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This multicenter retrospective cohort study from Japan found that children who sustained blunt liver and/or spleen injury of any grade has a potential risk of delayed pseudoaneurysm development and rupture even after the early phase of interventional radiology.

184 patients divided into three groups based on trauma severity were compared by the seroconversion rate of HIT antibody. Seroconversion rate increased with trauma severity and was 16.3% in all cases. HIT antibody was not detected on day 30 in 60.9% of seroconverted patients.

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We investigated the epidemiology and outcome of disseminated intravascular coagulation (DIC) in patients with sepsis.

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Introduction:Extracorporeal cardiopulmonary resuscitation (ECPR) can be used on patients with out-of-hospital cardiac arrest (OHCA) when the cause is potentially reversible. However, little is known about the optimal target populations for ECPR among those with refractory OHCA.Methods:We retrospectively analyzed nationwide OHCA registry data on 57,754 patients from 93 hospitals in Japan, 2014-2019. We identified 1,273 patients having a witness or initially shockable rhythms with refractory OHCA of presumed cardiac origin without return of spontaneous circulation after >3 doses of adrenaline administration and defibrillations when necessary at the emergency department (ED). We used the causal forest—a machine learning method to estimate heterogeneous treatment effects—to determine individual treatment effects of ECPR on a favorable 30-day neurologic outcome defined as the Cerebral Performance Category scale of 1 or 2, adjusting for confounders (e.g., age, sex, initial cardiac rhythms, and laboratory data). We compared patient characteristics in each quintile of individual ECPR effects to identify potential determinants of ECPR effects in patients with refractory OHCA. Finally, to determine optimal targets of ECPR, we evaluated how ECPR effects could vary depending on patient characteristics.Results:We found that the treatment effects of ECPR on a favorable neurologic outcome were heterogeneous (top 20% vs. others, 0.15 vs. 0.00; p<0.001) (Figure 1). The key determinants of ECPR effects were initial cardiac rhythms on the emergency medical service (EMS) and at ED arrival, regardless of EMS transport time or laboratory data. In addition, ECPR effects varied depending on the information on ED arrival (i.e., witness, bystander CPR, and initial cardiac rhythms) (Figure 2).Conclusion:Among patients with refractory OHCA, information available on arrival at the ED could effectively identify patients who may particularly benefit from ECPR.

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Background: There are two opposing possibilities for the main pathogenesis of trauma-induced coagulopathy: an acute coagulopathy of trauma shock and disseminated intravascular coagulation with the fibrinolytic phenotype. Objective: The objective of this study was to clarify the main pathogenesis of trauma-induced coagulopathy using a rat model of Noble-Collip drum trauma. Methods: Eighteen rats were divided into the control, trauma 0, and trauma 30 groups. The trauma 0 and 30 groups were exposed to Noble-Collip drum trauma. Blood samples were drawn without, immediately after, and 30 min after Noble-Collip drum trauma in the control, trauma 0, and trauma 30 groups, respectively. Coagulation and fibrinolysis markers were measured. Thrombin generation was assessed according to a calibrated automated thrombogram. Results: Spontaneous thrombin bursts resulting from circulating procoagulants were observed in the nonstimulated thrombin generation assay immediately after trauma. Soluble fibrin levels (a marker of thrombin generation in the systemic circulation) were 50-fold greater in the trauma groups than in the control group. The resultant coagulation activation consumed platelets, coagulation factors, and antithrombin. Endogenous thrombin potential and factor II ratio were significantly negatively correlated with antithrombin levels, suggesting insufficient control of thrombin generation by antithrombin. High levels of active tissue-type plasminogen activator induced hyperfibrin(ogen)olysis. Soluble thrombomodulin increased significantly. However, activated protein C levels did not change. Conclusions: The systemic thrombin generation accelerated by insufficient antithrombin control leads to the consumption of platelets and coagulation factors associated with hyperfibrin(ogen)olysis. These changes are collectively termed disseminated intravascular coagulationwith the fibrinolytic phenotype.

Trauma-induced tissue factor (TF) release into the systemic circulation is considered to play an important role in the development of disseminated intravascular coagulation (DIC) immediately after severe trauma. However, the relationship between TF and hyperfibrinolysis, especially fibrinogenolysis, has been unclear. A total of 18 rats were divided into three groups: (a) the control group was infused with normal saline; (b) the low-dose group was infused with 4 Ukg TF; and (c) the high-dose group was infused with 16 Ukg TF. Arterial blood was drawn immediately and 2 and 4 h after the start of TF infusion. At each sampling point, arterial blood gases, platelet counts, and coagulation variables were measured. The fibrinogen degradation products were evaluated by a Western blot analysis. Hypotension, hypoxemia, and lactic acidosis were not observed in any of the three groups. In proportion to the doses of TF, the platelet counts, coagulation, and fibrinolysis variables deteriorated in line with DIC. The 2-plasmin inhibitor levels significantly decreased in the high-dose group compared with the other groups. The amounts of fibrinogen degradation products increased in proportion to the doses of TF. The plasmin-2-plasmin inhibitor complex level in the high-dose group increased more than that of the other groups. In conclusion, TF can induce DIC associated with fibrinolysis and fibrinogenolysis without tissue hypoperfusion. The decrease in the 2-plasmin inhibitor level and the significant increase in the plasmin level may be the two main factors underlying the pathogenesis of hyperfibrin(ogen)olysis after TF administration.

