Biblio du mois : Novembre-Décembre 2019

7 janvier 2020ActualitésLa Biblio du Mois

 

 

 

 

La dernière biblio du mois de l’année 2019 ! Belle et riche, en ce début d’année 2020, on vous livre des vitamines !

Mais est-ce que ça sera utile ? C’est une autre histoire !

A part ça, des études intéressantes sur le point physiopath, de l’infectio, de la douleur, de l’ACR…

Des nouvelles molécules qui pourront nous aider ? En tout cas, une étude qui ne montre pas d’apport d’une aide d’ordinateur à la décision … Un répit avant le grand remplacement ? 😉

 

 

 

Supplémentation en vitamine D en Réa : NS

 

 

N Engl J Med 2019; 381:2529-2540
DOI: 10.1056/NEJMoa1911124

https://www.nejm.org/doi/full/10.1056/NEJMoa1911124?query=emergency-medicine

 

 

Background

Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.

Methods

We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D–deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.

Results

A total of 1360 patients were found to be vitamin D–deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, −2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.

Conclusions

Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D–deficient patients.

 

Antibiothérapie probabiliste en prévention de la PAVM précoce sur les ACR extra-hospitalier ?

 

 

François et al., NEJM, 2019

https://www.nejm.org/doi/full/10.1056/NEJMoa1812379

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.

 

 

 

 

Timing de la chirurgie du RAC très serré asymptomatique

Kang et al., NEJM 2020

DOI: 10.1056/NEJMoa1912846

https://www.nejm.org/doi/full/10.1056/NEJMoa1912846?query=TOC

 

Background

The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial.

Methods

In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up.

Results

In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P=0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years.

Conclusions

Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care.

 

Vitamine E comme marqueur diagnostique d’E-VALI ?

 

 

Blount et al, NEJM, 2019

https://www.nejm.org/doi/10.1056/NEJMoa1916433

DOI: 10.1056/NEJMoa1916433

 

 

Background

The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use–associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung.

Methods

BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.

Results

State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%).

Conclusions

Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States.

Etat de mal épileptique : quels médicaments utiliser ?

 

Kapur et al., NEJM, 2019

DOI: 10.1056/NEJMoa1905795

https://www.nejm/doi/10.1056/NEJMoa1905795

 

Background

The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.

Methods

In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents — levetiracetam, fosphenytoin, and valproate — in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.

Results

A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.

Conclusions

In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events.

Revue sur l’allergie à la pénicilline

 

 

N Engl J Med 2019; 381:2338-2351
DOI: 10.1056/NEJMra1807761

https://www.nejm.org/doi/full/10.1056/NEJMra1807761?query=infectious-disease

 

 

Revue sur la dysfonction du baroréflexe

 

Kaufmann et al., NEJM, 2020

https://www.nejm.org/doi/full/10.1056/NEJMra1509723?query=TOC

DOI: 10.1056/NEJMra1509723

 

 

Epidémie de grippe aux USA

 

https://www.cdc.gov/flu/weekly/#ClinicalLaboratories

 

 

 

Vitamines B1 et C, pas assez pour montrer une différence significative dans le choc septique ?

 

Tomoko Fujii, et al. for the VITAMINS Trial Investigators
JAMA. Published online January 17, 2020. doi:10.1001/jama.2019.22176

https://jamanetwork.com/journals/jama/fullarticle/2759414

 

Importance  It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.

Objective  To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock.

Design, Setting, and Participants  Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.

Interventions  Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days.

Main Outcomes and Measures  The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality.

Results  Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was –0.6 hours (95% CI, –8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported.

Conclusions and Relevance  In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.

 

Transport de polytrau > 20min : Apport des PFC pré-hospitaliers ?

 

 

JAMA Surg. Published online December 18, 2019.
doi:10.1001/jamasurg.2019.5085

 

 

Importance  Both military and civilian clinical practice guidelines include early plasma transfusion to achieve a plasma to red cell ratio approaching 1:1 to 1:2. However, it was not known how early plasma should be given for optimal benefit. Two recent randomized clinical trials were published, with apparently contradictory results. The Prehospital Air Medical Plasma (PAMPer) clinical trial showed a nearly 30% reduction in mortality with plasma transfusion in the prehospital environment, while the Control of Major Bleeding After Trauma (COMBAT) clinical trial showed no survival improvement.

Objective  To facilitate a post hoc combined analysis of the COMBAT and PAMPer trials to examine questions that could not be answered by either clinical trial alone. We hypothesized that prehospital transport time influenced the effects of prehospital plasma on 28-day mortality.

Design, Setting, and Participants  A total of 626 patients in the 2 clinical trials were included. Patients with trauma and hemorrhagic shock were randomly assigned to receive either standard care or 2 U of thawed plasma followed by standard care in the prehospital environment. Data analysis was performed between September 2018 and January 2019.

Interventions  Prehospital transfusion of 2 U of plasma compared with crystalloid-based resuscitation.

Main Outcomes and Measures  The main outcome was 28-day mortality.

