Biblio du mois : Novembre 2015

19 novembre 2015

Après le ciraparantag et le idarucizumab en août 2015, découvrez la biblio du mois de Novembre 2015 avec un nouvel article sur un antidote prometteur des AOD (anciennement appelés NACO) mais également de tous les anti-Xa. Et pour compléter l’étude HEROICS du Pr Combes, des méta-analyses, de la ventilation et une revue sur le mythique PRIS.

Andexanet Alfa comme antidote des Anti-Xa

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1510991

Siegal, et al., NEJM, 2015; DOI: 10.1056/NEJMoa1510991

BACKGROUND

Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of factor Xa inhibitors.

METHODS

Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebocontrolled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti–factor Xa activity, which is a measure of factor Xa inhibition by the anticoagulant.

RESULTS

Among the apixaban-treated participants, anti–factor Xa activity was reduced by 94% among those who received an andexanet bolus (24 participants), as compared with 21% among those who received placebo (9 participants) (P<0.001), and unbound apixaban concentration was reduced by 9.3 ng per milliliter versus 1.9 ng per milliliter (P<0.001); thrombin generation was fully restored in 100% versus 11% of the participants (P<0.001) within 2 to 5 minutes. Among the rivaroxabantreated participants, anti–factor Xa activity was reduced by 92% among those who received an andexanet bolus (27 participants), as compared with 18% among those who received placebo (14 participants) (P<0.001), and unbound rivaroxaban concentration was reduced by 23.4 ng per milliliter versus 4.2 ng per milliliter (P<0.001); thrombin generation was fully restored in 96% versus 7% of the participants (P<0.001). These effects were sustained when andexanet was administered as a bolus plus an infusion. In a subgroup of participants, transient increases in levels of d-dimer and prothrombin fragments 1 and 2 were observed, which resolved within 24 to 72 hours. No serious adverse or thrombotic events were reported.

CONCLUSIONS

Andexanet reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects.

L’impact de l’administration de Paracétamol pour contrôle thermique en Réanimation

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1508375

Young et al., NEJM, 2015; DOI: 10.1056/NEJMoa1508375

BACKGROUND

Acetaminophen is a common therapy for fever in patients in the intensive care unit (ICU) who have probable infection, but its effects are unknown.

METHODS

We randomly assigned 700 ICU patients with fever (body temperature, ≥38°C) and known or suspected infection to receive either 1 g of intravenous acetaminophen or placebo every 6 hours until ICU discharge, resolution of fever, cessation of antimicrobial therapy, or death. The primary outcome was ICU-free days (days alive and free from the need for intensive care) from randomization to day 28.

RESULTS

The number of ICU-free days to day 28 did not differ significantly between the acetaminophen group and the placebo group: 23 days (interquartile range, 13 to 25) among patients assigned to acetaminophen and 22 days (interquartile range, 12 to 25) among patients assigned to placebo (Hodges–Lehmann estimate of absolute difference, 0 days; 96.2% confidence interval [CI], 0 to 1; P=0.07). A total of 55 of 345 patients in the acetaminophen group (15.9%) and 57 of 344 patients in the placebo group (16.6%) had died by day 90 (relative risk, 0.96; 95% CI, 0.66 to 1.39; P=0.84).

CONCLUSIONS

Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days.

Méta-analyse sur la Thrombectomie endovasculaire dans l’AVC ischémique

http://jama.jamanetwork.com/article.aspx?articleid=2467553

Badhiwala et al., JAMA, 2015; doi:10.1001/jama.2015.13767.

Importance

Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition.

Objective

To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke.

Data Sources

We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015.

Study Selection

Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA).

Data Extraction and Synthesis

Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method.

Main Outcomes and Measures

Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days.

Results

Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14–2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27).

Conclusions and Relevance

Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

Solutés balancés versus NaCl 0.9% dans l’IRA en réanimation

http://jama.jamanetwork.com/article.aspx?articleid=2454911

Young, et al. JAMA 2015; doi:10.1001/jama.2015.12334.

