Ultrasound guidance for urgent arterial and venous catheterisation: randomised controlled study.

BACKGROUND: Haemodynamically unstable patients often require arterial and venous catheter insertion urgently. We hypothesised that ultrasound-guided arterial and venous catheterisation would reduce mechanical complications. METHODS: We performed a prospective RCT, where patients requiring both urgent arterial and venous femoral catheterisation were randomised to either ultrasound-guided or landmark-guided catheterisation. Complications and characteristics of catheter insertion (procedure duration, number of punctures, and procedure success) were recorded at the time of insertion (immediate complications). Late complications were investigated by ultrasound examination performed between the third and seventh days after randomisation. Primary outcome was the proportion of patients with at least one mechanical complication (immediate or late), by intention-to-treat analysis. Secondary outcomes included success rate, procedure time, and number of punctures. RESULTS: We analysed 136 subjects (102 [75%] male; age range: 27-62 yr) by intention to treat. The proportion of subjects with one or more complications was lower in 22/67 (33%) subjects undergoing ultrasound-guided catheterisation compared with landmark-guided catheterisation (40/69 [58%]; odds ratio: 0.35 [95% confidence interval: 0.18-0.71]; P=0.003). Ultrasound-guided catheterisation reduced both immediate (27%, compared with 51% in the landmark approach group; P=0.004) and late (10%, compared with 23% in the landmark approach group; P=0.047) complications. Ultrasound guidance also reduced the proportion of patients who developed deep vein thrombosis (4%, compared with 22% following landmark approach; P=0.012), and achieved a higher procedural success rate (96% vs 78%; P=0.004). CONCLUSIONS: An ultrasound-guided approach reduced mechanical complications after urgent femoral arterial and venous catheterisation, while increasing procedural success. CLINICAL TRIAL REGISTRATION: NCT02820909.

Early Detection of Patients at Risk of Developing a Post-Traumatic Stress Disorder After an ICU Stay.

OBJECTIVES: To evaluate the diagnostic accuracy of the Impact Event Scale-Revisited assessed following ICU discharge to predict the emergence of post-traumatic stress disorder symptoms at 3 months. DESIGN: Prospective cohort study. SETTING: Three medical or surgical ICU of a French university hospital (Lyon, France). PATIENTS: Patients greater than or equal to 18 years old, leaving ICU after greater than or equal to 2 nights of stay, between September 2017 and April 2018. INTERVENTIONS: Patients completed the Impact Event Scale-Revisited and the Peritraumatic Dissociative Experiences Questionnaire within 8 days after ICU discharge and the Impact Event Scale-Revisited again at 3 months by phone. Patients having an Impact Event Scale-Revisited greater than or equal to 35 at 3 months were considered as having post-traumatic stress disorder symptoms. MEASUREMENTS AND MAIN RESULTS: Among the 208 patients screened, 174 were included and 145 reassessed by phone at 3 months. Among the patients included at baseline, 43% presented symptoms of acute stress. At 3 months, 13% had an Impact Event Scale-Revisited greater than or equal to 35 and 17% had a score between 12 and 34. Regarding the performance of the Impact Event Scale-Revisited performed within 8 days after the ICU discharge to predict post-traumatic stress disorder symptoms at 3 months, the area under the curve was 0.90 (95% CI, 0.80-0.99), and an Impact Event Scale-Revisited greater than or equal to 12 had a sensitivity of 90%, a specificity of 71%, a positive predictive value of 32%, and a negative predictive value of 98%. History of anxiety disorder odds ratio = 3.7 (95% CI, 1.24-11.05; p = 0.02) and Impact Event Scale-Revisited greater than or equal to 12 odds ratio = 16.57 (95% CI, 3.59-76.46; p < 0.001) were identified as risk factors for post-traumatic stress disorder symptoms. CONCLUSIONS: Impact Event Scale-Revisited assessed at ICU discharge has a good ability for the detection of patients at risk of developing post-traumatic stress disorder symptoms. Patients with history of anxiety disorder and those presenting acute stress symptoms at ICU discharge are more at risk to develop post-traumatic stress disorder symptoms.

