Mechanical Insufflation-exsufflation for the Prevention of Ventilator-associated Pneumonia in Intensive Care Units: A Retrospective Cohort Study.

AIM: Ventilator-associated pneumonia (VAP) is the most common intensive care unit (ICU)-acquired infection. The current study aimed to assess the efficacy of mechanical insufflation-exsufflation (MI-E) in preventing VAP in critically ill patients. MATERIALS AND METHODS: This retrospective cohort study was conducted at the ICU of Chiba University Hospital between January 2014 and September 2017. The inclusion criteria were patients who required invasive mechanical ventilation ≥48 hours and those who underwent rehabilitation, including chest physical therapy (CPT). In 2015, the study institution started the use of MI-E in patients with impaired cough reflex. From January to December 2014, patients undergoing CPT were classified under the historical control group, and those who received treatment using MI-E from January 2015 to September 2017 were included in the intervention group. The patients received treatment using MI-E via the endotracheal or tracheostomy tube, with insufflation-exsufflation pressure of 15-40 cm H2O. The treatment frequency was one to three sessions daily, and a physical therapist who is experienced in using MI-E facilitated the treatment. RESULTS: From January 2015 to September 2017, 11 patients received treatment using MI-E. Of the 169 patients screened in 2014, 19 underwent CPT. The incidence of VAP was significantly different between the CPT and MI-E groups (84.2% [16/19] vs 26.4% [3/11], p = 0.011). After adjusting for covariates, a multivariate logistic regression analysis was performed, and results showed that the covariates were not associated with the incidence of VAP. CONCLUSION: This retrospective cohort study suggests that the use of MI-E in critically ill patients is independently associated with a reduced incidence of VAP. CLINICAL SIGNIFICANCE: Assessing the efficacy of MI-E to prevent VAP. HOW TO CITE THIS ARTICLE: Kuroiwa R, Tateishi Y, Oshima T, Inagaki T, Furukawa S, Takemura R, et al. Mechanical Insufflation-exsufflation for the Prevention of Ventilator-associated Pneumonia in Intensive Care Units: A Retrospective Cohort Study. Indian J Crit Care Med 2021;25(1):62-66.

Association between serum levels of interleukin-6 on ICU admission and subsequent outcomes in critically ill patients with acute kidney injury.

BACKGROUND: Exacerbated inflammatory response is considered one of the key elements of acute kidney injury (AKI). Interleukin-6 (IL-6) is an inflammatory cytokine that plays important roles in the inflammatory response and may be useful for predicting the clinical outcomes in patients with AKI. However, supporting evidence adapted to the current KDIGO criteria is lacking. METHODS: AKI patients admitted to the ICU between Jan 2011 and Dec 2015 were retrospectively screened. Patients were assigned to three groups by admission IL-6 tertiles. Associations between IL-6 on ICU admission and in-hospital 90-day mortality, short-term/long-term renal function were analyzed. RESULTS: Patients (n = 646) were divided into low (1.5-150.2 pg/mL), middle (152.0-1168 pg/mL), and high (1189-2,346,310 pg/mL) IL-6 on ICU admission groups. Patients in the high IL-6 group had higher in-hospital 90-day mortality (low vs. middle vs. high, P = 0.0050), lower urine output (low vs. middle vs. high, P < 0.0001), and an increased probability of persistent of anuria for ≥12 h (low vs. middle vs. high, P < 0.0001) within 72 h after ICU admission. In contrast, the high IL-6 group had a lower incidence of persistent AKI at 90 days after the ICU admission in survivors (low vs. middle vs. high, P = 0.013). CONCLUSIONS: Serum levels of IL-6 on ICU admission may predict short-term renal function and mortality in AKI patients and were associated with renal recovery in survivors.

Veno-arterial extracorporeal membrane oxygenation for Streptococcus pyogenes toxic shock syndrome in pregnancy.

Streptococcal toxic shock syndrome (STSS), an invasive Streptococcus pyogenes (Group A streptococcus) infection with hypotension and multiple organ failure, is quite rare in pregnancy but is characterized by rapid disease progression and high fatality rates. We present a case of STSS with infection-induced cardiac dysfunction in a pregnant woman who was treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO). A 24-year-old multiparous woman in the third trimester had early symptoms of high fever and diarrhea 1 day prior to admission to the hospital emergency department. On admission, she had multiple organ failure including circulatory failure. Due to fetal distress, emergency Cesarean section was carried out and transferred to intensive care units. She had refractory circulatory failure with depressed myocardial contractility with progressive multiple organ failure, despite receiving significant hemodynamic supports including high-dose catecholamine. Thus, VA-ECMO was initiated 18 h after intensive care unit admission. Consequently, ECMO provided extra time to recover from infection and myocardial depression. She was successfully weaned from VA-ECMO on day 7 and was discharged home on day 53. VA-ECMO can be a therapeutic option for refractory circulatory failure with significant myocardial depression in STSS.