Importance

Saline (0.9% sodium chloride) is the most commonly administered intravenous fluid; however, its use may be associated with acute kidney injury (AKI) and increased mortality.

Objective

To determine the effect of a buffered crystalloid compared with saline on renal complications in patients admitted to the intensive care unit (ICU).

Design and Setting

Double-blind, cluster randomized, double-crossover trial conducted in 4 ICUs in New Zealand from April 2014 through October 2014. Three ICUs were general medical and surgical ICUs; 1 ICU had a predominance of cardiothoracic and vascular surgical patients.

Participants

All patients admitted to the ICU requiring crystalloid fluid therapy were eligible for inclusion. Patients with established AKI requiring renal replacement therapy (RRT) were excluded. All 2278 eligible patients were enrolled; 1152 of 1162 patients (99.1%) receiving buffered crystalloid and 1110 of 1116 patients (99.5%) receiving saline were analyzed.

Interventions

Participating ICUs were assigned a masked study fluid, either saline or a buffered crystalloid, for alternating 7-week treatment blocks. Two ICUs commenced using 1 fluid and the other 2 commenced using the alternative fluid. Two crossovers occurred so that each ICU used each fluid twice over the 28 weeks of the study. The treating clinician determined the rate and frequency of fluid administration.

Main Outcomes and Measures

The primary outcome was proportion of patients with AKI (defined as a rise in serum creatinine level of at least 2-fold or a serum creatinine level of ≥3.96 mg/dL with an increase of ≥0.5 mg/dL); main secondary outcomes were incidence of RRT use and in-hospital mortality.

Results

In the buffered crystalloid group, 102 of 1067 patients (9.6%) developed AKI within 90 days after enrollment compared with 94 of 1025 patients (9.2%) in the saline group (absolute difference, 0.4% [95% CI, −2.1% to 2.9%]; relative risk [RR], 1.04 [95% CI, 0.80 to 1.36]; P = .77). In the buffered crystalloid group, RRT was used in 38 of 1152 patients (3.3%) compared with 38 of 1110 patients (3.4%) in the saline group (absolute difference, −0.1% [95% CI, −1.6% to 1.4%]; RR, 0.96 [95% CI, 0.62 to 1.50]; P = .91). Overall, 87 of 1152 patients (7.6%) in the buffered crystalloid group and 95 of 1110 patients (8.6%) in the saline group died in the hospital (absolute difference, −1.0% [95% CI, −3.3% to 1.2%]; RR, 0.88 [95% CI, 0.67 to 1.17]; P = .40).

Conclusions and Relevance

Among patients receiving crystalloid fluid therapy in the ICU, use of a buffered crystalloid compared with saline did not reduce the risk of AKI. Further large randomized clinical trials are needed to assess efficacy in higher-risk populations and to measure clinical outcomes such as mortality.

Préoxygénation avec ou sans PEP ? en VS ou en VNI ?

http://journals.lww.com/ejanaesthesiology/Abstract/2015/12000/Preoxygenation_by_spontaneous_breathing_or.10.aspx

Hanouz et al., EJA, 2015; doi: 10.1097/EJA.0000000000000297

BACKGROUND

In emergency situations requiring rapid airway control, shortening preoxygenate time is desirable.

OBJECTIVES

The objective of this study is to compare the time to achieve an expired O₂fraction FeO₂ of 90% (FeO₂ 90%) during preoxygenation with spontaneous breathing and positive pressure ventilation with and without positive end-expiratory pressure (PEEP).

DESIGN

A randomised controlled trial.

SETTING

Primary care in a university hospital in France from October 2006 to January 2008.

PATIENTS

Adults patients scheduled for elective surgery. Exclusion criteria were rapid sequence induction, anticipated difficult airway management and refusal to provide consent.

INTERVENTION

Patients were randomly allocated to preoxygenation with spontaneous breathing or positive pressure ventilation (positive inspiratory pressure: 12 cmH₂O) without PEEP and with PEEP (positive inspiratory pressure: 12 cmH₂O, PEEP: 6 cmH₂O).

