Junko Yamaguchi

Relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the Berlin definition

IntroductionThe Berlin definition divides acute respiratory distress syndrome (ARDS) into three severity categories. The relationship between these categories and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, remains to be elucidated. The aim of this study was to evaluate the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and to confirm the associated predictive validity for severity.MethodsThe extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) were measured using a transpulmonary thermodilution method for three consecutive days in 195 patients with an EVLWi of ≥10 mL/kg and who fulfilled the Berlin definition of ARDS. Collectively, these patients were seen at 23 ICUs. Using the Berlin definition, patients were classified into three categories: mild, moderate, and severe.ResultsCompared to patients with mild ARDS, patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores on the day of enrollment. Patients with severe ARDS had higher EVLWi (mild, 16.1; moderate, 17.2; severe, 19.1; P <0.05) and PVPI (2.7; 3.0; 3.2; P <0.05). When categories were defined by the minimum PaO2/FIO2 ratio observed during the study period, the 28-day mortality rate increased with severity categories: moderate, odds ratio: 3.125 relative to mild; and severe, odds ratio: 4.167 relative to mild. On independent evaluation of 495 measurements from 195 patients over three days, negative and moderate correlations were observed between EVLWi and the PaO2/FIO2 ratio (r = -0.355, P<0.001) as well as between PVPI and the PaO2/FIO2 ratio (r = -0.345, P <0.001). ARDS severity was associated with an increase in EVLWi with the categories (mild, 14.7; moderate, 16.2; severe, 20.0; P <0.001) in all data sets. The value of PVPI followed the same pattern (2.6; 2.7; 3.5; P <0.001).ConclusionsSeverity categories of ARDS described by the Berlin definition have good predictive validity and may be associated with increased extravascular lung water and pulmonary vascular permeability.Trial registrationUMIN-CTR ID UMIN000003627

Effects of Bag-mask versus Advanced Airway Ventilation for Patients Undergoing Prolonged Cardiopulmonary Resuscitation in Pre-hospital Setting

BACKGROUND There is no evidence that the advanced airway ventilation (AAV) method improves patient outcome in the pre-hospital cardiac arrest setting. OBJECTIVE The aim of this study was to estimate the effectiveness of AAV vs. bag-mask ventilation (BMV) for cardiopulmonary arrest (CPA) patients, when administered by a licensed emergency medical technician in the pre-hospital setting. METHODS The study used the database of patients who suffered out-of-hospital cardiogenic CPA from 2006 to 2007 in our hospital. Patient records were searched for the method of pre-hospital airway management (BMV or AAV) and the patients outcomes were compared between groups. The primary endpoint was a favorable neurological outcome; the secondary endpoints were rate of return of spontaneous circulation (ROSC) and rate of admission to the intensive care unit (ICU). RESULTS A total of 355 CPA patients (156 BMV and 199 AAV) were retrospectively enrolled. There was no significant difference in demographics between the two groups. The transportation time exceeded 30 min in both groups. The overall ROSC rate and ICU admission rate were significantly higher in the AAV group (p = 0.0352 and p = 0.0089, respectively). The data showed that AAV (odds ratio 1.960; 95% confidence interval 1.015-3.785) resulted in a higher overall ROSC rate than BMV, but there were no significant differences in either the rate of pre-hospital ROSC or in favorable neurological outcome. CONCLUSION AAV may yield advantages over BMV in the overall rate of ROSC in CPA patients, but both approaches for airway management in this study resulted in a comparably favorable neurological outcome. Earlier ROSC would be required for improved overall outcome.

Shorter time until return of spontaneous circulation is the only independent factor for a good neurological outcome in patients with postcardiac arrest syndrome

Objective Few studies have reported factors that result in a better neurological outcome in patients with postcardiac arrest syndrome (PCAS) following return of spontaneous circulation (ROSC). We investigated the factors affecting neurological outcome in terms of both prehospital care and treatments after arrival at hospital in patients with PCAS. Methods The study enrolled patients with cardiogenic cardiac arrest who were admitted to an intensive care unit after ROSC with PCAS. We investigated the association of the following factors with outcome: age, gender, witness to event present, bystander cardiopulmonary resuscitation (CPR) performed, ECG waveform at the scene, time interval from receipt of call to arrival of emergency personnel, time interval from receipt of call to arrival at hospital, prehospital defibrillation performed, special procedures performed by emergency medical technician, and time interval from receipt of call to ROSC, coronary angiography/percutaneous coronary intervention (PCI) and therapeutic hypothermia performed. Results The study enrolled 227 patients with PCAS. Compared with the poor neurological outcome group, the good neurological outcome group had a statistically significant higher proportion of the following factors: younger age, male, witness present, bystander CPR performed, first ECG showed ventricular fibrillation/pulseless ventricular tachycardia, defibrillation performed during transportation, short time interval from receipt of call to ROSC, coronary angiography/PCI and therapeutic hypothermia performed. Of these factors, the only independent factor associated with good neurological outcome was the short time interval from receipt of the call to ROSC. Conclusions In the present study, shortening time interval from receipt of call to ROSC was the only important independent factor to achieve good neurological outcome in patients with PCAS.

