Clinical significance of cerebrospinal fluid presepsin as adjunctive biomarker for postneurosurgical meningitis: A single-center prospective observational study.

Background: Postneurosurgical meningitis (PNM) is a serious complication in neurocritical care patients, leading to clinical deterioration and worsening outcomes. Accurate diagnosis of PNM is often difficult due to the lack of definitive diagnostic criteria. This study investigates the potential utility of cerebrospinal fluid (CSF) presepsin (PSP), blood PSP, and the CSF/blood PSP ratio as adjunctive biomarkers for the diagnosis of PNM. Methods: We conducted a single-center prospective observational study at Nara Prefecture General Medical Center in Nara, Japan, from April 2020 to March 2022. The postoperative neurosurgical patients with suspected PNM were included in the study and divided into PNM and non-PNM groups. We evaluated the sensitivity, specificity, area under curves (AUCs), positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of PNM with CSF PSP, blood PSP, and CSF/blood PSP ratio compared in the two groups. Results: We screened 241 consecutive patients with postoperative neurosurgery. Diagnosis of PNM was suspected in 27 patients, and the clinical diagnosis was confirmed in nine patients. The results of CSF PSP (cutoff: 736 pg/mL) for the diagnosis of PNM were sensitivity 89%, specificity 78%, PPV 67%, NPV 93%, AUC 0.81 (95% confidence interval [CI], 0.60-1.00), blood PSP (cut-off: 264 pg/mL) was 56%, 78%, 56%, and 78%, 0.65 (95% CI, 0.42-0.88), and those of CSF/blood PSP ratio (cutoff: 3.45) was 89%, 67%, 57%, and 92%, 0.83 (95% CI, 0.65-1.00). Conclusion: Elevated CSF PSP and CSF/blood PSP ratio may be associated with PNM and could serve as valuable adjunctive biomarkers for improving diagnostic accuracy.

"KAIZEN" method realizing implementation of deep-learning models for COVID-19 CT diagnosis in real world hospitals.

Numerous COVID-19 diagnostic imaging Artificial Intelligence (AI) studies exist. However, none of their models were of potential clinical use, primarily owing to methodological defects and the lack of implementation considerations for inference. In this study, all development processes of the deep-learning models are performed based on strict criteria of the "KAIZEN checklist", which is proposed based on previous AI development guidelines to overcome the deficiencies mentioned above. We develop and evaluate two binary-classification deep-learning models to triage COVID-19: a slice model examining a Computed Tomography (CT) slice to find COVID-19 lesions; a series model examining a series of CT images to find an infected patient. We collected 2,400,200 CT slices from twelve emergency centers in Japan. Area Under Curve (AUC) and accuracy were calculated for classification performance. The inference time of the system that includes these two models were measured. For validation data, the slice and series models recognized COVID-19 with AUCs and accuracies of 0.989 and 0.982, 95.9% and 93.0% respectively. For test data, the models' AUCs and accuracies were 0.958 and 0.953, 90.0% and 91.4% respectively. The average inference time per case was 2.83 s. Our deep-learning system realizes accuracy and inference speed high enough for practical use. The systems have already been implemented in four hospitals and eight are under progression. We released an application software and implementation code for free in a highly usable state to allow its use in Japan and globally.

Development of a partnership between academia, community, and government in response to the 2022 mpox outbreak in Japan.

Objectives　In response to the steady rise in the number of cases of mpox in nonendemic countries, starting with an outbreak in the United Kingdom in May 2022, the World Health Organization declared a public health emergency of international concern on July 23, 2022. As of November 13, 2022, seven cases of mpox have been reported in Japan.Methods　A community engagement approach was applied to prevent the spread of mpox in Japan.Results　A tripartite partnership between academia, community, and government (ACG) was established to promote multisectoral communication between vulnerable communities, medical personnel involved in diagnosis and treatment, public health specialists at public health centers, epidemiologists at the National Institute of Infectious Diseases (NIID), and government and public administration. Through information sharing, this ACG partnership can translate accurate information into effective infection control measures.Conclusion　By developing and maintaining the ACG partnership, an environment will be created that allows an immediate response to future public health crises affecting vulnerable communities. This Practice Report describes the process of establishing an ACG partnership.

