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

INTRODUCTION: Fever 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. METHODS: We 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. RESULTS: We 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 ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected]. CONCLUSIONS: In 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 REGISTRATION: ClinicalTrials.gov: NCT00940654.

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.

Applicability of care quality indicators for women with low-risk pregnancies planning hospital birth: a retrospective study of medical records.

Practices for planned birth among women with low-risk pregnancies vary by birth setting, medical professional, and organizational system. Appropriate monitoring is essential for quality improvement. Although sets of quality indicators have been developed, their applicability has not been tested. To improve the quality of childbirth care for low-risk mothers and infants in Japanese hospitals, we developed 35 quality indicators using existing clinical guidelines and quality indicators. We retrospectively analysed data for 347 women in Japan diagnosed with low-risk pregnancy in the second trimester, admitted between April 2015 and March 2016. We obtained scores for 35 quality indicators and evaluated their applicability, i.e., feasibility, improvement potential, and reliability (intra- and inter-rater reliability: kappa score, positive and negative agreement). The range of adherence to each indicator was 0-95.7%. We identified feasibility concerns for six indicators with over 25% missing data. Two indicators with over 90% adherence showed limited potential for improvement. Three indicators had poor kappa scores for intra-rater reliability, with positive/negative agreement scores 0.94/0.33, 0.33/0.95, and 0.00/0.97, respectively. Two indicators had poor kappa scores for inter-rater reliability, with positive/negative agreement scores 0.25/0.92 and 0.68/0.61, respectively. The findings indicated that these 35 care quality indicators for low-risk pregnant women may be applicable to real-world practice, with some caveats.

A case report of hepatorenal syndrome treated with plasma diafiltration (selective plasma filtration with dialysis).

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 of tetanus treated with Kampo medicines such as Kakkonto and Shakuyakukanzoto.

Case: 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. Outcome: After 30 days, the patient was discharged from the hospital without any sequelae. Conclusion: Kakkonto and shakuyakukanzoto may be useful for the control of muscle spasms resulting from generalized tetanus.

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

Aim: 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 ß-d-glucan and endotoxin to compare the quality of 5% HSA preparations from two different manufacturers. Methods: The quality of 5% HSA preparations in two different pharmaceutical products (groups A and B) was compared in terms of the percentage of reduced and oxidized albumin and the contaminant level of ß-d-glucan and endotoxin. Results: The percentage of human mercaptoalbumin in group A was significantly higher than that in group B (P < 0.01), whereas that of human non-mercaptoalbumin-2 in group A was significantly lower (P < 0.01). The concentration of ß-d-glucan in group A was significantly lower than in group B (P < 0.01). Conclusions: The present findings indicate the need for quality control of HSA preparations in applications involving the use of large volumes.

The dose of nafamostat mesilate during plasma exchange with continuous hemodiafiltration in the series-parallel circuit.

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.

Study of safe usage of high-flow three-way stopcocks in a blood circuit.

To examine the safety of using a high-flow three-way stopcock in a blood circuit during extracorporeal blood purification therapy, we studied the risk of development of hemolysis and clot formation in both ex vivo and in vivo extracorporeal circulation. In the ex vivo study, no significant difference was observed in the decrease in hematocrit (HCT) or increase in the potassium level between the three-way stopcock group and the control group. Nor was there a significant difference in the change in inlet pressure between the two groups. Thus, it was shown that the risk of hemolysis caused by the use of a high-flow three-way stopcock on both the outlet side and inlet side would be small. In the in vivo cases, there was no significant difference in the decrease in HCT or the increase in inlet pressure between the three-way stopcock group and control group, suggesting that it is clinically possible to incorporate a high-flow three-way stopcock into a blood 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.

Paralytic ileus induced by glyphosate intoxication successfully treated using Kampo medicine.

Case: A 65-year-old woman ingested glyphosate-surfactant herbicide in an attempt to commit suicide. She experienced glyphosate intoxication associated with multiple organ failure and developed a paralytic ileus. Daijokito, a traditional Japanese Kampo medicine was given to the patient to improve constipation and psychological symptoms. Next, rikkunshito was given to increase her gastric motility. Finally, daikenchuto was given to improve overall digestive peristalsis. Outcome: All abdominal symptoms ultimately improved after treatment with daikenchuto. Conclusion: Kampo medicines may help improve abdominal symptoms associated with glyphosate intoxication in cases where modern medical treatment alone proves inadequate.

Birth environment facilitation by midwives assisting in non-hospital births: a qualitative interview study.

