Biblio du Mois : Août-Septembre 2019


Et oui, c’est le grand retour, la grande rentrée de la Biblio du Mois de l’AJAR Paris !

Au programme,

-Petit retour sur les Recommandations ESC 2019.

-Retour de la CRP ?

-De la neurologie avec des études sur les Novoseven, Deferoxamine dans les hématomes intra-cérébraux

-De la Ventilation avec de multiples études intéressantes, on vous a fait un Best-of sur la NAVA

-L’impact de l’acidose hyperchlorhémique en études

-De nouvelles molécules ? Coagulation du au sepsis et traitement éventuel étudié : iloprost et eptifibatide / Vasopressine dans le choc hémorragique / Biomarqueur d’insuffisance cardiaque CA-125 avec les échecs d’autres Levosimendan / CTC …

Enjoy ! <3

Et pour ne plus louper une miette de l’AJAR Paris : suivez-nous sur nos réseaux sociaux et pour la biblio :






Intérêt de la CRP dans les décompensations de BPCO


Butler et al., NEJM, 2019

N Engl J Med 2019; 381:111-120
DOI: 10.1056/NEJMoa1803185




Point-of-care testing of C-reactive protein (CRP) may be a way to reduce unnecessary use of antibiotics without harming patients who have acute exacerbations of chronic obstructive pulmonary disease (COPD).


We performed a multicenter, open-label, randomized, controlled trial involving patients with a diagnosis of COPD in their primary care clinical record who consulted a clinician at 1 of 86 general medical practices in England and Wales for an acute exacerbation of COPD. The patients were assigned to receive usual care guided by CRP point-of-care testing (CRP-guided group) or usual care alone (usual-care group). The primary outcomes were patient-reported use of antibiotics for acute exacerbations of COPD within 4 weeks after randomization (to show superiority) and COPD-related health status at 2 weeks after randomization, as measured by the Clinical COPD Questionnaire, a 10-item scale with scores ranging from 0 (very good COPD health status) to 6 (extremely poor COPD health status) (to show noninferiority).


A total of 653 patients underwent randomization. Fewer patients in the CRP-guided group reported antibiotic use than in the usual-care group (57.0% vs. 77.4%; adjusted odds ratio, 0.31; 95% confidence interval [CI], 0.20 to 0.47). The adjusted mean difference in the total score on the Clinical COPD Questionnaire at 2 weeks was −0.19 points (two-sided 90% CI, −0.33 to −0.05) in favor of the CRP-guided group. The antibiotic prescribing decisions made by clinicians at the initial consultation were ascertained for all but 1 patient, and antibiotic prescriptions issued over the first 4 weeks of follow-up were ascertained for 96.9% of the patients. A lower percentage of patients in the CRP-guided group than in the usual-care group received an antibiotic prescription at the initial consultation (47.7% vs. 69.7%, for a difference of 22.0 percentage points; adjusted odds ratio, 0.31; 95% CI, 0.21 to 0.45) and during the first 4 weeks of follow-up (59.1% vs. 79.7%, for a difference of 20.6 percentage points; adjusted odds ratio, 0.30; 95% CI, 0.20 to 0.46). Two patients in the usual-care group died within 4 weeks after randomization from causes considered by the investigators to be unrelated to trial participation.


CRP-guided prescribing of antibiotics for exacerbations of COPD in primary care clinics resulted in a lower percentage of patients who reported antibiotic use and who received antibiotic prescriptions from clinicians, with no evidence of harm.

Revue des troubles hydro-électrolytiques et acide-base liés au Diabète



Défaillance respiratoire à cause d’e-cigarettes


Jennifer E. Layden, et al., NEJM, 2019

DOI: 10.1056/NEJMoa1911614



E-cigarettes are battery-operated devices that heat a liquid and deliver an aerosolized product to the user. Pulmonary illnesses related to e-cigarette use have been reported, but no large series has been described. In July 2019, the Wisconsin Department of Health Services and the Illinois Department of Public Health received reports of pulmonary disease associated with the use of e-cigarettes (also called vaping) and launched a coordinated public health investigation.


We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes. Medical record abstraction and case patient interviews were conducted with the use of standardized tools.


There were 53 case patients, 83% of whom were male; the median age of the patients was 19 years. The majority of patients presented with respiratory symptoms (98%), gastrointestinal symptoms (81%), and constitutional symptoms (100%). All case patients had bilateral infiltrates on chest imaging (which was part of the case definition). A total of 94% of the patients were hospitalized, 32% underwent intubation and mechanical ventilation, and one death was reported. A total of 84% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported. Syndromic surveillance data from Illinois showed that the mean monthly rate of visits related to severe respiratory illness in June through August of 2019 was twice the rate that was observed in the same months in 2018.


Case patients presented with similar clinical characteristics. Although the features of e-cigarette use that were responsible for injury have not been identified, this cluster of illnesses represents an emerging clinical syndrome or syndromes. Additional work is needed to characterize the pathophysiology and to identify the definitive causes.



AVC ischémique : PA < 130/80 mm Hg ?


Kazuo Kitagawa, et al. JAMA Neurol. 2019. doi:10.1001/jamaneurol.2019.2167


Importance  The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that a systolic blood pressure (BP) target less than 120 mm Hg was superior to less than 140 mm Hg for preventing vascular events. This trial excluded patients with prior stroke; therefore, the ideal BP target for secondary stroke prevention remains unknown.

Objective  To assess whether intensive BP control would achieve fewer recurrent strokes vs standard BP control.

Design, Setting, and Participants  Randomized clinical trial (RCT) of standard vs intensive BP control in an intent-to-treat population of patients who had a history of stroke. Patients were enrolled between October 20, 2010, and December 7, 2016. For an updated meta-analysis, PubMed and the Cochrane Central Library database were searched through September 30, 2018, using the Medical Subject Headings and relevant search terms for cerebrovascular disease and for intensive BP lowering. This was a multicenter trial that included 140 hospitals in Japan; 1514 patients who had a history of stroke within the previous 3 years were approached, but 234 refused to give informed consent.

Interventions  In total, 1280 patients were randomized 1:1 to BP control to less than 140/90 mm Hg (standard treatment) (n = 640) or to less than 120/80 mm Hg (intensive treatment) (n = 640). However, 17 patients never received intervention; therefore, 1263 patients assigned to standard treatment (n = 630) or intensive treatment (n = 633) were analyzed.

Main Outcomes and Measures  The primary outcome was stroke recurrence.

Results  The trial was stopped early. Among 1263 analyzed patients (mean [SD] age, 67.2 [8.8] years; 69.4% male), 1257 of 1263 (99.5%) completed a mean (SD) of 3.9 (1.5) years of follow-up. The mean BP at baseline was 145.4/83.6 mm Hg. Throughout the overall follow-up period, the mean BP was 133.2/77.7 (95% CI, 132.5-133.8/77.1-78.4) mm Hg in the standard group and 126.7/77.4 (95% CI, 125.9-127.2/73.8-75.0) mm Hg in the intensive group. Ninety-one first recurrent strokes occurred. Nonsignificant rate reductions were seen for recurrent stroke in the intensive group compared with the standard group (hazard ratio [HR], 0.73; 95% CI, 0.49-1.11; P = .15). When this finding was pooled in 3 previous relevant RCTs in a meta-analysis, the risk ratio favored intensive BP control (relative risk, 0.78; 95% CI, 0.64-0.96; P = .02; absolute risk difference, −1.5%; 95% CI, −2.6% to −0.4%; number needed to treat, 67; 95% CI, 39-250).