The Efficacy of Acute Myocardial Infarction Intensive Care Unit Management with a Collaborative Intensivists and Cardiologists in Japan: A Retrospective Observational Study.

Objective Dedicated intensive care unit (ICU) physician staffing is associated with a reduction in ICU mortality rates in general medical and surgical ICUs. However, limited data are available on the role of intensivists in ICU for cardiac disease, especially in Japan. This study investigated the association of collaborative intensivists and cardiologist care with clinical outcomes in patients with acute myocardial infarction (AMI) admitted to the ICU. Methods This study analyzed 106 patients admitted to the ICU at Nara Prefecture General Medical Center in Nara, Japan, from April 2017 to April 2019. Eligible patients were divided into either the high-intensity ICU management group (n=51) or the low-intensity ICU management group (n=55). The primary outcome of in-hospital mortality was compared in the two groups. Results The high-intensity ICU group was found to be associated with a lower mortality rate in a multivariate analysis than the low-intensity group [7.8% vs. 16.4%; odds ratio (OR): 0.07; 95% confidence interval (CI): 0.01-0.54; p=0.01]. There were no significant differences in the length of either the ICU stay or hospital stay or the hospital costs between the two groups. A subgroup analysis revealed that the in-hospital mortality rate was lower in the high-intensity ICU group than in the low-intensity ICU group among patients with Killip class IV (16.7% vs. 34.6%; OR, 0.08; 95% CI, 0.01-0.67; p=0.02). Conclusion The presence of dedicated intensivists in high-intensity ICU collaborating with cardiologists might reduce in-hospital mortality in patients with Killip class IV AMI who require critical care.

[Mitral Valve Repair via Right Thoracotomy Thirty-seven Years after Right Pneumonectomy:Report of a Case].

A 57-year-old man was referred to our hospital due to dyspnea on exertion with severe mitral regurgitation. Because he had underdone right pneumonectomy 37 years earlier due to congenital defect of the right pulmonary artery, his mediastinum was severely shifted to the right, and his pulmonary function was poor. Mitral valve repair was successfully performed with right thoracotomy approach, which made excellent exposure of the mitral valve. The patient was extubated three hours after the surgery. He was discharged on the 30th postoperative day without postoperative respiratory complications. With an appropriate plan of the surgery and postoperative optimal management, cardiac surgery can be performed on patients with a single lung.

Impact of Enteral Nutrition Within 24 Hours Versus Between 24 and 48 Hours in Patients With Severe Acute Pancreatitis: A Multicenter Retrospective Study.

OBJECTIVES: In patients with severe acute pancreatitis (SAP), early enteral nutrition (EN) is recommended by major clinical practice guidelines, but the exact timing for the initiation of EN is unknown. METHODS: We conducted a post hoc analysis of the database for a multicenter (44 institutions) retrospective study of patients with SAP in Japan. The patients were classified into 3 groups according to the timing of EN initiation after the diagnosis of SAP: within 24 hours, between 24 and 48 hours, and more than 48 hours. The primary outcome was in-hospital mortality. RESULTS: Of the 1094 study patients, 176, 120, and 798 patients started EN within 24 hours, between 24 and 48 hours, and more than 48 hours after SAP diagnosis, respectively. On multivariable analysis, hospital mortality was significantly better with EN within 48 hours than with more than 48 hours (adjusted odds ratio, 0.49; 95% confidence interval, 0.29-0.83; P < 0.001) but did not significantly differ between the groups with EN starting within 24 hours and between 24 and 48 hours (P = 0.29). CONCLUSIONS: Enteral nutrition within 24 hours may not confer any additional benefit on clinical outcomes compared with EN between 24 and 48 hours.

Infected thoracoabdominal aortic aneurysm related to an implanted long-term arterial catheter for chemotherapy: a case report.

