Biblio du Mois : Octobre-Novembre 2019

 

Ça y est l’hiver est bien arrivé mais c’est aussi bientôt Noël !

La biblio du mois de l’AJAR Paris vous régale sur cette version bimestrielle !

On fait dans la nouveauté avec l’utilisation de la fluoroscopie pour les APD, de nouveaux anti-grippaux, etc.

De la prise en charge multimodale/globale avec des études sur l’impact des visites de famille sur le delirium et du carnet de bord sur le sd de stress post-traumatique, une revue sur la musicothérapie, la publication de l’étude Crash 3 et de la physiologie avec un nouveau match réanimation guidée par la perfusion périphérique versus guidée par le lactate …

Des petits bonus comme l’étude sur les effets pro-bactéricide du Sevoflurane et de l’ischémie-reperfusion appliquée en transplantation rénale= à nous de jouer !

Et puis gros taquet du NEJM avec de belles études sur la cardio/ACR/Ventilation, bref parfait pour notre métier transversal !

Si vous voulez que la biblio du mois soit plus fréquente ou une version différente, n’hésitez pas à nous contacter, on a besoin de vous !

La biblio du mois de l’AJAR Paris : c’est la vôtre 😉

 

 

 

 

 

 

 

Revue sur l’immunodépression liée au sepsis

 

 

https://www.nature.com/articles/nrneph.2017.1653

 

 

  • Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection and represents the major cause of death in the intensive care unit
  • Acute kidney injury is a common organ dysfunction during sepsis, as a consequence of an initial exaggerated inflammatory response
  • Sepsis induces a marked and long-term immunosuppression that shares similarities with immunosenescence or the immune defects described in cancer
  • Immune cell metabolism, epigenetic reprogramming, immune checkpoint inhibitors, suppressive myeloid cells and long-term persistence of immune defects are the focus of current research
  • Immunostimulation is a novel therapeutic option in the most immunosuppressed patients with sepsis; results of clinical trials evaluating IL-7 and granulocyte–macrophage colony-stimulating factor (GM-CSF) in the treatment of sepsis are expected to be published in 2018
  • Companion biomarkers are desirable to evaluate immune status, better stratify patients and control immunostimulation effectiveness in a tailored approach to the treatment of sepsis

 

 

 

 

 

 

 

Hypothermie thérapeutique 33°C > 37°C : Retour pour les ACR sur rythmes non-choquables ?

 

https://www.nejm.org/doi/full/10.1056/NEJMoa1906661?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed

DOI: 10.1056/NEJMoa1906661

 

 

Background

Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated.

Methods

We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed.

Results

From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P=0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, −1.9 percentage points; 95% CI, −8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups.

Conclusions

Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia.

 

FiO2 restrictive chez les patients ventilés mécaniquement en réa ?

 

ICU-ROX Investigators

https://www.nejm.org/doi/full/10.1056/NEJMoa1903297?query=TOC

DOI: 10.1056/NEJMoa1903297

 

 

Background

Patients who are undergoing mechanical ventilation in the intensive care unit (ICU) often receive a high fraction of inspired oxygen (Fio2) and have a high arterial oxygen tension. The conservative use of oxygen may reduce oxygen exposure, diminish lung and systemic oxidative injury, and thereby increase the number of ventilator-free days (days alive and free from mechanical ventilation).

Methods

We randomly assigned 1000 adult patients who were anticipated to require mechanical ventilation beyond the day after recruitment in the ICU to receive conservative or usual oxygen therapy. In the two groups, the default lower limit for oxygen saturation as measured by pulse oximetry (Spo2) was 90%. In the conservative-oxygen group, the upper limit of the Spo2 alarm was set to sound when the level reached 97%, and the Fio2 was decreased to 0.21 if the Spo2 was above the acceptable lower limit. In the usual-oxygen group, there were no specific measures limiting the Fio2 or the Spo2. The primary outcome was the number of ventilator-free days from randomization until day 28.

Results

The number of ventilator-free days did not differ significantly between the conservative-oxygen group and the usual-oxygen group, with a median duration of 21.3 days (interquartile range, 0 to 26.3) and 22.1 days (interquartile range, 0 to 26.2), respectively, for an absolute difference of −0.3 days (95% confidence interval [CI], −2.1 to 1.6; P=0.80). The conservative-oxygen group spent more time in the ICU with an Fio2 of 0.21 than the usual-oxygen group, with a median duration of 29 hours (interquartile range, 5 to 78) and 1 hour (interquartile range, 0 to 17), respectively (absolute difference, 28 hours; 95% CI, 22 to 34); the conservative-oxygen group spent less time with an Spo2 exceeding 96%, with a duration of 27 hours (interquartile range, 11 to 63.5) and 49 hours (interquartile range, 22 to 112), respectively (absolute difference, 22 hours; 95% CI, 14 to 30). At 180 days, mortality was 35.7% in the conservative-oxygen group and 34.5% in the usual-oxygen group, for an unadjusted odds ratio of 1.05 (95% CI, 0.81 to 1.37).

Conclusions

In adults undergoing mechanical ventilation in the ICU, the use of conservative oxygen therapy, as compared with usual oxygen therapy, did not significantly affect the number of ventilator-free days.

SCA –> Brilique ou Efient alors ?

 

 

N Engl J Med 2019; 381:1524-1534
DOI: 10.1056/NEJMoa1908973

https://www.nejm.org/doi/full/10.1056/NEJMoa1908973?query=TOC

 

 

Background

The relative merits of ticagrelor as compared with prasugrel in patients with acute coronary syndromes for whom invasive evaluation is planned are uncertain.

Methods

In this multicenter, randomized, open-label trial, we randomly assigned patients who presented with acute coronary syndromes and for whom invasive evaluation was planned to receive either ticagrelor or prasugrel. The primary end point was the composite of death, myocardial infarction, or stroke at 1 year. A major secondary end point (the safety end point) was bleeding.

Results

A total of 4018 patients underwent randomization. A primary end-point event occurred in 184 of 2012 patients (9.3%) in the ticagrelor group and in 137 of 2006 patients (6.9%) in the prasugrel group (hazard ratio, 1.36; 95% confidence interval [CI], 1.09 to 1.70; P=0.006). The respective incidences of the individual components of the primary end point in the ticagrelor group and the prasugrel group were as follows: death, 4.5% and 3.7%; myocardial infarction, 4.8% and 3.0%; and stroke, 1.1% and 1.0%. Definite or probable stent thrombosis occurred in 1.3% of patients assigned to ticagrelor and 1.0% of patients assigned to prasugrel, and definite stent thrombosis occurred in 1.1% and 0.6%, respectively. Major bleeding (as defined by the Bleeding Academic Research Consortium scale) was observed in 5.4% of patients in the ticagrelor group and in 4.8% of patients in the prasugrel group (hazard ratio, 1.12; 95% CI, 0.83 to 1.51; P=0.46).

