飯塚 悠祐

OBJECTIVE: Systemic heparinization during cardiopulmonary bypass (CPB) can significantly affect thromboelastography (TEG). This study investigated the feasibility of adding protamine in vitro to allow assessment of coagulation status using the TEG 6s system during CPB. METHODS: In this prospective observational study, 21 patients undergoing elective cardiac valve surgery were evaluated. During CPB, protamine was added in vitro to the heparinized blood of these patients at a concentration of 0.05 mg/mL and analyzed with the TEG 6s (Pre). The TEG parameters were compared to those analyzed after CPB withdrawal and systemic protamine administration (Post). RESULTS: The citrated kaolin maximal amplitude (CK-MA) and the citrated functional fibrinogen maximal amplitude (CFF-MA) exhibited strong correlations between Pre and Post measurements (r = 0.790 and 0.974, respectively, P < 0.001 for both), despite significant mean differences (-2.23 mm for CK-MA and -0.68 mm for CFF-MA). Bland-Altman analysis showed a clinically acceptable agreement between Pre and Post measurement of CK-MA and CFF-MA (the percentage error was 10.6% and 12.2%, respectively). In contrast, the citrated kaolin reaction time (CK-R) showed no significant correlation between Pre and Post measurements (r = 0.328, P = 0.146), with a mean difference of 1.42 min (95% CI: -0.45 to 3.29). CONCLUSIONS: In vitro protamine addition allows assessment of coagulation status during CPB using the TEG 6s system. CK-MA and CFF-MA measured during CPB using this method revealed a strong correlation and agreement with post-CPB measurements, suggesting that our method potentially facilitates early prediction of post-CPB coagulation status and decision-making on transfusion strategies. CLINICAL TRIAL REGISTRATION: The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR, registration number: UMIN000041097, date of registration: July 13, 2020, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000046925 ) before the recruitment of participants.

BACKGROUND: Tracking preload dependency non-invasively to maintain adequate tissue perfusion in the perioperative period can be challenging.The effect of phenylephrine on stroke volume is dependent upon preload. Changes in stroke volume induced by phenylephrine administration can be used to predict preload dependency. The change in the peripheral perfusion index derived from photoplethysmography signals reportedly corresponds with changes in stroke volume in situations such as body position changes in the operating room. Thus, the peripheral perfusion index can be used as a non-invasive potential alternative to stroke volume to predict preload dependency. Herein, we aimed to determine whether changes in perfusion index induced by the administration of phenylephrine could be used to predict preload dependency. METHODS: We conducted a prospective single-centre observational study. The haemodynamic parameters and perfusion index were recorded before and 1 and 2 min after administering 0.1 mg of phenylephrine during post-induction hypotension in patients scheduled to undergo surgery. Preload dependency was defined as a stroke volume variation of ≥ 12% before phenylephrine administration at a mean arterial pressure of < 65 mmHg. Patients were divided into four groups according to total peripheral resistance and preload dependency. RESULTS: Forty-two patients were included in this study. The stroke volume in patients with preload dependency (n = 23) increased after phenylephrine administration. However, phenylephrine administration did not impact the stroke volume in patients without preload dependency (n = 19). The perfusion index decreased regardless of preload dependency. The changes in the perfusion index after phenylephrine administration exhibited low accuracy for predicting preload dependency. Based on subgroup analysis, patients with high total peripheral resistance tended to exhibit increased stroke volume following phenylephrine administration, which was particularly prominent in patients with high total peripheral resistance and preload dependency. CONCLUSION: The findings of the current study revealed that changes in the perfusion index induced by administering 0.1 mg of phenylephrine could not predict preload dependency. This may be attributed to the different phenylephrine-induced stroke volume patterns observed in patients according to the degree of total peripheral resistance and preload dependency. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000049994 on 9/01/2023).

BACKGROUND: It has been 50 years since the pulmonary artery catheter was introduced, but the actual use of pulmonary artery catheters in recent years is unknown. Some randomized controlled trials have reported no causality with mortality, but some observational studies have been published showing an association with mortality for patients with cardiogenic shock, and the association with a pulmonary artery catheter and mortality is unknown. The aim of this study was to investigate the utilization of pulmonary artery catheters (PACs) in the intensive care unit (ICU) and to examine their association with mortality, taking into account differences between hospitals. METHODS: This is a retrospective analysis using the Japanese Intensive care PAtient Database, a multicenter, prospective, observational registry in Japanese ICUs. We included patients aged 16 years or older who were admitted to the ICU for reasons other than procedures. We excluded patients who were discharged within 24 h or had missing values. We compared the prognosis of patients with and without PAC. The primary outcome was hospital mortality. We performed propensity score analysis to adjust for baseline characteristics and hospital characteristics. RESULTS: Among 184,705 patients in this registry from April 2015 to December 2020, 59,922 patients were included in the analysis. Most patients (94.0%) with a PAC in place had cardiovascular disease. There was a wide variation in the frequency of PAC use between hospitals, from 0 to 60.3% (median 14.4%, interquartile range 2.2-28.6%). Hospital mortality was not significantly different between the PAC use group and the non-PAC use group in patients after adjustment for propensity score analysis (3.9% vs 4.3%; difference, - 0.4%; 95% CI - 1.1 to 0.3; p = 0.32). Among patients with cardiac disease, those with post-open-heart surgery and those in shock, hospital mortality was also not significantly different between the two groups (3.4% vs 3.7%, p = 0.45, 1.7% vs 1.7%, p = 0.93, 4.8% vs 4.9%, p = 0.87). CONCLUSIONS: The frequency of PAC use varied among hospitals. PAC use for ICU patients was not associated with lower hospital mortality after adjusting for differences between hospitals.