Conclusions and Relevance  Intensive BP lowering tended to reduce stroke recurrence. The updated meta-analysis supports a target BP less than 130/80 mm Hg in secondary stroke prevention.





Lutte contre le Burn-Out : Coaching professionnel pour un vécu professionnel ?



Liselotte N. Dyrbye, et al, JAMA Intern Med. 2019;179(10):1406-1414. doi:10.1001/jamainternmed.2019.2425



Importance  Burnout symptoms among physicians are common and have potentially serious ramifications for physicians and their patients. Randomized studies testing interventions to address burnout have been uncommon.

Objective  To explore the effect of individualized coaching on the well-being of physicians.

Design, Setting, and Participants  A pilot randomized clinical trial involving 88 practicing physicians in the departments of medicine, family medicine, and pediatrics who volunteered for coaching was conducted between October 9, 2017, and March 27, 2018, at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Statistical analysis was conducted from August 24, 2018, to March 25, 2019.

Interventions  A total of 6 coaching sessions facilitated by a professional coach.

Main Outcomes and Measures  Burnout, quality of life, resilience, job satisfaction, engagement, and meaning at work using established metrics. Analysis was performed on an intent-to-treat basis.

Results  Among the 88 physicians in the study (48 women and 40 men), after 6 months of professional coaching, emotional exhaustion decreased by a mean (SD) of 5.2 (8.7) points in the intervention group compared with an increase of 1.5 (7.7) points in the control group by the end of the study (P < .001). Absolute rates of high emotional exhaustion at 5 months decreased by 19.5% in the intervention group and increased by 9.8% in the control group (−29.3% [95% CI, −34.0% to −24.6%]) (P < .001). Absolute rates of overall burnout at 5 months also decreased by 17.1% in the intervention group and increased by 4.9% in the control group (−22.0% [95% CI, −25.2% to −18.7%]) (P < .001). Quality of life improved by a mean (SD) of 1.2 (2.5) points in the intervention group compared with 0.1 (1.7) points in the control group (1.1 points [95% CI, 0.04-2.1 points]) (P = .005), and resilience scores improved by a mean (SD) of 1.3 (5.2) points in the intervention group compared with 0.6 (4.0) points in the control group (0.7 points [95% CI, 0.0-3.0 points]) (P = .04). No statistically significant differences in depersonalization, job satisfaction, engagement, or meaning in work were observed.

Conclusions and Relevance  Professional coaching may be an effective way to reduce emotional exhaustion and overall burnout as well as improve quality of life and resilience for some physicians.



Echec du Novoseven dans les hématomes intra-cérébraux



David J. Gladstone, et al. for the SPOTLIGHT and STOP-IT Investigators and Coordinators
JAMA Neurol. Published online August 19, 2019. doi:10.1001/jamaneurol.2019.2636



Importance  Intracerebral hemorrhage (ICH) is a devastating stroke type that lacks effective treatments. An imaging biomarker of ICH expansion—the computed tomography (CT) angiography spot sign—may identify a subgroup that could benefit from hemostatic therapy.

Objective  To investigate whether recombinant activated coagulation factor VII (rFVIIa) reduces hemorrhage expansion among patients with spot sign–positive ICH.

Design, Setting, and Participants  In parallel investigator-initiated, multicenter, double-blind, placebo-controlled randomized clinical trials in Canada (“Spot Sign” Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy [SPOTLIGHT]) and the United States (The Spot Sign for Predicting and Treating ICH Growth Study [STOP-IT]) with harmonized protocols and a preplanned individual patient–level pooled analysis, patients presenting to the emergency department with an acute primary spontaneous ICH and a spot sign on CT angiography were recruited. Data were collected from November 2010 to May 2016. Data were analyzed from November 2016 to May 2017.

Interventions  Eligible patients were randomly assigned 80 μg/kg of intravenous rFVIIa or placebo as soon as possible within 6.5 hours of stroke onset.

Main Outcomes and Measures  Head CT at 24 hours assessed parenchymal ICH volume expansion from baseline (primary outcome) and total (ie, parenchymal plus intraventricular) hemorrhage volume expansion (secondary outcome). The pooled analysis compared hemorrhage expansion between groups by analyzing 24-hour volumes in a linear regression model adjusted for baseline volumes, time from stroke onset to treatment, and trial.

Results  Of the 69 included patients, 35 (51%) were male, and the median (interquartile range [IQR]) age was 70 (59-80) years. Baseline median (IQR) ICH volumes were 16.3 (9.6-39.2) mL in the rFVIIa group and 20.4 (8.6-32.6) mL in the placebo group. Median (IQR) time from CT to treatment was 71 (57-96) minutes, and the median (IQR) time from stroke onset to treatment was 178 (138-197) minutes. The median (IQR) increase in ICH volume from baseline to 24 hours was small in both the rFVIIa group (2.5 [0-10.2] mL) and placebo group (2.6 [0-6.6] mL). After adjustment, there was no difference between groups on measures of ICH or total hemorrhage expansion. At 90 days, 9 of 30 patients in the rFVIIa group and 13 of 34 in the placebo group had died or were severely disabled (P = .60).

Conclusions and Relevance  Among patients with spot sign–positive ICH treated a median of about 3 hours from stroke onset, rFVIIa did not significantly improve radiographic or clinical outcomes.



Intérêt de petites doses d’Arginine-Vasopressine dans le choc hémorragique !


JAMA Surg. Published online August 28, 2019. doi:10.1001/jamasurg.2019.2884



Importance  Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, and supplementation of this hormone may decrease the need for blood products in resuscitation.

Objective  To determine whether low-dose supplementation of AVP in patients with trauma (hereinafter referred to as trauma patients) and with hemorrhagic shock decreases their need for transfused blood products during resuscitation.

Design, Setting, and Participants  This randomized, double-blind placebo-controlled clinical trial included adult trauma patients (aged 18-65 years) who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center from May 1, 2013, through May 31, 2017. Exclusion criteria consisted of prehospital cardiopulmonary resuscitation, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, traumatic brain injury requiring any neurosurgical intervention, pregnancy, prisoner status, or AVP administration before enrollment. Data were analyzed from May 1, 2013, through May 31, 2017, using intention to treat and per protocol.

Interventions  After administration of an AVP bolus (4 U) or placebo, participants received AVP (≤0.04 U/min) or placebo for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg.

Main Outcomes  The primary outcome was total volume of blood product transfused. Secondary end points included total volume of crystalloid transfused, vasopressor requirements, secondary complications, and 30-day mortality.

Results  One hundred patients underwent randomization (49 to the AVP group and 51 to the placebo group). Patients were primarily young (median age, 27 years [interquartile range {IQR}, 22-25 years]) and male (n = 93) with penetrating trauma (n = 79). Cohort characteristics before randomization were well balanced. At 48 hours, patients who received AVP required significantly less blood products (median, 1.4 [IQR, 0.5-2.6] vs 2.9 [IQR, 1.1-4.8] L; P = .01) but did not differ in requirements for crystalloids (median, 9.9 [IQR, 7.9-13.0] vs 11.0 [8.9-15.0] L; P = .22) or vasopressors (median, 400 [IQR, 0-5900] vs 1400 [IQR, 200-7600] equivalent units; P = .22). Although the groups had similar rates of mortality (6 of 49 [12%] vs 6 of 51 [12%]; P = .94) and total complications (24 of 44 [55%] vs 30 of 47 [64%]; P = .37), the AVP group had less deep venous thrombosis (5 of 44 [11%] vs 16 of 47 [34%]; P = .02).

