Biblio du mois : Février 2016

14 février 2016FormationLa Biblio du mois

Voici la Biblio de l’AJAR pour le mois de février 2016.

Au programme : Ventilation à petit volume courant et VNI, l’accès aux opioïdes dans le monde, l’obésité et l’insuffisance rénale aiguë, les recommandations en anesthésie obstétricale, la pléthysmographie vs doppler oesophagien pour estimer le débit cardiaque au bloc opératoire, quelques articles sur la dexmedetomidine et bien d’autres …

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Une étude randomisée contrôlée pour comparer deux antiseptiques dans la césarienne

Methodius G. Tuuli et al.


Preoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States.


In this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine–alcohol for preoperative skin antisepsis was superior to the use of iodine–alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine–alcohol or iodine–alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention.


From September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine–alcohol and 575 to iodine–alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine–alcohol group and in 42 (7.3%) in the iodine–alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P=0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine–alcohol group and 4.9% in the iodine–alcohol group (P=0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P=0.07). The frequency of adverse skin reactions was similar in the two groups.


The use of chlorhexidine–alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine–alcohol.



Effet de l’acétazolamide vs Placebo dans la durée de ventilation mécanique chez les patients BPCO

Christophe Faisy et al, JAMA. 2016;315(5):480-488


Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach.


To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis.

Design, Setting, and Participants

The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis.


Acetazolamide (500-1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days.

Main Outcomes and Measures

The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality.


Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (−16.0 hours; 95% CI, −36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (−0.9 hours; 95% CI, −4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation (−0.0 L/min; 95% CI, −0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (−0.3 mm Hg; 95% CI, −0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, −0.8 mEq/L; 95% CI, −1.2 to −0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, −1; 95% CI, −2 to −1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups.

Conclusions and Relevance

Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance.



Utilisation et limites à l’accès des opioïdes : une étude mondiale

Dr Stefano Berterame, PhD et al.


Despite opioid analgesics being essential for pain relief, use has been inadequate in many countries. We aim to provide up-to-date worldwide, regional, and national data for changes in opioid analgesic use, and to analyse the relation of impediments to use of these medicines.


We calculated defined daily doses for statistical purposes (S-DDD) per million inhabitants per day of opioid analgesics worldwide and for regions and countries from 2001 to 2013, and we used generalised estimating equation analysis to assess longitudinal change in use. We compared use data against the prevalence of some health disorders needing opioid use. We surveyed 214 countries or territories about impediments to availability of these medicines, and used regression analyses to establish the strength of associations between impediments and use.


The S-DDD of opioid analgesic use more than doubled worldwide between 2001–03 and 2011–13, from 1417 S-DDD (95% CI −732 to 3565; totalling about 3·01 billion defined daily doses per annum) to 3027 S-DDD (−1162 to 7215; totalling about 7·35 billion defined daily doses per annum). Substantial increases occurred in North America (16 046 S-DDD [95% CI 4032–28 061] to 31 453 S-DDD [8121–54 785]), western and central Europe (3079 S-DDD [1274–4883] to 9320 S-DDD [3969–14 672]), and Oceania (2275 S-DDD [763–3787] to 9136 S-DDD [2508–15 765]). Countries in other regions have shown no substantial increase in use. Impediments to use included an absence of training and awareness in medical professionals, fear of dependence, restricted financial resources, issues in sourcing, cultural attitudes, fear of diversion, international trade controls, and onerous regulation. Higher number of impediments reported was significantly associated with lower use (unadjusted incidence rate ratio 0·39 [95% CI 0·29–0·52]; p<0·0001), but not when adjusted for gross domestic product and human development index (0·91 [0·73–1·14]; p=0·4271).


Use of opioid analgesics has increased, but remains low in Africa, Asia, Central America, the Caribbean, South America, and eastern and southeastern Europe. Identified impediments to use urgently need to be addressed by governments and international agencies.




Traitement invasif vs conservateur dans le SCA ST- chez les les patients de plus de 80ans : une étude randomisée contrôlée. 

Nicolai Tegn, MD et al0


Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy.


In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used.


During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41–0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35–0·76; p=0·0010) for myocardial infarction, 0·19 (0·07–0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25–1·46; p=0·2650) for stroke, and 0·89 (0·62–1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications.


In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications.


Réduction de la pression artérielle pour pour la prévention des maladies cardiovasculaires et la mort : méta-analyse

Dena Ettehad, MSc et al.


The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences.


For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates.


We identified 123 studies with 613 815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk [RR] 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88), stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84–0·91). However, the effect on renal failure was not significant (0·95, 0·84–1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend>0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I2 statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%.


Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease


In the CHAMPION trial, significant reductions in admissions to hospital for heart failure were seen after 6 months of pulmonary artery pressure guided management compared with usual care. We examine the extended efficacy of this strategy over 18 months of randomised follow-up and the clinical effect of open access to pressure information for an additional 13 months in patients formerly in the control group.


