Usefulness of intraoperative transesophageal echocardiography for hemodynamic management of liver transplantation in a patient with massive polycystic liver disease: a case report.

BACKGROUND: Hemodynamic management during anesthesia in liver transplantation for patients with polycystic liver disease (PLD) can be more challenging because of the bleeding and hemodynamic alterations due to the markedly enlarged liver. We hereby report a case of PLD wherein transesophageal echocardiography (TEE) was employed for optimal hemodynamic monitoring during liver transplantation. CASE PRESENTATION: A 61-year-old man was scheduled to undergo liver transplantation for massive PLD. Hemodynamic instability was associated with mechanical displacement of the giant cystic liver. TEE results revealed the collapse of the inferior vena cava due to liver displacement. TEE also detected intrathoracic hemorrhage triggered by detachment from the markedly enlarged liver. CONCLUSION: TEE is a valuable monitoring tool for sharing information with surgeons and diagnostic modality for finding the source of bleeding in liver transplantation for PLD and may contribute majorly to the quality of perioperative management.

Promotion of a venous thromboembolism prevention protocol at a perioperative management center.

Objectives: Perioperative venous thromboembolism (VTE) is a potentially fatal complication, making preoperative VTE diagnosis and secondary thromboprophylaxis important. This study was performed to investigate the impact of promotion of a preoperative VTE protocol at a perioperative management center (PMC) on detecting the preoperative VTE rate and subsequent treatment. Methods: This retrospective study involved patients aged ≥20 years who underwent elective anesthesia. The patients were divided into two groups: the pre-PMC group (January to October 2014, before the opening of the PMC) and the post-PMC group (January to December 2019, after the opening of the PMC). The rates of preoperative lower-limb compression ultrasonography (CUS), VTE detection, anticoagulation therapy, and new postoperative pulmonary embolism (PE) were compared between the two groups. Results: The pre-PMC and post-PMC groups comprised 3737 and 5388 patients, respectively. The preoperative CUS and VTE detection rates were significantly higher in the post-PMC than pre-PMC group (7.2% and 1.43% vs. 25.6% and 3.93%, respectively; P<0.001). There was no significant difference in the rate of anticoagulation therapy in patients with preoperative VTE (88.9% vs. 84.7%, P=0.43). Heparin and direct oral anticoagulants were primarily used in the pre-PMC and post-PMC groups, respectively. The efficacy and safety were comparable between the two groups. No new postoperative PE was detected in either group. Conclusions: Promotion of the preoperative VTE protocol led by the PMC increased the rates of preoperative CUS and preoperative VTE detection. This may aid in secondary thromboprophylaxis in the preoperative period and prevention of postoperative PE.

Abnormal stenosis of a drainage cannula due to excessive negative pressure during venovenous extracorporeal membrane oxygenation management: a case report.

We report a case in which excessive negative pressure may have been applied to the proximal side hole of a drainage cannula during venovenous extracorporeal membrane oxygenation (V-V ECMO), resulting in abnormal stenosis of the drainage cannula. V-V ECMO was introduced in a 71-year-old male patient who was transferred from another hospital for severe respiratory failure associated with varicella pneumonia and acute respiratory distress syndrome. Drainage was performed using a PCKC-V™ 24Fr (MERA, Japan) cannula via the right femoral vein with the tip of the cannula near the level of the diaphragm under fluoroscopy. Reinfusion was performed via the right internal jugular vein. Due to poor systemic oxygenation, the drainage cannula was withdrawn caudally and refixed to reduce the effect of recirculation. Two days later, drainage pressure dropped rapidly, and frequent ECMO flow interruption occurred due to poor drainage. An abdominal X-ray revealed abnormal stenosis of the proximal side hole site of the drainage cannula. We diagnosed that the drainage cannula was damaged, and it was replaced with another, namely a Medtronic Bio-Medicus™ 25 Fr (GETINGE, Sweden) cannula. However, the removed drainage cannula was not damaged, suggesting that the cannula was temporarily stenosed by momentary excessive negative pressure. In a multi-stage drainage cannula, the main drainage site is the proximal side hole, with little negative pressure applied at the apical foramen in a mock experimental ex vivo drainage test in a water tank. Hence, improvement of a multi-stage drainage cannula is recommended, such as adequate reinforcement of the side hole site with a wire.

