Biblio du mois – Octobre 2018




Voici la biblio du mois !

Petit point des évènements :

  • N’oubliez pas notre Masterclass de formation au Management le 15 Novembre 2018 ! ici
  • Prochain Afterbloc dédié aux 1ers semestres avec un système inédit de parrainage pour mieux intégrer les nouveaux 😉
  • Des places gratuites à de multiples congrès ! ici
  • Et bien d’autres à venir !

Au programme de cette biblio, pas mal d’études négatives mais de belles revues ! On a des études très intéressantes sur l’effet néphroprotecteur du paracétamol dans les crises palustres ou comparant les différentes températures cibles dans l’hypothermie thérapeutique et de la prévention de PAVM, pour ne citer que celles-ci !

Et voici un tuto pour mieux profiter de la biblio chaque mois : lien !







IDEAL-ICU : Une autre étude sur le timing de l’épuration extra-rénale



Saber D. Barbar, et al., N Engl J Med 2018; 379:1431-1442

DOI: 10.1056/NEJMoa1803213






Acute kidney injury is the most frequent complication in patients with septic shock and is an independent risk factor for death. Although renal-replacement therapy is the standard of care for severe acute kidney injury, the ideal time for initiation remains controversial.


In a multicenter, randomized, controlled trial, we assigned patients with early-stage septic shock who had severe acute kidney injury at the failure stage of the risk, injury, failure, loss, and end-stage kidney disease (RIFLE) classification system but without life-threatening complications related to acute kidney injury to receive renal-replacement therapy either within 12 hours after documentation of failure-stage acute kidney injury (early strategy) or after a delay of 48 hours if renal recovery had not occurred (delayed strategy). The failure stage of the RIFLE classification system is characterized by a serum creatinine level 3 times the baseline level (or ≥4 mg per deciliter with a rapid increase of ≥0.5 mg per deciliter), urine output less than 0.3 ml per kilogram of body weight per hour for 24 hours or longer, or anuria for at least 12 hours. The primary outcome was death at 90 days.


The trial was stopped early for futility after the second planned interim analysis. A total of 488 patients underwent randomization; there were no significant between-group differences in the characteristics at baseline. Among the 477 patients for whom follow-up data at 90 days were available, 58% of the patients in the early-strategy group (138 of 239 patients) and 54% in the delayed-strategy group (128 of 238 patients) had died (P=0.38). In the delayed-strategy group, 38% (93 patients) did not receive renal-replacement therapy. Criteria for emergency renal-replacement therapy were met in 17% of the patients in the delayed-strategy group (41 patients).


Among patients with septic shock who had severe acute kidney injury, there was no significant difference in overall mortality at 90 days between patients who were assigned to an early strategy for the initiation of renal-replacement therapy and those who were assigned to a delayed strategy.


Plus de suicides & dépression chez les médecins ?

Karp et al. The New England Journal of Medicine




Traitement optimal du sepsis par l’Intelligence Artificielle ?



Komorowski. The Artificial Intelligence Clinician learns optimal treatment strategies for sepsis in intensive care. Nature Medicine 2018;epublished October 22nd






Extuber sans VS avec relai par VNI ne réduit pas la durée de ventilation totale



Gavin D. Perkins, et al., JAMA.  2018.





Importance  In adults in whom weaning from invasive mechanical ventilation is difficult, noninvasive ventilation may facilitate early liberation, but there is uncertainty about its effectiveness in a general intensive care patient population.

Objective  To investigate among patients with difficulty weaning the effects of protocolized weaning with early extubation to noninvasive ventilation on time to liberation from ventilation compared with protocolized invasive weaning.

Design, Setting, and Participants  Randomized, allocation-concealed, open-label, multicenter clinical trial enrolling patients between March 2013 and October 2016 from 41 intensive care units in the UK National Health Service. Follow-up continued until April 2017. Adults who received invasive mechanical ventilation for more than 48 hours and in whom a spontaneous breathing trial failed were enrolled.