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.

Cardiovascular autonomic dysfunction induced by mechanical insufflation-exsufflation in Guillain-Barré syndrome.

Mechanical insufflation-exsufflation (MI-E) is an effective airway clearance device for impaired cough associated with respiratory muscle weakness caused by neuromuscular disease. Its complications on the respiratory system, such as pneumothorax, are well-recognized, but the association of the autonomic nervous system dysfunction with MI-E has never been reported. We herein describe two cases of Guillain-Barré syndrome with cardiovascular autonomic dysfunction during MI-E: a 22-year-old man who developed transient asystole and an 83-year-old man who presented with prominent fluctuation of blood pressure. These episodes occurred during the use of MI-E with abnormal cardiac autonomic testing, such as heart rate variability in both patients. While Guillain-Barré syndrome itself may cause cardiac autonomic dysfunction, MI-E possibly caused or enhanced the autonomic dysfunction by an alternation of thoracic cavity pressure. The possibility of MI-E-related cardiovascular complications should be recognized, and its appropriate monitoring and management are necessary, particularly when used for Guillain-Barré syndrome patients.

Effects of a peripheral cholinesterase inhibitor on cytokine production and autonomic nervous activity in a rat model of sepsis.

PURPOSE: Recently, cholinergic anti-inflammatory pathway manipulation has been proposed as a new strategy to control cytokine production in sepsis. We investigated whether hypercytokinemia can be controlled via this pathway in an animal model of sepsis, with concomitant monitoring of autonomic nervous activity involving heart rate variability (HRV) analysis of electrocardiographic R-R intervals. METHODS: Sixty-eight adult male Sprague-Dawley rats were used (28 for examination of cytokine production and autonomic nervous activity; 40 for survival analysis). Each part of the study involved four animal groups, including two control groups without drug administration. Sepsis was induced by cecal ligation and puncture (CLP). Distigmine bromide, a peripheral, non-selective cholinesterase inhibitor (0.01mg/kg), was administered subcutaneously 90 min after surgery. Continuous electrocardiograms were recorded for 5 min before and after surgery (at intervals of 5h) in CLP and sham-operated animals for HRV analysis. Blood samples were collected 20 h after surgery for serum cytokine and catecholamine assay. RESULTS: On HRV analysis, distigmine inhibited reduction of total power and high-frequency components in CLP animals (P<0.05). Distigmine significantly inhibited cytokine induction (IL-6 and IL-10) (P<0.01) as well as increase in serum levels of noradrenaline and dopamine (P<0.05). Distigmine did not significantly improve CLP animal survival rate. CONCLUSIONS: The cholinesterase inhibitor distigmine inhibited induction of inflammatory cytokines and catecholamines as well as HRV suppression in a rat CLP model, suggesting that an agent modulating the cholinergic anti-inflammatory pathway can control excess cytokine production involved in the pathogenesis of severe sepsis/septic shock.

Duration of well-controlled core temperature correlates with neurological outcome in patients with post-cardiac arrest syndrome.

PURPOSE: Detailed procedures for optimal therapeutic hypothermia (TH) have yet to be established. We examined how duration of well-controlled core temperature within the first 24 hours after cardiac arrests (CA) correlated with neurological outcomes of successfully resuscitated out-of-hospital CA (OHCA) patients. METHODS: OHCA patients who survived over 24 hours and treated with TH were included. Core temperature was measured every hour. Physicians intended to maintain temperature at 33 °C ± 1 °C for 24 hours. Cerebral performance categories (CPC) of patients at 6 months were recorded and patients were retrospectively divided into favorable (CPC1,2) and poor (CPC3-5) neurological outcome groups. Total time while the core temperature reached to 33 °C ± 1 °C within the first 24 hours after CA was measured and this duration was defined that of well-controlled temperature. receiver-operating characteristic analysis was performed on duration of well-controlled temperature to select the optimal cutoff value. Neurological outcome predictors were investigated by logistic regression analysis. RESULTS: Fifty-six patients were included. Optimal cutoff value of duration of well-controlled temperature was 18 hours. Ratio of male sex, witnessed by emergency medical service (EMS) personnel, first electrocardiogram as shockable, and duration of well-controlled core temperature ≥ 18 h of favorable neurological outcome group (n = 21) were significantly larger than that of poor neurological outcome group (n = 35). Logistic regression analysis identified "witnessed by EMS", "performed bystander CPR," and "the duration ≥ 18 h" as independent predictors of favorable neurological outcome. CONCLUSION: TH maintained at target temperature of 33 °C ± 1 °C over 18 hours independently correlated with favorable neurological outcome. Therefore, stable core temperature control may improve neurological outcome of successfully resuscitated OHCA.

