Biblio du mois : Août 2017
Voici la biblio du mois ! A l’honneur ce mois-ci : la Cardiologie !
Pour fêter en parallèle le succès de l’ESC à Barcelone, les études phares qui vont (peut-être) chambouler la pratique (avec le coût et les complications aussi ?) des patients mais également des études plus spécifiques A-R.
Bref, ne soyez pas largués au retour de vos cardiologues adorés 😉 D’autant plus qu’on prépare avec le CCF et la SFC des invitations pour le congrès spécial cours avancé USIC les 26 et 27 octobre 2017 : Tenez-vous prêt pour les inscriptions ! Soyez imbattables en Cardiologie !
A part ça, de la chirurgie cardiaque (LICORN study Cf. image ci-contre) mais également de la neuro-réa et de l’anesthésie notamment sur l’Exacyl et la transfusion massive non-traumatique pour changer.
Et comme nous prenons en charge les patients de façon globale et que c’est un mois de fête, on ne marquera pas le 50ème anniversaire de la 1ère description du SDRA !
Bonus #1 sur la testostérone en pré-op et la parité en réanimation… Pas de machisme à l’AJAR !
Bonus #2 sur l’encéphalopathie des footballeurs américains, ça existerait aussi chez nos footballeurs ? Pas touche à Zizou !
Et puis si vous revenez de 2 mois de vacances, n’oubliez pas de relire la biblio du mois de Juillet 2017
Pour la rentrée, ne vous inquiétez pas, le programme est chargé, attendez avant de réserver vos vacances au ski et profitez du soleil…
L’angiotensine II dans l’état de choc vasoplégique ?
Khanna et al., NEJM, 2017
Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition.
We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 μg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors.
A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (−1.75 vs. −1.28, P=0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P=0.12).
Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors.
Confirmation de l’Idarucizumab en tant qu’antidote du Dabigatran
Pollack et al., NEJM, 2017
Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran.
We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures.
A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals.
In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran.
Aspirine versus placebo pour les grossesses à haut risque de pré-éclampsie
Rolnik et al., NEJM, 2017
Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.
In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle.
A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events.
Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo.
Pontage coronarien : vers le toto-cœur battant ?
Shroyer et al., NEJM, 2017
Coronary-artery bypass grafting (CABG) surgery may be performed either with cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump). We report the 5-year clinical outcomes in patients who had been included in the Veterans Affairs trial of on-pump versus off-pump CABG.
From February 2002 through June 2007, we randomly assigned 2203 patients at 18 medical centers to undergo either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The two primary 5-year outcomes were death from any cause and a composite outcome of major adverse cardiovascular events, defined as death from any cause, repeat revascularization (CABG or percutaneous coronary intervention), or nonfatal myocardial infarction. Secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction. Primary outcomes were assessed at a P value of 0.05 or less, and secondary outcomes at a P value of 0.01 or less.
The rate of death at 5 years was 15.2% in the off-pump group versus 11.9% in the on-pump group (relative risk, 1.28; 95% confidence interval [CI], 1.03 to 1.58; P=0.02). The rate of major adverse cardiovascular events at 5 years was 31.0% in the off-pump group versus 27.1% in the on-pump group (relative risk, 1.14; 95% CI, 1.00 to 1.30; P=0.046). For the 5-year secondary outcomes, no significant differences were observed: for nonfatal myocardial infarction, the rate was 12.1% in the off-pump group and 9.6% in the on-pump group (P=0.05); for death from cardiac causes, the rate was 6.3% and 5.3%, respectively (P=0.29); for repeat revascularization, the rate was 13.1% and 11.9%, respectively (P=0.39); and for repeat CABG, the rate was 1.4% and 0.5%, respectively (P=0.02).
In this randomized trial, off-pump CABG led to lower rates of 5-year survival and event-free survival than on-pump CABG.
Revue sur le SDRA
Taylor Thompson et al., NEJM, 2017
#Spécial ESC :
Dabigatran + Clopidogrel ou Ticagrelor > AVK + Clopidogrel ou Ticagrelor + Aspirine après coronarographie chez patients avec FA ?
Cannon et al., NEJM, 2017
Rivaroxaban à petites doses en prévention secondaire ?
Eikelboom et al., NEJM, 2017
Oxygénothérapie systématique (6L/min) inutile chez les patients ayant un infarctus ?
Hofmann et al., NEJM, 2017
Immunothérapie dans l’artériosclérose ?
Ridker et al., NEJM, 2017
Stratégie de prise en charge des OAP guidée par le NT-Pro-BNP ?
