Testing the validity of three acute care assessment tools for assessing residents' performance during in situ simulation: the ACAT-SimSit study.

BACKGROUND: The assessment of technical and nontechnical skills in emergency medicine requires reliable and usable tools. Three Acute Care Assessment Tools (ACATs) have been developed to assess medical learners in their management of cardiac arrest (ACAT-CA), coma (ACAT-coma) and acute respiratory failure (ACAT-ARF). OBJECTIVE: This study aims to analyze the reliability and usability of the three ACATs when used for in situ (bedside) simulation. METHODS: This prospective multicenter validation study tested ACATs using interprofessional in situ simulations in seven emergency departments and invited training residents to participate in them. Each session was rated by two independent raters using ACAT. Intraclass correlation coefficients (ICC) were used to assess interrater reliability, and Cronbach's alpha coefficient was used to assess internal consistency for each ACAT. The correlation between ACATs' scores and the learners' level of performance was also assessed. Finally, a questionnaire and two focus groups were used to assess the usability of the ACATs. RESULTS: A total of 104 in situ simulation sessions, including 85 residents, were evaluated by 37 raters. The ICC for ACAT-CA, ACAT-coma and ACAT-ARF were 0.95 [95% confidence interval (CI), 0.93-0.98], 0.89 (95% CI, 0.77-0.95) and 0.92 (95%CI 0.83-0.96), respectively. The Cronbach's alphas were 0.79, 0.80 and 0.73, respectively. The ACAT-CA and ARF showed good construct validity, as third-year residents obtained significantly higher scores than first-year residents (P < 0.001; P < 0.019). The raters supported the usability of the tools, even though they expressed concerns regarding the use of simulations in a summative way. CONCLUSION: This study reported that the three ACATs showed good external validity and usability.

Robotic surgery and work-related stress: A systematic review.

Despite robot-assisted surgery (RAS) becoming increasingly common, little is known about the impact of the underlying work organization on the stress levels of members of the operating room (OR) team. To this end, assessing whether RAS may impact work-related stress, identifying associated stress factors and surveying relevant measurement methods seems critical. Using three databases (Scopus, Medline, Google Scholar), a systematic review was conducted leading to the analysis of 20 articles. Results regarding OR team stress levels and measurement methods were heterogeneous, which could be explained by differing research conditions (i.e., lab. vs. real-life). Relevant stressors such as (in)experience with RAS and quality of team communication were identified. Development of a common, more reliable methodology of stress assessment is required. Research should focus on real-life conditions in order to develop valid and actionable knowledge. Surgical teams would greatly benefit from discussing RAS-related stressors and developing team-specific strategies to handle them.

Simulation-based summative assessment in healthcare: an overview of key principles for practice.

BACKGROUND: Healthcare curricula need summative assessments relevant to and representative of clinical situations to best select and train learners. Simulation provides multiple benefits with a growing literature base proving its utility for training in a formative context. Advancing to the next step, "the use of simulation for summative assessment" requires rigorous and evidence-based development because any summative assessment is high stakes for participants, trainers, and programs. The first step of this process is to identify the baseline from which we can start. METHODS: First, using a modified nominal group technique, a task force of 34 panelists defined topics to clarify the why, how, what, when, and who for using simulation-based summative assessment (SBSA). Second, each topic was explored by a group of panelists based on state-of-the-art literature reviews technique with a snowball method to identify further references. Our goal was to identify current knowledge and potential recommendations for future directions. Results were cross-checked among groups and reviewed by an independent expert committee. RESULTS: Seven topics were selected by the task force: "What can be assessed in simulation?", "Assessment tools for SBSA", "Consequences of undergoing the SBSA process", "Scenarios for SBSA", "Debriefing, video, and research for SBSA", "Trainers for SBSA", and "Implementation of SBSA in healthcare". Together, these seven explorations provide an overview of what is known and can be done with relative certainty, and what is unknown and probably needs further investigation. Based on this work, we highlighted the trustworthiness of different summative assessment-related conclusions, the remaining important problems and questions, and their consequences for participants and institutions of how SBSA is conducted. CONCLUSION: Our results identified among the seven topics one area with robust evidence in the literature ("What can be assessed in simulation?"), three areas with evidence that require guidance by expert opinion ("Assessment tools for SBSA", "Scenarios for SBSA", "Implementation of SBSA in healthcare"), and three areas with weak or emerging evidence ("Consequences of undergoing the SBSA process", "Debriefing for SBSA", "Trainers for SBSA"). Using SBSA holds much promise, with increasing demand for this application. Due to the important stakes involved, it must be rigorously conducted and supervised. Guidelines for good practice should be formalized to help with conduct and implementation. We believe this baseline can direct future investigation and the development of guidelines.