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, IL1ß -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 IL1ß -31) enabled more accurate prediction of ICU mortality (ROC-AUC=0.80). Significant association of two genetic polymorphisms, TNF -308 and IL1ß -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.

Comparison of interleukin-6 removal properties among hemofilters consisting of varying membrane materials and surface areas: an in vitro study.

BACKGROUND/AIMS: We sought to identify the most relevant hemofilter for cytokine removal based on the mechanisms of filtration and adsorption. METHODS: Ascites were filtered using four types of hemofilters composed of different membrane materials (polymethyl methacrylate, PMMA, cellulose triacetate, CTA, or polysulfone, PS) and different surface areas (1.0 or 2.1 m(2)) to investigate the rate of interleukin-6 (IL-6) filtration. Next, ascites were perfused through each hemofilter without obtaining a filtrate to study each filter's adsorptive capability. RESULTS: The PMMA hemofilters resulted in a marginal observed IL-6 filtration rates, whereas the CTA and PS hemofilters resulted in highly effective IL-6 filtration. Regarding the IL-6 adsorptive capabilities of the filters, the PMMA hemofilter with a large surface area showed the highest level of IL-6 clearance. CONCLUSION: The present findings suggest that when cytokine removal based on filtration is desired, CTA or PS hemofilters should be selected. When IL-6 removal based on adsorption is desired, a PMMA hemofilter with a large surface area should be selected.

Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia.

INTRODUCTION: Bacteremia is recognized as a critical condition that influences the outcome of sepsis. Although large-scale surveillance studies of bacterial species causing bacteremia have been published, the pathophysiological differences in bacteremias with different causative bacterial species remain unclear. The objective of the present study is to investigate the differences in pathophysiology and the clinical course of bacteremia caused by different bacterial species. METHODS: We reviewed the medical records of all consecutive patients admitted to the general intensive care unit (ICU) of a university teaching hospital during the eight-year period since introduction of a rapid assay for interleukin (IL)-6 blood level to routine ICU practice in May 2000. White blood cell count, C-reactive protein (CRP), IL-6 blood level, and clinical course were compared among different pathogenic bacterial species. RESULTS: The 259 eligible patients, as well as 515 eligible culture-positive blood samples collected from them, were included in this study. CRP, IL-6 blood level, and mortality were significantly higher in the septic shock group (n = 57) than in the sepsis group (n = 127) (P < 0.001). The 515 eligible culture-positive blood samples harbored a total of 593 isolates of microorganisms (Gram-positive, 407; Gram-negative, 176; fungi, 10). The incidence of Gram-negative bacteremia was significantly higher in the septic shock group than in the sepsis group (P < 0.001) and in the severe sepsis group (n = 75, P < 0.01). CRP and IL-6 blood level were significantly higher in Gram-negative bacteremia (n = 176) than in Gram-positive bacteremia (n = 407) (P < 0.001, <0.0005, respectively). CONCLUSIONS: The incidence of Gram-negative bacteremia was significantly higher in bacteremic ICU patients with septic shock than in those with sepsis or severe sepsis. Furthermore, CRP and IL-6 levels were significantly higher in Gram-negative bacteremia than in Gram-positive bacteremia. These findings suggest that differences in host responses and virulence mechanisms of different pathogenic microorganisms should be considered in treatment of bacteremic patients, and that new countermeasures beyond conventional antimicrobial medications are urgently needed.

S-100B and neuron-specific enolase as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation: a systematic review.