Recombinant human soluble thrombomodulin (TM-) was recently developed as an anticoagulant for patients with disseminated intravascular coagulation (DIC). However, the pharmacokinetics and pharmacodynamics of TM- in DIC patients with severe renal impairment have not yet been elucidated. We investigated the pharmacokinetics and pharmacodynamics of TM- in DIC patients with severe renal impairment. Eleven DIC patients with severe renal impairment (creatinine clearance <30 mLmin) and 10 DIC patients without severe renal impairment (creatinine clearance ≥30 mLmin) were included in this study. In all patients, a dose of 380 Ukg of TM- was administered during a 30-min infusion. Blood samples were taken before the start of the first TM- administration, and at 0.5, 2, 4, 8, and 24 h after the start of administration. Although the clearance of TM- in the patients with renal impairment was 80 of that in the patients without renal impairment, none of the pharmacokinetic values were significantly different between the groups. In the pharmacokinetic simulation, however, the trough levels of TM- increased gradually in the patients with renal impairment when the same dose of TM- was repeatedly administered. After the administration of TM-, the prothrombinase activities in the patients in both groups were sufficiently inhibited during the observation period. Although the pharmacokinetic values in DIC patients with severe renal impairment were only slightly different from those in DIC patients without severe renal impairment, we need to pay attention to the elevation of the trough levels of TM- when the same dose of TM- is repeatedly administered.

Neutrophil elastase plays an important role in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) in sepsis. Sivelestat is a selective neutrophil elastase inhibitor. It is possible that sivelestat improves the outcome of septic patients associated with ARDS and DIC. A retrospective data analysis of septic patients associated with ARDS and DIC was conducted to investigate the effects of sivelestat. Observational period was 5 days after admission to intensive care unit (ICU). The study included 167 septic patients associated with ARDS and DIC. Control group included 133 patients without sivelestat, and sivelestat group included 34 patients started to deadministered sivelestat on the admission to ICU. The lung injury scores and PaO2/FiO2ratio of the sivelestat group were significantly more severe than those of the control group from days 1 to 4. On day 5, the lung injury score and PaO2/FiO2ratio of the sivelestat group improved to the same levels of those of the control group. The DIC score of sivelestat group improved on day 3 in comparison to day 1, and those of control group remained unchanged until day 4. The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. A stepwise multiple logistic-regression analysis showed the sivelestat administration to be an independent predictor of survival of the septic patients associated with both ARDS and DIC. The length of ICU stay of the sivelestat group was significantly shorter than that of the control group. In addition, sivelestat administration was found to be an independent predictor of survival of those patients.

The decrease in the antithrombin III activity is thought to result from consumption by ongoing coagulation, degradation by neutrophil elastase, capillary leak syndrome, and impaired synthesis. A retrospective data analysis of patients with sepsis was conducted to investigate the response of antithrombin III activity after supplementation in patients with sepsis, and to determine what factors affect the response of antithrombin III activity. The study included 42 patients with sepsis, 75 patients with severe sepsis, and 65 patients with septic shock, who were administered antithrombin III. Antithrombin III activity, platelet counts, coagulation, and fibrinolytic markers were collected before administration and 24 h after the supplementation. In the patients with septic shock, the response of antithrombin III activity after supplementation was 0.37% ± 1.21%/IU per kg body weight, which was significantly lower in comparison with those in the patients with sepsis (1.81 ± 1.75; P< 0.001) or severe sepsis (1.36 ± 1.65; P< 0.001). The patients with liver dysfunction had significantly lower response to antithrombin III activity than that of the patients without liver dysfunction (P< 0.0001). A stepwise multiple linear regression analysis revealed that the severity of sepsis and liver function were independent predictors for the response to antithrombin III activity. These results suggest that the response to antithrombin III supplementation may be affected by both a systemic inflammation and impaired synthesis in patients with sepsis.

To investigate the relationship between the inflammatory responses and postresuscitation syndrome, we prospectively examined the serial changes of neutrophil elastase (NE), urinary trypsin inhibitor (UTI), and TNF-α) in successfully resuscitated patients after out-of-hospital cardiac arrest. This study included 36 patients with out-of-hospital cardiac arrests who were admitted to our intensive care unit after return of spontaneous circulation (ROSC). The 11 patients who restored to spontaneous circulation within 30 min after cardiac arrest were defined as the short cardiac arrest group. The 25 patients who restored to spontaneous circulation more than 30 min after cardiac arrest were defined as the long cardiac arrest group. Eight healthy volunteers served as control group. Daily plasma levels of NE, UTI, and TNF-α were measured from days 1 to 5 after ROSC. The releases of NE from activated neutrophil just after ROSC in the patients with long cardiac arrest were statistically higher than those of the short cardiac arrest group. There was a significant correlation between the NE levels and the duration of cardiac arrest. A high but insufficient production of UTI for NE release was observed on day 1, especially in the patients with a long duration of cardiac arrest. The cerebral performance category of the short cardiac arrest group was better than that of the long cardiac arrest group. Although high levels of TNF-α were sustained in the postresuscitation period, the levels of TNF-α were unrelated to the duration of cardiac arrest. In conclusion, a massive release of NE in proportion to the duration of cardiac arrest and an insufficient production of UTI for the NE release may contribute to the pathogenesis of postresuscitation syndrome after out-of-hospital cardiac arrest.

