Takashi Kanemura

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

High D-dimer levels predict a poor outcome in patients with severe trauma, even with high fibrinogen levels on arrival : a multicenter retrospective study

ABSTRACT Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicenter retrospective study. This study included 519 adult trauma patients with an injury severity score ≥16. Patients with ≥10 units of red cell concentrate transfusion and/or death during the first 24 h were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D-dimer values to be 190 mg/dL and 38 mg/L, respectively. On the basis of these values, patients were divided into four groups: low D-dimer (<38 mg/L)/high fibrinogen (>190 mg/dL), low D-dimer (<38 mg/L)/low fibrinogen (⩽190 mg/dL), high D-dimer (≥38 mg/L)/high fibrinogen (>190 mg/dL), and high D-dimer (≥38 mg/L)/low fibrinogen (⩽190 mg/dL). The survival rate was lower in the high D-dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels.

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.

Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: A retrospective cohort analysis: Effectiveness of linezolid in the elderly.

Objectives: Several reports have compared the efficacy of linezolid (LZD) in Methicillin‐resistant Staphylococcus aureus (MRSA) infections with that of vancomycin (VCM); however, these two antibiotics for the treatment of nosocomial MRSA pneumonia in elderly patients has not been well evaluated. The purpose of this study is to evaluate the efficacy and safety of LZD compared with VCM for the treatment of elderly patients with nosocomial MRSA pneumonia in a retrospective chart review of a cohort. Methods: We included 28 consecutive patients aged ≥ 65 years hospitalized with a confirmed diagnosis of MRSA pneumonia and treated with LZD (n = 11) or VCM (n = 17) between November 2010 and May 2015. We collected patient, disease, and laboratory data. The primary outcome was 30‐day mortality. The secondary outcomes were the sequential organ failure assessment (SOFA) total, respiratory, renal, coagulation, hepatic, cardiovascular, and central nervous system scores on days 1, 3, 7, and 14. Results: There were no significant differences between the two groups with regard to baseline characteristics. The 30‐day mortality rate was significantly lower in the LZD group than in the VCM group (0% vs. 41%, P = .02). The SOFA total score on days 3, 7, and 14 were significantly lower those at baseline in the LZD group (P < .05). The SOFA respiratory score on days 14 was also significantly lower than baseline in the LZD group (P < .05). Conclusion: LZD may be more efficacious than VCM for treating elderly patients with nosocomial MRSA pneumonia.

Development of Novel Criteria of the “lethal Triad” as an Indicator of Decision Making in Current Trauma Care: A Retrospective Multicenter Observational Study in Japan

Objectives: To evaluate the utility of the conventional lethal triad in current trauma care practice and to develop novel criteria as indicators of treatment strategy. Design: Retrospective observational study. Settings: Fifteen acute critical care medical centers in Japan. Patients: In total, 796 consecutive trauma patients who were admitted to emergency departments with an injury severity score of greater than or equal to 16 from January 2012 to December 2012. Interventions: None. Measurements and Main Results: All data were retrospectively collected, including laboratory data on arrival. Sensitivities to predict trauma death within 28 days of prothrombin time international normalized ratio greater than 1.50, pH less than 7.2, and body temperature less than 35°C were 15.7%, 17.5%, and 15.9%, respectively, and corresponding specificities of these were 96.4%, 96.6%, and 93.6%, respectively. The best predictors associated with hemostatic disorder and acidosis were fibrin/fibrinogen degradation product and base excess (the cutoff values were 88.8 µg/mL and –3.05 mmol/L). The optimal cutoff value of hypothermia was 36.0°C. The impact of the fibrin/fibrinogen degradation product and base excess abnormality on the outcome were approximately three- and two-folds compared with those of hypothermia. Using these variables, if the patient had a hemostatic disorder alone or a combined disorder with acidosis and hypothermia, the sensitivity and specificity were 80.7% and 66.8%. Conclusions: Because of the low sensitivity and high specificity, conventional criteria were unsuitable as prognostic indicators. Our revised criteria are assumed to be useful for predicting trauma death and have the potential to be the objective indicators for activating the damage control strategy in early trauma care.

Increasing or fluctuating bispectral index values during post-resuscitation targeted temperature management can predict clinical seizures after rewarming

AIM To investigate whether an increasing bispectral index (BIS) value during targeted temperature management (TTM) correlates with increased clinical seizures after TTM or worse neurological prognoses after TTM. METHODS We performed a retrospective prognostication study of patients who were treated with TTM after recovery of spontaneous circulation from cardiac arrest at a tertiary care hospital. We recorded the BIS regularly during TTM and calculated the correlations of the mean BIS values, standard deviations of the BIS values, and linear regression coefficient of the trend of the BIS values over time as index tests. Study outcomes included the occurrence of clinical seizures after TTM and unfavourable neurological outcomes (defined as a Cerebral Performance Scale score of 3-5). Receiver operating characteristics (ROC) analyses evaluated the predictability of the index tests for the study outcomes. RESULTS Of 534 patients with post-cardiac arrest who were admitted to the intensive care unit, 103 were enrolled in this study. Thirty-one patients (30.1%) experienced sequelae in the form of clinical seizures, and 52 (50.5%) had unfavourable neurological outcomes at 30days post-resuscitation. The standard deviation (area under the ROC curve [AUC]=0.763) and the regression coefficient (AUC=0.763) had higher predictability of clinical seizures than the mean BIS value (AUC=0.657); in contrast, the low mean BIS value best predicted unfavourable neurological outcomes (AUC=0.861) compared to the standard deviation (AUC=0.532) and regression coefficient (AUC=0.501). CONCLUSION An increase of, or greater fluctuation in, BIS during hypothermia may predict clinical seizures after TTM.