Interventions  Patients were randomized to receive either protocolized weaning via early extubation to noninvasive ventilation (n = 182) or protocolized standard weaning (continued invasive ventilation until successful spontaneous breathing trial, followed by extubation) (n = 182).

Main Outcomes and Measures  Primary outcome was time from randomization to successful liberation from all forms of mechanical ventilation among survivors, measured in days, with the minimal clinically important difference defined as 1 day. Secondary outcomes were duration of invasive and total ventilation (days), reintubation or tracheostomy rates, and survival.

Results  Among 364 randomized patients (mean age, 63.1 [SD, 14.8] years; 50.5% male), 319 were evaluable for the primary effectiveness outcome (41 died before liberation, 2 withdrew, and 2 were discharged with ongoing ventilation). The median time to liberation was 4.3 days in the noninvasive group vs 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% CI, 0.89-1.40). Competing risk analysis accounting for deaths had a similar result (adjusted hazard ratio, 1.1; 95% CI, 0.86-1.34). The noninvasive group received less invasive ventilation (median, 1 day vs 4 days; incidence rate ratio, 0.6; 95% CI, 0.47-0.87) and fewer total ventilator days (median, 3 days vs 4 days; incidence rate ratio, 0.8; 95% CI, 0.62-1.0). There was no significant difference in reintubation, tracheostomy rates, or survival. Adverse events occurred in 45 patients (24.7%) in the noninvasive group compared with 47 (25.8%) in the invasive group.

Conclusions and Relevance  Among patients requiring mechanical ventilation in whom a spontaneous breathing trial had failed, early extubation to noninvasive ventilation did not shorten time to liberation from any ventilation.




Bains de bouche de Chlorhex : pas de réduction d’infections à BLSE


JAMA. Published online October 22, 2018. doi:10.1001/jama.2018.13765



Importance  The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown.

Objective  To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance.

Design, Setting, and Participants  Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum β-lactamase–producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017.

Interventions  Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily.

Main Outcomes and Measures  The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period.

Results  A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, −0.6% to 1.1%), 0.6% (95% CI, −0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline.

Conclusions and Relevance  Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care.



Différence du timing des poussées chez les femmes en per-partum sous péridurale ?



JAMA. 2018;320(14):1444-1454. doi:10.1001/jama.2018.13986


Importance  It is unclear whether the timing of second stage pushing efforts affects spontaneous vaginal delivery rates and reduces morbidities.

Objective  To evaluate whether immediate or delayed pushing results in higher rates of spontaneous vaginal delivery and lower rates of maternal and neonatal morbidities.

Design, Setting, and Participants  Pragmatic randomized clinical trial of nulliparous women at or beyond 37 weeks’ gestation admitted for spontaneous or induced labor with neuraxial analgesia between May 2014 and December 2017 at 6 US medical centers. The interim analysis suggested futility for the primary outcome and recruitment was terminated with 2414 of 3184 planned participants. Follow-up ended January 4, 2018.

Interventions  Randomization occurred when participants reached complete cervical dilation. Immediate group participants (n = 1200) began pushing immediately. Delayed group participants (n = 1204) were instructed to wait 60 minutes.

Main Outcomes and Measures  The primary outcome was spontaneous vaginal delivery. Secondary outcomes included total duration of the second stage, duration of active pushing, operative vaginal delivery, cesarean delivery, postpartum hemorrhage, chorioamnionitis, endometritis, perineal lacerations (≥second degree), and a composite outcome of neonatal morbidity that included neonatal death and 9 other adverse outcomes.