We have applied a new methodology for noninvasive continuous blood glucose monitoring, proposed in our previous paper, to patients in ICU (intensive care unit), where strict controls of blood glucose levels are required. The new methodology can build calibration models essentially from numerical simulation, while the conventional methodology requires pre-experiments such as sugar tolerance tests, which are impossible to perform on ICU patients in most cases. The in vivoexperiments in this study consisted of two stages, the first stage conducted on healthy subjects as preliminary experiments, and the second stage on ICU patients. The prediction performance of the first stage was obtained as a correlation coefficient (r) of 0.71 and standard error of prediction (SEP) of 28.7 mg/dL. Of the 323 total data, 71.5% were in the A zone, 28.5% were in the B zone, and none were in the C, D, and E zones for the Clarke error-grid analysis. The prediction performance of the second stage was obtained as an rof 0.97 and SEP of 27.2 mg/dL. Of the 304 total data, 80.3% were in the A zone, 19.7% were in the B zone, and none were in the C, D, and E zones. These prediction results suggest that the new methodology has the potential to realize a noninvasive blood glucose monitoring system using near-infrared spectroscopy (NIRS) in ICUs. Although the total performance of the present monitoring system has not yet reached a satisfactory level as a stand-alone system, it can be developed as a complementary system to the conventional one used in ICUs for routine blood glucose management, which checks the blood glucose levels of patients every few hours.

Critically ill patients often have complications of acute renal failure induced by severe infection or sepsis. The patients need administration of broad-spectrum antibiotics as well as continuous renal replacement therapy (CRRT). However, there is no uniform pharmacokinetics of antibiotics during the CRRT because CRRT is performed with the various combinations of dialysate flows (QD) and ultrafiltrate flows (QF). The aims of this study were to estimate the pharmacokinetics of panipenem/beta Mipron (PAPM/BP) and to determine the appropriate treatment regimens for PAPM/BP in critically ill patients undergoing CRRT. In patients with CRRT, the PAPM total clearance (PAPM CLtot) was calculated as the sum of PAPM clearance dependent on the living body and CRRT and shown as follows:

To determine the existence of a close link between inflammation and coagulation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and to examine their prognostic value in the development of ARDS and clinical outcome, we made a prospective cohort study. The study subjects consisted of 57 patients: 19 patients with ARDS and 38 patients with ALI as defined by a Lung Injury Score of ≥2.5 and 1.0 to less than 2.5, respectively. According to the outcome, the patients were subdivided into the survivors and the nonsurvivors. Ten normal healthy volunteers served as control subjects. Plasma levels of soluble L-, P-, and E-selectins, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (sTM), and neutrophil elastase were measured within 24 h after the diagnosis of ALI or ARDS. The number of systemic inflammatory response syndrome (SIRS) criteria being met by the patients and the disseminated intravascular coagulation (DIC) scores were determined simultaneously. The number of SIRS criteria and the DIC scores of the patients with ALI or ARDS showed high values, and more than half of the patients were complicated by DIC. The levels of sL-selectin in both groups of the patients were significantly lower than those of the control subjects. All other soluble adhesion molecules, neutrophil elastase, and sTM in the patients with ALI and ARDS were markedly elevated than those in the control subjects. The levels sICAM-1, sVCAM-1, and sTM in the ARDS patients significantly increased compared with the ALI patients. The number of SIRS criteria and the DIC scores in the nonsurvivors showed higher values than those in the survivors. In addition, we found significant differences in the levels of soluble adhesion molecules, neutrophil elastase, and sTM between the survivors and the nonsurvivors. {In conclusion, we found a concurrent activation of both inflammation and coagulation in the patients with ALI or ARDS. The results also suggest that systemic activation of inflammation and coagulation associated with endothelial injury has prognostic value for the development of ARDS and poor outcome.}

Case. We report a case of severe methemoglobinemia due to sodium nitrite poisoning. A 28-year-old man was brought to our emergency department because of transient loss of consciousness and cyanosis. He was immediately intubated and ventilated with 100% oxygen. A blood test revealed a methemoglobin level of 92.5%. Outcome. We treated the patient with gastric lavage, activated charcoal, and methylene blue (2 mg/kg) administered intravenously. Soon after receiving methylene blue, his cyanosis resolved and the methemoglobin level began to decrease. After relocation to the intensive care unit, his consciousness improved and he could recall ingesting approximately 15 g sodium nitrite about 1 hour before he was brought to our hospital. The patient was discharged on day 7 without neurologic impairment. Conclusion. Severe methemoglobinemia may be fatal. Therefore, accurate diagnosis of methemoglobinemia is very important so that treatment can be started as soon as possible.