Association of circulating histone H3 and high mobility group box 1 levels with postoperative prognostic indicators in intensive care unit patients: a single-center observational study.

Objectives: Damage associated molecular patterns (DAMPs) levels are associated with sepsis severity and prognosis. Histone and high mobility group box 1 (HMGB1) levels are also potential indicators of prognosis. We investigated the relationship between serum histone H3 and HMGB1 levels and the illness severity score and prognosis in postoperative patients. Methods: Postoperative serum histone H3 and HMGB1 levels in 39 intensive care unit (ICU) patients treated at our institution were measured. The correlation between peak histone H3 and HMGB1 levels in each patient and clinical data (age, sex, surgical time, length of ICU stay, and survival after ICU discharge), which also included the patients' illness severity score, was examined. Results: Histone H3 but not HMGB1 levels were positively correlated with surgical time, the Sequential Organ Failure Assessment score, the Japanese Association for Acute Medicine acute phase disseminated intravascular coagulation diagnosis score, and the length of ICU stay. Both histone H3 and HMGB1 levels were negatively correlated with age. However, survival post-ICU discharge was not correlated with histone H3 or HMGB1 levels. Conclusions: Histone H3 levels are correlated with severity scores and the length of ICU stay. Serum histone H3 and HMGB1 levels are elevated postoperatively. These DAMPs, however, are not prognostic indicators in postoperative ICU patients.

Investigation of factors affecting COVID-19 pancreatic injury: a single-center, retrospective study.

Pancreatic injury is considered an organ-related complication in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether COVID-19 status affects pancreatic injury. This retrospective study aimed to determine whether COVID-19 affects the occurrence of pancreatic injuries. Consecutive patients diagnosed with sepsis admitted to the ICU between March 2020 and September 2021 were included. The primary endpoint was a pancreatic injury, which was defined as amylase or lipase levels > 3 times the upper limit of the normal range. Among the 177 patients included in the analysis, 40 (23%) were COVID-19 patients, and 54 (31%) had pancreatic injuries. Of these three patients, acute pancreatitis was diagnosed based on computed tomography. The pancreatic injury was significantly more common among COVID-19 patients (75 vs. 18%, p < 0.001). Multivariate analysis showed that COVID-19 and steroid use were independent risk factors for pancreatic injury (Odds Ratio (OR) 4.79 [95% confidence interval (CI) 1.48-15.5], p = 0.009; OR 4.02 [95% CI 1.42-11.4], p = 0.009). This study revealed that the proportion of pancreatic injury in septic patients with COVID-19 was significantly higher than in those without COVID-19. It may be difficult to diagnose pancreatitis based on amylase and lipase levels in COVID-19 patients.

A Larger Membrane Area Increases Cytokine Removal in Polymethyl Methacrylate Hemofilters.

Blood purification is performed to control cytokines in critically ill patients. The relationship between the clearance (CL) and the membrane area during adsorption is not clear. We hypothesized that the CL increases with the hydrophobic area when hydrophobic binding contributes to cytokine adsorption. We investigated the relationship between the hemofilter membrane area and the CL of the high mobility group box 1 protein (HMGB-1) and interleukin-6 (IL-6). We performed experimental hemofiltration in vitro using polymethyl methacrylate membranes CH-1.8W (1.8 m2) and CH-1.0N (1.0 m2), as well as polysulfone membrane NV-18X (1.8 m2). After adding 100 mg of HMGB1 or 10 µg of IL-6 into the test solution, experimental hemofiltration was conducted for 360 min in a closed-loop circulation system, and the same amount of HMGB1 and IL-6 was added after 180 min. With CH-1.8W and CH-1.0N, both HMGB-1 and IL-6 showed a rapid concentration decrease of more than 70% at 180 min and 360 min after the re-addition. At 15 min, the CL of HMGB-1 was CH-1.8W: 28.4 and CH-1.0N: 19.8, and that of IL-6 was CH-1.8W: 41.1 and CH-1.0N: 25.4. CH-1.8W and CH-1.0N removed HMGB1 and IL-6 by adsorption and CH-1.8W was superior in CL, which increased with a greater membrane area.