BACKGROUND: The incidence of delirium is high in older patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB). Intraoperative tissue hypoperfusion and re-reperfusion injury, which generate reactive oxygen species (ROS), are suggested to induce delirium. Ascorbic acid is an excellent antioxidant and may reduce organ damage by inhibiting the production of ROS. This prospective observational study aimed to measure pre- and postoperative plasma ascorbic acid levels and examine their association with delirium. METHODS: Patients older than 70 years of age scheduled for elective cardiovascular surgery using CPB were enrolled. From September 2020 to December 2021, we enrolled 100 patients, and the data of 98 patients were analyzed. RESULTS: In total, 31 patients developed delirium, while 67 did not. Preoperative plasma ascorbic acid levels did not differ between the non-delirium and delirium groups (6.0 ± 2.2 vs. 5.5 ± 2.4 µg/mL, p = 0.3). Postoperative plasma ascorbic acid levels were significantly different between the groups (2.8 [2.3-3.5] vs. 2.3 [1.6-3.3] µg/mL, p = 0.037). CONCLUSIONS: In patients who undergo cardiovascular surgery with CPB, lower postoperative plasma ascorbic acid levels may be associated with the development of delirium.

BACKGROUND: Procedural sedation is increasingly used for elderly patients, but there is no established ideal method for elderly patients who are prone to respiratory and circulatory depression. This study aims to investigate the association of respiratory complications and the combination of ketamine-propofol versus fentanyl-propofol in elderly patients undergoing prostate biopsy requiring deep sedation. METHODS: This was a single-center, retrospective, observational study conducted from April 2020 to March 2021. We included male patients aged 65 years and older scheduled for prostate biopsy under procedural sedation. Ketamine-propofol and fentanyl-propofol were administered at the discretion of the anesthesiologist. The primary outcome was the need for assisted ventilation. The secondary outcome was the duration of oxygen saturation (SpO2) below 90%. RESULTS: We enrolled 120 patients over 65 years, and 92 patients were included in the final analysis. The anesthesiologist administered an initial dose of ketamine and propofol of 1:1 to 1:4 of 1.0 mg kg-1 (interquartile range: 0.98 to 1.17) or administered an initial dose of fentanyl of 0.05 to 0.1 mg and a target-controlled infusion of propofol of 2.8 μg ml-1 (interquartile range: 2.0 to 3.0) followed by additional doses at the discretion of the anesthesiologist. Ketamine-propofol was associated with a reduced need for assisted ventilation and a shorter duration of SpO2 below 90% than propofol-fentanyl (95.7% vs. 4.3%, P < 0.05; 0.64 minutes vs. 0.17 minutes, P = 0.26). CONCLUSIONS: Ketamine-propofol is associated with a significantly reduced need for assisted ventilation compared to propofol-fentanyl during procedural sedation and analgesia for procedures requiring deep sedation for the elderly.

PURPOSE: Retained foreign bodies (RFBs) are a major complication of surgical procedures. However, the efficacy of preventive measures is not well defined. This study investigates the characteristics of potential (near miss) and actual RFBs, and the contributions of routine practice for the prevention of RFB events. METHODS: We conducted a retrospective review of incident reports regarding near-miss and RFB events in patients who underwent surgery under general anesthesia in our institution between October 2008 and November 2018. RESULTS: Among 49,831 operations under general anesthesia, there were 106 (2.13/1000) near-miss events and 24 (0.48/1000) RFB events. Counting surgical materials and intraoperative X-rays detected the remaining items before completion of surgery in 59 (56%) and 15 (14%) cases, respectively. The operator or staff noticed the surgical materials in the remaining 32 (30%) near-miss events. RFBs included 4 sponges (17%), 4 instruments (17%), 4 needles (17%), and 12 miscellaneous items (50%). Of these, 12 (50%) RFBs were discovered on postoperative X-rays and 16 (67%) patients required operative removal. Four incidents (17%) with RFBs were attributable to ignoring count discrepancies during surgery. CONCLUSION: The actual incidence of RFB events is higher than previously reported. A standardized counting protocol, communication among staff, and intra- and postoperative X-rays may contribute to the prevention and detection of RFBs.