Results  In this post hoc analysis of 626 patients (467 men [74.6%] and 159 women [25.4%]; median [interquartile range] age, 42 [27-57] years) who had trauma with hemorrhagic shock, a Cox regression analysis showed a significant overall survival benefit for plasma (hazard ratio [HR], 0.65; 95% CI, 0.47-0.90; P = .01) after adjustment for injury severity, age, and clinical trial cohort (COMBAT or PAMPer). A significant association with prehospital transport time was detected (from arrival on scene to arrival at the trauma center). Increased mortality was observed in patients in the standard care group when prehospital transport was longer than 20 minutes (HR, 2.12; 95% CI, 1.05-4.30; P = .04), while increased mortality was not observed in patients in the prehospital plasma group (HR, 0.78; 95% CI, 0.40-1.51; P = .46). No serious adverse events were associated with prehospital plasma transfusion.

Conclusions and Relevance  These data suggest that prehospital plasma is associated with a survival benefit when transport times are longer than 20 minutes and that the benefit-risk ratio is favorable for use of prehospital plasma.

 

 

Insuffisance cardiaque aigue : vasodilatation vs traitement standard

 

JAMA. 2019;322(23):2292-2302. doi:10.1001/jama.2019.18598

https://jamanetwork.com/journals/jama/fullarticle/2757580

 

 

Importance  Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).

Objective  To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF.

Design, Setting, and Participants  Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019.

Interventions  Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan.

Main Outcomes and Measures  The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days.

Results  Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, −3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%).

Conclusions and Relevance  Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

 

 

Rocuronium vs Succinylcholine en pré-hospitalier en séquence rapide

 

 

JAMA. 2019;322(23):2303-2312. doi:10.1001/jama.2019.18254

https://jamanetwork.com/journals/jama/fullarticle/2757578

 

 

Importance  Rocuronium and succinylcholine are often used for rapid sequence intubation, although the comparative efficacy of these paralytic agents for achieving successful intubation in an emergency setting has not been evaluated in clinical trials. Succinylcholine use has been associated with several adverse events not reported with rocuronium.

Objective  To assess the noninferiority of rocuronium vs succinylcholine for tracheal intubation in out-of-hospital emergency situations.

Design, Setting and Participants  Multicenter, single-blind, noninferiority randomized clinical trial comparing rocuronium (1.2 mg/kg) with succinylcholine (1 mg/kg) for rapid sequence intubation in 1248 adult patients needing out-of-hospital tracheal intubation. Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital emergency medical units. The date of final follow-up was August 31, 2016.

Interventions  Patients were randomly assigned to undergo tracheal intubation facilitated by rocuronium (n = 624) or succinylcholine (n = 624).

Main Outcomes and Measures  The primary outcome was the intubation success rate on first attempt. A noninferiority margin of 7% was chosen. A per-protocol analysis was prespecified as the primary analysis.

Results  Among 1248 patients who were randomized (mean age, 56 years; 501 [40.1%] women), 1230 (98.6%) completed the trial and 1226 (98.2%) were included in the per-protocol analysis. The number of patients with successful first-attempt intubation was 455 of 610 (74.6%) in the rocuronium group vs 489 of 616 (79.4%) in the succinylcholine group, with a between-group difference of −4.8% (1-sided 97.5% CI, −9% to ∞), which did not meet criteria for noninferiority. The most common intubation-related adverse events were hypoxemia (55 of 610 patients [9.0%]) and hypotension (39 of 610 patients [6.4%]) in the rocuronium group and hypoxemia (61 of 616 [9.9%]) and hypotension (62 of 616 patients [10.1%]) in the succinylcholine group.

Conclusions and Relevance  Among patients undergoing endotracheal intubation in an out-of-hospital emergency setting, rocuronium, compared with succinylcholine, failed to demonstrate noninferiority with regard to first-attempt intubation success rate.

 

 

Ouf ! On sait encore soigner sans être aidé par un ordinateur ?

 

JAMA Netw Open. 2019;2(12):e1917094. doi:10.1001/jamanetworkopen.2019.17094

Importance  Sophisticated evidence-based information resources can filter medical evidence from the literature, integrate it into electronic health records, and generate recommendations tailored to individual patients.

Objective  To assess the effectiveness of a computerized clinical decision support system (CDSS) that preappraises evidence and provides health professionals with actionable, patient-specific recommendations at the point of care.

Design, Setting, and Participants  Open-label, parallel-group, randomized clinical trial among internal medicine wards of a large Italian general hospital. All analyses in this randomized clinical trial followed the intent-to-treat principle. Between November 1, 2015, and December 31, 2016, patients were randomly assigned to the intervention group, in which CDSS-generated reminders were displayed to physicians, or to the control group, in which reminders were generated but not shown. Data were analyzed between February 1 and July 31, 2018.

Interventions  Evidence-Based Medicine Electronic Decision Support (EBMEDS), a commercial CDSS covering a wide array of health conditions across specialties, was integrated into the hospital electronic health records to generate patient-specific recommendations.

Main Outcomes and Measures  The primary outcome was the resolution rate, the rate at which medical problems identified and alerted by the CDSS were addressed by a change in practice. Secondary outcomes included the length of hospital stay and in-hospital all-cause mortality.