Conclusions

Among patients who presented with acute coronary syndromes with or without ST-segment elevation, the incidence of death, myocardial infarction, or stroke was significantly lower among those who received prasugrel than among those who received ticagrelor, and the incidence of major bleeding was not significantly different between the two groups.

PAC vs ATL/stent pour les coronaropathies de niveau de complexité bas ou intermédiaire

 

 

 

Gregg W. Stone, et al.

September 28, 2019
DOI: 10.1056/NEJMoa1909406

https://www.nejm.org/doi/10.1056/NEJMoa1909406

 

 

 

Background

Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established.

Methods

We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt–chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction.

Results

At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], −0.9 to 6.5; P=0.13). Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1). In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, −1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, −1.3 to 4.2) were not significantly different. All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, −1.9 percentage points; 95% CI, −3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, −0.8 percentage points; 95% CI, −2.4 to 0.9). Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0).

Conclusions

In patients with left main coronary artery disease of low or intermediate anatomical complexity, there was no significant difference between PCI and CABG with respect to the rate of the composite outcome of death, stroke, or myocardial infarction at 5 years.

Intérêt de l’Augmentin 48h dans la prévention de PAVM précoce post-ACR ?

Bruno François, et al. N Engl J Med 2019; 381:1831-1842

DOI: 10.1056/NEJMoa1812379

BACKGROUND

Patients who are treated with targeted temperature management after out-of-hospital cardiac arrest with shockable rhythm are at increased risk for ventilator-associated pneumonia. The benefit of preventive short-term antibiotic therapy has not been shown.

METHODS

We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving adult patients (>18 years of age) in intensive care units (ICUs) who were being mechanically ventilated after out-of-hospital cardiac arrest related to initial shockable rhythm and treated with targeted temperature management at 32 to 34°C. Patients with ongoing antibiotic therapy, chronic colonization with multidrug-resistant bacteria, or moribund status were excluded. Either intravenous amoxicillin–clavulanate (at doses of 1 g and 200 mg, respectively) or placebo was administered three times a day for 2 days, starting less than 6 hours after the cardiac arrest. The primary outcome was early ventilator-associated pneumonia (during the first 7 days of hospitalization). An independent adjudication committee determined diagnoses of ventilator-associated pneumonia.

RESULTS

A total of 198 patients underwent randomization, and 194 were included in the analysis. After adjudication, 60 cases of ventilator-associated pneumonia were confirmed, including 51 of early ventilator-associated pneumonia. The incidence of early ventilator-associated pneumonia was lower with antibiotic prophylaxis than with placebo (19 patients [19%] vs. 32 [34%]; hazard ratio, 0.53; 95% confidence interval, 0.31 to 0.92; P=0.03). No significant differences between the antibiotic group and the control group were observed with respect to the incidence of late ventilator-associated pneumonia (4% and 5%, respectively), the number of ventilator-free days (21 days and 19 days), ICU length of stay (5 days and 8 days if patients were discharged and 7 days and 7 days if patients had died), and mortality at day 28 (41% and 37%). At day 7, no increase in resistant bacteria was identified. Serious adverse events did not differ significantly between the two groups.

CONCLUSIONS

A 2-day course of antibiotic therapy with amoxicillin–clavulanate in patients receiving a 32-to-34°C targeted temperature management strategy after out-of-hospital cardiac arrest with initial shockable rhythm resulted in a lower incidence of early ventilator-associated pneumonia than placebo. No significant between-group differences were observed for other key clinical variables, such as ventilator-free days and mortality at day 28.

Colchicine 0.5mg/j comme traitement adjuvant débutée dans les 30j post-IDM ?

 

 

Jean-Claude Tardif, et al.

https://www.nejm.org/doi/10.1056/NEJMoa1912388

November 16, 2019
DOI: 10.1056/NEJMoa1912388

 

 

BACKGROUND

Experimental and clinical evidence support the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.

METHODS

We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.

RESULTS

A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P=0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P=0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P=0.03).

CONCLUSIONS

Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo.

CRASH-3 : Que vive l’Acide Tranexamique !

 

 

The CRASH-3 trial collaborators, October 14, 2019

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32233-0/fulltext

 

 

Background

Tranexamic acid reduces surgical bleeding and decreases mortality in patients with traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury (TBI) and can cause brain herniation and death. We aimed to assess the effects of tranexamic acid in patients with TBI.

Methods

This randomised, placebo-controlled trial was done in 175 hospitals in 29 countries. Adults with TBI who were within 3 h of injury, had a Glasgow Coma Scale (GCS) score of 12 or lower or any intracranial bleeding on CT scan, and no major extracranial bleeding were eligible. The time window for eligibility was originally 8 h but in 2016 the protocol was changed to limit recruitment to patients within 3 h of injury. This change was made blind to the trial data, in response to external evidence suggesting that delayed treatment is unlikely to be effective. We randomly assigned (1:1) patients to receive tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was head injury-related death in hospital within 28 days of injury in patients treated within 3 h of injury. We prespecified a sensitivity analysis that excluded patients with a GCS score of 3 and those with bilateral unreactive pupils at baseline. All analyses were done by intention to treat. This trial was registered with ISRCTN (ISRCTN15088122), ClinicalTrials.gov (NCT01402882), EudraCT (2011-003669-14), and the Pan African Clinical Trial Registry (PACTR20121000441277).

Results

Between July 20, 2012, and Jan 31, 2019, we randomly allocated 12 737 patients with TBI to receive tranexamic acid (6406 [50·3%] or placebo [6331 [49·7%], of whom 9202 (72·2%) patients were treated within 3 h of injury. Among patients treated within 3 h of injury, the risk of head injury-related death was 18·5% in the tranexamic acid group versus 19·8% in the placebo group (855 vs 892 events; risk ratio [RR] 0·94 [95% CI 0·86–1·02]). In the prespecified sensitivity analysis that excluded patients with a GCS score of 3 or bilateral unreactive pupils at baseline, the risk of head injury-related death was 12·5% in the tranexamic acid group versus 14·0% in the placebo group (485 vs 525 events; RR 0·89 [95% CI 0·80–1·00]). The risk of head injury-related death reduced with tranexamic acid in patients with mild-to-moderate head injury (RR 0·78 [95% CI 0·64–0·95]) but not in patients with severe head injury (0·99 [95% CI 0·91–1·07]; p value for heterogeneity 0·030). Early treatment was more effective than was later treatment in patients with mild and moderate head injury (p=0·005) but time to treatment had no obvious effect in patients with severe head injury (p=0·73). The risk of vascular occlusive events was similar in the tranexamic acid and placebo groups (RR 0·98 (0·74–1·28). The risk of seizures was also similar between groups (1·09 [95% CI 0·90–1·33]).

Interpretation

Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury.

Bolus de 500mL de cristalloïdes à l’intubation en Réa : inutile ?