Change in brain glucose after enteral nutrition in subarachnoid hemorrhage.

BACKGROUND The alteration of brain extracellular glucose after enteral nutrition (EN) remains unclear. In this study, we used brain microdialysis methods to estimate whether the physiologic elevation of plasma glucose following EN affects brain glucose metabolism of aneurysmal subarachnoid hemorrhage (SAH) patients. METHODS Brain extracellular glucose, lactate, glycerol, glutamate, and pyruvate were measured with a brain microdialysis probe in 12 patients (mean age: 60.0 y+/-7.8 y) after SAH. The EN was initially administered a mean of 3.2 d after the onset of SAH. All of the measured parameters were estimated before and after EN. RESULTS Cerebral perfusion pressure did not significantly change after SAH during the study period. Plasma glucose rose significantly after EN (141.4+/-11.6mg/dL before EN versus 183.8+/-26.2mg/dL immediately after EN (P=0.0006), 177.7+/-30.2mg/dL at 2h after EN (P=0.0033)). The brain extracellular glucose before EN (2.5+/-0.92mmol/L) was significantly lower than the levels measured just after (3.49+/-1.0mmol/L, P=0.0186) and 2h after the end of EN (3.70+/-1.0mmol/L, P=0.0053). Brain extracellular concentrations of lactate, glutamate, pyruvate, and glycerol showed no significant changes. CONCLUSIONS Brain extracellular glucose increased after the transient elevation of plasma glucose following EN. These results suggest that brief, physiologic elevations in plasma glucose after EN produced no changes in brain extracellular glutamate concentration or lactate/pyruvate ratio. These data may help determine the plasma glucose levels most effective for avoiding brain metabolic acidosis in patients after SAH. It remains unclear, however, how SAH itself influences these findings.

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

BackgroundAcute 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.MethodsA 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.ResultsIn 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.ConclusionsThe results of this study suggest the existence of several differences in the increased degree of pulmonary permeability between patients with ARDSexp and ARDSp.Trial registrationThis report is a sub-group analysis of the study registered with UMIN-CTR (IDUMIN000003627).

Limitations of global end-diastolic volume index as a parameter of cardiac preload in the early phase of severe sepsis: a subgroup analysis of a multicenter, prospective observational study

BackgroundIn patients with severe sepsis, depression of cardiac performance is common and is often associated with left ventricular (LV) dilatation to maintain stroke volume. Although it is essential to optimize cardiac preload to maintain tissue perfusion in patients with severe sepsis, the optimal preload remains unknown. This study aimed to evaluate the reliability of global end-diastolic volume index (GEDI) as a parameter of cardiac preload in the early phase of severe sepsis.MethodsNinety-three mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome secondary to sepsis were enrolled for subgroup analysis in a multicenter, prospective, observational study. Patients were divided into two groups—with sepsis-induced myocardial dysfunction (SIMD) and without SIMD (non-SIMD)—according to a threshold LV ejection fraction (LVEF) of 50% on the day of enrollment. Both groups were further subdivided according to a threshold stroke volume variation (SVV) of 13% as a parameter of fluid responsiveness.ResultsOn the day of enrollment, there was a positive correlation (r = 0.421, p = 0.045) between GEDI and SVV in the SIMD group, whereas this paradoxical correlation was not found in the non-SIMD group and both groups on day 2. To evaluate the relationship between attainment of cardiac preload optimization and GEDI value, GEDI with SVV ≤13% and SVV >13% was compared in both the SIMD and non-SIMD groups. SVV ≤13% implies the attainment of cardiac preload optimization. Among patients with SIMD, GEDI was higher in patients with SVV >13% than in patients with SVV ≤13% on the day of enrollment (872 [785–996] mL/m2 vs. 640 [597–696] mL/m2; p < 0.001); this finding differed from the generally recognized relationship between GEDI and SVV. However, GEDI was not significantly different between patients with SVV ≤13% and SVV >13% in the non-SIMD group on the day of enrollment and both groups on day 2.ConclusionsIn the early phase of severe sepsis in mechanically ventilated patients, there was no constant relationship between GEDI and fluid reserve responsiveness, irrespective of the presence of SIMD. GEDI should be used as a cardiac preload parameter with awareness of its limitations.