MAIN OUTCOME MEASURES

Time to achieve an expired O₂ fraction of 90% measured from positioning the face mask, and the time it took after endotracheal intubation for the SpO₂ to fall to 93% (SpO₂ 93%) while the patient was apnoeic. Patient discomfort was recorded (visual analogue scale). Data are median (quartile 25th to 75).

RESULTS

The time to achieve an FeO₂ 90% was shorter with positive pressure ventilation, with PEEP [140 (100 to 200) s] and without PEEP [153 (120 to 218) s], than with spontaneous breathing [190 (130 to 264) s; P = 0.002]. At 3 min, 47, 60 and 74% of patients achieved an FeO₂ of 90% or more in the spontaneous breathing, positive pressure ventilation without and with PEEP groups, respectively (P = 0.01). Cox proportional-hazards regression showed that positive pressure ventilation with PEEP [hazard ratio 2.18; 95% confidence interval (95% CI) 1.42 to 3.36); P < 0.001] and without PEEP (hazard ratio 1.62; 95% CI 1.05 to 2.50; P = 0.03) were associated with a shorter time to an FeO₂ 90%. The time until SpO₂ 93% was not significantly different between spontaneous breathing [305 (263 to 383) s], positive pressure ventilation without PEEP [370 (300 to 450) s] and with PEEP [345 (245 to 435) s; P = 0.08]. The discomfort reported was 0 (0 to 18) mm and was comparable between groups (P = 0.22).

CONCLUSION

Compared with spontaneous breathing, positive pressure ventilation with and without PEEP shortened preoxygenation time.

Emergence d’un plasmide de résistance à la Colimycine

http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00424-7/abstract

Liu et al., Lancet, 2015; DOI: http://dx.doi.org/10.1016/S1473-3099(15)00424-7

Background

Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.

Methods

The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli andKlebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model.

Findings

Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10⁻¹ to 10⁻³ cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection.

Interpretation

The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.

Méta-analyse sur la Musique comme aide à la récupération post-opératoire

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60169-6/abstract

Hole et al., Lancet, 2015; DOI: http://dx.doi.org/10.1016/S0140-6736(15)60169-6

Background

Music is a non-invasive, safe, and inexpensive intervention that can be delivered easily and successfully. We did a systematic review and meta-analysis to assess whether music improves recovery after surgical procedures.

Methods

We included randomised controlled trials (RCTs) of adult patients undergoing surgical procedures, excluding those involving the central nervous system or head and neck, published in any language. We included RCTs in which any form of music initiated before, during, or after surgery was compared with standard care or other non-drug interventions. We searched MEDLINE, Embase, CINAHL, and Cochrane Central. We did meta-analysis with RevMan (version 5.2), with standardised mean differences (SMD) and random-effects models, and used Stata (version 12) for meta-regression. This study is registered with PROSPERO, number CRD42013005220.

Findings

We identified 4261 titles and abstracts, and included 73 RCTs in the systematic review, with size varying between 20 and 458 participants. Choice of music, timing, and duration varied. Comparators included routine care, headphones with no music, white noise, and undisturbed bed rest. Music reduced postoperative pain (SMD −0·77 [95% CI −0·99 to −0·56]), anxiety (−0·68 [–0·95 to −0·41]), and analgesia use (−0·37 [–0·54 to −0·20]), and increased patient satisfaction (1·09 [0·51 to 1·68]), but length of stay did not differ (SMD −0·11 [–0·35 to 0·12]). Subgroup analyses showed that choice of music and timing of delivery made little difference to outcomes. Meta-regression identified no causes of heterogeneity in eight variables assessed. Music was effective even when patients were under general anaesthetic.

Interpretation

Music could be offered as a way to help patients reduce pain and anxiety during the postoperative period. Timing and delivery can be adapted to individual clinical settings and medical teams.

Méta-analyse sur l’indication transfusionnelle en Chirurgie Cardiaque

http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(15)00198-2/abstract

Patel et al., Lancet, 2015; DOI: http://dx.doi.org/10.1016/S2352-3026(15)00198-2

Background

Good blood management is an important determinant of outcome in cardiac surgery. Guidelines recommend restrictive red blood cell transfusion. Our objective was to systematically review the evidence from randomised controlled trials and observational studies that are used to inform transfusion decisions in adult cardiac surgery.

