Biblio du mois : Octobre 2016

31 octobre 2016ActualitésLa Biblio du moisNon classé





Tout d’abord, Joyeux Halloween et Joyeuse Toussaint !

Loin de nous l’idée macabre de vous souhaiter en tant qu’Anesthésistes-Réanimateurs une bonne fête des morts en cette fin de semestre…

Beaucoup d’études négatives mais un retour confirmé sur la mobilisation précoce en Réanimation, synonyme de simplicité ? A vous de voir !

Tout ceci agrémenté d’enfin une étude sur l’hypothermie pour les ACR intra-hospitaliers et des études sur les Outcomes à long terme de nos patients sortant de réanimation.

Bonus spéciaux sur la transplantation faciale pour ceux qui sont en panne d’inspiration pour les masques d’Halloween et à propos de quelques électrolytes dont le NaCl (et oui je sais que certains en sont amoureux… Hoho !).

Bref, de quoi vous faire froid dans le dos !





Levosimendan dans le sepsis : raté !


Gordon et al., NEJM, 2016



Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis.


We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events.


The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04).


The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia







Hypothermie thérapeutique post-ACR intra-hospitalier


Chan et al., JAMA, 2016



Therapeutic hypothermia is used for patients following both out-of-hospital and in-hospital cardiac arrest. However, randomized trials on its efficacy for the in-hospital setting do not exist, and comparative effectiveness data are limited.


To evaluate the association between therapeutic hypothermia and survival after in-hospital cardiac arrest.

Design, Setting, and Patients

In this cohort study, within the national Get With the Guidelines–Resuscitation registry, 26 183 patients successfully resuscitated from an in-hospital cardiac arrest between March 1, 2002, and December 31, 2014, and either treated or not treated with hypothermia at 355 US hospitals were identified. Follow-up ended February 4, 2015.


Induction of therapeutic hypothermia.

Main Outcomes and Measures

The primary outcome was survival to hospital discharge. The secondary outcome was favorable neurological survival, defined as a Cerebral Performance Category score of 1 or 2 (ie, without severe neurological disability). Comparisons were performed using a matched propensity score analysis and examined for all cardiac arrests and separately for nonshockable (asystole and pulseless electrical activity) and shockable (ventricular fibrillation and pulseless ventricular tachycardia) cardiac arrests.


Overall, 1568 of 26 183 patients with in-hospital cardiac arrest (6.0%) were treated with therapeutic hypothermia; 1524 of these patients (mean [SD] age, 61.6 [16.2] years; 58.5% male) were matched by propensity score to 3714 non–hypothermia-treated patients (mean [SD] age, 62.2 [17.5] years; 57.1% male). After adjustment, therapeutic hypothermia was associated with lower in-hospital survival (27.4% vs 29.2%; relative risk [RR], 0.88 [95% CI, 0.80 to 0.97]; risk difference, −3.6% [95% CI, −6.3% to −0.9%]; P = .01), and this association was similar (interaction P = .74) for nonshockable cardiac arrest rhythms (22.2% vs 24.5%; RR, 0.87 [95% CI, 0.76 to 0.99]; risk difference, −3.2% [95% CI, −6.2% to −0.3%]) and shockable cardiac arrest rhythms (41.3% vs 44.1%; RR, 0.90 [95% CI, 0.77 to 1.05]; risk difference, −4.6% [95% CI, −10.9% to 1.7%]). Therapeutic hypothermia was also associated with lower rates of favorable neurological survival for the overall cohort (hypothermia-treated group, 17.0% [246 of 1443 patients]; non–hypothermia-treated group, 20.5% [725 of 3529 patients]; RR, 0.79 [95% CI, 0.69 to 0.90]; risk difference, −4.4% [95% CI, −6.8% to −2.0%]; P < .001) and for both rhythm types (interaction P = .88).

Conclusions and Relevance

Among patients with in-hospital cardiac arrest, use of therapeutic hypothermia compared with usual care was associated with a lower likelihood of survival to hospital discharge and a lower likelihood of favorable neurological survival. These observational findings warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia for in-hospital cardiac arrest.


Hausse du risque de Clostridium difficile si le patient précédent a reçu des ATB ?


