Karim Asehnoune

Hydrocortisone Therapy for Patients With Multiple Trauma: The Randomized Controlled HYPOLYTE Study

CONTEXT The role of stress-dose hydrocortisone in the management of trauma patients is currently unknown. OBJECTIVE To test the efficacy of hydrocortisone therapy in trauma patients. DESIGN, SETTING, AND PATIENTS Multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study. From November 2006 to August 2009, 150 patients with severe trauma were included in 7 intensive care units in France. INTERVENTION Patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response. MAIN OUTCOME MEASURE Hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death. RESULTS One patient withdrew consent. An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30-0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25-0.86; P = .01). Mechanical ventilation-free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2-11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, -9%; 95% CI, -16% to -3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, -5% to 11%; P = .44). CONCLUSION In intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00563303.

Early embolization and vasopressor administration for management of life-threatening hemorrhage from pelvic fracture.

BACKGROUND In this retrospective study, we reviewed our protocol for management of hemodynamically unstable patients with pelvic injury. METHODS We managed the patients with the same predetermined plan including controlled hemodynamic resuscitation with early use of vasopressors and pelvic angiography as a first-line treatment. RESULTS Of 311 patients with pelvic fracture, 32 hemodynamically unstable patients (10.3%) underwent pelvic angiography, which was followed by embolization in 25 cases. Angiography was successful for 24 patients (96%) and extrapelvic bleeding was diagnosed in 5 patients (15%). Three of six laparotomies performed before angiography were nontherapeutic. One of seven laparotomies performed after angiography was negative. CONCLUSION A protocol for management of patients with pelvic injury and hemodynamic instability that is associated with controlled resuscitation including vasopressor and early pelvic angioembolization is effective for treating pelvic hemorrhage and diagnosing extrapelvic hemorrhage. Further studies are needed to confirm the respective place of angiographic and surgical control of bleeding.

Early identification of patients at risk for difficult intubation in the intensive care unit: development and validation of the MACOCHA score in a multicenter cohort study.

RATIONALE Difficult intubation in the intensive care unit (ICU) is a challenging issue. OBJECTIVES To develop and validate a simplified score for identifying patients with difficult intubation in the ICU and to report related complications. METHODS Data collected in a prospective multicenter study from 1,000 consecutive intubations from 42 ICUs were used to develop a simplified score of difficult intubation, which was then validated externally in 400 consecutive intubation procedures from 18 other ICUs and internally by bootstrap on 1,000 iterations. MEASUREMENTS AND MAIN RESULTS In multivariate analysis, the main predictors of difficult intubation (incidence = 11.3%) were related to patient (Mallampati score III or IV, obstructive sleep apnea syndrome, reduced mobility of cervical spine, limited mouth opening); pathology (severe hypoxia, coma); and operator (nonanesthesiologist). From the β parameter, a seven-item simplified score (MACOCHA score) was built, with an area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.85-0.94). In the validation cohort (prevalence of difficult intubation = 8%), the AUC was 0.86 (95% CI, 0.76-0.96), with a sensitivity of 73%, a specificity of 89%, a negative predictive value of 98%, and a positive predictive value of 36%. After internal validation by bootstrap, the AUC was 0.89 (95% CI, 0.86-0.93). Severe life-threatening events (severe hypoxia, collapse, cardiac arrest, or death) occurred in 38% of the 1,000 cases. Patients with difficult intubation (n = 113) had significantly higher severe life-threatening complications than those who had a nondifficult intubation (51% vs. 36%; P < 0.0001). CONCLUSIONS Difficult intubation in the ICU is strongly associated with severe life-threatening complications. A simple score including seven clinical items discriminates difficult and nondifficult intubation in the ICU. Clinical trial registered with www.clinicaltrials.gov (NCT 01532063).

Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in Intensive Care Unit: an observational study

BackgroundThis study was design to investigate the prognostic value for death at day-28 of lactate course and lactate clearance during the first 24 hours in Intensive Care Unit (ICU), after initial resuscitation.MethodsProspective, observational study in one surgical ICU in a university hospital. Ninety-four patients hospitalized in the ICU for severe sepsis or septic shock were included. In this septic cohort, we measured blood lactate concentration at ICU admission (H0) and at H6, H12, and H24. Lactate clearance was calculated as followed: [(lactateinitial - lactatedelayed)/ lactateinitial] x 100%].ResultsThe mean time between severe sepsis diagnosis and H0 (ICU admission) was 8.0 ± 4.5 hours. Forty-two (45%) patients died at day 28. Lactate clearance was higher in survivors than in nonsurvivors patients for H0-H6 period (13 ± 38% and −13 ± 7% respectively, p = 0.021) and for the H0-H24 period (42 ± 33% and −17 ± 76% respectively, p < 0.001). The best predictor of death at day 28 was lactate clearance for the H0-H24 period (AUC = 0.791; 95% CI 0.6-0.85). Logistic regression found that H0-H24 lactate clearance was independently correlated to a survival status with a p = 0.047 [odds ratio = 0.35 (95% CI 0.01-0.76)].ConclusionsDuring the first 24 hr in the ICU, lactate clearance was the best parameter associated with 28-day mortality rate in septic patients. Protocol of lactate clearance-directed therapy should be considered in septic patients, even after the golden hours.