BACKGROUND: Capillary refill time (CRT) is the gold standard for evaluating peripheral organ perfusion; however, intraoperative CRT measurement is rarely used because it cannot be conducted continuously, and it is difficult to perform during general anesthesia. The peripheral perfusion index (PI) is another noninvasive method for evaluating peripheral perfusion. The PI can easily and continuously evaluate peripheral perfusion and could be an alternative to CRT for use during general anesthesia. This study aimed to determine the cutoff PI value for low peripheral perfusion status (prolonged CRT) by exploring the relationship between CRT and the PI during general anesthesia. METHODS: We enrolled 127 surgical patients. CRT and the PI were measured in a hemodynamically stable state during general anesthesia. A CRT >3 s indicated a low perfusion status. RESULTS: Prolonged CRT was observed in 27 patients. The median PI values in the non-prolonged and prolonged CRT groups were 5.0 (3.3-7.9) and 1.5 (1.2-1.9), respectively. There was a strong negative correlation between the PI and CRT (r = -0.706). The area under the receiver operating characteristic curve generated for the PI was 0.989 (95% confidence interval, 0.976-1.0). The cutoff PI value for detecting a prolonged CRT was 1.8. CONCLUSION: A PI <1.8 could accurately predict a low perfusion status during general anesthesia in the operating room. A PI <1.8 could be used to alert the possibility of a low perfusion status in the operating room. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000043707; retrospectively registered on March 22, 2021, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno = R000049905).

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D), we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D), we suggest against routinely implementing NO inhalation therapy (GRADE 2C), and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jsicm.org/publication/guideline.html ). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

BACKGROUND: The joint committee of the Japanese Society of Intensive Care Medicine/Japanese Respiratory Society/Japanese Society of Respiratory Care Medicine on ARDS Clinical Practice Guideline has created and released the ARDS Clinical Practice Guideline 2021. METHODS: The 2016 edition of the Clinical Practice Guideline covered clinical questions (CQs) that targeted only adults, but the present guideline includes 15 CQs for children in addition to 46 CQs for adults. As with the previous edition, we used a systematic review method with the Grading of Recommendations Assessment Development and Evaluation (GRADE) system as well as a degree of recommendation determination method. We also conducted systematic reviews that used meta-analyses of diagnostic accuracy and network meta-analyses as a new method. RESULTS: Recommendations for adult patients with ARDS are described: we suggest against using serum C-reactive protein and procalcitonin levels to identify bacterial pneumonia as the underlying disease (GRADE 2D); we recommend limiting tidal volume to 4-8 mL/kg for mechanical ventilation (GRADE 1D); we recommend against managements targeting an excessively low SpO2 (PaO2) (GRADE 2D); we suggest against using transpulmonary pressure as a routine basis in positive end-expiratory pressure settings (GRADE 2B); we suggest implementing extracorporeal membrane oxygenation for those with severe ARDS (GRADE 2B); we suggest against using high-dose steroids (GRADE 2C); and we recommend using low-dose steroids (GRADE 1B). The recommendations for pediatric patients with ARDS are as follows: we suggest against using non-invasive respiratory support (non-invasive positive pressure ventilation/high-flow nasal cannula oxygen therapy) (GRADE 2D); we suggest placing pediatric patients with moderate ARDS in the prone position (GRADE 2D); we suggest against routinely implementing NO inhalation therapy (GRADE 2C); and we suggest against implementing daily sedation interruption for pediatric patients with respiratory failure (GRADE 2D). CONCLUSIONS: This article is a translated summary of the full version of the ARDS Clinical Practice Guideline 2021 published in Japanese (URL: https://www.jrs.or.jp/publication/jrs_guidelines/). The original text, which was written for Japanese healthcare professionals, may include different perspectives from healthcare professionals of other countries.

After publication of the original article, the authors selfverified their study protocol and determined that their clinical trial was registered after the study was initiated. Therefore the authors would like to clarify that the registration in the University hospital Medical Information Network (UMIN000040159) was retrospective.

Introduction: The end-expiratory occlusion test (EEOT) may predict the response to fluid administration in patients undergoing lung-protective ventilation, but arterial catheter insertion is necessary to evaluate changes in stroke volume (SV). The peripheral perfusion index is a potential noninvasive alternative to evaluate SV. The aim of this study is to investigate whether changes in perfusion index during an intraoperative EEOT can predict the response to fluid administration in patients undergoing lung-protective ventilation (tidal volume 7 ml/kg predicted body weight). Methods: Forty-one elective surgical patients were enrolled. The SV and perfusion index were recorded before (baseline), during a 40-s EEOT and after volume expansion (250 ml of lactated Ringer’s solution over 10 min). Patients with an increase in SV greater than 10% after volume expansion were defined as responders. ΔPI (change in perfusion index between baseline and 20 (ΔPI20) or 40 s (ΔPI40) after the beginning of EEOT were calculated using: ΔPI20 (%) = [(PI at 20 s after EEOT beginning − PIbaseline)/PIbaseline] × 100, ΔPI40 (%) = [(PI at 40 s after EEO beginning − PIbaseline)/PIbaseline] × 100). Results: Sixteen patients were responders, and 25 were non-responders. The area under the receiver operating characteristics curves generated for ΔPI20 and ΔPI40 to predict response to a fluid challenge were 0.561 (95% CI 0.374–0.749) and 0.688 (95% CI 0.523–0.852), respectively. Conclusion: Changes in perfusion index during intraoperative EEOT in patients undergoing lung-protective ventilation (7 ml/kg) were unable to predict the response to fluid administration.

