Noritomo Fujisaki

Can carbon monoxide-poisoned victims be organ donors?

The increasing demand for organ allografts to treat end-stage organ failure has driven changes in traditional donor criteria. Patients who have succumbed to carbon monoxide (CO) poisoning, a common cause of toxicological mortality, are usually rejected as organ donors. To fulfill the increasing demand, selection criteria must be expanded to include CO-poisoned donors. However, the use of allografts exposed to high CO concentrations is still under debate. Basic research and literature review data suggest that patients with brain death caused by CO poisoning should be considered appropriate organ donors. Accepting organs from CO-poisoned victims could increase the number of potential donors and lower the death rate of patients on the waiting lists. This review and reported cases may increase awareness among emergency department physicians, as well as transplant teams, that patients dying of CO exposure may be acceptable organ donors.

Application of carbon monoxide for treatment of acute kidney injury

Acute kidney injury in critically ill patients is common and associated with a substantial increase in morbidity and mortality. Even with aggressive medical care and renal replacement therapy, acute kidney injury remains a significant health care concern. Recent published reports offer new strategies for the prevention and amelioration of acute kidney injury using carbon monoxide. Although considered a toxic environmental gas, carbon monoxide has recently aroused scientific and clinical interest, as its beneficial effects and mechanisms of action have been substantially defined in various in vitro and in vivo experiments. The exogenous application of carbon monoxide can confer cytoprotection by modulating intracellular signaling pathways through its anti‐inflammatory, anti‐apoptotic, vasodilative, antithrombotic and antiproliferative properties. Thus, evidence is accumulating to support the notion of carbon monoxide treatment for acute kidney disease. In this review, we focus on the extensively analyzed advantageous value of treatment with inhaled/soluble carbon monoxide in the context of kidney injury. Mechanisms such as signaling pathways, as well as an expanded view regarding toxicity and side‐effects, are described broadly. In addition, we discuss the clinical applicability of carbon monoxide as a promising therapeutic strategy for the treatment of patients with acute kidney disease based on translating basic experimental findings into clinical application.

Liver Injury Associated with Chest Compression in Cardiopulmonary Arrest Patients

Introduction: Although chest compression is an effective emergency maneuver for cardiopulmonary arrest (CPA), it carries the risk of complications such as rib fracture, sternal fracture, and organ injury. Methods: We summarized thirteen case reports of CPA patients presenting with liver injury associated with CPR including chest compression reported between 1993 and 2015 in Japan. Five were male and eight were female; their ages ranged from 31 to 83 years old. Unfractionated heparin was administered to ten patients as a treatment for embolism or indication of veno-arterial extra corporeal membrane oxygenation (VA-ECMO). Twelve cases survived surgery or non-surgical management, but one could not survive with non-surgical management. Case: Two cases of CPA due to pulmonary thromboembolism were admitted to our department. Spontaneous circulation was restored due to cardiopulmonary resuscitation (CPR), including chest compression. After use of an anticoagulant drug and indication of VA-ECMO, contrast-enhanced computed tomography (CE-CT) revealed infra-diaphragmatic liver injury in both cases. One patient could survive with damage control surgery (DCS), while the other patient could not survive with non-surgical management. Conclusion: Patients with hemorrhagic diathesis are at critical risk for complications from chest compression. Aggressive treatments, including DCS, might be effective, even for patients treated with anticoagulant drugs.

Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

Because inhaled carbon monoxide (CO) provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects.Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors.

Oxygen management in mechanically ventilated patients: A multicenter prospective observational study

Purpose: To observe arterial oxygen in relation to fraction of inspired oxygen (FIO2) during mechanical ventilation (MV). Materials and methods: In this multicenter prospective observational study, we included adult patients required MV for >48 h during the period from March to May 2015. We obtained FIO2, PaO2 and SaO2 from commencement of MV until the 7th day of MV in the ICU. Results: We included 454 patients from 28 ICUs in this study. The median APACHE II score was 22. Median values of FIO2, PaO2 and SaO2 were 0.40, 96 mm Hg and 98%. After day two, patients spent most of their time with a FIO2 between 0.3 and 0.49 with median PaO2 of approximately 90 mm Hg and SaO2 of 97%. PaO2 was ≥100 mm Hg during 47.2% of the study period and was ≥130 mm Hg during 18.4% of the study period. FIO2 was more likely decreased when PaO2 was ≥130 mm Hg or SaO2 was ≥99% with a FIO2 of 0.5 or greater. When FIO2 was <0.5, however, FIO2 was less likely decreased regardless of the value of PaO2 and SaO2. Conclusions: In our multicenter prospective study, we found that hyperoxemia was common and that hyperoxemia was not corrected. HIGHLIGHTSThis is multicentre prospective study to observe the oxygen management in ventilated patients.Hyperoxemia was common as PaO2 was ≥100 mm Hg during 47.2% of the study period.Hyperoxemia was not corrected as FIO2 was less likely decreased when FIO2 was <0.5.

Inhaled hydrogen ameliorates endotoxin-induced bowel dysfunction

Gastrointestinal dysmotility frequently occurs during sepsis and multiple organ failure, remaining a major cause of morbidity and mortality in critically ill patients. Previous studies have shown that hydrogen, a new therapeutic gas, can improve various organ damage associated with sepsis. In this study, we investigated the protective efficacies of inhaled hydrogen against lipopolysaccharide (LPS)‐induced ileus.

Clinical Feature: Community-acquired Pneumonia Caused by Panton-Valentine Leukocidin-positive Staphylococcus aureus

Panton-Valentine leukocidin (PVL), first verified in 1932, is one type of exotoxin secreted by Staphylococcus aureus (SA). A significant feature of this toxin is that it has two components, LukS-PV (33 kDa) and LukF-PV (34 kDa), which express high specificity to leukocyte for cytolytic activity. They assemble on the surface of polymorphonuclear leukocytes (PMNs) and macrophages to create pores in the membranes of target cells. A high concentration of secreted PVL into cells leads to cytolysis and activates inflammatory cytokines and reactive oxygen species, which cause tissue necrosis, whereas a low concentration activates the cytochrome caspase-activated PMN apoptosis pathway (Figure 1) [1]. Two opinions regarding SA virulence factors conflict with one another. In a study on a sepsis and abscess mouse model infected with methicillin-resistant SA (MRSA) either carrying or not carrying PVL strains, Voyich et al. concluded in 2006 that PVL was not the major virulence factor [2]. On the other hand, Labandeira-Ray and colleges elucidated that PVL is a SA virulence factor of necrotizing pneumonia, which enhanced inflammation in the lung parenchyma and bronchial epithelium in cooperation with Staphylococcal protein A. They also claimed that the expression of PVL induced cell wallanchored and secreted proteins’ genes at the transcriptional level [3]. In addition, Diep et al. showed that PVL directly affected the peripheral lung tissue in a rabbit model, in which PMN sensitivity is more similar to that of humans than the rodent model [4]. Although the pathogenicity of PVL in humans has not yet been demonstrated, PVL is regarded as a predictive virulence manifestation in pulmonary infections.

Ileum perforation due to cytomegalovirus infection in a patient with adult T-cell leukemia

A 73‐year‐old woman was transferred to our department due to severe abdominal pain with peritonitis. Her laboratory data showed that her white blood cell count was elevated to more than 50,000/mm3. Antibodies to HTLV‐I were positive and we made the diagnosis of adult T‐cell leukemia (ATL).