The CHAMPION trial was a prospective, parallel, single-blinded, multicentre study that enrolled participants with New York Heart Association (NYHA) Class III heart failure symptoms and a previous admission to hospital. Patients were randomly assigned (1:1) by centre in block sizes of four by a secure validated computerised randomisation system to either the treatment group, in which daily uploaded pulmonary artery pressures were used to guide medical therapy, or to the control group, in which daily uploaded pressures were not made available to investigators. Patients in the control group received all standard medical, device, and disease management strategies available. Patients then remained masked in their randomised study group until the last patient enrolled completed at least 6 months of study follow-up (randomised access period) for an average of 18 months. During the randomised access period, patients in the treatment group were managed with pulmonary artery pressure and patients in the control group had usual care only. At the conclusion of randomised access, investigators had access to pulmonary artery pressure for all patients (open access period) averaging 13 months of follow-up. The primary outcome was the rate of hospital admissions between the treatment group and control group in both the randomised access and open access periods. Analyses were by intention to treat. This trial is registered with, number NCT00531661.


Between Sept 6, 2007, and Oct 7, 2009, 550 patients were randomly assigned to either the treatment group (n=270) or to the control group (n=280). 347 patients (177 in the former treatment group and 170 in the former control group) completed the randomised access period in August, 2010, and transitioned to the open access period which ended April 30, 2012. Over the randomised access period, rates of admissions to hospital for heart failure were reduced in the treatment group by 33% (hazard ratio [HR] 0·67 [95% CI 0·55–0·80]; p<0·0001) compared with the control group. After pulmonary artery pressure information became available to guide therapy during open access (mean 13 months), rates of admissions to hospital for heart failure in the former control group were reduced by 48% (HR 0·52 [95% CI 0·40–0·69]; p<0·0001) compared with rates of admissions in the control group during randomised access. Eight (1%) device-related or system related complications and seven (1%) procedure-related adverse events were reported.


Management of NYHA Class III heart failure based on home transmission of pulmonary artery pressure with an implanted pressure sensor has significant long-term benefit in lowering hospital admission rates for heart failure.



Delirium is common in mechanically ventilated patients and is associated with cognitive impairment lasting at least 1 year after hospital discharge. Preclinical and observational studies suggest that the use of statins might reduce delirium in intensive care. We assessed whether the pleiotropic effects of statins can reduce delirium in intensive care and decrease subsequent cognitive impairment in a randomised controlled trial.


We did this ancillary study within the SAILS trial, a randomised controlled trial assessing mortality and ventilator-free days for rosuvastatin versus placebo for patients with sepsis-associated acute respiratory distress syndrome. This study was done at 35 hospitals in the USA. Patients were randomly assigned in permuted blocks of eight and stratified by hospital to receive either rosuvastatin (40 mg loading dose and then 20 mg daily until the earliest of 3 days after discharge from intensive care, study day 28, or death) or placebo. Patients and investigators were masked to treatment assignment. Delirium was assessed with the validated Confusion Assessment Method for intensive care. Cognitive function was assessed with tests for executive function, language, verbal reasoning and concept formation, and working, immediate, and delayed memory. We defined cognitive impairment as having one of these domains at least two SDs below population norms or at least two domains at least 1·5 SDs below norms. The primary endpoint was daily delirium status in intensive care up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6 months and 12 months. This trial is registered with and NCT00719446).


272 patients were assessed for delirium daily in intensive care. The mean proportion of days with delirium was 34% (SD 30%) in the rosuvastatin group versus 31% (29%) in the placebo group; hazard ratio 1·14, 95% CI 0·92–1·41, p=0·22. At 6 months, 19 (36%) of 53 patients in the rosuvastatin group versus 29 (38%) of 77 in the placebo group had cognitive impairment, with no significant difference between groups (treatment effect 0·93, 95% CI 0·39–2·22; p=0·87). At 12 months, 20 (30%) of 67 patients versus 23 (28%) of 81 patients had cognitive impairment, with no significant difference between groups (treatment effect 1·1, 95% CI 0·5–2·6; p=0·82).


Most patients had delirium, with around a third of survivors having cognitive impairment over 1 year of follow-up. Despite encouraging preclinical and observational studies, this trial shows no benefit of rosuvastatin in reducing delirium in intensive care or cognitive impairment during 12 months of follow-up although the study was not powered for superiority. Thus, there is continued need to evaluate interventions aimed at attenuating intensive care and post-intensive-care cognitive impairments commonly observed in this population.



Incidence et mortalité du choc septique. Estimations et limites

Carolin Fleischmann et al.


Reducing the global burden of sepsis, a recognized global health challenge, requires comprehensive data on the incidence and mortality on a global scale.


To estimate the worldwide incidence and mortality of sepsis and identify knowledge gaps based on available evidence from observational studies.


We systematically searched 15 international citation databases for population-level estimates of sepsis incidence rates and fatality in adult populations using consensus criteria and published in the last 36 years.

