Preoperative endothelial dysfunction for the prediction of acute kidney injury after cardiac surgery using cardiopulmonary bypass: a pilot study based on a second analysis of the MONS study.

BACKGROUND: Up to 42% of patients develop acute kidney injury (AKI) after cardiac surgery. The aim of this study was to describe the relationship between preoperative microcirculatory function and postoperative AKI after cardiac surgery using cardiopulmonary bypass (CPB). METHODS: The prospective observational cohort MONS enrolled 60 patients scheduled for valvular (n = 30, 50%) or coronary (n = 30, 50%) surgery using CPB. Preoperative microcirculation was assessed during preoperative consultation from January 2019 to April 2019 at the University Hospital of Angers, France, using endothelium-dependent and endothelium-independent reactivity tests on the forearm (iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively). Skin blood flow was measured by laser speckle contrast imaging. The primary endpoint was the occurrence of AKI according to the KDIGO classification during the hospital stay. RESULTS: Forty-three (71.7%) patients developed AKI during the in-hospital follow-up, and 15 (25%) were classified as KDIGO stage 1, 20 (33%) KDIGO stage 2, and 8 (13%) KDIGO stage 3. Regarding preoperative microcirculation, a higher peak amplitude of vasodilation in response to iontophoresis of ACh was found in patients with postoperative occurrence of AKI (35 [20-49] vs 23 [9-44] LSPU, p = 0.04). Iontophoresis of SNP was not significantly different according to AKI occurrence (34 [22-49] vs 36 [20-50] LSPU, p = 0.95). In a multivariable model, the preoperative peak amplitude at iontophoresis of ACh was independently associated with postoperative AKI (OR 1.045 [1.001-1.092], p = 0.045). CONCLUSIONS: The preoperative peak amplitude of endothelium-dependent vasodilation is independently associated with the postoperative occurrence of AKI. TRIAL REGISTRATION: Clinical-Trials.gov, NCT03631797. Registered 15 August 2018, https://clinicaltrials.gov/ct2/show/NCT03631797.

Interferon-Gamma-Release assay and absolute CD8 lymphocyte count for acquired immunosuppression monitoring in critically ill patients.

Guided biomarker-personalized immunotherapy is advancing rapidly as a means to rejuvenate immune function in injured patients who are the most immunosuppressed. A recent study introduced a fully automated interferon-γ release assay (IGRA) for monitoring the functionality of T lymphocytes in patients with septic shock. While a significant decrease in IFN-γ release capacity was observed, a significant correlation with CD8 lymphocyte absolute count was also reported, raising the question of whether ex-vivo IFN-γ production would be only a surrogate marker for lymphocyte count or if these two parameters conveyed distinct and complementary information. In a large cohort of more than 353 critically ill patients following various injuries (sepsis, trauma, major surgery), the primary objective of the present study was to simultaneously evaluate the association between ex vivo IFN-γ release and CD8 cell count with regard to adverse outcome. Our findings provide a clear-cut result, as they distinctly demonstrate that IGRA offers higher-quality information than CD8 count in terms of an independent association with the occurrence of an adverse outcome. These results strengthen the case for incorporating IGRA into the array of biomarkers of interest for defining endotypes in sepsis. This holds especially true given that fully automated tests are now readily available and could be used in routine clinical practice.

Economic burden of in-hospital AKI: a one-year analysis of the nationwide French hospital discharge database.

BACKGROUND: Although Acute Kidney Injury (AKI) incidence is increasing worldwide, data investigating its cost are lacking. This population-wide study aimed to describe the characteristics and costs of hospital stays with, and without AKI, and to estimate the AKI-associated increases in costs and length of stay (LOS) in three subgroups (major open visceral surgery (MOV), cardiovascular surgery with extracorporeal circulation (CVEC), and sepsis). METHODS: All hospital stays that occurred in France in 2018 were included. Stay and patient characteristics were collected in the French hospital discharge database and described. Medical conditions were identified using the 10th International Classification of Diseases and the medical acts classification. In each subgroup, the adjusted increase in cost and LOS associated with AKI was estimated using a generalized linear model with gamma distribution and a log link function. RESULTS: 26,917,832 hospital stays, of which 415,067 (1.5%) with AKI, were included. AKI was associated with 83,553 (19.8%), 7,165 (17.9%), and 15,387 (9.2%) of the stays with sepsis, CVEC, and MOV, respectively. Compared to stays without AKI, stays with AKI were more expensive (median [IQR] €4,719[€2,963-€7782] vs. €735[€383-€1,805]) and longer (median [IQR] 9[4-16] vs. 0[0-2] days). AKI was associated with a mean [95%CI] increase in hospitalization cost of 70% [69;72], 48% [45;50], and 68% [65;70] in the sepsis, CVEC, and MOV groups respectively, after adjustment. CONCLUSION: This study confirms the major economic burden of in-hospital AKI in a developed country. Interventions to prevent AKI are urgently needed and their cost should be balanced with AKI-related costs.