INTRODUCTION: The end-expiratory occlusion test (EEOT) may predict the response to fluid administration in patients undergoing lung-protective ventilation, but arterial catheter insertion is necessary to evaluate changes in stroke volume (SV). The peripheral perfusion index is a potential noninvasive alternative to evaluate SV. The aim of this study is to investigate whether changes in perfusion index during an intraoperative EEOT can predict the response to fluid administration in patients undergoing lung-protective ventilation (tidal volume 7 ml/kg predicted body weight). METHODS: Forty-one elective surgical patients were enrolled. The SV and perfusion index were recorded before (baseline), during a 40-s EEOT and after volume expansion (250 ml of lactated Ringer's solution over 10 min). Patients with an increase in SV greater than 10% after volume expansion were defined as responders. ΔPI (change in perfusion index between baseline and 20 (ΔPI20) or 40 s (ΔPI40) after the beginning of EEOT were calculated using: ΔPI20 (%) = [(PI at 20 s after EEOT beginning - PIbaseline)/PIbaseline] × 100, ΔPI40 (%) = [(PI at 40 s after EEO beginning - PIbaseline)/PIbaseline] × 100). RESULTS: Sixteen patients were responders, and 25 were non-responders. The area under the receiver operating characteristics curves generated for ΔPI20 and ΔPI40 to predict response to a fluid challenge were 0.561 (95% CI 0.374-0.749) and 0.688 (95% CI 0.523-0.852), respectively. CONCLUSION: Changes in perfusion index during intraoperative EEOT in patients undergoing lung-protective ventilation (7 ml/kg) were unable to predict the response to fluid administration.

To assess the general Japanese population's thoughts on coronavirus disease of 2019 related discrimination by Tweets.Tweets were retrieved from search queries using the keywords "health care providers and discrimination (no hashtags)" and "corona and rural area (no hashtags)" via the Twitter application programming interface. Subsequently, a text-mining analysis was conducted on tokenized text data. R version 4.0.2 was used for the analysis.In total, 51,906 tweets for "corona and health care providers", 59,560 tweets for "corona and rural" were obtained between the search period of July 29, 2020 and September 30, 2020. The most common 20 words from the tokenized text data were translated to English. Word clouds with the original Japanese words are presented.Tweets for corona and health care providers did not suggest significant evidence of discrimination toward health care providers on Twitter. Results for corona and rural area, however, showed the unexpected word "murahachibu" (an outmoded word meaning ostracism), suggesting persistent strong social pressure to prevent bringing the disease to the community. This kind of pressure may not be supported by scientific facts. These results demonstrate the need for continued educational efforts to disseminate factual information to the public.

PURPOSE: Thoracentesis and chest tube insertion are procedures commonly performed in routine clinical practice and are considered mandatory skills for all physicians. Adverse events secondary to these procedures have been widely reported; however, epidemiology data concerning life-threatening events associated with these procedures are lacking. METHODS: We retrospectively analyzed data from the Japan Council for Quality Health Care open database regarding subject safety incidents involving thoracentesis and chest tube insertion. The adverse events extracted from the database included only events associated with thoracentesis and chest tube insertion reported between January 2010 and April 2020. RESULTS: We identified 137 adverse events due to thoracentesis or chest tube insertion. Our analysis also revealed at least 15 fatal adverse events and 17 cases of left/right misalignment. Not only resident doctors but also physicians with 10 years or more of clinical experience had been mentioned in these reports. The most common complications due to adverse events were lung injury (55%), thoracic vascular injury (21%), and liver injury (10%). Surgical treatment was required for 43 (31%) of the 137 cases, and the mortality risk was significantly higher for thoracic vascular injury than for other complications (p = 0.02). CONCLUSION: We identified at least 15 fatal adverse events and 17 cases of left/right misalignment over a 10-year period in the Japan Council for Quality Health Care open database. Our findings also suggest that care should be taken to avoid thoracic vascular injury during chest tube insertion and that immediate intervention is required should such an injury occur.