Conclusions and Relevance  Low-dose AVP during the resuscitation of trauma patients in hemorrhagic shock decreases blood product requirements. Additional research is necessary to determine whether including AVP improves morbidity or mortality.



Mais… Pas d’effet sur la microcirculation ?


Background & aims

Sepsis is hypothesized as an arginine deficient state, with lack of nitric oxide (NO) for adequate microcirculation and local perfusion. This study aimed to investigate if prolonged (72-h) intravenous l-arginine administration in sepsis patients improves microcirculation. Secondly, effects on arginine and protein metabolism, and organ function were studied.


Critically ill patients with a diagnosis of septic shock participated in a long-term (72 h) randomized double-blind placebo-controlled parallel-group study. l-arginine-HCl (1.2 μmol kg−1 min−1; n = 9) or l-alanine (isocaloric control: 2.4 μmol kg−1 min−1; n = 9) was continuously infused. Primary study outcome was microcirculation, assessed as gastric mucosal perfusion by gastric tonometry (Pr-aCO2 gap) and skin perfusion by Laser Doppler flowmetry. Secondary endpoints were whole body (WB) arginine and protein metabolism, organ function and clinical outcomes. We measured global hemodynamics continuously for safety monitoring. Statistical analyses were performed by mixed model for repeated measures with treatment by time interaction as estimate for between-group difference.


Pr-aCO2 increased only in the l-arginine group (p = 0.006), without a significant between-group difference (p = 0.17). We found no significant differences in skin perfusion parameters. l-arginine infusion resulted in a larger increase of plasma arginine and ornithine concentrations (p < 0.01), WB (endogenous) arginine appearance (p < 0.001), WB NO synthesis (p = 0.027) and WB arginine to urea conversion (p < 0.001) than infusion of l-alanine. We found no effect on global hemodynamics, and protein metabolism by l-arginine infusion. Organ function parameters were unaffected, except for a significant difference between groups in intra-abdominal pressure over time (p = 0.029).


Prolonged intravenous l-arginine administration does not improve local perfusion and organ function despite an increase in WB NO synthesis. Administration is safe with regard to global hemodynamics, but the observed increase in Pr-aCO2 and intra-abdominal pressure warrants careful application of l-arginine infusion and further research, especially in the early stage of septic shock.



Oui à la spirométrie incitative post-chir cardiaque



Adam E. M. Eltorai, et al. JAMA Surg. 2019;154(7):579-588.



Importance  Incentive spirometers (ISs) were developed to reduce atelectasis and are in widespread clinical use. However, without IS use adherence data, the effectiveness of IS cannot be determined.

Objective  To evaluate the effect of a use-tracking IS reminder on patient adherence and clinical outcomes following coronary artery bypass grafting (CABG) surgery.

Design, Setting, and Participants  This randomized clinical trial was conducted from June 5, 2017, to December 29, 2017, at a tertiary referral teaching hospital and included 212 patients who underwent CABG, of whom 160 participants were randomized (intent to treat), with 145 completing the study per protocol. Participants were stratified by surgical urgency (elective vs nonelective) and sex (men vs women).

Interventions  A use-tracking, IS add-on device (SpiroTimer) with an integrated use reminder bell recorded and timestamped participants’ inspiratory breaths. Patients were randomized by hourly reminder “bell on” (experimental group) or “bell off” (control group).

Main Outcomes and Measures  Incentive spirometer use was recorded for the entire postoperative stay and compared between groups. Radiographic atelectasis severity (score, 0-10) was the primary clinical outcome. Secondary respiratory and nonrespiratory outcomes were also evaluated.

Results  A total of 145 per-protocol participants (112 men [77%]; mean age, 69 years [95% CI, 67-70]; 90 [62%] undergoing a nonelective procedure) were evaluated, with 74 (51.0%) in the bell off group and 71 (49.0%) in the bell on group. The baseline medical and motivation-to-recover characteristics of the 2 groups were similar. The mean number of daily inspiratory breaths was greater in bell on (35; 95% CI, 29-43 vs 17; 95% CI, 13-23; P < .001). The percentage of recorded hours with an inspiratory breath event was greater in bell on (58%; 95% CI, 51-65 vs 28%; 95% CI, 23-32; P < .001). Despite no differences in the first postoperative chest radiograph mean atelectasis severity scores (2.3; 95% CI, 2.0-2.6 vs 2.4; 95% CI, 2.2-2.7; P = .48), the mean atelectasis severity scores for the final chest radiographs conducted before discharge were significantly lower for bell on than bell off group (1.5; 95% CI, 1.3-1.8 vs 1.8; 95% CI, 1.6-2.1; P = .04). Of those with early postoperative fevers, fever duration was shorter for bell on (3.2 hours; 95% CI, 2.3-4.6 vs 5.2 hours; 95% CI, 3.9-7.0; P = .04). Having the bell turned on reduced noninvasive positive pressure ventilation use rates (37.2%; 95% CI, 24.1%-52.5% vs 19.2%; 95% CI, 10.2%-33.0%; P = .03) for participants undergoing nonelective procedures. Bell on reduced the median postoperative length of stay (7 days; 95% CI, 6-9 vs 6 days; 95% CI, 6-7; P = .048) and the intensive care unit length of stay for patients undergoing nonelective procedures (4 days; 95% CI, 3-5 vs 3 days; 95% CI, 3-4; P = .02). At 6 months, the bell off mortality rate was higher than bell on (9% vs 0%, P = .048) for participants undergoing nonelective procedures.

Conclusions and Relevance  The incentive spirometer reminder improved patient adherence, atelectasis severity, early postoperative fever duration, noninvasive positive pressure ventilation use, ICU and length of stay, and 6-month mortality in certain patients. With the reminder, IS appears to be clinically effective when used appropriately.







Revue spéciale ESC 2019 avec



Nouvelles recommandations ESC sur l’Embolie Pulmonaire


Choc électrique et FA : Il faut taper fort d’entrée de jeu !


AS Schmidt, Randers Ne, Danemark,

“Maximum find energy shocks for cardioverting Atrial fibrillation”

European Heart Journal.!-Analyse-detaillee


La cardioversion électrique élective de fibrillation atriale est plus efficace lorsque le ou les chocs sont délivrés à énergie d’emblée maximale et constante en comparaison aux chocs à énergie croissante, 88% contre 66% ou différence de 22% (IC-95% 13-32), p < 0,001.



Surmortalité des patients avec un RAC moyen (dès 20mmHg de gradient moyen ou une Vmax>3m/s)

Et une extension des indications à soigner les RAC moyens … ?


Geoffrey Strange (Sylvania, Australia)

« Prognostic implications of moderate aortic stenosis among 247,353 individuals : Insights from the National Echocardiography Database of Australia Study »



Echec du Mitra-Clip ?


Il ne faut pas administrer systématiquement de l’oxygène dans les SCA !