A Cognitive Aid Improves Adherence to Guidelines for Critical Endotracheal Intubation in the Resuscitation Room: A Randomized Controlled Trial With Manikin-Based In Situ Simulation.

INTRODUCTION: Emergency endotracheal intubation (ETI) is a high-risk procedure. Some of its adverse events are life-threatening, and guidelines emphasize the need to anticipate complications by thorough preparation. The emergency department (ED) can be an unpredictable environment, and we tested the hypothesis that a cognitive aid would help the emergency practitioners better follow guidelines. The main objective of this study was to determine whether the use of a cognitive aid focusing on both preintubation and postintubation items could improve ETI preparation and implementation in the ED resuscitation room regarding adherence to guidelines. The secondary objective was to measure and describe procedure times. METHODS: We conducted a single-blind randomized controlled trial with manikin-based in situ simulation. The participants were not aware of the purpose of the study. The cognitive aid was developed using national guidelines and current scientific literature. The most relevant items were the preparation and implementation of a rapid sequence induction for ETI followed by mechanical ventilation. Emergency department physician-nurse pairs were randomized into a "cognitive aid" group and a "control" group. All pairs completed the same scenario that led to ETI in their own resuscitation room. An adherence to guidelines score of 30, derived from the 30 items of the cognitive aid (1 point per item), and preparation and intubation times were collected. RESULTS: Seventeen pairs were included in each group. Adherence to guidelines scores were significantly higher in the cognitive aid group than in the control group (median = 28 of 30, interquartile range = 25-28, vs. median = 24 of 30, interquartile range = 21-26, respectively, P < 0.01). Preparation, intubation, and total procedure times were slightly longer in the cognitive aid group, but these results were not significant. CONCLUSIONS: In an in situ simulation, a cognitive aid for the preparation and implementation of an emergency intubation procedure in the ED resuscitation room significantly improved adherence to guidelines without increasing procedure times. Further work is needed in a larger sample and in different settings to evaluate the optimal use of cognitive aids in critical situations.

Safety of day surgery for patients with special needs.

BACKGROUND: The objective of this study was to assess the safety and quality of day care management for dental surgery under general anaesthesia in a population with special needs and to compare the results with a control population. METHODS: A retrospective observational cohort study was performed. The study population included all patients who had day care dental surgery under general anaesthesia for one year. The primary endpoint was the rate of unscheduled admission, which was defined as the unplanned need to maintain a hospital stay on the evening of the surgical procedure. Secondary endpoints included occurrence of complications during the perioperative period (either anaesthesia or surgery related) on the day of surgery (D0) and on day 1 and satisfaction of patients or their relatives. RESULTS: Data from 138 patients (70 with special needs and 68 controls) were analysed. In both groups, patients were young (mean age 33 years ± 14 in each group). Special needs were mainly related to autism (34%), cerebral palsy (19%), intellectual disability (19%) and Down syndrome (10 %). Surgical procedures were more extensive in the control group. There was 1 unscheduled admission in the special needs group and 3 in the control group (RR 0.32, 95% CI [0.03; 3.04]). There was no difference in the rate of complications. CONCLUSION: In our cohort, day care management for dental surgery under general anaesthesia is safe and effective for patients with special needs.

Double Direct Injection of Blood into the Cisterna Magna as a Model of Subarachnoid Hemorrhage.

