Yoh Hirayama

Treatment of Severe Sepsis and Septic Shock by CHDF Using a PMMA Membrane Hemofilter as a Cytokine Modulator

It has been reported that various types of blood purification intended for the removal of humoral mediators, such as cytokines, were performed in patients with severe sepsis/septic shock. While high-volume hemofiltration, hemofiltration using high cut-off membrane filters, and direct hemoperfusion with a polymyxin-B immobilized column are widely used in the treatment of severe sepsis/septic shock, we perform continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF), which shows an excellent cytokine-adsorbing capacity, for the treatment of severe sepsis/septic shock. In our previous study, it was found that PMMA-CHDF could efficiently remove various pro-inflammatory cytokines such as TNFalpha, IL-6 and IL-8 from the bloodstream, resulting in early recovery from septic shock. Furthermore, PMMA-CHDF could remove anti-inflammatory cytokines such as IL-10 from bloodstream, suggesting that it might improve immunoparalysis as well. These findings suggest that PMMA-CHDF is useful for the treatment of patients with severe sepsis/septic shock as a cytokine modulator.

Differential pattern of cell-surface and soluble TREM-1 between sepsis and SIRS

OBJECTIVE Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to play a key roll in amplification of production of inflammatory cytokines. TREM-1 is suggested to be a specific biomarker for sepsis for this reason, but the clinical significance of TREM-1 has not been elucidated. We investigated TREM-1 expression on the cell-surface, and plasma levels of soluble TREM-1 (sTREM-1) in patients with non-infectious systemic inflammatory response syndrome (SIRS) and sepsis admitted to the ICU. METHODS Thirty-five patients with SIRS and 21 patients with sepsis admitted to ICU were subjected to the study. TREM-1 expressions on the surfaces of monocytes and neutrophils were measured by flow cytometry. Plasma sTREM-1 level and serum interleukin (IL)-6 level were measured. RESULTS Septic patients had decreased TREM-1 expression, clearly on neutrophils or to a lesser extent on monocyte compared to SIRS patients on ICU admission (neutrophils p<0.001, monocyte p<0.05). TREM-1 expression on neutrophils had a significant inverse correlation with serum IL-6 level (r=-0.64, p<0.0001). Plasma sTREM-1 level in septic patients was significantly higher than that in SIRS patients (p<0.05). Plasma sTREM-1 level positively correlated with severity score and non-survivors had increased plasma sTREM-1 level compared to survivors in all SIRS/sepsis patients (p<0.05). CONCLUSIONS Patients with sepsis had increased soluble TREM-1 and decreased TREM-1 expression on neutrophil compared to SIRS patients. sTREM-1 may be useful to evaluate disease severity and outcome of patients with SIRS or sepsis.

Outcome prediction in sepsis combined use of genetic polymorphisms - A study in Japanese population.

Genetic polymorphisms have recently been found to be related to clinical outcome in septic patients. The present study investigated to evaluate the influence of genetic polymorphisms in Japanese septic patients on clinical outcome and whether use of genetic polymorphisms as predictors would enable more accurate prediction of outcome. Effects of 16 genetic polymorphisms related to pro-inflammatory mediators and conventional demographic/clinical parameters (age, sex, past medical history, and APACHE II score) on ICU mortality as well as disease severity during ICU stay were examined in the septic patients (n=123) admitted to the ICU between October 2001 and November 2007 by multivariable logistic regression analysis. ICU mortality was significantly associated with TNF -308GA, IL1β -31CT/TT, and APACHE II score. Receiver-operating characteristics (ROC) analysis demonstrated that, compared with APACHE II score alone (ROC-AUC=0.68), use of APACHE II score and two genetic parameters (TNF -308 and IL1β -31) enabled more accurate prediction of ICU mortality (ROC-AUC=0.80). Significant association of two genetic polymorphisms, TNF -308 and IL1β -31, with ICU mortality was observed in septic patients. In addition, combined use of these genetic parameters with APACHE II score may enable more accurate prediction of outcome in septic patients.

The role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the treatment with continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF).

OBJECTIVE To examine the role of hypercytokinemia in the pathophysiology of tumor lysis syndrome (TLS) and the efficacy of continuous hemodiafiltration in the treatment of TLS. DESIGN AND SETTING Retrospective observational study in a general intensive care unit of a university hospital. PATIENTS Four patients with hematological disorder developing TLS after the treatment of anti-tumor chemotherapy. INTERVENTIONS Continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA-CHDF) was performed at the onset of TLS. Blood samples were collected daily after ICU admission, and clinical parameters and blood levels of cytokines were evaluated. MEASUREMENTS AND RESULTS All four patients underwent induction anti-tumor chemotherapy, during which they developed hyperuricemia, hyperkalemia, and acute renal failure. Two of them also developed multiple organ failure. Serum levels of tumor necrosis factor (TNF) -alpha, interleukin-6 (IL-6), and IL-10 prior to the initiation of PMMA-CHDF were 102+/-85 pg/mL, 1097+/-546 pg/mL, and 98+/-83 pg/mL, respectively (mean +/- SD). After three days of PMMA-CHDF treatment, corresponding blood levels were 37+/-55 pg/mL, 326+/-511pg/mL, and 9+/-8 pg/mL, respectively. Thus, all cytokine levels were significantly decreased by three days of PMMA-CHDF treatment (p<0.05, paired t-test). Following three days of PMMA-CHDF treatment, blood urea nitrogen (BUN) and serum creatinine (Cre.) were significantly decreased (pre/post BUN 42.3+/-15.4/16.5+/-8.4 mg/dL, p<0.05, pre/post Cre. 2.7+/-1.2/1.2+/-0.6 mg/dL, mean +/- SD, p<0.05). Furthermore, the clinical condition of each patient was improved after the treatment of PMMA-CHDF, and all of four patients were survived. CONCLUSION Hypercytokinemia plays a pivotal role in the pathophysiology of TLS and PMMA-CHDF may be an effective therapeutic modality for TLS patients not only as renal replacement therapy but also as a cytokine modulator.

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

Abstract:  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.

Partial liquid ventilation with FC-77 suppresses the release of lipid mediators in rat acute lung injury model.

Objective:To investigate whether the release of lipid mediators is suppressed in rats with experimentally induced acute lung injury managed with partial liquid ventilation (PLV) using FC-77. Design:Prospective, randomized controlled study. Setting:Research laboratory in a university. Subjects:Male Sprague-Dawley rats. Interventions:After tracheostomy was performed under general anesthesia, lung injury was induced by intratracheal instillation of HCl. The PLV group was then subjected to conventional gas ventilation for 30 mins, followed by PLV using FC-77. The control group was subjected to conventional gas ventilation throughout the study period. Measurements and Main Results:In the PLV group the following results were obtained: a) impaired oxygenation was markedly improved; b) the increase in the serum levels of lipid mediators such as leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1&agr; was suppressed; and c) the increase in the concentrations of leukotriene B4, thromboxane A2, and 6-keto-prostaglandin F1&agr; in the total lung homogenate at 180 mins after lung injury was also suppressed. Conclusion:This study indicates that PLV using FC-77 suppresses the release of lipid mediators in our rat model of acute lung injury. However, further investigation is needed to clarify the precise mechanism of this effect.

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.