Background

Tracheal intubation is common in the care of critically ill adults and is frequently complicated by hypotension, cardiac arrest, or death. We aimed to evaluate administration of an intravenous fluid bolus to prevent cardiovascular collapse during intubation of critically ill adults.

Methods

We did a pragmatic, multicentre, unblinded, randomised trial in nine sites (eight ICUs and one emergency department) around the USA. Critically ill adults (≥18 years) undergoing tracheal intubation were randomly assigned (1:1, block sizes of 2, 4, and 6, stratified by study site) to either an intravenous infusion of 500 mL of crystalloid solution or no fluid bolus. The primary outcome, assessed in the intention-to-treat population, was cardiovascular collapse, defined as a new systolic blood pressure <65 mm Hg; new or increased vasopressor receipt between induction and 2 min after tracheal intubation; or cardiac arrest or death within 1 h of tracheal intubation. Adverse events were assessed in the as-treated population. This trial, which is now complete, is registered with ClinicalTrials.gov, number NCT03026777.

Findings

Patients were enrolled from Feb 6, 2017, to Jan 9, 2018, when the data and safety monitoring board stopped the trial on the basis of futility. By trial termination, 337 (63%) of 537 screened adults had been randomly assigned. Cardiovascular collapse occurred in 33 (20%) of 168 patients in the fluid bolus group compared with 31 (18%) of 169 patients in the no fluid bolus group (absolute difference 1·3% [95% CI −7·1% to 9·7%]; p=0·76). The individual components of the cardiovascular collapse composite outcome did not differ between groups (new systolic blood pressure <65 mm Hg 11 [7%] in the bolus group vs ten [6%] in the no-bolus group, new or increased vasopressor 32 [19%] vs 31 [18%], cardiac arrest within 1 h seven [4%] vs two [1%], death within 1 h of intubation two [1%] vs one [1%]). In-hospital mortality was not significantly different in the fluid bolus group (48 [29%]) compared with no fluid bolus (59 [35%]).

Interpretation

Administration of an intravenous fluid bolus did not decrease the overall incidence of cardiovascular collapse during tracheal intubation of critically ill adults compared with no fluid bolus in this trial.

 

Nouveaux anti-grippaux ?

 

  • Ig anti-grippe IV

https://www.sciencedirect.com/science/article/pii/S221326001930253X?via%3Dihub

  • Plasma anti-grippe

https://www.sciencedirect.com/science/article/abs/pii/S2213260019301997?via%3Dihub

 

E-VALI : Nouvelle entité à connaitre ?

Background

Since June, 2019, more than 1000 new cases of e-cigarette, or vaping, product use associated lung injury (EVALI) have been reported in the USA. Patients presented with dyspnoea, cough, and were found to be hypoxaemic with bilateral airspace opacities on chest imaging. Most patients required management in the intensive care unit and steroid therapy. All patients recovered with cessation of vaping, supportive care, and steroid therapy and remained symptom free at follow up. E-cigarette use continues to rapidly escalate in the USA, particularly among youth.

Methods

Cases were defined as patients admitted to the University of Rochester Medical Center (Rochester, NY, USA) who had used e-cigarettes or another vaping device in the 30 days before presentation, and who had bilateral airspace opacification on chest imaging (CT or x-ray). Case details were obtained via medical record review and patient interviews over the past 3 months including symptomatology, physical exam data, imaging studies, laboratory data, vaping history, and subsequent outpatient follow-up data. In collaboration with the New York State Department of Health, our hospital developed a novel clinical practice algorithm based on statewide physician feedback along with input from experts in environmental health, medical toxicology, infectious disease, epidemiology, and chronic disease prevention.

Findings

We report 12 cases treated for suspected EVALI at our medical centre between June 6, 2019, and Sept 15, 2019. Ten (83%) patients had dyspnoea, fever, and emesis and nine (75%) had cough. 11 (92%) patients reported the use of e-cigarette cartridges containing tetrahydrocannabinol oil. Although eight (67%) patients required admission to the intensive care unit for hypoxaemic respiratory failure, no deaths occurred. The median hospitalisation duration was 7 days (IQR 7–8). All patients completing follow up (6 [50%]) had resolution of previous chest CT findings and normal spirometry. The clinical algorithm focuses on the key signs and symptoms of EVALI and the importance of ruling out infection and other cardiopulmonary conditions before making a presumptive diagnosis of EVALI.

Interpretation

Patients with suspected EVALI in our cohort had life-threatening hypoxaemia, with 67% requiring management in the intensive care unit. Despite the severity of presentation, similar to previous reports of patients with EVALI, most patients improved within 1–2 weeks of initial presentation after vaping cessation and administration of systemic corticosteroids when needed. Almost all (92%) patients with suspected EVALI reported vaping a THC product, making THC containing e-liquids or oils a key focus on the ongoing nationwide investigations into the cause of EVALI. Additional research is required to understand the potential toxins, underlying pathophysiological mechanisms, and identification of susceptible individuals at higher risk for hospitalisation due to EVALI. To our knowledge we present the first clinical practice algorithm for the evaluation and management of EVALI, which will be useful for both acute management and improved accurate reporting of this life-threatening respiratory illness.

 

 

 

AG vs Sédation pour les thrombectomies d’AVC

 

JAMA. 2019;322(13):1283-1293. doi:10.1001/jama.2019.11455

https://jamanetwork.com/journals/jama/article-abstract/2752061

 

 

 

 

Importance  General anesthesia during thrombectomy for acute ischemic stroke has been associated with poor neurological outcome in nonrandomized studies. Three single-center randomized trials reported no significantly different or improved outcomes for patients who received general anesthesia compared with procedural sedation.

Objective  To detect differences in functional outcome at 3 months between patients who received general anesthesia vs procedural sedation during thrombectomy for anterior circulation acute ischemic stroke.

Data Source  MEDLINE search for English-language articles published from January 1, 1980, to July 31, 2019.

Study Selection  Randomized clinical trials of adults with a National Institutes of Health Stroke Scale score of at least 10 and anterior circulation acute ischemic stroke assigned to receive general anesthesia or procedural sedation during thrombectomy.

Data Extraction and Synthesis  Individual patient data were obtained from 3 single-center, randomized, parallel-group, open-label treatment trials with blinded end point evaluation that met inclusion criteria and were analyzed using fixed-effects meta-analysis.

Main Outcomes and Measures  Degree of disability, measured via the modified Rankin Scale (mRS) score (range 0-6; lower scores indicate less disability), analyzed with the common odds ratio (cOR) to detect the ordinal shift in the distribution of disability over the range of mRS scores.