Risk factors and events in the adult intensive care unit associated with pain as self-reported at the end of the intensive care unit stay.

BACKGROUND: The short-term and long-term consequences of the most frequent painful procedures performed in the ICU are unclear. This study aimed to identify the risk factors associated with pain-related discomfort perceived by critically ill patients during the whole ICU stay as self-reported by patients at the end of their ICU stay. METHODS: The study involved 34 ICUs. Adult patients who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Discomforts, including the pain-related discomfort, were assessed using the French 18-item questionnaire on discomfort in ICU patients, the "Inconforts des Patients de REAnimation" (IPREA). Patients scored each item from 0 (minimal discomfort) to 10 (maximal discomfort). Associations between patient characteristics at ICU admission, life support therapies and main potentially painful procedures performed during the ICU stay and pain-related discomfort scores assessed at the end of the ICU stay were analyzed. RESULTS: Patients with complete IPREA questionnaires (n = 2130) were included. The median pain-related discomfort score was 3 (IQR 0-5). From the univariate analysis, pain-related discomfort scores were negatively correlated with age and positively correlated with ICU stay duration; surgical patients reported significant higher pain-related discomfort scores than medical patients; chest drain insertion, chest drain removal, use of bladder catheter, central venous catheter (CVC) insertion, complex dressing change, and intra-hospital transport were associated with pain-related discomfort scores. From the multivariate analyses using generalized estimating equations models, only age, chest drain removal, use of a bladder catheter, CVC insertion, and intra-hospital transport were the main risk factors associated with pain-related discomfort scores. CONCLUSION: Patients who underwent chest drain removal, bladder catheter, CVC insertion, and intra-hospital transport during their ICU stay reported higher pain-related discomfort scores (with respect to the whole ICU stay and assessed at the end of their ICU stay) than patients who did not experience these events. This study may pave the way for further targeted studies aiming at investigating a causal link between these common procedures in the ICU and adult critically ill patients' perceptions of their ICU stay regarding recalled pain. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT02442934, retrospectively registered on May 13, 2015.

Being Convinced and Taking Responsibility: A Qualitative Study of Family Members' Experience of Organ Donation Decision and Bereavement After Brain Death.

OBJECTIVES: Family members of brain dead patients experience an unprecedented situation in which not only they are told that their loved one is dead but are also asked to consider organ donation. The objective of this qualitative study was to determine 1) what it means for family members to make the decision and to take responsibility, 2) how they interact with the deceased patient in the ICU, 3) how family members describe the impact of the process and of the decision on their bereavement process. DESIGN: Qualitative study using interviews with bereaved family members who were approached for organ donation after the death of their relative in the ICU (brain death). SETTING: Family members from 13 ICUs in France. SUBJECTS: Bereaved family members who were approached for organ donation after the death of their relative in the ICU (brain death). INTERVENTION: None. MEASUREMENTS AND RESULTS: Twenty-four interviews were conducted with 16 relatives of organ donor patients and with eight relatives of nonorgan donor patients. Three themes emerged: 1) taking responsibility-relatives explain how they endorse decisional responsibility but do not experience it as a burden, on the contrary; 2) ambiguous perceptions of death-two groups of relatives emerge: those for whom ambiguity hinders their acceptance of the patient's death; those for whom ambiguity is an opportunity to accept the death and say goodbye; and 3) donation as a comfort during bereavement. CONCLUSIONS: In spite of caregivers' efforts to focus organ donation discussions and decision on the patient, family members feel a strong decisional responsibility that is not experienced as a burden but a proof of their strong connection to the patient. Brain death however creates ambivalent experiences that some family members endure whereas others use as an opportunity to perform separation rituals. Last, organ donation can be experienced as a form of comfort during bereavement provided family members remain convinced their decision was right.

Assessment of patients' self-perceived intensive care unit discomforts: Validation of the 18-item version of the IPREA.