Results  In this randomized clinical trial, 20 563 patients were admitted to the hospital. Of these, 6480 (31.5%) were admitted to the internal medicine wards (study population) and randomized (3242 to CDSS and 3238 to control). The mean (SD) age of patients was 70.5 (17.3) years, and 54.5% were men. In total, 28 394 reminders were generated throughout the course of the trial (median, 3 reminders per patient per hospital stay; interquartile range [IQR], 1-6). These messages led to a change in practice in approximately 4 of 100 patients. The resolution rate was 38.0% (95% CI, 37.2%-38.8%) in the intervention group and 33.7% (95% CI, 32.9%-34.4%) in the control group, corresponding to an odds ratio of 1.21 (95% CI, 1.11-1.32; P < .001). The length of hospital stay did not differ between the groups, with a median time of 8 days (IQR, 5-13 days) for the intervention group and a median time of 8 days (IQR, 5-14 days) for the control group (P = .36). In-hospital all-cause mortality also did not differ between groups (odds ratio, 0.95; 95% CI, 0.77-1.17; P = .59). Alert fatigue did not differ between early and late study periods.

Conclusions and Relevance  An international commercial CDSS intervention marginally influenced routine practice in a general hospital, although the change did not statistically significantly affect patient outcomes.

 

 

 

 

L’addiction aux opioides problème de santé publique majeur aux states, un mal plus profond que de simples prescriptions abusives ?

« Perhaps the pertinent question isn’t why people turned to opioids, but why didn’t even more people take that path? »

 

https://www.nature.com/articles/d41586-019-02671-9

 

 

 

 

Incidence et mortalité globale, régionale et nationale du sepsis

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32989-7/fulltext

 

 

Background

Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates. Accurate estimates are important to inform and monitor health policy interventions, allocation of resources, and clinical treatment initiatives. We estimated the global, regional, and national incidence of sepsis and mortality from this disorder using data from GBD 2017.

Methods

We used multiple cause-of-death data from 109 million individual death records to calculate mortality related to sepsis among each of the 282 underlying causes of death in GBD 2017. The percentage of sepsis-related deaths by underlying GBD cause in each location worldwide was modelled using mixed-effects linear regression. Sepsis-related mortality for each age group, sex, location, GBD cause, and year (1990–2017) was estimated by applying modelled cause-specific fractions to GBD 2017 cause-of-death estimates. We used data for 8·7 million individual hospital records to calculate in-hospital sepsis-associated case-fatality, stratified by underlying GBD cause. In-hospital sepsis-associated case-fatality was modelled for each location using linear regression, and sepsis incidence was estimated by applying modelled case-fatality to sepsis-related mortality estimates.

Findings

In 2017, an estimated 48·9 million (95% uncertainty interval [UI] 38·9–62·9) incident cases of sepsis were recorded worldwide and 11·0 million (10·1–12·0) sepsis-related deaths were reported, representing 19·7% (18·2–21·4) of all global deaths. Age-standardised sepsis incidence fell by 37·0% (95% UI 11·8–54·5) and mortality decreased by 52·8% (47·7–57·5) from 1990 to 2017. Sepsis incidence and mortality varied substantially across regions, with the highest burden in sub-Saharan Africa, Oceania, south Asia, east Asia, and southeast Asia.

Interpretation

Despite declining age-standardised incidence and mortality, sepsis remains a major cause of health loss worldwide and has an especially high health-related burden in sub-Saharan Africa.

 

 

Amikacine inhalée : non ?

 

Niederman et al., Lancet ID, 2019

https://www.sciencedirect.com/science/article/pii/S1473309919305742?via%3Dihub

https://doi.org/10.1016/S1473-3099(19)30574-2

 

Background

Treatment of ventilated pneumonia is often unsuccessful, even when patients are treated according to established guidelines. Therefore, we aimed to investigate the efficacy of the combination drug device Amikacin Inhale as an adjunctive therapy to intravenous standard-of-care antibiotics for pneumonia caused by Gram-negative pathogens in intubated and mechanically ventilated patients.

Methods

INHALE was a prospective, double-blind, randomised, placebo-controlled, phase 3 study comprising two trials (INHALE 1 and INHALE 2) done in 153 hospital intensive-care units in 25 countries. Eligible patients were aged 18 years or older; had pneumonia that had been diagnosed by chest radiography and that was documented as being caused by or showing two risk factors for a Gram-negative, multidrug-resistant pathogen; were intubated and mechanically ventilated; had impaired oxygenation within 48 h before screening; and had a modified Clinical Pulmonary Infection Score of at least 6. Patients were stratified by region and disease severity (according to their Acute Physiology and Chronic Health Evaluation [APACHE] II score) and randomly assigned (1:1) via an interactive voice-recognition system to receive 400 mg amikacin (Amikacin Inhale) or saline placebo, both of which were aerosolised, administered every 12 h for 10 days via the same synchronised inhalation system, and given alongside standard-of-care intravenous antibiotics. All patients and all staff involved in administering devices and monitoring outcomes were masked to treatment assignment. The primary endpoint, survival at days 28–32, was analysed in all patients who received at least one dose of study drug, were infected with a Gram-negative pathogen, and had an APACHE II score of at least 10 at diagnosis. Safety analyses were done in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, numbers NCT01799993 and NCT00805168.

