Takashi Tagami

Validation of extravascular lung water measurement by single transpulmonary thermodilution: human autopsy study

IntroductionGravimetric validation of single-indicator extravascular lung water (EVLW) and normal EVLW values has not been well studied in humans thus far. The aims of this study were (1) to validate the accuracy of EVLW measurement by single transpulmonary thermodilution with postmortem lung weight measurement in humans and (2) to define the statistically normal EVLW values.MethodsWe evaluated the correlation between pre-mortem EVLW value by single transpulmonary thermodilution and post-mortem lung weight from 30 consecutive autopsies completed within 48 hours following the final thermodilution measurement. A linear regression equation for the correlation was calculated. In order to clarify the normal lung weight value by statistical analysis, we conducted a literature search and obtained the normal reference ranges for post-mortem lung weight. These values were substituted into the equation for the correlation between EVLW and lung weight to estimate the normal EVLW values.ResultsEVLW determined using transpulmonary single thermodilution correlated closely with post-mortem lung weight (r = 0.904, P < 0.001). A linear regression equation was calculated: EVLW (mL) = 0.56 × lung weight (g) - 58.0. The normal EVLW values indexed by predicted body weight were approximately 7.4 ± 3.3 mL/kg (7.5 ± 3.3 mL/kg for males and 7.3 ± 3.3 mL/kg for females).ConclusionsA definite correlation exists between EVLW measured by the single-indicator transpulmonary thermodilution technique and post-mortem lung weight in humans. The normal EVLW value is approximately 7.4 ± 3.3 mL/kg.Trial registrationUMIN000002780.

Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study

The association between antithrombin use and mortality in patients with sepsis‐associated disseminated intravascular coagulation (DIC) remains controversial.

Low-dose corticosteroid use and mortality in severe community-acquired pneumonia patients

The relationship between low-dose corticosteroid use and mortality in patients with severe community-acquired pneumonia (CAP) remains unclear. 6925 patients with severe CAP who received mechanical ventilation with or without shock (defined as use of catecholamines) at 983 hospitals were identified using a Japanese nationwide administrative database. The main outcome measure was 28-day mortality. 2524 patients with severe CAP who received catecholamines were divided into corticosteroid (n=631) and control (n=1893) groups. The 28-day mortality was significantly different between corticosteroid and control groups (unmatched: 24.6% versus 36.3%, p<0.001; propensity score-matched: 25.3% versus 32.6%, p=0.01; inverse probability-weighted: 27.5% versus 34.2%, p<0.001). 4401 patients with severe CAP who did not receive catecholamines were also divided into corticosteroid (n=1112) and control (n=3289) groups. The 28-day mortality was not significantly different between corticosteroid and control groups in propensity score-matched analyses (unmatched: 16.0% versus 19.4%, p=0.01; propensity score-matched: 17.7% versus 15.6%, p=0.22; inverse probability-weighted: 18.8% versus 18.2%, p=0.44). Low-dose corticosteroid use may be associated with reduced 28-day mortality in patients with septic shock complicating CAP. Low-dose corticosteroids in severe CAP patients was associated with better prognosis only in those with septic shock http://ow.ly/AWqZW

Implementation of the Fifth Link of the Chain of Survival Concept for Out-of-Hospital Cardiac Arrest

Background— The American Heart Association 2010 resuscitation guidelines recommended adding a fifth link (multidisciplinary postresuscitation care in a regional center) to the previous 4 in the chain of survival concept for out-of-hospital cardiac arrest. Our study aimed to determine the effectiveness of this fifth link. Methods and Results— This multicenter prospective cohort study involved all eligible out-of-hospital cardiac arrest patients in the Aizu region (n=1482, suburban/rural, Fukushima, Japan). Proportions of favorable neurological outcomes were evaluated before (January 2006–April 2008) and after (January 2009–December 2010) the implementation of the fifth link. After implementation, all patients were transported directly from the field to the tertiary-level hospital or secondarily from an outlying hospital to the tertiary-level hospital after restoration of circulation. The tertiary hospital provided intensive postresuscitation care, including appropriate hemodynamic and respiratory management, therapeutic hypothermia, and percutaneous coronary intervention. One-month survival with a favorable neurological outcome among all patients treated by emergency medical services providers improved significantly after implementation (4 of 770 [0.5%] versus 21 of 712 [3.0%]; P<0.001). The adjusted odds ratios of favorable neurological outcome were 0.9 (95% confidence interval, 0.7–1.1) for early access to emergency medical care, 3.1 (95% confidence interval, 0.7–14.2) for bystander resuscitation, 14.7 (95% confidence interval, 3.2–67.0) for early defibrillation, 1.0 (95% confidence interval, 1.0–1.1) for early advanced life support, and 7.8 (95% confidence interval, 1.6–39.0) for the fifth link. Conclusion— The proportion of out-of-hospital cardiac arrest patients with a favorable neurological outcome improved significantly after the implementation of the fifth link, which may be an independent predictor of outcome. Clinical Trial Registration— URL: http://www.apps.who.int/trialsearch. Unique identifier: UMIN000001607.

Recombinant human soluble thrombomodulin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study.

The association between recombinant human soluble thrombomodulin (rhTM) use and mortality in patients with sepsis‐associated disseminated intravascular coagulation (DIC) remains controversial.

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

Optimal range of global end-diastolic volume for fluid management after aneurysmal subarachnoid hemorrhage: a multicenter prospective cohort study.