Results  Among 2414 women randomized (mean age, 26.5 years), 2404 (99.6%) completed the trial. The rate of spontaneous vaginal delivery was 85.9% in the immediate group vs 86.5% in the delayed group, and was not significantly different (absolute difference, −0.6% [95% CI, −3.4% to 2.1%]; relative risk, 0.99 [95% CI, 0.96 to 1.03]). There was no significant difference in 5 of the 9 prespecified secondary outcomes reported, including the composite outcome of neonatal morbidity (7.3% for the immediate group vs 8.9% for the delayed group; between-group difference, −1.6% [95% CI, −3.8% to 0.5%]) and perineal lacerations (45.9% vs 46.4%, respectively; between-group difference, −0.4% [95% CI, −4.4% to 3.6%]). The immediate group had significantly shorter mean duration of the second stage compared with the delayed group (102.4 vs 134.2 minutes, respectively; mean difference, −31.8 minutes [95% CI, −36.7 to −26.9], P < .001), despite a significantly longer mean duration of active pushing (83.7 vs 74.5 minutes; mean difference, 9.2 minutes [95% CI, 5.8 to 12.6], P < .001), lower rates of chorioamnionitis (6.7% vs 9.1%; between-group difference, −2.5% [95% CI, −4.6% to −0.3%], P = .005), and fewer postpartum hemorrhages (2.3% vs 4.0%; between-group difference, −1.7% [95% CI, −3.1% to −0.4%], P = .03).

Conclusions and Relevance  Among nulliparous women receiving neuraxial anesthesia, the timing of second stage pushing efforts did not affect the rate of spontaneous vaginal delivery. These findings may help inform decisions about the preferred timing of second stage pushing efforts, when considered with other maternal and neonatal outcomes.


Revue sur la maladie veineuse thromboembolique


JAMA. 2018;320(15):1583-1594. doi:10.1001/jama.2018.14346



🚫 Manoeuvre de Sellick dans l’intubation en urgence : l’étude IRIS échoue à demontrer la non-infériorité de l’absence de pression

A. Birenbaum et al. in JAMA Surgery











Recommandation sur la prise en charge nutritionnel des patients de réanimation



Signer et al., Clinical Nutrition, 2018




ECCO2R : Présent & Futur



Boyle et al., Lancet, 2018




As a result of technical improvements, extracorporeal carbon dioxide removal (ECCO 2R) now has the potential to play an important role in the management of adults with acute respiratory failure. There is growing interest in the use of ECCO 2R for the management of both hypoxaemic and hypercapnic respiratory failure. However, evidence to support its use is scarce and several questions remain about the best way to implement this therapy, which can be associated with serious side-effects. This Review reflects the consensus opinion of an international group of clinician scientists with expertise in managing acute respiratory failure and in using ECCO 2R therapies in this setting. We concisely review clinically relevant aspects of ECCO 2R, and provide a series of recommendations for clinical practice and future research, covering topics that include the practicalities of ECCO 2R delivery, indications for use, and service delivery.



Association entre Grippe et Aspergilloses pulmonaire invasive ?




, et al., Lancet, 2018






Invasive pulmonary aspergillosis typically occurs in an immunocompromised host. For almost a century, influenza has been known to set up for bacterial superinfections, but recently patients with severe influenza were also reported to develop invasive pulmonary aspergillosis. We aimed to measure the incidence of invasive pulmonary aspergillosis over several seasons in patients with influenza pneumonia in the intensive care unit (ICU) and to assess whether influenza was an independent risk factor for invasive pulmonary aspergillosis.

Methods : We did a retrospective multicentre cohort study. Data were collected from adult patients with severe influenza admitted to seven ICUs across Belgium and The Netherlands during seven influenza seasons. Patients were older than 18 years, were admitted to the ICU for more than 24 h with acute respiratory failure, had pulmonary infiltrates on imaging, and a confirmed influenza infection based on a positive airway PCR test (influenza cohort). We used logistic regression analyses to determine if influenza was independently associated with invasive pulmonary aspergillosis in non-immunocompromised (ie, no European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [EORTC/MSG] host factor) influenza-positive patients (influenza case group) compared with non-immunocompromised patients with severe community-acquired pneumonia who had a negative airway influenza PCR test (control group).