Freedberg, et al., JAMA Int Med, 2016



To assess whether receipt of antibiotics by prior hospital bed occupants is associated with increased risk for CDI in subsequent patients who occupy the same bed.

Design, Setting, and Participants

This is a retrospective cohort study of adult patients hospitalized in any 1 of 4 facilities between 2010 and 2015. Patients were excluded if they had recent CDI, developed CDI within 48 hours of admission, had inadequate follow-up time, or if their prior bed occupant was in the bed for less than 24 hours.

Main Outcomes and Measures

The primary exposure was receipt of non-CDI antibiotics by the prior bed occupant and the primary outcome was incident CDI in the subsequent patient to occupy the same bed. Incident CDI was defined as a positive result from a stool polymerase chain reaction for the C difficile toxin B gene followed by treatment for CDI. Demographics, comorbidities, laboratory data, and medication exposures are reported.


Among 100 615 pairs of patients who sequentially occupied a given hospital bed, there were 576 pairs (0.57%) in which subsequent patients developed CDI. Receipt of antibiotics in prior patients was significantly associated with incident CDI in subsequent patients (log-rank P < .01). This relationship remained unchanged after adjusting for factors known to influence risk for CDI including receipt of antibiotics by the subsequent patient (adjusted hazard ratio [aHR], 1.22; 95% CI, 1.02-1.45) and also after excluding 1497 patient pairs among whom the prior patients developed CDI (aHR, 1.20; 95% CI, 1.01-1.43). Aside from antibiotics, no other factors related to the prior bed occupants were associated with increased risk for CDI in subsequent patients.

Conclusions and Relevance

Receipt of antibiotics by prior bed occupants was associated with increased risk for CDI in subsequent patients. Antibiotics can directly affect risk for CDI in patients who do not themselves receive antibiotics.


Revue sur les nausées-vomissements pendant la grossesse


McParlin et al., JAMA , 2016





Mobilisation précoce en Réanimation Chirurgicale


Schaller, et al., Lancet, 2016



Immobilisation predicts adverse outcomes in patients in the surgical intensive care unit (SICU). Attempts to mobilise critically ill patients early after surgery are frequently restricted, but we tested whether early mobilisation leads to improved mobility, decreased SICU length of stay, and increased functional independence of patients at hospital discharge.


We did a multicentre, international, parallel-group, assessor-blinded, randomised controlled trial in SICUs of five university hospitals in Austria (n=1), Germany (n=1), and the USA (n=3). Eligible patients (aged 18 years or older, who had been mechanically ventilated for <48 h, and were expected to require mechanical ventilation for ≥24 h) were randomly assigned (1:1) by use of a stratified block randomisation via restricted web platform to standard of care (control) or early, goal-directed mobilisation using an inter-professional approach of closed-loop communication and the SICU optimal mobilisation score (SOMS) algorithm (intervention), which describes patients’ mobilisation capacity on a numerical rating scale ranging from 0 (no mobilisation) to 4 (ambulation). We had three main outcomes hierarchically tested in a prespecified order: the mean SOMS level patients achieved during their SICU stay (primary outcome), and patient’s length of stay on SICU and the mini-modified functional independence measure score (mmFIM) at hospital discharge (both secondary outcomes). This trial is registered with (NCT01363102).


Between July 1, 2011, and Nov 4, 2015, we randomly assigned 200 patients to receive standard treatment (control; n=96) or intervention (n=104). Intention-to-treat analysis showed that the intervention improved the mobilisation level (mean achieved SOMS 2·2 [SD 1·0] in intervention groupvs 1·5 [0·8] in control group, p<0·0001), decreased SICU length of stay (mean 7 days [SD 5–12] in intervention group vs 10 days [6–15] in control group, p=0·0054), and improved functional mobility at hospital discharge (mmFIM score 8 [4–8] in intervention group vs 5 [2–8] in control group, p=0·0002). More adverse events were reported in the intervention group (25 cases [2·8%]) than in the control group (ten cases [0·8%]); no serious adverse events were observed. Before hospital discharge 25 patients died (17 [16%] in the intervention group, eight [8%] in the control group). 3 months after hospital discharge 36 patients died (21 [22%] in the intervention group, 15 [17%] in the control group).