R. Stewart (Auckland, New Zealand)

« Nzotacs : The New Zealand Oxygen Therapy in Acute Coronary Syndromes » Trial



Un anticorps monoclonal anti-DPP3 efficace dans le choc cardiogénique



Alexandre Mebazaa (Paris, France)

Late Breaking Science « Circulating dipeptidyl peptidase 3 is a myocardial depressant factor: dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics »

En vidéo :




GALACTIC : Une stratégie vasodilatatrice intensive et précoce dans l’insuffisance cardiaque aigue ne réduit pas la mortalité à 180 jours !



Christian Mueller, Basel

GALACTIC TRIAL (Goal-directed AfterLoad Reduction in Acute Congestive Cardiac Decompensation : a randomized controlled trial)



SCA ST+ : la revascularisation myocardique doit être complète et peut être étagée



D.J. Hausenloy, Aarhus, Danemark




Registre GARFIELD-AF : les AOD font moins saigner que les AVK dans la vraie vie!



Jean-Pierre BASSAND (Thise, France)

« Early and late prognostic implications of bleeding in patients with newly diagnosed atrial fibrillation: real world evidence

from the GARFIELD-AF (Global Anticoagulation Registry in the Field- Atrial Fibrillation) Registry »




Comme en Chirurgie cardiaque : échec du préconditionnement ischémique par occlusion brachiale au brassard dans les SCA ST+ avant revascularisation



D.J. Hausenloy, Aarhus, Danemark




Nouveau biomarqueur de surcharge hydro-sodée ? Le CA-125 ?!



Mortalité de l’ACR extra-hospitalier : Femme > Homme…



European Heart Journal, ehz297,




Previous studies on sex differences in out-of-hospital cardiac arrest (OHCA) had limited scope and yielded conflicting results. We aimed to provide a comprehensive overall view on sex differences in care utilization, and outcome of OHCA.

Methods and results

We performed a population-based cohort-study, analysing all emergency medical service (EMS) treated resuscitation attempts in one province of the Netherlands (2006–2012). We calculated odds ratios (ORs) for the association of sex and chance of a resuscitation attempt by EMS, shockable initial rhythm (SIR), and in-hospital treatment using logistic regression analysis. Additionally, we provided an overview of sex differences in overall survival and survival at successive stages of care, in the entire study population and in patients with SIR. We identified 5717 EMS-treated OHCAs (28.0% female). Women with OHCA were less likely than men to receive a resuscitation attempt by a bystander (67.9% vs. 72.7%; P <0.001), even when OHCA was witnessed (69.2% vs. 73.9%; P <0.001). Women who were resuscitated had lower odds than men for overall survival to hospital discharge [OR 0.57; 95% confidence interval (CI) 0.48–0.67; 12.5% vs. 20.1%; P <0.001], survival from OHCA to hospital admission (OR 0.88; 95% CI 0.78–0.99; 33.6% vs. 36.6%; P =0.033), and survival from hospital admission to discharge (OR 0.49, 95% CI 0.40–0.60; 33.1% vs. 51.7%). This was explained by a lower rate of SIR in women (33.7% vs. 52.7%; P <0.001). After adjustment for resuscitation parameters, female sex remained independently associated with lower SIR rate.


In case of OHCA, women are less often resuscitated by bystanders than men. When resuscitation is attempted, women have lower survival rates at each successive stage of care. These sex gaps are likely explained by lower rate of SIR in women, which can only partly be explained by resuscitation characteristics.




Echec du Pantoprazole pour prévenir les hémorragies digestives hautes chez les patients sous AOD ou AAP ?


Paul Moayyedi et al.



Ventilation mécanique personnalisée à la morphologie pulmonaire ?


The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remains uncertain and needs to be evaluated. We aimed to test whether a mechanical ventilation strategy that was personalised to individual patients’ lung morphology would improve the survival of patients with ARDS when compared with standard of care.


We designed a multicentre, single-blind, stratified, parallel-group, randomised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France. Patients older than 18 years with early ARDS for less than 12 h were randomly assigned (1:1) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site, lung morphology, and duration of mechanical ventilation. Only the patients were masked to allocation. In the control group, patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure (PEEP) was selected according to a low PEEP and fraction of inspired oxygen table, and early prone position was encouraged. In the personalised group, the treatment approach was based on lung morphology; patients with focal ARDS received a tidal volume of 8 mL/kg, low PEEP, and prone position. Patients with non-focal ARDS received a tidal volume of 6 mL/kg, along with recruitment manoeuvres and high PEEP. The primary outcome was 90-day mortality as established by intention-to-treat analysis. This study is registered online with, NCT02149589.


From June 12, 2014, to Feb 2, 2017, 420 patients were randomly assigned to treatment. 11 patients were excluded in the personalised group and nine patients were excluded in the control group; 196 patients in the personalised group and 204 in the control group were included in the analysis. In a multivariate analysis, there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis (hazard ratio [HR] 1·01; 95% CI 0·61–1·66; p=0·98). However, misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 (21%) of 400 patients. We found a significant interaction between misclassification and randomised group allocation with respect to the primary outcome (p<0·001). In the subgroup analysis, the 90-day mortality of the misclassified patients was higher in the personalised group (26 [65%] of 40 patients) than in the control group (18 [32%] of 57 patients; HR 2·8; 95% CI 1·5–5·1; p=0·012.


Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS, possibly because of the misclassification of 21% of patients. A ventilator strategy misaligned with lung morphology substantially increases mortality. Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial.




Deferoxamine dans les hémorragies intra-cérébrales ?





Iron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial.


We did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18–80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0–2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with, number NCT02175225, and is completed.


We recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0–2 (adjusted absolute risk difference 0·6% [90% upper confidence bound 6·8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related.


Deferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0–2) at day 90 would be futile.




Echec de la stratégie « Maximal Recruitement Open Lung » dans le SDRA ?



Rationale: Open lung ventilation strategies have been recommended in patients with acute respiratory distress syndrome (ARDS).

Objective: To determine whether a maximal lung recruitment strategy reduces ventilator-free days in patients with ARDS. Methods: A phase II multicenter, randomized, controlled trial in adults with moderate to severe ARDS. Patients received either maximal lung recruitment, titrated positive end expiratory pressure and further tidal volume limitation or control ‘protective’ ventilation. Measurements: The primary outcome was ventilator-free days at day 28. Secondary outcomes included mortality, barotrauma, new use of hypoxemic adjuvant therapies, ICU and hospital stay.

Main Results: Enrolment halted on 2nd October 2017 following publication of the Alveolar Recruitment Trial, when 115 of a planned 340 patients had been randomized (57% male, mean age 53.6 years). At 28-days after randomization, there was no difference in ventilator-free days between the maximal lung recruitment and the control ventilation strategies, median [IQR] 16[0-21], n=57 versus 14.5[0-21.5], n=56, P=0.95, mortality 24.6% (n=14/56) versus 26.8% (n=15/56), P=0.79, or the rate of barotrauma 5.2% (n=3/57) versus 10.7% (n=6/56), P=0.32. However, in the intervention group there was reduced use of new hypoxemic adjuvant therapies (i.e. inhaled nitric oxide, extracorporeal membrane oxygenation, prone) (median [IQR] change from baseline 0 (0-1) vs 1 (0-1); P=0.004) and increased rates of new cardiac arrhythmia (n=17, 29% versus n=7, 13%, P=0.03).

Conclusions: Compared to control ventilation, maximal lung recruitment did not reduce the duration of ventilation free days or mortality and was associated with increased cardiovascular adverse events but lower use of hypoxemic adjuvant therapies.




