Successful treatment of pulmonary embolism-induced cardiac arrest by thrombolysis and targeted temperature management during pregnancy.

BACKGROUND: Thrombolysis for pulmonary embolism and targeted temperature management for cardiac arrest are controversial treatments in pregnancy. CASE: A 37-year-old woman at 23 weeks gestation presented with persistent dyspnea. She experienced cardiac arrest soon after arrival at the emergency room. Massive right ventricular dilatation on echocardiography during the transient return of spontaneous circulation suggested pulmonary embolism. We administered recombinant tissue plasminogen activator for suspected pulmonary embolism to successfully resuscitate the patient experiencing refractory cardiac arrest despite heparin infusion. After an additional dose of monteplase for persistent shock with remaining right ventricular dilatation on echocardiography, maternal hemodynamics dramatically improved, but fetal heart rate transiently decreased. Targeted temperature management was initiated for delayed recovery of consciousness. She fully recovered consciousness without neurological deficit. However, the fetus was aborted because of fetal hydrops. CONCLUSION: Thrombolysis and targeted temperature management should be considered as treatment options for pulmonary embolism-induced cardiac arrest during pregnancy.

A successful salvage therapy with daptomycin and linezolid for right-sided infective endocarditis and septic pulmonary embolism caused by methicillin-resistant Staphylococcus aureus.

Although vancomycin administration is recommended for the treatment of infective endocarditis (IE) caused by methicillin-resistant Staphylococcus aureus (MRSA), it is unclear whether an alternative agent, daptomycin, can be used to treat IE with pulmonary complications. A 26-year-old female who had undergone surgical repair of a ventricular septal defect as an early teenager presented with fever, headache, and vomiting. She was admitted to our hospital and diagnosed with right-sided IE with septic pulmonary embolism caused by MRSA. Vancomycin, rifampicin, and gentamicin were administered; however, exacerbation of drug eruption due to the antimicrobial agents on the 11th day led us to switch from vancomycin and rifampicin to daptomycin. Furthermore, we included linezolid to treat lung abscesses that accompanied the septic pulmonary embolism. We confirmed negative blood cultures on the 18th day. On the same day, a patch closure for the ventricular septal defect and tricuspid valve replacement were performed. She was discharged on the 65th day with an uneventful postoperative course. This experience suggests that daptomycin and linezolid are effective salvage therapies for right-sided IE caused by MRSA and accompanied by pulmonary complications.

Brorin is required for neurogenesis, gliogenesis, and commissural axon guidance in the zebrafish forebrain.

Bmps regulate numerous neural functions with their regulators. We previously identified Brorin, a neural-specific secreted antagonist of Bmp signaling, in humans, mice, and zebrafish. Mouse Brorin has two cysteine-rich domains containing 10 cysteine residues in its core region, and these are located in similar positions to those in the cysteine-rich domains of Chordin family members, which are secreted Bmp antagonists. Zebrafish Brorin had two cysteine-rich domains with high similarity to those of mouse Brorin. We herein examined zebrafish brorin in order to elucidate its in vivo actions. Zebrafish brorin was predominantly expressed in developing neural tissues. The overexpression of brorin led to the inactivation of Bmp signaling. On the other hand, the knockdown of brorin resulted in the activation of Bmp signaling and brorin morphants exhibited defective development of the ventral domain in the forebrain. Furthermore, the knockdown of brorin inhibited the generation of γ-aminobutyric acid (GABA)ergic interneurons and oligodendrocytes and promoted the generation of astrocytes in the forebrain. In addition, brorin was required for axon guidance in the forebrain. The present results suggest that Brorin is a secreted Bmp antagonist predominantly expressed in developing neural tissues and that it plays multiple roles in the development of the zebrafish forebrain.

Blood ammonia and lactate levels on hospital arrival as a predictive biomarker in patients with out-of-hospital cardiac arrest.