OBJECTIVE: midwifery homes (similar to birth centres) are rich in midwifery wisdom and skills that differ from those in hospital obstetrical departments, and a certain percentage of pregnant women prefer birth in these settings. This study aimed to understand the organisation of the perinatal environment considered important by independent midwives in non-hospital settings and to clarify the processes involved. DESIGN: semi-structured qualitative interview study and constant comparative analysis. PARTICIPANTS: 14 independent midwives assisting at births in midwifery homes in Japan, and six independent midwives assisting at home births. SETTING: Osaka, Kyoto, Nara, and Shiga, Japan. FINDINGS: midwives assisting at non-hospital births organised the birth environment based on the following four categories: 'an environment where the mother and family are autonomous'; 'a physical environment that facilitates birth'; 'an environment that facilitates the movement of the mother for birth'; and 'scrupulous safety preparation'. These, along with their sub-categories, are presented in this paper. KEY CONCLUSIONS: independent midwives considered it important to create a candid relationship between the midwife and the woman/family from the period of pregnancy to facilitate birth in which the woman and her family were autonomous. They also organised a distinctive environment for non-hospital birth, with preparations to guarantee safety. Experiential knowledge and skills played a major part in creating an environment to facilitate birth, and the effectiveness of this needs to be investigated objectively in future research.

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.

Physical and psychologic effects of aromatherapy inhalation on pregnant women: a randomized controlled trial.

OBJECTIVES: Stress reduction care is important for pregnant women to decrease obstetric complications and children's health problems after birth. The aim of this study is to clarify the physical and psychologic effects of inhalation aromatherapy on pregnant women. Essential oils with high linalool and linalyl acetate content that may be used during pregnancy were selected and among these, and the one preferred by the participant was used. DESIGN: This was a prospective, randomized, controlled trial. SETTINGS/LOCATION: This trial was performed at a gynecology outpatient department in a hospital in Kyoto, Japan. PARTICIPANTS: The study included pregnant women in week 28 of a single pregnancy with a normal course. INTERVENTIONS: Participants were randomly assigned into an aromatherapy group and a control group. They were seated in the resting, seated position for 10 minutes. During the latter 5 minutes of each 10-minute session, aromatherapy inhalation was performed for the aromatherapy group. OUTCOME MEASURES: Before and after the intervention, the Profile of Mood States (POMS) was measured. During the trial, the heart-rate fluctuations were measured for the autonomic nervous system regulation. RESULTS: A total of 13 pregnant women participated in the trial. Seven (7) participants were assigned to the aromatherapy group and 6 participants to the control group. The results of the POMS were such that based on an intragroup comparison, significant differences were observed in the Tension-Anxiety score (p<0.05) and the Anger-Hostility score (p<0.05), and the respective improvements observed were due to aromatherapy. The results of the autonomic nervous system regulation were such that based on an intragroup comparison within the aromatherapy group, the parasympathetic nerve activity increased significantly (p<0.05). CONCLUSIONS: Aromatherapy inhalation using essential oils containing linalyl acetate and linalool was found to be effective for the POMS and parasympathetic nerve activity, based on an intragroup comparison. However, based on a comparison between the groups, no substantial difference was observed; hence, further study is necessary in the future.

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.

Serum aconitine concentrations after taking powdered processed Aconiti tuber.

Processed Bushi powder for ethical dispensing, called TJ-3022, is a herbal drug of processed Aconiti tuber (Aconitum carmichaeli Debeaux) and TJ-3023 is newly developed to contain a higher proportion of diester alkaloid of aconitine (Aconitum carmichaeli Debeaux and Aconitum japonicum Thunberg). Safety of TJ-3022 and TJ-3023 was evaluated by measuring the level of aconitum alkaloids in healthy adult volunteers. Forty subjects were assigned to one of two groups (each 20 subjects): TJ-3022 group or TJ-3023 group. The subjects received the powdered processed Aconiti tuber 3 g/day and the blood concentrations of aconitum alkaloids were measured at 90 min and 72 h after taking the study drug. The serum concentrations of aconitum alkaloids after 90 min and 72 h in the TJ-3023 group were higher than those in the TJ-3022 group. As for the chronological changes in the serum concentration, a significant decrease was observed in the TJ-3022 group, while no significant decrease was seen in the TJ-3023 group, which suggests that an analgesic effect in TJ-3023 was stronger than in TJ-3022. Aconitum alkaloids, which always have been believed to have the blood concentration below the measurement limit in human, were detected for the first time, although the detected amounts were minute. The results suggest that TJ-3023 shows sufficient analgesic effect with smaller dose than TJ-3022.

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

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 patient's 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.