Excess mortality among non-COVID-19 surgical patients attributable to the exposure of French intensive and intermediate care units to the pandemic.

PURPOSE: The mobilization of most available hospital resources to manage coronavirus disease 2019 (COVID-19) may have affected the safety of care for non-COVID-19 surgical patients due to restricted access to intensive or intermediate care units (ICU/IMCUs). We estimated excess surgical mortality potentially attributable to ICU/IMCUs overwhelmed by COVID-19, and any hospital learning effects between two successive pandemic waves. METHODS: This nationwide observational study included all patients without COVID-19 who underwent surgery in France from 01/01/2019 to 31/12/2020. We determined pandemic exposure of each operated patient based on the daily proportion of COVID-19 patients among all patients treated within the ICU/IMCU beds of the same hospital during his/her stay. Multilevel models, with an embedded triple-difference analysis, estimated standardized in-hospital mortality and compared mortality between years, pandemic exposure groups, and semesters, distinguishing deaths inside or outside the ICU/IMCUs. RESULTS: Of 1,870,515 non-COVID-19 patients admitted for surgery in 655 hospitals, 2% died. Compared to 2019, standardized mortality increased by 1% (95% CI 0.6-1.4%) and 0.4% (0-1%) during the first and second semesters of 2020, among patients operated in hospitals highly exposed to pandemic. Compared to the low-or-no exposure group, this corresponded to a higher risk of death during the first semester (adjusted ratio of odds-ratios 1.56, 95% CI 1.34-1.81) both inside (1.27, 1.02-1.58) and outside the ICU/IMCU (1.98, 1.57-2.5), with a significant learning effect during the second semester compared to the first (0.76, 0.58-0.99). CONCLUSION: Significant excess mortality essentially occurred outside of the ICU/IMCU, suggesting that access of surgical patients to critical care was limited.

Hypobaric Unilateral Spinal Anesthesia Versus General Anesthesia for Hip Fracture Surgery in the Elderly: A Randomized Controlled Trial.

BACKGROUND: Hypotension during surgery is frequent in the elderly population and is associated with acute kidney and myocardial injury, which are, themselves, associated with increased 30-day mortality. The present study compared the hemodynamic effects of hypobaric unilateral spinal anesthesia (HUSA) to general anesthesia (GA) in patients ≥70 years of age undergoing hip fracture surgery. METHODS: We conducted a single-center, prospective, randomized study. In the HUSA group, patients were positioned with the operated hip above, and the hypobaric anesthetic solution was composed of 9 mg ropivacaine, 5 µg sufentanil, and 1 mL of sterile water. Anesthesia was adjusted for the GA group. Mean arterial pressure (MAP) was measured with a noninvasive blood pressure upper arm cuff every 3 minutes. Hypotension was treated with a bolus of ephedrine and then a continuous intravenous of norepinephrine to obtain a MAP ≥65 mm Hg. Primary outcome was the occurrence of severe hypotension, defined as a MAP <65 mm Hg for >12 consecutive minutes. RESULTS: A total of 154 patients were included. Severe hypotension was more frequent in the GA group compared to the HUSA group (odds ratio, 5.6; 95% confidence interval, 2.7-11.7; P < .001). There was no significant difference regarding the short-term outcomes between the HUSA and GA groups: acute kidney injury (respectively, 5.1% vs 11.3%; P = .22), myocardial injury (18.0% vs 14.0%; P = .63), and 30-day mortality (2.4% vs 4.7%; P = .65). CONCLUSIONS: HUSA leads to fewer episodes of severe intraoperative hypotension compared to GA in an elderly population undergoing hip fracture surgery.

A stratification strategy to predict secondary infection in critical illness-induced immune dysfunction: the REALIST score.

