Eleven-year retrospective study characterizing patients with severe brain damage and poor neurological prognosis -role of physicians' attitude toward life-sustaining treatment.

BACKGROUND: Severe brain hemorrhage/infarction and cardiac arrest constitute the most critical situations leading to poor neurological prognosis. Characterization of these patients is required to offer successful end-of-life care, but actual practice is affected by multiple confounding factors, including ethicolegal issues, particular in Japan and Asia. The aim of this study is to evaluate the clinical courses of patients with severe brain damage and to assess the preference of end-of-life care for these patients in Japanese hospitals. METHODS: A retrospective observational study was conducted between 2008 and 2018. All intracranial hemorrhage/infarction and cardiac arrest out-patients (n = 510) who were admitted to our two affiliated hospitals and survived but with poor neurologic outcomes were included. Demographic characteristics as well as prognosis and treatment policies were also assessed. RESULTS: Patients were divided into two categories; cases with absent brainstem reflex (BSR) (BSR[-]) and those with preserved BSR (BSR[ +]). The survival rate was higher and the length of hospitalization was longer in patients with BSR[ +] than in those with BSR[-]. Among three life-sustaining policies (i.e., aggressive treatment, withdrawal of treatment, and withholding of treatment), withholding of treatment was adopted to most patients. In BSR[-], the proportion of three treatment policies performed at the final decision did not differ from that at the initial diagnosis on neurological status (p = 0.432). In contrast, this proportion tended to be altered in BSR[ +] (p = 0.072), with a decreasing tendency of aggressive treatment and a modest increasing tendency of withdrawal of treatment. Furthermore, the requests from patients' families to withdraw life-sustaining treatment, including discontinuation of mechanical ventilation, increased, but actual implementation of withdrawal by physicians was less than half of the requests. CONCLUSIONS: BSR constitutes a crucial determinant of mortality and length of hospitalization in comatose patients with severe brain damage. Although the number of withdrawal of life-sustaining treatment tends to increase over time in BSR[ +] patients, there are many more requests from patients' families for withdrawal. Since physicians has a tendency to desist from withdrawing life-sustaining treatment, more in-depth communication between medical staff and patients' families will facilitate mutual understanding over ethicolegal and religious issues and may thus improve end-of-life care.

Monitoring tissue oxygenation index using near-infrared spectroscopy during pre-hospital resuscitation among out-of-hospital cardiac arrest patients: a pilot study.

BACKGROUND: Tissue oxygenation index (TOI) using the near infrared spectroscopy (NIRS) has been demonstrated as a useful indicator to predict return of spontaneous circulation (ROSC) among out-of-hospital cardiac arrest (OHCA) patients in hospital setting. However, it has not been widely examined based on pre-hospital setting. METHODS: In this prospective observational study, we measured TOI in pre-hospital setting among OHCA patients receiving cardio-pulmonary resuscitation (CPR) during ambulance transportation between 2017 and 2018. Throughout the pre-hospital CPR procedure, TOI was continuously measured. The study population was divided into two subgroups: ROSC group and non-ROSC group. RESULTS: Of the 81 patients included in the final analysis, 26 achieved ROSC and 55 did not achieve ROSC. Patients in the ROSC group were significantly younger, had higher ∆TOI (changes in TOI) (5.8 % vs. 1.3 %; p < 0.01), and were more likely to have shockable rhythms and event witnessed than patients in the non-ROSC group. ∆TOI cut-off value of 5 % had highest sensitivity (65.4 %) and specificity (89.3 %) for ROSC. Patients with a cut-off value ≤-2.0 % did not achieve ROSC and while all OHCA patient with a cut-off value ≥ 8.0 % achieved ROSC. In addition, ROSC group had stronger positive correlation between mean chest compression rate and ∆TOI (r = 0.82) than non-ROSC group (r = 0.50). CONCLUSIONS: This study suggests that ∆ TOI could be a useful indicator to predict ROSC in a pre-hospital setting.