INTRODUCTION: No reliable predictor for the prognosis of out-of-hospital cardiac arrest (OHCA) on arrival at hospital has been identified so far. We speculate that ammonia and lactate may predict patient outcome. METHODS: This is a prospective observational study. Non-traumatic OHCA patients who gained sustained return of spontaneous circulation and were admitted to acute care unit were included. Blood ammonia and lactate levels were measured on arrival at hospital. The patients were classified into two groups: 'favourable outcome' group (Cerebral Performance Category CPC1-2 at 6-months' follow-up) and 'poor outcome' group (CPC3-5). Basal characteristics obtained from the Utstein template and biomarker levels were compared between these two outcome groups. Independent predictors were selected from all candidates using logistic regression analysis. RESULTS: A total of 98 patients were included. Ammonia and lactate levels in the favourable outcome group (n=10) were significantly lower than those in poor outcome group (n=88) (p<0.05, respectively). On receiver operating characteristic analysis, the optimal cut-off value for predicting favourable outcome was determined as 170 µg dl(-1) of ammonia and 12.0 mmol l(-1) of lactate (area under the curve; 0.714 and 0.735, respectively). Logistic regression analysis identified ammonia (≤170 µg dl(-1)), therapeutic hypothermia and witnessed by emergency medical service personnel as independent predictors of favourable outcome. When both these biomarker levels were over threshold, positive predictive value (PPV) for poor outcome was calculated as 100%. CONCLUSIONS: Blood ammonia and lactate levels on arrival are independent prognostic factors for OHCA. PPV with the combination of these biomarkers predicting poor outcome is high enough to be useful in clinical settings.

Serum S-100B is superior to neuron-specific enolase as an early prognostic biomarker for neurological outcome following cardiopulmonary resuscitation.

INTRODUCTION: Most patients with cardiac arrest (CA) admitted to hospitals after successful cardiopulmonary resuscitation (CPR) are discharged with various degree of neurological deficits. To determine predictor of neurological outcome early and accurately, and to determine cutoff values, serum levels of protein S-100B and neuron-specific enolase (NSE) within 24h after CA were assessed. METHODS AND RESULTS: A multicenter prospective observational study was conducted between May 2007 and April 2008 at three medical institutions in Japan on 107 consecutive non-traumatic CA patients with return of spontaneous circulation after CPR. Based on "best-ever achieved" Glasgow-Pittsburgh cerebral performance categories (CPC) score within 6 months after CA, patients were classified into a "poor neurological outcome" group (CPC3 to CPC5) (n=67) and "favorable neurological outcome" group (CPC1 and CPC2) (n=13). Blood was sampled on admission, at 6 and 24h after CA. Serum S-100B and NSE in "poor outcome" group were higher than those in "favorable outcome" group (P<0.01). On ROC analysis, area under the curve of S-100B was 0.85, 0.94 and 1.0, respectively. These were greater than those of NSE at all sampling points. The "100%-specific" cutoff values of S-100B predictive of poor neurological outcome were 1.41, 0.21, and 0.05ng/mL, respectively. These values corresponded to sensitivities of 20.9%, 62.8%, and 100%, respectively, each of which was higher than those of NSE. CONCLUSIONS: S-100B is more reliable as an early predictor of poor neurological outcome within 24h after CA than NSE and can be applied clinically.

[Efficacy of micafungin sodium on fungal infection in critical care].

The clinical effects and tolerability of micafungin sodium in daily practice for the treatment of fungal infection in critically ill patients were evaluated in an open-labeled, non-comparative, observational study. All patients admitted to intensive care units (ICUs) of 3 hospitals in Chiba prefecture between June 2003 and March 2005, who were treated with micafungin because of known or suspected fungal infection, were included in the study. A total of 34 patients received micafungin and 29 cases of them were subjected to analysis. Fungal infections were classified as "proven" in 3 patients (10.3%) and "possible" in 26 (89.7%). Candida was detected in 16 patients, most of them were Candida albicans and 4 cases were non-albicans Candida. Clinical effects of micafungin were "cured" and "improved" in 20 patients (77%), "failure" in 6 (23%), and "undetermined" in 3 cases. Adverse events were reported in 10 patients, but there was no significant event. In conclusion, micafungin was effective in 77% of proven or suspected fungal infections in critically ill patients admitted to the ICU. The drug was well tolerated and discontinuation of its treatment due to adverse events was not experienced during the study period.

Intracranial pressure monitoring in patients with fulminant hepatic failure treated with plasma exchange and continuous hemodiafiltration.

BACKGROUND/AIMS: To study the influence of our artificial liver support (ALS) on intracranial pressure (ICP) and to evaluate the significance of ICP monitoring in fulminant hepatic failure (FHF) patients treated with ALS. METHODS: ICP was measured in 13 consecutive FHF patients treated with ALS. Maximum value in ICP every day was employed as ICPmax of the day. We analyzed the correlation: (a) between ICPmax and consciousness level; (b) between ICP and colloid osmotic pressure (COP), and (c) between ICP and PaCO2. RESULTS: ICP in 11 patients of 13 was controlled < 20 mm Hg through our ALS. A significant positive correlation between ICPmax and consciousness level was found (p < 0.01). Although there was a significantly negative correlation between ICP and COP (p < 0.001), there was no correlation between ICP and PaCO2. CONCLUSIONS: We conclude that our ALS does not have any adverse effects on ICP and that ICP monitoring is one of the inevitable monitorings in the management of FHF.

Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis.

This study was undertaken to investigate whether sequential measurement of blood interleukin (IL)-6 levels using chemiluminescent enzyme immunoassay (CLEIA) would be useful for the management of patients with systemic inflammatory response syndrome (SIRS)/sepsis. Forty consecutive patients with SIRS/sepsis admitted to ICU were involved in the study. Blood IL-6 level was measured everyday throughout their ICU stay at the clinical laboratory by CLEIA method. The platelet count and the sequential organ failure assessment (SOFA) score were measured consecutively. The blood IL-6 levels were elevated in SIRS/sepsis patients and were extremely high in patients with septic shock. There was no significant difference in the blood IL-6 level on admission between survivors (n=27) and non-survivors (n=13). However, the mean blood IL-6 level during ICU stay was significantly higher in the non-survivors (p<0.05). There were significant correlation between the peak IL-6 blood level and the lowest platelet count, and between the peak IL-6 blood level and the maximum SOFA score, respectively. The platelet count became lowest 2.0+/-2.0 days later on average, and the SOFA score became maximal 2.5+/-1.4 days later on average following the day when IL-6 reached its peak value. Sequential measurement of blood IL-6 levels by CLEIA is useful in evaluating the severity and in predicting the outcome of the patients with SIRS/sepsis.

Cytokine adsorptive property of various adsorbents in immunoadsorption columns and a newly developed adsorbent: an in vitro study.

BACKGROUND/AIMS: Cytokines play important roles in the pathophysiology of systemic inflammatory response syndrome (SIRS) and sepsis. Therefore, some effective measures to remove cytokines from the bloodstream could be effective in the treatment of SIRS and sepsis. The aim of this study was to evaluate the cytokine adsorptive property of various adsorbents for the purpose of the development of new selective cytokine adsorption columns. METHODS: The cytokine adsorptive property of adsorbent in a CF-X column, which consists of cellulose beads cross-linked with hexamethylene-di-isocyanate, was compared with those of various adsorbents in currently available immunoadsorption columns, such as Immusorba TR, Immusorba PH, Selesorb, and Lixelle, in vitro batchwise test using patients' plasma. A newly developed adsorbent, MPCF-X, which was modified by coating the surface of the adsorbent in CF-X with 2-methacryloyloxyethyl phosphorylcholine (MPC), was also tested for its cytokine adsorptive property. RESULTS: The adsorbent in CF-X showed a significantly higher adsorption rate for TNF-alpha, interleukin (IL)-6 and IL-10 compared with other adsorbents (p < 0.05). Adsorbent in Lixelle showed good affinity to TNF-alpha and IL-8. Especially, the adsorbent in CF-X almost completely removed TNF-alpha, whereas it also had considerable affinity to normal IgG. MPCF-X showed decreased affinity to IgG with considerable adsorptive properties to cytokines. CONCLUSION: Selective cytokine adsorption columns could be developed with improvement of currently available adsorbents. Such a new selective cytokine adsorption column could be clinically applied for the treatment of SIRS/sepsis.

Catheter-related infections in continuous hemodiafiltration in intensive care patients.

BACKGROUND/AIMS: Infection control is of key importance especially in the application of long-term continuous hemodiafiltration (CHDF) involving invasive vascular catheterization to critically ill patients. We investigated hemodialysis catheter-related infections in long-term CHDF. METHODS: We examined catheter infections in 54 patients who were admitted to the intensive care unit and underwent CHDF for 2 weeks or longer. RESULTS: With a total of 155 catheters (1,071 catheter days) studied, catheter colonization and catheter-related bloodstream infection were noted with an incidence rate of 4.8 and 2.7 per 1,000 catheter days, respectively. No difference in catheter colonization rate was observed depending on the catheterization sites or duration of catheterization. Infections were identified in 39 patients (72%) and blood culture positivity was noted in 25 patients (46%). CONCLUSIONS: Since the majority of cases requiring long-term CHDF are complicated with a variety of infections, it is difficult to control infections associated with hemodialysis catheters separately from infections of other types. Systemic infection control should serve as a strategy finally leading to successful control of catheter-related infection.

Modulation of polymorphonuclear leukocyte apoptosis in the critically ill by removal of cytokines with continuous hemodiafiltration.