BACKGROUND: An infected aortic aneurysm is a rare and life-threatening vascular condition with a high incidence of arterial rupture and recurrence even after treatment. One of the most common causes of an infected aortic aneurysm is catheter-related bloodstream infection. Although infection due to indwelling catheters is possible, the incidence of this is rare, especially for long-term implanted arterial catheters. CASE PRESENTATION: A 78-year-old Japanese man with a past medical history of rectal cancer with metastasis to the liver presented to our hospital as a result of low back pain. Remission had been achieved following surgery and adjuvant chemotherapy via an implanted catheter for arterial infusion. However, the original catheter that was inserted from the femoral artery to the hepatic artery via the celiac artery was still present more than 10 years after diagnosis, without being replaced, in case of a recurrence. On the day of admission, computed tomography scan of the chest and abdomen with contrast revealed an irregularly shaped aortic aneurysm at the origin of the celiac artery and a partially expanded common hepatic artery with disproportionate fat stranding along the implanted arterial catheter without extravasation. Although the initial impression was an impending rupture of the acute thoracoabdominal aortic aneurysm, a catheter-related infection was considered as a differential diagnosis. Surgery was performed, which revealed a catheter-related infected aortic aneurysm based on images along the catheter, pus cultures, and tissue pathology examination results. CONCLUSIONS: This is an extremely rare case of an infectious aneurysm caused by prolonged implantation of an arterial catheter for chemotherapy. It should be noted that an indwelling arterial catheter not only causes bloodstream infections but can also cause an infection of a thoracoabdominal aortic aneurysm.

Etiology and mortality in severe acute pancreatitis: A multicenter study in Japan.

BACKGROUND/OBJECTIVES: Severe acute pancreatitis (SAP) has a high mortality rate despite ongoing attempts to improve prognosis through a various therapeutic modalities. This study aimed to delineate etiology-based routes that may guide clinical decisions for the treatment of SAP. METHODS: Using data from a recent retrospective multicenter study in Japan, we analyzed the association between clinical outcomes, mainly in-hospital mortality and pancreatic infection, and various etiologies while considering confounding factors. We performed additional multivariate analyses and built decision tree models. RESULTS: The 1097 participating patients were classified into the following groups by etiology: alcohol (n = 436, 39.7%); cholelithiasis (n = 230, 21.0%); idiopathic (n = 227, 20.7%); and others (n = 204, 18.6%). Mortality at hospital discharge was 8.4%, 12.2%, 16.7%, and 16.2% in the alcohol, cholelithiasis, idiopathic, and others groups, respectively. According to multivariable analysis, early enteral nutrition (EN) was significantly associated with reduced in-hospital mortality only in the cholelithiasis group. However, there was a consistent association between age and the need for mechanical ventilation and increased mortality, regardless of etiology. Our decision tree models presented different contributing factors depending on the etiology and patient background. Interaction analysis showed that EN and the use of prophylactic antibiotics may influence these results differently according to etiology. CONCLUSIONS: No study has yet used comprehensive models to investigate etiology-related prognostic factors for SAP; our results can, therefore, be used as a reference for improving clinical decisions.

Incidence, risk factors, and outcomes for sepsis-associated delirium in patients with mechanical ventilation: A sub-analysis of a multicenter randomized controlled trial.

PURPOSE: This study aimed to investigate incidence, risk factors, and outcomes for sepsis-associated delirium (SAD) in mechanically ventilated patients. MATERIALS AND METHODS: We performed a retrospective post-hoc analysis of the DExmedetomidine for Sepsis in Intensive care unit Randomized Evaluation (DESIRE) trial. Outcomes included 28-day mortality, ventilator-free days, length of ICU stay, self-extubation, and re-intubation. Multivariable analysis was performed to identify variables independently associated with SAD. RESULTS: We retrospectively divided the patients into two groups: delirium group (n = 89) and non-delirium group (n = 98). There were no significant differences between the groups in 28-day mortality, self-extubation, and re-intubation. The number of ventilator-free days was significantly less in the delirium vs. non-delirium group (17 vs. 22 days, p = .006), and the length of ICU stay was significantly longer in the delirium group (10 vs. 5 days, p = .04). Multivariable analyses revealed that emergency surgery, more doses of midazolam, and fentanyl were independent predictors for SAD. CONCLUSIONS: SAD was associated with a less number of ventilator-free days and longer length of ICU stay. Emergency surgery, more doses of midazolam, and fentanyl may be independent risk factors for SAD in mechanically ventilated patients with sepsis.