Early, goal-directed mobilisation improved patient mobilisation throughout SICU admission, shortened patient length of stay in the SICU, and improved patients’ functional mobility at hospital discharge.



Dexmedetomidine dans la prévention de Delirium post-opératoire non cardiaque


Su et al., Lancet, 2016



Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery.


We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry,, number ChiCTR-TRC-10000802.


Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 [9%] of 350 patients) than in the placebo group (79 [23%] of 350 patients; odds ratio [OR] 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 [18%] of 350 patients) than with dexmedetomidine (34 [10%] of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 [14%] of 350 patients) than in patients given dexmedetomidine (23 [7%] of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups.


For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe.


Monitorage de l’agrégation plaquettaire : NS


Cayla et al., Lancet, 2016




Elderly patients are at high risk of ischaemic and bleeding events. Platelet function monitoring offers the possibility to individualise antiplatelet therapy to improve the therapeutic risk–benefit ratio. We aimed to assess the effect of platelet function monitoring with treatment adjustment in elderly patients stented for an acute coronary syndrome.


We did this multicentre, open-label, blinded-endpoint, randomised controlled superiority study at 35 centres in France. Patients aged 75 years or older who had undergone coronary stenting for acute coronary syndrome were randomly assigned (1:1), via a central interactive voice-response system based on a computer-generated permuted-block randomisation schedule with randomly selected block sizes, to receive oral prasugrel 5 mg daily with dose or drug adjustment in case of inadequate response (monitoring group) or oral prasugrel 5 mg daily with no monitoring or treatment adjustment (conventional group). Randomisation was stratified by centre. Platelet function testing was done 14 days after randomisation and repeated 14 days after treatment adjustment in patients in the monitoring group. Study investigators and patients were not masked to treatment allocation, but allocation was concealed from an independent clinical events committee responsible for endpoint adjudication. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularisation, and Bleeding Academic Research Consortium-defined bleeding complications (types 2, 3, or 5) at 12 months’ follow-up. We did analysis by intention to treat. This trial is registered with, number NCT01538446.


Between March 27, 2012, and May 19, 2015, we randomly assigned 877 patients to the monitoring group (n=442) or the conventional group (n=435). The primary endpoint occurred in 120 (28%) patients in the monitoring group compared with 123 (28%) patients in the conventional group (hazard ratio [HR], 1·003, 95% CI 0·78–1·29; p=0·98). Rates of bleeding events did not differ significantly between groups.


Platelet function monitoring with treatment adjustment did not improve the clinical outcome of elderly patients treated with coronary stenting for an acute coronary syndrome. Platelet function testing is still being used in many centres and international guidelines still recommend platelet function testing in high-risk situations. Our study does not support this practice or these recommendations.



Edoxaban versus Enoxaparine-Warfarin pour la cardioversion de FA


Goette, et al., Lancet, 2016


Edoxaban, an oral factor Xa inhibitor, is non-inferior for prevention of stroke and systemic embolism in patients with atrial fibrillation and is associated with less bleeding than well controlled warfarin therapy. Few safety data about edoxaban in patients undergoing electrical cardioversion are available.


We did a multicentre, prospective, randomised, open-label, blinded-endpoint evaluation trial in 19 countries with 239 sites comparing edoxaban 60 mg per day with enoxaparin–warfarin in patients undergoing electrical cardioversion of non-valvular atrial fibrillation. The dose of edoxaban was reduced to 30 mg per day if one or more factors (creatinine clearance 15–50 mL/min, low bodyweight [≤60 kg], or concomitant use of P-glycoprotein inhibitors) were present. Block randomisation (block size four)—stratified by cardioversion approach (transoesophageal echocardiography [TEE] or not), anticoagulant experience, selected edoxaban dose, and region—was done through a voice-web system. The primary efficacy endpoint was a composite of stroke, systemic embolic event, myocardial infarction, and cardiovascular mortality, analysed by intention to treat. The primary safety endpoint was major and clinically relevant non-major (CRNM) bleeding in patients who received at least one dose of study drug. Follow-up was 28 days on study drug after cardioversion plus 30 days to assess safety. This trial is registered with, number NCT02072434.