Felker et al., JAMA, 2017
Importance The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels (“guided therapy”) with inconsistent results.
Objective To determine whether an amino-terminal pro–B-type natriuretic peptide (NT-proBNP)–guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF).
Design, Settings, and Participants The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP–guided strategy or usual care.
Interventions Patients were randomized to either an NT-proBNP–guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group.
Main Outcomes and Measures The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events.
Results The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups.
Conclusions and Relevance In high-risk patients with HFrEF, a strategy of NT-proBNP–guided therapy was not more effective than a usual care strategy in improving outcomes.
Fin des corticoïdes dans les bronchopneumopathies sans asthme ?
Hay et al., JAMA, 2017
Importance Acute lower respiratory tract infection is common and often treated inappropriately in primary care with antibiotics. Corticosteroids are increasingly used but without sufficient evidence.
Objective To assess the effects of oral corticosteroids for acute lower respiratory tract infection in adults without asthma.
Design, Setting, and Participants Multicenter, placebo-controlled, randomized trial (July 2013 to final follow-up October 2014) conducted in 54 family practices in England among 401 adults with acute cough and at least 1 lower respiratory tract symptom not requiring immediate antibiotic treatment and with no history of chronic pulmonary disease or use of asthma medication in the past 5 years.
Interventions Two 20-mg prednisolone tablets (n = 199) or matched placebo (n = 202) once daily for 5 days.
Main Outcomes and Measures The primary outcomes were duration of moderately bad or worse cough (0 to 28 days; minimal clinically important difference, 3.79 days) and mean severity of symptoms on days 2 to 4 (scored from 0 [not affected] to 6 [as bad as it could be]; minimal clinically important difference, 1.66 units). Secondary outcomes were duration and severity of acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, and adverse events.
Results Among 401 randomized patients, 2 withdrew immediately after randomization, and 1 duplicate patient was identified. Among the 398 patients with baseline data (mean age, 47 [SD, 16.0] years; 63% women; 17% smokers; 77% phlegm; 70% shortness of breath; 47% wheezing; 46% chest pain; 42% abnormal peak flow), 334 (84%) provided cough duration and 369 (93%) symptom severity data. Median cough duration was 5 days (interquartile range [IQR], 3-8 days) in the prednisolone group and 5 days (IQR, 3-10 days) in the placebo group (adjusted hazard ratio, 1.11; 95% CI, 0.89-1.39; P = .36 at an α = .05). Mean symptom severity was 1.99 points in the prednisolone group and 2.16 points in the placebo group (adjusted difference, −0.20; 95% CI, −0.40 to 0.00; P = .05 at an α = .001). No significant treatment effects were observed for duration or severity of other acute lower respiratory tract infection symptoms, duration of abnormal peak flow, antibiotic use, or nonserious adverse events. There were no serious adverse events.
Conclusions and Relevance Oral corticosteroids should not be used for acute lower respiratory tract infection symptoms in adults without asthma because they do not reduce symptom duration or severity.
Echec du Levosimendan de dysfonction cardiaque post-op de chirurgie cardiaque ?
Cholley et al., JAMA, 2017
Importance Low cardiac output syndrome after cardiac surgery is associated with high morbidity and mortality in patients with impaired left ventricular function.
Objective To assess the ability of preoperative levosimendan to prevent postoperative low cardiac output syndrome.
Design, Setting, and Participants Randomized, double-blind, placebo-controlled trial conducted in 13 French cardiac surgical centers. Patients with a left ventricular ejection fraction less than or equal to 40% and scheduled for isolated or combined coronary artery bypass grafting with cardiopulmonary bypass were enrolled from June 2013 until May 2015 and followed during 6 months (last follow-up, November 30, 2015).
Interventions Patients were assigned to a 24-hour infusion of levosimendan 0.1 µg/kg/min (n = 167) or placebo (n = 168) initiated after anesthetic induction.
Main Outcomes and Measures Composite end point reflecting low cardiac output syndrome with need for a catecholamine infusion 48 hours after study drug initiation, need for a left ventricular mechanical assist device or failure to wean from it at 96 hours after study drug initiation when the device was inserted preoperatively, or need for renal replacement therapy at any time postoperatively. It was hypothesized that levosimendan would reduce the incidence of this composite end point by 15% in comparison with placebo.
Results Among 336 randomized patients (mean age, 68 years; 16% women), 333 completed the trial. The primary end point occurred in 87 patients (52%) in the levosimendan group and 101 patients (61%) in the placebo group (absolute risk difference taking into account center effect, −7% [95% CI, −17% to 3%]; P = .15). Predefined subgroup analyses found no interaction with ejection fraction less than 30%, type of surgery, and preoperative use of β-blockers, intra-aortic balloon pump, or catecholamines. The prevalence of hypotension (57% vs 48%), atrial fibrillation (50% vs 40%), and other adverse events did not significantly differ between levosimendan and placebo.