The Effect of an Invasive Strategy for Treating Pancreatic Necrosis on Mortality: a Retrospective Multicenter Cohort Study.

BACKGROUND: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. METHODS: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. RESULTS: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09-2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40-25.6) were significantly associated with mortality. CONCLUSIONS: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

Impact of Antimicrobial Prophylaxis for Severe Acute Pancreatitis on the Development of Invasive Candidiasis: A Large Retrospective Multicenter Cohort Study.

OBJECTIVE: Antimicrobial prophylaxis is not generally recommended for patients with severe acute pancreatitis (SAP) owing to the limited clinical benefits. Nonetheless, it is frequently administered in actual practice given the patients' critical condition and the lack of solid evidence showing adverse effects of antimicrobial prophylaxis. We evaluated herein an association between antimicrobial prophylaxis and invasive pancreatic candidiasis as an adverse effect in patients with SAP. METHODS: This is a retrospective cohort study of all consecutive patients with SAP who were admitted to the study institutions (n = 44) between January 1, 2009, and December 31, 2013. We performed multivariable logistic regression analysis adjusting for the extent of pancreatic necrosis and surgical interventions for invasive pancreatic candidiasis. RESULTS: Of the 1097 patients with SAP, 850 (77.5%) received antimicrobial prophylaxis, and 21 (1.9%) had invasive pancreatic candidiasis. In multivariable logistic regression analysis, antimicrobial prophylaxis was significantly associated with the development of invasive pancreatic candidiasis (adjusted odds ratio, 4.23; 95% confidence interval, 1.14-27.6) (P = 0.029). CONCLUSIONS: The results suggest that antimicrobial prophylaxis may contribute to the development of invasive pancreatic candidiasis, and therefore, the routine use of antimicrobial prophylaxis for SAP may be discouraged.

Large Volume Fluid Resuscitation for Severe Acute Pancreatitis is Associated With Reduced Mortality: A Multicenter Retrospective Study.

BACKGROUND AND AIMS: Although fluid resuscitation is critical in acute pancreatitis, the optimal fluid volume is unknown. The aim of this study is to evaluate the association between the volume of fluid administered and clinical outcomes in patients with severe acute pancreatitis (SAP). METHODS: We conducted a multicenter retrospective study at 44 institutions in Japan. Inclusion criteria were age 18 years or older, and diagnosed with SAP from 2009 to 2013. Patients were stratified into 2 groups: administered fluid volume <6000 and ≥6000 mL in the first 24 hours. We evaluated the association between the 2 groups and clinical outcomes using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. Secondary outcomes included the incidence of pancreatic infection and the need for surgical intervention. RESULTS: We analyzed 1097 patients, and the mean fluid volume administered was 5618±3018 mL (mean±SD), with 708 and 389 patients stratified into the fluid <6000 mL and fluid ≥6000 mL groups, respectively. Overall in-hospital mortality was 12.3%. The fluid ≥6000 mL group had significantly higher mortality than the fluid <6000 mL group (univariable analysis, 15.9% vs. 10.3%; P<0.05). In multivariable logistic regression analysis, administration of ≥6000 mL of fluid within the first 24 hours was significantly associated with reduced mortality (odds ratio, 0.58; P<0.05). No significant association was found between the administered fluid volume and pancreatic infection, or between the volume administered and the need for surgical intervention. CONCLUSIONS: In patients with SAP, administration of a large fluid volume within the first 24 hours is associated with decreased mortality.

