Published papers

Background: Supraphysiologic oxygen administration causes unfavorable clinical outcomes in various diseases, including traumatic brain injury, post–cardiac arrest syndrome, and acute lung injury. Accidental hypothermia is a critical illness that reduces oxygen demands, and excessive oxygen is likely to emerge. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with accidental hypothermia. Methods: A post-hoc analysis of a nationwide multicenter prospective observational study (ICE-CRASH study) on patients with accidental hypothermia admitted in 2019–2022 was conducted. Adult patients without cardiac arrest whose core body temperature was < 32 °C and whose arterial partial pressure of oxygen (PaO2) was measured at the emergency department were included. Hyperoxia was defined as a PaO2 level of 300 mmHg or higher, and 28-day mortality was compared between patients with and without hyperoxia before rewarming. Inverse probability weighting (IPW) analyses with propensity scores were performed to adjust patient demographics, comorbidities, etiology and severity of hypothermia, hemodynamic status and laboratories on arrival, and institution characteristics. Subgroup analyses were conducted according to age, chronic cardiopulmonary diseases, hemodynamic instability, and severity of hypothermia. Results: Of the 338 patients who were eligible for the study, 65 had hyperoxia before rewarming. Patients with hyperoxia had a higher 28-day mortality rate than those without (25 (39.1%) vs. 51 (19.5%); odds ratio (OR) 2.65 (95% confidence interval 1.47–4.78); p < 0.001). IPW analyses with propensity scores revealed similar results (adjusted OR 1.65 (1.14–2.38); p = 0.008). Subgroup analyses showed that hyperoxia was harmful in the elderly and those with cardiopulmonary diseases and severe hypothermia below 28 °C, whereas hyperoxia exposure had no effect on mortality in patients with hemodynamic instability on hospital arrival. Conclusions: Hyperoxia with PaO2 levels of 300 mmHg or higher before initiating rewarming was associated with increased 28-day mortality in patients with accidental hypothermia. The amount of oxygen to administer to patients with accidental hypothermia should be carefully determined. Trial Registration: The ICE-CRASH study was registered at the University Hospital Medical Information Network Clinical Trial Registry on April 1, 2019 (UMIN-CTR ID, UMIN000036132).

INTRODUCTION: Post-contrast acute kidney injury (PC-AKI) is a major complication of contrast media usage; risks for PC-AKI are generally evaluated before computed tomography (CT) with contrast at the emergency department (ED). Although persistent hypotension (systolic blood pressure [sBP] <80 mm Hg for 1 h) is associated with increased PC-AKI incidence, it remains unclear whether transient hypotension that is haemodynamically stabilized before CT is a risk of PC-AKI. We hypothesized that hypotension on ED arrival would be associated with higher PC-AKI incidence even if CT with contrast was performed after patients are appropriately resuscitated. METHODS: This multicentre retrospective observational study was conducted at three tertiary care centres during 2013-2014. We identified 280 patients who underwent CT with contrast at the ED. Patients were classified into two groups based on sBP on arrival (<80 vs. ≥80 mm Hg); hypotension was considered as transient because CT with contrast has always been performed after patients were stabilized at participating hospitals. PC-AKI incidence was compared between the groups; inverse probability weighting (IPW) was conducted to adjust background characteristics. RESULTS: Eighteen patients were excluded due to chronic haemodialysis, cardiac arrest on arrival, or death within 72 h; 262 were eligible for this study. PC-AKI incidence was higher in the transient hypotension group than the normotension group {7/27 (28.6%) vs. 24/235 (10.2%), odds ratio (OR) 3.08 (95% confidence interval [CI] 1.18-8.03), p = 0.026}, which was confirmed by IPW (OR 3.25 [95% CI 1.99-5.29], p < 0.001). CONCLUSION: Transient hypotension at the ED was associated with PC-AKI development.