BACKGROUND AND AIMS: We reported the validation of the 18-item version of the 'Inconforts des Patients de REAnimation (IPREA)' questionnaire that includes 2 new items exploring feeling depressed and shortness of breath during an intensive care unit (ICU) stay. METHODS: The validation process was integrated in a multicenter, cluster-randomized, controlled, two-parallel group study built to assess the effectiveness of a tailored multicomponent program for reducing self-perceived discomfort in the ICU. All patients aged 18 years or older who survived an ICU stay of 3 calendar days or more were eligible for inclusion. Data collection included demographics (sex, age), type of admission (medical and surgical), health status scores at admission (Knaus score and McCabe index, Simplified Acute Physiology Score (SAPS) II), specific ICU therapeutics such as mechanical ventilation (MV), noninvasive ventilation (NIV), use of vasopressors, or renal replacement therapy (RRT), and ICU stay duration. RESULTS: A total of 994 patients were included. The initial structure of IPREA was confirmed using confirmatory factor analysis showing satisfactory fit (RMSEA at 0.042, CFI at 0.912). No multidimensional structure was identified, allowing the calculation of an overall discomfort score. The three highest discomforts were sleep deprivation, thirst, and perfusion lines and other devices, and the 3 lowest discomforts were limited visiting hours, hunger, and isolation. The overall discomfort score of the 18-item version of IPREA did not differ between men and women. Higher age was significantly correlated with a lower overall discomfort score. While MV was not linked to self-reported discomfort, patients treated by NIV reported higher overall discomfort scores than patients not treated by NIV. CONCLUSION: The 18-item version of IPREA is easy to use and possesses satisfactory psychometric properties. The availability of a reliable and valid French questionnaire asking about patients' self-perceived ICU discomforts enables feedback from the health care team to be incorporated in a continuous quality health care improvement strategy. TRIAL REGISTRATION: clinicaltrial.gov NCT02442934 (registration date: May 18, 2015, retrospectively registered).

Grief Symptoms in Relatives Who Experienced Organ Donation Requests in the ICU.

RATIONALE: Studies show that the quality of end-of-life communication and care have a significant impact on the living long after the death of a relative and have been implicated in the burden of psychological symptoms after the ICU experience. In the case of organ donation, the patient's relatives are centrally involved in the decision-making process; yet, few studies have examined the impact of the quality of communication on the burden of psychological symptoms after death. OBJECTIVES: To assess the experience of the organ donation process and grief symptoms in relatives of brain-dead patients who discussed organ donation in the ICU. METHODS: We conducted a multicenter longitudinal study in 28 ICUs in France. Participants were the relatives of brain-dead patients who were approached to discuss organ donation. Relatives were followed-up by phone at three time points: at 1 month, to complete a questionnaire describing their experience of the organ donation process; at 3 months, to complete the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised; and at 9 months, to complete the Impact of Event Scale-Revised and the Inventory of Complicated Grief. MEASUREMENTS AND MAIN RESULTS: In total, 202 relatives of 202 patients were included, of whom 158 consented to and 44 refused organ donation. Interviews were conducted at 1, 3, and 9 months with 78%, 68%, and 58% of relatives, respectively. The overall experience of the organ donation process was significantly more burdensome for relatives of nondonors. They were more dissatisfied with communication (27% vs. 10%; P = 0.021), more often shocked by the request (65% vs. 19%; P < 0.0001), and more often found the decision difficult (53% vs. 27%; P = 0.017). However, there were no significant differences in grief symptoms measured at 3 and 9 months between the two groups. Understanding of brain death was associated with grief symptoms; our results show a higher prevalence of complicated grief symptoms among relatives who did not understand the brain death process than among those who did (75% vs. 46.1%; P = 0.026). CONCLUSIONS: Experience of the organ donation process varied between relatives of donor versus nondonor patients, with relatives of nondonors experiencing lower-quality communication, but the decision was not associated with subsequent grief symptoms. Importantly, understanding of brain death is a key element of the organ donation process for relatives.

