Yoichi Kase

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

Removal of 2-Arachidonylglycerol by Direct Hemoperfusion Therapy With Polymyxin B Immobilized Fibers Benefits Patients With Septic Shock

Arachidonylethanolamide (AEA) and 2‐arachidonylglycerol (2‐AG) are endocannabinoids involved in septic shock, and 8‐epi prostaglandin F2α (F2‐isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B‐immobilized fibers (PMX‐DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX‐DHP, we measured the changes in levels of endocannabinoids and F2‐isoprostane in patients with septic shock. Twenty‐six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX‐DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non‐responder group; N = 13). Levels of AEA did not change after PMX‐DHP in either the non‐responder or responder groups, whereas levels of 2‐AG decreased significantly after PMX‐DHP in the responder group, but not in the non‐responder group. F2‐isoprostane gradually increased after PMX‐DHP treatment; on the other hand, levels of F2‐isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2‐AG plays an important role in the cardiovascular status of these patients. The removal of 2‐AG by PMX‐DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long‐term oxidative stress.

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.

Prospective external validation of the new scoring system for disseminated intravascular coagulation by Japanese Association for Acute Medicine (JAAM).

INTRODUCTION A new disseminated intravascular coagulation (DIC) scoring system was recently announced by Japanese Association for Acute Medicine (JAAM). We have conducted a prospective external validation study to assess the accuracy of this scoring system. MATERIALS AND METHODS All patients admitted to the ICU in a tertiary academic hospital in 2007 were prospectively observed. All patients younger than 15 years of age, those who stayed in the ICU for less than 24 hours, had cardiac surgery, hematological diseases, recent chemotherapy or radiotherapy or liver cirrhosis were excluded. The remaining patients were then screened using the JAAM DIC scoring system. RESULTS DIC was diagnosed by the JAAM DIC scoring system in 45 of the 242 patients screened (18.6%). The DIC patients were older, had a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and stayed in the ICU longer in comparison to the non-DIC patients. However, hospital mortality was similar between the two groups (p=0.98). There was no difference in the JAAM DIC score between the surviving and non-surviving DIC patients (p=0.40). A multivariate logistic regression analysis revealed the DIC diagnosed by JAAM to have a non-significant low odds ratio for hospital mortality (OR 0.29, 95%CI 0.08-1.08, p=0.066). CONCLUSION We have reported an external validation study of the JAAM DIC scoring system, which was conducted outside of the centers where data for developing the score were collected. DIC diagnosed by this scoring system was not related to hospital mortality.

Impact of withdrawing antithrombin III administration from management of septic patients with or without disseminated intravascular coagulation.

Antithrombin III (ATIII) of low doses (1500–3000 units per day for 3–5 days) has been used for treatment of disseminated intravascular coagulation (DIC) for decades in Japan. In this study, we have examined the impact of ATIII practice change on outcome in critically ill patients with sepsis and DIC. From April 2005 to September 2008, all septic patients admitted to our ICU were divided into two groups: before withdrawing ATIII (period 1) and after withdrawing ATIII (period 2). Patients treated with ATIII in the period 1 and those not treated with ATIII in the period 2 were then matched according to the similar Acute Physiology and Chronic Health Evaluation II scores (±3) and the same diagnosis grouping. Sensitivity analysis was also conducted for patients with DIC. Forty-one out of 98 patients (41.8%) in the period 1 and only one out of 80 patients (1.3%) in the period 2 were treated with ATIII. Thirty pairs of the patients were matched. There was no difference between the two groups regarding the platelet counts and Sepsis-related Organ Failure Assessment scores at day 1 and day 4. A subgroup analysis was conducted with 12 patients diagnosed with DIC out of the 30 pairs. There was no difference between the two DIC groups for platelet counts, Sepsis-related organ failure assessment scores and DIC score at day 1 and also day 4. Although not significant, hospital mortality tended lower in the period 2. This study found that withdrawing ATIII administration from management of septic patients with or without DIC did not influence outcome.

Arterio-vena caval fistula detected by monitoring of transpulmonary thermodilution curves

To the Editor: The pulmonary artery catheter (PAC) and PiCCO monitor (Pulsion Medical Systems, Munich, Germany) use the thermodilution technique to measure cardiac output [1]. Because the indicator injection site (central vein) and temperature measurement site (femoral artery) are more distant in PiCCO than in PAC (right atrium and pulmonary artery), PiCCO can potentially detect a wider variety of left-to-right shunts (LRS) than PAC. A 68-year-old man was admitted to the ICU for presumed diagnoses of septic shock and acute kidney injury resulting from an infected right common iliac artery (CIA) aneurysm. He was treated with continuous veno-venous hemodialysis (CVVHD) and vasopressin infusion with massive fluid resuscitation and noradrenaline infusion for septic shock. Ten days after ICU admission, he still required a small amount of noradrenaline and CVVHD. To evaluate his cardiac function and manage his shock state more meticulously, a 5-Fr. catheter (Pulsioncath; Pulsion Medical Systems, Munich, Germany) was inserted in his left femoral artery and was connected to the PiCCO Plus monitor. Despite the absence of hypoxemia and lung infiltrates in the chest X-ray, hemodynamic variables showed low cardiac index (CI, 1.37 l/min/m) and very low intrathoracic blood volume index (ITBVI, 336 ml), with massively increased extravascular lung water index (EVLWI, 43.7 ml/kg) for an average value of two measurements. The thermodilution curve showed a significantly prolonged flattening of the descending portion of the curve, suggesting an LRS. A dynamic computed tomography (CT) scan of the abdomen was subsequently conducted, which revealed an arteriovenous fistula between the right CIA aneurysm and the inferior vena cava. To repair the fistula, endovascular stenting was planned. However, on the day of surgery, the patient suddenly developed cardiac arrest and could not be resuscitated. Although an autopsy was not performed, the cause of cardiac arrest was thought to be rupture of the aneurysm. The dilution curve of LRS is characterized by an early recirculation of the cold indicator, which results in premature flattening of the descending portion of the curve. Previously, only two cases of LRS detected by PiCCO have been reported [2]. One patient had a ventricular septal defect and the other had an aorto-vena caval fistula. One patient had an ITBVI of 857 ml/m, EVLWI of 31.7 ml/kg, and CI of 2.66 l/min/m. Our case showed even more abnormal values of ITBVI and EVLWI than the previous cases. Retrospectively, our patient had probably developed the LRS before ICU admission, when his condition deteriorated. The persistent LRS could have contributed to the sustained shock state and acute kidney injury and might have deteriorated gradually during his stay in the ICU. We think that this is the reason why we found exceptionally low ITBVI and high EVLWI values compared with previous cases. Electronic supplementary material The online version of this article (doi:10.1007/s00540-014-1788-8) contains supplementary material, which is available to authorized users.