BACKGROUND: Immediate whole-body CT (about 10 min after arrival) in an all-in-one resuscitation room equipped with CT has been found to be associated with shorter time to haemostasis and lower in-hospital mortality. The aim of this study was to elucidate the benefits of immediate whole-body CT after hospital arrival in patients with severe trauma with the hypothesis that immediate CT within 10 min is associated with lower in-hospital mortality. METHOD: This retrospective cohort study of patients with an injury severity score of more than 15 who underwent whole-body CT was conducted using the Japanese Trauma Databank (2019-2020). An immediate CT was conducted within 10 min after arrival. In-hospital mortality, frequency of subsequent surgery, and time to surgery were compared with immediate and non-immediate CT. Inverse probability weighting was conducted to adjust for patient backgrounds, including mechanism and severity of injury, prehospital treatment, vital signs, and institutional characteristics. RESULTS: Among the 7832 patients included, 646 underwent immediate CT. Immediate CT was associated with lower in-hospital mortality (12.5 versus 15.7 per cent; adjusted OR 0.77 (95 per cent c.i. 0.69 to 0.84); P < 0.001) and fewer damage-control surgeries (OR 0.75 (95 per cent c.i. 0.65 to 0.87)). There was a 10 to 20 min difference in median time to craniotomy, laparotomy, and angiography. These benefits were observed regardless of haemodynamic instability on hospital arrival, while they were identified only in elderly patients with severe injury and altered consciousness. CONCLUSION: Immediate CT within 10 min after arrival was associated with decreased in-hospital mortality in severely injured trauma patients.

Introduction: Open abdomen (OA) is a widely used technique for managing abdominal organ injury, abdominal compartment syndrome, and abdominal sepsis. While various methods have contributed to successful primary closure of the abdominal fascia after OA, some patients still develop enteroatmospheric fistulas that impede abdominal fascia closure. We report a case of successful epithelialization of the incision by sequential partial split-thickness skin grafting (STSG) in a patient who had failure in primary abdominal fascia closure due to enteroatmospheric fistulas after OA for incisional dehiscence and anastomotic leakage. Presentation of case: A 73-year-old male patient underwent pancreaticoduodenectomy for duodenal adenocarcinoma. The abdominal incision was then necrosed and dehisced due to anastomotic leakage on postoperative day (POD) 6, and multiple intra-abdominal lavages with OA were performed. On POD 15, the patient developed enteroatmospheric fistulas; thus, primary fascia closure was considered impossible. On PODs 72 and 106, STSG was conducted on the granulation tissue at the incisional wound, and complete epithelialization was achieved on POD 111. Discussion: Sequential partial STSG only needed basic surgical skills and standard devices for surgery. Conclusion: We reported the case with successful epithelialization of the incision by sequential partial STSG, in which primary abdominal fascia closure was failed due to enteroatmospheric fistulas after OA for incisional dehiscence and anastomotic leakage.

Background: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. Methods: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. Discussion: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. Trial registration: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

BACKGROUND: Supraphysiological oxygen administration causes unfavourable clinical outcomes in various diseases. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with severe infection. METHODS: A post-hoc analysis of a nationwide multicentre prospective observational study on sepsis (SPICE Study) was conducted, including adult patients admitted to the intensive care unit with available arterial partial pressure of oxygen (PaO2) at the treatment initiation for severe infection. Hyperoxia was defined as a PaO2 level of ≥300 mm Hg and in-hospital mortality was compared between patients with and without hyperoxia. RESULTS: Of the 563 patients eligible for the study, 49 had hyperoxia at treatment initiation for severe infection. The in-hospital all-cause mortality rates of patients with and without hyperoxia were 14 (29.2%) and 90 (17.6%), respectively. Inverse probability weighting analyses with propensity scores revealed the association between hyperoxia and increased in-hospital mortality rate (28.8% vs 18.8%; adjusted OR 1.75 (1.03 to 2.97); p=0.038), adjusting for patient demographics, comorbidities, site of infection, severity of infection, haemodynamic and respiratory status, laboratory data and location of patient at infection development. Acute lung injury developed more frequently in patients with hyperoxia on the following days after infection treatment, whereas sepsis-related mortality was comparable regardless of hyperoxia exposure. CONCLUSION: Hyperoxia with PaO2 ≥300 mm Hg at treatment initiation of severe infection was associated with an increased in-hospital mortality rate in patients requiring intensive care. The amount of oxygen to administer to patients with severe infection should be carefully determined. TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry (UMIN000027452).