Background: The aim of this study was to evaluate the utility of collapsibility of the internal jugular veins (IJVs) and subclavian veins (SCVs) in comparison with collapsibility of the inferior vena cava (IVC) in patients receiving pressure support ventilation. Methods: Patients receiving pressure support ventilation were prospectively enrolled when fluid bolus administration was clinically indicated. The antero-posterior diameters of IJVs, SCVs and IVC were measured. Fluid responsiveness was defined as an 8% increase in stroke volume calculated with arterial pulse contour analysis after a passive leg raising maneuver. Results: Twenty-seven patients (34 measurements) were included. Eighteen measurements were deemed fluid responsive. The area under the receiver operating characteristic curve of collapsibility of the right IJV antero-posterior diameter was 0.88 (95% confidence interval (CI): 0.75 - 0.99), while the area under the ROC curves for the antero-posterior diameter of the left IJV, right SCV, left SCV and the IVC were 0.57 (95% CI: 0.37 - 0.77), 0.61 (95% CI: 0.41 - 0.80), 0.55 (95% CI: 0.35 - 0.76) and 0.57 (95% CI: 0.37 - 0.77), respectively. Conclusions: These results suggest that collapsibility of the right IJV is a useful predictor of fluid responsiveness in patients receiving pressure support ventilation. Collapsibility of the IVC did not predict fluid responsiveness in these patients.

Background: Considering the adverse effects of sleep disturbance in critical care settings, accurate assessment could aid therapy; however, methodological inadequacies mean that no viable option is currently available. Research in healthy population has recently shown that a non-wearable sleep measurement device placed under the mattress of the bed could be beneficial in intensive care settings. Therefore, we aimed to validate this device compared with polysomnography (PSG) and to assess how it related to subjective sleep evaluations. Methods: This observational study measured the sleep of critically ill adult patients. The primary goal was to validate the Nemuri SCAN (NSCAN; Paramount Bed Co., Ltd., Tokyo, Japan) against the reference standard PSG for 24 h. The secondary goal was to evaluate the association between the objective parameters obtained from NSCAN and PSG and the subjective report data obtained using the Richards-Campbell Sleep Questionnaire (RCSQ) for the nighttime. Results: Eleven participants were evaluated. The median of the total sleep time scored by PSG was 456.0 (353.0-517.5) min during the nighttime and 305.0 (186.2-542.5) min during the daytime. PSG over 24 h revealed significant decreases in restorative sleep, with excessive daytime sleep, but with a normal quantity of nighttime sleep. The agreement, sensitivity, and specificity rates (with 95% confidence intervals) for the NSCAN compared with PSG were 68.4% (67.9-69.0%), 90.1% (89.7-90.6%), and 38.7% (37.9-39.7%), respectively. The median RCSQ value when subjectively evaluating nighttime sleep was 68.0 (26.3-83.5); this showed no correlation with the NSCAN sleep parameters, despite a positive correlation with the ratio of the stage N2 isolated or combined with restorative sleep in the PSG assessment. Conclusions: NSCAN had moderate agreement, high sensitivity, and poor specificity in intensive care settings, which is most likely due to its inability to identify immobile wakefulness often observed in critically ill patients or sleep depth. This remains a barrier to its use in the assessment of subjective sleep quality. Trial registration: This investigation was part of an interventional trial registered with the University Hospital Medical Information Network Individual Clinical Trials Registry (UMIN000026350, http://www.umin.ac.jp/icdr/index-j.html) on March 1, 2017.

PURPOSE: We investigated the epidemiology and outcome of disseminated intravascular coagulation (DIC) in patients with sepsis. MATERIALS AND METHODS: We analyzed data from a multicenter observational study (Japan Septic Disseminated Intravascular Coagulation [JSEPTIC-DIC] study) conducted in 42 intensive care units in Japan. DIC scores were calculated using two scoring systems: the International Society on Thrombosis and Haemostasis (ISTH) and Japanese Association for Acute Medicine (JAAM) criteria. We compared demographics and clinical characteristics of patients with and without DIC, and performed multivariable logistic regression analyses to assess the association of diagnosis and scores for DIC with in-hospital mortality. RESULTS: Of 1895 eligible patients, 1162 (61%) and 554 patients (29%) were diagnosed as having DIC by the JAAM and ISTH criteria, respectively. Patients with DIC had higher in-hospital mortality compared with those without DIC (33% vs. 20% in JAAM and 38% vs. 24% in ISTH). However, in multivariable analysis, the JAAM score (odds ratio 1.026, 95% confidence interval 0.958-1.097; p = 0.465) and the ISTH score (odds ratio 1.049, 95% confidence interval 0.969-1.135; p = 0.238) did not have an independent association with in-hospital mortality. CONCLUSIONS: Patients with sepsis and DIC have high mortality. However, the DIC are not independently associated with in-hospital mortality.