Between March 25, 2014, and Oct 28, 2015, 2199 patients were enrolled and randomly assigned to receive edoxaban (n=1095) or enoxaparin–warfarin (n=1104). The mean age was 64 years (SD 10·54) and mean CHA2DS2-VASc score was 2·6 (SD 1·4). Mean time in therapeutic range on warfarin was 70·8% (SD 27·4). The primary efficacy endpoint occurred in five (<1%) patients in the edoxaban group versus 11 (1%) in the enoxaparin–warfarin group (odds ratio [OR] 0·46, 95% CI 0·12–1·43). The primary safety endpoint occurred in 16 (1%) of 1067 patients given edoxaban versus 11 (1%) of 1082 patients given enoxaparin–warfarin (OR 1·48, 95% CI 0·64–3·55). The results were independent of the TEE-guided strategy and anticoagulation status.


ENSURE-AF is the largest prospective randomised clinical trial of anticoagulation for cardioversion of patients with non-valvular atrial fibrillation. Rates of major and CRNM bleeding and thromboembolism were low in the two treatment groups.



Revascularisation précoce pour les SCA ST- ?


Wallentin, et al., Lancet, 2016



The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years’ follow-up.


The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat.


At a minimum of 15 years’ follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204–888; p=0·0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402–1175; pinteraction=0·0182), patients with elevated troponin T (778 days, 357–1165; pinteraction=0·0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507–1650; pinteraction=0·0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830–1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (p<0·0001).


During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.


Bonus : Retour sur la transplantation faciale


Lantieri, et al., Lancet, 2016






Dysfonction musculaire après VM en Réanimation


Dos Santos, AJRCCM, 2016



Rationale: Critical illness survivors often experience permanent functional disability due to intensive care unit (ICU)-acquired weakness. The mechanisms responsible for long-term weakness persistence versus resolution are unknown.

Objectives: To delineate cellular mechanisms underlying long-term weakness persistence in ICU survivors.

Methods: We conducted a nested, prospective study of critically ill patients mechanically ventilated for 7 days or longer. The patients were recruited from the RECOVER program and serially assessed over 6 months after ICU discharge. Twenty-seven of 82 patients consented to participate; 15 and 11 patients were assessed at 7 days and 6 months after ICU discharge, respectively.

Measurements and Main Results: We assessed motor functional capacity, quadriceps size, strength, and voluntary contractile capacity and performed electromyography, nerve conduction studies, and vastus lateralis biopsies for histologic, cellular, and molecular analyses. Strength and quadriceps cross-sectional areas were decreased 7 days after ICU discharge. Weakness persisted to 6 months and correlated with decreased function. Quadriceps atrophy resolved in 27% patients at 6 months. Muscle mass reconstitution did not correlate with resolution of weakness, owing to persistent impaired voluntary contractile capacity. Compared with Day 7, increased ubiquitin–proteasome system–mediated muscle proteolysis, inflammation, and decreased mitochondrial content all normalized at 6 months. Autophagy markers were normal at 6 months. Patients with sustained atrophy had decreased muscle progenitor (satellite) cell content.

Conclusions: Long-term weakness in ICU survivors results from heterogeneous muscle pathophysiology with variable combinations of muscle atrophy and impaired contractile capacity. These findings are not explained by ongoing muscle proteolysis, inflammation, or diminished mitochondrial content. Sustained muscle atrophy is associated with decreased satellite cell content and compromised muscle regrowth, suggesting impaired regenerative capacity.

Recul à 1 an chez les patients ayant eu au moins 7 jours de VM


Herridge, et al., AJRCCM, 2016


Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design.


To stratify patients for post-ICU disability and recovery to 1 year after critical illness.


We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling.

Measurements and Main Results

The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year.


ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity.



Une étude bien salée : the SALT study


Semler, et al.




Saline is the intravenous fluid most commonly administered to critically ill adults, but may be associated with acute kidney injury and death. Whether use of balanced crystalloids rather than saline affects patient outcomes remains unknown.


To pilot a cluster-randomized, multiple-crossover trial using software tools within the electronic health record to compare saline to balanced crystalloids.