Measurements and Main Results:

The search yielded 1,553 reports from 1979 to 2015, of which 45 met our criteria. A total of 27 studies from seven high-income countries provided data for metaanalysis. For these countries, the population incidence rate was 288 (95% confidence interval [CI], 215–386; τ = 0.55) for hospital-treated sepsis cases and 148 (95% CI, 98–226; τ = 0.99) for hospital-treated severe sepsis cases per 100,000 person-years. Restricted to the last decade, the incidence rate was 437 (95% CI, 334–571; τ = 0.38) for sepsis and 270 (95% CI, 176–412; τ = 0.60) for severe sepsis cases per 100,000 person-years. Hospital mortality was 17% for sepsis and 26% for severe sepsis during this period. There were no population-level sepsis incidence estimates from lower-income countries, which limits the prediction of global cases and deaths. However, a tentative extrapolation from high-income country data suggests global estimates of 31.5 million sepsis and 19.4 million severe sepsis cases, with potentially 5.3 million deaths annually.


Population-level epidemiologic data for sepsis are scarce and nonexistent for low- and middle-income countries. Our analyses underline the urgent need to implement global strategies to measure sepsis morbidity and mortality, particularly in low- and middle-income countries.


Oxygénation apnéique lors de l’intubation oro-trachéale en réanimation : étude randomisée contrôlée

Matthew W. Semler et al.


Hypoxemia is common during endotracheal intubation of critically ill patients and may predispose to cardiac arrest and death. Administration of supplemental oxygen during laryngoscopy (apneic oxygenation) may prevent hypoxemia.


To determine if apneic oxygenation increases the lowest arterial oxygen saturation experienced by patients undergoing endotracheal intubation in the intensive care unit.


This was a randomized, open-label, pragmatic trial in which 150 adults undergoing endotracheal intubation in a medical intensive care unit were randomized to receive 15 L/min of 100% oxygen via high-flow nasal cannula during laryngoscopy (apneic oxygenation) or no supplemental oxygen during laryngoscopy (usual care). The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after completion of endotracheal intubation.

Measurements and Main Results:

Median lowest arterial oxygen saturation was 92% with apneic oxygenation versus 90% with usual care (95% confidence interval for the difference, −1.6 to 7.4%; P = 0.16). There was no difference between apneic oxygenation and usual care in incidence of oxygen saturation less than 90% (44.7 vs. 47.2%; P = 0.87), oxygen saturation less than 80% (15.8 vs. 25.0%; P = 0.22), or decrease in oxygen saturation greater than 3% (53.9 vs. 55.6%; P = 0.87). Duration of mechanical ventilation, intensive care unit length of stay, and in-hospital mortality were similar between study groups.


Apneic oxygenation does not seem to increase lowest arterial oxygen saturation during endotracheal intubation of critically ill patients compared with usual care. These findings do not support routine use of apneic oxygenation during endotracheal intubation of critically ill adults.




La sédation à la Dexmedetomidine versus Propofol  réduit le délirium post-opératoire en chirurgie cardiaque

George Djaiani, M.D  Anesthesiology  2016


Postoperative delirium (POD) is a serious complication after cardiac surgery. Use of dexmedetomidine to prevent delirium is controversial. The authors hypothesized that dexmedetomidine sedation after cardiac surgery would reduce the incidence of POD.


After institutional ethics review board approval, and informed consent, a single-blinded, prospective, randomized controlled trial was conducted in patients 60 yr or older undergoing cardiac surgery. Patients with a history of serious mental illness, delirium, and severe dementia were excluded. Upon admission to intensive care unit (ICU), patients received either dexmedetomidine (0.4 μg/kg bolus followed by 0.2 to 0.7 μg kg−1 h−1 infusion) or propofol (25 to 50 μg kg−1 min−1 infusion) according to a computer-generated randomization code in blocks of four. Assessment of delirium was performed with confusion assessment method for ICU or confusion assessment method after discharge from ICU at 12-h intervals during the 5 postoperative days. Primary outcome was the incidence of POD.


POD was present in 16 of 91 (17.5%) and 29 of 92 (31.5%) patients in dexmedetomidine and propofol groups, respectively (odds ratio, 0.46; 95% CI, 0.23 to 0.92; P = 0.028). Median onset of POD was on postoperative day 2 (1 to 4 days) versus 1 (1 to 4 days), P = 0.027, and duration of POD 2 days (1 to 4 days) versus 3 days (1 to 5 days), P = 0.04, in dexmedetomidine and propofol groups, respectively.


When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of POD in elderly patients after cardiac surgery. The absolute risk reduction for POD was 14%, with a number needed to treat of 7.1.


Interactions complexes entre les agents anesthésiques et l’endothélium

Aguirre, José A. et al.