Efficacy of prehospital National Early Warning Score to predict outpatient disposition at an emergency department of a Japanese tertiary hospital: a retrospective study.

OBJECTIVES: The National Early Warning Score (NEWS) was originally developed to assess hospitalised patients in the UK. We examined whether the NEWS could be applied to patients transported by ambulance in Japan. DESIGN: This retrospective study assessed patients and calculated the NEWS from paramedic records. Emergency department (ED) disposition data were categorised into the following groups: discharged from the ED, admitted to the ward, admitted to the intensive care unit (ICU) or died in the ED. The predictive performance of NEWS for patient disposition was assessed using receiver operating characteristic curve analysis. Patient dispositions were compared among NEWS-based categories after adjusting for age, sex and presence of traumatic injury. SETTING: A tertiary hospital in Japan. PARTICIPANTS: Overall, 2847 patients transported by ambulance between April 2017 and March 2018 were included. RESULTS: The mean (±SD) NEWS differed significantly among patients discharged from the ED (n=1330, 3.7±2.9), admitted to the ward (n=1263, 60.3±3.8), admitted to the ICU (n=232, 9.4±4.0) and died in the ED (n=22, 110.7±2.9) (p<0.001). The prehospital NEWS C-statistics (95% CI) for admission to the ward, admission to the ICU or death in the ED; admission to the ICU or death in the ED; and death in the ED were 0.73 (0.72-0.75), 0.81 (0.78-0.83) and 0.90 (0.87-0.93), respectively. After adjusting for age, sex and trauma, the OR (95% CI) of admission to the ICU or death in the ED for the high-risk (NEWS ≥7) and medium-risk (NEWS 5-6) categories was 13.8 (8.9-21.6) and 4.2 (2.5-7.1), respectively. CONCLUSION: The findings from this Japanese tertiary hospital setting showed that prehospital NEWS could be used to identify patients at a risk of adverse outcomes. NEWS stratification was strongly correlated with patient disposition.

Independent lung ventilation with use of a double-lumen endotracheal tube for refractory hypoxemia and shock complicating severe unilateral pneumonia: A case report.

BACKGROUND: The indications for independent lung ventilation (ILV) in critical care settings have not been fully clarified, especially because extracorporeal membrane oxygenation (ECMO) is being used increasingly in cases of severe respiratory failure. CASE REPORT: A 90-year-old man presented with severe unilateral pneumonia, and despite conventional mechanical ventilation management with use of a single lumen endotracheal tube and high positive endo-expiratory pressure (PEEP), oxygenation and hemodynamics deteriorated. We then performed ILV using a double-lumen endotracheal tube (DLT) and two ventilators, each set at a different respiratory mode. With continuous administration of a neuromuscular blocking agent, the ventilator for the left lung (non-affected lung) was set to pressure-controlled ventilation (PCV) mode, whereas the ventilator for the right lung (affected lung) was set to bi-level mode, 1 breath/min, and high PEEP. ILV and the high PEEP applied to the affected lung prevented hyperinflation of the non-affected lung and increased pulmonary blood perfusion on the non-affected side. Thus, ILV immediately improved oxygenation and hemodynamics by correcting ventilation/perfusion mismatch. DISCUSSION: Although ECMO is a valid treatment option for patients with severe respiratory failure, it is highly invasive intervention. ILV performed with use of a DLT is less invasive and more useful than ECMO. Thus, ILV should be kept in mind as a treatment option, especially in cases of refractory respiratory failure and circulatory failure in which the pathophysiology of the left and right lungs differs markedly.

Exploratory Observational Study of Extracorporeal Cardiopulmonary Resuscitation for Nonshockable Out-Of-Hospital Cardiac Arrest Occurring After an Emergency Medical Services Arrival: SOS-KANTO 2012 Study Report.