Methods

We did a systematic review by searching PubMed, Embase, Cochrane Library, and DARE, from inception to May 1, 2015, databases from specialist societies, and bibliographies of included studies and recent relevant review articles. We included randomised controlled trials that assessed the effect of liberal versus restrictive red blood cell transfusion in patients undergoing cardiac and non-cardiac surgery, and observational studies that assessed the effect of red blood cell transfusion compared with no transfusion on outcomes in adult cardiac patients after surgery. We pooled adjusted odds ratios using fixed-effects and random-effects meta-analyses. The primary outcome was 30-day mortality.

Findings

We included data from six cardiac surgical randomised controlled trials (3352 patients), 19 non-cardiac surgical trials (8361 patients), and 39 observational studies (232 806 patients). The pooled fixed effects mortality odds ratios comparing liberal versus restrictive transfusion thresholds was 0·70 (95% CI 0·49–1·02; p=0·060) for cardiac surgical trials and 1·10 (95% CI 0·96–1·27; p=0·16) for trials in settings other than cardiac surgery. By contrast, observational cohort studies in cardiac surgery showed that red blood cell transfusion compared with no transfusion was associated with substantially higher mortality (random effects odds ratio 2·72, 95% CI 2·11–3·49; p<0·0001) and other morbidity, although with substantial heterogeneity and small study effects.

Interpretation

Evidence from randomised controlled trials in cardiac surgery refutes findings from observational studies that liberal thresholds for red blood cell transfusion are associated with a substantially increased risk of mortality and morbidity. Observational studies and trials in non-cardiac surgery should not be used to inform treatment decisions or guidelines for patients having cardiac surgery.

Etude de cohorte sur la corticothérapie chez les enfants en état de choc : CONTRE

http://journals.lww.com/shockjournal/Fulltext/2015/11000/A_Cohort_Study_of_Pediatric_Shock___Frequency_of.4.aspx

Kusum et al., Shock, 2015; doi: 10.1097/SHK.0000000000000355

Introduction

Pediatric shock is associated with significant morbidity and limited evidence suggests treatment with corticosteroids. The objective of this study was to describe practice patterns and outcomes associated with corticosteroid use in children with shock.

Methods

We conducted a retrospective, cohort study in four pediatric intensive care units (PICU) in Canada. Patients aged newborn to 17 years admitted to PICU with shock between January 2010 and June 2011 were eligible.

Results

364 patients were included. The frequency of hydrocortisone administration was 22.3% overall (95% CI: 18.0, 26.5) and 59.4% in patients who received at least 60 cc/kg of fluid and were on two or more vasoactive agents. Patients administered hydrocortisone had higher PRISM scores (19, IQR 11–24 versus 9, IQR 5–16; P < 0.0001), higher inotrope scores (15, IQR 10–25 versus 7.5, IQR 3.3–10.6, P < 0.0001) and were more likely to have received 60 cc/kg of fluid resuscitation (59.3% versus 33.6%, OR 2.88, 95% CI: 2.09, 3.96). In an adjusted analysis, patients who received hydrocortisone spent more time on vasoactive infusions (64 versus 34 hours, hazard ratio 0.72, 95% CI: 0.62, 0.84) and had a higher incidence of positive cultures between day 4 and day 28 post admission (24.7% versus 14.5%, OR 1.79, 95% CI: 1.58, 2.04).

Conclusion

Hydrocortisone administration was associated with longer time on vasopressors and increased incidence of positive cultures even after correcting for illness severity. Caution should be exercised in administering hydrocortisone for shock until there is clear evidence for benefit in this patient population.

Une étude HEROICS sur l’Hémofiltration précoce à Haut Volume en post-opératoire de chirurgie cardiaque

www.atsjournals.org/doi/abs/10.1164/rccm.201503-0516OC#.Vk5E0NIveUk

Combes et al., ARJCCM, 2015; doi: 10.1164/rccm.201503-0516OC

Rationale

Post–cardiac surgery shock is associated with high morbidity and mortality. By removing toxins and proinflammatory mediators and correcting metabolic acidosis, high-volume hemofiltration (HVHF) might halt the vicious circle leading to death by improving myocardial performance and reducing vasopressor dependence.