Echec du Levosimendan chez les patients en choc septique avec dysfonction cardiaque associée







Myocardial dysfunction is common in sepsis but optimal treatment strategies are unclear. The inodilator, levosimendan was suggested as a possible therapy; however, the levosimendan to prevent acute organ dysfunction in Sepsis (LeoPARDS) trial found it to have no benefit in reducing organ dysfunction in septic shock. In this study we evaluated the effects of levosimendan in patients with and without biochemical cardiac dysfunction and examined its non-inotropic effects.


Two cardiac biomarkers, troponin I (cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and five inflammatory mediators were measured in plasma from patients recruited to the LeoPARDS trial at baseline and over the first 6 days. Mean total Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were compared between patients with normal and raised cTnI and NT-proBNP values, and between patients above and below median values.


Levosimendan produced no benefit in SOFA score or 28-day mortality in patients with cardiac dysfunction. There was a statistically significant treatment by subgroup interaction (p = 0.04) in patients with NT-proBNP above or below the median value. Those with NT-proBNP values above the median receiving levosimendan had higher SOFA scores than those receiving placebo (mean daily total SOFA score 7.64 (4.41) vs 6.09 (3.88), mean difference 1.55, 95% CI 0.43–2.68). Levosimendan had no effect on the rate of decline of inflammatory biomarkers.


Adding levosimendan to standard care in septic shock was not associated with less severe organ dysfunction nor lower mortality in patients with biochemical evidence of cardiac dysfunction.



Nutrition entérale > parentérale


Gaël Piton et al., ICM, 2019




The effects of the route of nutrition on the gut mucosa of patients with shock are unclear. Plasma citrulline concentration is a marker of enterocyte mass, and plasma intestinal fatty acid binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to study the effect of the route of nutrition on plasma citrulline concentration measured at day 3 of nutrition.

Materials and methods

Ancillary study of the NUTRIREA-2 trial. Ventilated adults with shock were randomly assigned to receive enteral or parenteral nutrition. Enterocyte biomarkers were measured at baseline, day 3, and day 8 of nutrition.


A total of 165 patients from 13 French ICUs were included in the study: 85 patients in the enteral group and 80 patients in the parenteral group. At baseline, plasma citrulline was low without difference between groups (12.2 µmol L−1 vs 13.3 µmol L−1). At day 3, plasma citrulline concentration was higher in the enteral group than in the parenteral group (18.7 µmol L−1 vs 15.3 µmol L−1, p = 0.01). Plasma I-FABP concentration was increased at baseline, without difference between groups (245 pg mL−1 vs 244 pg mL−1). Plasma I-FABP concentration was higher in the enteral group than in the parenteral group at day 3 and day 8 (158 pg mL−1 vs 50 pg mL−1, p = 0.005 and 225 pg mL−1 vs 50 pg mL−1, p = 0.03).


Plasma citrulline concentration was higher after 3 days of enteral nutrition than after 3 days of parenteral nutrition. This result raises the question of the possibility that enteral nutrition is associated with a more rapid restoration of enterocyte mass than parenteral nutrition.



Intérêt du monitorage ORI ?




  • Sigismond LasockiEmail author et al., ICM, 2019





Machine learning sur l’IRA : AKIpredictor



Marine Flechet, et al., CC, 2019



Early diagnosis of acute kidney injury (AKI) is a major challenge in the intensive care unit (ICU). The AKIpredictor is a set of machine-learning-based prediction models for AKI using routinely collected patient information, and accessible online. In order to evaluate its clinical value, the AKIpredictor was compared to physicians’ predictions.


Prospective observational study in five ICUs of a tertiary academic center. Critically ill adults without end-stage renal disease or AKI upon admission were considered for enrollment. Using structured questionnaires, physicians were asked upon admission, on the first morning, and after 24 h to predict the development of AKI stages 2 or 3 (AKI-23) during the first week of ICU stay. Discrimination, calibration, and net benefit of physicians’ predictions were compared against the ones by the AKIpredictor.


Two hundred fifty-two patients were included, 30 (12%) developed AKI-23. In the cohort of patients with predictions by physicians and AKIpredictor, the performance of physicians and AKIpredictor were respectively upon ICU admission, area under the receiver operating characteristic curve (AUROC) 0.80 [0.69–0.92] versus 0.75 [0.62–0.88] (n = 120, P = 0.25) with net benefit in ranges 0–26% versus 0–74%; on the first morning, AUROC 0.94 [0.89–0.98] versus 0.89 [0.82–0.97] (n = 187, P = 0.27) with main net benefit in ranges 0–10% versus 0–48%; after 24 h, AUROC 0.95 [0.89–1.00] versus 0.89 [0.79–0.99] (n = 89, P = 0.09) with main net benefit in ranges 0–67% versus 0–50%.


The machine-learning-based AKIpredictor achieved similar discriminative performance as physicians for prediction of AKI-23, and higher net benefit overall, because physicians overestimated the risk of AKI. This suggests an added value of the systematic risk stratification by the AKIpredictor to physicians’ predictions, in particular to select high-risk patients or reduce false positives in studies evaluating new and potentially harmful therapies. Due to the low event rate, future studies are needed to validate these findings.



iloprost et eptifibatide contre la coagulo/vasculopathie liée au sepsis ?





Part of the pathophysiology in septic shock is a progressive activation of the endothelium and platelets leading to widespread microvascular injury with capillary leakage, microthrombi and consumption coagulopathy. Modulating the inflammatory response of endothelium and thrombocytes might attenuate this vicious cycle and improve outcome.


The CO-ILEPSS trial was a randomised, placebo-controlled, double-blind, pilot trial. Patients admitted to the intensive care unit with septic shock were randomised and allocated in a 2:1 ratio to active treatment with dual therapy of iloprost 1 ng/kg/min and eptifibatide 0.5 μg/kg/min for 48 h or placebo. The primary outcomes were changes in biomarkers reflecting endothelial activation and disruption, platelet consumption and fibrinolysis. We compared groups with mixed models, post hoc Wilcoxon signed-rank test and Mann-Whitney U test.


We included 24 patients of which 18 (12 active, 6 placebo) completed the full 7-day trial period and were included in the per-protocol analyses of the primary outcomes. Direct comparison between groups showed no differences in the primary outcomes. Analyses of within-group delta values revealed that biomarkers of endothelial activation and disruption changed differently between groups with increasing levels of thrombomodulin (p = 0.03) and nucleosomes (p = 0.02) in the placebo group and decreasing levels of sE-Selectin (p = 0.007) and sVEGFR1 (p = 0.005) in the active treatment group. Platelet count decreased the first 48 h in the placebo group (p = 0.049) and increased from baseline to day 7 in the active treatment group (p = 0.023). Levels of fibrin monomers declined in the active treatment group within the first 48 h (p = 0.048) and onwards (p = 0.03). Furthermore, there was a significant reduction in SOFA score from 48 h (p = 0.024) and onwards in the active treatment group.

Intention-to-treat analyses of all included patients showed no differences in serious adverse events including bleeding, use of blood products or mortality.


Our results could indicate benefit from the experimental treatment with reduced endothelial injury, reduced platelet consumption and ensuing reduction in fibrinolytic biomarkers along with improved SOFA score. The results of the CO-ILEPSS trial are exploratory and hypothesis generating and warrant further investigation in a large-scale trial.





