute respiratory distress syndrome (ALI/ARDS) (permeability edema). Methods: In this multicenter study, 91 patients ventilated for acute respiratory failure with a P/F ratio < 300 and bilateral infiltration on chest radiographs, necessitating transpulmonary thermodilution technique monitoring, were enrolled. We assessed the pulmonary vascular permeability index (PVPI) as the extravascular lung water index (ELWI)/pulmonary blood volume index. Pulmonary edema was defined as ELWI > 10 ml/kg. The cause of pulmonary edema was determined by three or more experts, taking into account medical history, clinical features, respiratory and hemodynamic variables, and clinical course with therapy. The experts were blinded to the PVPI data. Results: ALI/ARDS was diagnosed in 58 cases, pleural effusion/atelectasis in 11, and cardiogenic pulmonary edema in 6 (16 suspected cases). The ELWI of pleural effusion/atelectasis was below that of pulmonary edema (7.7±1.2 ml/kg). The PVPI in ALI/ARDS was significantly higher than that of non-ALI/ARDS (ALI/ARDS, 2.91±0.92; pleural effusion/atelectasis, 1.51±0.55; cardiogenic pulmonary edema, 1.53±0.31). The area under the curve (AUC) of receiver operating characteristic (ROC) curve using the PVPI to distinguish ALI/ARDS from non-ALI/ARDS was 0.926. A PVPI of 2.0–2.2 was thus proposed as the differential value. There was a positive correlation between PVPI and ELWI in ALI/ARDS (Sr = 0.652, P < 0.001), but not in non-ALI/ARDS. Conclusions: PVPI combined with ELWI may be useful for determining the pathologic mechanisms of pulmonary edema and respiratory failure in the critical care setting. (UMIN-CTR number, UMIN 000003627)

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Objective: To evaluate ICU performance under a diagnosis procedure combination (DPC) system, we attempted to clarify the influence of the operating policies of the ICU, such as staffing and the decision-making process, on patient outcome. Methods: The Japanese Society of Intensive Care Medicine ICU performance evaluation committee, in cooperation with the Ministry of Health, Labour, and Welfare's “DPC” group (Matsuda research group), collected and analyzed information from an ICU investigation study performed in 2008. The Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system was used to evaluate the severity and outcome of ICU patients. The standardized mortality ratio (SMR) was used to compare subgroups. Moreover, when a difference in the average predicted mortality rate among the subgroups was not observed, the observed mortality rates were compared. Results: The median number of ICU beds was 8/hospital, although there was a large difference among hospitals (from 2 to 67). The length of the ICU stay was shorter at ICUs where a full-time intensivist made decisions regarding ICU discharge, compared with the other ICUs (3.53±3.35 days vs. 4.07±5.47 days, P<0.001). The SMR of ICUs where a full-time intensivist was present at 20:00 was lower than that of the other ICUs. The observed mortality rate in ICUs where a full-time intensivist was present at 20;00 was higher than that of ICUs where a full-time intensivist was not present (odds ratio: 1.394, confidence interval [CI]: 1.078–1.803; chi-squared, 6.16; P=0.013). The SMR of ICUs where a full-time intensivist made decisions regarding ventilator use was lower than that of the other ICUs. The observed mortality rate was lower in ICUs where a full-time intensivist made decisions regarding ventilator use than in other ICUs (odds ratio: 0.849, CI: 0.596–1.209; chi-squared, 0.665; P=0.415). Having a clinical engineer and an intensive care-certified nurse on staff had a positive influence on patient outcome. Whether the presence of a society-certified intensive care specialist or a society-certified ICUs improved patient outcome could not be clarified. Conclusion: Having a full-time intensivist on staff shortened the length of ICU stay and improved the SMR. Having a certified-nurse and a clinical engineer on staff also improved the SMR.

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