Effect of an ICU Diary on Posttraumatic Stress Disorder Symptoms Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Keeping a diary for patients while they are in the intensive care unit (ICU) might reduce their posttraumatic stress disorder (PTSD) symptoms. Objectives: To assess the effect of an ICU diary on the psychological consequences of an ICU hospitalization. Design, Setting, and Participants: Assessor-blinded, multicenter, randomized clinical trial in 35 French ICUs from October 2015 to January 2017, with follow-up until July 2017. Among 2631 approached patients, 709 adult patients (with 1 family member each) who received mechanical ventilation within 48 hours after ICU admission for at least 2 days were eligible, 657 were randomized, and 339 were assessed 3 months after ICU discharge. Interventions: Patients in the intervention group (n = 355) had an ICU diary filled in by clinicians and family members. Patients in the control group (n = 354) had usual ICU care without an ICU diary. Main Outcomes and Measures: The primary outcome was significant PTSD symptoms, defined as an Impact Event Scale-Revised (IES-R) score greater than 22 (range, 0-88; a higher score indicates more severe symptoms), measured in patients 3 months after ICU discharge. Secondary outcomes, also measured at 3 months and compared between groups, included significant PTSD symptoms in family members; significant anxiety and depression symptoms in patients and family members, based on a Hospital Anxiety and Depression Scale score greater than 8 for each subscale (range, 0-42; higher scores indicate more severe symptoms; minimal clinically important difference, 2.5); and patient memories of the ICU stay, reported with the ICU memory tool. Results: Among 657 patients who were randomized (median [interquartile range] age, 62 [51-70] years; 126 women [37.2%]), 339 (51.6%) completed the trial. At 3 months, significant PTSD symptoms were reported by 49 of 164 patients (29.9%) in the intervention group vs 60 of 175 (34.3%) in the control group (risk difference, -4% [95% CI, -15% to 6%]; P = .39). The median (interquartile range) IES-R score was 12 (5-25) in the intervention group vs 13 (6-27) in the control group (difference, -1.47 [95% CI, -1.93 to 4.87]; P = .38). There were no significant differences in any of the 6 prespecified comparative secondary outcomes. Conclusions and Relevance: Among patients who received mechanical ventilation in the ICU, the use of an ICU diary filled in by clinicians and family members did not significantly reduce the number of patients who reported significant PTSD symptoms at 3 months. These findings do not support the use of ICU diaries for preventing PTSD symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT02519725.

Specialist Advice Support for Management of Severe Hereditary Angioedema Attacks: A Multicenter Cluster-Randomized Controlled Trial.

STUDY OBJECTIVE: Hereditary angioedema is a rare disease associated with unpredictable, recurrent attacks of potentially life-threatening edema. Management of severe attacks is currently suboptimal because emergency medical teams are often unaware of new specific treatments. The objective of this trial is to test whether a dedicated national telephone care-management strategy would reduce resource use during severe hereditary angioedema attacks. METHODS: We conducted a cluster-randomized multicenter prospective trial of patients with a documented diagnosis of hereditary angioedema (type I, II or FXII hereditary angioedema). Participants were enrolled between March 2013 and June 2014 at 8 participating reference centers. The randomized units were the reference centers (clusters). Patients in the intervention arm were given a national free telephone number to call in the event of a severe attack. Emergency physicians in the SOS-hereditary angiœdema (SOS-HAE) call center were trained to advise or prescribe specific treatments. The primary outcome was number of admissions for angioedema attacks. Economic evaluation was also performed. RESULTS: We included 100 patients in the SOS-HAE group and 100 in the control group. During the 2 years, there were 2,368 hereditary angioedema attacks among 169 patients (85%). Mean number of hospital admissions per patient in the 2-year period was significantly greater in the usual-practice group (mean 0.16 [range 0 to 2] versus 0.03 [range 0 to 1]); patient risk difference was significant: -0.13 (95% confidence interval -0.22 to -0.04; P=.02). Probabilistic sensitivity graphic analysis indicated a trend toward increased quality-adjusted life-years in the SOS-HAE group. CONCLUSION: A national dedicated call center for management of severe hereditary angioedema attacks is associated with a decrease in hospital admissions and may be cost-effective if facilities and staff are available to deliver the intervention alongside existing services.