BACKGROUND: The outcomes of patients with nonshockable out-of-hospital cardiac arrest (OHCA) are poor, but may be improved by extracorporeal cardiopulmonary resuscitation (E-CPR). OBJECTIVE: To examine the effects of veno-arterial extracorporeal membranous oxygenation (ECMO) as E-CPR in patients with nonshockable OHCA after emergency medical services (EMS) arrival for whom satisfactory cardiopulmonary resuscitation (CPR) was immediately performed. METHODS: Among 16,452 patients enrolled in the SOS-KANTO 2012 study, we examined data on 531 patients aged ≥ 18 years who performed activities of daily living (ADL) well or had moderate disability before the onset of cardiac arrest (CA) and those with normal spontaneous respiration or pulse palpation upon EMS arrival. CPR was performed immediately after CA onset, and advanced life support was provided upon hospital arrival for these patients. We divided patients into ECMO and non-ECMO groups. We retrospectively analyzed background factors and clinical outcomes. RESULTS: E-CPR was performed on 38 (7.2%) patients. In the univariate analysis, the mean age of the ECMO group was lower, ADL function before onset was more favorable, mean body weight was higher, and the mean interval from onset until hospital arrival was shorter than those in the non-ECMO group. One-to 3-month survival or favorable cerebral function outcome rates were higher in the ECMO group than in the non-ECMO group. In the multivariate analysis, ECMO use and the interval from onset until hospital arrival were independent prognostic factors for favorable cerebral functional outcomes at 1 and 3 months. CONCLUSION: E-CPR may be associated with favorable outcomes in carefully selected patients with nonshockable OHCA.

Can the global end-diastolic volume index guide fluid management in septic patients? A multicenter randomized controlled trial.

AIM: An index that accurately measures intravascular volume is paramount for the optimal resuscitation of sepsis. Selecting an adequate indicator to substitute for central venous pressure (CVP) has remained an issue. The objective of our study was to compare the usefulness of standard early goal-directed therapy (EGDT) with CVP (EGDT-CVP) and modified EGDT with global end-diastolic volume index (GEDI; EGDT-GEDI) for sepsis. METHODS: This was a multicenter prospective randomized controlled study. All patients with sepsis who were expected to require mechanical ventilator support for a minimum of 48 h were included. The patients were classified into an EGDT-CVP group and an EGDT-GEDI group. All participants underwent the extubation protocol. The primary outcome was the ventilator-free days over a 28-day period. RESULTS: The ventilator-free days was not significantly different between the two groups (P = 0.59). However, the EGDT-GEDI group showed a trend of shorter ventilator support duration (5.1 days [2.0-8.7 days] versus 3.9 days [2.4-5.7 days], P = 0.27) and length of stay in the intensive care unit (7.2 days [3.8-10.7 days] versus 5.1 days [3.7-8.8 days], P = 0.05) and a smaller 3-day infusion balance than the EGDT-CVP group (4,405 mL [1,092-8,163 mL] versus 3,046 mL [830-6,806 mL], P = 0.34), but the differences were not statistically significant. CONCLUSION: Although there was no significant efficacy, EGDT guided by GEDI showed a trend of shorter length of stay in the intensive care unit and lower 3-day infusion balance than the EGDT-CVP group in sepsis. The GEDI monitoring did not appear to improve the ventilator-free days over a 28-day period.

Clinical outcomes of urinary tract infection caused by extended spectrum beta-lactamase producing Enterobacteriaceae: a retrospective observational study comparing patients with and without systemic inflammatory response syndrome.