Cluster-randomized, multiple-crossover trial among 974 adults admitted to a tertiary medical intensive care unit from February 3, 2015 through May 31, 2015. The intravenous crystalloid used in the unit alternated monthly between saline (0.9% sodium chloride) and balanced crystalloids (Lactated Ringer’s solution or Plasma-Lyte A®). Enrollment, fluid delivery, and data collection were performed using software tools within the electronic health record. The primary outcome was the difference between study groups in the proportion of isotonic crystalloid administered that was saline. The secondary outcome was the Major Adverse Kidney Events within 30 days (MAKE30) composite of death, dialysis, or persistent renal dysfunction.


Patients assigned to saline (n=454) and balanced crystalloids (n=520) were similar at baseline and received similar volumes of crystalloid by 30 days (median [IQR]: 1424 [500–3377] mL vs 1617 [500–3628] mL; P = 0.40). Saline comprised a larger proportion of the isotonic crystalloid given in the saline group than in the balanced crystalloid group (91% vs 21%; P < 0.001). MAKE30 did not differ between groups (24.7% vs 24.6%, P = 0.98).


An electronic health record-embedded, cluster-randomized, multiple-crossover trial comparing saline with balanced crystalloids can produce well-balanced study groups and separation in crystalloid receipt.






Antagonisez les curares !


Simons et al., Anesthesiology, 2016



Residual postoperative paralysis from nondepolarizing neuromuscular blocking agents (NMBAs) is a known problem. This paralysis has been associated with impaired respiratory function, but the clinical significance remains unclear. The aims of this analysis were two-fold: (1) to investigate if intermediate-acting NMBA use during surgery is associated with postoperative pneumonia and (2) to investigate if nonreversal of NMBAs is associated with postoperative pneumonia.


Surgical cases (n = 13,100) from the Vanderbilt University Medical Center National Surgical Quality Improvement Program database who received general anesthesia were included. The authors compared 1,455 surgical cases who received an intermediate-acting nondepolarizing NMBA to 1,455 propensity score–matched cases who did not and 1,320 surgical cases who received an NMBA and reversal with neostigmine to 1,320 propensity score–matched cases who did not receive reversal. Postoperative pneumonia incidence rate ratios (IRRs) and bootstrapped 95% CIs were calculated.


Patients receiving an NMBA had a higher absolute incidence rate of postoperative pneumonia (9.00 vs. 5.22 per 10,000 person-days at risk), and the IRR was statistically significant (1.79; 95% bootstrapped CI, 1.08 to 3.07). Among surgical cases who received an NMBA, cases who were not reversed were 2.26 times as likely to develop pneumonia after surgery compared to cases who received reversal with neostigmine (IRR, 2.26; 95% bootstrapped CI, 1.65 to 3.03).


Intraoperative use of intermediate nondepolarizing NMBAs is associated with developing pneumonia after surgery. Among patients who receive these agents, nonreversal is associated with an increased risk of postoperative pneumonia.




Intérêt du ballon de contre-pulsion avec l’ECMO V-A ?


Shotaro, et al., CCM, 2016



The role of intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation in cardiogenic shock patients remains unknown. This study investigated the effect of intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation on reducing mortality of cardiogenic shock patients.


Retrospective cohort study.


The Japanese Diagnosis Procedure Combination national inpatient database.


Cardiogenic shock adult patients receiving peripheral venoarterial extracorporeal membrane oxygenation at admission were identified in the Japanese Diagnosis Procedure Combination database from July 1, 2010, to March 31, 2013.



Measurements and Main Results

The primary outcomes were all-cause 28-day mortality and in-hospital mortality, and the secondary outcome was the proportion of patients weaned from venoarterial extracorporeal membrane oxygenation, using propensity score matching. Eligible patients (n = 1,650) were divided into the intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation group (n = 604) and the venoarterial extracorporeal membrane oxygenation–alone group (n = 1,064). Propensity score matching created matched cohort of 533 pairs. In the propensity score–matched analysis, all-cause 28-day mortality and in-hospital mortality were significantly lower in the intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation group than the venoarterial extracorporeal membrane oxygenation–alone group (48.4% vs 58.2%; p = 0.001 and 55.9% vs 64.5%; p = 0.004, respectively). In Cox regression, there was a significant difference in survival between the intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation group and the venoarterial extracorporeal membrane oxygenation–alone group (hazard ratio, 0.74; 95% CI, 0.63–0.86; p < 0.001). The proportion of patients weaned from venoarterial extracorporeal membrane oxygenation was significantly higher in the intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation group than in the venoarterial extracorporeal membrane oxygenation–alone group (82.6% vs 73.4%; p < 0.001).