Uncontrolled donation after circulatory death: comparison of two kidney preservation protocols on graft outcomes.

BACKGROUND: Kidney transplantation following uncontrolled donation after circulatory death (uDCD) presents a high risk of delayed graft function due to prolonged warm ischemia time. In order to minimise the effects of ischemia/reperfusion injury during warm ischemia, normothermic recirculation recently replaced in situ perfusion prior to implantation in several institutions. The aim of this study was to compare these preservation methods on kidney graft outcomes. METHODS: The primary endpoint was the one-year measured graft filtration rate (mGFR). We collected retrospective data from 64 consecutive uDCD recipients transplanted over a seven-year period in a single centre. RESULTS: Thirty-two grafts were preserved by in situ perfusion and 32 by normothermic recirculation. The mean ± SD mGFR at 1 year post-transplantation was 43.0 ± 12.8 mL/min/1.73 m2 in the in situ perfusion group and 53.2 ± 12.8 mL/min/1.73 m2 in the normothermic recirculation group (p = 0.01). Estimated GFR levels were significantly higher in the normothermic recirculation group at 12 months (p = 0.01) and 24 months (p = 0.03) of follow-up. We did not find any difference between groups regarding patient and graft survival, delayed graft function, graft rejection, or interstitial fibrosis. CONCLUSIONS: Function of grafts preserved by normothermic recirculation was better at 1 year and the results suggest that this persists at 2 years, although no difference was found in short-term outcomes. Despite the retrospective design, this study provides an additional argument in favour of normothermic recirculation.

Hepatic Compartment Syndrome Following Percutaneous Cholecystostomy: A Case Report.

OBJECTIVE: To describe a case of hepatic subcapsular hematoma causing an acute Budd-Chiari-like syndrome, leading to hepatic compartment syndrome, which combines compression of intrahepatic vessels on CT, acute liver failure, and refractory shock. DESIGN: Case report. SETTING: Surgical ICU of a university teaching hospital. PATIENT: Single case: A 64-year-old man hospitalized for 1 month in the ICU after multiple complications following bypass surgery, under anticoagulation after a recent aortic valve replacement and without a medical history of hepatic disease, underwent a percutaneous cholecystostomy for acute calculous cholecystitis. Fifteen days later, he presented with acute anemia, abdominal tenderness, severe hepatic cytolysis, metabolic acidosis, and hemodynamic dysfunction. CT showed a voluminous subcapsular hematoma compressing the hepatic parenchyma, which appeared ischemic with a flattened right lobar portal vein and vena cava without any visible active bleeding. INTERVENTIONS: Arteriography and evacuation of the hematoma under ultrasound guidance (while managing hemodynamic dysfunction) were preferred to surgery given the patient's instability and surgical history. MEASUREMENTS AND MAIN RESULTS: Evidence of vessels and parenchymal compression with no source of bleeding was found despite removal of the cholecystostomy catheter. Two right sectorial inferior hepatic arteries were embolized. Hematoma was punctured to relieve pressure on hepatic parenchyma, retrieving 300 mL of blood. Unfortunately, liver failure worsened dramatically while patient developed refractory shock and died. CONCLUSIONS: Hepatic compartment syndrome must be suspected when acute liver failure occurs in patients with subcapsular hematoma. Only early management may avoid a fatal outcome or the need for an emergency liver transplantation.

Decreased CX3CR1 messenger RNA expression is an independent molecular biomarker of early and late mortality in critically ill patients.