Perturbation of monoamine metabolism and enhanced fear responses in mice defective in the regeneration of tetrahydrobiopterin.

Increasing evidence suggests the involvement of peripheral amino acid metabolism in the pathophysiology of neuropsychiatric disorders, whereas the molecular mechanisms are largely unknown. Tetrahydrobiopterin (BH4) is a cofactor for enzymes that catalyze phenylalanine metabolism, monoamine synthesis, nitric oxide production, and lipid metabolism. BH4 is synthesized from guanosine triphosphate and regenerated by quinonoid dihydropteridine reductase (QDPR), which catalyzes the reduction of quinonoid dihydrobiopterin. We analyzed Qdpr-/- mice to elucidate the physiological significance of the regeneration of BH4. We found that the Qdpr-/- mice exhibited mild hyperphenylalaninemia and monoamine deficiency in the brain, despite the presence of substantial amounts of BH4 in the liver and brain. Hyperphenylalaninemia was ameliorated by exogenously administered BH4, and dietary phenylalanine restriction was effective for restoring the decreased monoamine contents in the brain of the Qdpr-/- mice, suggesting that monoamine deficiency was caused by the secondary effect of hyperphenylalaninemia. Immunohistochemical analysis showed that QDPR was primarily distributed in oligodendrocytes but hardly detectable in monoaminergic neurons in the brain. Finally, we performed a behavioral assessment using a test battery. The Qdpr-/- mice exhibited enhanced fear responses after electrical foot shock. Taken together, our data suggest that the perturbation of BH4 metabolism should affect brain monoamine levels through alterations in peripheral amino acid metabolism, and might contribute to the development of anxiety-related psychiatric disorders. Cover Image for this issue: https://doi.org/10.1111/jnc.15398.

Hyperchloremia and Postoperative Acute Kidney Injury in Adult Cardiac Patients: A Propensity-Matched Cohort Study.

OBJECTIVES: Hyperchloremia is a potential risk factor for acute kidney injury (AKI) in critically ill patients. However, the relationship between hyperchloremia and postoperative AKI in adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB) remains unclear. The authors aimed to determine whether postoperative hyperchloremia was associated with postoperative AKI in these populations. OBJECTIVES: Retrospective, single-center study. SETTING: Tertiary care hospital. PARTICIPANTS: Adult patients who underwent cardiovascular surgery with CPB. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with and without postoperative hyperchloremia were matched (1:1). The primary outcome was the rate of postoperative AKI diagnosed using the Kidney Disease: Improving Global Outcomes consensus criteria. Postoperative hyperchloremia was defined as postoperative serum chloride levels of >110 mmol/L during the first 48 hours. An increase in serum chloride levels (Δ[Cl-]) was defined as the difference between the preoperative and maximum postoperative serum chloride levels during the first 48 hours ([Cl-]max). Propensity-score matching and univariate and multivariate logistic regression analyses were employed. A total of 323 patients were included. Propensity-score matching selected 55 pairs for the final comparison. The incidence of postoperative AKI did not differ between the two groups (47% v 46%, p = 1.0). In the multivariate logistic regression analysis, Δ[Cl-] was associated independently with the development of postoperative AKI (odds ratio, 1.13; 95% confidence interval, 1.06-1.21; p < 0.001). CONCLUSIONS: Exposure to postoperative hyperchloremia was not associated with postoperative AKI in adult patients undergoing cardiovascular surgery with CPB. However, an increase in the serum chloride level might be associated with postoperative AKI.

Current status of antimicrobial prophylaxis during extracorporeal membrane oxygenation in Japan: a national survey.

