Manabu Sugita

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.

Preventive Effects of Suvorexant on Delirium: A Randomized Placebo-Controlled Trial

OBJECTIVE No highly effective pharmacologic interventions to prevent delirium have been identified. We examined whether suvorexant, a potent and selective orexin receptor antagonist, is effective for the prevention of delirium. METHODS We conducted a multicenter, rater-blinded, randomized, placebo-controlled clinical trial in intensive care units and regular acute wards between April 2015 and March 2016. Eligible patients were 65 to 89 years old, newly admitted due to emergency, and able to take medicine orally and had an expected stay or life expectancy of 48 hours or more. Seventy-two patients were randomly assigned using the sealed envelope method to receive suvorexant (15 mg/d; 36 patients) or placebo (36 patients) every night for 3 days. The primary outcome measure was incidence of delirium as determined by the DSM-5. Trained psychiatrists assessed for delirium. RESULTS We found that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (0% [n/N = 0/36] vs 17% [6/36], respectively, P = .025). Comparison by log-rank test also showed that delirium developed significantly less often among patients taking suvorexant than among those taking placebo (χ² = 6.46, P = .011). Analysis of variance revealed a tendency for main effect of treatment (F = 3.79, P = .053) on the sleep-wake cycle disturbance score (item 1) of the Japanese version of the Delirium Rating Scale-Revised-98 (DRS-R-98-J). There were no significant differences in adverse events. CONCLUSIONS Suvorexant administered nightly to elderly patients admitted for acute care may provide protection against delirium. Larger studies are needed to show the potential of suvorexant to improve the circadian core domain of delirium. TRIAL REGISTRATION UMIN Clinical Trials Registry identifier: UMIN000015681​.

Intravascular large B cell lymphoma with hepatic portal vein, splenic vein and mesenteric vein tumour embolism.

1. Mutter GL, Baak JPA, Crum CP, Richart RM, Ferenczy A, Farquir W. Endometrial precancer diagnosis by histopathology, clonal analysis and computerized morphometry. J. Pathol. 2000; 190; 462–469. 2. Mutter GL, The Endometrial Collaborative Group. Endometrial intraepithelial neoplasia (EIN): will it bring order of chaos? Gynecol. Oncol. 2000; 76; 287–290. 3. Mutter GL. Diagnosis of premalignant endometrial disease. J. Clin. Pathol. 2002; 55; 326–331. 4. Baak JP, Mutter GL. EIN and WHO 94. J. Clin. Pathol. 2005; 58; 1– 6. 5. Mutter GL. PTEN: a protean tumor suppressor. Am. J. Pathol. 2001; 158; 1895–1898. 6. Dunton C, Baak J, Van Diest P, McHugh M, Widra E. Use of computerized morphometric analysis of endometrial hyperplasia in the prediction of coexistent cancer. Am. J. Obstet. Gynecol. 1996; 174; 1518–1521.

A case of the vacuum phenomenon as a mechanism of gas production in the abdominal wall

A 40-year-old man experienced a collision with a car while driving a motorcycle in which the car was in the opposite lane and made a right turn. The patient was thrown approximately 10 m from the point of collision and, as he exhibited a consciousness disturbance, was transferred to our department. He had a score of 13 on the Glasgow Coma Scale with sinus tachycardia on arrival. He showed guarding of the abdomen. A pan scan disclosed traumatic subarachnoid hemorrhage, intraventricular hemorrhage, fractures of the atlas, thoracic spine, sternum and left femur, and gas in the abdomen located just in front of the stomach. As the gas in the abdomen was initially judged to be free air, the patient underwent emergency laparotomy. However, no signs of perforation or injury were detected throughout the entire digestive tract. The accumulation of minute gas (vacuum phenomenon) occurs as traumatic impact. As representative mimics of free air were not observed during surgery in the present case, we believe that the traumatic impact to the patients abdomen as a result of the collision caused the accumulation of gas in the abdominal wall due to vacuum phenomenon. Physicians should be aware of this clinical entity to accurately recognize the mechanism of gas formation in patients showing negative laparotomy findings for gas in the abdomen. This unique case adds additional information regarding the documented etiologies of mimics of pneumoperitoneum.

A simple algorithm for predicting bacteremia using food consumption and shaking chills: a prospective observational study

BACKGROUND: Predicting the presence of true bacteremia based on clinical examination is unreliable. OBJECTIVE: We aimed to construct a simple algorithm for predicting true bacteremia by using food consumption and shaking chills. DESIGN: A prospective multicenter observational study. SETTING: Three hospital centers in a large Japanese city. PARTICIPANTS: In total, 1,943 hospitalized patients aged 14 to 96 years who underwent blood culture acquisitions between April 2013 and August 2014 were enrolled. Patients with anorexia‐inducing conditions were excluded. INTERVENTIONS: We assessed the patients’ oral food intake based on the meal immediately prior to the blood culture with definition as “normal food consumption” when >80% of a meal was consumed and “poor food consumption” when <80% was consumed. We also concurrently evaluated for a history of shaking chills. MEASUREMENTS: We calculated the statistical characteristics of food consumption and shaking chills for the presence of true bacteremia, and subsequently built the algorithm by using recursive partitioning analysis. RESULTS: Among 1,943 patients, 223 cases were true bacteremia. Among patients with normal food consumption, without shaking chills, the incidence of true bacteremia was 2.4% (13/552). Among patients with poor food consumption and shaking chills, the incidence of true bacteremia was 47.7% (51/107). The presence of poor food consumption had a sensitivity of 93.7% (95% confidence interval [CI], 89.4%‐97.9%) for true bacteremia, and the absence of poor food consumption (ie, normal food consumption) had a negative likelihood ratio (LR) of 0.18 (95% CI, 0.17–0.19) for excluding true bacteremia, respectively. Conversely, the presence of the shaking chills had a specificity of 95.1% (95% CI, 90.7%‐99.4%) and a positive LR of 4.78 (95% CI, 4.56–5.00) for true bacteremia. CONCLUSION: A 2‐item screening checklist for food consumption and shaking chills had excellent statistical properties as a brief screening instrument for predicting true bacteremia.

