Toshiko Igarashi

Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study

IntroductionFever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.MethodsWe designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality.ResultsWe recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU 36.5°C to 37.4°C), MAXICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).ConclusionsIn non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.Trial registrationClinicalTrials.gov: NCT00940654

A Case Report of Hepatorenal Syndrome Treated With Plasma Diafiltration (Selective Plasma Filtration with Dialysis)

Abstract:  Plasma diafiltration (PDF) (selective plasma filtration with dialysis) is blood purification therapy in which simple plasma exchange is performed using a membrane plasma separator (Evacure EC‐2A) while dialysate flows outside of the hollow‐fibers. A 74‐year old man with hepatorenal syndrome underwent four sessions of PDF and three sessions of HDF. Finally he recovered from hepatorenal syndrome. In this therapy, the levels of total bilirubin, interleukin‐18, creatinine, and cystatin C were significantly reduced. On the other hand, there were no significant differences in the total protein and albumin levels before and after PDF. PDF may be one of the most useful blood purification therapies for hepatorenal syndrome in terms of medical economics.

A case report of pediatric fulminant hepatitis treated with plasma diafiltration.

Abstract:  Plasma diafiltration (PDF) is blood purification therapy in which simple plasma exchange is performed with a membrane plasma separator while dialysate flows outside the hollow fibers. A 14‐year‐old boy with fulminant hepatitis underwent two sessions of PDF and one session of hemodiafiltration. We infused filtered replacement fluid for artificial kidneys at a dialysate flow rate of 600 mL/h and a replacement flow rate of 450 mL/h. We infused fresh frozen plasma (1200 mL) and 25% albumin solution (50 mL) intravenously over 8 h. Each PDF session lasted 8 h. The patients total bilirubin, interleukin‐18, and cystatin C levels decreased with treatment, and he recovered from hepatic failure. PDF may be an extremely useful blood purification therapy for pediatric fulminant hepatitis in terms of both medical economics and cytokine removal.

Selective Plasma Exchange With Dialysis in Patients With Acute Liver Failure

Selective plasma exchange with dialysis is a blood purification therapy in which simple plasma exchange is performed using a selective membrane plasma separator while the dialysate flows out of the hollow fibers. To evaluate the effect of plasma exchange with dialysis, biochemical examination of the blood, for example, the oxidative stress regulation system and interleukin 18 levels, was performed in patients with acute liver failure. We studied four patients with acute liver failure in whom the therapy was performed (nine times in total). The degree of hepatic encephalopathy and interleukin 18 levels decreased significantly after treatment. However, total protein levels did not change significantly. The level of reactive oxygen species and total antioxidant capacity did not change significantly. Plasma exchange with dialysis may be a useful blood purification therapy in cases of acute liver failure in terms of the removal of water‐soluble and albumin‐bound toxins.

The Dose of Nafamostat Mesilate During Plasma Exchange With Continuous Hemodiafiltration in the Series‐Parallel Circuit

Abstract:  We studied nafamostat mesilate (NM) and interleukin (IL)‐18 levels to determine whether the dose of NM is reduced during plasma exchange (PE) with continuous hemodiafiltration (CHDF) when the series‐parallel circuit is used. The subjects of the current study included four patients with acute hepatic failure who underwent PE with CHDF. The four patients underwent a total 15 PE + CHDF procedures, and for each procedure, they were randomized to receive either a half‐dose of NM or no NM in the CHDF circuit. Eight procedures were carried out with NM administration, and seven were carried out without NM administration. The dose of NM in the NM group was significantly higher than that in the non‐NM group (P = 0.040). No significant differences were observed between the two groups in the inlet NM concentration, the outlet NM concentration, or the rate of IL‐18 removal. No statistical correlation was observed between the IL‐18 level and the NM dose, the inlet NM concentration, or the outlet NM concentration. There was no blood access difficulty such as catheter failure or clotting of the filter. Thus, it might be possible to carry out PE and CHDF with the series‐parallel method without administration of NM in the CHDF circuit.