Infection during extracorporeal membrane oxygenation (ECMO) is a common complication that leads to increased mortality. Thus, antimicrobial prophylaxis during ECMO is often performed to prevent of nosocomial infections. However, the current status of antimicrobial prophylaxis during ECMO in Japan is unclear. Therefore, we conducted a national survey of members of the Japanese Society of Intensive Care Medicine (JSICM) to clarify the current status of antimicrobial prophylaxis during ECMO in intensive care units. An 11-question survey was devised to assess antimicrobial prophylaxis and surveillance practices during ECMO. A total of 253 hospitals responded. Of these, 235 hospitals were the JSICM-certified hospitals, and the response rate was 64%. A total of 96 hospitals (39%) administered antimicrobial prophylaxis during ECMO, and 17% of hospitals had a standardized protocol for antimicrobial prophylaxis during ECMO. Of these 96 hospitals, 79% used single agents. First-generation cephalosporins were the most commonly used (54%), followed by penicillins or penicillin-derived combinations (24%), second-generation cephalosporins (7%), and anti-methicillin-resistant Staphylococcus aureus agents (6%). In conclusion, our survey revealed 39% of hospitals administered antimicrobial prophylaxis during ECMO in Japan. First-generation cephalosporins were the agents most commonly used.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Japanese rapid/living recommendations on drug management for COVID-19.

The coronavirus disease (COVID-19) has spread worldwide since early 2020, and there are still no signs of resolution. The Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock (J-SSCG) 2020 Special Committee created the Japanese rapid/living recommendations on drug management for COVID-19 using the experience of creating the J-SSCGs. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to determine the certainty of the evidence and strength of the recommendations. The first edition of this guideline was released on 9 September, 2020, and this document is the revised edition (version 3.1) (released 30 March, 2021). Clinical questions (CQs) were set for the following seven drugs: favipiravir (CQ1), remdesivir (CQ2), hydroxychloroquine (CQ3), corticosteroids (CQ4), tocilizumab (CQ5), ciclesonide (CQ6), and anticoagulants (CQ7). Favipiravir is recommended for patients with mild COVID-19 not requiring supplemental oxygen (GRADE 2C); remdesivir for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Hydroxychloroquine is not recommended for all COVID-19 patients (GRADE 1B). Corticosteroids are recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 1B) and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 1A); however, their use is not recommended for mild COVID-19 patients not requiring supplemental oxygen (GRADE 1B). Tocilizumab is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization (GRADE 2B). Anticoagulant therapy is recommended for moderate COVID-19 patients requiring supplemental oxygen/hospitalization and severe COVID-19 patients requiring ventilator management/intensive care (GRADE 2C). We hope that these clinical practice guidelines will aid medical professionals involved in the care of COVID-19 patients.

Comparison of myoglobin clearance in three types of blood purification modalities.

Myoglobin, which can cause acute kidney injury, has a relatively high molecular weight and is poorly cleared by diffusion. We compared and examined myoglobin clearance by changing the blood purification membrane and modality in patients with a myoglobin blood concentration ≥ 1000 ng/ml. We retrospectively analyzed three patient groups based on the following three types of continuous hemofiltration (CHF): AN69ST membrane, polymethylmethacrylate (PMMA) membrane, and high-flow hemodiafiltration (HDF) with increased dialysate flow rate using the PMMA membrane. There was no significant difference in clearance in CHF between AN69ST and PMMA membranes. However, the high-flow HDF group showed the highest myoglobin clearance (p = 0.003). In the PMMA membrane, changing the treatment modality to high-flow HDF increased clearance above the theoretical value, possibly due to internal filtration. To remove myoglobin by kidney replacement therapy from patients with hypermyoglobinemia, a modality such as high-flow HDF would be desirable.

Adsorption kinetics of high mobility group box 1 protein in a polyacrylonitrile hemofiltration membrane.

The high mobility group box 1 protein (HMGB1) is recognized as a prototypical endogenous danger cytokine in sepsis. We previously reported that a polyacrylonitrile (AN69ST) membrane rapidly adsorbed HMGB1. Herein, an in vitro hemofiltration system was designed to assess the HMGB1 adsorption capacity, adsorption sites, and adsorption mechanism of the AN69ST membrane. HMGB1 was repeatedly added seven times during hemofiltration. A rapid decrease in circulating HMGB1 was observed after every addition with no sign of saturation. Presence of HMGB1 on the filter membrane was observed on both membrane surfaces and within the bulk layer using a high concentration of HMGB1 by immunoelectron microscopy. We hypothesized that the addition of heparin to the membrane surface or filtration rate would contribute to the adsorption mechanism. We could not measure the influence of heparin and filtration. Although the membrane was too large to saturate under the µg/mL HMGB1 conditions, our results show that the AN69ST membrane has a robust absorption capacity that could be used to treat sepsis.