Objectives

To determine whether early HVHF decreases all-cause mortality 30 days after randomization.

Methods

This prospective, multicenter randomized controlled trial included patients with severe shock requiring high-dose catecholamines 3–24 hours post–cardiac surgery who were randomized to early HVHF (80 ml/kg/h for 48 h), followed by standard-volume continuous venovenous hemodiafiltration (CVVHDF) until resolution of shock and recovery of renal function, or conservative standard care, with delayed CVVHDF only for persistent, severe acute kidney injury.

Measurements and Main Results

On Day 30, 40 of 112 (36%) HVHF and 40 of 112 (36%) control subjects (odds ratio, 1.00; 95% confidence interval, 0.64–1.56; P = 1.00) had died; only 57% of the control subjects had received renal-replacement therapy. Between-group survivors’ Day-60, Day-90, intensive care unit, and in-hospital mortality rates, Day-30 ventilator-free days, and renal function recovery were comparable. HVHF patients experienced faster correction of metabolic acidosis and tended to be more rapidly weaned off catecholamines but had more frequent hypophosphatemia, metabolic alkalosis, and thrombocytopenia.

Conclusions

For patients with post–cardiac surgery shock requiring high-dose catecholamines, the early HVHF onset for 48 hours, followed by standard volume until resolution of shock and recovery of renal function, did not lower Day-30 mortality and did not impact other important patient-centered outcomes compared with a conservative strategy with delayed CVVHDF initiation only for patients with persistent, severe acute kidney injury.

Entrainement du diaphragme en ventilation mécanique

http://www.atsjournals.org/doi/abs/10.1164/rccm.201503-0620OC#.Vk5FFdIveUk

Goligher et al., ARJCCM, 2015; doi: 10.1164/rccm.201503-0620OC

Rationale

Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine mechanical ventilation for critically ill patients are unknown.

Objectives

To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon.

Methods

In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound.

Measurements and Main Results

Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison).

Conclusions

Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.

Nouveau Biomarqueur pour le diagnostic de pneumonie communautaire à l’admission en réanimation

http://www.atsjournals.org/doi/abs/10.1164/rccm.201502-0355OC#.Vk5FYtIveUk

Scicluna, et al., ARJCCM, 2015; doi: 10.1164/rccm.201502-0355OC

Rationale

Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions for respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment.

Objectives

To characterize the blood genomic response in patients with suspected CAP and identify a candidate biomarker for the rapid diagnosis of CAP on ICU admission.

Methods

The study comprised two cohorts of consecutively enrolled patients treated for suspected CAP on ICU admission. Patients were designated CAP (cases) and no-CAP patients (control subjects) by post hoc assessment. The first (discovery) cohort (101 CAP and 33 no-CAP patients) was enrolled between January 2011 and July 2012; the second (validation) cohort (70 CAP and 30 no-CAP patients) between July 2012 and June 2013. Blood was collected within 24 hours of ICU admission.

Measurements and Main Results

Blood microarray analysis of CAP and no-CAP patients revealed shared and distinct gene expression patterns. A 78-gene signature was defined for CAP, from which a FAIM3:PLAC8 gene expression ratio was derived with area under curve of 0.845 (95% confidence interval, 0.764–0.917) and positive and negative predictive values of 83% and 81%, respectively. Robustness of the FAIM3:PLAC8 ratio was ascertained by quantitative polymerase chain reaction in the validation cohort. The FAIM3:PLAC8 ratio outperformed plasma procalcitonin and IL-8 and IL-6 in discriminating between CAP and no-CAP patients.

Conclusions

CAP and no-CAP patients presented shared and distinct blood genomic responses. We propose the FAIM3:PLAC8 ratio as a candidate biomarker to assist in the rapid diagnosis of CAP on ICU admission.