Conclusions and Relevance Among patients with low ejection fraction who were undergoing coronary artery bypass grafting with cardiopulmonary bypass, levosimendan compared with placebo did not result in a significant difference in the composite end point of prolonged catecholamine infusion, use of left ventricular mechanical assist device, or renal replacement therapy. These findings do not support the use of levosimendan for this indication.
Echec d’un système de protection des AVC ischémiques post-op de Remplacement valvulaire aortique chirurgical ?
Mack et al., JAMA, 2017
Importance Stroke is a major complication of surgical aortic valve replacement (SAVR).
Objective To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR.
Design, Setting, and Participants A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016.
Interventions Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR.
Main Outcomes and Measures The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition.
Results Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, −1.3%; 95% CI, −13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, −6.9%; 95% CI, −17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, −2.8% [95% CI, −13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, −1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, −9.1%; 95% CI, −17.1% to −1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, −7.4%; 95% CI, −15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004).
Conclusions and Relevance Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up.
Quel traitement endovasculaire des AVC ischémiques ?
Lapergue et al., JAMA, 2017
Importance The benefits of endovascular revascularization using the contact aspiration technique vs the stent retriever technique in patients with acute ischemic stroke remain uncertain because of lack of evidence from randomized trials.
Objective To compare efficacy and adverse events using the contact aspiration technique vs the standard stent retriever technique as a first-line endovascular treatment for successful revascularization among patients with acute ischemic stroke and large vessel occlusion.
Design, Setting, and Participants The Contact Aspiration vs Stent Retriever for Successful Revascularization (ASTER) study was a randomized, open-label, blinded end-point clinical trial conducted in 8 comprehensive stroke centers in France (October 2015-October 2016). Patients who presented with acute ischemic stroke and a large vessel occlusion in the anterior circulation within 6 hours of symptom onset were included.
Interventions Patients were randomly assigned to first-line contact aspiration (n = 192) or first-line stent retriever (n = 189) immediately prior to mechanical thrombectomy.
Main Outcomes and Measures The primary outcome was the proportion of patients with successful revascularization defined as a modified Thrombolysis in Cerebral Infarction score of 2b or 3 at the end of all endovascular procedures. Secondary outcomes included degree of disability assessed by overall distribution of the modified Rankin Scale (mRS) score at 90 days, change in National Institutes of Health Stroke Scale (NIHSS) score at 24 hours, all-cause mortality at 90 days, and procedure-related serious adverse events.
Results Among 381 patients randomized (mean age, 69.9 years; 174 women [45.7%]), 363 (95.3%) completed the trial. Median time from symptom onset to arterial puncture was 227 minutes (interquartile range, 180-280 minutes). For the primary outcome, the proportion of patients with successful revascularization was 85.4% (n = 164) in the contact aspiration group vs 83.1% (n = 157) in the stent retriever group (odds ratio, 1.20 [95% CI, 0.68-2.10]; P = .53; difference, 2.4% [95% CI, −5.4% to 9.7%]). For the clinical efficacy outcomes (change in NIHSS score at 24 hours, mRS score at 90 days) and adverse events, there were no significant differences between groups.
Conclusions and Relevance Among patients with ischemic stroke in the anterior circulation undergoing thrombectomy, first-line thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful revascularization rate at the end of the procedure.
Controverse sur l’incitation financière aux bonnes pratiques ?
Chen et al., JAMA, 2017
Importance Medicare recently launched the Physician Value-Based Payment Modifier (PVBM) Program, a mandatory pay-for-performance program for physician practices. Little is known about performance by practices that serve socially or medically high-risk patients.
Objective To compare performance in the PVBM Program by practice characteristics.
Design, Setting, and Participants Cross-sectional observational study using PVBM Program data for payments made in 2015 based on performance of large US physician practices caring for fee-for-service Medicare beneficiaries in 2013.
Exposures High social risk (defined as practices in the top quartile of proportion of patients dually eligible for Medicare and Medicaid) and high medical risk (defined as practices in the top quartile of mean Hierarchical Condition Category risk score among fee-for-service beneficiaries).
Main Outcomes and Measures Quality and cost z scores based on a composite of individual measures. Higher z scores reflect better performance on quality; lower scores, better performance on costs.
