Kaoru Koike

Expert consensus for the treatment of disseminated intravascular coagulation in Japan

The present report from The Japanese Society of Thrombosis and Hemostasis provides an expert consensus for the treatment of disseminated intravascular coagulation (DIC) in Japan. Disseminated intravascular coagulation (DIC) may be classified as follows: asymptomatic type, marked bleeding type, and organ failure type. Although treatment of DIC is important, adequate treatment differs according to type of DIC. In asymptomatic DIC, low molecular weight heparin (LMWH), synthetic protease inhibitor (SPI), and antithrombin (AT) are recommended, although these drugs have not yet been proved to have a high degree of effectiveness. Unfractionated heparin (UFH) and danaparoid sodium (DS) are sometimes administrated in this type, but their usefulness is not clear. In the marked bleeding type, LMWH, SPI, and AT are recommended although these drugs do not have high quality of evidence. LMWH, UFH, and DS are not recommended in case of life threatening bleeding. In case of severe bleeding, SPI is recommended since it does not cause a worsening of bleeding. Blood transfusions, such as fresh frozen plasma and platelet concentrate, are also required in cases of life threatening bleeding. In the organ failure type, including sepsis, AT has been recommended based on the findings of several clinical trials. DIC is frequently associated with thrombosis and may thus require strong anticoagulant therapy, such as LMWH, UFH, and DS.

Gut ischemia/reperfusion produces lung injury independent of endotoxin

ObjectiveBacterial translocation from the gut has been invoked as a common inciting event for postinjury multiple organ failure. We previously showed that gut ischemia/reperfusion induces remote organ injury. The purpose of this study was to ascertain if endotoxin has a pivotal mechanistic role in this process. DesignProspective, randomized study. SettingAnimal laboratory. SubjectsSprague-Dawley rats weighing 300 to 350 g. InterventionsAnesthetized animals underwent 45 mins of superior mesenteric artery occlusion and 2 hrs of reperfusion; sham laparotomy served as controls. Endotoxin was eliminated with the murine immunoglobulin (Ig) M antibody E5, 3 mg/kg iv before the study. Measurements and Main ResultsPlasma endotoxin was measured by the limulus amebocyte lysate assay. At 2 hrs of reperfusion, circulating neutrophil priming was determined by the difference in superoxide generation with and without the activating stimulus, N-formyl-Met-Leu-Phe. Neutrophil sequestration in the lung was quantitated by myeloperoxidase activity, and by lung endothelial permeability by 125I albumin lung/blood ratio. Endotoxin concentrations were not significantly (significance determined as p < .05) different between the gut ischemia/reperfusion and laparotomy groups (n = ≥5) during ischemia or reperfusion. Circulating neutrophil priming, neutrophil accumulation in the lung, and lung injury were provoked by gut ischemia/reperfusion, but not altered by endotoxin elimination. ConclusionGut ischemia/reperfusion primes circulating neutrophils and produces lung injury by a mechanism independent of endotoxin. (Crit Care Med 1994; 22:1438–1444)

Endotoxin after gut ischemia/reperfusion causes irreversible lung injury☆

We have recently reported that 45 min of gut ischemia causes moderate 125I-albumin lung leak at 6 hr of reperfusion which was reversed at 18 hr. Our purpose was to determine the effect of a second insult, low dose endotoxin (LPS, 2.5 mg/kg), given 6 hr after gut ischemia/reperfusion (I/R) on this lung injury as assessed by 125I-albumin leak, neutrophil influx (myeloperoxidase assay, MPO), histopathology, and mortality. Rats were randomized to either sham laparotomy (LAP) or 45 min of superior mesenteric artery occlusion and 6 hr later were treated with LPS or saline. At 18 hr reperfusion the lungs were harvested, assayed for 125I-albumin leak and MPO, and microscopically examined by an unbiased observer after routine H&E staining. We observed that LPS increased lung neutrophil levels both with or without gut I/R. However, only the combined insult (I/R + LPS) increased 125I-albumin leak at 18 hr of reperfusion. Lung histology confirmed that the sequential combination of I/R + LPS caused marked interstitial edema and neutrophil sequestration accompanied by alveolar edema, hemorrhage, and fibrinous exudate, while I/R or LAP + LPS did not. The mortality rate of I/R + LPS was 39% which was significantly higher than LAP alone (0%), gut I/R alone (0%), or LAP + LPS (4%). In conclusion, a delayed exposure to low dose endotoxin converts moderate gut I/R-induced lung dysfunction into advanced organ failure.

Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW Study

The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18xa0years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs).1898 patients with a mean age of 51.6xa0years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients.827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses.The overall mortality rate was 10.5% (199/1898).According to stepwise multivariate analysis (PRu2009=u20090.005 and PEu2009=u20090.001), several criteria were found to be independent variables predictive of mortality, including patient age (ORu2009=u20091.1; 95%CIu2009=u20091.0-1.1; pu2009<u20090.0001), the presence of small bowel perforation (ORu2009=u20092.8; 95%CIu2009=u20091.5-5.3; pu2009<u20090.0001), a delayed initial intervention (a delay exceeding 24xa0hours) (ORu2009=u20091.8; 95%CIu2009=u20091.5-3.7; pu2009<u20090.0001), ICU admission (ORu2009=u20095.9; 95%CIu2009=u20093.6-9.5; pu2009<u20090.0001) and patient immunosuppression (ORu2009=u20093.8; 95%CIu2009=u20092.1-6.7; pu2009<u20090.0001).

Group Iia Phospholipase A2 Mediates Lung Injury in Intestinal Ischemia–reperfusion

OBJECTIVEnTo assess the mechanistic role of group IIA phospholipase A2 (PLA2) in the process of local and distant organ injury after intestinal ischemia-reperfusion.nnnSUMMARY BACKGROUND DATAnIntestinal ischemia-reperfusion produces lung injury by a mechanism that involves PLA2 activation, but it is unclear which isozyme is responsible for this phenomenon. Group IIA PLA2, one of the secreted forms of PLA2, is known to play a pivotal role in a variety of inflammatory reactions.nnnMETHODSnRats underwent 45 minutes of superior mesenteric artery occlusion in the presence and absence of pretreatment with group IIA PLA2 inhibitor, S-5920/LY315920Na (20 mg/kg, subcutaneously, 30 minutes before clamping). At 2 hours of reperfusion, intestinal and lung leak was assessed by 125I-albumin tissue/blood ratio, and liver injury was estimated by serum alanine aminotransferase. PLA2 activities in tissues and sera were quantitated by phosphatidyl-glycerol/sodium cholate mixed micelle assay. PLA2 activities in tissues were also measured after in vitro preincubation with EDTA, S-5920/LY315920Na, or antirat group IIA PLA2 antibody.nnnRESULTSnIntestinal ischemia-reperfusion provoked intestinal leak, liver injury, and lung leak, whereas tissue PLA2 activity was decreased in the intestine, unchanged in the liver, and increased in the lung. Serum PLA2 activities were increased in the portal and systemic circulation during ischemia. Pretreatment with S-5920/LY315920Na eliminated PLA2 activities in all tissues and sera and only abolished lung leak. The in vitro experiment revealed that most of the intestinal and lung PLA2 activities were inhibited by EDTA, S-5920/LY315920Na, and antirat group IIA PLA2 antibody, but hepatic PLA2 activity was not.nnnCONCLUSIONnIntestinal ischemia-reperfusion appears to produce lung injury by a mechanism that involves group IIA PLA2 activation. Intestinal ischemia-reperfusion is likely to promote intestinal and hepatic injury independent of group IIA PLA2.

NEW DIAGNOSTIC PERITONEAL LAVAGE CRITERIA FOR DIAGNOSIS OF INTESTINAL INJURY

BACKGROUNDnAlthough diagnostic peritoneal lavage (DPL) is a well-established, reliably objective method of diagnosis of intraperitoneal injury, it is too sensitive to be used as an indicator for emergency celiotomy. Therefore, since the development of ultrasonography and advanced computed tomographic scanners, the role of DPL has been markedly reduced. Despite such remarkable advances, however, radiologic diagnosis of intestinal injury cannot always provide definitive results, and DPL may still be valuable in such instances. We have developed a new DPL criteria specifically designed to aid in the diagnosis of intestinal injury and have evaluated its effectiveness.nnnMETHODSnFrom August 1988 to December 1995, we performed DPL in 250 patients with blunt abdominal trauma and analyzed the diagnostic accuracy of our new criteria. We used the standard quantitative white blood cell (WBC) criterion for detection of intestinal injury supplemented by a positive-negative borderline adjusted to WBC > or = red blood cell (RBC)/150, where RBC > or = 10 x 10(4)/mm3.nnnRESULTSnOur criteria had a diagnostic sensitivity of 96.6% and a specificity of 99.4% for intestinal injury after exclusion of 57 patients in whom DPL was performed within 3 hours or after 18 hours from the time of injury. In 133 patients with hemoperitoneum, emergency celiotomy was performed in only 48; the remaining 85 patients with negative DPL based on the WBC criterion avoided surgery, and conservative management resulted in no complications.nnnCONCLUSIONnWith the proposed criteria, DPL can be used to diagnose or exclude intestinal injury even in the presence of hemoperitoneum.