The vascular endothelium is one of the largest organs in the body and consists of a single layer of highly specialized cells with site-specific morphology and functions. Endothelial cells play a vital role in the regulation of vascular tone in arterial, venous, microvascular, and lymphatic vascular beds. The endothelium also coordinates angiogenesis and controls cell adhesion, fluid homeostasis, and both innate and adaptive immunity. Fundamental research has shown that general and local anesthetics markedly modulate the biological activities of endothelial cells under aerobic and ischemia-reperfusion conditions, making the endothelium an important target of anesthetics in the cardiovascular system. Halogenated volatile anesthetics provide significant anti-inflammatory actions and protect the endothelium against ischemia-reperfusion injury, despite their inhibiting effects on endothelium-dependent vasorelaxation. They provide not only acute but also potential long-term, beneficial effects. Although many effects of IV anesthetics on endothelial function are controversial, or completely unexplored, propofol and opioids appear to have the most favorable profile with respect to the preservation of endothelial function. Some opioids and ketamine have stereoselective effects on the endothelium. Finally, there is experimental evidence to suggest important effects of anesthetics on the regulation of vascular permeability, proliferation of stem cells, including endothelial progenitor cells, and promotion or inhibition of tumor growth, potentially related to alterations in angiogenesis. However, most of these findings are from in vitro experiments and await confirmation in an in vivo setting. Thus, the clinical implications of these interactions remain uncertain.


Comparaison de la photopléthysmographie et du doppler oesophagien dans l’estimation du débit cardiaque en chirurgie non cardiaque

Blanié, Antonia MD; Soued, Mickael MD; Benhamou, Dan MD; Mazoit, Jean Xavier MD, PhD; Duranteau, Jacques MD, PhD




In this prospective observational study, we compared changes in cardiac index (CI) during fluid challenge using photoplethysmography (PPG; Nexfin™) (CIPPG) versus esophageal Doppler (ED) (CIED) in major noncardiac surgery patients.


Measurements were obtained when the attending anesthesiologist decided to perform a fluid challenge. Correlations with linear regression, Bland-Altman analysis, and analysis of covariance were performed. Trending ability was studied using 2 different methods: a 4-quadrant plot and a polar plot.


Forty-three patients were analyzed with a total of 111 fluid challenges. There was a significant linear relationship between CIPPG and CIED (r2 = 0.34; P < 0.001). The bias between the ED and the PPG measurements of CI was −0.114 (95% confidence interval [CI95], −1.9 to 1.7) L/min/m2, with a mean percentage error of 55%. The correlation between the changes in CI during a fluid challenge was significant (r2 = 0.25; P = 0.002). The concordance rate of directional changes (increase or decrease) of CIPPG and CIED during fluid challenge was 67% (CI95, 57–75) for the whole data set and 85% (CI95, 70–94) with an exclusion zone of 15%. When considering ED as a reference, the sensitivity and specificity to give an additional bolus with PPG (increase in CIPPG ≥15%) were 35% (CI95, 19–55) and 90% (CI95, 81–96), respectively, with a positive predictive value of 58% (CI95, 33–80) and a negative predictive value of 78% (CI95, 68–86).


In major noncardiac surgery patients, the evaluation of CI using PPG is not interchangeable with the evaluation of CI using ED. When considering the ED as an accurate device to assess changes in CI, PPG is not appropriate to assess the need for additional fluid administration. These results clearly indicate the limitations of PPG as an accurate device to track changes in CI compared with ED.



Facteurs de risque d’instabilité hémodynamique lors de l’utilisation de la dexmedétomidine en réanimation

Ice, Calvin J. PharmD




The reported incidence of hypotension and bradycardia in patients receiving dexmedetomidine for sedation commonly exceeds 50%. In this study, we describe the incidence of, patient- and treatment-specific risk factors for, and clinical significance of dexmedetomidine-associated hemodynamic instability.


This retrospective cohort study was conducted in critically ill adults receiving dexmedetomidine for sedation at Mayo Clinic Hospital in Rochester, MN, during a 1-year period. The primary end point was hemodynamic instability: a composite of hypotension and/or bradycardia, defined as systolic blood pressure <80 mm Hg, diastolic blood pressure <50 mm Hg, or heart rate <50 beats per minute during dexmedetomidine therapy. Cox proportional hazards models were constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability.


Hemodynamic instability occurred in 197 of the analyzed 300 patients receiving dexmedetomidine, resulting in a cumulative incidence of 71% at 24 hours via Kaplan-Meier estimation. In addition to dexmedetomidine, univariate analysis identified age, vasopressor use, low baseline arterial blood pressure, and concomitant sedatives as associated with increased risk of hemodynamic instability. Multivariable analysis demonstrated associations between age (HR, 1.23 per 10 years, 95% CI, 1.10–1.38) and low baseline blood pressure (HR, 2.42 at dexmedetomidine initiation, 95% CI, 1.68–3.49) and risk of hemodynamic instability. Variables such as concomitantly administered cardiac medications or sedative therapies and dexmedetomidine infusion rates >0.7 μg/kg/h were not found to be predictors of hemodynamic instability among the analyzed sample.