Findings

Between April 13, 2013, and April 7, 2017, 807 patients were assessed for eligibility and 725 were randomly assigned to Amikacin Inhale (362 patients) or aerosolised placebo (363 patients). 712 patients received at least one dose of study drug (354 in the Amikacin Inhale group and 358 in the placebo group), although one patient assigned to Amikacin Inhale received placebo in error and was included in the placebo group for safety analyses. 508 patients (255 in the Amikacin Inhale group and 253 in the placebo group) were assessed for the primary endpoint. We found no between-group difference in survival: 191 (75%) patients in the Amikacin Inhale group versus 196 (77%) patients in the placebo group survived until days 28–32 (odds ratio 0·841, 95% CI 0·554–1·277; p=0·43). Similar proportions of patients in the two treatment groups had a treatment-emergent adverse event (295 [84%] of 353 patients in the Amikacin Inhale group vs 303 [84%] of 359 patients in the placebo group) or a serious treatment-emergent adverse event (101 [29%] patients vs 97 [27%] patients).

Interpretation

Our findings do not support use of inhaled amikacin adjunctive to standard-of-care intravenous therapy in mechanically ventilated patients with Gram-negative pneumonia.

 

Cefto-Tazo : c’est 3g x3/j

 

 

Kollef et al., Lancet ID, 2019

https://www.sciencedirect.com/science/article/pii/S1473309919304037?via%3Dihub

 

https://doi.org/10.1016/S1473-3099(19)30403-7

 

 

 

https://academic.oup.com/cid/article/70/3/538/5523199

 

https://link.springer.com/article/10.1007/s10096-019-03785-8

L’adjonction de métronidazole IV à la vancomycine orale améliore-t-elle le pronostic des infections à Clostridioides difficile ?

 

 

Une association vancomycine (orale/par tube nasogastrique tube/en lavement rectal) et métronidazole IV est recommandé seulement pour le traitement des infections à Clostridioides difficile (ICD) graves, particulièrement dans les situations d’iléus ou de mégacolon (IDSA2017) et si associées à l’impossibilité d’utiliser la voie orale (ESCMID2014). L’objectif de cette étude a été de comparer l’association métronidazole IV + vancomycine orale versus vancomycine monotherapie.

Methode
Etude rétrospective conduite dans 2 centres des USA entre 2010 et 2018. Les patients adultes hospitalisés ont été inclus s’il présentaient une ICD et étaient traités par vancomycine orale. Ils ont été classés en monotherapie (vancomycine seule) ou association (si du métronidazole IV était associé). La gravité des ICD a été classifiée selon les recommandations de lIDSA. Le critère d’évaluation était le décès ou la colectomie dans les 90 jours.

Resultats
2,114 patients ont été inclus (association: 993; monothérapie: 1,121). 23% d’entre eux ont atteint le critère d’évaluation. 34% des patients étaient classés non graves, 41% graves, et 25% fulminants.
Aucune association entre bi-thérapie et critère d’évaluation n’a été trouvé :

  • Dans la cohorte entière (OR ajusté 1.07, 95% CI 0.79-1.45)
  • Si l’analyse concernait les seuls patients classés ICD fulminate (aOR 1.17, 95% CI 0.65-2.10).

Il n’a pas été trouvé non plus d’association entre bithérapie et récidive

Conclusions
Les auteurs concluent que l’association métronidazole IV + vancomycine orale était largement utilisée pour les formes fulminantes et non fulminantes d’ICD ; mais n’était pas associée à une amélioration du pronostic comparée à vancomycine orale monothérapie.

Interprétation / commentaire
Les preuves appuyant les recommandations d’association proviennent de 2 publications : Olson et al 1994 (52 patient avec ileus), et Rokas et al 2015 (88 patients en USI).
L’argument principal avancé en faveur d’une association repose sur la crainte de concentrations infra thérapeutiques de vancomycine dans la lumière colique du fait d’une perte de la mobilité colique.
Mais les concentrations fécales de vancomycine restent élevées même en cas d’ileus (> 1000 mg/L) et demeurent largement au dessus des CMI de C. difficile (0.75 mg/L à 2 mg/L de selles), même si la fréquence des selles est élevée. La recommandation d’associer métronidazole IV + vancomycine orale chez les patients présentant une forme fulminate d’ICD mérite d’être reconsidérée. La recommandation de ne l’utiliser qu’en situation ou la voie orale est impossible semble avoir du sens.

 

Une association vancomycine (orale/par tube nasogastrique tube/en lavement rectal) et métronidazole IV est recommandé seulement pour le traitement des infections à Clostridioides difficile (ICD) graves, particulièrement dans les situations d’iléus ou de mégacolon (IDSA2017) et si associées à l’impossibilité d’utiliser la voie orale (ESCMID2014). L’objectif de cette étude a été de comparer l’association métronidazole IV + vancomycine orale versus vancomycine monotherapie.

Methode
Etude rétrospective conduite dans 2 centres des USA entre 2010 et 2018. Les patients adultes hospitalisés ont été inclus s’il présentaient une ICD et étaient traités par vancomycine orale. Ils ont été classés en monotherapie (vancomycine seule) ou association (si du métronidazole IV était associé). La gravité des ICD a été classifiée selon les recommandations de lIDSA. Le critère d’évaluation était le décès ou la colectomie dans les 90 jours.

