Hidetoshi Shiga

Management of intra-abdominal hypertension in patients with severe acute pancreatitis with continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter

Abstract:  To evaluate, with a prospective observational study, whether continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter (PMMA‐CHDF) is effective for prevention and treatment of  intra‐abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on patients with severe acute pancreatitis (SAP). The study was carried out in the general intensive care unit (ICU) of a university hospital. Seventeen consecutive patients with SAP were treated in the intensive care unit and underwent PMMA‐CHDF whether or not they had renal failure. Blood level of interleukin (IL)‐6, as an indicator of cytokine network activation, and intra‐abdominal pressure (IAP) were measured daily to investigate their time‐course of changes and the correlation between the two. The blood level of IL‐6 was high at 1350 ± 1540 pg/mL on admission to the ICU. However, it significantly decreased to 679 ± 594 pg/mL 24 h after initiation of PMMA‐CHDF (P < 0.05), and thereafter decreased rapidly. Mean intra‐abdominal pressure (IAP) on admission was high, at 14.6 ± 5.3 mm Hg, with an IAP of 20 mm Hg or over in 2 of 17 patients, showing that they had already developed IAH. The IAP was significantly lower (P < 0.05) 24 h after initiation of PMMA‐CHDF, and subsequently decreased. There was a significant positive correlation between blood level of IL‐6 and IAP, suggesting that PMMA‐CHDF improved vascular permeability through elimination of cytokines, and that it thereby decreased interstitial edema to lower IAP. Sixteen of the 17 patients were discharged from the hospital in remission from SAP without development of complications. Continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter appears to be effective for prevention and treatment of IAH in patients with SAP through the removal of causative cytokines of hyperpermeability.

Usefulness of plasma exchange plus continuous hemodiafiltration to reduce adverse effects associated with plasma exchange in patients with acute liver failure.

ObjectiveTo efficiently remove middle-molecular-weight substances such as hepatic toxins and minimize adverse effects associated with plasma exchange implementation, we have performed plasma exchange slowly in combination with continuous hemodiafiltration. This study was designed to determine the usefulness of plasma exchange with continuous hemodiafiltration in reducing the adverse effects associated with implementation of plasma exchange alone. DesignA retrospective clinical study. SettingUniversity teaching hospital. PatientsThe study involved 90 patients with liver failure who had been treated with plasma exchange in our department over the past 12 yrs. We examined these patients by dividing them into two groups (48 patients treated with plasma exchange alone and 42 patients treated with plasma exchange plus continuous hemodiafiltration at the time of plasma exchange implementation). Measurements and Main Results Baseline blood Na+ concentration, HCO3− concentration, and colloid osmotic pressure were followed after implementation of plasma exchange to compare the frequency of development of three adverse effects (hypernatremia, metabolic alkalosis, and sharp decrease in colloid osmotic pressure) in the two groups. Hypernatremia was found in 26.7% of treatments in the group with plasma exchange alone and 3.3% in the group of plasma exchange plus continuous hemodiafiltration, and metabolic alkalosis was found in 30.6% of treatments in the group with plasma exchange alone and 4.9% in the group of plasma exchange plus continuous hemodiafiltration; both percentages were significantly higher in the group with plasma exchange alone (p < .001). A sharp decrease in colloid osmotic pressure occurred in 13.3% of treatments in the group with plasma exchange alone but was not observed at all in the patients treated with plasma exchange plus continuous hemodiafiltration. ConclusionsWe conclude that adverse effects associated with plasma exchange for artificial liver support for liver failure can be alleviated with use of plasma exchange plus continuous hemodiafiltration instead of plasma exchange alone.

Cytokine-related Genotypic Differences in Peak Interleukin-6 Blood Levels of Patients with Sirs and Septic Complications

BACKGROUND The aim of the present study was to investigate whether tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6-related genotypic differences affect IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS) in an intensive care unit (ICU). METHODS Seven polymorphisms of TNF, IL-1, and IL-6-related polymorphisms were studied with an allele-specific polymerase chain reaction. One hundred and thirteen patients diagnosed with SIRS whose sequential organ failure assessment scores were > or =5 at the time when their daily measured IL-6 blood level peaked during the ICU stay (IL-6 max) were examined. IL-6 max, survival, and septic complications were compared between carriers and non-carriers of less frequent alleles, indicated as allele*2, in each polymorphism. RESULTS In single nucleotide polymorphism (SNP) at position -238 site of TNF-alpha (TNF-alpha-238*G/A), IL-6-596*G/A, and IL-6-174*C/T, allele*2 frequencies were much lower in the Japanese than in the Caucasian population. IL-6 max was significantly higher in allele*2 carriers of IL-1beta-511*C/T. Associations were found between susceptibility to septic shock and allele*2 carriage for both IL-1beta-511*C/T and TNF-alpha-308*G/A, and also between poor prognosis and allele*2 carriage in both IL-1 receptor antagonist second intron various number of tandem repeats polymorphism (IL-1raRN*1-5) and TNF-alpha-308*G/A. IL-1beta-511*C/T and IL-1raRN*1-5 were in linkage disequilibrium in this study population. CONCLUSIONS Carriers of less frequent alleles in IL-1-related polymorphisms appear to have significant vulnerability to production of excessive IL-6 blood levels and to deterioration in septic shock.