Results  A total of 368 patients (mean [SD] age, 71.5 [12.9] years; 163 [44.3%] women; median [interquartile range] National Institutes of Health Stroke Scale score, 17 [14-21]) were included in the analysis, including 183 (49.7%) who received general anesthesia and 185 (50.3%) who received procedural sedation. The mean 3-month mRS score was 2.8 (95% CI, 2.5-3.1) in the general anesthesia group vs 3.2 (95% CI, 3.0-3.5) in the procedural sedation group (difference, 0.43 [95% CI, 0.03-0.83]; cOR, 1.58 [95% CI, 1.09-2.29]; P = .02). Among prespecified adverse events, only hypotension (decline in systolic blood pressure of more than 20% from baseline) (80.8% vs 53.1%; OR, 4.26 [95% CI, 2.55-7.09]; P < .001) and blood pressure variability (systolic blood pressure >180 mm Hg or <120 mm Hg) (79.7 vs 62.3%; OR, 2.42 [95% CI, 1.49-3.93]; P < .001) were significantly more common in the general anesthesia group.

Conclusions and Relevance  Among patients with acute ischemic stroke involving the anterior circulation undergoing thrombectomy, the use of protocol-based general anesthesia, compared with procedural sedation, was significantly associated with less disability at 3 months. These findings should be interpreted tentatively, given that the individual trials examined were single-center trials and disability was the primary outcome in only 1 trial.

 

 

 

 

 

Impact des horaires de visite des familles sur le Delirium

 

Regis Goulart Rosa, et al. for the ICU Visits Study Group Investigators and the Brazilian Research in Intensive Care Network (BRICNet)
JAMA. 2019;322(3):216-228. doi:10.1001/jama.2019.8766

https://jamanetwork.com/journals/jama/article-abstract/2738289

 

 

Importance  The effects of intensive care unit (ICU) visiting hours remain uncertain.

Objective  To determine whether a flexible family visitation policy in the ICU reduces the incidence of delirium.

Design, Setting and Participants  Cluster-crossover randomized clinical trial involving patients, family members, and clinicians from 36 adult ICUs with restricted visiting hours (<4.5 hours per day) in Brazil. Participants were recruited from April 2017 to June 2018, with follow-up until July 2018.

Interventions  Flexible visitation (up to 12 hours per day) supported by family education (n = 837 patients, 652 family members, and 435 clinicians) or usual restricted visitation (median, 1.5 hours per day; n = 848 patients, 643 family members, and 391 clinicians). Nineteen ICUs started with flexible visitation, and 17 started with restricted visitation.

Main Outcomes and Measures  Primary outcome was incidence of delirium during ICU stay, assessed using the CAM-ICU. Secondary outcomes included ICU-acquired infections for patients; symptoms of anxiety and depression assessed using the HADS (range, 0 [best] to 21 [worst]) for family members; and burnout for ICU staff (Maslach Burnout Inventory).

Results  Among 1685 patients, 1295 family members, and 826 clinicians enrolled, 1685 patients (100%) (mean age, 58.5 years; 47.2% women), 1060 family members (81.8%) (mean age, 45.2 years; 70.3% women), and 737 clinicians (89.2%) (mean age, 35.5 years; 72.9% women) completed the trial. The mean daily duration of visits was significantly higher with flexible visitation (4.8 vs 1.4 hours; adjusted difference, 3.4 hours [95% CI, 2.8 to 3.9]; P < .001). The incidence of delirium during ICU stay was not significantly different between flexible and restricted visitation (18.9% vs 20.1%; adjusted difference, −1.7% [95% CI, −6.1% to 2.7%]; P = .44). Among 9 prespecified secondary outcomes, 6 did not differ significantly between flexible and restricted visitation, including ICU-acquired infections (3.7% vs 4.5%; adjusted difference, −0.8% [95% CI, −2.1% to 1.0%]; P = .38) and staff burnout (22.0% vs 24.8%; adjusted difference, −3.8% [95% CI, −4.8% to 12.5%]; P = .36). For family members, median anxiety (6.0 vs 7.0; adjusted difference, −1.6 [95% CI, −2.3 to −0.9]; P < .001) and depression scores (4.0 vs 5.0; adjusted difference, −1.2 [95% CI, −2.0 to −0.4]; P = .003) were significantly better with flexible visitation.

Conclusions and Relevance  Among patients in the ICU, a flexible family visitation policy, vs standard restricted visiting hours, did not significantly reduce the incidence of delirium.

 

 

Carnet de bord en réa

 

 

 

Garrouste-Orgeas.

Effect of an ICU Diary on Posttraumatic Stress Disorder Symptoms Among Patients Receiving Mechanical Ventilation. A Randomized Clinical Trial.

JAMA 2019;322(3):229-239

 

 

 

 

Importance  Keeping a diary for patients while they are in the intensive care unit (ICU) might reduce their posttraumatic stress disorder (PTSD) symptoms.

Objectives  To assess the effect of an ICU diary on the psychological consequences of an ICU hospitalization.

Design, Setting, and Participants  Assessor-blinded, multicenter, randomized clinical trial in 35 French ICUs from October 2015 to January 2017, with follow-up until July 2017. Among 2631 approached patients, 709 adult patients (with 1 family member each) who received mechanical ventilation within 48 hours after ICU admission for at least 2 days were eligible, 657 were randomized, and 339 were assessed 3 months after ICU discharge.

Interventions  Patients in the intervention group (n = 355) had an ICU diary filled in by clinicians and family members. Patients in the control group (n = 354) had usual ICU care without an ICU diary.

Main Outcomes and Measures  The primary outcome was significant PTSD symptoms, defined as an Impact Event Scale-Revised (IES-R) score greater than 22 (range, 0-88; a higher score indicates more severe symptoms), measured in patients 3 months after ICU discharge. Secondary outcomes, also measured at 3 months and compared between groups, included significant PTSD symptoms in family members; significant anxiety and depression symptoms in patients and family members, based on a Hospital Anxiety and Depression Scale score greater than 8 for each subscale (range, 0-42; higher scores indicate more severe symptoms; minimal clinically important difference, 2.5); and patient memories of the ICU stay, reported with the ICU memory tool.

Results  Among 657 patients who were randomized (median [interquartile range] age, 62 [51-70] years; 126 women [37.2%]), 339 (51.6%) completed the trial. At 3 months, significant PTSD symptoms were reported by 49 of 164 patients (29.9%) in the intervention group vs 60 of 175 (34.3%) in the control group (risk difference, −4% [95% CI, −15% to 6%]; P = .39). The median (interquartile range) IES-R score was 12 (5-25) in the intervention group vs 13 (6-27) in the control group (difference, −1.47 [95% CI, −1.93 to 4.87]; P = .38). There were no significant differences in any of the 6 prespecified comparative secondary outcomes.

Conclusions and Relevance  Among patients who received mechanical ventilation in the ICU, the use of an ICU diary filled in by clinicians and family members did not significantly reduce the number of patients who reported significant PTSD symptoms at 3 months. These findings do not support the use of ICU diaries for preventing PTSD symptoms.

 

 

Pas d’effets de la Selepressine dans le choc septique ?

 

Pierre-Francois Laterre, et al. for the SEPSIS-ACT Investigators
JAMA. 2019;322(15):1476-1485. doi:10.1001/jama.2019.14607

https://jamanetwork.com/journals/jama/article-abstract/2752580

 

 

Importance  Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects.