Among strokes, subarachnoid hemorrhage (SAH) consecutive to the rupture of a cerebral arterial aneurysm represents 5-9% but is responsible for about 30% of the total stroke-related mortality with an important morbidity in terms of neurological outcome. A delayed cerebral vasospasm (CVS) may occur most often in association with a delayed cerebral ischemia. Different animal models of SAH are now being used including endovascular perforation and direct injection of blood into the cisterna magna or even the prechiasmatic cistern, each exhibiting distinct advantages and disadvantages. In this article, a standardized mouse model of SAH by double direct injection of determined volumes of autologous whole blood into the cisterna magna is presented. Briefly, mice were weighed and then anesthetized by isoflurane inhalation. Then, the animal was placed in a reclining position on a heated blanket maintaining a rectal temperature of 37 °C and positioned in a stereotactic frame with a cervical bend of about 30°. Once in place, the tip of an elongated glass micropipette filled with the homologous arterial blood taken from carotid artery of another mouse of the same age and gender (C57Bl/6J) was positioned at a right angle in contact with the atlanto-occipital membrane by means of a micromanipulator. Then 60 µL of blood was injected in the cisterna magna followed by a 30° downward tilt of the animal for 2 minutes. The second infusion of 30 µL of blood into the cisterna magna was performed 24 h after the first one. The individual follow-up of each animal is carried out daily (careful evaluation of weight and well-being). This procedure allows a predictable and highly reproducible distribution of blood, likely accompanied by intracranial pressure elevation that can be mimicked by an equivalent injection of an artificial cerebral spinal fluid (CSF), and represents an acute to mild-model of SAH inducing low mortality.

Investigation of pulmonary embolism in patients with chest pain in the emergency department: a retrospective multicenter study.

INTRODUCTION: Chest pain is a common main complaint in the emergency department. Among its associated differential diagnoses, pulmonary embolism remains a key concern for the clinician. There are no clear recommendations on which patients should have a formal workup for pulmonary embolism diagnosis. The objective of this study was to determine the proportion of patients with chest pain who were investigated for pulmonary embolism diagnosis and to determine the clinical profile of these patients. METHODS: This was a retrospective multicenter study conducted in three French Emergency Departments. We included all patients who presented to these centers for chest pain during a 2-month period. The primary outcome was the initiation of pulmonary embolism workup. We also aimed to find factors associated with this outcome. RESULTS: We included 881 patients with a main complaint of chest pain. Mean age was 50 years and 481 (56%) were men. A total of 263 patients (30%, 95% confidence interval 27-33%) had a formal pulmonary embolism workup, and pulmonary embolism was ultimately diagnosed in 7 cases (prevalence of 2.6%, 95% confidence interval 1.1-5.3%). Five factors were identified as independently associated with a workup for pulmonary embolism diagnosis: female sex, young age, no ischemic heart disease, recent flight and associated dyspnea. CONCLUSION: Among patients presenting to emergency department with chest pain, 30% had a workup for pulmonary embolism. We report five clinical variables independently associated with a higher probability of pulmonary embolism workup in our sample.

A Protocol to Set Up Needle-Free Connector with Positive Displacement on Central Venous Catheter in Intensive Care Unit.

Needle-free connectors were initially designed and promoted to avoid blood exposure for healthcare workers. Some recent data suggest that the latest generation of connectors (with positive displacement) may be of interest for reducing central venous line infections. We have been using needle-free connectors for several years in our intensive care unit and here we present a protocol for installing these connectors on central venous catheters. After insertion of the catheter and control of the permeability of the lines, the connectors must be purged with 0.9% NaCl before being connected. The connectors replace all disposable caps used on infusion stopcocks and manifolds. All the connectors are changed every 7 days as recommended by the manufacturer (except when there is macroscopic contamination, which requires an immediate change of the connector). Before each injection, the connector must be disinfected for at least 3 seconds with 70% isopropyl alcohol. The connectors must not be disconnected (unless changed), as the injection is done through the device. Setting up the connectors slightly increases the total time required to place the catheter and there is no formal evidence that these connectors reduce the incidence of infectious or thrombotic complications. However, these devices simplify the management of central venous lines and prevent the catheter circuit from "opening" once it has been sterilely installed.

Association between vasoactive peptide urotensin II in plasma and cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a potential therapeutic target.