Inhibition of lipopolysaccharide stimulated interleukin-1β production after subarachnoid hemorrhage

Abstract Purpose: To identify the characteristics of cytokine production from peripheral blood mononuclear cells (PBMCs) in response to lipopolysaccharide (LPS) in patients with subarachnoid hemorrhage (SAH). Methods: Blood samples were collected on the first day and 3 days after SAH (n=12) to measure plasma concentrations of catecholamines, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-10. PBMCs from SAH patients or healthy volunteers were incubated with LPS (1 μg) for 24 hours. In the second phase, PBMCs from healthy volunteers (n=6) were incubated with or without catecholamine (10 μmol/l) for 6 hours. After pre-treatment, the cells were treated with LPS (1 μg) for 18 hours. Supernatants were extracted and subjected to measurement by enzyme-linked immunosorbent assay. Results: Plasma concentrations of epinephrine or dopamine prolong increased significantly 3 days after SAH, involved in elevation of plasma IL-10. In the PBMCs from the SAH patients, LPS-stimulated IL-1β production was inhibited significantly. Pre-treatment with epinephrine or dopamine inhibited LPS-stimulated IL-1β production significantly in the PBMCs from the healthy volunteers. Conclusions: The initial SAH involved in an impaired production of pro-inflammatory cytokines in response to LPS with an elevation of plasma epinephrine, dopamine and IL-10 after acute stressful conditions. This phenomenon may play an important role of an early immnosupression in patients with poor grade SAH.

Increased oxidative stress and renal injury in patients with sepsis

Sepsis remains one of the leading causes of death in intensive care units. The early phase of sepsis is characterized by a massive formation of reactive oxygen and nitrogen species such as superoxide and nitric oxide. However, few comprehensive studies on plasma antioxidants have been reported. Increased oxidative stress was confirmed in sepsis patients (n = 18) at the time of hospitalization by a significant decrease in plasma ascorbic acid and a significant increase in the percentage of oxidized form of coenzyme Q10 in total coenzyme Q10 compared to age-matched healthy controls (n = 62). Tissue oxidative damage in patients was suggested by a significant decrease in polyunsaturated fatty acid contents and a significant increase in oleic acid contents in total free fatty acids. Thus, it is reasonable that plasma uric acid (end product of purines) would be significantly elevated. However, uric acid levels were continuously decreased during hospitalization for 7 days, indicating a continuous formation of peroxynitrite. A greater decrease in free cholesterol (FC) compared to cholesterol esters (CE) was observed. Thus, the FC/CE ratio significantly increased, suggesting deficiency of lecithin-cholesterol acyltransferase secreted from the liver. Plasma levels of prosaposin, a coenzyme Q10 binding protein, significantly decreased as compared to healthy controls. This may be correlated with renal injury in sepsis patients, since the kidney is thought to be a major secretor of prosaposin.

Delayed augmentation effect of cytokine production after hyperthermia stimuli

Heatstroke is considered an important condition that may contribute to endothelial cell damage. The aim of this study was to assess temporal profiles of the cytokine (IL-6 and IL-8) and mRNA production when endothelial cells undergo higher temperature stimuli. In the first group, human umbilical vascular endothelial cells (HUVECs) were cultured at 4 different temperatures (37, 38, 39 or 40°C) for 1, 3 and 5 h. In the second group, HUVECs were cultured at 37°C for 4 h or 23 h, after stimulation by heating for one hour at the same culture temperatures used in the first group (37°C to 40°C). After culturing, IL-6 and IL-8 mRNA and protein levels were measured. It has been found the cytokine mRNA levels being significantly higher (p < 0.001) in all cells incubated at higher temperaturesthan those in the control (cultivation at 37°C). At the same time, the production of IL-6 and 8 at a higher temperature (39, 40°C) was significantly lower (p < 0.001) than at 37°C (control), and the decrease was temperature dependent. However, IL-6 and IL-8 levelswere significantly greater in the cells at 23 h after transient hyperthermic (40°C, 1 h) stimulation than in control ones (p < 0.001). After a transient hyperthermia, the production of the cytokinesin HUVECs is initially inhibited and then augmented. The results indicated that tissue injury might continue to develop after a hyperthermic event. There might be a potent risk for underestimation of cytokine induced tissue injury in the acute phase of a heatstroke.

The Importance of the Time that Elapses Before Spontaneous Circulation is Established Following an Out-of-Hospital Cardiac Arrest

Methods: Patients who recorded an ABR wave V immediately after resuscitation from OHCA were kept at 34 °C for 48 hours. The cohort was divided into two groups: A favorable neurological outcome group (F group: N=12) and an unfavorable neurological outcome group (U group: N=14). Favorable neurological outcome was defined as Pittsburgh Cerebral-Performance Scale (CPC) 1 or 2 and unfavorable as CPC 3-5. Data used to compare the groups included whether CA was witnessed, if a bystander initiated cardiopulmonary resuscitation, presence of cardiac etiology, initial cardiac rhythm and elapsed time from emergency call receipt until Return of Spontaneous Circulation (ROSC).