Objective  To test whether selepressin improves outcome in septic shock.

Design, Setting, and Participants  An adaptive phase 2b/3 randomized clinical trial comprising 2 parts that included adult patients (n = 868) with septic shock requiring more than 5 μg/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018.

Interventions  Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng/kg/min; n = 585) or to placebo (n = 283), all administered as continuous infusions titrated according to hemodynamic parameters.

Main Outcomes and Measures  Primary end point was ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy–free days, and ICU-free days.

Results  Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR, 17.8-72.4). There were no significant differences in the primary end point (ventilator- and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups; difference, 0.6 [95% CI, −1.3 to 2.4]; P = .30) or key secondary end points (90-day mortality, 40.6% vs 39.4%; difference, 1.1% [95% CI, −6.5% to 8.8%]; P = .77; kidney replacement therapy–free days: 18.5 vs 18.2; difference, 0.3 [95% CI, −2.1 to 2.6]; P = .85; ICU-free days: 12.6 vs 12.2; difference, 0.5 [95% CI, −1.2 to 2.2]; P = .41). Adverse event rates included cardiac arrhythmias (27.9% vs 25.2% of patients), cardiac ischemia (6.6% vs 5.6%), mesenteric ischemia (3.2% vs 2.6%), and peripheral ischemia (2.3% vs 2.3%).

Conclusions and Relevance  Among patients with septic shock receiving norepinephrine, administration of selepressin, compared with placebo, did not result in improvement in vasopressor- and ventilator-free days within 30 days. Further research would be needed to evaluate the potential role of selepressin for other patient-centered outcomes in septic shock.

 

 

 

Pas d’intérêt à un contrôle glycémique strict

 

 

Karen C. Johnston, et al.; for the Neurological Emergencies Treatment Trials Network and the SHINE Trial Investigators
JAMA. 2019;322(4):326-335. doi:10.1001/jama.2019.9346

 

Importance  Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown.

Objectives  To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke.

Design, Setting, and Participants  The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria.

Interventions  Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours.

Main Outcomes and Measures  The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity.

Results  Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, −0.83% [95% CI, −5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]).

Conclusions and Relevance  Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting.

 

 

 

Lefamuline : Nouvel antibiotique pour la PAC ?

 

 

JAMA. 2019;322(17):1661-1671. doi:10.1001/jama.2019.15468

 

Importance  New antibacterials are needed to treat community-acquired bacterial pneumonia (CABP) because of growing antibacterial resistance and safety concerns with standard care.

Objective  To evaluate the efficacy and adverse events of a 5-day oral lefamulin regimen in patients with CABP.

Design, Setting, and Participants  A phase 3, noninferiority randomized clinical trial conducted at 99 sites in 19 countries that included adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 or more CABP symptoms; and 2 or more vital sign abnormalities. The first patient visit was on August 30, 2016, and patients were followed up for 30 days; the final follow-up visit was on January 2, 2018.

Interventions  Patients were randomized 1:1 to receive oral lefamulin (600 mg every 12 hours for 5 days; n = 370) or moxifloxacin (400 mg every 24 hours for 7 days; n = 368).

Main Outcomes and Measures  The US Food and Drug Administration (FDA) primary end point was early clinical response at 96 hours (within a 24-hour window) after the first dose of either study drug in the intent-to-treat (ITT) population (all randomized patients). Responders were defined as alive, showing improvement in 2 or more of the 4 CABP symptoms, having no worsening of any CABP symptoms, and not receiving any nonstudy antibacterial drug for current CABP episode. The European Medicines Agency coprimary end points (FDA secondary end points) were investigator assessment of clinical response at test of cure (5-10 days after last dose) in the modified ITT population and in the clinically evaluable population. The noninferiority margin was 10% for early clinical response and investigator assessment of clinical response.

Results  Among 738 randomized patients (mean age, 57.5 years; 351 women [47.6%]; 360 had a PORT risk class of III or IV [48.8%]), 707 (95.8%) completed the trial. Early clinical response rates were 90.8% with lefamulin and 90.8% with moxifloxacin (difference, 0.1% [1-sided 97.5% CI, –4.4% to ∞]). Rates of investigator assessment of clinical response success were 87.5% with lefamulin and 89.1% with moxifloxacin in the modified ITT population (difference, –1.6% [1-sided 97.5% CI, –6.3% to ∞]) and 89.7% and 93.6%, respectively, in the clinically evaluable population (difference, –3.9% [1-sided 97.5% CI, –8.2% to ∞]) at test of cure. The most frequently reported treatment-emergent adverse events were gastrointestinal (diarrhea: 45/368 [12.2%] in lefamulin group and 4/368 [1.1%] in moxifloxacin group; nausea: 19/368 [5.2%] in lefamulin group and 7/368 [1.9%] in moxifloxacin group).

Conclusions and Relevance  Among patients with CABP, 5-day oral lefamulin was noninferior to 7-day oral moxifloxacin with respect to early clinical response at 96 hours after first dose.

 

 

 

Mécanismes de la néphrotoxicité induite par les antibiotiques chez l’enfant

Downes et al, JAC, 2019

https://academic.oup.com/jac/advance-article-abstract/doi/10.1093/jac/dkz325/5542610?redirectedFrom=fulltext

https://doi.org/10.1093/jac/dkz325

 

 

 

Pas d’intérêt à la pose d’un filtre cave chez les polytrau ?

 

 

Kwok M. Ho,et al., NEJM 2019

https://www.nejm.org/doi/full/10.1056/NEJMoa1806515?query=BUL

DOI: 10.1056/NEJMoa1806515

 

 

Whether early placement of an inferior vena cava filter reduces the risk of pulmonary embolism or death in severely injured patients who have a contraindication to prophylactic anticoagulation is not known.

Methods

In this multicenter, randomized, controlled trial, we assigned 240 severely injured patients (Injury Severity Score >15 [scores range from 0 to 75, with higher scores indicating more severe injury]) who had a contraindication to anticoagulant agents to have a vena cava filter placed within the first 72 hours after admission for the injury or to have no filter placed. The primary end point was a composite of symptomatic pulmonary embolism or death from any cause at 90 days after enrollment; a secondary end point was symptomatic pulmonary embolism between day 8 and day 90 in the subgroup of patients who survived at least 7 days and did not receive prophylactic anticoagulation within 7 days after injury. All patients underwent ultrasonography of the legs at 2 weeks; patients also underwent mandatory computed tomographic pulmonary angiography when prespecified criteria were met.

Results

The median age of the patients was 39 years, and the median Injury Severity Score was 27. Early placement of a vena cava filter did not result in a significantly lower incidence of symptomatic pulmonary embolism or death than no placement of a filter (13.9% in the vena cava filter group and 14.4% in the control group; hazard ratio, 0.99; 95% confidence interval [CI], 0.51 to 1.94; P=0.98). Among the 46 patients in the vena cava filter group and the 34 patients in the control group who did not receive prophylactic anticoagulation within 7 days after injury, pulmonary embolism developed in none of those in the vena cava filter group and in 5 (14.7%) in the control group, including 1 patient who died (relative risk of pulmonary embolism, 0; 95% CI, 0.00 to 0.55). An entrapped thrombus was found in the filter in 6 patients.