BACKGROUND: Chemokine (C-X3-C motif) receptor 1 (CX3CR1) was identified as the most differentially expressed gene between survivors and non-survivors in two independent cohorts of septic shock patients and was proposed as a marker of sepsis-induced immunosuppression. Whether such a biomarker is associated with mortality in the heterogeneous group of critically ill patients is unknown. The primary objective of this study was to evaluate the association between CX3CR1 messenger RNA (mRNA) expression and mortality in intensive care unit (ICU) patients. The secondary objective was to evaluate similar endpoints in the subgroup of septic shock patients. METHODS: We performed a prospective, multicentre, non-interventional study in six ICUs of university hospitals in Lyon, France. Every consecutive adult patient with systemic inflammatory response syndrome and an expected length of stay in the ICU over 2 days was included. Whole-blood CX3CR1 mRNA expression was measured by quantitative real-time polymerase chain reaction at day 1 (D1) and D3 after inclusion. RESULTS: In ICU patients (n = 725), decreased CX3CR1 mRNA expression at D1 was associated with high D7 mortality (AUC 0.70, adjusted OR [aOR] 2.03, 95 % CI 1.19-3.46), while decreased expression at D3 was associated with increased D28 mortality (AUC 0.64, aOR 2.34, 95 % CI 1.45-3.77). In septic shock patients (n = 279), similar associations were observed between decreased D1 CX3CR1 mRNA expression and D7 mortality (AUC 0.69, aOR 2.76, 95 % CI 1.32-5.75) as well as decreased D3 expression and D28 mortality (AUC 0.72, aOR 3.98, 95 % CI 1.72-9.23). These associations were independent of lactacidaemia, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score and Charlson comorbidity index. CONCLUSIONS: This study represents the largest evaluation of such an mRNA marker in a heterogeneous cohort of severely injured patients. Our results show that decreased CX3CR1 mRNA expression is associated with increased mortality in ICU patients. This suggests a link between injury-induced immunosuppression and mortality in critically ill patients. In this context, the monitoring of such a host response molecular biomarker could prove very helpful for the identification of patients at high risk of death in the ICU.

Outbreak of pulmonary Pseudomonas aeruginosa and Stenotrophomonas maltophilia infections related to contaminated bronchoscope suction valves, Lyon, France, 2014.

In April 2014, pulmonary Pseudomonas aeruginosa and Stenotrophomonas maltophilia co-infections potentially related to bronchoscopic procedures were identified in the intensive care units of a university hospital in Lyon, France. A retrospective cohort of 157 patients exposed to bronchoscopes from 1 December 2013 to 17 June 2014 was analysed. Environmental samples of suspected endoscopes were cultured. Bronchoscope disinfection was reviewed. Ten cases of pulmonary P. aeruginosa/S. maltophilia co-infections were identified, including two patients with secondary pneumonia. Eight cases were linked to bronchoscope A1 and two to bronchoscope A2. Cultures deriving from suction valves were positive for P. aeruginosa/S. maltophilia. Exposure to bronchoscopes A1 and A2 was independently coupled with increased risk of co-infection (adjusted odds ratio (aOR) = 84.6; 95% confidence interval (CI): 9.3-771.6 and aOR = 11.8, 95% CI: 1.2-121.3). Isolates from suction valves and clinical samples presented identical pulsotypes. The audit detected deficiencies in endoscope disinfection. No further cases occurred after discontinuation of the implicated bronchoscopes and change in cleaning procedures. This outbreak of pulmonary P. aeruginosa/S. maltophilia co-infections was caused by suction valve contamination of two bronchoscopes of the same manufacturer. Our findings underscore the need to test suction valves, in addition to bronchoscope channels, for routine detection of bacteria.

Complicated grief after death of a relative in the intensive care unit.

An increased proportion of deaths occur in the intensive care unit (ICU). We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months. Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives). End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements.

Comparative effectiveness of inhospital trauma resuscitation at a French trauma center and matched patients treated in the United States.