BACKGROUND: Although multiple individual immune parameters have been demonstrated to predict the occurrence of secondary infection after critical illness, significant questions remain with regards to the selection, timing and clinical utility of such immune monitoring tests. RESEARCH QUESTION: As a sub-study of the REALISM study, the REALIST score was developed as a pragmatic approach to help clinicians better identify and stratify patients at high risk for secondary infection, using a simple set of relatively available and technically robust biomarkers. STUDY DESIGN AND METHODS: This is a sub-study of a single-centre prospective cohort study of immune profiling in critically ill adults admitted after severe trauma, major surgery or sepsis/septic shock. For the REALIST score, five immune parameters were pre-emptively selected based on their clinical applicability and technical robustness. Predictive power of different parameters and combinations of parameters was assessed. The main outcome of interest was the occurrence of secondary infection within 30 days. RESULTS: After excluding statistically redundant and poorly predictive parameters, three parameters remained in the REALIST score: mHLA-DR, percentage of immature (CD10- CD16-) neutrophils and serum IL-10 level. In the cohort of interest (n = 189), incidence of secondary infection at day 30 increased from 8% for patients with REALIST score of 0 to 46% in patients with a score of 3 abnormal parameters, measured ad D5-7. When adjusted for a priori identified clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5-7), a higher REALIST score was independently associated with increased risk of secondary infection (42 events (22.2%), adjusted HR 3.22 (1.09-9.50), p = 0.034) and mortality (10 events (5.3%), p = 0.001). INTERPRETATION: We derived and presented the REALIST score, a simple and pragmatic stratification strategy which provides clinicians with a clear assessment of the immune status of their patients. This new tool could help optimize care of these individuals and could contribute in designing future trials of immune stimulation strategies.

Effects of opioid-free anesthesia on postoperative morphine consumption after bariatric surgery.

STUDY OBJECTIVES: The objective of this study was to determine whether postoperative morphine requirement in obese patients undergoing laparoscopic bariatric surgery was reduced by opioid-free anesthesia (OFA), as compared to an anesthetic strategy using opioids (opioid balanced anesthesia (OBA)) and to investigate the differences that may exist between the use of clonidine and dexmedetomidine in the context of OFA. DESIGN: Retrospective cohort study. SETTING: Academic medical center in Lyon, France. PATIENTS: 257 patients who underwent laparoscopic bariatric surgery between March 2017 and March 2019. 77 patients were included in the OBA group and 180 in the OFA group. The OFA group was subdivided in two: 90 patients received OFA with clonidine (OFAC) and 90 received OFA with dexmedetomidine (OFAD). MEASUREMENTS: Proportion of patients who did not receive morphine during the first 24 postoperative hours. MAIN RESULTS: During the first 24 postoperative hours, the proportion of patients who did not require morphine was significantly higher in the OFA (87%) than in the OBA (52%) group (OR: 6.31; 95% CI [3.38; 11.80], P < 0.001). This difference remained significant after adjustment for age, body mass index, sex, type and duration of surgery (OR: 7.99; 95% CI [4.05; 16.48], P < 0.001). A greater proportion of patients in the OFAD (93%) than in the OFAC group (81%, P = 0.026) did not receive morphine during the same period. CONCLUSIONS: OFA is associated with a lower morphine requirement than with OBA during the first 24 h after bariatric surgery. In addition, OFAD seems to be more effective than OFAC in order to reduce morphine consumption.

Characterising acute kidney injury: The complementary roles of biomarkers of renal stress and renal function.

PURPOSE: Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. MATERIALS & METHODS: Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119-159 2 were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2-3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). RESULTS: 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76-0.84) to 0.85 (0.81-0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). CONCLUSIONS: The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone.

A retrospective comparison of COVID-19 and seasonal influenza mortality and outcomes in the ICUs of a French university hospital.

BACKGROUND: SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019. OBJECTIVE: To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France. DESIGN: A retrospective study. SETTING: Six ICUs in a single institution in Lyon, France. PATIENTS: Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021. MAIN OUTCOMES AND MEASURES: Differences in 90-day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model. RESULTS: COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P = 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P < 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P < 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement. CONCLUSION: After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different.