Objectives:Limited evidence supports the use of hemodynamic variables that correlate with delayed cerebral ischemia or pulmonary edema after aneurysmal subarachnoid hemorrhage. The aim of this study was to identify those hemodynamic variables that are associated with delayed cerebral ischemia and pulmonary edema after subarachnoid hemorrhage. Design:A multicenter prospective cohort study. Setting:Nine university hospitals in Japan. Patients:A total of 180 patients with aneurysmal subarachnoid hemorrhage. Interventions:None. Measurements and Main Results:Patients were prospectively monitored using a transpulmonary thermodilution system in the 14 days following subarachnoid hemorrhage. Delayed cerebral ischemia was developed in 35 patients (19.4%) and severe pulmonary edema was developed in 47 patients (26.1%). Using the Cox proportional hazards model, the mean global end-diastolic volume index (normal range, 680–800 mL/m2) was the independent factor associated with the occurrence of delayed cerebral ischemia (hazard ratio, 0.74; 95% CI, 0.60–0.93; p = 0.008). Significant differences in global end-diastolic volume index were detected between the delayed cerebral ischemia and non–delayed cerebral ischemia groups (783 ± 25 mL/m2 vs 870 ± 14 mL/m2; p = 0.007). The global end-diastolic volume index threshold that best correlated with delayed cerebral ischemia was less than 822 mL/m2, as determined by receiver operating characteristic curves. Analysis of the Cox proportional hazards model indicated that the mean global end-diastolic volume index was the independent factor that associated with the occurrence of pulmonary edema (hazard ratio, 1.31; 95% CI, 1.02–1.71; p = 0.03). Furthermore, a significant positive correlation was identified between global end-diastolic volume index and extravascular lung water (r = 0.46; p < 0.001). The global end-diastolic volume index threshold that best correlated with severe pulmonary edema was greater than 921 mL/m2. Conclusions:Our findings suggest that global end-diastolic volume index impacts both delayed cerebral ischemia and pulmonary edema after subarachnoid hemorrhage. Maintaining global end-diastolic volume index slightly above normal levels has promise as a fluid management goal during the treatment of subarachnoid hemorrhage.

Intravenous Immunoglobulin and Mortality in Pneumonia Patients with Septic Shock: An Observational Nationwide Study

BACKGROUND The role of intravenous immunoglobulin (IVIG) as an adjunctive treatment for severe sepsis remains controversial. We hypothesized that IVIG could be effective for treating pneumonia patients who have septic shock. METHODS Mechanically ventilated pneumonia patients with septic shock were identified in the nationwide Japanese Diagnosis Procedure Combination inpatient database from 1 July 2010 to 31 March 2013. The effect of IVIG use on 28-day mortality was evaluated using propensity score and instrumental variable analyses. RESULTS Eligible patients (n = 8264) from 1014 hospitals were divided into an IVIG group (n = 1324) and a control group (n = 6940). Propensity score matching created a matched cohort of 1045 pairs with and without IVIG treatment. There was no significant difference in 28-day mortality between the IVIG and control groups in the unmatched analysis (37.8%, 501/1324 vs 35.3%, 2453/6940; difference, 2.5%; 95% confidence interval [CI], -.3 to 5.3) or the propensity score-matched analysis (36.7%, 383/1045 vs 36.0%, 376/1045; difference, 0.7%; 95% CI, -3.5 to 4.8). Logistic regression analysis did not show a significant association between IVIG use and 28-day mortality in propensity score-matched patients (1.03; 95% CI, .86 to 1.23). Analysis using the pattern of hospital IVIG use as an instrumental variable found that IVIG use was not associated with a reduction in 28-day mortality (difference, -3.1%; 95% CI, -13.2 to 7.0). CONCLUSIONS In this large retrospective nationwide study, we found that there may be no significant association between IVIG use and mortality in mechanically ventilated pneumonia patients with septic shock.

Prophylactic Antibiotics May Improve Outcome in Patients With Severe Burns Requiring Mechanical Ventilation: Propensity Score Analysis of a Japanese Nationwide Database

In this large nationwide study, we found that the use of prophylactic antibiotics was associated with improvement of all-cause mortality in mechanically ventilated patients with severe burns but not in those without mechanical ventilation.

Supplemental dose of antithrombin use in disseminated intravascular coagulation patients after abdominal sepsis

The effectiveness of supplemental dose antithrombin administration (1,500 to 3,000 IU/ day) for patients with sepsis-associated disseminated intravascular coagulation (DIC), especially sepsis due to abdominal origin, remains uncertain. This was a retrospective cohort study of patients with mechanically ventilated septic shock and DIC after emergency surgery for perforation of the lower intestinal tract using a nationwide administrative database, Japanese Diagnosis Procedure Combination inpatient database. A total of 2,164 patients treated at 612 hospitals during the 33-month study period between 2010 and 2013 were divided into an antithrombin group (n=1,021) and a control group (n=1,143), from which 518 propensity score-matched pairs were generated. Although there was no significant 28-day mortality difference between the two groups in the unmatched groups (control vs antithrombin: 25.7 vs 22.9 %; difference, 2.8 %; 95 % confidence interval [CI], -0.8-6.4), a significant difference existed between the two groups in propensity-score weighted groups (26.3 vs 21.7 %; difference, 4.6 %; 95 % CI, 2.0-7.1) and propensity-score matched groups (27.6 vs 19.9 %; difference, 7.7 %; 95 % CI, 2.5-12.9). Logistic regression analyses showed a significant association between antithrombin use and lower 28-day mortality in propensity-matched groups (odds ratio, 0.65; 95 % CI, 0.49-0.87). Analysis using the hospital antithrombin-prescribing rate as an instrumental variable showed that receipt of antithrombin was associated with a 6.5 % (95 % CI, 0.05-13.0) reduction in 28-day mortality. Supplemental dose of antithrombin administration may be associated with reduced 28-day mortality in sepsis-associated DIC patients after emergency laparotomy for intestinal perforation.