Resultats
2,114 patients ont été inclus (association: 993; monothérapie: 1,121). 23% d’entre eux ont atteint le critère d’évaluation. 34% des patients étaient classés non graves, 41% graves, et 25% fulminants.
Aucune association entre bi-thérapie et critère d’évaluation n’a été trouvé :

  • Dans la cohorte entière (OR ajusté 1.07, 95% CI 0.79-1.45)
  • Si l’analyse concernait les seuls patients classés ICD fulminate (aOR 1.17, 95% CI 0.65-2.10).

Il n’a pas été trouvé non plus d’association entre bithérapie et récidive

Conclusions
Les auteurs concluent que l’association métronidazole IV + vancomycine orale était largement utilisée pour les formes fulminantes et non fulminantes d’ICD ; mais n’était pas associée à une amélioration du pronostic comparée à vancomycine orale monothérapie.

Interprétation / commentaire
Les preuves appuyant les recommandations d’association proviennent de 2 publications : Olson et al 1994 (52 patient avec ileus), et Rokas et al 2015 (88 patients en USI).
L’argument principal avancé en faveur d’une association repose sur la crainte de concentrations infra thérapeutiques de vancomycine dans la lumière colique du fait d’une perte de la mobilité colique.
Mais les concentrations fécales de vancomycine restent élevées même en cas d’ileus (> 1000 mg/L) et demeurent largement au dessus des CMI de C. difficile (0.75 mg/L à 2 mg/L de selles), même si la fréquence des selles est élevée. La recommandation d’associer métronidazole IV + vancomycine orale chez les patients présentant une forme fulminate d’ICD mérite d’être reconsidérée. La recommandation de ne l’utiliser qu’en situation ou la voie orale est impossible semble avoir du sens.

 

 

 

Hyperoxygénation contre les infections post-op : foutaises ?

 

 

Ferrando, et al.

https://doi.org/10.1016/j.bja.2019.10.009

https://www.sciencedirect.com/science/article/pii/S0007091219307767?via%3Dihub

 

 

Background

We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery.

Methods

We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality.

Results

We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59–1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48–1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups.

Conclusions

An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.

 

Cristalloïdes vs colloïdes sur la pression tissulaire en oxygène

 

 

Reiterer et al.

https://doi.org/10.1016/j.bja.2019.08.027

https://www.sciencedirect.com/science/article/abs/pii/S0007091219306816?via%3Dihub

 

 

Background

Sufficient tissue oxygen tension may reduce the risk of postoperative wound infections. Supplemental administration of crystalloids increases subcutaneous oxygen tension (Psqo2). Colloids remain longer in the intravascular system and might therefore increase Psqo2 even more than crystalloids. Therefore, we tested the hypothesis that goal-directed colloid administration increases the perioperative Psqo2 more compared with crystalloid administration.

Methods

We randomly assigned 80 patients undergoing elective open abdominal surgery to receive fluid boluses of hydroxyethyl starch (HES) or lactated Ringer’s (LR) solution guided by oesophageal Doppler. Intraoperative Psqo2 was measured in the upper arm. After operation, we measured the Psqo2 in the upper arm and in the surgical wound.

Results

Forty patients were enrolled in each group. Patients in the colloid group received HES solution 750 ml (500; 1000) and LR solution 1500 ml (1000; 2000). Patients in the crystalloid group received LR solution 2825 ml (2000; 3960). The goal-directed administration of colloids did not improve intraoperative Psqo2 in the arm compared with crystalloid administration (11.4 kPa [9.0; 16.6] vs 11.2 kPa [8.6; 15.1], respectively; P=0.58). Postoperative arm Psqo2 was 8.1 kPa (6.5; 9.6) in the colloid group and 7.3 kPa (5.7; 9.1) in the crystalloid group (P=0.11). Postoperative surgical wound Psqo2 was 10.7 kPa (8.6; 13.4) in the colloid group and 10.1 kPa (8.1; 12.7) in the crystalloid group (P=0.68).

Conclusions

Goal-directed colloid administration did not increase Psqo2 compared with goal-directed crystalloid administration in patients undergoing open abdominal surgery.

 

 

 

 

 

Entérobactéries du groupe 3 –> Méta-analyse sur Carbapénèmes vs Beta-lactamine+Inhibiteur de Beta-lactamase

 

 

Open Forum Infectious Diseases, Volume 6, Issue 7, July 2019, ofz248,

https://academic.oup.com/ofid/article/6/7/ofz248/5498096#.XOfCX9dNLwo.twitter

 

The optimal treatment for potential AmpC-producing Enterobacteriaceae, including Serratia, Providencia, Citrobacter, Enterobacter, and Morganella species, remains unknown. An updated systematic review and meta-analysis of studies comparing beta-lactam/beta-lactamase inhibitors with carbapenems in the treatment of bloodstream infections with these pathogens found no significant difference in 30-day mortality (OR, 1.13; 95% CI, 0.58 – 2.20).

 

Epidémie de la grippe aux USA –> Ce qui nous attend en France ?

 

 

https://www.cdc.gov/flu/weekly/#ClinicalLaboratories

 

 

 

Reclassification des AVC ischémiques selon l’étiologie

 

 

https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.027970

 

Background and Purpose—

Carotid artery plaque with <50% luminal stenosis may be an underappreciated stroke mechanism. We assessed how many stroke causes might be reclassified after accounting for nonstenosing plaques with high-risk features.