Hemodynamic instability commonly occurs in critically ill adults receiving dexmedetomidine, with more than two thirds of this cohort experiencing hypotension and/or bradycardia within 24 hours of initiation. Increasing age and low baseline arterial blood pressure were associated with the development of hemodynamic instability. These findings suggest that clinicians should be aware of the potential risk of hemodynamic instability when using dexmedetomidine in patients with advanced age or low baseline arterial blood pressure


Utilisation de l’acide Tranexamique est associée à un réduction de la transfusion dans la chirurgie des os de la base du crâne : étude rétrospective

Mebel, Dmitry MD et al.



Compared with other procedures, complex skull base neurosurgery has the potential for increased intraoperative blood loss yet coagulation near eloquent cranial structures should be minimized. The safety and efficacy of the antifibrinolytic, tranexamic acid in elective neurosurgical procedures is not known. Our primary objective was to determine the relationship between the use of tranexamic acid and transfusion at our institution. Our secondary objective was to determine the incidence of adverse events associated with the use of tranexamic acid.


In this retrospective cohort study, we included all patients who underwent complex skull base neurosurgical procedures at our institution between 2001 and 2013. Tranexamic acid was introduced during these procedures in 2006. Patient and surgical variables, transfusion data, and adverse events in the perioperative period were abstracted from the medical record. The rates of transfusion and adverse events were compared between patients who did and did not receive tranexamic acid. Multivariate regression was used to identify independent predictors of perioperative transfusion.


We compared 245 patients who received tranexamic acid with 274 patients who did not receive the drug during the study period. The 2 groups were similar, with the exception that patients who received tranexamic acid had larger tumors (mean, 3.5 vs 2.9 cm; P < 0.001) and longer procedures (mean, 7.2 vs 6.2 hours, P < 0.001). The rate of perioperative transfusion in patients who received tranexamic acid was lower (7% vs 13%, P = 0.04). After adjusting for preoperative hemoglobin, tumor diameter, and surgical procedure category, the use of tranexamic acid was independently predictive of perioperative transfusion (adjusted odds ratio, 0.32; 95% confidence interval, 0.15–0.65, P = 0.002). The rates of thromboembolic events and seizure were similar between the 2 groups.


Our results demonstrate that tranexamic acid use is associated with reduced transfusion rates in our study population, with no apparent increase in seizure or thrombotic complications. Our data support the need for further randomized clinical trials to evaluate the efficacy and safety of tranexamic acid on perioperative blood loss during complex skull base neurosurgery.


La Tizanidine (alpha-2 agoniste) pour le traitement de la douleur post-opératoire après hernie inguinale : étude randomisée contrôlée vs placebo.

Yazicioğlu, Dilek et al.


α2-Agonists are used postoperatively as a component of multimodal analgesia. Tizanidine is a centrally acting α2-agonist with muscle relaxant properties.


The aim of this study was to compare the efficacy of tizanidine with placebo in terms of postoperative pain scores, analgesic consumption, return to daily activity and health-related quality of life.


A randomised double-blind study.


Diskapi Yildirim Beyazit Training and Research Hospital.


After obtaining ethical approval and informed patient consent, 60 patients undergoing inguinal hernia repair under general anaesthesia were randomly allocated into one of the two groups. The patients in Group T received tizanidine 4 mg orally 1 h before surgery and twice daily during the first postoperative week. The patients in Group P received the same treatment with a placebo pill. Both the groups received a standard analgesic treatment regimen comprising intravenous dexketoprofen 25 mg prior to induction of anaesthesia, dexketoprofen 25 mg orally three times daily for 1 week and intravenous paracetamol 1 g at the end of surgery. Supplemental analgesia was provided with paracetamol if the visual numerical rating scale (NRS) was at least 4 cm.


Postoperative pain was assessed using the NRS. Total analgesic consumption was determined. Return to normal daily activity was evaluated using a five-point daily activity score after the first postoperative week, and health-related quality of life was evaluated using the short form-36 one month after surgery.


The patients in Group T had significantly lower NRS pain scores than those in Group P 6, 12 and 24 h postoperatively both at rest and during movement (P < 0.001), and on postoperative days 1, 2, 3 and 4. The analgesic consumption was also lower in patients who received tizanidine. Ten patients (33%) in Group T and 23 patients (77%) in Group P consumed supplemental paracetamol (P < 0.001) after discharge. The daily activity score was lower in Group T than in Group P (P < 0.001), and the short form-36 scores were significantly different in the pain dimension [74 (74 to 100) in Group T and 74 (31 to 80) in Group P, (P < 0.001)] and in the physical component summary score.


The addition of tizanidine to the postoperative pain therapy after herniorrhaphy decreased postoperative pain and analgesic consumption and improved return to normal activity and quality of life.


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L’hypothermie modérée améliore le pronostic neurologique des patients survivants l’accident vasculaire cérébral ischémique hémisphérique

Yingying Su, MD et al.