A case of spontaneous rectus sheath hematoma induced by lateral semi-prone positional changes during extracorporeal membrane oxygenation.

Spontaneous abdominal wall hematomas are relatively rare and mainly attributed to anticoagulation and severe cough. Despite the high incidence of anticoagulation-related bleeding complications, there are no reports of spontaneous abdominal wall hematomas during extracorporeal membrane oxygenation (ECMO). We report a case of a spontaneous rectus sheath hematoma caused by alternation of the lateral semi-prone position during ECMO in a 76-year-old female patient with severe acute respiratory distress syndrome. Unfractionated heparin 12,000-14,000 units/day was administered for anticoagulation during ECMO. From Day 6 of ECMO, the patient who was under deep sedation was alternately placed in the left and right lateral semi-prone positions every 4 h, for approximately 20 h per day. On Day 12 of ECMO, the patient developed hypotension with anemia and a palpable mass in the right lower abdomen. Abdominal ultrasonographic imaging revealed a huge echo-free space centered in the right lower abdomen. Emergency contrast-enhanced computed tomography (CT) scanning showed extravasation from the superior and inferior epigastric arteries as well as a rectus sheath hematoma. Despite no apparent contrast leakage, an inferior epigastric artery embolization was undertaken because the patient was on ECMO. On Day 13 after ECMO initiation, ECMO and anticoagulation were discontinued. On CT scanning a week later, the hematoma had reduced. In conclusion, spontaneous abdominal wall hematoma is a rare and important complication that might occur during ECMO. Thus, careful physical examination should be routinely conducted when the patient is semi-prone during ECMO.

Impact of Blood Type O on Mortality of Sepsis Patients: A Multicenter Retrospective Observational Study.

ABO blood groups have been implicated as potential risk factors for various diseases. However, no study has investigated the association between sepsis mortality and ABO blood types. We aimed to evaluate the impact of these blood types on mortality in patients with sepsis and septic shock. This retrospective observational study was conducted at two general hospitals in Japan. Patients diagnosed with sepsis or septic shock were included and divided into four groups based on blood type (O, A, B, and AB). The association between type O vs. other types and 28- and 90-day mortalities was evaluated using multivariate logistic regression analysis adjusted for age, sex, and Sequential (Sepsis-related) Organ Failure Assessment score. This study included 415 patients, of whom 131 (31.6%), 171 (41.2%), 81 (19.5%), and 32 (7.7%) had type O, A, B, and AB, respectively. Blood type O was not associated with 28-day (odds ratio: 1.7 p = 0.08) or 90-day mortality (odds ratio: 1.53, p = 0.091). However, type O was significantly associated with higher 90-day mortality (odds ratio: 3.26, p = 0.009) in patients with septic shock. The role of ABO blood type in risk stratification for septic shock and the mechanisms that potentially affect the prognosis of sepsis patients need further investigation.

Nafamostat mesilate inhibits linezolid metabolism via its antioxidant effects.

Patients who undergo renal replacement therapy often exhibit a high plasma linezolid concentration. Linezolid is metabolized via oxidation. Nafamostat mesilate has antioxidant effects and is frequently used as an anticoagulant during renal replacement therapy. We aimed to investigate the effect of nafamostat mesilate on plasma linezolid concentration. We examined whether the co-administration of linezolid and nafamostat had any effect on plasma linezolid concentration. Mice were randomly allocated to two groups (n = 18/group): linezolid (100 mg kg-1 , subcutaneous injection) + nafamostat (30 mg kg-1 , intraperitoneal injection) and linezolid + saline. At 5 hours, the linezolid concentration was significantly higher in the linezolid + nafamostat co-administration group than that in the linezolid + saline group (20.6 ± 9.8 vs 3.6 ± 1.2 µg/mL, respectively P < .001). The antioxidant effects of nafamostat may inhibit linezolid metabolism, resulting in the adverse event of high linezolid concentration if both are administered concurrently during renal replacement therapy.