OBJECTIVE: The objective of this paper is to compare mortality outcomes between patients treated at a trauma center in France and matched patients in the United States. BACKGROUND: Although trauma systems in France and the United States differ significantly in prehospital and inhospital management, previous comparisons have been challenged by the lack of comparable data. METHODS: Coarsened exact matching identified matching patients between a single center trauma database from Lyon, France, and the National Trauma Data Bank (NTDB) of the United States. Moderate to severely injured [injury severity score (ISS) > 8] adult patients (age ≥ 16) presenting alive to level 1 trauma centers from 2002 to 2005 with blunt or penetrating injuries were included. After matching patients, multivariate regression analyses were performed to determine difference in mortality between patients in Lyon and the NTDB. RESULTS: A total of 1043 significantly injured patients were presented to the Lyon center. Matching eligible patients with complete records were sought from 219,985 patients in the NTDB. The unadjusted odds of mortality at the Lyon center was 2.5 times higher than that of the NTDB [95% confidence interval (CI) = 2.18-2.98]. However, the Lyon center received patients with higher ISS, lower Glasgow Coma Score (GCS), and lower systolic blood pressure (SBP) (all P < 0.001). After 1:1 matching, 858 patient pairs were produced, and the odds of mortality became equivalent [odds ratio (OR) = 1.3, 95% CI = 0.91-1.73]. Similar results were found in multiple subset analyses. CONCLUSIONS: Trauma patients admitted to a single French trauma center had an equal chance of survival compared with similarly injured patients treated at US trauma centers.

Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema.

BACKGROUND: Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS: In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS: A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS: In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

Metabolic phenotyping of traumatized patients reveals a susceptibility to sepsis.

Sepsis is one of the leading causes of morbidity and mortality in patients admitted in intensive care units (ICU) for trauma. The identification of biochemical mechanisms and prediction of patients at risk of early sepsis remain unsolved. Metabolic phenotyping allows the recovery of coordinated metabolic concentration variations. There are no predictive metabolic phenotyping studies based on noninvasive human samples to identify the later development of sepsis in traumatized patients. The aim of this study was to investigate whether the metabolic phenotype could help in the discrimination of patients according to the later development of sepsis. Plasma samples were taken from severely injured patients in the hours following their admission in the ICU. Nuclear magnetic resonance (NMR) based metabolic phenotyping was performed on this prospective cohort. Statistical analyses were run on NMR spectra to discriminate patients according to the later development of sepsis. Twenty-two patients were included. One was excluded because of aberrant metabolic phenotype. Orthogonal partial least-squares analysis allowed the recovery of a predictive metabolic phenotype identifying patients with a later development of sepsis (1 + 4 component model, R(2) = 0.855, Q(2) = 0.384). A cross-validated receiver operator characteristic curve showed a remarkable prediction capacity (AUC = 0.778). Eight metabolic hotspots were identified. NMR-based metabolic phenotyping allows the prediction of patients at high risk of early sepsis after ICU admission for trauma. A larger cohort is necessary to validate and complete this study, understand biochemical mechanisms promoting sepsis development, and identify patients at risk.

Evolution of Practices in a French Trauma Centre: Decrease in Blood Transfusions and Fresh Frozen Plasma to Red Blood Cell Ratios.

OBJECTIVE: The aim of this study was to describe the evolution of transfusion practices following the introduction of tranexamic acid (TXA) and ROTEMVR in a trauma resuscitation unit (TRU) from a French teaching hospital (FTH). METHODS: This is a single-centre, retrospective study at a TRU from a FTH. All trauma patients aged 18 years or more and transfused with at least 4 red blood cells (RBCs) within 24 hours after trauma, from 2011 to 2016, were included. The primary objective was to analyse transfusion practices over this time period. The secondary objectives aimed at assessing differences between populations according to the fresh frozen plasma (FFP):RBC ratio applied. RESULTS: A total of 122 patients were included. There was a significant decrease in the proportion of patients requiring at least 4 RBCs 24 hours after trauma (9% vs. 3%, P trend < .0001) as well as a decrease in the proportion of patients with a high FFP:RBC ratio (86% vs. 62% at 6 hours, P trend » .0056 and 86% vs. 56% at 24 hours, P trend » .0047). After 2013, fibrinogen was administered to more than 70% of patients and TXA to 100% of them. The observed mortality was lower than the predicted one, irrespective of FFP:RBC ratio. CONCLUSION: An important evolution of practices occurred including a decrease in the proportion of transfusions and use of high FFP:RBC ratios. The origin of these changes is multifactorial, likely including the systematic use of TXA and optimisation of the ROTEM protocol for fibrinogen administration.