Findings : Data were collected from patients admitted to the ICU between Jan 1, 2009, and June 30, 2016. Invasive pulmonary aspergillosis was diagnosed in 83 (19%) of 432 patients admitted with influenza (influenza cohort), a median of 3 days after admission to the ICU. The incidence was similar for influenza A and B. For patients with influenza who were immunocompromised, incidence of invasive pulmonary aspergillosis was as high as 32% (38 of 117 patients), whereas in the non-immunocompromised influenza case group, incidence was 14% (45 of 315 patients). Conversely, only 16 (5%) of 315 patients in the control group developed invasive pulmonary aspergillosis. The 90-day mortality was 51% in patients in the influenza cohort with invasive pulmonary aspergillosis and 28% in the influenza cohort without invasive pulmonary aspergillosis (p=0·0001). In this study, influenza was found to be independently associated with invasive pulmonary aspergillosis (adjusted odds ratio 5·19; 95% CI 2·63–10·26; p<0·0001), along with a higher APACHE II score, male sex, and use of corticosteroids.

Interpretation: Influenza was identified as an independent risk factor for invasive pulmonary aspergillosis and is associated with high mortality. Future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis.



Corticoïdes et sepsis : comment interpréter conjointement les résultats contradictoires des récentes études APROCCHSS et ADRENAL ?





DOI: S2213-2600(18)30265-0




Glucocorticoids have been used as adjunctive therapy in patients with sepsis and septic shock for more than four decades. The rationale for the use of glucocorticoids is that this class of drugs downregulates the proinflammatory response and limits the anti-inflammatory response while preserving innate immunity. Between 1976 and 2017, 22 randomised placebo-controlled trials have been published evaluating the benefit of glucocorticoids in patients with community-acquired pneumonia, sepsis, and septic shock. These studies produced conflicting results. In 2018, two large randomised controlled trials (RCTs) were published evaluating the role of hydrocortisone in patients with septic shock. The Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial reported a reduction in 90-day mortality whereas the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial reported no mortality benefit. This Viewpoint critically appraises these two RCTs and evaluates the use of glucocorticoids in the treatment of sepsis and septic shock in the modern era.







Vasopresseur et neuromyopathie de réanimation ?



Krysta S. Wolfe, et al., Chest, 2018





Vasoactive medications are commonly used in the treatment of critically ill patients, but their impact on the development of ICU-acquired weakness is not well described. The objective of this study is to evaluate the relationship between vasoactive medication use and the outcome of ICU-acquired weakness.


This is a secondary analysis of mechanically ventilated patients (N = 172) enrolled in a randomized clinical trial of early occupational and physical therapy vs conventional therapy, which evaluated the end point of ICU-acquired weakness on hospital discharge. Patients underwent bedside muscle strength testing by a therapist blinded to study allocation to evaluate for ICU-acquired weakness. The effects of vasoactive medication use on the incidence of ICU-acquired weakness in this population were assessed.


On logistic regression analysis, the use of vasoactive medications increased the odds of developing ICU-acquired weakness (odds ratio [OR], 3.2; P = .01) independent of all other established risk factors for weakness. Duration of vasoactive medication use (in days) (OR, 1.35; P = .004) and cumulative norepinephrine dose (μg/kg/d) (OR, 1.01; P = .02) (but not vasopressin or phenylephrine) were also independently associated with the outcome of ICU-acquired weakness.


In mechanically ventilated patients enrolled in a randomized clinical trial of early mobilization, the use of vasoactive medications was independently associated with the development of ICU-acquired weakness. Prospective trials to further evaluate this relationship are merited.




Limitation du flux expiratoire chez le patient ventilé : diagnostic, implication et traitement