INTRODUCTION: Neurological prognostic factors after cardiopulmonary resuscitation (CPR) in patients with cardiac arrest (CA) as early and accurately as possible are urgently needed to determine therapeutic strategies after successful CPR. In particular, serum levels of protein neuron-specific enolase (NSE) and S-100B are considered promising candidates for neurological predictors, and many investigations on the clinical usefulness of these markers have been published. However, the design adopted varied from study to study, making a systematic literature review extremely difficult. The present review focuses on the following three respects for the study design: definitions of outcome, value of specificity and time points of blood sampling. METHODS: A Medline search of literature published before August 2008 was performed using the following search terms: "NSE vs CA or CPR", "S100 vs CA or CPR". Publications examining the clinical usefulness of NSE or S-100B as a prognostic predictor in two outcome groups were reviewed. All publications met with inclusion criteria were classified into three groups with respect to the definitions of outcome; "dead or alive", "regained consciousness or remained comatose", and "return to independent daily life or not". The significance of differences between two outcome groups, cutoff values and predictive accuracy on each time points of blood sampling were investigated. RESULTS: A total of 54 papers were retrieved by the initial text search, and 24 were finally selected. In the three classified groups, most of the studies showed the significance of differences and concluded these biomarkers were useful for neurological predictor. However, in view of blood sampling points, the significance was not always detected. Nevertheless, only five studies involved uniform application of a blood sampling schedule with sampling intervals specified based on a set starting point. Specificity was not always set to 100%, therefore it is difficult to indiscriminately assess the cut-off values and its predictive accuracy of these biomarkers in this meta analysis. CONCLUSIONS: In such circumstances, the findings of the present study should aid future investigators in examining the clinical usefulness of these markers and determination of cut-off values.

Continuous hemodiafiltration in the treatment of reactive hemophagocytic syndrome refractory to medical therapy.

Reactive (or secondary) hemophagocytic syndrome (RHS) is a potentially lethal condition and characterized by hypercytokinemia. Immune modulating drugs sometimes fail to achieve satisfactory control. Therefore we investigate the efficacy of continuous hemodiafiltration using a polymethyl methacrylate membrane hemofilter (PMMA-CHDF) for cytokine removal in patients with RHS. Eight consecutive patients who admitted to our ICU with RHS complicating organ failures and refractory to medical therapy were initiated intensive care including PMMA-CHDF. Although remission was achieved in six patients, remaining two patients died of exacerbation of underlying diseases. Changes in blood levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) as indices of cytokine network activation, and serum ferritin level as an index of severity of RHS were investigated during PMMA-CHDF. PMMA-CHDF performed for 3 days significantly reduced blood TNF-alpha level (183+/-159 pg/ml to 84+/-98 pg/ml, p<0.05) and also blood IL-6 level (1113+/-903 pg/ml to 402+/-411 pg/ml, p<0.01). Furthermore, serum ferritin level was significantly decreased 3 days after initiation of PMMA-CHDF (52390+/-65168 ng/ml to 4136+/-2932 ng/ml, p<0.05) although it tended to increase before initiation of PMMA-CHDF. No PMMA-CHDF-related adverse events were observed in any of the patients. PMMA-CHDF was effective to remove cytokine and improved disease severity. Thus, PMMA-CHDF may be an adjunctive treatment in RHS refractory to medical therapy.

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.

Establishing extracorporeal membrane oxygenation team increased number of patients and improved data recording.

BACKGROUND: For patients treated with extracorporeal membrane oxygenation (ECMO), employing a well-coordinated, multidisciplinary team specializing in ECMO has reportedly been effective in delivering better clinical outcomes. This study aims to assess the impact of establishing such a specialized team for patients treated with ECMO. METHOD: This retrospective cohort study was performed at a tertiary-care hospital in Japan. We reviewed medical records of all consecutive patients treated with ECMO during October 2010-September 2016. The results obtained in pre-ECMO team cases (PRE group; October 2011-September 2012) and post-ECMO team cases (POST group; October 2014-September 2015) were compared. RESULTS: The results obtained in pre-ECMO team cases (PRE group; October 2011-September 2012) and post-ECMO team cases (POST group; October 2014-September 2015) were compared. During the study period, 177 patients were treated with ECMO. Before the introduction of ECMO team, an average of 22.7 patients underwent ECMO treatment per year; after establishing ECMO team, this number increased to 36.3 patients per year. ECMO was applied mainly to cardiac arrest patients 52/69 (75%). The PRE (n = 27) and POST (n = 42) groups did not differ with regard to the survival rate to hospital discharge, ECMO duration, ventilator days, and length of hospital stay. However, PaO2 and positive end-expiratory pressure were significantly higher in the POST group at 6 h after ECMO initiation than those in the PRE group [367 (186-490) vs. 239 (113-430) mmHg, p = 0.047 and 8 (5-10) vs. 7 (5-8) cmH2O, p = 0.01, respectively]. In addition, data recording the detailed time points of ECMO initiation was conducted in significantly more cases in the POST group (28/126 (22%) than in the PRE group (6/81 (7%); p = 0.01). CONCLUSIONS: Following the establishment of an ECMO team, the survival rate of patients treated with ECMO, ECMO duration, and length of hospital stay were not improved. However, the number of ECMO cases increased and the recording of clinical data was improved.