Background and Purpose

We conducted this randomized controlled trial to investigate the effects of therapeutic hypothermia on mortality and neurological outcome in patients with massive cerebral hemispheric infarction.


Patients within 48 hours of symptom onset were randomized to either a hypothermia group or a control group. Patients in the hypothermia group were given standard medical treatment plus endovascular hypothermia with a target temperature of 33 or 34°C. Hypothermia was maintained for a minimum of 24 hours. Patients in the control group were given standard medical treatment only with a target temperature of normothermia. The primary end points were mortality and the modified Rankin Scale score at 6 months.


There were 16 patients in the hypothermia group and 17 patients in the control group. At 6 months, 8 patients had died in the hypothermia group versus 7 patients in the control group (P=0.732). The main cause of death was fatal herniation caused by a pronounced rise in intracranial pressure. Seven patients (43.8%) had a modified Rankin Scale of 1 to 3 in the hypothermia group versus 4 patients (23.5%) in the control group (P=0.282). Additionally, of the survivors, patients in the hypothermia group achieved better neurological outcomes compared with those in the control group (7/8, 87.5% versus 4/10, 40.0%; P=0.066; odds ratio=10.5; 95% confidence interval, 0.9–121.4).


Mild hypothermia seems to not reduce mortality in patients with massive cerebral hemispheric infarction but may improve the neurological outcome in survivors. An adequately powered multicenter randomized controlled trial seems warranted.

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Parce que cholestase ne rime pas toujours avec défaillance hépatique au cours du sepsis…

Marc Jenniskens et al.


In ICU patients, abnormal liver tests are common. Markers of cholestasis are associated with adverse outcome. Research has focused on the possibility that mild hyperbilirubinemia, instead of indicating inadvertent cholestasis, may be adaptive and beneficial. These new insights are reviewed and integrated in the state-of-the-art knowledge on hepatobiliary alterations during sepsis and other critical illnesses.

Data sources

Relevant publications were searched in Medline with search terms bile, bile acids, cholestasis, critical illness, intensive care, sepsis, alone or in combination.

Data synthesis

Studies have shown that bilirubin, but also bile acids, the main active constitutes of bile, are increased in plasma of patients with critical illnesses. In particular the conjugated fractions of bilirubin and bile acids are high, indicating that during critical illness the liver is capable of converting these molecules to less toxic forms. In human liver biopsies of prolonged critically ill patients, expression of bile acid excretion pumps towards the bile canaliculi was lower, while alternative transporters towards the systemic circulation were upregulated. Remarkably, in the presence of increased circulating bile acids, expression of enzymes controlling synthesis of bile acids was not suppressed. This suggested loss of feedback inhibition of bile acids synthesis, possibly explained by the observed cytoplasmic retention of the nuclear FXR/RXR heterodimer. As macronutrient restriction during acute critical illness, an intervention that improved outcome, was found to further increase plasma bilirubin while reducing other markers of cholestasis, a potentially protective role of hyperbilirubinemia was suggested.


The increase in circulating levels of conjugated bile acids and bilirubin in response to acute sepsis/critical illnesses may not necessarily point to cholestasis as a pathophysiological entity. Instead it may be the result of an adaptively altered bile acid production and transport back towards the systemic circulation. How these changes could be beneficial for survival should be further investigated.

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition

Aude Gibelin| Antoine Parrot| Bernard Maitre| Christian Brun-Buisson| Armand Mekontso Dessap| Muriel Fartoukh| Nicolas de Prost


Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDSCRF−) in comparison with others (ARDSCRF+).


Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.


The prevalence of ARDSCRF− was 7.5 % (95 % CI [5.5–9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDSCRF− patients had a lower logistic organ dysfunction score (4 [3–8] vs. 10 [6–13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46–74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02–4.18]; p = 0.044). Among ARDSCRF− patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03–0.62]) was associated with ICU survival.


The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids


Hyperlactatémie sévère, clairance du lactate et mortalité chez les patients de réanimation

Sebastian A. Haas et al


Hyperlactatemia may occur for a variety of reasons and is a predictor of poor clinical outcome. However, only limited data are available on the underlying causes of hyperlactatemia and the mortality rates associated with severe hyperlactatemia in critically ill patients. We therefore aimed to evaluate the etiology of severe hyperlactatemia (defined as a lactate level >10 mmol/L) in a large cohort of unselected ICU patients. We also aimed to evaluate the association between severe hyperlactatemia and lactate clearance with ICU mortality.


In this retrospective, observational study at an University hospital department with 11 ICUs during the study period between 1 April 2011 and 28 February 2013, we screened 14,040 ICU patients for severe hyperlactatemia (lactate >10 mmol/L).