Detajin Junhasavasdikul, et al., Chest, 2018



Expiratory flow limitation (EFL) is present when the flow cannot rise despite an increase in the expiratory driving pressure. The mechanisms of EFL are debated but are believed to be related to the collapsibility of small airways. In patients who are mechanically ventilated, EFL can exist during tidal ventilation, representing an extreme situation in which lung volume cannot decrease, regardless of the expiratory driving forces. It is a key factor for the generation of auto- or intrinsic positive end-expiratory pressure (PEEP) and requires specific management such as positioning and adjustment of external PEEP. EFL can be responsible for causing dyspnea and patient-ventilator dyssynchrony, and it is influenced by the fluid status of the patient. EFL frequently affects patients with COPD, obesity, and heart failure, as well as patients with ARDS, especially at low PEEP. EFL is, however, most often unrecognized in the clinical setting despite being associated with complications of mechanical ventilation and poor outcomes such as postoperative pulmonary complications, extubation failure, and possibly airway injury in ARDS. Therefore, prompt recognition might help the management of patients being mechanically ventilated who have EFL and could potentially influence outcome. EFL can be suspected by using different means, and this review summarizes the methods to specifically detect EFL during mechanical ventilation.







Le Paracétamol comme néphro-protecteur dans les crises palustres graves ?



Clinical Infectious Diseases, Volume 67, Issue 7, 14 September 2018, Pages 991–999,




Acute kidney injury independently predicts mortality in falciparum malaria. It is unknown whether acetaminophen’s capacity to inhibit plasma hemoglobin-mediated oxidation is renoprotective in severe malaria.


This phase 2, open-label, randomized controlled trial conducted at two hospitals in Bangladesh assessed effects on renal function, safety, pharmacokinetic (PK) properties and pharmacodynamic (PD) effects of acetaminophen. Febrile patients (>12 years) with severe falciparum malaria were randomly assigned to receive acetaminophen (1 g 6–hourly for 72 hours) or no acetaminophen, in addition to intravenous artesunate. Primary outcome was the proportional change in creatinine after 72 hours stratified by median plasma hemoglobin.


Between 2012 and 2014, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31). Median (interquartile range) reduction in creatinine after 72 hours was 23% (37% to 18%) in patients assigned to acetaminophen, versus 14% (29% to 0%) in patients assigned to no acetaminophen (P = .043). This difference in reduction was 37% (48% to 22%) versus 14% (30% to −71%) in patients with hemoglobin ≥45000 ng/mL (P = .010). The proportion with progressing kidney injury was higher among controls (subdistribution hazard ratio, 3.0; 95% confidence interval, 1.1 to 8.5; P= .034). PK–PD analyses showed that higher exposure to acetaminophen increased the probability of creatinine improvement. No patient fulfilled Hy’s law for hepatotoxicity.


In this proof-of-principle study, acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, particularly in those with prominent intravascular hemolysis.





Pour : la perfusion prolongée de beta-lactamines pour les patients neutropéniques !


Ron Ram et al.,  Clinical Infectious Diseases, Volume 67, Issue 8, 28 September 2018, Pages 1153–1160,




Febrile neutropenia may be a sign of severe infection and is associated with significant morbidity and mortality in high-risk patients with hematologic malignancies. Extended infusion of β-lactam antibiotics is associated with greater clinical response than is bolus infusion in nonneutropenic critically ill patients, but data are lacking for febrile neutropenic patients.


We designed a single-center, nonblinded, randomized trial to compare extended infusion (4 hours) and bolus infusion (30 minutes) of piperacillin-tazobactam or ceftazidime in high-risk patients with febrile neutropenia. The primary endpoint was overall response on day 4, defined as the combination of resolution of fever, sterile blood cultures, resolution of clinical signs and symptoms, and no need for a change in the antibiotic regimen. Outcome was adjudicated by investigators blinded to treatment allocation.


Of 123 enrolled patients, 105 had febrile neutropenia and were included in the intention-to-treat analysis: 47 in the extended infusion arm and 58 in the bolus infusion arm. Overall response occurred in 35 (74.4%) patients treated with extended infusion and 32 (55.1%) patients treated with bolus infusion (P = .044). The superiority of extended infusion was greatest for patients with clinically documented infections (overall response, 68.4% [13/19] vs 35.7% [10/28]; P = .039) and specifically for those with pneumonia (80% [4/5] vs 0% [0/8]; P = .007).


Extended infusion of β-lactams is associated with superior treatment outcomes compared with bolus infusion for high-risk patients with febrile neutropenia. The benefit of extended β-lactam infusion may be greatest for patients with pulmonary infections.