Factors Associated with Clostridioides (Clostridium) Difficile Infection and Colonization: Ongoing Prospective Cohort Study in a French University Hospital.

INTRODUCTION: Clostridioides (Clostridium) difficile can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. C. difficile, the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from C. difficile infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by C. difficile and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for C. difficile testing are obtained on admission, every 3-5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l'Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.

Lack of recovery in monocyte human leukocyte antigen-DR expression is independently associated with the development of sepsis after major trauma.

INTRODUCTION: Major trauma is characterized by an overwhelming pro-inflammatory response and an accompanying anti-inflammatory response that lead to a state of immunosuppression, as observed after septic shock. Diminished monocyte Human Leukocyte Antigen DR (mHLA-DR) is a reliable marker of monocyte dysfunction and immunosuppression. The main objective of this study was to determine the relation between mHLA-DR expression in severe trauma patients and the development of sepsis. METHODS: We conducted a prospective observational study over 23 months in a trauma intensive care unit at a university hospital. Patients with an Injury Severity Score (ISS) over 25 and age over 18 were included. mHLA-DR was assessed by flow cytometry protocol according to standardized protocol. Mann-Whitney U-test for continuous non-parametric variables, independent paired t test for continuous parametric variables and chi-square test for categorical data were used. RESULTS: mHLA-DR was measured three times a week during the first 14 days. One hundred five consecutive severely injured patients were monitored (ISS 38 ± 17, SAPS II 37 ± 16). Thirty-seven patients (35%) developed sepsis over the 14 days post-trauma. At days 1-2, mHLA-DR was diminished in the whole patient population, with no difference with the development of sepsis. At days 3-4, a highly significant difference appeared between septic and non-septic patients. Non- septic patients showed an increase in mHLA-DR levels, whereas septic patients did not (13,723 ± 7,766 versus 9,271 ± 6,029 antibodies per cell, p = .004). Most importantly, multivariate logistic regression analysis, after adjustment for usual clinical confounders (adjusted OR 5.41, 95% CI 1.42-20.52), revealed that a slope of mHLA-DR expression between days1-2 and days 3-4 below 1.2 remained associated with the development of sepsis. CONCLUSIONS: Major trauma induced an immunosuppression, characterized by a decrease in mHLA-DR expression. Importantly, after multivariate regression logistic analysis, persistent decreased expression was assessed to be in relation with the development of sepsis. This is the first study in trauma patients showing a link between the lack of immune recovery and the development of sepsis on the basis of the standardized protocol. Monitoring immune function by mHLA-DR measurement could be useful to identify trauma patients at a high risk of infection.

Written information that relatives of adult intensive care unit patients would like to receive--a comparison to published recommendations and opinion of staff members.

OBJECTIVE: Information booklets have not been assessed by the families of intensive care unit (ICU) patients. This study explored the information that the relatives of adult ICU patients wanted to find in the information booklets. DESIGN: Multicenter survey. SETTING: Twenty-three French ICUs. SUBJECTS: One close relative of each of 250 consecutive adult patients. METHODS: Relatives were asked about the desirability of finding information on each of the 24 topics identified by ICU physicians and listed in guidelines as deserving inclusion in information booklets. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 250 patients (61% men) had a mean age of 60 +/- 18 years and a mean Simplified Acute Physiology Score II of 48 +/- 19; 57% had chronic comorbidities and 41% were surgical patients. At least 72% of the relatives felt that booklets should discuss nosocomial infections, treatment-limitation decisions, access to medical information on the patient, access to medical records, and the meaning of medical terms. Overall, relatives wanted more information than that anticipated by ICU physicians, suggested in guidelines, or found in booklets. However, for at least one of the 24 topics, 38% of relatives indicated that fear or poor comprehension made them unwilling to receive written information. These relatives were younger and had fewer years of formal education than did the other relatives, and they were more likely to be visiting conscious unrestrained patients. CONCLUSIONS: Opinions of relatives should be taken into account when designing ICU information booklets. Relatives want more information than that anticipated by physicians or suggested in guidelines, but the youngest or the less-educated ones may respond less favorably to written information.