Ionizing irradiation induces apoptotic damage of salivary gland acinar cells via NADPH oxidase 1-dependent superoxide generation.

Reactive oxygen species (ROS) have important roles in various physiological processes. Recently, several novel homologues of the phagocytic NADPH oxidase have been discovered and this protein family is now designated as the Nox family. We investigated the involvement of Nox family proteins in ionizing irradiation-induced ROS generation and impairment in immortalized salivary gland acinar cells (NS-SV-AC), which are radiosensitive, and immortalized ductal cells (NS-SV-DC), which are radioresistant. Nox1-mRNA was upregulated by gamma-ray irradiation in NS-SV-AC, and the ROS level in NS-SV-AC was increased to approximately threefold of the control level after 10Gy irradiation. The increase of ROS level in NS-SV-AC was suppressed by Nox1-siRNA-transfection. In parallel with the suppression of ROS generation and Nox1-mRNA expression by Nox1-siRNA, ionizing irradiation-induced apoptosis was strongly decreased in Nox1-siRNA-transfected NS-SV-AC. There were no large differences in total SOD or catalase activities between NS-SV-AC and NS-SV-DC although the post-irradiation ROS level in NS-SV-AC was higher than that in NS-SV-DC. In conclusion, these results indicate that Nox1 plays a crucial role in irradiation-induced ROS generation and ROS-associated impairment of salivary gland cells and that Nox1 gene may be targeted for preservation of the salivary gland function from radiation-induced impairment.

Potential role for emergency physicians with endoscopy training in the treatment of upper gastrointestinal hemorrhage: a retrospective observational study.

AIM: Urgent endoscopy is essential in gastrointestinal (GI) bleeding. Emergency physicians with endoscopy training treat patients with GI bleeding in our hospital. We compared the management and clinical outcomes of GI bleeding cases between those treated by an emergency physician (EP) and those treated by a non-emergency physician (NEP; e.g., gastroenterologist or general surgeon). METHODS: We undertook a retrospective chart review of upper GI bleeding cases treated using endoscopy in the emergency department between 2012 and 2014. We examined patients characteristics, endoscopic findings, hemostatic procedures, need for transfusion, rebleeding and adverse events, length of hospital stay, and mortality. RESULTS: The EP group included 33 patients (39%) and the NEP group included 51 (61%). Patient characteristics and diseases did not differ between the groups. The EP group underwent urgent endoscopy more often (100% versus 86%, P = 0.04). Procedure times were not statistically different between the groups. The EP group had fewer hemostatic procedures (42% versus 65%, P = 0.04). Transfusion requirements were lower in the EP group (0.5 U versus 2.1 U, P = 0.006). There were no statistical differences in rebleeding and adverse events. The length of hospital stay was shorter (8 versus 11 days, P = 0.03) and the in-hospital mortality rate was lower in the EP group (0% versus 13.7%, P = 0.04). CONCLUSION: Short-term outcomes in GI bleeding cases managed by emergency physicians with endoscopy training were comparable to those by gastroenterologists and general surgeons. However, the extent of endoscopic training and experience emergency physicians should have remains unclear.

Veno-venous extracorporeal membrane oxygenation bridged living-donor lung transplantation for rapid progressive respiratory failure with pleuroparenchymal fibroelastosis after allogeneic hematopoietic stem cell transplantation.

Cases of extracorporeal membrane oxygenation (ECMO) bridged lung transplantation (LTx) are rare in Japan because an allocation system to prioritize patients based on urgency remains to be established. For critically ill patients who cannot wait for a brain-dead donor LTx, ECMO bridge to living-donor LTx may be the only practical option. A 21-year-old woman with pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation was admitted to our hospital with rapidly progressive respiratory failure. She was waitlisted for 6 months before admission, but veno-venous ECMO was initiated. She was transported under ECMO support via a jet plane and underwent successful living-donor LTx.

Depressed heart rate variability is associated with high IL-6 blood level and decline in the blood pressure in septic patients.