Revue sur les diagnostics de PIC élevées



BMJ 2019;366:l4225



Méta-analyse sur Optiflow versus Oxygénothérapie conventionnelle en péri-opératoire







Objective To evaluate the effect of high-flow nasal cannula oxygen therapy (HFNC) versus conventional oxygen therapy (COT) on the reintubation rate, rate of escalation of respiratory support and clinical outcomes in postextubation adult surgical patients.

Design Systematic review and meta-analysis of published literature.

Data sources PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Index and Wan fang databases were searched up to August 2018.

Eligibility criteria Studies in postoperative adult surgical patients (≥18 years), receiving HFNC or COT applied immediately after extubation that reported reintubation, escalation of respiratory support, postoperative pulmonary complications (PPCs) and mortality were eligible for inclusion.

Data extraction and synthesis The following data were extracted from the included studies: first author’s name, year of publication, study population, country of origin, study design, number of patients, patients’ baseline characteristics and outcomes. Associations were evaluated using risk ratio (RR) and 95% CIs.

Results This meta-analysis included 10 studies (1327 patients). HFNC significantly reduced the reintubation rate (RR 0.38, 95% CI 0.23 to 0.61, p<0.0001) and rate of escalation of respiratory support (RR 0.43, 95% CI 0.26 to 0.73, p=0.002) in postextubation surgical patients compared with COT. There were no differences in the incidence of PPCs (RR 0.87, 95% CI 0.70 to 1.08, p=0.21) or mortality (RR 0.45, 95% CI 0.16 to 1.29, p=0.14).

Conclusion HFNC is associated with a significantly lower reintubation rate and rate of escalation of respiratory support compared with COT in postextubation adult surgical patients, but there is no difference in the incidence of PPCs or mortality. More well-designed, large randomised controlled trials are needed to determine the subpopulation of patients who are most likely to benefit from HFNC therapy.



Bienvenue à l’HFO nasale !



Ramin Iranpour, et al., BMJ, 2019



Background Currently, various forms of non-invasive respiratory support have been used in the management of respiratory distress syndrome (RDS) in preterm neonates. However, nasal high-frequency oscillatory ventilation (nHFOV) has not yet been applied commonly as an initial treatment.

Objectives This study was designed to investigate the efficacy and safety of nHFOV compared with nasal continuous positive airway pressure (NCPAP) in preterm and near-term infants with RDS.

Methods In a randomised clinical trial, a total of 68 neonates (gestational age (GA) between 30 and 36 weeks and 6 days) with a clinical diagnosis of RDS were randomly assigned to either the NCPAP (n=34) or the nHFOV (n=34) group. The primary outcome was the duration of non-invasive respiratory support (duration of using NCPAP or nHFOV).

Result The median (IQR) duration of non-invasive respiratory support, was significantly shorter in the nHFOV group than that in the NCPAP group (20 (15–25.3) versus 26.5 (15–37.4) hours, respectively; p=0.02). The need for a ventilator occurred in 4 out of 34 (11.8%) neonates in the NCPAP group and in none of the neonates in the nHFOV group (p=0.03). In addition, intraventricular haemorrhage (IVH) occurred in nine cases (6.9%) in the NCPAP group and two cases (3.3%) in the nHFOV group, which showed a significant difference (p=0.04). The incidence of pneumothorax, chronic lung disease, pulmonary haemorrhage and necrotising enterocolitis was similar between the two groups.

Conclusion This study showed that nHFOV significantly reduced the duration of non-invasive respiratory support and decreased the need for intubation compared with NCPAP in infants with RDS. Furthermore, nHFOV seems to reduce the incidence of IVH without increasing other complications.



Méta-analyse : SDD > SOD


Denise van Hout et al., BMJ Open, 2019



Méta-analyse sur le Trauma spinal : Pas d’intérêt de hautes doses de corticoïdes



Zhongyu Liu, Yang Yang, Lei He, Mao Pang, Chunxiao Luo, Bin Liu, Limin Rong





Bactériémie à BGN : 7 vs 14 jours



Dafna Yahav, et al., Clinical Infectious Diseases, 1 October 2019, Pages 1091–1098,





Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.


This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%.


We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, –2.6% [95% confidence interval, –10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm.


In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention.






Méta-analyse sur l’hémopurification dans le sepsis



Anesthesiology 9 2019, Vol.131, 580-593.



Fin du démon nommé « Hyperchlorhémie » ?




Recent data suggest that hyperchloremia induced by fluid resuscitation is associated with acute kidney injury (AKI) and mortality, particularly in sepsis. Experimental studies showed that hyperchloremia could affect organ functions. In patients with septic shock, we examined the relationship between serum chloride concentration and both renal function and survival.


Post hoc analysis of the “HYPER2S” trial database (NCT01722422) including 434 patients with septic shock randomly assigned for resuscitation with 0.9% or 3% saline. Metabolic parameters were recorded up to 72 h. Metabolic effects of hyperchloremia (> 110 mmol/L) were studied stratified for hyperlactatemia (> 2 mmol/L). Cox models were constructed to assess the association between chloride parameters, day-28 mortality and AKI.


413 patients were analysed. The presence of hyperlactatemia was significantly more frequent than hyperchloremia (62% versus 71% of patients, respectively, p = 0.006). Metabolic acidosis was significantly more frequent in patients with hyperchloremia, no matter the presence of hyperlactatemia, p < 0.001. Adjusted risk of AKI and mortality were not significantly associated with serum chloride, hyperchloremia, maximal chloremia and delta chloremia (maximal-H0 [Cl]).


Despite more frequent metabolic acidosis, hyperchloremia was not associated with an increased risk for AKI or mortality.




Mais…Solutés balancés versus NaCl 0.9% : impact sur la mortalité ?!




Rationale: Administration of intravenous crystalloid solutions is a fundamental therapy for sepsis, but the effect of crystalloid composition on patient outcomes remains unknown.

Objectives: To compare the effect of balanced crystalloids versus saline on 30-day in-hospital mortality among critically ill adults with sepsis.

Methods: Secondary analysis of patients from the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) admitted to the medical intensive care unit with an ICD-10-CM code for sepsis, using multivariable regression to control for potential confounders.

Measurements and Main Results: Of 15,802 patients enrolled in SMART, 1,641 patients were admitted to the medical intensive care unit with a diagnosis of sepsis. A total of 217 patients (26.3%) in the balanced crystalloids group experienced 30-day in-hospital morality, compared with 255 patients (31.2%) in the saline group (adjusted odds ratio, 0.74; 95% confidence interval, 0.59 – 0.93; P = 0.01). Patients in the balanced group experienced a lower incidence of major adverse kidney events within 30 days (35.4% vs 40.1%; aOR 0.78; 95% CI 0.63 – 0.97) and a greater number of vasopressor-free days (20 ± 12 vs 19 ± 13; aOR 1.25; 95% CI 1.02 – 1.54) and renal replacement therapy-free days (20 ± 12 vs 19 ± 13; aOR 1.35 [1.08 – 1.69]), compared to the saline group.

Conclusions: Among patients with sepsis in a large randomized trial, use of balanced crystalloids was associated with a lower 30-day in-hospital mortality compared to use of saline.



Hyperlactatémie dans le sepsis : Davantage liée à un défaut d’utilisation que de transport ?