Methods—

We included patients enrolled in the Cornell Acute Stroke Academic Registry from 2011 to 2015 who had anterior circulation infarction, magnetic resonance imaging of the brain, and magnetic resonance angiography of the neck. High-risk plaque was identified by intraplaque hemorrhage ascertained from routine neck magnetic resonance angiography studies using validated methods. Infarct location was determined from diffusion-weighted imaging. Intraplaque hemorrhage and infarct location were assessed separately in a blinded fashion by a neuroradiologist. We used the McNemar test for matched data to compare the prevalence of intraplaque hemorrhage ipsilateral versus contralateral to brain infarction. We reclassified stroke subtypes by including large-artery atherosclerosis as a cause if there was intraplaque hemorrhage ipsilateral to brain infarction, regardless of the degree of stenosis.

Results—

Among the 1721 acute ischemic stroke patients registered in the Cornell Acute Stroke Academic Registry from 2011 to 2015, 579 were eligible for this analysis. High-risk plaque was more common ipsilateral versus contralateral to brain infarction in large-artery atherosclerotic (risk ratio [RR], 3.7 [95% CI, 2.2–6.1]), cryptogenic (RR, 2.1 [95% CI, 1.4–3.1]), and cardioembolic strokes (RR, 1.7 [95% CI, 1.1–2.4]). There were nonsignificant ipsilateral-contralateral differences in high-risk plaque among lacunar strokes (RR, 1.2 [95% CI, 0.4–3.5]) and strokes of other determined cause (RR, 1.5 [95% CI, 0.7–3.3]). After accounting for ipsilateral high-risk plaque, 88 (15.2%) patients were reclassified: 38 (22.6%) cardioembolic to multiple potential etiologies, 6 (8.5%) lacunar to multiple, 3 (15.8%) other determined cause to multiple, and 41 (20.8%) cryptogenic to large-artery atherosclerosis.

Conclusions—

High-risk carotid plaque was more prevalent ipsilateral to brain infarction across several ischemic stroke subtypes. Accounting for such plaques may reclassify the etiologies of up to 15% of cases in our sample.

 

 

Méta-analyse : OK pour la thrombolyse chez le patient sous AOD

 

 

https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.026426

 

Pas d’intérêt des valves anti-retour dans les infections ?

 

Koeppen et al., ICM Exp, 2019

https://icm-experimental.springeropen.com/articles/10.1186/s40635-019-0277-7

 

 

Background

In the critically ill, catheter-related bloodstream infection can result from bacterial contamination of infusion hubs of intravascular catheters. Needle-free connectors (NFC) have been suggested to reduce the rate of bacterial contamination and subsequent catheter-related bloodstream infection (CRBSI), but data remains ambiguous. Thus, we tested if a novel NFC would reduce bacterial contamination and subsequent CRBSI.

Results

In a prospective, randomized controlled trial, surgical ICU patients were randomized to three-way hubs closed by caps or Bionecteur® (Vygon, Inc.) of central venous catheters. Every 72 h, infusion lines were renewed and microbiological samples were taken. Bacterial growth was analyzed by blinded microbiologists. Incidence of bacterial contamination and CRSBI were assessed. Outcome parameters like length of stay on ICU and outcome were retrospectively assessed. Two thousand seven hundred patients were screened, 111 were randomized to the NFC, and 109 into the control group. Finally, 24 patients in the NFC and 23 control patients were analyzed. The majority of samples (NFC 77%; control 70%) found no bacterial growth. Coagulase-negative staphylococci were most commonly detected on CVC samples (NFC 17%; control 21%). We found CRBSI (defined as identical pathogens in blood culture and catheter line tip culture, and clinical manifestations of infection) in two control patients and one patient of the NFC group. Their length of ICU stay did not differ between groups (NFC 19 days; control 23 days).

Conclusion

The use of NFC does not influence the rate of bacterial contamination of infusion hubs of central venous catheters.

 

 

Revue sur les décisions de « ne pas intuber » chez les patients en insuffisance respiratoire aigue

 

Wilson et al., Intensive Care Med (2020) 46:36–45

https://doi.org/10.1007/s00134-019-05828-2

https://link.springer.com/epdf/10.1007/s00134-019-05828-2?shared_access_token=pOX_VasJOjzXxwJlkeGQ6_e4RwlQNchNByi7wbcMAY5BvcRVrmqQgSuChqmwsT_JzYQskVb1PR2EtdAv8CxfYdUrRLe0cM7mm4iw_T9qQhhAMvj2mHN9uzQPtlY7wXrtur9wl2giidC-E5eALts5ow%3D%3D&utm_source=newsletter_489&utm_medium=email&utm_campaign=critical-care-reviews-newsletter

 

 

 

Les facteurs associés au risque de décès après la sortie de réa

 

 

Rosa,et al. Critical Care Medicine: January 2020 – Volume 48 – Issue 1 – p 64-72

doi: 10.1097/CCM.0000000000004024

https://journals.lww.com/ccmjournal/fulltext/2020/01000/Early_and_Late_Mortality_Following_Discharge_From.9.aspx

 

 

 

Objectives:To identify the frequency, causes, and risk factors of early and late mortality among general adult patients discharged from ICUs.Design:Multicenter, prospective cohort study.Setting:ICUs of 10 tertiary hospitals in Brazil.