In a national inpatient database, intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation was associated with improved mortality and successful weaning from venoarterial extracorporeal membrane oxygenation. Randomized controlled studies are required to confirm the mortality-reducing effect of intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation.


Revue sur la corrélation Curares et Dysfonction neuro-musculaire


Price, CCM, 2016




The relationship between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness remains unclear. We examined the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, and critical illness myopathy.

Data Sources

PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and bibliographies of included studies were searched from database inception until September 24, 2015.

Study Selection

Randomized controlled trials and prospective observational studies examining the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, or critical illness myopathy.

Data Extraction

One author screened titles/abstracts. Two authors independently reviewed full text and extracted data from included studies. Meta-analysis was performed using the DerSimonian-Laird random effects model (OpenMetaAnalyst 10.10 for OS.X). We assessed reporting bias with funnel plots and heterogeneity with the I2 statistic.

Data Synthesis

Of 2,170 titles/abstracts screened, 99 full texts were selected for review, yielding one randomized controlled trial and 18 prospective observational studies, for a total of 2,254 patients. The randomized controlled trial did not show an association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness (odds ratio, 1.21; 95% CI, 0.67–2.19), but pooled data from all included studies suggested a modest association (odds ratio, 1.25; 95% CI, 1.06–1.48; I2 = 16%). Funnel plots suggested reporting bias, and sensitivity analyses showed a disproportionate contribution from critical illness polyneuropathy/critical illness myopathy and severe sepsis/septic shock studies.


This meta-analysis suggests a modest association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness; limitations include studies with a high risk of bias and a disproportionate contribution from studies examining patients for critical illness polyneuropathy/critical illness myopathy and those with severe sepsis/septic shock.



Capture d’écran 2016-02-14 à 22.02.35

Intérêt de l’ECMO dans le SDRA


Serpa Neto et al., ICM, 2016



Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients.


In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality.


Nine studies including 545 patients were included. Initiation of ECMO was accompanied by significant decreases in tidal volume size, positive end-expiratory pressure (PEEP), plateau pressure, and driving pressure (plateau pressure − PEEP) levels, and respiratory rate and minute ventilation, and resulted in higher PaO2/FiO2, higher arterial pH and lower PaCO2levels. Higher age, male gender and lower body mass index were independently associated with mortality. Driving pressure was the only ventilatory parameter during ECMO that showed an independent association with in-hospital mortality [adjusted HR, 1.06 (95 % CI, 1.03–1.10)].


In this series of ARDS patients receiving ECMO for refractory hypoxemia, driving pressure during ECMO was the only ventilator setting that showed an independent association with in-hospital mortality.



IRONMAN : défi perdu



Litton, et al., ICM, 2016



Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit. Whilst intravenous iron may decrease anaemia and RBC transfusion requirement, the safety and efficacy of administering iron intravenously to critically ill patients is uncertain.


The multicentre, randomized, placebo-controlled, blinded Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was designed to test the hypothesis that, in anaemic critically ill patients admitted to the intensive care unit, early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge.


Of 140 patients enrolled, 70 were assigned to intravenous iron and 70 to placebo. The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence interval (0.43–1.18), P = 0.19]. Overall, median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [107 (interquartile ratio IQR 97–115) vs. 100 g/L (IQR 89–111), P = 0.02]. There was no significant difference between the groups in any safety outcome.


In patients admitted to the intensive care unit who were anaemic, intravenous iron, compared with placebo, did not result in a significant lowering of red blood cell transfusion requirement during hospital stay. Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge.





Le sulfate de Magnesium comme adjuvant analgésique ?


Shin et al., BJA, 2016




We evaluated the effect of magnesium sulphate on increased pain in 44 patients undergoing staged bilateral total knee arthroplasty (TKA).