[Surgical Experience of Papillary Fibroelastoma Revealed by Cerebral Infarction].

Primary cardiac tumors are relatively rare. Among them, papillary fibroelastoma (PFE) is the 2nd most common benign cardiac tumor after myxoma. However, despite its benign status, PFE may trigger fatal embolic events in some cases. Therefore, once PFE is diagnosed, immediate surgical resection of the tumor is recommended. We report our experience of 3 patients with cerebral infarction that were diagnosed as having PFE. All cases were complicated with cerebral infarction probably originating from a tumor embolus or thrombus. For that reason, after the tumor had been detected, urgent surgical resection of the tumor was considered to be necessary. Given the generally good postoperative outcomes, simple resection of the tumor while preserving valve function is considered sufficient to achieve a favorable outcome.

Can we predict delayed undesirable events after blunt injury to the torso visceral organs?

Aim: Blunt injuries to visceral organs have the potential to lead to delayed pseudoaneurysm formation or organ rupture, but current trauma and surgical guidelines do not recommend repetitive imaging. This study examined the incidence and timing of delayed undesirable events and established advisable timing for follow-up imaging and appropriate observational admission. Methods: Patients with blunt splenic (S), liver (L), or kidney (K) injury treated with non-operative management (NOM) in our institution were included and retrospectively reviewed. Results: From January 2013 to January 2017, 57 patients were admitted with documented blunt visceral organ injuries and 22 patients were excluded. Of 35 patients (L, 10; S, 17; K, 6; L & S, 1; S & K, 1) treated with NOM, 14 (L, 4; S, 9; K, 1) patients underwent transcatheter arterial embolization. Delayed undesirable events occurred in four patients: three patients with splenic pseudoaneurysm on hospital day 6-7 and one patient with splenic delayed rupture on hospital day 7. The second follow-up computed tomography scan carried out 1-2 days after admission did not show any significant findings that could help predict undesirable results of delayed events. The patients with delayed events had longer continuous abdominal pain than that of event-free patients (P = 0.04). Conclusions: Undesirable delayed events were recognized on follow-up computed tomography scans in 11.4% of NOM patients at hospital day 6-7 and tended to be associated with high-grade splenic injuries and continuous symptoms. Repetitive screening of these patients 6-7 days after injury might be warranted because of the potential risk of delayed events.

Effect of norepinephrine dosage on mortality in patients with septic shock.

BACKGROUND: Use of high-dose norepinephrine is thought to have an immunosuppressive action that increases mortality. This study aimed to evaluate the correlation between norepinephrine dosage and prognosis of patients with septic shock. METHODS: This study was a nested cohort of the DExmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) trial. We evaluated 112 patients with septic shock and an initial Sequential Organ Failure Assessment Cardiovascular (SOFA-C) category score > 2 and initial lactate level > 2 mmol/L. We divided the patients into two groups according to the norepinephrine dosage administered over the initial 7 days: high dose (≥ 416 µg/kg/week) (H group, n = 56) and low dose (< 416 µg/kg/week) (L group, n = 56). The primary outcome of interest was 28-day mortality. Secondary outcomes were ventilator-free days, initial 24-h infusion volume, initial 24- to 48-h infusion volume, and the need for renal replacement therapy. For comparisons between the H group and L group, we used the chi-square test or Fisher's exact test for categorical variables and the t test or Wilcoxon rank sum test for continuous variables. For time-to-event outcomes, Cox proportional hazards models were used. Kaplan-Meier survival curves were created for graphical representation. RESULTS: Patient characteristics appeared to be similar between the two groups except for the SOFA-C score and fibrinogen degradation product level. The cumulative incidence of death at 28 days was 29.9% (16 patients) in the L group and 29.7% (15 patients) in the H group (p = 0.99). The median number of 28-day ventilator-free days was 20 (0, 25) in the L group and 16 (0, 22) in the H group (p < 0.05). Initial infusion volume at 0-24 h in the H group was significantly higher than that in the L group (p = 0.004). Infusion volume at 24-48 h in the H group was also significantly higher than that in the L group (p = 0.03). CONCLUSIONS: No statistically significant difference was observed in 28-day mortality between patients with septic shock treated with high-dose norepinephrine compared with those treated with low-dose norepinephrine. However, the number of ventilator-free days in the L group was higher than that in the H group. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01760967 Date of trial registration: January 4, 2013.