We examined the institutional variations in anticoagulation therapy for sepsis-induced disseminated intravascular coagulation (DIC) and their effects on patient outcomes. This post hoc analysis of a cohort study included 3195 patients with severe sepsis across 42 intensive care units. To evaluate differences in the intensity of anticoagulation therapy, the proportion of patients receiving anticoagulation therapy and the total number of patients with sepsis-induced DIC were compared. Predicted in-hospital mortality for each patient was calculated using logistic regression analysis. To evaluate survival outcomes, the actual/mean predicted in-hospital mortality ratio in each institution was calculated. Thirty-eight institutions with 2897 patients were included. Twenty-five institutions treated 60% to 100% (high-intensity institutions), while the rest treated 0% to 50% (low-intensity institutions) of patients with sepsis-induced DIC having anticoagulant therapy. Every 10-unit increase in the intensity of anticoagulant therapy was associated with lower in-hospital mortality (odds ratio: 0.904). A higher number of high-intensity institutions (compared to low-intensity institutions) had lower in-hospital mortality and fewer bleeding events than predicted. In conclusion, institutional variations existed in the use of anticoagulation therapy in patients with sepsis-induced DIC. High-intensity anticoagulation therapy was associated with better outcomes.

Sepsis is a syndrome with physiologic, pathologic, and biochemical abnormalities induced by infection. Sepsis can induce the dysregulation of systemic coagulation and fibrinolytic systems, resulting in disseminated intravascular coagulation (DIC), which is associated with a high mortality rate. Although there is no international consensus on available treatments for sepsis-induced DIC, DIC diagnosis and treatment are commonly performed in Japanese clinical settings. Therefore, clinical data related to sepsis-induced DIC diagnosis and treatment can be obtained from Japanese clinical settings. We performed a retrospective nationwide observational study (Japan Septic Disseminated Intravascular Coagulation [J-SEPTIC DIC] study) to collect data regarding characteristics of sepsis patients in Japan, with a focus on coagulofibrinolytic dysregulation and DIC treatment received by each patient. The J-SEPTIC DIC study collected information for a total of 3,195 patients with severe sepsis and septic shock and is the largest data set in Japan on DIC diagnosis and treatment in clinical settings.

BACKGROUND: Benzodiazepine use is a risk factor for the development of delirium in adult intensive care unit (ICU) patients. Suvorexant is an alternative to benzodiazepines to induce sleep, but the incidence of delirium in critically ill patients is unknown. We undertook this retrospective study to investigate the incidence of delirium in patients who receive suvorexant in the ICU. METHODS: This retrospective cohort study was conducted in a closed 12-bed ICU at a tertiary teaching hospital. Patients admitted to the ICU for 72 h or longer between January and June 2015 were evaluated for delirium using the Confusion Assessment Method for the Intensive Care Unit tool. We evaluated the incidence of delirium in patients who received suvorexant and those who did not. To adjust for confounding factors, multivariable logistic regression analysis was conducted. RESULTS: Study subjects included 118 patients, with a median age of 72 years and a median Acute Physiology and Chronic Health Evaluation II score of 18 points. Eighty-two patients (69.5%) were admitted after cardiovascular surgery. In the suvorexant group, there were fewer post-cardiovascular surgical patients and more medical patients. The duration of mechanical ventilation during ICU stay was longer in the suvorexant group, and sedatives and sleep inducers other than suvorexant were used more frequently in the suvorexant group. The incidence of delirium was 43.8% in the suvorexant group and 58.8% in the non-suvorexant group (P = 0.149). After adjustment for risk factors using multivariable logistic regression analysis, suvorexant was associated with a lower incidence of delirium (odds ratio = 0.23, 95% confidence interval: 0.07-0.73; P = 0.012). CONCLUSIONS: Suvorexant was associated with decreased odds of transitioning to delirium in critically ill patients. The use of suvorexant may lower the incidence of delirium in ICU patients. Future prospective studies are warranted.

Purpose: The lack of recognition of respiratory distress may result in emergency tracheal intubation in the general ward. However, few studies have examined the differences in the frequency of vital sign measurement between patients with and without emergency tracheal intubation in the general ward. Thus, this study aimed to investigate the differences in the frequency of vital sign measurements between patients with and without emergency tracheal intubation. Patients and methods: This is a single-center, retrospective, observational study of unplanned intensive care unit (ICU) admissions from the general wards between December 2015 and February 2017. This study included patients with emergency medical intubations in the general ward who were then transferred to the ICU. Vital signs measured within 24 hours prior to ICU admission were compared between patients who did and did not require emergency tracheal intubation in the general ward. A survey was also conducted to explore the nurses' attitudes toward vital sign measurements. Results: Compared with other vital signs, the respiratory rate was significantly less frequently measured. Moreover, the frequency of respiratory rate measurement was lower in the 38 patients who were intubated than in the 102 patients who were not intubated in the general ward (P=0.07). The survey revealed that 54% of the participating nurses considered assessment of the respiratory rate as the most troublesome nursing task and ~15% of nurses did not routinely measure respiratory rates. Conclusion: Respiratory rate was less frequently assessed in deteriorating patients in the general ward, possibly because it was considered a troublesome task.