Purpose: This study aimed to elucidate whether immediate angiography within 30 min is associated with lower in-hospital mortality compared with non-immediate angiography. Materials and Methods: We conducted a retrospective cohort study using a nationwide trauma databank (2019–2020). Adult trauma patients who underwent emergency angiography within 12 h after hospital arrival were included. Patients who underwent surgery before angiography were excluded. Immediate angiography was defined as one performed within 30 min after arrival (door-to-angio time ≤ 30 min). In-hospital mortality and non-operative management (NOM) failure were compared between patients with immediate and non-immediate angiography. Inverse probability weighting with propensity scores was conducted to adjust patient demographics, injury mechanism and severity, vital signs on hospital arrival, and resuscitative procedures. A restricted cubic spline curve was drawn to reveal survival benefits by door-to-angio time. Results: Among 1,455 patients eligible for this study, 92 underwent immediate angiography. Angiography ≤ 30 min was associated with decreased in-hospital mortality (5.0% vs 11.1%; adjusted odds ratio [OR], 0.42 [95% CI, 0.31–0.56]; p < 0.001), as well as lower frequency of NOM failure: thoracotomy and laparotomy after angiography (0.8% vs. 1.8%; OR, 0.44 [0.22–0.89] and 2.6% vs. 6.5%; OR, 0.38 [0.26–0.56], respectively). The spline curve showed a linear association between increasing mortality and prolonged door-to-angio time in the initial 100 min after arrival. Conclusion: In trauma patients, immediate angiography ≤ 30 min was associated with lower in-hospital mortality and fewer NOM failures. Level of Evidence: Level 3b, non randomized controlled cohort/follow up study. Graphical Abstract: (Figure presented.).

BACKGROUND: Primary fascia closure is often difficult following an open abdomen (OA). While negative-pressure wound therapy (NPWT) is recommended to enhance successful primary fascia closure, the optimal methods and degree of negative pressure remain unclear. This study aimed to elucidate optimal methods of NPWT as a tentative abdominal closure for OA to achieve primary abdominal fascia closure. MATERIALS AND METHODS: A multicenter, retrospective, cohort study of adults who survived OA greater than 48 h was conducted in 12 institutions between 2010 and 2022. The achievement of primary fascia closure and incidence of enteroatmospheric fistula were examined based on methods (homemade, superficial NPWT kit, or open-abdomen kit) or degrees of negative pressure (<50, 50-100, or >100 mmHg). A generalized estimating equation was used to adjust for age, BMI, comorbidities, etiology for laparotomy requiring OA, vital signs, transfusion, severity of critical illness, and institutional characteristics. RESULTS: Of the 279 included patients, 252 achieved primary fascia closure. A higher degree of negative pressure (>100 mmHg) was associated with fewer primary fascia closures than less than 50 mmHg [OR, 0.18 (95% CI: 0.50-0.69), P =0.012] and with more frequent enteroatmospheric fistula [OR, 13.83 (95% CI: 2.30-82.93)]. The methods of NPWT were not associated with successful primary fascia closure. However, the use of the open-abdomen kit was related to a lower incidence of enteroatmospheric fistula [OR, 0.02 (95% CI: 0.00-0.50)]. CONCLUSION: High negative pressure (>100 mmHg) should be avoided in NPWT during tentative abdominal closure for OA.

Emergency department thoracotomy (EDT) was incorporated into traumatic out-of-hospital cardiac arrest (t-OHCA) resuscitation. Although current guidelines recommend EDT with survival predictors, futility following EDT has been demonstrated and the potential risks have not been thoroughly investigated. This study aimed to elucidate the benefits and harms of EDT for persistent cardiac arrest following injury until hospital arrival. This retrospective cohort study used a nationwide trauma registry (2019-2021) and included adult patients with t-OHCA both at the scene and on hospital arrival. Survival to discharge, hemostatic procedure frequency, and transfusion amount were compared between patients treated with and without EDT. Inverse probability weighting using a propensity score was conducted to adjust age, sex, comorbidities, mechanism of injury, prehospital resuscitative procedure, prehospital physician presence, presence of signs of life, degree of thoracic injury, transportation time, and institutional characteristics. Among 1289 patients, 374 underwent EDT. The longest transportation time for survivors was 8 and 23 min in patients with and without EDT, respectively. EDT was associated with lower survival to discharge (4/374 [1.1%] vs. 22/915 [2.4%]; adjusted odds ratio [OR], 0.43 [95% CI 0.22-0.84]; p = 0.011), although patients with EDT underwent more frequent hemostatic surgeries (46.0% vs. 5.0%; adjusted OR, 16.39 [95% CI 12.50-21.74]) and received a higher amount of transfusion. Subgroup analyses revealed no association between EDT and lower survival in patients with severe chest injuries (1.0% vs. 1.4%; adjusted OR, 0.72 [95% CI 0.28-1.84]). EDT was associated with lower survival till discharge in trauma patients with persistent cardiac arrests after adjusting for various patient backgrounds, including known indications for EDT. The idea that EDT is the last resort for t-OHCA should be reconsidered and EDT indications need to be deliberately determined.Trial registration This study is retrospectively registered at University Hospital Medical Information Network (UMIN ID: UMIN000050840).