Patients:One-thousand five-hundred fifty-four adult ICU survivors with an ICU stay greater than 72 hours for medical and emergency surgical admissions or greater than 120 hours for elective surgical admissions.

Interventions:None.

Measurements and Main Results:The main outcomes were early (30 d) and late (31 to 365 d) mortality. Causes of death were extracted from death certificates and medical records. Twelve-month cumulative mortality was 28.2% (439 deaths). The frequency of early mortality was 7.9% (123 deaths), and the frequency of late mortality was 22.3% (316 deaths). Infections were the leading cause of death in both early (47.2%) and late (36.4%) periods. Multivariable analysis identified age greater than or equal to 65 years (hazard ratio, 1.65; p = 0.01), pre-ICU high comorbidity (hazard ratio, 1.59; p = 0.02), pre-ICU physical dependence (hazard ratio, 2.29; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.008; p = 0.03), ICU-acquired infections (hazard ratio, 2.25; p < 0.001), and ICU readmission (hazard ratio, 3.76; p < 0.001) as risk factors for early mortality. Age greater than or equal to 65 years (hazard ratio, 1.30; p = 0.03), pre-ICU high comorbidity (hazard ratio, 2.28; p < 0.001), pre-ICU physical dependence (hazard ratio, 2.00; p < 0.001), risk of death at ICU admission (hazard ratio per 1% increase, 1.010; p < 0.001), and ICU readmission (hazard ratios, 4.10, 4.17, and 1.82 for death between 31 and 60 days, 61 and 90 days, and greater than 90 days after ICU discharge, respectively; p < 0.001 for all comparisons) were associated with late mortality.

Conclusions:Infections are the main cause of death after ICU discharge. Older age, pre-ICU comorbidities, pre-ICU physical dependence, severity of illness at ICU admission, and ICU readmission are associated with increased risk of early and late mortality, while ICU-acquired infections are associated with increased risk of early mortality.

 

Revue : N’ayez pas peur de l’Adré IVSE ?

 

 

Belletti, et al., Critical Care Medicine: November 27, 2019 – Volume Online First – Issue –

doi: 10.1097/CCM.0000000000004127

https://journals.lww/ccmjournal/Abstract/onlinefirst/Effect_of_Continuous_Epinephrine_Infusion_on.95782.aspx

 

 

 

 

Revue sur les complications neurologiques sous ECMO

Cho, Sung-Min DO;et al.

Critical Care Medicine
doi: 10.1097/CCM.0000000000004060

https://journals.lww.com/ccmjournal/Abstract/2019/12000/Neurocritical_Care_for_Extracorporeal_Membrane.13.aspx

 

 

 

 

Magic Bullet : Colistine vs Méropénème pour les PAVM

 

 

Cisneros et al., CC, 2020

https://ccforum.biomedcentral.com/articles/10.1186/s13054-019-2627-y

 

 

Background

Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined.

Methods

A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved.

Results

A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p = 0.015).

Conclusions

This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination.

 

 

 

 

 

Un modèle prédictif pour décider de la pose d’une ECMO ?

 

Luregn J. Schlapbach et al., CC, 2019

https://ccforum.biomedcentral.com/articles/10.1186/s13054-019-2685-1

 

 

Background

The surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.

Methods

Retrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO.

Results

Five thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864–0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89–2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39–0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10–0.98, p = 0.046) as significant predictors of survival for those treated with VA-ECMO.

Conclusions

This binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.

 

 

Levosimendan prophylactique en péri-opératoire de chirurgie cardique ?

 

Wang et al., CC, 2019

https://ccforum.biomedcentral.com/articles/10.1186/s13054-019-2704-2

 

Background

The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts.

Methods

This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study.

Results

A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19–1.13; p = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14–3.69, p = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS.

Conclusions

Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo.

 

 

 

Attention à la charge de travail de vos infirmières de réa !

 

Margadant,et al. Critical Care Medicine: January 2020 – Volume 48 – Issue 1 – p 3-9

doi: 10.1097/CCM.0000000000004005
https://journals.lww.com.sirius/ccmjournal/fulltext/2020/01000/The_Nursing_Activities_Score_Per_Nurse_Ratio_Is.2.aspx

 

Objectives:

Studies have shown contradicting results on the association of nursing workload and mortality. Most of these studies expressed workload as patients per nurse ratios; however, this does not take into account that some patients require more nursing time than others. Nursing time can be quantified by tools like the Nursing Activities Score. We investigated the association of the Nursing Activities Score per nurse ratio, respectively, the patients per nurse ratio with in-hospital mortality in ICUs.

Design:

Retrospective analysis of the National Intensive Care Evaluation database.

Setting:

Fifteen Dutch ICUs.

Patients:

All ICU patients admitted to and registered ICU nurses working at 15 Dutch ICUs between January 1, 2016, and January 1, 2018, were included. The association of mean or day 1 patients per nurse ratio and Nursing Activities Score per nurse ratio with in-hospital mortality was analyzed using logistic regression models.

Interventions:

None.

Measurements and Main Results:

Nursing Activities Score per nurse ratio greater than 41 for both mean Nursing Activities Score per nurse ratio as well as Nursing Activities Score per nurse ratio on day 1 were associated with a higher in-hospital mortality (odds ratios, 1.19 and 1.17, respectively). After case-mix adjustment the association between a Nursing Activities Score per nurse ratio greater than 61 for both mean Nursing Activities Score per nurse ratio as well as Nursing Activities Score per nurse ratio on day 1 and in-hospital mortality remained significant (odds ratios, 1.29 and 1.26, respectively). Patients per nurse ratio was not associated with in-hospital mortality.