Results Among 899 physician practices with 5 189 880 beneficiaries, 547 practices were categorized as low risk (neither high social nor high medical risk) (mean, 7909 beneficiaries; mean, 320 clinicians), 128 were high medical risk only (mean, 3675 beneficiaries; mean, 370 clinicians), 102 were high social risk only (mean, 1635 beneficiaries; mean, 284 clinicians), and 122 were high medical and social risk (mean, 1858 beneficiaries; mean, 269 clinicians). Practices categorized as low risk performed the best on the composite quality score (z score, 0.18 [95% CI, 0.09 to 0.28]) compared with each of the practices categorized as high risk (high medical risk only: z score, −0.55 [95% CI, −0.77 to −0.32]; high social risk only: z score, −0.86 [95% CI, −1.17 to −0.54]; and high medical and social risk: −0.78 [95% CI, −1.04 to −0.51]) (P < .001 across groups). Practices categorized as high social risk only performed the best on the composite cost score (z score, −0.52 [95% CI, −0.71 to −0.33]), low risk had the next best cost score (z score, −0.18 [95% CI, −0.25 to −0.10]), then high medical and social risk (z score, 0.40 [95% CI, 0.23 to 0.57]), and then high medical risk only (z score, 0.82 [95% CI, 0.65 to 0.99]) (P < .001 across groups). Total per capita costs were $9506 for practices categorized as low risk, $13 683 for high medical risk only, $8214 for high social risk only, and $11 692 for high medical and social risk. These patterns were associated with fewer bonuses and more penalties for high-risk practices.
Conclusions and Relevance During the first year of the Medicare Physician Value-Based Payment Modifier Program, physician practices that served more socially high-risk patients had lower quality and lower costs, and practices that served more medically high-risk patients had lower quality and higher costs.
Recommandations sur le traitement des lombalgies
Wenger et al., JAMA, 2017
Encéphalopathie liée au Footbal US ?
Mez et al., JAMA, 2017
Méta-analyse sur la fibrinolyse dans les ST+
Jinatongthai et al., Lancet, 2017
Méta-analyse sur le timing de la coronarographie dans les ST-
Intérêt de la PCT chez les nouveaux-nés ? 10h d’ATB ?
Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment.
We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned [1:1] using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932.
Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI −4·6 to 4·8) in the intention-to-treat analysis (5 [0·6%] of 866 neonates in the procalcitonin group vs 4 [0·5%] of 844 neonates in the standard group) and 0·1% (−5·2 to 5·3) in the per-protocol analysis (5 [0·7%] of 745 neonates in the procalcitonin group vs 4 [0·6%] of 663 neonates in the standard group).
Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death.
SSR post-AVC ischémique par la famille ?
Réparation valvulation mitrale per-cutanée : on y est ?
Praz, et al., Lancet, 2017
Severe mitral regurgitation is associated with impaired prognosis if left untreated. Using the devices currently available, transcatheter mitral valve repair (TMVr) remains challenging in complex anatomical situations. We report the procedural and 30-day results of the first-in-man study of the Edwards PASCAL TMVr system.
In this multicentre, prospective, observational, first-in-man study, we collected data from seven tertiary care hospitals in five countries that had a compassionate use programme in which patients underwent transcatheter mitral valve repair using the Edwards PASCAL TMVr system. Eligible patients were those with symptomatic, severe functional, degenerative, or mixed mitral regurgitation deemed at high risk or inoperable. Safety and efficacy of the procedure were prospectively assessed at device implantation, discharge, and 30 days after device implantation. The key study endpoints were technical success assessed at the end of the procedure and device success 30 days after implantation using the Mitral Valve Academic Research Consortium definitions.
Between Sept 1, 2016, and March 31, 2017, 23 patients (median age 75 years [IQR 61–82]) had treatment for moderate-to-severe (grade 3+) or severe (grade 4+) mitral regurgitation using the Edwards PASCAL TMVr system. At baseline, the median EuroScore II score was 7·1% (IQR 3·6–12·8) and the median Society of Thoracic Surgeons predicted risk of mortality for mitral valve repair was 4·8% (2·1–9·0) and 6·8% (2·9–10·1) for mitral valve replacement. 22 (96%) of 23 patients were New York Heart Association (NYHA) class III or IV at baseline. The implantation of at least one device was successful in all patients, resulting in procedural residual mitral regurgitation of grade 2+ or less in 22 (96%) patients. Six (26%) of 23 patients had two implants. Periprocedural complications occurred in two (9%) of 23 patients (one minor bleeding event and one transient ischaemic attack). Despite the anatomical complexity of mitral regurgitation in the patients in this compassionate use cohort, technical success was achieved in 22 (96%) of 23 patients, and device success at 30 days was achieved in 18 (78%) patients. Three patients (13%) died during the 30 day follow-up. 19 (95%) of 20 patients alive 30 days after implantation were NYHA class I or II.