AIM: In severe urinary tract infection (UTI), susceptible antibiotics should be given. With the recent increase of multidrug-resistant bacteria, especially extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), broad-spectrum antibiotics, such as carbapenems, are used more frequently, which could lead to a further increase of multidrug-resistant bacteria. We aimed to analyze the relationship between initial empirical antibiotic appropriateness and clinical outcomes in UTI, especially in patients with systemic inflammatory response syndrome (SIRS) and ESBL-E. METHODS: A retrospective observational study from 2012 to 2017. RESULTS: Among urine culture-positive cases with ≥105 colony-forming units/mL (n = 1,880), true UTI cases were extracted (n = 844) and divided into the SIRS group (n = 336 [ESBL-E12.8% (43/336)]) and non-SIRS group (n = 508 [ESBL-E12.6% (64/508)]). In the SIRS ESBL-E group, the initial antibiotics were susceptible in 55.8% (24/43), among which 91.7% (22/24) improved and 8.3% (2/24) deteriorated or died. The initial antibiotics were resistant in 44.2% (19/43), among which 47.4% (9/19) improved with the initial antibiotics, 47.4% (9/19) improved after escalating antibiotics, and 5.3% (1/19) deteriorated or died. In the SIRS group, 14 cases had true bacteremia with ESBL-E. Seven cases were initiated with inappropriate antibiotics; four cases showed improvement before or without antibiotic change and three cases improved after antibiotic escalation. CONCLUSION: Initiation of narrow-spectrum antibiotics in septic UTI with ESBL-E might not deteriorate the clinical outcome if promptly escalated on clinical deterioration or with ESBL-E culture results. Further investigation is warranted to guide judicious use of initial antibiotics.

Compartment syndrome due to Capnocytophaga canimorsus infection: a case report.

BACKGROUND: Purpura fulminans secondary to Capnocytophaga canimorsus (C. canimorsus) infection without a wound is rare and often misdiagnosed initially. We report a patient who died due to C. canimorsus bacteremia with purpura fulminans and acute compartment syndrome of all extremities. CARE PRESENTATION: A 38-year-old Japanese man with a history of alcoholism presented with a 2-day history of gastroenteritis. The chief complaints were abdominal pain and diarrhea, and he had abdominal tenderness. Laboratory findings showed multiple organ failure. On day 2, pain in the lower extremities associated with motor and sensory dysfunction developed. On day 3, purpura on the whole body spread to all extremities. All four extremities became rigid, and acute compartment syndrome developed. The patient died due to uncontrolled hyperkalemia and lactic acidosis. CONCLUSIONS: Capnocytophaga canimorsus transmission can occur through licking or even close contact with animals when a risk factor of C. canimorsus infection, such as alcoholism, is present.

Cardiac arrest during hemodialysis: a survey of five Japanese hospitals.

AIM: Intraprocedural cardiac arrest is a serious complication among patients receiving hemodialysis. However, the frequency and reaction to these events remain unclear. This study aimed to explore the clinical picture of cardiac arrest during hemodialysis. METHODS: Ten cardiac arrests that had occurred during 217,984 hemodialysis treatments in five Japanese hospitals, between 2008 and 2017, were reviewed. We investigated the underlying disease, vital signs, emergency responses, and outcomes using patient medical records. RESULTS: The cardiac arrest rate ranged from 1.1 to 7.5 per 100,000 hemodialysis sessions. All included cases of cardiac arrest occurred in a hemodialysis unit and had been witnessed and reported by supervising clinicians. The initial rhythm was ventricular fibrillation/ventricular tachycardia in six patients (60%) and pulseless electrical activity/asystole in four patients (40%). Seven (70%) patients showed a return of spontaneous circulation (ROSC), and two (20%) patients were discharged with a cerebral performance category score of 1. There was a statistically significant difference in the ROSC rate (P = 0.048) only in the event of an emergency call. The SpO2 and respiratory rates had not been recorded in six patients. There was no significant difference in ROSC between initial rhythms of ventricular fibrillation/ventricular tachycardia and pulseless electrical activity/asystole. CONCLUSION: We evaluated the frequency of cardiac arrest during hemodialysis. Overall assessment including respiratory status is needed at initiation of hemodialysis. In case of a sudden change in a patient's status, high-quality resuscitation treatment that includes an emergency call can improve prognosis.

The downside of aggressive volume administration in critically ill patients-"aggressive" may lead to "excessive".