Spinal anesthesia using single injection small-dose bupivacaine versus continuous catheter injection techniques for surgical repair of hip fracture in elderly patients.

Aging and disease may make elderly patients particularly susceptible to hypotension during spinal anesthesia. We compared the hemodynamic effect of continuous spinal anesthesia (CSA) and small dose single injection spinal anesthesia (SA) regarding the incidence of hypotension. Seventy-four patients aged >75 yr undergoing surgical repair of hip fracture were randomized into 2 groups of 37 patients each. Group CSA received a continuous spinal anesthetic with a titration of 2.5 mg boluses every 15 min of isobaric bupivacaine, while group SA received a single injection spinal anesthetic with 7.5 mg of isobaric bupivacaine. The overall variations in noninvasive automated arterial blood pressure were not statistically significantly different in the 2 groups at baseline and after CSA or SA (not significant). In the SA group, 68% of patients experienced at least one episode of hypotension (decrease in systolic arterial blood pressure greater than 20% of baseline value) versus 31% of patients in the CSA group (P = 0.005). In the SA group, 51% of patients experienced at least one episode of severe hypotension (decrease in systolic arterial blood pressure more than 30% of baseline value) versus 8% of patients in the CSA group (P < 0.0001). In the CSA group, 4.5 ± 2 mg of ephedrine was injected versus 11 ± 2 mg in the SA group (P = 0.005). In the CSA group, 5 mg (2.5–10) of anesthetic solution was required versus 7.5 mg in the SA group (P < 0.0001). We conclude that, in elderly patients undergoing hip fracture repair, CSA provides fewer episodes of hypotension and severe hypotension compared with a single intrathecal injection of 7.5 mg bupivacaine.

Effect of oropharyngeal povidone-iodine preventive oral care on ventilator-associated pneumonia in severely brain-injured or cerebral hemorrhage patients: a multicenter, randomized controlled trial.

Objective:To evaluate the efficacy and safety of oral care with povidone-iodine on the occurrence of ventilator-associated pneumonia in a high-risk population. Design:A multicenter, placebo-controlled, randomized, double-blind, two-parallel-group trial performed between May 2008 and May 2011. Setting:Six ICUs in France. Patients:One hundred seventy-nine severely brain-injured patients (Glasgow Coma Scale ⩽ 8) or cerebral hemorrhage expected to be mechanically ventilated for more than 24 hours. Interventions:Participants were randomly assigned to receive oropharyngeal care with povidone-iodine (n = 91) or placebo (n = 88) six times daily until mechanical ventilation withdrawal. Measurements and Main Results:Primary endpoint was the rate of ventilator-associated pneumonia. Secondary endpoint included the rates of ventilator-associated tracheobronchitis and acute respiratory distress syndrome and patient’s outcome. The number of patients evaluable for the primary endpoint (preplanned modified intention-to-treat population) was 150 (78 in the povidone-iodine group, 72 in the placebo group). Ventilator-associated pneumonia occurred in 24 patients (31%) in the povidone-iodine group and 20 (28%) in the placebo group (relative risk, 1.11 [95% CI, 0.67–1.82]; p = 0.69). There was no significant difference between the two groups for ventilator-associated tracheobronchitis: eight patients (10%) in the povidone-iodine group and five patients (7%) in the placebo group (relative risk, 1.48 [95% CI, 0.51–4.31]; p = 0.47). Acute respiratory distress syndrome occurred in five patients in the povidone-iodine group but not in the placebo group (p = 0.06). There was no difference between groups for ICU and hospital lengths of stay, as well as ICU and 90-day mortality. Conclusions:There is no evidence to recommend oral care with povidone-iodine to prevent ventilator-associated pneumonia in high-risk patients. Furthermore, this strategy seems to increase the rate of acute respiratory distress syndrome.

Pneumonia Prevention to Decrease Mortality in Intensive Care Unit: A Systematic Review and Meta-analysis