Severe acidemia on arrival not predictive of neurologic outcomes in post-cardiac arrest patients.

PURPOSE This study aimed to determine whether severe acidemia (pH <7.2) on arrival at the emergency department (ED) is a predictive factor for neurologic outcomes of post-cardiac arrest patients treated with targeted temperature management (TTM). MATERIALS AND METHODS Data in the National Disaster Medical Center, a tertiary care hospital, were used to perform a case-control study on post-cardiac arrest patients treated with TTM from January 2013 to April 2015. The case group comprised patients with good neurologic outcomes (cerebral performance categories 1 and 2), whereas the control group comprised patients with poor neurologic outcomes (cerebral performance categories 3-5). Exposure was defined as arterial pH less than 7.2 on arrival at the ED. RESULTS We identified 32 patients matching our criteria, of which 13 had good outcomes and 19 poor outcomes. Arterial pH on arrival was not significantly associated with neurologic outcomes (P = .47; odds ratio, 0.5; 95% confidence interval, 0.09-2.61). In 24 patients with cardiogenic causes of cardiac arrest, pH on arrival was not significantly associated with neurologic outcomes (P = .68; odds ratio, 0.5; 95% confidence interval, 0.09-2.73) after matched-pair analysis by age, sex, and presence of light reflex. CONCLUSION Severe acidemia on arrival at the ED is not a significant predictive factor for neurologic outcomes in post-cardiac arrest patients treated with TTM, particularly in patients with cardiogenic causes of cardiac arrest. These results suggest that treatment should not be withheld in post-cardiac arrest patients with severe acidemia.

Fibrinogen level on admission is a predictor for massive transfusion in patients with severe blunt trauma: Analyses of a retrospective multicentre observational study

INTRODUCTION In the early phase of trauma, fibrinogen (Fbg) plays an important role in clot formation. However, to the best of our knowledge, few studies have analysed methods of predicting the need for massive transfusion (MT) based on Fbg levels using multiple logistic regression. Therefore, the present study aimed to evaluate whether Fbg levels on admission can be used to predict the need for MT in patients with trauma. METHODS We conducted a retrospective multicentre observational study. Patients with blunt trauma with ISS ≥16 who were admitted to 15 tertiary emergency and critical care centres in Japan participating in the J-OCTET were enrolled in the present study. MT was defined as the transfusion of packed red blood cells (PRBC) ≥10 units or death caused by bleeding within 24h after admission. Patients were divided into non-MT and MT groups. Multiple logistic-regression analysis was used to assess the predictive value of the variables age, sex, vital signs, Glasgow Coma Scale (GCS) score, and Fbg levels for MT. We also evaluated the discrimination threshold of MT prediction via receiver operating characteristic curve (ROC) analysis for each variable. RESULTS Higher heart rate (HR; per 10 beats per minutes [bpm]), systolic blood pressure (SBP; per 10mm Hg), GCS, and Fbg levels (per 10mg/dL) were independent predictors of MT (odds ratio [OR] 1.480, 95% confidence interval [CI] 1.326-1.668; OR 0.851, 95% CI 0.789-0.914; OR 0.907, 95% CI 0.855-0.962; and OR 0.931, 95% CI 0.898-0.963, respectively). The optimal cut-off values for HR, SBP, GCS, and Fbg levels were ≥100 bpm (sensitivity 62.4%, specificity 79.8%), ≤120mm Hg (sensitivity 61.5%, specificity 70.5%), ≤12 points (sensitivity 63.3%, specificity 63.6%), and ≤190mg/dL (sensitivity 55.1%, specificity 78.6%), respectively. CONCLUSIONS Our findings suggest that vital signs, GCS, and decreased Fbg levels can be regarded as predictors of MT. Therefore, future studies should consider Fbg levels when devising models for the prediction of MT.

Successful treatment of ileocolic intussusception with air enema reduction in an adult patient

Intussusception is a rare condition in adults, representing only 1% of all bowel obstructions. In adult cases, operative explorations are recommended to treat the bowel obstruction and to diagnose underlying diseases. The objective of the current case report was to describe the successful treatment of ileocolic intussusception with air enema reduction in an adult patient. A previously healthy 21-year-old woman had a 20-hour history of colicky abdominal pain and vomiting and was diagnosed as having idiopathic ileocolic intussusception by abdominal computed tomography. We treated the patient with air enema reduction under fluoroscopic guidance instead of an operative procedure. She received oxygen and intravenous midazolam to provide some degree of pain relief. Air was carefully pumped manually into the rectum, and the air pressure was monitored with a manometer. Because of air leakage from the rectum through the void to the outside the body, we continued to provide air to maintain the air pressure between 40 and 60 mm Hg. Three minutes after initiation of the air enema, when the patient experienced increasing abdominal pain and vomiting, the pressure was temporarily increased to greater than 100 mm Hg, and the air reached the terminal ileum. We considered the reduction successful and confirmed it with an abdominal ultrasound examination. We believe that air enema reduction is effective for treating idiopathic intussusception within 24 hours of symptom onset in young, previously healthy adult patients.