Management of fluid therapy in an intensive care unit (ICU) tends to be volume restriction after initial fluid resuscitation, since it has been the consensus that volume overload is associated with complications and poor clinical outcomes. Aggressive volume administration without cautious monitoring should be avoided in the ICU, because it could lead to excessive volume administration. However, there are limited consensus on determining the completion of resuscitation phase, in other words, when to stop aggressive infusion and initiate infusion restriction.

Association Between Therapeutic Hypothermia and Outcomes in Patients with Non-shockable Out-of-Hospital Cardiac Arrest Developed After Emergency Medical Service Arrival (SOS-KANTO 2012 Analysis Report).

BACKGROUND/OBJECTIVE: The outcomes of patients with non-shockable out-of-hospital cardiac arrest (non-shockable OHCA) are poorer than those of patients with shockable out-of-hospital cardiac arrest (shockable OHCA). In this retrospective study, we selected patients from the SOS-KANTO 2012 study with non-shockable OHCA that developed after emergency medical service (EMS) arrival and analyzed the effect of therapeutic hypothermia (TH) on non-shockable OHCA patients. METHODS: Of 16,452 patients who have definitive data on the 3-month outcome in the SOS-KANTO 2012 study, we selected 241 patients who met the following criteria: age ≥ 18 years, normal spontaneous respiration or palpable pulse upon emergency medical services arrival, no ventricular fibrillation or pulseless ventricular tachycardia before hospital arrival, and achievement of spontaneous circulation without cardiopulmonary bypass. Patients were divided into two groups based on the presence or absence of TH and were analyzed. RESULTS: Of the 241 patients, 49 underwent TH. Univariate analysis showed that the 1-/3-month survival rates and favorable 3-month cerebral function outcome rates in the TH group were significantly better than the non-TH group (46% vs 19%, respectively, P < 0.001, 35% vs 12%, respectively, P < 0.001, 20% vs 7%, respectively, P = 0.01). Multivariate logistic regression analysis showed that TH was a significant, independent prognostic factor for cerebral function outcome. CONCLUSIONS: In this study, TH was an independent prognostic factor for the 3-month cerebral function outcome. Even in patients with non-shockable OHCA, TH may improve outcome if the interval from the onset of cardiopulmonary arrest is relatively short, and adequate cardiopulmonary resuscitation is initiated immediately after onset.

Near-infrared spectroscopy monitoring during out-of-hospital cardiac arrest: can the initial cerebral tissue oxygenation index predict ROSC?

STUDY OBJECTIVES: Near-infrared spectroscopy is a modality that can monitor tissue oxygenation index (TOI) and has potential to evaluate return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR). This study's objectives were to evaluate whether TOI could be associated with ROSC and used to help guide the decision to either terminate CPR or proceed to extracorporeal CPR (ECPR). METHODS: In this observational study, we assessed the patients with out-of-hospital cardiac arrest with non-traumatic cause receiving CPR on arrival at our ED between 2013 and 2016. TOI monitoring was discontinued either on CPR termination after ROSC was reached or on patient death. Patients were classified into two groups: ROSC and non-ROSC group. RESULTS: Out of 141 patients, 24 were excluded and the remaining 117 were classified as follows: ROSC group (n=44) and non-ROSC group (n=73). ROSC group was significantly younger and more likely to have their event witnessed and bystander CPR. ROSC group showed a higher initial TOI than non-ROSC group (60.5%±17.0% vs 37.9%±13.7%: p<0.01). Area under the curve analysis was more accurate with the initial TOI than without it for predicting ROSC (0.88, 95% CI 0.82 to 0.95 vs 0.79, 95% CI 0.70 to 0.87: p<0.01). TOI cut-off value ≥59% appeared to favour survival to hospital discharge whereas TOI ≤24% was associated with non-ROSC. CONCLUSIONS: This study demonstrated an association between higher initial TOI and ROSC. Initial TOI could increase the accuracy of ROSC prognosis and may be a clinical factor in the decision to terminate CPR and select patients who are to proceed to ECPR.

Oxygen management in mechanically ventilated patients: A multicenter prospective observational study.