Lower blood return temperature than core temperature as a causal factor of decreased cardiac output assessed by transpulmonary thermodilution during blood purification.

We aimed to evaluate whether cardiac output assessed by transpulmonary thermodilution during blood purification is affected by the difference between the blood return temperature and core temperature. We applied different blood return temperatures using a thermostat bath during blood purification in four pigs. After the blood return temperature stabilized and blood purification process stopped, the cardiac output assessed by transpulmonary thermodilution was measured. The thermostat bath was set at 35°C, 40°C, 45°C, and 50°C, with the order changed at random; four measurements were made at each temperature. Cardiac function was evaluated by echocardiography when ice-cold saline was administered in a pig. A decrease in the blood return temperature resulted in decreased cardiac output assessed by transpulmonary thermodilution, whereas an increase resulted in increased cardiac output assessed by transpulmonary thermodilution. Echocardiography revealed that the change in the blood return temperature did not affect the left ventricular ejection fraction.

In vitro Evaluation of Linezolid and Doripenem Clearance with Different Hemofilters.

INTRODUCTION: Renal replacement therapy (RRT) is widely used in the treatment of septic acute kidney injury. However, little is known about how the adsorption properties of hemofilters used in RRT affect antibiotic concentration. Because a cytokine-adsorption membrane is frequently used in RRT, it is important to determine the antibiotic adsorption capacity of this membrane. OBJECTIVE: The present study aimed to investigate the antibiotic adsorption capacity of different hemofilter membranes by in vitro experiments using 2 antibacterial agents (linezolid and doripenem). METHODS: We performed experimental hemofiltration in vitro using polyacrylonitrile (AN69ST), polymethylmethacrylate (PMMA), and polysulfone (PS) hemofilters for 1,440 min. The test solution was a 1,000-mL substitution fluid containing 30 µg/mL linezolid and 120 µg/mL doripenem. We measured drug concentrations at the inlet, outlet, and filtrate ports of the hemofilters for 1,440 min and calculated the sieving coefficient (SC) and adsorption rate (Ra) of the drugs onto the hemofilters. RESULTS: The amount of linezolid adsorbed onto AN69ST, PMMA, and PS membranes was decreased relative to that in the control group at 15 min (p < 0.05). However, no SC for linezolid was obtained thereafter. The Ra of linezolid onto AN69ST, PMMA, and PS membranes was higher than that in the control group (p < 0.05). In contrast, no significant differences were observed in the concentrations and Ra values of doripenem adsorbed onto AN69ST, PMMA, and PS membranes compared with those in the control group. CONCLUSIONS: Doripenem was not adsorbed onto PMMA, PS, and AN69ST membranes. Linezolid was adsorbed onto PMMA, PS, and AN69ST membranes, but only temporarily, and this did not affect drug bioavailability.

Suppressive effects of the neutrophil elastase inhibitor sivelestat sodium hydrate on interleukin-1ß production in lipopolysaccharide-stimulated porcine whole blood.

OBJECTIVE: Sivelestat sodium hydrate (Siv) is expected to be an effective therapy for acute respiratory distress syndrome, although its mechanism of action is not understood. In this study, we investigated which myeloid cells-derived cytokines were suppressed by Siv. METHODS: Continuous hemofiltration was performed by circulating fresh porcine blood through a semi-closed circuit. To ensure that leukocytes survived for 360 min, 5% glucose, heparin, and air were continuously injected. The control group received continuous administration of lipopolysaccharide (LPS) only, whereas the Siv group received LPS and Siv. Complete blood count, levels of various cytokines, and other variables were compared between the groups. RESULTS: Interleukin (IL)-1ß level was significantly suppressed in the Siv group compared with that in the control group (p<0.05). CONCLUSIONS: The results suggested that Siv suppressed the production of IL-1ß and possibly other cytokines by myeloid cells. Whether this suppression of cytokine production is caused directly by Siv or mediated via suppression of granulocyte elastase should be evaluated in the future.