Background: Extracorporeal membrane oxygenation (ECMO) indications in patients with accidental hypothermia (AH) and hemodynamic instability before cardiac arrest (CA) are unclear. We aimed to identify a subgroup of these patients who would benefit from ECMO rewarming. Methods: This study was a post-hoc analysis of the ICE-CRASH study (2019–2022), a prospective, multicenter, observational study throughout Japan. Among the 499 patients (core temperature < 32 °C, age > 18 years), 175 with AH and hemodynamic instability were selected. The primary outcome was 28-day mortality. We examined the effect of ECMO on 28-day mortality after risk stratification based on age, activities of daily living (ADLs), core temperature, Glasgow coma scale (GCS) score, systolic blood pressure (SBP), arrhythmia, pH, and lactate levels. The secondary outcomes were rewarming rate, event-free days (ICU-, ventilator-, and catecholamine-free days), and complications. Results: The patients were divided into ECMO (N = 17) and non-ECMO (N = 158) groups. No significant difference was observed in the 28-day survival rates between the ECMO (13/17, 77%) and non-ECMO (120/158, 76%) groups (p = 0.96). The restricted cubic spline curve showed that the 28-day mortality increased with a GCS score ≤ 8; no relationship was observed between 28-day mortality and decreased SBP or core temperature. No significant difference was observed in the effectiveness of ECMO based on age (< 80 vs. ≥ 80 years), ADLs (independent vs. assistance needed/unknown), core temperature (≥ 26 vs. < 26 °C), GCS (> 8 vs. ≤ 8), SBP (≥ 60 vs. < 60 mmHg), arrhythmia (sinus rhythm vs. arrhythmia), pH (≥ 7.1 vs. < 7.1), and serum lactate level (< 3.0 vs. ≥ 3.0 mmol/L). The rewarming rate was significantly higher in the ECMO group than in the non-ECMO group (2.5 °C/h vs. 1.3 °C/h, p < 0.001), and ICU-, ventilator-, and catecholamine-free days were significantly higher in the non-ECMO group than in the ECMO group. Bleeding complications were significantly more common in the ECMO group than in the non-ECMO group (77% vs. 26%, p < 0.001). Conclusions: We were unable to identify a subgroup of older adult patients with AH and hemodynamic instability who would benefit from ECMO. The ICE-CRASH study was registered with the University Hospital Medical Information Network Clinical Trial Registry on April 1, 2019 (UMIN-CTR ID: UMIN000036132).

The Japan Trauma Data Bank (JTDB) is a nationwide database established by the Quality Assessment Indicators for Clinical Practice Committee of the Japanese Association for Acute Medicine and the Trauma Registry Review Committee of the Japanese Association for the Surgery of Trauma. Over 200 studies utilizing the JTDB have been published, contributing to the improvement of quality for trauma care not only in Japan but also worldwide. The Trauma Registry Review Committee of the Japanese Association for the Surgery of Trauma took the first step in verifying the accuracy of JTDB data by focusing on “definitional variability” in the current version of JTDB's data items. The committee conducted a survey to investigate how each registered item reflects real-world data, aiming to ensure that researchers using JTDB in the future can interpret the data correctly. This process consists of three steps : (1) identifying data items where definitions are expected to vary depending on the registerer, (2) proposing specific possible definitions for the identified data items, and (3) conducting a questionnaire survey of JTDB participating facilities based on the possible definitions. The survey is currently underway.

The Japan Trauma Data Bank (JTDB) is a nationwide trauma registry established primarily by the Committee for Quality Indicators for Emergency Medicine of the Japanese Association for Acute Medicine and the Trauma Registry Committee of the Japanese Association for the Surgery of Trauma. Since the transition to a new data system in 2019, the use of JTDB for research purposes by members of the Japanese Association for the Surgery of Trauma has become increasingly widespread. In this context, the Trauma Registry Committee welcomed new members and launched several projects aimed at further promoting the utilization of JTDB. At the 39th Annual Meeting of the Japanese Association for the Surgery of Trauma, a special session was held to share the progress of these initiatives with the members. This special issue presents an overview of the session and introduces our efforts toward an international trauma registry project, one of the key initiatives currently underway.