Background: The Japanese Society of Respiratory Care Medicine and the Japanese Society of Intensive Care Medicine provide here a clinical practice guideline for the management of adult patients with ARDS in the ICU. Method: The guideline was developed applying the GRADE system for performing robust systematic reviews with plausible recommendations. The guideline consists of 13 clinical questions mainly regarding ventilator settings and drug therapies (the last question includes 11 medications that are not approved for clinical use in Japan). Results: The recommendations for adult patients with ARDS include: we suggest against early tracheostomy (GRADE 2C), we suggest using NPPV for early respiratory management (GRADE 2C), we recommend the use of low tidal volumes at 6-8 mL/kg (GRADE 1B), we suggest setting the plateau pressure at 30cmH20 or less (GRADE2B), we suggest using PEEP within the range of plateau pressures less than or equal to 30cmH2O, without compromising hemodynamics (Grade 2B), and using higher PEEP levels in patients with moderate to severe ARDS (Grade 2B), we suggest using protocolized methods for liberation from mechanical ventilation (Grade 2D), we suggest prone positioning especially in patients with moderate to severe respiratory dysfunction (GRADE 2C), we suggest against the use of high frequency oscillation (GRADE 2C), we suggest the use of neuromuscular blocking agents in patients requiring mechanical ventilation under certain circumstances (GRADE 2B), we suggest fluid restriction in the management of ARDS (GRADE 2A), we do not suggest the use of neutrophil elastase inhibitors (GRADE 2D), we suggest the administration of steroids, equivalent to methylprednisolone 1-2mg/kg/ day (GRADE 2A), and we do not recommend other medications for the treatment of adult patients with ARDS (GRADE1B; inhaled/intravenous β2 stimulants, prostaglandin E1, activated protein C, ketoconazole, and lisofylline, GRADE 1C; inhaled nitric oxide, GRADE 1D; surfactant, GRADE 2B; granulocyte macrophage colony-stimulating factor, N-acetylcysteine, GRADE 2C; Statin.) Conclusions: This article was translated from the Japanese version originally published as the ARDS clinical practice guidelines 2016 by the committee of ARDS clinical practice guideline (Tokyo, 2016, 293p, available from http://www.jsicm.org/ARDSGL/ARDSGL2016.pdf ). The original article, written for Japanese healthcare providers, provides points of view that are different from those in other countries.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

日本集中治療医学会/日本呼吸療法医学会ARDS診療ガイドライン作成委員会は、今回、日本呼吸器学会ARDS診療ガイドライン作成委員会と合同で「ARDS診療ガイドライン2016」を作成し公開した。今回は13の診療疑問(clinical question)について、国内でもまだ取りあげられることの少ないGRADE(Grading of Recommendations Assessment、Development and Evaluation)systemを用いたシステマティックレビューとその推奨度決定の手法を取り入れた。これにより、従来に比して信頼性の高い診療ガイドラインを作成することができた。(著者抄録)

INTRODUCTION: Nonocclusive mesenteric ischemia (NOMI) after surgery has an extremely poor prognosis with a mortality rate of 30-100%. We report a patient with NOMI following aortic valve replacement who failed to improve despite continuous intra-arterial infusion of papaverine, but was successfully treated with alprostadil (prostaglandin E1 [PGE1]) infusion. PRESENTATION OF CASE: The patient is a 77-year-old man who underwent aortic valve replacement. Due to elevated serum lactate levels five hours after intensive care unit admission, superior mesenteric arteriography was performed, establishing the diagnosis of NOMI. Although continuous intra-arterial infusion of papaverine was begun, lactate levels remained elevated. Repeat angiography and laparotomy revealed extensive ischemic changes of the intestine. The vasodilator was changed to PGE1, which improved arterial spasm. The patient ultimately needed an ileocecal resection, but the extent of the resection was limited with concomitant PGE1 administration. DISCUSSION: In the present patient, although NOMI was unresponsive to appropriate treatment including intra-arterial infusion of papaverine, continuous intra-arterial infusion of PGE1 salvaged most of the intestine. CONCLUSIONS: In a patient with recurrent NOMI despite appropriate treatment including intra-arterial infusion of papaverine, continuous intra-arterial infusion of PGE1 may limit the extent of intestinal resection needed. Continuous intra-arterial infusion of PGE1 may be a useful treatment for patients with refractory NOMI.