Rationale: Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy.

Objectives: To understand the relationship among central venous oxygen saturation (ScvO2), lactate, and base excess to better determine the origin of lactate.

Methods: This was a post hoc analysis of baseline variables of 1,741 patients with sepsis enrolled in the multicenter trial ALBIOS (Albumin Italian Outcome Sepsis). Variables were analyzed as a function of sextiles of lactate concentration and sextiles of ScvO2. We defined the “alactic base excess,” as the sum of lactate and standard base excess.

Measurements and Main Results: Organ dysfunction severity scores, physiologic variables of hepatic, metabolic, cardiac, and renal function, and 90-day mortality were measured. ScvO2 was lower than 70% only in 35% of patients. Mortality, organ dysfunction scores, and lactate were highest in the first and sixth sextiles of ScvO2. Although lactate level related strongly to mortality, it was associated with acidemia only when kidney function was impaired (creatinine >2 mg/dl), as rapidly detected by a negative alactic base excess. In contrast, positive values of alactic base excess were associated with a relative reduction of fluid balance.

Conclusions: Hyperlactatemia is powerfully correlated with severity of sepsis and, in established sepsis, is caused more frequently by impaired tissue oxygen use, rather than by impaired oxygen transport. Concomitant acidemia was only observed in the presence of renal dysfunction, as rapidly detected by alactic base excess. The current strategy of fluid resuscitation could be modified according to the origin of excess lactate.




Impédance tomographique pulmonaire : exemple chez les patients à risque d’échec d’extubation


Federico Longhini, et al.




This study aims to assess the changes in lung aeration and ventilation during the first spontaneous breathing trial (SBT) and after extubation in a population of patients at risk of extubation failure.


We included 78 invasively ventilated patients eligible for their first SBT, conducted with low positive end-expiratory pressure (2 cm H2O) for 30 min. We acquired three 5-min electrical impedance tomography (EIT) records at baseline, soon after the beginning (SBT_0) and at the end (SBT_30) of SBT. In the case of SBT failure, ventilation was reinstituted; otherwise, the patient was extubated and two additional records were acquired soon after extubation (SB_0) and 30 min later (SB_30) during spontaneous breathing. Extubation failure was defined by the onset of post-extubation respiratory failure within 48 h after extubation. We computed the changes from baseline of end-expiratory lung impedance (∆EELI), tidal volume (∆Vt%), and the inhomogeneity index. Arterial blood was sampled for gas analysis. Data were compared between sub-groups stratified for SBT and extubation success/failure.


Compared to SBT success (n = 61), SBT failure (n = 17) showed a greater reduction in ∆EELI at SBT_0 (p < 0.001) and SBT_30 (p = 0.001) and a higher inhomogeneity index at baseline (p = 0.002), SBT_0 (p = 0.003) and SBT_30 (p = 0.005). RR/Vt was not different between groups at baseline but was significantly greater at SBT_0 and SBT_30 in SBT failures, compared to SBT successes (p < 0.001 for both). No differences in ∆Vt% and arterial blood gases were observed between SBT success and failure. The ∆Vt%, ∆EELI, inhomogeneity index and arterial blood gases were not different between patients with extubation success (n = 39) and failure (n = 22) (p > 0.05 for all comparisons).


Compared to SBT success, SBT failure was characterized by more lung de-recruitment and inhomogeneity. Whether EIT may be useful to monitor SBT remains to be determined. No significant changes in lung ventilation, aeration or homogeneity related to extubation outcome occurred up to 30 min after extubation.




Physio : intérêt d’une compression externe dans le choc septique ?






Fluid overload in septic intensive care unit (ICU) patients is common and strongly associated with poor outcome. There is currently no treatment for capillary leak, which is mainly responsible for high positive fluid balance (FB) in sepsis. We hypothesized that increasing interstitial pressure with extensive corporeal compression would reduce FB. The objective of this study was to evaluate the feasibility, efficacy, and safety of a compression treatment during sepsis. This pilot, two-center, single-arm trial enrolled critically ill, non-surgical, septic patients receiving mechanical ventilation. The therapeutic intervention was the early application of compression bandages on more than 80% of the body surface. The primary outcome was negative net FB on day 7. The primary endpoint was reached in 29 of 45 patients (64%) with available data, for a planned objective of 26. By day 4, cumulative FB was 7280 ml [3300–9700]. SOFA- and aged-matched patients from a historical cohort had a significantly higher FB at 1, 2 and 7 days. Tolerance was good, although low-stage pressure ulcers were observed in 16 patients (26%). No effect on intra-abdominal pressure or respiratory plateau pressure was observed. In conclusion, corporeal compression demonstrated potential efficacy in limiting FB during septic shock, with acceptable feasibility and tolerance.



Revue sur la coagulopathie induite par le sepsis





Méta-analyse sur la NAVA !




Chongxiang Chen1,2#, Tianmeng Wen3#, Wei Liao1

doi: 10.21037/atm.2019.07.60




Background: The objective of this study was to conduct a meta-analysis comparing neurally adjusted ventilatory assist (NAVA) with pressure support ventilation (PSV) in adult ventilated patients with patient-ventilator interaction and clinical outcomes.

Methods: The PubMed, the Web of Science, Scopus, and Medline were searched for appropriate clinical trials (CTs) comparing NAVA with PSV for the adult ventilated patients. RevMan 5.3 was performed for comparing NAVA with PSV in asynchrony index (AI), ineffective efforts, auto-triggering, double asynchrony, premature asynchrony, breathing pattern (Peak airway pressure (Pawpeek), mean airway pressure (Pawmean), tidal volume (VT, mL/kg), minute volume (MV), respiratory muscle unloading (peak electricity of diaphragm (EAdipeak), P 0.1, VT/EAdi), clinical outcomes (ICU mortality, duration of ventilation days, ICU stay time, hospital stay time).

Results: Our meta-analysis included 12 studies involving a total of 331 adult ventilated patients, AI was significantly lower in NAVA group [mean difference (MD) −12.82, 95% confidence interval (CI): −21.20 to −4.44, I2=88%], and using subgroup analysis, grouped by mechanical ventilation, the results showed that NAVA also had lower AI than PSV (Mechanical ventilation, MD −9.52, 95% CI: −17.85 to −1.20, I2=87%), (Non-invasive ventilation (NIV), MD −24.55, 95% CI: −35.40 to −13.70, I2=0%). NAVA was significantly lower than the PSV in auto-triggering (MD −0.28, 95% CI: −0.51 to −0.05, I2=10%), and premature triggering (MD −2.49, 95% CI: −3.77 to −1.21, I2=29%). There were no significant differences in double triggering, ineffective efforts, breathing pattern (Pawmean, Pawpeak, VT, MV), and respiratory muscle unloading (EAdipeak, P 0.1, VT/EAdi). For clinical outcomes, NAVA was significantly lower than the PSV (MD −2.82, 95% CI: −5.55 to −0.08, I2=0%) in the duration of ventilation, but two groups did not show significant differences in ICU mortality, ICU stay time, and hospital stay time.

Conclusions: NAVA is more beneficial in patient-ventilator interaction than PSV, and could decrease the duration of ventilation.




Pré-oxygénation de l’Obèse : VNI > Optiflow ?





In obese patients, preoxygenation with non-invasive ventilation (NIV) was reported to improve outcomes compared with facemask. In this setting, high-flow nasal cannulae (HFNC) used before and during intubation has never been studied against NIV.