PURPOSE: To observe arterial oxygen in relation to fraction of inspired oxygen (FIO2) during mechanical ventilation (MV). MATERIALS AND METHODS: In this multicenter prospective observational study, we included adult patients required MV for >48h during the period from March to May 2015. We obtained FIO2, PaO2 and SaO2 from commencement of MV until the 7th day of MV in the ICU. RESULTS: We included 454 patients from 28 ICUs in this study. The median APACHE II score was 22. Median values of FIO2, PaO2 and SaO2 were 0.40, 96mmHg and 98%. After day two, patients spent most of their time with a FIO2 between 0.3 and 0.49 with median PaO2 of approximately 90mmHg and SaO2 of 97%. PaO2 was ≥100mmHg during 47.2% of the study period and was ≥130mmHg during 18.4% of the study period. FIO2 was more likely decreased when PaO2 was ≥130mmHg or SaO2 was ≥99% with a FIO2 of 0.5 or greater. When FIO2 was <0.5, however, FIO2 was less likely decreased regardless of the value of PaO2 and SaO2. CONCLUSIONS: In our multicenter prospective study, we found that hyperoxemia was common and that hyperoxemia was not corrected.

Utility of Glissonean Pedicle Transection for Surgical Treatment of Severe Liver Trauma.

The most common initial strategy for treatment of severe liver trauma is damage control in which hemostasis is achieved by perihepatic gauze packing and/or vascular embolization. However, we encounter patients in whom this strategy alone is not adequate. We have applied the principles of Glissonean pedicle transection, a technique that was originally devised to ensure safe and quick performance of planned hepatectomy for liver cancer, to 3 cases of severe liver trauma. We performed Glissonean pedicle ligation during damage control surgery in 2 patients and Glissonean pedicle transection during the definitive surgery in 1 patient. We describe the approaches and our experience with them, including operation times and outcomes. From our experience thus far, it seems that 8-12 h after the damage control procedure is appropriate for performing the definitive surgery. Although there are some problems posed by this strategy and cases to which it will not be applicable, the method seems to be particularly useful for cases of severe liver trauma in which the damage is extensive and involves the Glissonean pedicles near the hepatic hilus. We describe our 3 cases in detail and review our experience in light of the available literature.

Light irradiation for treatment of acute carbon monoxide poisoning: an experimental study.

BACKGROUND: Because treatment modalities for carbon monoxide (CO) poisoning, especially normobaric oxygen and hyperbaric oxygen therapies, have limited effects and hyperbaric oxygen is not available at the scene where treatment is most needed, we conducted a study to determine and compare rates of carboxyhemoglobin (COHb) dissociation achieved in human in vitro blood samples under light radiation emitted at three levels of illuminance. This was done with a view toward eventual on-site application. METHODS: We drew blood from 10 volunteers, prepared 10 red blood cell solutions, and subjected each solution to a CO bubbling procedure to increase the COHb saturation. Samples of each bubbled solution were then divided between 3 beakers (beakers A, B, and C) for a total of 30 beakers. The solution in each beaker was exposed to a continuous flow of oxygen at 50 mL/min, and simultaneously for a period of 15 min, the beaker A and B solutions were irradiated with light emitted at 500,000 and 100,000 lux, respectively, from a halogen light source. The beaker C solutions were exposed to room light. At 3, 6, 9, 12, and 15 min, a 50-µL sample was pipetted from each of the 30 beakers for determination of its light absorbance and the COHb dissociation rate. RESULTS: Under each of the experimental conditions, dissociation progressed but at different rates, and starting at 3 min, the differences in rates between conditions were significant (P < 0.01). The dissociation rate was greatest with light emitted at 500,000 lux. CONCLUSIONS: Our results point toward the possibility of readily performed, acute photodissociation therapy for patients with CO poisoning.

Human mannose-binding lectin inhibitor prevents Shiga toxin-induced renal injury.

Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC HUS) is a worldwide endemic problem, and its pathophysiology is not fully elucidated. Here we tested whether the mannose-binding lectin (MBL2), an initiating factor of lectin complement pathway activation, plays a crucial role in STEC HUS. Using novel human MBL2-expressing mice (MBL2 KI) that lack murine Mbls (MBL2(+/+)Mbl1(-/-)Mbl2(-/-)), a novel STEC HUS model consisted of an intraperitoneal injection with Shiga toxin-2 (Stx-2) with or without anti-MBL2 antibody (3F8, intraperitoneal). Stx-2 induced weight loss, anemia, and thrombocytopenia and increased serum creatinine, free serum hemoglobin, and cystatin C levels, but a significantly decreased glomerular filtration rate compared with control/sham mice. Immunohistochemical staining revealed renal C3d deposition and fibrin deposition in glomeruli in Stx-2-injected mice. Treatment with 3F8 completely inhibited serum MBL2 levels and significantly attenuated Stx-2 induced-renal injury, free serum hemoglobin levels, renal C3d, and fibrin deposition and preserved the glomerular filtration rate. Thus, MBL2 inhibition significantly protected against complement activation and renal injury induced by Stx-2. This novel mouse model can be used to study the role of complement, particularly lectin pathway-mediated complement activation, in Stx-2-induced renal injury.

Difference in pulmonary permeability between indirect and direct acute respiratory distress syndrome assessed by the transpulmonary thermodilution technique: a prospective, observational, multi-institutional study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by the increased pulmonary permeability secondary to diffuse alveolar inflammation and injuries of several origins. Especially, the distinction between a direct (pulmonary injury) and an indirect (extrapulmonary injury) lung injury etiology is gaining more attention as a means of better comprehending the pathophysiology of ARDS. However, there are few reports regarding the quantitative methods distinguishing the degree of pulmonary permeability between ARDS patients due to pulmonary injury and extrapulmonary injury. METHODS: A prospective, observational, multi-institutional study was performed in 23 intensive care units of academic tertiary referral hospitals throughout Japan. During a 2-year period, all consecutive ARDS-diagnosed adult patients requiring mechanical ventilation were collected in which three experts retrospectively determined the pathophysiological mechanisms leading to ARDS. Patients were classified into two groups: patients with ARDS triggered by extrapulmonary injury (ARDSexp) and those caused by pulmonary injury (ARDSp). The degree of pulmonary permeability using the transpulmonary thermodilution technique was obtained during the first three intensive care unit (ICU) days. RESULTS: In total, 173 patients were assessed including 56 ARDSexp patients and 117 ARDSp patients. Although the Sequential Organ Failure Assessment (SOFA) score was significantly higher in the ARDSexp group than in the ARDSp group, measurements of the pulmonary vascular permeability index (PVPI) were significantly elevated in the ARDSp group on all days: at day 0 (2.9 ± 1.3 of ARDSexp vs. 3.3 ± 1.3 of ARDSp, p = .008), at day 1 (2.8 ± 1.5 of ARDSexp vs. 3.2 ± 1.2 of ARDSp, p = .01), at day 2 (2.4 ± 1.0 of ARDSexp vs. 2.9 ± 1.3 of ARDSp, p = .01). There were no significant differences in mortality at 28 days, mechanical ventilation days, and hospital length of stay between the two groups. CONCLUSIONS: The results of this study suggest the existence of several differences in the increased degree of pulmonary permeability between patients with ARDSexp and ARDSp. TRIAL REGISTRATION: This report is a sub-group analysis of the study registered with UMIN-CTR (IDUMIN000003627).

Global end-diastolic volume is an important contributor to increased extravascular lung water in patients with acute lung injury and acuterespiratory distress syndrome: a multicenter observational study.