Hypothermie thérapeutique post-ACR : 32, 33 ou 34 degrés ?




Esteban Lopez-de-Sa, et al., ICM, 2018





To obtain initial data on the effect of different levels of targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA).



We designed a multicentre pilot trial with 1:1:1 randomization to either 32 °C (n = 52), 33 °C (n = 49) or 34 °C (n = 49), via endovascular cooling devices during a 24-h period in comatose survivors of witnessed OHCA and initial shockable rhythm. The primary endpoint was the percentage of subjects surviving with good neurologic outcome defined by a modified Rankin Scale (mRS) score of ≤ 3, blindly assessed at 90 days.


At baseline, different proportions of patients who had received defibrillation administered by a bystander were assigned to groups of 32 °C (13.5%), 33 °C (34.7%) and 34 °C (28.6%; p = 0.03). The percentage of patients with an mRS ≤ 3 at 90 days (primary endpoint) was 65.3, 65.9 and 65.9% in patients assigned to 32, 33 and 34 °C, respectively, non-significant (NS). The multivariate Cox proportional hazards model identified two variables significantly related to the primary outcome: male gender and defibrillation by a bystander. Among the 43 patients who died before 90 days, 28 died following withdrawal of life-sustaining therapy, as follows: 7/16 (43.8%), 10/13 (76.9%) and 11/14 (78.6%) of patients assigned to 32, 33 and 34 °C, respectively (trend test p = 0.04). All levels of cooling were well tolerated.



There were no statistically significant differences in neurological outcomes among the different levels of TTM. However, future research should explore the efficacy of TTM at 32 °C.




Réduction de 70% des PAVM grâce à un protocole de 9 interventions



C. Landelle, et al., ICM, 2018




We describe the impact of a multifaceted program for decreasing ventilator-associated pneumonia (VAP) after implementing nine preventive measures, including selective oropharyngeal decontamination (SOD).



We compared VAP rates during an 8-month pre-intervention period, a 12-month intervention period, and an 11-month post-intervention period in a cohort of patients who received mechanical ventilation (MV) for > 48 h. The primary objective was to assess the effect on first VAP occurrence, using a Cox cause-specific proportional hazards model. Secondary objectives included the impact on emergence of antimicrobial resistance, antibiotic consumption, duration of MV, and ICU mortality.



Pre-intervention, intervention and post-intervention VAP rates were 24.0, 11.0 and 3.9 VAP episodes per 1000 ventilation-days, respectively. VAP rates decreased by 56% [hazard ratio (HR) 0.44, 95% CI 0.29–0.65; P < 0.001] in the intervention and by 85% (HR 0.15, 95% CI 0.08–0.27; P < 0.001) in the post-intervention periods. During the intervention period, VAP rates decreased by 42% (HR 0.58, 95% CI 0.38–0.87; P < 0.001) after implementation of eight preventive measures without SOD, and by 70% after adding SOD (HR 0.30, 95% CI 0.13–0.72; P < 0.001) compared to the pre-intervention period. The incidence density of intrinsically resistant bacteria (to colistin or tobramycin) did not increase. We documented a significant reduction of days of therapy per 1000 patient-days of broad-spectrum antibiotic used to treat lower respiratory tract infection (P < 0.028), median duration of MV (from 7.1 to 6.4 days; P < 0.003) and ICU mortality (from 16.2 to 13.5%; P < 0.049) for patients ventilated > 48 h between the pre- and post-intervention periods.



Our preventive program produced a sustained decrease in VAP incidence. SOD provides an additive value.




So far so good : Réflexion sur l’information donnée aux patients



Fabrizio Elia, et al., ICM, 2018




Rapport P/F, la physiologie pour comprendre ses bénéfices et ses limites



L. Gattinoni et al., ICM, 2018






EEG lors de l’administration de Dexmedetomidine




BACKGROUND: The depth of dexmedetomidine-induced sedation is difficult to assess without arousing the patient. We evaluated frontal electroencephalogram (EEG) as an objective measure of dexmedetomidine-induced sedation. Our aims were to characterize the response patterns of EEG during a wide range of dexmedetomidine-induced sedation and to determine which spectral power best correlated with assessed levels of dexmedetomidine-induced sedation.