The magnesium group (n=22) and the control group (n=22) received magnesium sulphate and isotonic saline, respectively, throughout the surgery. Postoperative pain (visual analogue scale, VAS) at rest and the amounts of patient-controlled analgesia (PCA, fentanyl) and rescue analgesia (ketoprofen) administered during the first 48 h were compared between the two groups and within each group between the first and second TKA.


The VAS scores were significantly higher in the control group than in the magnesium group not only after the first TKA [29 (11) vs 19 (9) at 24 h and 33 (8) vs 24 (10) at 48 h; P=0.001] but also after the second TKA [44 (17) vs 20 (10) at 24 h and 43 (14) vs 25 (10) at 48 h; P<0.001]. In the control group, VAS scores were significantly higher for the second than for the first operated knee [44 (17) vs 29 (11) at 24 h and 43 (14) vs 33 (8) at 48 h; P<0.001 and P=0.006, respectively]. In the magnesium group, there were no significant differences in VAS scores between the first and second TKA. Magnesium significantly reduced the amounts of rescue analgesics and fentanyl administered over the first 48 h postoperatively.


Magnesium sulphate administration significantly reduced postoperative pain and minimized the difference in pain intensity between the first and second operations.


Suivre les recommandations avant d’utiliser le Novoseven


Payen et al., BJA, 2016



Management of trauma patients with severe bleeding has led to criteria before considering use of recombinant activated factor VII (rFVIIa), including haemoglobin >8 g dl−1, serum fibrinogen ≥1.0 g l−1, platelets >50,000 x 109 l−1, arterial pH ≥ 7.20, and body temperature ≥34 °C. We hypothesized that meeting these criteria is associated with improved outcomes.


In this prospective cohort study of 26 French trauma centres, subjects were included if they received rFVIIa for persistent massive bleeding despite appropriate care after severe blunt and/or penetrating trauma.


After surgery and/or embolization as haemostatic interventions, 112 subjects received a first dose of 103 μg kg−1 rFVIIa (82-200) (median, 25th-75th percentile) at 420 min (285-647) post-trauma. Of these, 71 (63%) “responders” were still alive at 24h post-trauma and had their transfusion requirements reduced by > 2 packed red blood cell units after rFVIIa treatment. Mortality was 54% on day 30 post-trauma. There were 21%, 44% and 35% subjects who fulfilled 0-1, 2-3 or 4-5, respectively, of the guidelines before receiving rFVIIa. Survival at day 30 was 13%, 49% and 64% and the proportion of responders was 39%, 64% and 82%, when subjects fulfilled 0-1, 2-3 or 4-5 conditions, respectively (both P <0.01).


In actively bleeding trauma patients, meeting guideline criteria before considering rFVIIa was associated with lower mortality and a higher proportion of responders to the rFVIIa.


Saturation Cérébrale en Oxygène : Position assise Safe ?


Schramm et al., BJA, 2016



Neurosurgical operations in the dorsal cranium often require the patient to be positioned in a sitting position. This can be associated with decreased cardiac output and cerebral hypoperfusion, and possibly, inadequate cerebral oxygenation. In the present study, cerebral oxygen saturation was measured during neurosurgery in the sitting position and correlated with cardiac output.


Perioperative cerebral oxygen saturation was measured continuously with two different monitors, INVOS® and FORE-SIGHT®. Cardiac output was measured at eight predefined time points using transoesophageal echocardiography.


Forty patients were enrolled, but only 35 (20 female) were eventually operated on in the sitting position. At the first time point, the regional cerebral oxygen saturation measured with INVOS® was 70 (SD 9)%; thereafter, it increased by 0.0187% min−1 (P<0.01). The cerebral tissue oxygen saturation measured with FORE-SIGHT® started at 68 (SD 13)% and increased by 0.0142% min−1 (P<0.01). The mean arterial blood pressure did not change. Cardiac output was between 6.3 (SD 1.3) and 7.2 (1.8) litre min−1 at the predefined time points. Cardiac output, but not mean arterial blood pressure, showed a positive and significant correlation with cerebral oxygen saturation.


During neurosurgery in the sitting position, the cerebral oxygen saturation slowly increases and, therefore, this position seems to be safe with regard to cerebral oxygen saturation. Cerebral oxygen saturation is stable because of constant CO and MAP, while the influence of CO on cerebral oxygen saturation seems to be more relevant.



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