The PREOPTIPOP study is a randomised, single-centre, open-labelled, controlled trial including obese patients requiring intubation before scheduled surgery. Patients were randomised to receive preoxygenation by HFNC or NIV. HFNC was maintained throughout intubation whereas NIV was removed when apnea occurred to perform laryngoscopy. The study was designed to assess the superiority of HNFC. The primary outcome was the lowest level of end-tidal oxygen concentration (EtO2) within 2 min after intubation. Secondary outcomes included drop in pulse oximetry and complications related to intubation.

Main findings

A total of 100 patients were randomised. The intent-to-treat analysis found median [IQR] lowest EtO2 of 76% [66–82] for HFNC and 88% [82–90] for NIV (mean difference − 12·1 [− 15·1 to − 8·5], p < 0·0001). Mild desaturation below 95% was more frequent with HFNC (30%) than with NIV (12%) (relative risk 2·5, IC 95% [1·1 to 5·9], p = 0·03) and median lowest SpO2 during intubation was 98% [93–99] in HFNC vs. 99% [97–100] in NIV (p = 0·03). Severe and moderate complications were not different but patients reported more discomfort with NIV (28%) vs. HFNC (4%), p = 0·001.


Compared with NIV, preoxygenation with HFNC in obese patients provided lower EtO2 after intubation and a higher rate of desaturation < 95%.



Pré-oxygénation de l’Obèse : Optiflow > VS au masque seul ?




Wong, David T. MD*; et al. Anesthesia & Analgesia: October 2019 – Volume 129 – Issue 4 – p 1130-1136

doi: 10.1213/ANE.0000000000003966



BACKGROUND: Morbidly obese patients undergoing general anesthesia are at risk of hypoxemia during anesthesia induction. High-flow nasal oxygenation use during anesthesia induction prolongs safe apnea time in nonobese surgical patients. The primary objective of our study was to compare safe apnea time, between patients given high-flow nasal oxygenation or conventional facemask oxygenation during anesthesia induction, in morbidly obese surgical patients.

METHODS: Research ethics board approval was obtained. Elective surgical patients ≥18 years with body mass index ≥40 kg·m−2 were included. Patients with severe comorbidity, gastric reflux disease, known difficult airway, or nasal obstruction were excluded. After obtaining informed consent patients were randomized. In the intervention (high-flow nasal oxygenation) group, preoxygenation was provided by 100% nasal oxygen for 3 minutes at 40 L·minute−1; in the control group, preoxygenation was delivered using a facemask with 100% oxygen, targeting end-tidal O2 >85%. Anesthesia was induced with propofol, remifentanil, and rocuronium. Bag-mask ventilation was not performed. At 2 minutes after rocuronium, videolaryngoscopy was performed. If the laryngoscopy grade was I or II, laryngoscope was left in place and the study was continued; if grade III or IV was observed, the patient was excluded from the study. During the apnea period, high-flow nasal oxygenation patients received nasal oxygen at 60 L·minute−1; control group patients received no supplemental oxygen. The primary outcome, safe apnea time, was reached when oxygen saturation measured by pulse oximetry (Spo2) fell to 95% or maximum 6 minutes of apnea. The patient was then intubated. T tests and χ2 analyses were used to compare groups. P < .05 was considered significant.

RESULTS: Forty patients completed the study. Baseline parameters were comparable between groups. Safe apnea time was significantly longer (261.4 ± 77.7 vs 185.5 ± 52.9 seconds; mean difference [95% CI], 75.9 [33.3–118.5]; P = .001) and the minimum peri-intubation Spo2 was higher (91.0 ± 3.5 vs 88.0 ± 4.8; mean difference [95% CI], 3.1 [0.4–5.7]; P = .026) in the high-flow nasal oxygenation group compared to the control group.

CONCLUSIONS: High-flow nasal oxygenation, compared to conventional oxygenation, provided a longer safe apnea time by 76 seconds (40%) and higher minimum Spo2 in morbidly obese patients during anesthesia induction. High-flow oxygenation use should be considered in morbidly obese surgical patients.




Diurétiques : Continu > Bolus


Simone Frea et al., Clinical Research in Cardiology, 2019




Diuretic resistance is a common issue in patients with acute decompensation of advanced chronic heart failure (ACHF). The aim of this trial was to compare boluses and continuous infusion of furosemide in a selected population of patients with ACHF and high risk for diuretic resistance.


In this single-centre, double-blind, double-dummy, randomized trial, we enrolled 80 patients admitted for acute decompensation of ACHF (NYHA IV, EF ≤ 30%) with criteria of high risk for diuretic resistance (SBP ≤ 110 mmHg, wet score ≥ 12/18, and sodium ≤ 135 mMol/L). Patients were assigned in a 1:1 ratio to receive furosemide by bolus every 12 h or by continuous infusion. Diuretic treatment and dummy treatment were prepared by a nurse unassigned to patients’ care. The study treatment was continued for up to 72 h. Coprimary endpoints were total urinary output and freedom from congestion at 72 h.


80 patients were enrolled with 40 patients in each treatment arm. Mean daily furosemide was 216 mg in continuous-infusion arm and 195 mg in the bolus intermittent arm. Freedom from congestion (defined as jugular venous pressure of < 8 cm, with no orthopnea and with trace peripheral edema or no edema) occurred more in the continuous infusion than in the bolus arm (48% vs. 25%, p = 0.04), while total urinary output after 72 h was 8612 ± 2984 ml in the bolus arm and 10,020 ± 3032 ml in the continuous arm (p = 0.04). Treatment failure occurred less in the continuous-infusion group (15% vs. 38%, p = 0.02), while there was no significant difference between groups in the incidence of worsening of renal function.


Among patients with acute decompensation of ACHF and high risk of diuretic resistance, continuous infusion of intravenous furosemide was associated with better decongestion.

Pose de KTc : Sous-clav versus Jug = NS



The use of real-time ultrasound (US) has been shown to reduce complications of central venous (CV) catheterization. However, complication rates have not been compared according to insertion points for CV catheterization using US. Accordingly, this study aimed to compare the complication rates of internal jugular vein (IJV) with those of subclavian vein (SCV) catheterization.


Three tertiary academic hospitals in South Korea participated in this multicenter, randomized study. A total of 1484 patients were preoperatively randomized into two groups. The IJV group (n = 742) was cannulated via the right IJV, and the SCV group (n = 742) was cannulated via the right SCV under US guidance. The primary outcome measure was total complication rate. Secondary outcomes included access time for the first attempt, number of attempts, and catheter position.


The total complication rate did not demonstrate a significant difference between the IJV (0.1%) and SCV (0.7%) groups (P = 0.248). In the IJV group, arterial puncture occurred in 0.1% of patients; in the SCV group, arterial puncture occurred in 0.6% and pneumothorax in 0.1%. The success rate on the first attempt was significantly higher in the IJV group (98.4%) than in the SCV group (95.9%) (P = 0.004). The access time for the first attempt (P < 0.001) and the median number of attempts (P = 0.006) were significantly lower in the IJV group than in the SCV group. More catheter misplacements were observed in the SCV group (5.9%) than in the IJV group (0.4%) (P < 0.001).


Results demonstrated that the complication rates of IJV and SCV catheterizations using US are very low, showing no superiority of the SCV approach compared to the IJV.


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