BACKGROUND: Interruption of enteral nutrition (EN) in the intensive care unit (ICU) occurs frequently for various reasons including feeding intolerance and the conduct of diagnostic and therapeutic procedures. However, few studies have investigated the details of EN interruption practices including reasons for and duration of interruptions. There is no standard protocol to minimize EN interruptions. METHODS: This is a retrospective review of 100 patients in the ICU staying more than 72 h and receiving EN in a 12-bed, medical/surgical ICU in a tertiary care center in 2013. Data collected include total time designated for EN; the number of EN interruption episodes; reason for each interruption categorized as diagnostic study, therapeutic intervention, or gastrointestinal (GI) event, and their individual subcategories; duration of each interruption; and the presence of written orders for interruptions. RESULTS: One hundred patients staying in the ICU for at least 72 h and receiving EN were included. There were 567 episodes of EN interruption over a median ICU length of stay of 17.1 (interquartile range 8.0-22.0) days. There were a median of three EN interruption episodes per patient. EN interruption was performed for undetermined reasons (166 episodes, 29%), airway manipulation (103 episodes, 18%), GI events (78 episodes, 14%), and intermittent dialysis (71 episodes, 13%). Median duration of EN interruption in all patients was 5.5 (3.0-10.0) h. The cumulative interruption time corresponds to 19% of the total time designated for EN. Duration of EN interruption varied according to reason, including airway manipulation (9.0 [5.0-21.0] h), tracheostomy (9.5 [7.5-14.0] h), and GI events (6.5 [3.0-14.0] h). The average calorie deficits due to interruptions were 11.5% of daily target calories. Only 60 episodes (12%) had clear written orders for interruption. CONCLUSIONS: Based on this single-center retrospective chart review, interruption of EN in the ICU is frequent, reasons for and duration of interruption varied, and airway procedures are associated with a relatively longer duration of interruption. Documentation and orders were frequently missing. These results warrant development of a protocol for EN interruption.

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

日本呼吸療法医学会/日本集中治療医学会ARDS診療ガイドライン作成委員会は、日本呼吸器学会(JRS)ARDS診療ガイドライン作成委員会と合同で「ARDS診療ガイドライン2016」を作成し公開した。今回は13の診療疑問(clinical question:CQ)について、国内でもまだ取り上げられることの少ないGRADE(Grading of Recommendations Assessment、Development and Evaluation)systemを用いたシステマティックレビューとその推奨度決定の手法を取り入れた。これにより従来に比して信頼性の高い診療ガイドラインを作成することができた。(著者抄録)

Recombinant human soluble thrombomodulin (rhTM) is a novel class of anticoagulants for treating disseminated intravascular coagulation (DIC). Although rhTM is widely used in clinical settings throughout Japan, there is limited clinical evidence supporting the use of rhTM in patients with sepsis-induced DIC. Furthermore, rhTM is not approved for DIC treatment in other countries. This study aimed to clarify the survival benefits of rhTM administration in critically ill patients. Data from 3,195 consecutive adult patients who were admitted to 42 intensive care units for the treatment of severe sepsis or septic shock between January 2011 and December 2013 were retrospectively analysed, and 1,784 patients were diagnosed with DIC based on the scoring algorithm from the Japanese Association for Acute Medicine DIC (n = 645, rhTM group; n = 1,139, control group). Propensity score matching created 452 matched pairs, and logistic regression analysis revealed a significant association between rhTM administration and lower in-hospital all-cause mortality in the propensity score-matched groups (odds ratio, 0.757; 95 % confidence interval, 0.574-0.999, p = 0.049). Inverse probability of treatment weighted and quintile-stratified analyses also revealed significant associations between rhTM administration and lower in-hospital all-cause mortality. Survival time in the propensity score-matched rhTM group was significantly longer than that in the propensity score-matched control group (hazard ratio, 0.781; 95 % confidence interval, 0.624-0.977, p = 0.03). Bleeding complications were not more frequent in the rhTM groups. In conclusion, this study demonstrated that rhTM administration is associated with reduced in-hospital all-cause mortality among patients with sepsis-induced DIC.

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.

A 69-year-old woman underwent thoraco-abdominal aortic aneurysm repair with cerebrospinal fluid drainage (CSFD). The initial CSF pressure was elevated to approximately 25 cmH(2)O, and clear CSF was continuously drained at a rate of 30 ml/h with the drainage level at 10-20 cmH(2)O. The CSF became bloody when cardiopulmonary bypass was terminated. The total volume of CSF drained was approximately 300 ml at the conclusion of the 638 min operation. Three hours later, she suffered a series of generalized seizures because of intracranial hemorrhage (ICH). It was suggested that excessive drainage of CSF was associated with ICH. Meticulous control of drainage volume combined with standard pressure-based management may be the key to avoiding these complications.

We reported a 72-year-old woman who had a massive hemoptysis due to traction bronchiectasis in the left upper lobe. The patient underwent left radical mastectomy followed by thoracic radiotherapy for left breast cancer. The chest computed tomography showed traction bronchiectasis in the atrophic left upper lobe and the bronchial angiography showed hypervascularization of bronchial and internal thoracic arteries to the left upper lobe. Left upper lobectomy was performed after bronchial embolization for recurrent massive hemoptysis. Postoperative course was uneventful. Pathologic findings showed non-anatomical but clearly-bordered traction bronchiectasis with hypervascularized bronchial artery in the left upper lobe. These lesions were consistent with the field of the previous radiotherapy. Traction bronchiectasis causing massive hemoptysis should be considered as one of pulmonary sequelae after thoracic radiotherapy.