OBJECTIVECerebral vasospasm (VS) is a severe complication of aneurysmal subarachnoid hemorrhage (SAH). Urotensin II (UII) is a potent vasoactive peptide activating the urotensin (UT) receptor, potentially involved in brain vascular pathologies. The authors hypothesized that UII/UT system antagonism with the UT receptor antagonist/biased ligand urantide may be associated with post-SAH VS. The objectives of this study were 2-fold: 1) to leverage an experimental mouse model of SAH with VS in order to study the effect of urotensinergic system antagonism on neurological outcome, and 2) to investigate the association between plasma UII level and symptomatic VS after SAH in human patients.METHODSA mouse model of SAH was used to study the impacts of UII and the UT receptor antagonist/biased ligand urantide on VS and neurological outcome. Then a clinical study was conducted in the setting of a neurosurgical intensive care unit. Plasma UII levels were measured in SAH patients daily for 9 days, starting on the 1st day of hospitalization, and were compared with plasma UII levels in healthy volunteers.RESULTSIn the mouse model, urantide prevented VS as well as SAH-related fine motor coordination impairment. Seventeen patients with SAH and external ventricular drainage were included in the clinical study. The median plasma UII level was 43 pg/ml (IQR 14-80 pg/ml). There was no significant variation in the daily median plasma UII level (median value for the 17 patients) from day 0 to day 8. The median level of plasma UII during the 9 first days post-SAH was higher in patients with symptomatic VS than in patients without VS (77 pg/ml [IQR 33.5-111.5 pg/ml] vs 37 pg/ml [IQR 21-46 pg/ml], p < 0.05). Concerning daily measures of plasma UII levels in VS, non-VS patients, and healthy volunteers, we found a significant difference between SAH patients with VS (median 66 pg/ml [IQR 30-110 pg/ml]) and SAH patients without VS (27 pg/ml [IQR 15-46 pg/ml], p < 0.001) but no significant difference between VS patients and healthy volunteers (44 pg/ml [IQR 27-51 pg/ml]) or between non-VS patients and healthy volunteers.CONCLUSIONSThe results of this study suggest that UT receptor antagonism with urantide prevents VS and improves neurological outcome after SAH in mice and that an increase in plasma UII is associated with cerebral VS subsequent to SAH in humans. The causality link between circulating UII and VS after SAH remains to be established, but according to our data the UT receptor is a potential therapeutic target in SAH.

Dietary aquaculture by-product hydrolysates: impact on the transcriptomic response of the intestinal mucosa of European seabass (Dicentrarchus labrax) fed low fish meal diets.

BACKGROUND: Aquaculture production is expected to double by 2030, and demands for aquafeeds and raw materials are expected to increase accordingly. Sustainable growth of aquaculture will require the development of highly nutritive and functional raw materials to efficiently replace fish meal. Enzymatic hydrolysis of marine and aquaculture raw materials could bring new functionalities to finished products. The aim of this study was to determine the zootechnical and transcriptomic performances of protein hydrolysates of different origins (tilapia, shrimp, and a combination of the two) in European seabass (Dicentrarchux labrax) fed a low fish meal diet (5%), for 65 days. RESULTS: Results were compared to a positive control fed with 20% of fish meal. Growth performances, anterior intestine histological organization and transcriptomic responses were monitored and analyzed. Dietary inclusion of protein hydrolysates in the low fish meal diet restored similar growth performances to those of the positive control. Inclusion of dietary shrimp hydrolysate resulted in larger villi and more goblet cells, even better than the positive control. Transcriptomic analysis of the anterior intestine showed that dietary hydrolysate inclusion restored a pattern of intestinal gene expression very close to the pattern of the positive control. However, as compared to the low fish meal diet and depending on their origin, the different hydrolysates did not modulate metabolic pathways in the same way. Dietary shrimp hydrolysate inclusion modulated more metabolic pathways related to immunity, while nutritional metabolism was more impacted by dietary tilapia hydrolysate. Interestingly, the combination of the two hydrolysates enhanced the benefits of hydrolysate inclusion in diets: more genes and metabolic pathways were regulated by the combined hydrolysates than by each hydrolysate tested independently. CONCLUSIONS: Protein hydrolysates manufactured from aquaculture by-products are promising candidates to help replace fish meal in aquaculture feeds without disrupting animal metabolism and performances.

Long-Lasting Cerebral Vasospasm, Microthrombosis, Apoptosis and Paravascular Alterations Associated with Neurological Deficits in a Mouse Model of Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and morbidity. Long-term cognitive and sensorimotor deficits are serious complications following SAH but still not well explained and described in mouse preclinical models. The aim of our study is to characterize a well-mastered SAH murine model and to establish developing pathological mechanisms leading to cognitive and motor deficits, allowing identification of specific targets involved in these long-term troubles. We hereby demonstrate that the double blood injection model of SAH induced long-lasting large cerebral artery vasospasm (CVS), microthrombosis formation and cerebral brain damage including defect in potential paravascular diffusion. These neurobiological alterations appear to be associated with sensorimotor and cognitive dysfunctions mainly detected 10 days after the bleeding episode. In conclusion, this characterized model of SAH in mice, stressing prolonged neurobiological pathological mechanisms and associated sensitivomotor deficits, will constitute a validated preclinical model to better decipher the link between CVS, long-term cerebral apoptosis and cognitive disorders occurring during SAH and to allow investigating novel therapeutic approaches in transgenic mice.