The Prognosis of Severe Acute Pancreatitis Varies According to the Segment Presenting With Low Enhanced Pancreatic Parenchyma on Early Contrast-Enhanced Computed Tomography: A Multicenter Cohort Study.

OBJECTIVE: The aim of this study was to investigate the outcomes of severe acute pancreatitis (SAP) according to the segment presenting with low enhanced pancreatic parenchyma (LEPP) on early contrast-enhanced computed tomography. METHODS: This was a post hoc analysis of a multicenter, retrospective study conducted at 44 institutions in Japan. Patients diagnosed as having SAP according to the Japanese Severity Score between January 2009 and December 2013 were included. We compared the effect of LEPP in each segment on mortality. RESULTS: A total of 1097 patients were assessed. The numbers of patients with LEPP in the pancreatic head (Ph), body (Pb), or tail (Pt) were 272, 273, and 204 (with some overlaps), respectively. In multivariate analysis, LEPP in Ph and Pt was significantly related to mortality (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.11-3.40 [P < 0.05], for LEPP in Ph; OR, 2.44; 95% CI, 1.27-4.67 [P < 0.05], for LEPP in Pt), but LEPP in Pb was unrelated to mortality (OR, 0.70; 95% CI, 0.35-1.37; P = 0.30). CONCLUSIONS: Presence of LEPP in Ph and Pt on early contrast-enhanced computed tomography was independently associated with increased mortality in SAP. These patients require close observation to ensure timely and adequate intervention.

Validation of the efficacy of the prognostic factor score in the Japanese severity criteria for severe acute pancreatitis: A large multicenter study.

BACKGROUND: The Japanese severity criteria for acute pancreatitis (AP), which consist of a prognostic factor score and contrast-enhanced computed tomography grade, have been widely used in Japan. OBJECTIVE: This large multicenter retrospective study was conducted to validate the predictive value of the prognostic factor score for mortality and complications in severe AP patients in comparison to the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. METHODS: Data of 1159 patients diagnosed with severe AP according to the Japanese severity criteria for AP were retrospectively collected in 44 institutions. RESULTS: The area under the curve (AUC) for the receiver-operating characteristic curve of the prognostic factor score for predicting mortality was 0.78 (95% confidence interval (CI), 0.74-0.82), whereas the AUC for the APACHE II score was 0.80 (95% CI, 0.76-0.83), respectively. There were no significant differences in the AUC for predicting mortality between two scoring systems. The AUCs of the prognostic factor scores for predicting the need for mechanical ventilation, the development of pancreatic infection, and severe AP according to the revised Atlanta classification were 0.84 (95% CI, 0.81-0.86), 0.73 (95% CI, 0.69-0.77), and 0.83 (95% CI, 0.81-0.86), respectively, which were significantly greater than the AUCs for the APACHE II score; 0.81 (95% CI, 0.78-0.83) for the need for mechanical ventilation (p = 0.03), 0.68 (95% CI, 0.63-0.72) for the development of pancreatic infection (p = 0.02), and 0.80 (95% CI, 0.77-0.82) for severe AP according to the revised Atlanta classification (p = 0.01). CONCLUSION: The prognostic factor score has an equivalent ability for predicting mortality compared with the APACHE II score. Regarding the ability for predicting the development of severe complications during the clinical course of AP, the prognostic factor score may be superior to the APACHE II score.

Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial.

Importance: Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis. Objectives: To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation. Design, Setting, and Participants: Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours. Interventions: Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam. Main Outcomes and Measures: The co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes. Results: Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively. Conclusions and Relevance: Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further. Trial Registration: clinicaltrials.gov Identifier: NCT01760967.