Selective Plasma Exchange for Critically Ill Patients Accompanied With Thrombocytopenia

Selective plasma exchange is a blood purification therapy in which simple plasma exchange is performed using a selective membrane plasma separator (pore size of 0.03 µm). Seven critically ill patients accompanied with thrombocytopenia were treated with selective plasma exchange using fresh frozen plasma. The total bilirubin levels and prothrombin time international normalized ratios decreased significantly after treatment. The total protein, albumin, and fibrinogen levels increased significantly after treatment. Selective plasma exchange may be a useful blood purification therapy for removing causal substances and retaining coagulation factors in patients accompanied with thrombocytopenia.

Removal of Toxic Substances by a Selective Membrane Plasma Separator

We devised a method of plasma exchange with dialysis (PED), in which selective plasma exchange (sPE) is performed using a selective membrane plasma separator (EC‐2A) with an albumin‐sieving coefficient of 0.3 while the dialysate flows outside the hollow fibers, and reported the usefulness of the system for treating acute liver failure. Thereafter, EC‐4A with an albumin‐sieving coefficient of 0.6 was developed, which was expected to be even more effective for removing protein‐bound substances. In order to examine whether or not EC‐4A might be applicable to blood purification therapy against drug poisoning, we compared the efficacies of sPE, PED, and direct hemoperfusion (DHP) using an activated carbon column for the removal of phenobarbital and lithium. Subjects undergoing the extracorporeal circulation study were assigned to the sPE group, PED group, or DHP group, and the changes in the blood concentrations of phenobarbital and lithium were measured over 180 min. A significant decrease of the phenobarbital concentration over time was seen in the PED group, as compared to that in the sPE group (P < 0.0001), while no significant difference in the concentration was observed between the PED and DHP groups. The PED group showed a significant decrease of the lithium concentration over time, as compared to the DHP group (P < 0.0001), while no significant difference in the concentration was observed between the PED and sPE groups. Thus, PED was as effective as DHP for removing phenobarbital and was as effective as sPE for removing lithium. These results suggest that PED therapy using EC‐4A may be a feasible modality for the treatment of drug poisoning.

Catheter‐related Infections via Temporary Vascular Access Catheters: A Randomized Prospective Study

Temporary vascular access catheters (VACs) are important devices used in acute blood purification therapies. The aim of this study was to determine whether a catheterization duration of 2 weeks increased the risk of nosocomial complications when compared with a 1-week duration. Fifty-six patients with 90 double lumen VACs were randomly chosen, and received either 1- or 2-week catheterizations from operators experienced in the placement of such catheters at three sites such as the internal jugular, subclavian, or femoral vein. The characteristics of the VACs, including the sites, procedures, and lengths, were similar in both groups. No significant difference in the rate of catheter colonization was observed between the groups (14.6% vs 26.2%, P = 0.1371). No significant difference in the rate of catheter-related bloodstream infections was observed between the groups (2.1% vs 4.8%, P = 0.5967). Two-week indwelling did not increase the risk of infection compared with 1-week indwelling at any of the sites in critically ill patients.

Comparison of quality of human serum albumin preparations in two pharmaceutical products

Human serum albumin (HSA) is known for its multiple functions, such as maintenance of colloid osmotic pressure, transport of endogenous and exogenous substances, and antioxidation. The aim of this study was to measure the redox state and concentrations of β‐d‐glucan and endotoxin to compare the quality of 5% HSA preparations from two different manufacturers.

A case of tetanus treated with Kampo medicines such as Kakkonto and Shakuyakukanzoto

A 74‐year‐old man developed tetanus 3 days after working with cow and poultry manure. Kakkonto and shakuyakukanzoto, traditional Japanese herbal medicines that are effective for the relief of pain primarily related to muscle contraction, were given to control the trismus and painful contracture of the neck. Generalized convulsions were controlled without the use of muscle relaxants.