Ketamine and Etomidate Down-regulate the Hypothalamic-Pituitary-Adrenal Axis in an Endotoxemic Mouse Model.

BACKGROUND: We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis. METHODS: Mice (n = 5/group) were injected intraperitoneally with lipopolysaccharide (10 mg/kg) and 6 h later randomized to receive ketamine (100 mg/kg), etomidate (30 mg/kg), or saline. At two time points (12 and 48 h), messenger RNA levels of hypothalamic corticotropin-releasing hormone, pituitary proopiomelanocortin, and four adrenal enzymes (P450 side-chain cleavage, 3ß-hydroxysteroid deshydrogenase, 21-hydroxylase, and 11ß-hydroxylase) were measured by in situ hybridization (results are presented as optical density), and plasma levels of corticosterone and adrenocorticotropin hormones were measured by enzyme-linked immunosorbent assay (mean ± SD). RESULTS: At 12 h, lipopolysaccharide induced an overexpression of corticotropin-releasing hormone (32 ± 5 vs. 18 ± 6, P < 0.01), proopiomelanocortin (21 ± 3 vs. 8 ± 0.9, P < 0.0001), P450 side-chain cleavage (32 ± 4 vs. 23 ± 10, P < 0.05), 21-hydroxylase (17 ± 5 vs. 12 ± 2, P < 0.05), and 11ß-hydroxylase (11 ± 4 vs. 6 ± 0.5, P = 0.001), and an elevation of corticosterone (642 ± 165 vs. 98.3 ± 63 ng/ml, P < 0.0001). Etomidate and ketamine reduced P450 side-chain cleavage (19 ± 7 and 19 ± 3 vs. 32 ± 4, P < 0.01), 21-hydroxylase (8 ± 0.8 and 8 ± 1 vs. 17 ± 5, P < 0.001), 11ß-hydroxylase (4 ± 0.5 and 7 ± 1 vs. 11 ± 4, P < 0.001 and P < 0.05), and corticosterone (413 ± 189 and 260 ± 161 vs. 642 ± 165 ng/ml, P < 0.05 and P < 0.01). Ketamine also inhibited adrenocorticotropin hormone production (2.5 ± 3.6 vs. 36 ± 15 pg/ml, P < 0.05). At 48 h, all four adrenal enzymes were down-regulated by lipopolysaccharide administration with corticosterone levels similar to the control group. Ketamine and etomidate did not modify corticosterone plasma levels. CONCLUSIONS: Our endotoxemic model induces an initial activation of the hypothalamic-pituitary-adrenal axis, followed by a secondary inhibition of adrenal steroidogenesis processes. Ketamine and etomidate inhibit the enzyme expression and activity of the adrenal gland at the early stage.

Background noise lowers the performance of anaesthesiology residents' clinical reasoning when measured by script concordance: A randomised crossover volunteer study.

BACKGROUND: Noise, which is omnipresent in operating rooms and ICUs, may have a negative impact not only patients but also on the concentration of and communication between clinical staff. OBJECTIVE: The present study attempted to evaluate the impact of noise on the performance of anaesthesiology residents' clinical reasoning. Changes in clinical reasoning were measured by script concordance tests (SCTs). DESIGN: This was a randomised and crossover study. SETTING: Single centre at Rouen University Hospital in April 2014. POPULATION: All year 1 to 4 residents enrolled in the anaesthesiology training programme were included. INTERVENTION: Performance was assessed using a 56-item SCT. Two resident groups were formed, and each was exposed to both quiet and noisy atmospheres during SCT assessment. Group A did the first part of the assessment (28 SCT) in a quiet atmosphere and the second part (28 SCT) in a noisy atmosphere. Group B did the same in reverse order. MAIN OUTCOME MEASURES: The primary outcome of this study was residents' performance as measured by SCT, with and without noise (mean of 100 points 95% confidence interval). RESULTS: Forty-two residents were included. Residents' performance, measured by SCT, was weaker in a noisy environment than in a quiet environment [59.0 (56.0 to 62.0) vs 62.8 (60.8 to 64.9), P = 0.04]. This difference lessened as medical training advanced, as this difference in performance in noisy vs quiet environments was not observed in year 3 and 4 residents [62.9 (59.2 to 66.5) vs 64.0 (61.9 to 66.1), P = 0.60], whereas it was higher for year 1 and 2 residents [54.8 (50.6 to 59.1) vs 61.5 (57.9 to 65.1), P = 0.02]. CONCLUSION: Our study suggests that noise affects clinical reasoning of anaesthesiology residents especially junior residents when measured by SCT. This observation supports the hypothesis that noise should be prevented in operating rooms especially when junior residents are providing care.