Delay of polymorphonuclear leukocyte (PMN) apoptosis caused by hypercytokinemia is considered to be a potential cause of tissue damage and resultant organ failure. We evaluated whether continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF), which can remove cytokines in the circulating blood, can modulate apoptosis in peripheral blood neutrophils and thereby reduce tissue damage and organ dysfunction in 25 critically ill patients. Following the completion of a 3-day PMMA-CHDF session, serum cytokine levels were significantly decreased and the percentage of apoptotic PMNs was significantly increased. A significant correlation was observed between the PMMA-CHDF-induced increase in the percentage of apoptotic PMNs and the degree of decrease in the serum interleukin-6 level. A significant correlation was also found between the increase in the percentage of apoptotic PMNs and improvement in sequential organ failure assessment score following PMMA-CHDF. These results suggest that PMMA-CHDF in critically ill patients with hypercytokinemia and concomitant delay in apoptosis of PMNs can alleviate the delay of PMN apoptosis through the removal of serum cytokines and thus may result in avoidance of organ dysfunction.

The change in renal replacement therapy on acute renal failure in a general intensive care unit in a university hospital and its clinical efficacy: a Japanese experience.

The aim of our study was to examine renal replacement therapies (RRT) that have been used for acute renal failure (ARF) in our intensive care unit (ICU) patients and to compare their outcomes. Sixteen patients who underwent intermittent hemodialysis (IHD), 14 patients who underwent continuous hemofiltration (CHF) in combination with IHD (CHF + IHD), and 38 patients who underwent continuous hemodiafiltration (CHDF) were evaluated. Regarding the effects of blood purification on hemodynamics and renal function, the percentage increase in blood pressure and percent rapid increase in urinary output were the greatest in the CHDF group. The hourly urinary output after the start of initial blood purification increased only in the CHDF group. The survival rate was significantly higher in the CHDF group. These results suggest that CHDF should be the first-line therapy for patients with ARF and that we are moving in the right direction regarding the application of RRT to treat ARF in ICU patients.

Coagulation/fibrinolysis abnormality and vascular endothelial damage in the pathogenesis of thrombocytopenic multiple organ failure.

OBJECTIVE: Until recently, attention has been directed to disseminated intravascular coagulation as a cause of multiple organ failure (MOF). On the other hand, it has now become clear that humoral mediators play important roles in the pathogenesis of MOF. Therefore, we performed the present study in patients with thrombocytopenic MOF to investigate the relationship between various humoral mediators and vascular endothelial damage reported to be triggered by such humoral mediators in the pathogenesis of MOF. DESIGN: A retrospective clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS: The study included 18 thrombocytopenic patients whose conditions progressed to septic MOF (MOF group) and 20 others who did not progress to MOF (non-MOF group). The MOF group and non-MOF group were also presented with infection and with platelet counts of <100,000/mm3. MEASUREMENTS AND MAIN RESULTS: The MOF group had fibrinolysis abnormality, as indicated by increased plasminogen activator inhibitor-1 level. On the other hand, the MOF group had increased polymorphonuclear elastase and polymorphonuclear-mediated fibrinogen degradation product levels with consequent prolonged elevation of thrombomodulin. In addition, both polymorphonuclear elastase and polymorphonuclear-fibrinogen degradation products were significantly positively correlated with thrombomodulin in the MOF group, but no such positive correlation was observed between interleukin-6 or plasminogen activator inhibitor-1 and thrombomodulin. In the non-MOF group, on the other hand, thrombomodulin exhibited no significant positive correlation with polymorphonuclear elastase, polymorphonuclear-fibrinogen degradation products, interleukin-6, or plasminogen activator inhibitor-1. CONCLUSIONS: Our study provided evidence that vascular endothelial damage was the primary cause of organ failures in patients with thrombocytopenic MOF and that humoral mediators played a major role in the development of vascular endothelial damage in such patients. These results suggest that it is important to treat thrombocytopenic MOF as a condition of vascular endothelial damage, with weight placed on countermeasures against disorders of humoral mediators.

Efficacy of continuous hemodiafiltration for patients with congestive heart failure.

BACKGROUND/AIMS: The basic principle of treatment of congestive heart failure is achieving adequate control of preload and afterload through enhancement of cardiac contractility. In severe cases, however, we have usually applied continuous hemodiafiltration (CHDF) as a type of mechanical support. In this study, we investigated hemodynamic changes caused by CHDF in patients with congestive heart failure. METHODS: We treated seven patients with congestive heart failure complicated by multiple organ failure by CHDF over 72 h, during which we measured hemodynamic parameters to determine their changes. RESULTS: Implementation of CHDF resulted in a significant decrease in pulmonary artery occluded pressure and significant increases in cardiac index and left ventricular stroke work index. In addition, 72-hour cumulative water balance was found to be -1,791 +/- 2,119 ml, and systemic vascular resistance index decreased significantly. CONCLUSION: Hemodynamics of patients were improved with CHDF through strict control of preload and consequently tissue oxygen metabolism was improved.