This study establishes feasibility of the Edwards PASCAL TMVr system with a high rate of technical success and reduction of mitral regurgitation severity. Further research is needed on procedural and long-term clinical outcomes.
Un bolus d’Acide Tranexamique suffit dans la chirurgie de hanche ?
Zufferey et al., Anesthesiology, 2017
Background: Preoperative administration of the antifibrinolytic agent tranexamic acid reduces bleeding in patients undergoing hip arthroplasty. Increased fibrinolytic activity is maintained throughout the first day postoperation. The objective of the study was to determine whether additional perioperative administration of tranexamic acid would further reduce blood loss.
Methods: This prospective, double-blind, parallel-arm, randomized, superiority study was conducted in 168 patients undergoing unilateral primary hip arthroplasty. Patients received a preoperative intravenous bolus of 1 g of tranexamic acid followed by a continuous infusion of either tranexamic acid 1 g (bolus-plus-infusion group) or placebo (bolus group) for 8 h. The primary outcome was calculated perioperative blood loss up to day 5. Erythrocyte transfusion was implemented according to a restrictive transfusion trigger strategy.
Results: The mean perioperative blood loss was 919 ± 338 ml in the bolus-plus-infusion group (84 patients analyzed) and 888 ± 366 ml in the bolus group (83 patients analyzed); mean difference, 30 ml (95% CI, −77 to 137; P = 0.58). Within 6 weeks postsurgery, three patients in each group (3.6%) underwent erythrocyte transfusion and two patients in the bolus group experienced distal deep-vein thrombosis. A meta-analysis combining data from this study with those of five other trials showed no incremental efficacy of additional perioperative administration of tranexamic acid.
Conclusions: A preoperative bolus of tranexamic acid, associated with a restrictive transfusion trigger strategy, resulted in low erythrocyte transfusion rates in patients undergoing hip arthroplasty. Supplementary perioperative administration of tranexamic acid did not achieve any further reduction in blood loss.
Le propofol impliqué dans l’autophagie des neurones ?
Qiao et al., Anesthesiology, 2017
Background: In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis.
Methods: The dose–response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays. The effects of propofol on cytosolic calcium concentration were evaluated using Fura-2, and autophagy activity was determined by LC3II expression levels with Western blot. Proliferation and differentiation were evaluated by bromodeoxyuridine incorporation and immunostaining with neuronal and glial markers.
Results: Propofol dose- and time-dependently induced cell damage and elevated LC3II expression, most robustly at 200 µM for 24 h (67 ± 11% of control, n = 12 to 19) and 6 h (2.4 ± 0.5 compared with 0.6 ± 0.1 of control, n = 7), respectively. Treatment with 200 μM propofol also increased cytosolic calcium concentration (346 ± 71% of control, n = 22 to 34). Propofol at 10 µM stimulated neural progenitor cell proliferation and promoted neuronal cell fate, whereas propofol at 200 µM impaired neuronal proliferation and promoted glial cell fate (n = 12 to 20). Cotreatment with ryanodine and inositol 1,4,5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca2+ chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation, and differentiation.
Conclusions: These results suggest that propofol-mediated cell survival or neurogenesis is closely associated with propofol’s effects on autophagy by activation of ryanodine and inositol 1,4,5-trisphosphate receptors.
Testostérone pré-op de chirurgie cardiaque ?
Argalious et al., Anesthesiology, 2017
Background: Whether patients on testosterone replacement therapy undergoing noncardiac surgery have an increased risk of postoperative in-hospital mortality and cardiovascular events remains unknown. We therefore sought to identify the impact of testosterone replacement on the incidence of a composite of postoperative in-hospital mortality and cardiovascular events in men undergoing noncardiac surgery.
Methods: Data from male American Society of Anesthesiologists I through IV patients 40 yr or older who underwent noncardiac surgery between May 2005 and December 2015 at the Cleveland Clinic (Cleveland, Ohio) main campus were included. The primary exposure was preoperative testosterone use. The primary outcome was a composite of postoperative in-hospital mortality and cardiovascular events. We compared patients who received testosterone and those who did not using propensity score matching within surgical procedure matches.