Increased Hypothalamic Levels of Endozepines, Endogenous Ligands of Benzodiazepine Receptors, in a Rat Model of Sepsis.

BACKGROUND: The mechanisms involved in septic anorexia are mainly related to the secretion of inflammatory cytokines. The term endozepines designates a family of neuropeptides, including the octadecaneuropeptide (ODN), originally isolated as endogenous ligands of benzodiazepine receptors. Previous data showed that ODN, produced and released by astrocytes, is a potent anorexigenic peptide. We have studied the effect of sepsis by means of a model of cecal ligation and puncture (CLP) on the hypothalamic expression of endozepines (DBI mRNA and protein levels), as well as on the level of neuropeptides controlling energy homeostasis mRNAs: pro-opiomelanocortin, neuropeptide Y, and corticotropin-releasing hormone. In addition, we have investigated the effects of two inflammatory cytokines, TNF-α and IL-1ß, on DBI mRNA levels in cultured rat astrocytes. METHODS: Studies were performed on Sprague-Dawley male rats and on cultures of rat cortical astrocytes. Sepsis was induced using the CLP method. Sham-operated control animals underwent the same procedure, but the cecum was neither ligated nor incised. RESULTS: Sepsis caused by CLP evoked an increase of DBI mRNA levels in ependymal cells bordering the third ventricle and in tanycytes of the median eminence. CLP-induced sepsis was also associated with stimulated ODN-like immunoreactivity (ODN-LI) in the hypothalamus. In addition, TNF-α, but not IL-1ß, induced a dose-dependent increase in DBI mRNA in cultured rat astrocytes. An increase in the mRNA encoding the precursor of the anorexigenic peptide α-melanocyte stimulating hormone, the pro-opiomelanocortin, and the corticotropin-releasing hormone was observed in the hypothalamus. CONCLUSION: These results suggest that during sepsis, hypothalamic mRNA encoding endozepines, anorexigenic peptide as well as stress hormone could play a role in the anorexia/cachexia associated with inflammation due to sepsis and we suggest that this hypothalamic mRNA expression could involve TNF-α.

Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study.

INTRODUCTION: Recent work has shown that benzodiazepines interact with the immune system and exhibit anti-inflammatory effects. By using in vitro models, researchers in several studies have shown that the peptidergic endogenous ligands of benzodiazepine receptors, named endozepines, are involved in the immune response. All endozepines identified so far derive from diazepam-binding inhibitor (DBI), which generates several biologically active fragments. The aim of the present study was to measure plasma levels of DBI-like immunoreactivity (DBI-LI) in a rat model of sepsis and in patients with systemic inflammation from septic or non-septic origin. METHODS: Cecal ligation and puncture (CLP) or sham surgery was performed in rats. Blood samples were taken from animals, patients hospitalized for digestive surgery with inflammatory diseases, and healthy volunteers. Measurements of plasma DBI-related peptides were carried out by radioimmunoassay in animal and human samples. RESULTS: In the rats, CLP provoked an increase of plasma DBI-LI (+37%) 6 hours postsurgery. In humans, DBI-LI levels were significantly higher in the systemic inflammation group than in the healthy volunteer group (48.6 (32.7 to 77.7) pg/ml versus 11.1 (5.9 to 35.3) pg/ml, P < .001). We found a positive correlation between endozepine levels and Acute Physiology and Chronic Health Evaluation II score (r s = 0.33 (0.026 to 0.58), P < 0.05) and tumor necrosis factor α levels (r s = 0.43 (0.14 to 0.65), P < 0.01). The area under the receiver operating characteristic curve for endozepines was 0.842 (95% CI (0.717 to 0.966), P < 0.0001) for discriminating patients with inflammation from healthy volunteers. CONCLUSIONS: Endozepines might be involved in the inflammatory response in patients with systemic inflammation.