METHODS: Sedline EEG sensor was positioned on the forehead of 16 volunteers. Frontal EEG data were collected at 250 Hz using the Sedline monitor. A computer-controlled infusion pump was used to infuse dexmedetomidine to four 15-minute target plasma concentrations of 0.3, 0.6, 1.2, and 2.4 ng/mL. Arterial blood samples for dexmedetomidine plasma concentration and sedation (self-reported numerical rating scale) and arousal were measured at baseline and at the end of each infusion step. The EEG signal was used to estimate spectral power in sequential 4-second data segments with 75% overlap for 3 power bands: delta = 0.5–1.5 Hz, alpha = 9–14 Hz, beta = 15–24 Hz. We quantified the relationships among the plasma concentrations of dexmedetomidine, level of sedation, and various EEG parameters.

RESULTS: EEG data at the end of the dexmedetomidine infusion steps show progressive loss of high frequencies (beta) and increase in alpha and delta powers, with increasing dexmedetomidine concentrations. Beta prearousal spectral power was best in predicting dexmedetomidine-induced level of sedation (R = −0.60, 95% CI, −0.43 to −0.75). The respective values for delta and alpha powers were R = 0.28 (95% CI, 0.03–0.45) and R = 0.16 (95% CI, −0.09 to 0.38). When the beta power has dropped below −16 dB or the delta power is above 15 dB, the subjects show moderate to deep levels of sedation. When awakening the subject, there is a reduction in power in the delta and alpha bands at the 0.6, 1.2, and 2.4 ng/mL dexmedetomidine target levels (P < .001 for all). In beta band, there is a rapid awakening-induced increase in power (P < .001) followed by a slow return toward baseline values. After arousing the subjects, the EEG powers returned toward baseline values significantly slower than our clinical observation of the subjects’ wakefulness would have suggested.

CONCLUSIONS: Using a wide range of dexmedetomidine doses, we found that frontal EEG beta power of less than −16 dB and/or a delta power of over 15 dB was associated with a state of moderate to deep sedation and that poststimulus return of EEG powers toward baseline values took significantly longer than expected from observation of the arousal response. It is unclear whether these observations are robust enough for clinical applicability.



Recommandations sur la prise en charge per-opératoire des patients avec un syndrome d’apnée du sommeil





Méta-analyse sur les complications post-opératoires induites par les opioïdes chez les patients avec un syndrome d’apnée du sommeil




The intrinsic nature of opioids to suppress respiratory function is of particular concern among patients with obstructive sleep apnea (OSA). The association of OSA with increased perioperative risk has raised the question of whether patients with OSA are at higher risk for opioid-induced respiratory depression (OIRD) compared to the general population. The aims of this systematic review were to summarize current evidence with respect to perioperative OIRD, changes in sleep-disordered breathing, and alterations in pain and opioid sensitivity in patients with OSA. A systematic literature search of studies published between 1946 and October 2017 was performed utilizing the following databases: Medline, ePub Ahead of Print/Medline In-process, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed—NOT-Medline and ClinicalTrials.Gov. Of 4321 initial studies, 40 met the inclusion criteria. The Oxford level of evidence was assessed. Overall, high-quality evidence on the comparative impact of acute opioid analgesia in OSA versus non-OSA patients is lacking. The current body of evidence is burdened by significant limitations including risk of bias and large heterogeneity among studies with regard to OSA severity, perioperative settings, outcome definitions, and the presence or absence of various perioperative drivers. These factors complicate an accurate interpretation and robust analysis of the true complication risk. Nevertheless, there is some consistency among studies with regard to a detrimental effect of opioids in the presence of OSA. Notably, the initial 24 hours after opioid administration appear to be most critical with regard to life-threatening OIRD. Further, OSA-related increased pain perception and enhanced opioid sensitivity could predispose patients with OSA to a higher risk for OIRD without overdosing. While high-quality evidence is needed, retrospective analyses indicate that critical, life-threatening OIRD may be preventable with a more cautious approach to opioid use, including adequate monitoring.