Results: Among 49,273 patients who met inclusion and exclusion criteria, 947 patients on testosterone were matched to 4,598 nontestosterone patients. The incidence of in-hospital mortality was 1.3% in the testosterone group and 1.1% in the nontestosterone group, giving an odds ratio of 1.17 (99% CI, 0.51 to 2.68; P = 0.63). The incidence of myocardial infarction was 0.2% in the testosterone group and 0.6% in the nontestosterone group (odds ratio = 0.34; 99% CI, 0.05 to 2.28; P = 0.15). Similarly, no significant difference was found in stroke (testosterone vs. nontestosterone: 2.0% vs. 2.1%), pulmonary embolism (0.5% vs. 0.7%), or deep venous thrombosis (2.0% vs. 1.7%).
Conclusions: Preoperative testosterone is not associated with an increased incidence of a composite of postoperative in-hospital mortality and cardiovascular events.
La réponse de l’hôte aux infections impliquées dans les infections nosocomiales suivantes ?
van Vught et al., AJRCCM, 2017
Rationale: Sepsis can be complicated by secondary infections. We explored the possibility that patients with sepsis developing a secondary infection while in the intensive care unit (ICU) display sustained inflammatory, vascular, and procoagulant responses.
Objectives: To compare systemic proinflammatory host responses in patients with sepsis who acquire a new infection with those who do not.
Methods: Consecutive patients with sepsis with a length of ICU stay greater than 48 hours were prospectively analyzed for the development of ICU-acquired infections. Twenty host response biomarkers reflective of key pathways implicated in sepsis pathogenesis were measured during the first 4 days after ICU admission and at the day of an ICU-acquired infection or noninfectious complication.
Measurements and Main Results: Of 1,237 admissions for sepsis (1,089 patients), 178 (14.4%) admissions were complicated by ICU-acquired infections (at Day 10 [6–13], median with interquartile range). Patients who developed a secondary infection showed higher disease severity scores and higher mortality up to 1 year than those who did not. Analyses of biomarkers in patients who later went on to develop secondary infections revealed a more dysregulated host response during the first 4 days after admission, as reflected by enhanced inflammation, stronger endothelial cell activation, a more disturbed vascular integrity, and evidence for enhanced coagulation activation. Host response reactions were similar at the time of ICU-acquired infectious or noninfectious complications.
Conclusions: Patients with sepsis who developed an ICU-acquired infection showed a more dysregulated proinflammatory and vascular host response during the first 4 days of ICU admission than those who did not develop a secondary infection.
Importance de la parité en Réanimation ?
Mehta et al., AJRCCM, 2017
Vers une pression de perfusion cérébrale individualisée ?
Donnelly et al., CCM, 2017
In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying “one” autoregulation-guided cerebral perfusion pressure target—called “cerebral perfusion pressure optimal”. We investigated whether a cerebral perfusion pressure autoregulation range—which uses a continuous estimation of the “lower” and “upper” cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)—has prognostic value.
Single-center retrospective analysis of prospectively collected data.
The neurocritical care unit at a tertiary academic medical center.
Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol.
Methods and Main Results
Cerebral perfusion pressure-pressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this “U-shaped curve” crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the “lower” and “upper” cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02–1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04–1.08; p < 0.001).
Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical.
Les statines contre le delirium en réanimation médicale ?
Mather et al., CCM, 2017
To examine the association between statin use and the risk of delirium in hospitalized patients with an admission to the medical ICU.
Retrospective propensity-matched cohort analysis with accrual from September 1, 2012, to September 30, 2015.
Hartford Hospital, Hartford, CT.
An initial population of patients with an admission to a medical ICU totaling 10,216 visits were screened for delirium by means of the Confusion Assessment Method. After exclusions, a population of 6,664 was used to match statin users and nonstatin users. The propensity-matched cohort resulted in a sample of 1,475 patients receiving statin matched 1:1 with control patients not using statin.
Measurements and Main Results
Delirium defined as a positive Confusion Assessment Method assessment was the primary end point. The prevalence of delirium was 22.3% in the unmatched cohort and 22.8% in the propensity-matched cohort. Statin use was associated with a significant decrease in the risk of delirium (odds ratio, 0.47; 95% CI, 0.38–0.56). Considering the type of statin used, atorvastatin (0.51; 0.41–0.64), pravastatin (0.40; 0.28–0.58), and simvastatin (0.33; 0.21–0.52) were all significantly associated with a reduced frequency of delirium.
The use of statins was independently associated with a reduction in the risk of delirium in hospitalized patients. When considering types of statins used, this reduction was significant in patients using atorvastatin, pravastatin, and simvastatin. Randomized trials of various statin types in hospitalized patients prone to delirium should validate their use in protection from delirium.
Le don d’organes : motivant ou stressant ?