Conclusions

Early prophylactic placement of a vena cava filter after major trauma did not result in a lower incidence of symptomatic pulmonary embolism or death at 90 days than no placement of a filter.

On refait le match à la Bayesienne : Réanimation guidée par la perfusion périphérique > guidée par le lactate ?

 

 

Rationale: A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared to lactate-guided resuscitation strategy in patients with septic shock, but the difference in the main outcome, 28-day mortality, did not reach the proposed statistical significance threshold(p=0.06). We tested different analytic methods to aid in the interpretation of these clinically relevant results.

Objectives: To reassess trial results using both Bayesian and frequentist frameworks.

Methods: All patients recruited in the ANDROMEDA-Shock trial were included. Both a post-hoc Bayesian and mixed logistic regression approaches were performed. The first included 4 different priors (optimistic, neutral, null and pessimistic) for mortality endpoints. The probability of having a SOFA in the lower quartile at 72 hours was assessed using Bayesian networks.

Measurements and Main Results: Through a Bayesian approach, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28-days was above 90% for all priors; the probability of benefit at 90-days was also above 90% for all but the pessimistic prior. Using an optimistic prior, the Bayesian intervention odds ratio was 0.63 (95% credible interval 0.41-0.90) and 0.69 (95% credible interval 0.47-1.01) for 28-and 90-days mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were 0.61 (95% CI 0.38-0.92) and 0.70 (95% CI 0.45-1.08), respectively. The odds that that patients in the peripheral perfusion-targeted resuscitation arm had SOFA scores in the lower quartile at 72-hours was 1.55 (95% confidence interval 1.02-2.37).

Conclusions: Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared to a lactated-targeted resuscitation strategy. This reanalysis can aid clinicians interpret the results of the trial

 

 

QUID de la ventilation sous ECMO

 

 

https://www.atsjournals.org/doi/full/10.1164/rccm.201906-1164ED

 

 

 

 

Corticoïdes dans le choc septique : Ce n’était pas un problème de définition…

 

 

Balasubramanian Venkatesh et al.

Anesthesiology. Publish Ahead of Print():, OCTOBER 16, 2019

DOI: 10.1097/ALN.0000000000002955

https://insights.ovid.com/crossref?an=00000542-900000000-96417

 

 

 

Background:

Two recent randomized controlled trials (Adjunctive Glucocorticoid Therapy in Patients with Septic Shock [ADRENAL] and Activated Protein C and Corticosteroids for Human Septic Shock [APROCCHSS]) of corticosteroids in patients with septic shock reported different treatment effects on 90-day mortality. Both trials enrolled patients who met the criteria for septic shock using the second international consensus definitions for sepsis and septic shock (Sepsis-2), but the APROCCHSS trial mandated a greater severity of shock as an inclusion criterion.

Methods:

The authors conducted post hoc sensitivity analyses of the ADRENAL trial to determine the effects of hydrocortisone versus placebo in subgroups selected using third international consensus definitions for sepsis and septic shock (Sepsis-3) diagnostic criteria or APROCCHSS inclusion criteria.

Results:

There were 1,950 subjects (973 hydrocortisone and 977 placebo) who met the Sepsis-3 criteria (ADRENAL–Sepsis-3 cohort) and 905 patients (455 hydrocortisone and 450 placebo) who met the APROCCHSS criteria (ADRENAL–APROCCHSS cohort). At 90 days after randomization, in the ADRENAL–Sepsis-3 cohort, 312 of 963 (32.4%) and 337 of 958 (35.2%) patients assigned to hydrocortisone and placebo, respectively, had died (odds ratio, 0.86; 95% CI, 0.70 to 1.06; P = 0.166). The corresponding figures for the ADRENAL–APROCCHSS cohorts were 187 of 453 (41.3%) and 200 of 445 (44.9%), respectively (odds ratio, 0.84; 95% CI, 0.60 to 1.17; P = 0.303). There was no statistically significant difference in the time to death between the groups during the 90 days after randomization (hazard ratio = 0.87; 95% CI, 0.75 to 1.02; P = 0.082 for ADRENAL–Sepsis-3; and hazard ratio = 0.86; 95% CI, 0.71 to 1.06; P = 0.156 for ADRENAL–APROCCHSS cohorts). In both cohorts, patients assigned to hydrocortisone had faster resolution of shock. In the ADRENAL–Sepsis-3 cohort, patients assigned to hydrocortisone had an increase in the number of days alive and free of mechanical ventilation (57.0 ± 37.2 vs. 53.7 ± 38.2 days; 95% CI, 0.40 to 7.04; P = 0.028) and the number of days alive and free of the intensive care unit (54.3 ± 36.0 vs. 51.0 ± 37.1; 95% CI, 0.82 to 7.24; P = 0.014).

Conclusions:

In a post hoc analysis of the ADRENAL trial participants who fulfilled either the Sepsis-3 or the APROCCHSS inclusion criteria, a continuous infusion of hydrocortisone did not result in a lower 90-day mortality than placebo in septic shock.

 

 

Etude sur l’impact de l’ALR pour la chirurgie de l’épaule

 

 

 

Anesthesiology 12 2019, Vol.131, 1254-1263. doi:https://doi.org/10.1097/ALN.0000000000002865

https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2739448

 

 

 

 

Background: Nerve blocks improve early pain after ambulatory shoulder surgery; impact on postdischarge outcomes is poorly described. Our objective was to measure the association between nerve blocks and health system outcomes after ambulatory shoulder surgery.

Methods: We conducted a population-based cohort study using linked administrative data from 118 hospitals in Ontario, Canada. Adults having elective ambulatory shoulder surgery (open or arthroscopic) from April 1, 2009, to December 31, 2016, were included. After validation of physician billing codes to identify nerve blocks, we used multilevel, multivariable regression to estimate the association of nerve blocks with a composite of unplanned admissions, emergency department visits, readmissions or death within 7 days of surgery (primary outcome) and healthcare costs (secondary outcome). Neurology consultations and nerve conduction studies were measured as safety indicators.

Results: We included 59,644 patients; blocks were placed in 31,073 (52.1%). Billing codes accurately identified blocks (positive likelihood ratio 16.83, negative likelihood ratio 0.03). The composite outcome was not significantly different in patients with a block compared with those without (2,808 [9.0%] vs. 3,424 [12.0%]; adjusted odds ratio 0.96; 95% CI 0.89 to 1.03; P = 0.243). Healthcare costs were greater with a block (adjusted ratio of means 1.06; 95% CI 1.02 to 1.10; absolute increase $325; 95% CI $316 to $333; P = 0.005). Prespecified sensitivity analyses supported these results. Safety indicators were not different between groups.