WSES consensus conference: Guidelines for first-line management of intra-abdominal infections

Intra-abdominal infections are still associated with high rate of morbidity and mortality.A multidisciplinary approach to the management of patients with intra-abdominal infections may be an important factor in the quality of care. The presence of a team of health professionals from various disciplines, working in concert, may improve efficiency, outcome, and the cost of care.A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bologna on July 2010, during the 1st congress of the WSES, involving surgeons, infectious disease specialists, pharmacologists, radiologists and intensivists with the goal of defining recommendations for the early management of intra-abdominal infections.This document represents the executive summary of the final guidelines approved by the consensus conference.

World Society of Emergency Surgery (WSES) guidelines for management of skin and soft tissue infections

Skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions ranging from simple superficial infections to severe necrotizing soft tissue infections. Necrotizing soft tissue infections (NSTIs) are potentially life-threatening infections of any layer of the soft tissue compartment associated with widespread necrosis and systemic toxicity. Successful management of NSTIs involves prompt recognition, timely surgical debridement or drainage, resuscitation and appropriate antibiotic therapy. A worldwide international panel of experts developed evidence-based guidelines for management of soft tissue infections. The multifaceted nature of these infections has led to a collaboration among surgeons, intensive care and infectious diseases specialists, who have shared these guidelines, implementing clinical practice recommendations.

Evaluation of haemostatic molecular markers for diagnosis of disseminated intravascular coagulation in patients with infections

Early treatment of disseminated intravascular coagulation (DIC) is recommended but global coagulation tests used in authorized DIC criteria are not sensitive for diagnosis of early-phase DIC. We examined the plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC) and D-dimer in patients with suspected DIC to determine the cutoff values for diagnosis of DIC. Plasma levels of D-dimer, TAT and PPIC were significantly elevated in patients with DIC and correlated with DIC score. The cutoff values were determined using the receiver operative curve analysis. The cutoff value represented the point at which the sensitivity curve crossed the specificity curve. The cutoff values of D-dimer, TAT and PPIC for DIC were 12.0 mug/ml, 11.0 ng/ml and 1.8 mug/ml, respectively. These values were moderately to highly sensitive for the diagnosis of DIC but not for poor outcome. The combination of D-dimer, TAT and PPIC showed high sensitivity and low specificity when one or more tests were positive, but showed low sensitivity and high specificity when all three tests were positive. We conclude that hemostatic molecular markers might be useful for the diagnosis of DIC and should be confirmed by several trials.

Complicated Intra-Abdominal Infections in a Worldwide Context: An Observational Prospective Study (CIAOW Study)

Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The World Society of Emergency Surgery (WSES) has designed the CIAOW study in order to describe the clinical, microbiological, and management-related profiles of both community- and healthcare-acquired complicated intra-abdominal infections in a worldwide context. The CIAOW study (Complicated Intra-Abdominal infection Observational Worldwide Study) is a multicenter observational study currently underway in 57 medical institutions worldwide. The study includes patients undergoing surgery or interventional drainage to address complicated intra-abdominal infections. This preliminary report includes all data from almost the first two months of the six-month study period. Patients who met inclusion criteria with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 702 patients with a mean age of 49.2 years (range 18–98) were enrolled in the study. 272 patients (38.7%) were women and 430 (62.3%) were men. Among these patients, 615 (87.6%) were affected by community-acquired IAIs while the remaining 87 (12.4%) suffered from healthcare-associated infections. Generalized peritonitis was observed in 304 patients (43.3%), whereas localized peritonitis or abscesses was registered in 398 (57.7%) patients.The overall mortality rate was 10.1% (71/702). The final results of the CIAOW Study will be published following the conclusion of the study period in March 2013.