Kentish-Barnes et al., CCM, 2017
ICU clinicians are primarily involved in organ donation after brain death of ICU patients. Their perceptions of organ donation may affect outcomes. Our objective was to describe ICU clinician’s perceptions and experience of organ donation.
Design and Setting
Cross-sectional study among physicians and nurses (90 ICUs in France). We used factorial correspondence analysis to describe categories of clinicians regarding their perceptions and experience of organ donation. Factors associated with a positive (motivating) or negative (stressful) experiences were studied using multivariate logistic regression.
Physicians and nurses.
Measurements and Main Results
Three thousand three hundred twenty-five clinicians working in 77 ICUs returned questionnaires. Professionals who experienced organ donation as motivating were younger (odds ratio, 0.41; 95% CI, 0.32–0.53; p < 0.001), more often potential organ donors (odds ratio, 1.92; 95% CI, 1.56–2.35; p < 0.001), less likely to describe inconsistency (odds ratio, 0.43; 95% CI, 0.23–0.8) or complexity (odds ratio, 0.55; 95% CI, 0.45–0.67) of their feelings versus their professional activity, less likely to report that organ donation was not a priority in their ICU (odds ratio, 0.68; 95% CI, 0.55–0.84), and more likely to have participated in meetings of transplant coordinators with relatives (odds ratio, 1.71; 95% CI, 1.37–2.14; p < 0.001). Professionals who felt organ donation was stressful were older (odds ratio, 1.84; 95% CI, 1.34–2.54; p < 0.001), less often physicians (odds ratio, 0.58; 95% CI, 0.44–0.77; p < 0.001), more likely to describe shift from curative care to organ donation as emotionally complex (odds ratio, 1.83; 95% CI, 1.52–2.21; p < 0.001), care of relatives of brain-dead patients as complex (odds ratio, 1.59; 95% CI, 1.32–1.93; p < 0.001), and inconsistency and complexity of personal feelings about organ donation versus professional activity (odds ratio, 3.25; 95% CI, 1.92–5.53; p < 0.001), and more likely to have little experience with caring for potential organ donors (odds ratio, 1.49; 95% CI, 1.09–2.04).
Significant differences exist among ICU clinician’s perceptions of organ donation. Whether these differences affect family experience and consent rates deserves investigation.
Vers une décontamination de SARM universelle aux USA ?
Whittington et al., CCM, 2017
Objective: Patients in the ICU are at the greatest risk of contracting healthcare-associated infections like methicillin-resistant Staphylococcus aureus. This study calculates the cost-effectiveness of methicillin-resistant S aureus prevention strategies and recommends specific strategies based on screening test implementation.
Design: A cost-effectiveness analysis using a Markov model from the hospital perspective was conducted to determine if the implementation costs of methicillin-resistant S aureus prevention strategies are justified by associated reductions in methicillin-resistant S aureus infections and improvements in quality-adjusted life years. Univariate and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness.
Patients: Hypothetical cohort of adults admitted to the ICU.
Interventions: Three prevention strategies were evaluated, including universal decolonization, targeted decolonization, and screening and isolation. Because prevention strategies have a screening component, the screening test in the model was varied to reflect commonly used screening test categories, including conventional culture, chromogenic agar, and polymerase chain reaction.
Measurements and Main Results: Universal and targeted decolonization are less costly and more effective than screening and isolation. This is consistent for all screening tests. When compared with targeted decolonization, universal decolonization is cost-saving to cost-effective, with maximum cost savings occurring when a hospital uses more expensive screening tests like polymerase chain reaction. Results were robust to sensitivity analyses.
Conclusions: As compared with screening and isolation, the current standard practice in ICUs, targeted decolonization, and universal decolonization are less costly and more effective. This supports updating the standard practice to a decolonization approach.
La dysglycémie, facteur de mauvais pronostic post-ACR et plus fréquent à 33°C ?
Borgquist et al., CCM, 2017
Dysglycemia and glycemic variability are associated with poor outcomes in critically ill patients. Targeted temperature management alters blood glucose homeostasis. We investigated the association between blood glucose concentrations and glycemic variability and the neurologic outcomes of patients randomized to targeted temperature management at 33°C or 36°C after cardiac arrest.
Post hoc analysis of the multicenter TTM-trial. Primary outcome of this analysis was neurologic outcome after 6 months, referred to as “Cerebral Performance Category.”
Thirty-six sites in Europe and Australia.
All 939 patients with out-of-hospital cardiac arrest of presumed cardiac cause that had been included in the TTM-trial.
Targeted temperature management at 33°C or 36°C.