BACKGROUND To determine the strategies of prevention of hospital-acquired pneumonia that reduce mortality in intensive care unit (ICU). METHODS We followed PRISMA (Preferred Reported Items for Systemic Reviews and Meta-Analyses) guidelines. We searched MEDLINE and the Cochrane Controlled Trials Register (through 10 June 2014) as well as reference lists of articles. We included all randomized controlled trials conducted in critically ill adult patients hospitalized in ICUs and evaluating digestive prophylactic methods (selective digestive decontamination [SDD], acidification of gastric content, early enteral feeding, prevention of microinhalation); circuit prophylactic methods (closed suctioning systems, early tracheotomy, aerosolized antibiotics, humidification, lung secretion drainage, silver-coated endotracheal tubes) or oropharyngeal prophylactic methods (selective oropharyngeal decontamination, patient position, sinusitis prophylaxis, subglottic secretion drainage, tracheal cuff monitoring). One reviewer extracted data that were checked by 3 others. The primary outcome was the mortality rate in the ICU. RESULTS We identified 157 randomized trials to pool in a meta-analysis. The primary outcome was available in 145 studies (n = 37 156). The risk ratio (RR) for death was 0.95 (95% confidence interval [CI], .92-.99; P = .02) in the intervention groups. In subgroup analysis, only SDD significantly decreased mortality compared with control (n = 10 227; RR, 0.84 [95% CI, .76-.92; P < .001]). The RR for in-ICU death was 0.78 (95% CI, .69-.89; P < .001; I(2) = 33%) in trials investigating SDD with systemic antimicrobial therapy and 1.00 (.84-1.21; P = .96; I(2) = 0%) without systemic antimicrobial therapy. CONCLUSIONS Selective digestive decontamination with systemic antimicrobial therapy reduced mortality and should be considered in critically ill patients at high risk for death.

The μ Opioid Receptor Mediates Morphine-induced Tumor Necrosis Factor and Interleukin-6 Inhibition in Toll-like Receptor 2-stimulated Monocytes

BACKGROUND: Morphine possesses immunomodulatory effects but its intrinsic mechanisms, especially in the toll-like receptor 2 (TLR2) signaling pathway, are only partially understood. In this study, we evaluated the effects of morphine on tumor necrosis factor (TNF), interleukin-6 (IL-6), and interleukin-10 (IL-10) production in TLR2-stimulated human monocytes and identified the involvement of the different opioid receptors, and of the lymphocyte-to-monocyte contact. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from fresh blood by centrifugation on a density gradient. Monocytes were secondarily separated using a high-gradient magnetic cell sorting kit with specific anti-CD14 antibodies. Monocytes or PBMCs were pretreated with opioid receptors antagonists before being cultured with morphine and peptidoglycan (PGN) from Staphylococcus aureus (specific TLR2 agonist). The amount of TNF, IL-6, and IL-10 was measured in the supernatant enzyme-linked immunosorbent assay. RESULTS: Proinflammatory cytokines: Morphine significantly inhibited the production of cytokines in a dose and concentration-dependent manner in PGN-stimulated monocytes. &mgr; Opioid receptor activation specifically mediated this morphine-induced TNF and IL-6 inhibition in monocytes. Morphine significantly inhibited the TNF, but not the IL-6 production, in PGN-stimulated PBMCs. The &mgr; opioid receptor was not involved in this morphine-induced TNF inhibition in PBMCs. Antiinflammatory cytokines: IL-10 was not a factor for the inhibition of TNF and IL-6 production after PGN stimulation in either monocytes or PBMCs cultures. CONCLUSIONS: The &mgr; opioid receptor mediates morphine-induced TNF and IL-6 inhibition in PGN-stimulated monocytes, but not in PBMCs. A direct monocyte-to-lymphocyte contact (PBMCs) alters the inhibitory effects of morphine observed on monocytes alone. IL-10 is not a factor for the inhibition of TNF or for IL-6 production. Interactions between TLR2 and &mgr; opioid intracellular pathways remain to be studied to delineate these morphine immunosuppressive effects.

CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

Gut bacterium Faecalibacterium prausnitzii activates a newly identified set of human IL-10-producing Treg cells (CD4CD8αα lymphocytes), revealing a mechanism by which commensal microbes contribute to host immunity.

Prehospital intravenous line placement assessment in the French emergency system: a prospective study

Background and objective: Out‐of‐hospital intravenous line placement is used daily. All available studies take place using paramedics, e.g. US‐American emergency medical system. The aim of this study was to assess the intravenous line placement feasibility (time and success rate) in the French emergency medical system. Methods: A prospective observational study was performed by a French out‐of‐hospital team during 3‐month assessing the timing and success rates for intravenous line placement. All patients were enrolled at the emergency medical service of a university hospital in France. Six hundred and sixty‐nine consecutive patients were included, 388 (58%) had at least one intravenous line placement in the out‐of‐hospital setting. Results: Success rate was 76% at the first attempt and 98% at the second attempt. The overall success rate for intravenous line placement was 99.7% (only one failure), and the average successful intravenous line time was 4.4 ± 2.8 min. Attempts ranged from 1 to 8. The time for intravenous line placement with blood sampling (58% of patients) is statistically longer than without (4.6 ± 2.5 vs. 4.3 ± 3 min, P < 0.05). Seventeen of the enrolled patients were trauma patients, and 83% were non‐trauma patients. Four hundred and twenty‐seven intravenous lines were placed, intravenous 10% had more than one intravenous line. Seventy‐one percent of the intravenous lines were used to infuse drugs, the others were security intravenous. No significant difference was noticed between trauma and non‐trauma patients in regard to the success rate and the time to place the intravenous line. Conclusion: The out‐of‐hospital team was skilled at intravenous line placement (success rate = 99.7%), and the time required to performed intravenous line access was short.