Continuous hemofiltration/hemodiafiltration in critical care.

Continuous hemofiltration and continuous hemodiafiltration (CHF/CHDF) were developed as continuous renal replacement therapy for patients with severe conditons and has come to be widely performed mainly in critical care, taking the place of intermittent hemodialysis. The membrane pore size of a hemofilter used for CHF/CHDF allows passage of substances ranging from 30,000 to 50,000 Da, and the method for solute removal in CHF/CHDF employs the principle of convection, which is advantageous for removing middle- to high-molecular-weight substances. As apheresis therapy to remove pathogenic substances in blood, CHF/CHDF is therefore being investigated for its possible effect on various morbid conditions. It has recently been found that CHF/CHDF removes humoral mediators including cytokines, particularly in severe systemic inflammatory response syndromes such as septic shock and severe acute pancreatitis. CHF/CHDF is thus beginning to be performed for the prevention and treatment of organ dysfunction secondary to septic shock, trauma, or acute pancreatitis. CHF/CHDF is also efficacious as artificial liver support in preventing adverse effects caused by plasma exchange (PE) and for continuous removal of hepatic coma-inducing substances. CHF/CHDF is effective for various morbid conditions not only as renal replacement therapy, but also as apheresis therapy and is expected to be applied more widely in critical care in the future.

Long-term survivors with artificial liver support in fulminant hepatic failure.

Clinical ability of artificial liver support (ALS) has been improved greatly in recent years which has allowed us to encounter long-term survivors with fulminant hepatic failure (FHF) whose liver function has been almost completely lost. This suggests that application of ALS in patients with FHF gains time while awaiting transplantation as well as time for functional recovery and regeneration of the liver graft following receipt of the graft with marginal function and/or size. Thus, ALS will contribute greatly to extending the indications for liver transplantation and increase the number of patients receiving and benefiting from this treatment. On the other hand, introduction of ALS prolongs the duration of intensive treatment which increases the risk of infection and increases medical costs. In addition, when to discontinue intensive treatment of patients whose level of consciousness is maintained only by ALS is controversial. Thus, further investigation will be needed to establish a consensus on indications for long-term ALS in FHF.

A patient with severe acute pancreatitis successfully treated with a new critical care procedure.

It has been accepted widely that excessive humoral mediators play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP) and that infection of the pancreas due to bacterial translocation (BT) is the most frequent cause of death in SAP. On the other hand, it has been reported that continuous hemodiafiltration (CHDF) removes humoral mediators on hypercytokinemic patients such as those with systemic inflammatory response syndrome. Furthermore, several clinical studies have demonstrated that selective digestive decontamination (SDD) effectively eliminates aerobic Gram-negative bacteria from the intestinal tract and reduces the incidence of septic complications in SAP. Herein we report a case of SAP who was treated successfully with intensive care including CHDF and SDD. Thus, this case report suggests that CHDF aimed at removing causative humoral mediators and SDD for the prevention of BT are useful new tools for the management of SAP.

Endothelin receptor remodeling induces the portal venous hyper-response to endothelin-1 following endotoxin pretreatment.

The purpose of this study was to determine the changes in endothelin (ET) receptor subtype expression and their functional significance after endotoxin pretreatment. Rats were pretreated with lipopolysaccharide (LPS) or sterile saline (control). After 24 h, liver samples were homogenized and competitive receptor binding assays were performed. There was no significant difference in ET receptor binding affinity between the control and LPS groups. However, the receptor subtype density showed a significant increase in ET(B) receptors in LPS-treated rats, whereas the amount of ET(A) receptors was almost identical between the two groups. In control, almost all ET receptors (95%) were displaced by using combined ET(A) antagonist (BQ-610) and ET(B) agonist (IRL-1620) as competitors, whereas only 80% (P < 0.05 versus control) was displaced in LPS group, raising the possibility of novel type of ET receptor expression. An infusion of ET(B) agonist (Sarafotoxin 6c, S6c) through portal vein in isolated perfused livers produced the same pressure response in both LPS and control groups; however, the portal pressure increase in response to the ET-1, which binds all ET receptors, was significantly potentiated in LPS-treated rats compared to controls. We conclude that altered regulation of ET receptors, in particular, the appearance of ET binding capacity that is not displaced by ET(A) or ET(B) competitors, may explain the hyper-response of the portal venous system to ET-1 during endotoxemia.