Overall mortality in the 14,040 ICU patients was 9.8 %. Of these, 400 patients had severe hyperlactatemia and ICU mortality in this group was 78.2 %. Hyperlactatemia was associated with death in the ICU [odds ratio 1.35 (95 % CI 1.23; 1.49; p < 0.001)]. The main etiology for severe hyperlactatemia was sepsis (34.0 %), followed by cardiogenic shock (19.3 %), and cardiopulmonary resuscitation (13.8 %). Patients developing severe hyperlactatemia >24 h of ICU treatment had a significantly higher ICU mortality (89.1 %, 155 of 174 patients) than patients developing severe hyperlactatemia ≤24 h of ICU treatment (69.9 %, 158 of 226 patients; p < 0.0001). Lactate clearance after 12 h showed a receiver-operating-characteristics area under the curve (ROC-AUC) value of 0.91 to predict ICU mortality (cut-off showing highest sensitivity and specifity was a 12 h lactate clearance of 32.8 %, Youden Index 0.72). In 268 patients having a 12-h lactate clearance <32.8 % ICU mortality was 96.6 %.


Severe hyperlactatemia (>10 mmol/L) is associated with extremely high ICU mortality especially when there is no marked lactate clearance within 12 h. In such situations, the benefit of continued ICU therapy should be evaluated

Les médecins de réanimations moins performants la nuit…

François Maltese et al.


The relationship between tiredness and the risk of medical errors is now commonly accepted. The main objective of this study was to assess the impact of an intensive care unit (ICU) night shift on the cognitive performance of a group of intensivists. The influence of professional experience and the amount of sleep on cognitive performance was also investigated.


A total of 51 intensivists from three ICUs (24 seniors and 27 residents) were included. The study participants were evaluated after a night of rest and after a night shift according to a randomized order. Four cognitive skills were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test.


All cognitive abilities worsened after a night shift: working memory capacity (11.3 ± 0.3 vs. 9.4 ± 0.3; p < 0.001), speed of processing information (13.5 ± 0.4 vs. 10.9 ± 0.3; p < 0.001), perceptual reasoning (10.6 ± 0.3 vs. 9.3 ± 0.3; p < 0.002), and cognitive flexibility (41.2 ± 1.2 vs. 44.2 ± 1.3; p = 0.063). There was no significant difference in terms of level of cognitive impairment between the residents and ICU physicians. Only cognitive flexibility appeared to be restored after 2 h of sleep. The other three cognitive skills were altered, regardless of the amount of sleep during the night shift.


The cognitive abilities of intensivists were significantly altered following a night shift in the ICU, regardless of either the amount of professional experience or the duration of sleep during the shift. The consequences for patients’ safety and physicians’ health should be further evaluated.

Trachéotomie percutanée sous fibroscopie vs échographie : une étude de non infériorité en réanimation (TRACHUS)

André Luiz Nunes Gobatto et al.


Percutaneous dilational tracheostomy (PDT) is routinely performed in the intensive care unit with bronchoscopy guidance. Recently, ultrasound has emerged as a potentially useful tool to assist PDT and reduce procedure-related complications.


An open-label, parallel, non-inferiority randomized controlled trial was conducted comparing an ultrasound-guided PDT with a bronchoscopy-guided PDT in mechanically ventilated critically ill patients. The primary outcome was procedure failure, defined as a composite end-point of conversion to a surgical tracheostomy, unplanned associated use of bronchoscopy or ultrasound during PDT, or the occurrence of a major complication.


A total of 4965 patients were assessed for eligibility. Of these, 171 patients were eligible and 118 underwent the procedure, with 60 patients randomly assigned to the ultrasound group and 58 patients to the bronchoscopy group. Procedure failure occurred in one (1.7 %) patient in the ultrasound group and one (1.7 %) patient in the bronchoscopy group, with no absolute risk difference between the groups (90 % confidence interval, −5.57 to 5.85), in the “as treated” analysis, not including the prespecified margin of 6 % for noninferiority. No other patient had any major complication in either group. Procedure-related minor complications occurred in 20 (33.3 %) patients in the ultrasound group and in 12 (20.7 %) patients in the bronchoscopy group (P = 0.122). The median procedure length was 11 [7–19] vs. 13 [8–20] min (P = 0.468), respectively, and the clinical outcomes were also not different between the groups.


Ultrasound-guided PDT is noninferior to bronchoscopy-guided PDT in mechanically ventilated critically ill patients.

Pas de différence entre une alimentation normo et hypercalorique en réanimation : résultat d’une méta-analyse

Paul E. Marik et al.


Current clinical practice guidelines recommend providing ICU patients a daily caloric intake estimated to match 80–100 % of energy expenditure (normocaloric goals). However, recent clinical trials of intentional hypocaloric feeding question this approach.


We performed a systematic review and meta-analysis to compare the outcomes of ICU patients randomized to intentional hypocaloric or normocaloric goals. We included randomized controlled trials that enrolled ICU patients and compared intentional hypocaloric with normocaloric nutritional goals. We included studies that evaluated both trophic feeding as well as permissive underfeeding. Data sources included MEDLINE, Cochrane Register of Controlled Trials and citation review of relevant primary and review articles. The outcomes of interest included hospital acquired infection, hospital mortality, ICU length of stay (LOS) and ventilator-free days (VFDs).