Depressed heart rate variability (HRV) in septic patients is known to be associated with poor outcome. However, neither etiology of depression of HRV nor its clinical significance has been clearly determined. Because hypercytokinemia plays an important role in sepsis, we investigated the relationships between depressed HRV and IL-6 blood level. The subjects of this study were 45 septic patients treated in our intensive care unit. IL-6 blood level upon admission exhibited significant negative correlations with two HRV indices, low-frequency power (LF) (r = -0.76; P < 0.01) and high-frequency power (HF) (r = -0.53; P < 0.01). Multivariate analysis revealed strong correlations between IL-6 blood level and LF (P = 0.01) and HF (P = 0.01), respectively, even when the effects of patient background factors and therapeutic intervention were taken into account. Among the patients who developed septic shock, a high IL-6 blood level and a low LF were observed in both the survivor and nonsurvivor groups on the day of admission. The HF was lower than normal at the same time points in both groups. However, the HF was significantly higher in the nonsurvivor group than in the survivor group. By the time of discharge from the intensive care unit, both IL-6 blood level and HRV indices had become significantly closer to the normal ranges in the survivor group, but not in the nonsurvivor group. A significant negative correlation was observed between LF upon admission and percent decline in blood pressure (r = -0.76, P < 0.01). These findings indicate that reduction in HRV indices is associated with hypercytokinemia, indicating that the autonomic nervous system and the inflammatory response mediated by the cytokine network affect each other. These results also suggest that depression of HRV is closely related to rapid changes in blood pressure. Thus, heart rate variability indices are associated with both the severity and poor outcome of sepsis.

Pharmacokinetics of Standard- and Reduced-Dose Recombinant Human Soluble Thrombomodulin in Patients with Septic Disseminated Intravascular Coagulation during Continuous Hemodiafiltration.

INTRODUCTION: Recombinant human soluble thrombomodulin (rTM) is reportedly excreted by the kidneys; therefore, the recommended dose for patients with renal impairment is one-third of the standard dose. The aim of this study was to evaluate whether this reduced dose of rTM achieves effective drug concentrations that are comparable to those of the standard dose in treating sepsis-induced disseminated intravascular coagulation (DIC) during continuous hemodiafiltration (CHDF). METHODS: Eight patients in an intensive care unit were randomized to receive either reduced-dose (0.02 mg/kg, n = 4) or standard-dose (0.06 mg/kg, n = 4) rTM. We evaluated the effect of standard dose in comparison to that of reduced dose on the pharmacokinetics (PKs) of rTM for the sepsis-induced DIC patients receiving CHDF. Patients received rTM during a 30-min infusion for six consecutive days. PK parameters of rTM were analyzed using the one-compartment model. RESULTS: The elimination half-life, clearance (T1/2), and distribution volume of sTM were similar between the reduced and standard doses. The maximum concentration (Cmax) and area under the concentration-time curve (AUC) of sTM were approximately 2.5 times higher with standard-dose daily infusions than that with reduced-dose drip infusions (p = 0.041 and 0.062, respectively). The time when the blood concentration of sTM was >500 ng/mL, i.e., the holding time, was significantly longer with standard-dose infusions than those with reduced dose (p = 0.039). CONCLUSION: rTM displayed dose-dependent PK behavior at clinically relevant doses. During CHDF, effective blood concentration of rTM was not achieved with the reduced dose, and rTM was found to not bioaccumulate. Therefore, this pilot study suggests that reducing the rTM dose is unnecessary, even in sepsis-induced DIC patients who require CHDF. However, we need to perform a definitive study to determine the dosage of rTM for the case.

[Efficacy of micafungin sodium on fungal infection in critical care].

The clinical effects and tolerability of micafungin sodium in daily practice for the treatment of fungal infection in critically ill patients were evaluated in an open-labeled, non-comparative, observational study. All patients admitted to intensive care units (ICUs) of 3 hospitals in Chiba prefecture between June 2003 and March 2005, who were treated with micafungin because of known or suspected fungal infection, were included in the study. A total of 34 patients received micafungin and 29 cases of them were subjected to analysis. Fungal infections were classified as "proven" in 3 patients (10.3%) and "possible" in 26 (89.7%). Candida was detected in 16 patients, most of them were Candida albicans and 4 cases were non-albicans Candida. Clinical effects of micafungin were "cured" and "improved" in 20 patients (77%), "failure" in 6 (23%), and "undetermined" in 3 cases. Adverse events were reported in 10 patients, but there was no significant event. In conclusion, micafungin was effective in 77% of proven or suspected fungal infections in critically ill patients admitted to the ICU. The drug was well tolerated and discontinuation of its treatment due to adverse events was not experienced during the study period.