Emergence of immunosuppressive LOX-1+ PMN-MDSC in septic shock and severe COVID-19 patients with acute respiratory distress syndrome.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells with immunosuppressive properties. In cancer patients, the expression of lectin-type oxidized LDL receptor 1 (LOX-1) on granulocytic MDSC identifies a subset of MDSC that retains the most potent immunosuppressive properties. The main objective of the present work was to explore the presence of LOX-1+ MDSC in bacterial and viral sepsis. To this end, whole blood LOX-1+ cells were phenotypically, morphologically, and functionally characterized. They were monitored in 39 coronavirus disease-19 (COVID-19, viral sepsis) and 48 septic shock (bacterial sepsis) patients longitudinally sampled five times over a 3 wk period in intensive care units (ICUs). The phenotype, morphology, and immunosuppressive functions of LOX-1+ cells demonstrated that they were polymorphonuclear MDSC. In patients, we observed the significant emergence of LOX-1+ MDSC in both groups. The peak of LOX-1+ MDSC was 1 wk delayed with respect to ICU admission. In COVID-19, their elevation was more pronounced in patients with acute respiratory distress syndrome. The persistence of these cells may contribute to long lasting immunosuppression leaving the patient unable to efficiently resolve infections.

Herpes DNAemia and TTV Viraemia in Intensive Care Unit Critically Ill Patients: A Single-Centre Prospective Longitudinal Study.

Introduction: We analysed blood DNAemia of TTV and four herpesviruses (CMV, EBV, HHV6, and HSV-1) in the REAnimation Low Immune Status Marker (REALISM) cohort of critically ill patients who had presented with either sepsis, burns, severe trauma, or major surgery. The aim was to identify common features related to virus and injury-associated pathologies and specific features linking one or several viruses to a particular pathological context. Methods: Overall and individual viral DNAemia were measured over a month using quantitative PCR assays from the 377 patients in the REALISM cohort. These patients were characterised by clinical outcomes [severity scores, mortality, Intensive Care Unit (ICU)-acquired infection (IAI)] and 48 parameters defining their host response after injury (cell populations, immune functional assays, and biomarkers). Association between viraemic event and clinical outcomes or immune markers was assessed using χ2-test or exact Fisher's test for qualitative variables and Wilcoxon test for continuous variables. Results: The cumulative incidence of viral DNAemia increased from below 4% at ICU admission to 35% for each herpesvirus during the first month. EBV, HSV1, HHV6, and CMV were detected in 18%, 12%, 10%, and 9% of patients, respectively. The incidence of high TTV viraemia (>10,000 copies/ml) increased from 11% to 15% during the same period. Herpesvirus viraemia was associated with severity at admission; CMV and HHV6 viraemia correlated with mortality during the first week and over the month. The presence of individual herpesvirus during the first month was significantly associated (p < 0.001) with the occurrence of IAI, whilst herpesvirus DNAemia coupled with high TTV viraemia during the very first week was associated with IAI. Herpesvirus viraemia was associated with a lasting exacerbated host immune response, with concurrent profound immune suppression and hyper inflammation, and delayed return to immune homeostasis. The percentage of patients presenting with herpesvirus DNAemia was significantly higher in sepsis than in all other groups. Primary infection in the hospital and high IL10 levels might favour EBV and CMV reactivation. Conclusion: In this cohort of ICU patients, phenotypic differences were observed between TTV and herpesviruses DNAemia. The higher prevalence of herpesvirus DNAemia in sepsis hints at further studies that may enable a better in vivo understanding of host determinants of herpesvirus viral reactivation. Furthermore, our data suggest that EBV and TTV may be useful as additional markers to predict clinical deterioration in ICU patients.

Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

[Study of monocytic myeloid-derived suppressor cells and CD4 lymphopenia in septic shock-induced immunosuppression]. / Étude des cellules myéloïdes immunosuppressives monocytaires au cours de l'immunodépression associée au choc septique.