Conclusions: In ambulatory shoulder surgery, nerve blocks were not associated with a significant difference in adverse postoperative outcomes. Costs were statistically higher with a block, but this increase is not likely clinically relevant.

 

 

Les effets pro-bactéricide du Sevoflurane ?!

 

 

Anesthesiology 12 2019, Vol.131, 1301-1315. doi:https://doi.org/10.1097/ALN.0000000000002992

 

 

 

Background: Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties.

Methods: Murine bone marrow–derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry.

ResultsIn vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group.

Conclusions: Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase–dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.

 

 

 

 

 

Machine Learning pour prédire la mortalité péri-opératoire

 

 

Brian L. Hill1,† et al.

 

 

 

Background

Rapid, preoperative identification of patients with the highest risk for medical complications is necessary to ensure that limited infrastructure and human resources are directed towards those most likely to benefit. Existing risk scores either lack specificity at the patient level or utilise the American Society of Anesthesiologists (ASA) physical status classification, which requires a clinician to review the chart.

Methods

We report on the use of machine learning algorithms, specifically random forests, to create a fully automated score that predicts postoperative in-hospital mortality based solely on structured data available at the time of surgery. Electronic health record data from 53 097 surgical patients (2.01% mortality rate) who underwent general anaesthesia between April 1, 2013 and December 10, 2018 in a large US academic medical centre were used to extract 58 preoperative features.

Results

Using a random forest classifier we found that automatically obtained preoperative features (area under the curve [AUC] of 0.932, 95% confidence interval [CI] 0.910–0.951) outperforms Preoperative Score to Predict Postoperative Mortality (POSPOM) scores (AUC of 0.660, 95% CI 0.598–0.722), Charlson comorbidity scores (AUC of 0.742, 95% CI 0.658–0.812), and ASA physical status (AUC of 0.866, 95% CI 0.829–0.897). Including the ASA physical status with the preoperative features achieves an AUC of 0.936 (95% CI 0.917–0.955).

Conclusions

This automated score outperforms the ASA physical status score, the Charlson comorbidity score, and the POSPOM score for predicting in-hospital mortality. Additionally, we integrate this score with a previously published postoperative score to demonstrate the extent to which patient risk changes during the perioperative period.

 

 

 

Pré-Conditionnement ischémique pré-AG pour la transplantation rénale !

 

 

Kristin V. Veighey et al. BJA, 2019

https://bjanaesthesia.org/article/S0007-0912(19)30593-8/fulltext

DOI: https://doi.org/10.1016/j.bja.2019.07.019

 

 

Background

The REnal Protection Against Ischaemia–Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation.

Methods

In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor–recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss.

Results

There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min−1 (1.73 m)−2 [95% confidence interval, CI: 1.54–7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43–1.43]).

Conclusions

RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia.

 

 

 

 

Consensus/recommandations pour la ventilation protectrice péri-opératoire… Enfin ?

 

 

Christopher C. Young et al.

https://bjanaesthesia.org/article/S0007-0912(19)30647-6/fulltext

DOI: https://doi.org/10.1016/j.bja.2019.08.017

 

 

Revue sur les effets anti-inflammatoires de la Dexmedetomidine

 

https://bjanaesthesia.org/article/S0007-0912(19)30639-7/fulltext

 

 

Recommandations EACTS/EACTA/EBCP sur la CEC

 

https://bjanaesthesia.org/article/S0007-0912(19)30687-7/fulltext

 

 

 

Dégradation du glycocalyx endothélial par les solutés de remplissage

Hippensteel, et al., Crit Care, 2019

https://ccforum.biomedcentral.com/articles/10.1186/s13054-019-2534-2

Background

Intravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfate-enriched structure necessary for vascular homeostasis. We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation.

Methods

We used mass spectrometry to measure plasma heparan sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. We compared plasma heparan sulfate concentrations between sepsis and non-sepsis patients, as well as between sepsis survivors and sepsis non-survivors. We used multivariable linear regression to model the association between volume of intravenous fluids and changes in plasma heparan sulfate.

Results

Consistent with previous studies, median plasma heparan sulfate was elevated in septic shock patients (118 [IQR, 113–341] ng/ml 6 h after presentation) compared to non-infected controls (61 [45–79] ng/ml), as well as in a second cohort of sepsis patients (283 [155–584] ng/ml) at emergency department presentation) compared to controls (177 [144–262] ng/ml). In the larger sepsis cohort, heparan sulfate predicted in-hospital mortality. In both cohorts, multivariable linear regression adjusting for age and severity of illness demonstrated a significant association between volume of intravenous fluids administered during resuscitation and plasma heparan sulfate. In the second cohort, independent of disease severity and age, each 1 l of intravenous fluids administered was associated with a 200 ng/ml increase in circulating heparan sulfate (p = 0.006) at 24 h after enrollment.

Conclusions

Glycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. The volume of intravenous fluids administered during sepsis resuscitation is independently associated with the degree of glycocalyx degradation. These findings suggest a potential mechanism by which intravenous fluid resuscitation strategies may induce iatrogenic endothelial injury.

 

 

 

Revue sur l’ischémie de membre sur ECMO V-A et sa prévention

https://ccforum.biomedcentral.com/articles/10.1186/s13054-019-2541-3

 

Revue sur la vitamine C en Réa

https://ccforum.biomedcentral.com/articles/10.1186/s13054-019-2538-y

Anitra C. Carr Critical Carevolume 23, Article number: 265 (2019)

 

 

Dexamethasone : efficace pour les PTG sur douleurs en plus des NVPO

 

 

 

BACKGROUND: Pain after total knee arthroplasty (TKA) affects postoperative recovery and patient satisfaction. The analgesic benefits of corticosteroids have not been well studied. We, therefore, investigated the analgesic effects of intravenous (IV) dexamethasone (DEX) in patients undergoing a TKA.

METHODS: This was a randomized, double-blind, placebo-controlled trial of 0.15 mg/kg of IV DEX vs saline placebo in unilateral TKA. Fifty patients/arm were recruited. Primary outcomes were pain level, determined by a visual analog scale, and the amount of morphine consumption (mg) =48 hours post-TKA. Secondary outcomes were rates of nausea and vomiting, C-reactive protein concentrations, and functional outcomes.

RESULTS: The DEX group had a significantly lower mean visual analog scale score both at rest and during motion at 12, 15, 18, and 21 hours (P < .05). At 21 hours, the mean difference (?) in pain at rest was -11 points (95% confidence interval [CI], -21 to -2 points; P = .02) while the mean difference in pain during motion was -15 points (95% CI, -25 to -5 points; P = .004). The DEX group also had lower rates of nausea and vomiting: 29/50 (58%) vs 42/50 (84%) (P = .008) and lower mean C-reactive protein level: 89 vs 167, ? = -78 mg/L (95% CI, -100 to -58 mg/L, P < .0001). There were no significant differences in mean morphine consumption by 48 hours, modified Western Ontario and McMaster University Osteoarthritis Index scores, and range of motion of the knee at 3-month follow-up (P > .05).

