Hiroo Izumino

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

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.

Portable system for monitoring of regional cerebral oxygen saturation during prehospital cardiopulmonary resuscitation: a pilot study

We aimed to create a system for monitoring of regional cerebral oxygen saturation (rSO2) in patients with prehospital cardiopulmonary arrest and clarify the changes in rSO2 during cardiopulmonary resuscitation.

Infectious Episodes Lead to the Oxidative Stress Response after Lung Transplantation

Case series Patient: Male, 30 • Female, 44 Final Diagnosis: Post-transplant respiratory infection Symptoms: Oxidative stress Medication: — Clinical Procedure: — Specialty: Transplantology Objective: Challenging differential diagnosis Background: Reactive oxygen species function as key metabolites that can impair biological processes. In lung transplantation, severe oxidative stress is expected when ischemia/reperfusion injury, acute allograft rejection, and various infections occur. Case Report: Two clinical cases in which serial measurements of the oxidative stress response (levels of diacron-reactive oxygen metabolites) were taken during hospitalization using a Free Radical Elective Evaluator are reported. In the first case, a 30-year-old man underwent right single lung transplantation for juvenile pulmonary emphysema. Immunosuppression was maintained using tacrolimus, mycophenolate mofetil, and steroid. The oxidative stress response fluctuated significantly (p<0.01) during the infections caused by bronchial stenosis compared to the stable condition. No acute rejection was seen during hospitalization. In the second case, a 44-year-old woman underwent right single lung transplantation for lymphangioleiomyomatosis. Immunosuppression was maintained by the same regimen as in case 1. The patient’s postoperative course was uneventful, and there was no allograft rejection or infection. The oxidative stress response remained at the non-stress level. Conclusions: The oxidative stress response was measured by the levels of diacron-reactive oxygen metabolites in lung transplantation. High oxidative stress responses were seen during exposure to infections. This might become a noninvasive marker of complications after transplantation.