Sepsis is one of the leading causes of in-hospital mortality. In some patients, sepsis-induced immunosuppression is associated with increased risk of death and secondary infections. In oncology, myeloid-derived suppressor cells (MDSCs) have been described to inhibit various immune functions. Monocytic MDSCs (M-MDSCs) represent a subtype of MDSCs. The objectives of the present study was to determine by flow cytometry the % M-MDSCs (among total monocyte population) in a cohort of septic shock patients and to assess its association with deleterious outcomes: 28-day mortality and occurrence of nosocomial infections. The cohort included 301 patients. They presented with immune alterations usually found 3-4 days after the onset of shock: lymphopenia (median T CD4: 362/µL, quartiles: 235-591/µL) and low monocytic HLA-DR expression (median: 4,944 AB/C, quartiles: 3,104-8,266 AB/C). From admission until the end of the first week, % M-MDSCs was significantly increased in patients compared with healthy donors (p < 0.01). In early samples, no association with deleterious outcomes was identified. However, after one week, patients who were going to die or to develop nosocomial infections presented with significantly higher % M-MDSCs than non-survivors and non-infected patients (p < 0.01). These associations remained significant in multivariate analyses, odds ratio of 4.4 (p = 0.001) regarding 28-day mortality and 2.4 (p = 0.013) regarding occurrence of nosocomial infections. In conclusion, % M-MDSCs was markedly increased after septic shock. One week-persistence of an increased proportion of M-MDSCs was associated with unfavorable outcomes.

Concomitant Assessment of Monocyte HLA-DR Expression and Ex Vivo TNF-α Release as Markers of Adverse Outcome after Various Injuries-Insights from the REALISM Study.

Intensive care unit (ICU) patients develop an altered host immune response after severe injuries. This response may evolve towards a state of persistent immunosuppression that is associated with adverse clinical outcomes. The expression of human leukocyte antigen DR on circulating monocytes (mHLA-DR) and ex vivo release of tumor necrosis factor α (TNF-α) by lipopolysaccharide-stimulated whole blood are two related biomarkers offered to characterize this phenomenon. The purpose of this study was to concomitantly evaluate the association between mHLA-DR and TNF-α release and adverse clinical outcome (i.e., death or secondary infection) after severe trauma, sepsis or surgery in a cohort of 353 ICU patients. mHLA-DR and TNF-α release was similarly and significantly reduced in patients whatever the type of injury. Persistent decreases in both markers at days 5-7 (post-admission) were significantly associated with adverse outcomes. Overall, mHLA-DR (measured by flow cytometry) appears to be a more robust and standardized parameter. Each marker can be used individually as a surrogate of immunosuppression, depending on center facilities. Combining these two parameters could be of interest to identify the most immunosuppressed patients presenting with a high risk of worsening. This last aspect deserves further exploration.

Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study.

The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a "healthy-immune response" and a "sepsis-related host response". The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.

Characterization of Circulating IL-10-Producing Cells in Septic Shock Patients: A Proof of Concept Study.

Sepsis is a worldwide health priority characterized by the occurrence of severe immunosuppression associated with increased risk of death and secondary infections. Interleukin 10 (IL-10) is a potent immunosuppressive cytokine which plasma concentration is increased in septic patients in association with deleterious outcomes. Despite studies evaluating IL-10 production in specific subpopulations of purified cells, the concomitant description of IL-10 production in monocytes and lymphocytes in septic patients' whole blood has never been performed. In this pilot study, we characterized IL-10 producing leukocytes in septic shock patients through whole blood intracellular staining by flow cytometry. Twelve adult septic shock patients and 9 healthy volunteers were included. Intracellular tumor necrosis factor-α (TNFα) and IL-10 productions after lipopolysaccharide stimulation by monocytes and IL-10 production after PMA/Ionomycine stimulation by lymphocytes were evaluated. Standard immunomonitoring (HLA-DR expression on monocytes, CD4+ T lymphocyte count) of patients was also performed. TNFα expression by stimulated monocytes was reduced in patients compared with controls while IL-10 production was increased. This was correlated with a reduced monocyte HLA-DR expression. B cells, CD4+, and CD4- T lymphocytes were the three circulating IL-10 producing lymphocyte subsets in both patients and controls. No difference in IL-10 production between patients and controls was observed for B and CD4- T cells. However, IL-10 production by CD4+ T lymphocytes significantly increased in patients in parallel with reduced CD4+ T cells number. Parameters reflecting altered monocyte (increased IL-10 production, decreased HLA-DR expression and decreased TNFα synthesis) and CD4+ T lymphocyte (increased IL-10 production, decreased circulating number) responses were correlated. Using a novel technique for intracellular cytokine measurement in whole blood, our results identify monocytes and CD4+ T cells as the main IL-10 producers in septic patients' whole blood and illustrate the development of a global immunosuppressive profile in septic shock. Overall, these preliminary results add to our understanding of the global increase in IL-10 production induced by septic shock. Further research is mandatory to determine the pathophysiological mechanisms leading to such increased IL-10 production in monocytes and CD4+ T cells.