Measurements and Main Results
Nonparametric tests as well as multiple logistic regression and mixed effects logistic regression models were used. Median glucose concentrations on hospital admission differed significantly between Cerebral Performance Category outcomes (p < 0.0001). Hyper- and hypoglycemia were associated with poor neurologic outcome (p = 0.001 and p = 0.054). In the multiple logistic regression models, the median glycemic level was an independent predictor of poor Cerebral Performance Category (Cerebral Performance Category, 3–5) with an odds ratio (OR) of 1.13 in the adjusted model (p = 0.008; 95% CI, 1.03–1.24). It was also a predictor in the mixed model, which served as a sensitivity analysis to adjust for the multiple time points. The proportion of hyperglycemia was higher in the 33°C group compared with the 36°C group.
Higher blood glucose levels at admission and during the first 36 hours, and higher glycemic variability, were associated with poor neurologic outcome and death. More patients in the 33°C treatment arm had hyperglycemia.
ECMO dans la décompensation cardiaque aigue ?
Dangers et al., CCM, 2017
Long-term outcomes of patients treated with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure (i.e., cardiogenic shock complicating chronic cardiomyopathy) have not yet been reported. This study was undertaken to describe their outcomes and determine mortality-associated factors.
Retrospective analysis of data prospectively collected.
Twenty-six–bed tertiary hospital ICU.
One hundred five patients implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure.
Measurements and Main Results
From March 2007 to January 2015, 105 patients were implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure in our ICU (67% of them had an intraaortic balloon pump to unload the left ventricle). Their 1-year survival rate was 42%; most of the survivors were transplanted either directly or after switching to central bilateral centrifugal pump, ventricular-assist device, or total artificial heart. Most deaths occurred early after multiple organ failure. Multivariable analyses retained (odds ratio [95% CI]) pre–extracorporeal membrane oxygenation Sequential Organ Failure Assessment score of more than 11 (3.3 [1.3–8.3]), idiopathic cardiomyopathy (0.4 [0.2–1]), cardiac disease duration greater than 2 years pre–extracorporeal membrane oxygenation (2.8 [1.2–6.9]), and pre–extracorporeal membrane oxygenation blood lactate greater than 4 mmol/L (2.6 [1.03–6.4]) as independent predictors of 1-year mortality. Only 17% of patients with pre–extracorporeal membrane oxygenation Sequential Organ Failure Assessment scores of 14 or more survived, whereas 52% of those with scores less than 7 and 60% of those with scores 7 or more and less than 11 were alive 1 year later.
Among this selected cohort of 105 patients implanted with venoarterial-extracorporeal membrane oxygenation for acute decompensated heart failure, 1-year survival was 42%, but better for patients with pre–extracorporeal membrane oxygenation Sequential Organ Failure Assessment scores of less than 11. Venoarterial-extracorporeal membrane oxygenation should be considered for patients with acute decompensated heart failure, but timing of implantation is crucial.
Transfusion massive non traumatique : vers des recommandations différentes ?
Etchill et al., CCM, 2017
Although balanced resuscitation has become integrated into massive transfusion practice, there is a paucity of evidence supporting the delivery of high ratios of plasma and platelet to RBCs in the nontrauma setting. This study investigated the administration of blood component ratios in the massively transfused nontrauma demographic.
Retrospective analysis of a prospective, observational cohort of massively bleeding patients.
Surgical and critically ill patients at a tertiary medical center between 2011 and 2015.
Massively transfused nontrauma patients.
Patients receiving plasma, platelet, and RBC transfusions were categorized into high and low ratio groups and analyzed for differences in characteristics and clinical outcomes.
Measurements and Main Results
The primary outcome was 30-day mortality. Secondary outcomes included 48-hour mortality, hospital length of stay, ICU length of stay, and ventilator-free days. Among 601 massively transfused nontrauma patients, cardiothoracic surgery and gastrointestinal or hepato-pancreatico-biliary bleeds were the most common indications for massive transfusion. Higher fresh frozen plasma ratios (> 1:2) were not associated with increased 30-day mortality. A high platelets-to-packed RBCs ratio (> 1:2) was associated with decreased 48-hour mortality (10.5% vs 19.3%; p = 0.032), but not 30-day mortality. Fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs ratios were not associated with 30-day mortality hazard ratios after controlling for baseline characteristics and disease severity.
The benefits of higher ratios of fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs described in trials of trauma patients were not observed in this analysis of a nontrauma, massively transfused population. These data suggest that greater than 1:2 ratio transfusion in the setting of massive hemorrhage may not be appropriate for all patients, and that further research to guide appropriate resuscitation strategies in nontrauma patients is warranted.