BACKGROUND: Extravascular lung water (EVLW), as measured by the thermodilution method, reflects the extent of pulmonary edema. Currently, there are no clinically effective treatments for preventing increases in pulmonary vascular permeability, a hallmark of lung pathophysiology, in patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). In this study, we examined the contributions of hemodynamic and osmolarity factors, for which appropriate interventions are expected in critical care, to EVLW in patients with ALI/ARDS. METHODS: We performed a subgroup analysis of a multicenter observational study of patients with acute pulmonary edema. Overall, 207 patients with ALI/ARDS were enrolled in the study. Multivariate regression analysis was used to evaluate the associations of hemodynamic and serum osmolarity parameters with the EVLW index (EVLWI; calculated as EVLW/Ideal body weight). We analyzed factors measured on the day of enrollment (day 0), and on days 1 and 2 after enrollment. RESULTS: Multivariate regression analysis showed that global end-diastolic volume index (GEDVI) was significantly associated with EVLWI measured on days 0, 1, and 2 (P = 0.002, P < 0.001, and P = 0.003, respectively), whereas other factors were not significantly associated with EVLWI measured on all 3 days. CONCLUSIONS: Among several hemodynamic and serum osmolarity factors that could be targets for appropriate intervention, GEDVI appears to be a key contributor to EVLWI in patients with ALI/ARDS. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000003627.

Separately or combined, LukG/LukH is functionally unique compared to other staphylococcal bicomponent leukotoxins.

Staphylococcus aureus is a major human pathogen that elaborates several exotoxins. Among these are the bicomponent leukotoxins (BCLs), which include γ-hemolysin, Panton-Valentine leukocidin (PVL), and LukDE. The toxin components are classified as either F or S proteins, which are secreted individually and assemble on cell surfaces to form hetero-oligomeric pores resulting in lysis of PMNs and/or erythrocytes. F and S proteins of γ-hemolysin, PVL and LukDE have ∼ 70% sequence homology within the same class and several heterologous combinations of F and S members from these three bicomponent toxin groups are functional. Recently, an additional BCL pair, LukGH (also called LukAB) that has only 30% homology to γ-hemolysin, PVL and LukDE, has been characterized from S. aureus. Our results showed that LukGH was more cytotoxic to human PMNs than PVL. However, LukGH-induced calcium ion influx in PMNs was markedly attenuated and slower than that induced by PVL and other staphylococcal BCLs. In contrast to other heterologous BCL combinations, LukG in combination with heterologous S components, and LukH in combination with heterologous F components did not induce calcium ion entry or cell lysis in human PMNs or rabbit erythrocytes. Like PVL, LukGH induced IL-8 production by PMNs. While individual components LukG and LukH had no cytolytic or calcium influx activity, they each induced high levels of IL-8 transcription and secretion. IL-8 production induced by LukG or LukH was dependent on NF-κB. Therefore, our results indicate LukGH differs functionally from other staphylococcal BCLs.

A new method to detect cerebral blood flow waveform in synchrony with chest compression by near-infrared spectroscopy during CPR.

OBJECTIVE: The objective of the study is to demonstrate the utility of near-infrared spectroscopy (NIRS) in evaluating chest compression (CC) quality in cardiac arrest (CA) patients as well as determine its prognosis predictive value. METHODS: We present a nonconsecutive case series of adult patients with CA whose cardiopulmonary resuscitation (CPR) was monitored with NIRS and collected the total hemoglobin concentration change (ΔcHb), the tissue oxygen index (TOI), and the ΔTOI to assess CC quality in a noninvasive fashion. RESULTS: During CPR, ΔcHb displayed waveforms monitor, which we regarded as a surrogate for CC quality. Total hemoglobin concentration change waveforms responded accurately to variations or cessations of CCs. In addition, a TOI greater than 40% measured upon admission appears to be significant in predicting patient's outcome. Of 15 patients, 6 had a TOI greater than 40% measured upon admission, and 67% of the latter were in return of spontaneous circulation after CPR and were found to be significantly different between return of spontaneous circulation and death (P = .047; P < .05). CONCLUSION: Near-infrared spectroscopy reliably assesses the quality of CCs in patients with CA demonstrated by synchronous waveforms during CPR and possible prognostic predictive value, although further investigation is warranted.