CONCLUSION: IV DEX relieves postoperative pain between 12 to 21 hours after TKA and may be a useful adjunct for controlling pain in patients undergoing TKA.

 

 

 

 

Sédation à la Dexmedetomidine pour la VNI ?

 

https://www.sciencedirect.com/science/article/pii/S235255681930092X?via%3Dihub

 

 

Background

Although non-invasive ventilation (NIV) is recommended in patients with chest trauma, this procedure may expose to discomfort and even failure due to agitation or excessive pain. We tested the impact of dexmedetomidine on the duration of the first session of NIV.

Methods

This randomised, crossover study enrolled 19 patients with blunt chest trauma who needed NIV. During one cycle comprising two NIV sessions, patients received in a random order an intravenous infusion of dexmedetomidine (0.7 mcg/kg/h) and placebo (saline solution) that was initiated 60 min prior to NIV. Dexmedetomidine (or placebo) was titrated to maintain a Richmond Agitation Sedation Scale (RASS) score between 0 and −3. A 6-h washout period was observed between NIV sessions. The reproducibility of the drug-related effects was tested during a second cycle of two NIV sessions.

Results

During the first cycle, dexmedetomidine prolonged the duration of NIV compared to placebo: 280 min (118–450) (median, 25–75th quartiles) versus 120 min (68–287) respectively, corresponding to a median increased duration of 96 min (12–180) (P = 0.03). Dexmedetomidine was associated with a lower score for RASS: −0.8 (−1.0;0.0) versus 0.0 (−0.5;0.0) (P < 0.01), and reduced respiratory discomfort according to the 10 cm visual similar scale: 0.6 cm (0.0–3.0) versus 2.2 cm (0.0–5.3) (P = 0.05). Pain scores, morphine consumption, and blood gas measurements were comparable between groups. No difference in the duration of non-invasive ventilation was found during the second cycle.

Conclusions

In this pilot trial, dexmedetomidine could facilitate the acceptance of the first session of non-invasive ventilation for patients with chest trauma.

 

 

 

Nouvelle technique fluoroscopique pour trouver l’espace péridural ?

 

 

doi: 10.1213/ANE.0000000000003873

https://journals.lww.com/anesthesia-analgesia/Abstract/2019/11000/Objective_Epidural_Space_Identification_Using.22.aspx

 

 

 

BACKGROUND: Performance of epidural anesthesia and analgesia depends on successful identification of the epidural space (ES). While multiple investigations have described objective and alternative methodologies to identify the ES, traditional loss of resistance (LOR) and fluoroscopy (FC) are currently standard of care in labor and delivery (L&D) and chronic pain (CP) management, respectively. While FC is associated with high success, it exposes patients to radiation and requires appropriate radiological equipment. LOR is simple but subjective and consequently associated with higher failure rates. The purpose of this investigation was to compare continuous, quantitative, real-time, needle-tip pressure sensing using a novel computer-controlled ES identification technology to FC and LOR for lumbar ES identification.

METHODS: A total of 400 patients were enrolled in this prospective randomized controlled noninferiority trial. In the CP management arm, 240 patients scheduled to receive a lumbar epidural steroid injection had their ES identified either with FC or with needle-tip pressure measurement. In the L&D arm, 160 female patients undergoing lumbar epidural catheter placements were randomized to either LOR or needle-tip pressure measurement. Blinded observers determined successful ES identification in both arms. A modified intention-to-treat protocol was implemented, with patients not having the procedure for reasons preceding the intervention excluded. Noninferiority of needle-tip pressure measurement regarding the incidence of successful ES identification was claimed when the lower limit of the 97.27% confidence interval (CI) for the odds ratio (OR) was above 0.50 (50% less likely to identify the ES) and P value for noninferioirty <.023.

RESULTS: Demographics were similar between procedure groups, with a mild imbalance in relation to gender when evaluated through a standardized difference. Noninferiority of needle-tip pressure measurement was demonstrated in relation to FC where pain management patients presented a 100% success rate of ES identification with both methodologies (OR, 1.1; 97.27% CI, 0.52–8.74; P = .021 for noninferiority), and L&D patients experienced a noninferior success rate with the novel technology (97.1% vs 91%; OR, 3.3; 97.27% CI, 0.62–21.54; P = .019) using a a priori noninferiority delta of 0.50.

CONCLUSIONS: Objective lumbar ES identification using continuous, quantitative, real-time, needle-tip pressure measurement with the CompuFlo Epidural Computer Controlled Anesthesia System resulted in noninferior success rates when compared to FC and LOR for CP management and L&D, respectively. Benefits of this novel technology may include nonexposure of patients to radiation and contrast medium and consequently reduced health care costs.

 

 

NICOM : Monitorage ni con ni commode

 

 

https://www.sciencedirect.com/science/article/pii/S1071916419307560?via%3Dihub

 

 

 

Background

The bioreactance technique is a relatively new, totally non-invasive technique used to measure cardiac output that is easy to use. Non Invasive Cardiac Output Monitor (NICOM) is one such system (Cheetah Medical Inc). Although approved by FDA for measurement of stroke volume, there is a paucity of literature validating this technology in decompensated heart failure and cardiogenic shock (CS).

Methods and Results

Fifty patients admitted to our cardiac intensive care unit (CICU) for CS and Swan Ganz catheter guided therapy were prospectively enrolled in the study after informed consent. Simultaneous measurements of cardiac output (CO) were obtained using NICOM, indirect Fick (IF) and bolus thermodilution (TD). Intraclass correlation coefficient (ICC) was used to assess the precision of NICOM for CO using the three repeated measurements of CO over the pooled data. The agreement of the NICOM device in the defined clinical population compared to IF and TD, was evaluated by comparing the Pearson Correlation Coefficient, the Bland-Altman plot, and Lin’s Concordance Correlation Coefficient.

ICC for cardiac output measured by NICOM showed excellent repeatability (ICC = 0.93, 95% CI = 0.92 – 0.94, n = 262) in the pooled data. Pearson Correlation Coefficient for cardiac output measured by NICOM was poor when compared to IF (n = 263, r = 0.132, p = 0.033) and TD (n = 258, r = 0.275, p < 0.001).

Conclusions

NICOM technology is not a reliable method of measuring CO in patients with decompensated heart failure and CS.

 

 

Revue sur la musicothérapie en Réanimation pour le delirium et al sédation/analgésie

 

https://doi.org/10.1016/j.jcrc.2019.06.006

https://www.sciencedirect.com/science/article/abs/pii/S0883944119303193?via%3Dihub

 

 

 

 

Méta-analyse Bithérapie avec aminoside vs Monothérapie : NS

 

 

https://www.sciencedirect.com/science/article/pii/S0924857919303000?via%3Dihub

 

 

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