Revue systématique sur le rôle des benzodiazépines sur le delirium de réanimation

Kok, Lotte et al., CCM 2018
DOI: 10.1097/CCM.0000000000003300
Objectives: A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission.
Data Sources: PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO.
Study Selection: Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction.
Data Extraction: Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist.
Data Synthesis: Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high methodological quality generally found benzodiazepine use to be a risk factor for the development of delirium. Five studies reported an association between benzodiazepine use and symptoms of posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction after ICU admission; five studies reported mixed findings, and in four studies, no association was found. No association was found with methodological quality and sample size for these findings. Meta-analysis was not feasible due to major differences in study methods.
Conclusions: The majority of included studies indicated that benzodiazepine use in the ICU is associated with delirium, symptoms of posttraumatic stress disorder, anxiety, depression, and cognitive dysfunction. Future well-designed studies and randomized controlled trials are necessary to rule out confounding by indication.

Réduction de la mortalité et meilleure clairance de la créatinine dans le choc septique avec supplémentation en B1 ?


Woolum, Jordan A. et al., CCM 2018
DOI: 10.1097/CCM.0000000000003311
Objectives: Mounting evidence has shown that critically ill patients are commonly thiamine deficient. We sought to test the hypothesis that critically ill patients with septic shock exposed to thiamine would demonstrate improved lactate clearance and more favorable clinical outcomes compared with those not receiving thiamine.
Design: Retrospective, single-center, matched cohort study.
Setting: Tertiary care academic medical center.
Patients: Adult patients admitted with an International Classification of Diseases, 9th Edition, or International Classification of Diseases, 10th Edition, diagnosis code of septic shock to either the medicine or surgery ICU.
Interventions: None.
Measurements and Main Results: Patients who received IV thiamine supplementation within 24 hours of hospital admission were identified and compared with a matched cohort of patients not receiving thiamine. The primary objective was to determine if thiamine administration was associated with a reduced time to lactate clearance in septic shock. Secondary outcomes included 28-day mortality, acute kidney injury, and need for renal replacement therapy, and vasopressor and mechanical ventilation-free days. Two-thousand two-hundred seventy-two patients were screened, of whom 1,049 were eligible. The study consisted of 123 thiamine-treated patients matched with 246 patients who did not receive thiamine. Based on the Fine-Gray survival model, treatment with thiamine was associated with an improved likelihood of lactate clearance (subdistribution hazard ratio, 1.307; 95% CI, 1.002–1.704). Thiamine administration was also associated with a reduction in 28-day mortality (hazard ratio, 0.666; 95% CI, 0.490–0.905). There were no differences in any secondary outcomes.
Conclusions: Thiamine administration within 24 hours of admission in patients presenting with septic shock was associated with improved lactate clearance and a reduction in 28-day mortality compared with matched controls.

Revue sur les traitement adjuvants dans le SDRA

Fielding-Singh, Vikram et al., CCM 2018
DOI: 10.1097/CCM.0000000000003406

Modes de ventilation et complications post-opératoires chez le patient obèse

L. Ball et. al, BJA 2018
DOI: 10.1016/j.bja.2018.04.021


There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients.Methods
We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery’ (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end-point.



We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th–75th percentiles: 7.8–9.9] ml kg−1 predicted body weight, PEEP was 4 [1–5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m−2(P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001).



Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients.




Revue systématique sur les conséquences de l’hypotension artérielle per-opératoire



E.M. Wesselink et. al, BJA 2018
DOI: 10.1016/j.bja.2018.04.036

Recommandations sur la gestion thermique des patients cérébrolésés

P.J.D. Andrews et al., BJA 2018
DOI: 10.1016/j.bja.2018.06.018





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