Background Enteral nutrition is preferable over parenteral nutrition for critically ill patients, but is often discontinued due to enteral feeding intolerance. Diarrhea is one of the most common causes of the discontinuation of enteral nutrition and may be attributed to the composition of enteral formulas. Dietary fiber attenuates diarrhea by normalizing the intestinal microbiota, providing energy for colonic epithelial cells, and exerting a thickening effect on intestinal contents. We herein conducted a randomized controlled trial (RCT) to test the hypothesis that the administration of an enteral formula containing low-methoxy pectin, a type of dietary fiber, more effectively ameliorates diarrhea in critically ill adult patients than a similar composition without pectin. Methods A protocol for planning a multicenter, parallel-group, open-label RCT is described herein. Enrolled patients are those ≥18 years of age with the indication of enteral nutrition by gastric access. Overall, 200 patients will be randomized into an intervention group administered an enteral formula containing low-methoxy pectin and a control group administered an enteral formula with similar components, but without pectin at a ratio of 1:1. Each enteral formula will be administered for 3 days or longer. There are no restrictions on other treatments. The primary outcome is the incidence of diarrhea as defined by Bristol Scale 5, 6, or 7. Secondary outcomes include the rate of EN failure, the survival rate, the lengths of ICU and hospital stays, and nutritional endpoints. Discussion The present study examines the effects of a low-methoxy pectin-containing enteral formula on enteral feeding intolerance, including diarrhea, in critically ill patients. The results obtained may provide new considerations regarding the selection of enteral formulas for critically ill patients.

While both physician-staffed ground ambulances (GA) and air ambulances (AA) can function as viable transportation options in severe trauma cases, no study has directly compared their efficacies. We aimed to compare the effects of physician-staffed GA and AA on the outcomes of patients with trauma. This retrospective cohort study used records from the Japan Trauma Data Bank collected between April 2004 and December 2021. Data from patients aged ≥ 15 years with an Injury Severity Score > 15, who were directly transferred from the injury scenes, were analyzed. Patients were categorized into two groups based on the transportation method: physician-staffed GA and AA. The primary outcome measure (in-hospital mortality) and secondary outcomes (time to emergency department arrival, time to physician contact and prehospital treatment) were compared between the propensity score-matched groups. Of the 3,508 propensity score-matched pairs, the AA group exhibited significantly lower in-hospital mortality (810 [23.0%]) than the GA group (894 [25.4%]), odds ratio: 0.88 (95% confidence interval [CI] 0.79–0.98). Time to emergency department was significantly longer in the AA group than in the GA group. While patients in the GA group were likely to receive more treatments during transportation, patients in the AA group were likely to receive more surgical interventions after hospital arrival.

Background: Physical impairment has been gaining attention as a fundamental outcome in nutrition therapy for critically ill patients. This review aims to evaluate current evidence and identify knowledge gaps regarding nutrition therapy for physical function and muscle mass, based on 17 systematic reviews developed for the Japanese Critical Care Nutrition Guideline 2024. Methods: Literature searches were performed in MEDLINE, CENTRAL, and ICHUSHI until April 2023, with additional searches up to September 2024. Studies were categorized by nutritional intervention and key findings were summarized. Results: Overfeeding—of both energy and protein—increased adverse outcomes including impaired physical function. Excessive energy restriction also impaired physical outcomes, even during the hyperacute phase. Although adequate energy intake is physiologically necessary during recovery phases, most studies did not report nutritional intake during this period. Protein intake above the standard level helped preserve muscle mass. Nutrition therapy combined with early rehabilitation appears to support physical function. Under the equivalent energy intake, the route and method of administration had minimal impact, but can help ensure adequate delivery. The effects of specific nutrients remain unclear due to limited studies and insufficient or unreported energy intake. Nevertheless, omega-3 fatty acids, beta-hydroxy-beta-methylbutyrate, and synbiotics showed potential benefits. Conclusions: Although overfeeding may be harmful during the hyperacute phase, adequate energy intake, at least in the late period of the acute phase and subsequent phases, could play an important role in supporting the recovery of muscle mass and physical function. This approach may enhance the effectiveness of nutritional interventions in improving physical outcomes.