Conclusions:

A higher Nursing Activities Score per nurse ratio was associated with higher in-hospital mortality. In contrast, no association was found between patients per nurse ratios and in-hospital mortality in The Netherlands. Therefore, we conclude that it is more important to focus on the nursing workload that the patients generate rather than on the number of patients the nurse has to take care of in the ICU.

 

 

 

Revue sur l’ADN mitochondrial comme prédicteur de mortalité des patients en réa

 

https://www.sciencedirect.com/science/article/abs/pii/S0012369219313893?via%3Dihub

 

John S.Harrington et al.

https://doi.org/10.1016/j.chest.2019.07.014

 

 

 

Intérêt de la VS en ATC (Compensation automatique du tube)  ?

 

Guérin et al., AIC, 2019

https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-019-0611-y

 

Background

During spontaneous breathing trial, low-pressure support is thought to compensate for endotracheal tube resistance, but it actually should provide overassistance. Automatic tube compensation is an option available in the ventilator to compensate for flow-resistance of endotracheal tube. Its effects on patient effort have been poorly investigated. We aimed to compare the effects of low-pressure support and automatic tube compensation during spontaneous breathing trial on breathing power and lung ventilation distribution.

Results

We performed a randomized crossover study in 20 patients ready to wean. Each patient received both methods for 30 min separated by baseline ventilation: pressure support 0 cmH2O and automatic tube compensation 100% in one period and pressure support 7 cmH2O without automatic tube compensation in the other period, a 4 cmH2O positive end-expiratory pressure being applied in each. Same ventilator brand (Evita XL, Draeger, Germany) was used. Breathing power was assessed from Campbell diagram with esophageal pressure, airway pressure, flow and volume recorded by a data logger. Lung ventilation distribution was assessed by using electrical impedance tomography (Pulmovista, Draeger, Germany). During the last 2 min of low-pressure support and automatic compensation period breathing power and lung ventilation distribution were measured on each breath. Breathing power generated by the patient’s respiratory muscles was 7.2 (4.4–9.6) and 9.7 (5.7–21.9) J/min in low-pressure support and automatic tube compensation periods, respectively (P = 0.011). Lung ventilation distribution was not different between the two methods.

Conclusions

We found that ATC was associated with higher breathing power than low PS during SBT without altering the distribution of lung ventilation.

 

 

 

shock

 

Revue : Noradrénaline vs Vasopressine

Wu, Zongsheng; et al.

doi: 10.1097/SHK.0000000000001345

 

 

Methoxyflurane inhalé comme nouvel agent analgésique ?

 

Borobia et al.

https://www.annemergmed.com/article/S0196-0644(19)30614-6/pdf

 

 

Study objective:The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over thefirst 20min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This thefirst randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe.

Methods:This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score4 on the11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 tomethoxyflurane (up to 23 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in NumericRating Scale pain intensity score during thefirst 20 minutes of treatment and time tofirst pain relief.

Results:Three hundredfive patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients inthe standard analgesic treatment group (70%) received intravenousfirst-step analgesics and 9.4% of patients were treated withopioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standardanalgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time tofirst pain relief was significantlyshorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient andclinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinicianexpectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment.

Conclusion:These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting,first-linealternative to currently available analgesic treatments for trauma pain.

 

 

La Quetiapine comme nouvel agent contre le Delirium ?

 

Kim et al., J. Clin. Med. 2020, 9(1), 69;

https://www.mdpi.com/2077-0383/9/1/69

 

 

Purpose: To evaluate the efficacy of short-term low-dose quetiapine for delirium prevention in critically ill patients.

Methods: In this prospective, a single-center, randomized, double-blind, placebo-controlled trial, adult patients who were admitted from July 2015 to July 2017 to a medical intensive care unit (ICU) of a tertiary teaching hospital affiliated to Seoul National University were included. Quetiapine (12.5 mg or 25 mg oral at night; N = 16) or placebo (N = 21) was administered according to randomization until ICU discharge or the 10th ICU day. The primary endpoint was the incidence of delirium within the first 10 ICU days. Secondary endpoints included the rate of positive Confusion Assessment Method for the ICU (CAM-ICU) (the number of positive CAM-ICU counts/the number of total CAM-ICU counts), delirium duration, successful extubation, and overall mortality.

Result: The incidence of delirium during the 10 days after ICU admission was 46.7% (7/15) in the quetiapine group and 55.0% (11/20) in the placebo group (p = 0.442). In the quetiapine group, the rate of positive CAM-ICU was significantly lower than in the placebo group (14.4% vs. 37.4%, p = 0.048), delirium duration during the study period was significantly shorter (0.28 day vs. 1.83 days, p = 0.018), and more patients in the quetiapine than in the placebo group were weaned from mechanical ventilation successfully (84.6% vs. 47.1%, p = 0.040).

Conclusions: Our study suggests that prophylactic use of low-dose quetiapine could be helpful for preventing delirium in critically ill patients. A further large-scale prospective study is needed.

 

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