Six studies which enrolled 2517 patients met our inclusion criteria. The mean age and body mass index (BMI) across the studies were 53 ± 5 years and 29.1 ± 1.5 kg/m2, respectively. Two studies compared normocaloric feeding (77 % of goal) with trophic feeding (20 % of goal), while four studies compared normocaloric feeding (72 % of goal) with permissive underfeeding (49 % of goal). Overall, there was no significant difference in the risk of infectious complications (OR 1.03; 95 % CI 0.84–1.27, I 2 = 16 %), hospital mortality (OR 0.91; 95 % CI 0.75–1.11, I 2 = 8 %) or ICU LOS (mean difference 0.05 days; 95 % CI 1.33–1.44 days; I 2 = 37 %) between groups. VFDs were reported in three studies with no significant difference between the normocaloric and intentional hypocaloric groups (data not pooled).


This meta-analysis demonstrated no difference in the risk of acquired infections, hospital mortality, ICU length of stay or ventilator-free days between patients receiving intentional hypocaloric as compared to normocaloric nutritional goals.

Manoeuvre de recrutement et titration de PEEP  chez les patients obèses en réanimation

Pirrone, Massimiliano MD et al.


The approach to applying positive end-expiratory pressure in morbidly obese patients is not well defined. These patients frequently require prolonged mechanical ventilation, increasing the risk for failed liberation from ventilatory support. We hypothesized that lung recruitment maneuvers and titration of positive end-expiratory pressure were both necessary to improve lung volumes and the elastic properties of the lungs, leading to improved gas exchange.


Prospective, crossover, nonrandomized interventional study.


Medical and surgical ICUs at Massachusetts General Hospital.


Critically ill, mechanically ventilated morbidly obese (body mass index > 35 kg/m2) patients (n = 14).


This study evaluated two methods of titrating positive end-expiratory pressure; both trials were done utilizing positive end-expiratory pressure titration and recruitment maneuvers while measuring hemodynamics and respiratory mechanics. Measurements were obtained at the baseline positive end-expiratory pressure set by the clinicians, at zero positive end-expiratory pressure, at best positive end-expiratory pressure identified through esophageal pressure measurement before and after a recruitment maneuver, and at best positive end-expiratory pressure identified through a best decremental positive end-expiratory pressure trial.

Measurements and Main Results:

The average body mass index was 50.7 ± 16.0 kg/m2. The two methods of evaluating positive end-expiratory pressure identified similar optimal positive end-expiratory pressure levels (20.7 ± 4.0 vs 21.3 ± 3.8 cm H2O; p = 0.40). End-expiratory pressure titration increased end-expiratory lung volumes (Δ11 ± 7 mL/kg; p < 0.01) and oxygenation (Δ86 ± 50 torr; p < 0.01) and decreased lung elastance (Δ5 ± 5 cm H2O/L; p < 0.01). Recruitment maneuvers followed by titrated positive end-expiratory pressure were effective at increasing end-expiratory lung volumes while decreasing end-inspiratory transpulmonary pressure, suggesting an improved distribution of lung aeration and reduction of overdistension. The positive end-expiratory pressure levels set by the clinicians (11.6 ± 2.9 cm H2O) were associated with lower lung volumes, worse elastic properties of the lung, and lower oxygenation.


Commonly used positive end-expiratory pressure by clinicians is inadequate for optimal mechanical ventilation of morbidly obese patients. A recruitment maneuver followed by end-expiratory pressure titration was found to significantly improve lung volumes, respiratory system elastance, and oxygenation.


Obésité, insuffisance rénale aiguë et mortalité en réanimation

Danziger, John MD et al.


Although obesity is associated with risk for chronic kidney disease and improved survival, less is known about the associations of obesity with risk of acute kidney injury and post acute kidney injury mortality.


In a single-center inception cohort of almost 15,000 critically ill patients, we evaluated the association of obesity with acute kidney injury and acute kidney injury severity, as well as in-hospital and 1-year survival. Acute kidney injury was defined using the Kidney Disease Outcome Quality Initiative criteria.

Measurements and Main Results:

The acute kidney injury prevalence rates for normal, overweight, class I, II, and III obesity were 18.6%, 20.6%, 22.5%, 24.3%, and 24.0%, respectively, and the adjusted odds ratios of acute kidney injury were 1.18 (95% CI, 1.06–1.31), 1.35 (1.19–1.53), 1.47 (1.25–1.73), and 1.59 (1.31–1.87) when compared with normal weight, respectively. Each 5-kg/m2 increase in body mass index was associated with a 10% risk (95% CI, 1.06–1.24; p < 0.001) of more severe acute kidney injury. Within-hospital and 1-year survival rates associated with the acute kidney injury episodes were similar across body mass index categories.


Obesity is a risk factor for acute kidney injury, which is associated with increased short- and long-term mortality.

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