Higher efficacy of direct hemoperfusion using coated activated-charcoal column for disopyramide poisoning: A case report

Rationale: Cases of severe disopyramide poisoning are rare and few have been reported. We report a case in which activated-charcoal column hemoperfusion was dramatically effective for life-threatening disopyramide poisoning. Patient concerns: A teenage girl who had overdosed on disopyramide (total dose, 4950 mg) was brought to our hospital. She was resuscitated from short period cardiopulmonary arrest and subsequently showed severe cardiogenic shock and ventricular arrhythmia. Diagnoses: Disopyramide poisoning (self-evident). Interventions: As hemodynamics remained unstable after providing percutaneous cardiopulmonary support and intra-aortic balloon pumping, we attempted direct hemoperfusion using a coated activated-charcoal hemoperfusion column. Outcomes: Hemodynamics including electrocardiography and serum disopyramide concentration were dramatically improved, and the patient was ambulatory by hospital day 14. Lessons: Because disopyramide has low molecular weight and a small distribution volume, blood purification is considered to be the most effective therapy. We selected direct hemoperfusion for relatively high protein-binding rate. In fact, clinical status was dramatically improved, and the calculated half-life of the direct hemoperfusion phase was the shortest of all phases. In cases of severe or life-threatening disopyramide poisoning, blood purification therapy including direct hemoperfusion using a coated activated-charcoal column should be performed.

A patient with clear consciousness even with a glucose level of 5 mg/dL (0.2 mmol/L) ☆ ☆☆

A 74-year-old man noted dysarthria and right hemiparesis. His history included a gastric ulcer 2 years previously, and he had gradually lost 10 kg over a 2-year period due to appetite loss. He daily consumed 120 mg of alcohol. Upon arrival, he had clear consciousness and stable vital signs. He was malnourished. Neurologic findings included a positive finding of Barre sign in the right hand and dysarthria. A venous blood gas analysis demonstrated the following: pH 7.059; PCO2, 21.5 mm Hg; PO2, 59.1 mm Hg; HCO(3-), 5.8 mmol/L; base excess, -22.7 mmol/L; lactate,17 mmol/L; and glucose, 4 mg/dL. After the administration of an infusion of thiamine and glucose, his abnormal neurologic findings subsided completely. Head magnetic resonance image (MRI; diffusion weighted image) disclosed 3 spotty, high-intensity signals in the brain. The main results of biochemical analyses of the blood collected on arrival were as follows: hemoglobin, 5.5 g/dL; glucose, 5 mg/dL; aspartate aminotransferase, 89 IU/L. He was admitted for further examination and was diagnosed as having alcoholic ketoacidosis with hypoglycemic encephalopathy and anemia due to colon cancer.

The diagnostic efficacy for combination of nurse-assesed food consumptions and shaking chills in predicting bacteremia at the time of blood culture

Characteristics of patients Acknowledgement We thank Dr. H. Honda for discussion, Ms. K. Takigawa for collection of data, and Ms. T. Oguri for providing infectious disease consultation on the pathogenicity of organism. #1. Department of Emergency and Critical Care Medicine, Juntendo University Nerima Hospital, Tokyo, Japan #2. Department of Internal Medicine, Nerima General Hospital, Tokyo, Japan #3. Department of General Medicine, Oizumi Health Cooperative Hospital, Tokyo, Japan #4. Clinical Research Support Center, Juntendo University School of Medicine, Tokyo, Japan #5. Department of General Internal Medicine, Shonan Kamakura Hospital, Kanagawa, Japan #6. Consultant of Sakura Seiki Co Ltd, Japan #7. Department of Internal Medicine, University of California San Francisco, San Francisco, USA #8. Department of Cardiology, Juntendo University Nerima Hospital, Tokyo, Japan The Diagnostic Efficacy for Combination of Nurse-assessed Food Consumptions and Shaking Chills in Predicting Bacteremia at The Time of Blood Culture Takayuki Komatsu, MD, PhD#1, Erika Takahashi, MD#1 Kentaro Mishima, MD#1, Takeo Toyoda, MD, PhD#2 Fumihiro Saitoh, MD#3, Joe Matsuoka, PhD#4 Manabu Sugita, MD, PhD#1 Joel Branch, MD#5, Makoto Aoki, MD#6 Lawrence M Tierney Jr, MD#7 and Kenji Inoue MD, PhD#8