Cellular injury score for multiple organ failure severity scoring system.

BACKGROUND Cellular Injury Score (CIS) is an index of cellular injury, being calculated from three parameters of intracellular metabolism: arterial ketone body ratio, osmolality gap, and blood lactate. METHODS The usefulness of CIS as a severity scoring system for patients with multiple organ failure was prospectively evaluated in 157 consecutive patients with MOF (58 survivors, 99 nonsurvivors). RESULTS CISs in nonsurvivors were significantly higher compared with those in survivors throughout the clinical courses. CIS was significantly correlated with the number of failing organs and mortality rate. The optimal cutoff point of CIS from receiver operating characteristics curve analysis was 4 for the maximal value during the clinical course. The changes in CIS well reflected the severity of injury in survivors and nonsurvivors who died within 2 weeks. CONCLUSION CIS could be a useful index for mortality risk prediction and is potentially applicable as a severity scoring system for individual patients with MOF.

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-Xshowed a significantly higher adsorption rate for TNF-α, interleukin (IL)-6 and IL-10 compared with other adsorbents (p < 0.05). Adsorbent in Lixelle® showed good affinity to TNF-α and IL-8. Especially, the adsorbent in CF-X almost completely removed TNF-α, 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.

Endotoxin adsorption or hemodiafiltration in the treatment of multiple organ failure

Recently, blood purification has come to be considered as a useful modality for the removal of humoral mediators of sepsis and septic multiple organ failure. An endotoxin-adsorbing column and continuous hemofiltration (CHF) or continuous hemodiafiltration (CHDF) are most frequently applied for this purpose. However, as for the endotoxin-adsorbing column, indications seem to be limited, since the number of patients in whom endotoxin plays an important role is relatively small. Furthermore, the endotoxin-adsorbing column itself should be improved to achieve better removing capacity. As for CHF and CHDF, their removal capacity for cytokine is dependent on the membrane material, because adsorption of cytokines to the membrane is an important mechanism of cytokine removal. Clearance of cytokine with CHF or CHDF also depends on the pretreatment blood level of cytokines. Therefore, CHF and CHDF can remove cytokines from circulation when proper membranes with adsorbing capacity are used and when prefiltration blood level of these cytokines is high. There has been no large-scale clinical trial reporting the efficacy of CHF or CHDF as a method for cytokine removal, however. A prospective randomized clinical trial is badly needed before these modalities can be widely used for the treatment of sepsis.

Continuous Hemodiafiltration with a Cytokine-Adsorbing Hemofilter in Patients with Septic Shock: A Preliminary Report

Background/Aim: We investigated the clinical efficacy of continuous hemodiafiltration (CHDF) with AN69ST hemofilter (AN69ST-CHDF) in patients with septic shock. Materials and Methods: A prospective, multicenter, single-arm study was conducted. Patients with sepsis and shock defined by hyperlactemia were enrolled. The patients were treated with CHDF and in accordance with the Surviving Sepsis Campaign guidelines (SSCG). Results: Thirty-four patients were enrolled. On ICU admission, the mean blood IL-6 level was 44,800 ± 77,700 pg/ml, and the mean blood lactate level was 69.0 ± 49.4 mg/dl. Both the mean blood IL-6 and lactate levels had significantly decreased to normal ranges after 72 h of AN69ST-CHDF. Though the mean APACHE II score was 32.7 ± 9.8, 28-day survival was 73.5%. Conclusion: The current study suggested that adding AN69ST-CHDF to the treatments outlined in the SSCG might lead to good outcomes for patients with septic shock, probably via the removal of cytokines from the bloodstream.

Continuous Hemodiafiltration with a Cytokine-Adsorbing Hemofilter for Sepsis

Since the introduction of the new pathophysiological concept of pathogen-associated molecular patterns (PAMPS) and alarmins, endotoxin has been recognized as only one of the PAMPS. It is widely accepted that hypercytokinemia plays a pivotal role in the pathophysiology of sepsis. Many kinds of blood purification modalities have been proposed as a therapeutic tool against sepsis, including high-volume continuous hemofiltration whose efficacy has recently been questioned. We report that continuous hemodiafiltration (CHDF) with a cytokine-adsorbing hemofilter (CAH), such as polymethyl methacrylate hemofilter and AN69ST hemofilter (CAH-CHDF), can remove many kinds of cytokines and has been very effective in the treatment of severe sepsis and septic shock. Based on the understanding of the recent pathophysiology, we suggest that CAH-CHDF is an alternate therapy to direct hemoperfusion with endotoxin-adsorbing column in the treatment of sepsis.

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.

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.