Serum Concentrations of Lidocaine During Bariatric Surgery.

Lidocaine has been shown to be clinically beneficial during bariatric surgery. However, information about lidocaine serum concentrations in this setting is scarce. This prospective clinical trial included 42 obese patients undergoing laparoscopic bariatric surgery. They received lidocaine based on adjusted body weight. Administration began with a 1.5 mg·kg bolus of intravenous lidocaine followed by a continuous infusion of 2 mg·kg·hour. After skin closure, administration was decreased to 1 mg·kg·hour until discharge from the recovery room. No serum concentrations of lidocaine were outside the usual accepted range (1.5-5 µg·mL).

Simulation of difficult airway management for residents: prospective comparative study / Simulação de manejo de via aérea difícil para residentes: estudo comparativo prospectivo

Abstract Background and objectives Procedural simulation training for difficult airway management offers acquisition opportunities. The hypothesis was that 3 hours of procedural simulation training for difficult airway management improves: acquisition, behavior, and patient outcomes as reported 6 months later. Methods This prospective comparative study took place in two medical universities. Second-year residents of anesthesiology and intensive care from one region participated in 3 h procedural simulation (intervention group). No intervention was scheduled for their peers from the other region (control). Prior to simulation and 6 months later, residents filled-out the same self-assessment form collecting experience with different devices. The control group filled-out the same forms simultaneously. The primary endpoint was the frequency of use of each difficult airway management device within groups at 6 months. Secondary endpoints included modifications of knowledge, skills, and patient outcomes with each device at 6 months. Intervention cost assessment was provided. Results 44 residents were included in the intervention group and 16 in the control group. No significant difference was observed for the primary endpoint. In the intervention group, improvement of knowledge and skills was observed at 6 months for each device, and improvement of patient outcomes was observed with the use of malleable intubation stylet and Eschmann introducer. No such improvement was observed in the control group. Estimated intervention cost was 406€ per resident. Conclusions A 3 h procedural simulation training for difficult airway management did not improve the frequency of use of devices at 6 months by residents. However, other positive effects suggest exploring the best ratio of time/acquisition efficiency with difficult airway management simulation. ClinicalTrials.gov Identifier NCT02470195.

Resumo Justificativa e objetivos O treinamento em simulação para o manejo de via aérea difícil oferece oportunidades de aprendizagem. A hipótese foi que um treinamento em simulação de procedimentos de três horas, para o manejo de via aérea difícil, melhoraria o aprendizado, o comportamento e os resultados dos pacientes, conforme relatado seis meses após o treinamento. Métodos Este estudo comparativo prospectivo foi realizado em duas universidades médicas. Residentes do segundo ano de anestesiologia e terapia intensiva de uma região participaram de um curso de três horas em simulação de procedimentos (grupo intervenção). Nenhuma intervenção foi programada para seus pares da outra região (grupo controle). Antes da simulação e seis meses após, os residentes preencheram a mesma ficha de autoavaliação sobre sua experiência com diferentes dispositivos. O grupo controle preencheu os mesmos formulários simultaneamente. O desfecho primário foi a frequência de uso de cada dispositivo para o manejo de via aérea difícil dentro dos grupos aos seis meses. Os pontos de corte secundários incluíram modificações em relação ao conhecimento, às habilidades e aos resultados dos pacientes com cada dispositivo aos seis meses. A avaliação do custo da intervenção foi registrada. Resultados Foram incluídos no grupo intervenção 44 residentes e 16 no grupo controle. Nenhuma diferença significativa foi observada para o ponto de corte primário. No grupo intervenção, a melhoria do conhecimento e das habilidades foi observada aos seis meses para cada dispositivo e a melhoria dos desfechos dos pacientes foi analisada com o uso de estilete maleável e do introdutor de Eschmann para intubação. Nenhuma melhoria foi observada no grupo controle. O custo da intervenção estimado foi de 406€ por residente. Conclusões Um treinamento simulado de três horas para o manejo de via aérea difícil não melhorou a frequência do uso de dispositivos pelos residentes aos seis meses. No entanto, outros efeitos positivos sugerem a exploração da melhor relação tempo/eficiência de aquisição de conhecimento com a simulação do manejo de via aérea difícil. ClinicalTrials.gov Identifier NCT02470195.