Biblio du mois : Octobre 2017
6 novembre 2017
Et oui, on vous a épargné à la rentrée mais on ne vous a pas oublié : Voici la biblio du mois de l’AJAR !
Au programme, de la ventilation, histoire de souffler un peu après cette 1ère semaine entre autres articles intéressants en pharmaco (révisions révisions) ou en infectiologie !
Et puis si vous avez manqué le congrès USIC avec nos amis cardiologues, n’oubliez pas que nous brassons la Cardiologie en Anesthésie-Réanimation avec la biblio (on n’oublie pas notamment celle du mois d’août forte en émotion : https://www.ajar-online.fr/biblio-du-mois-aout-2017/).
Ce mois-ci, le thème est aux astuces ! En effet, de nombreux articles pour vous donner des petits trucs pour améliorer (ou au moins discuter de l’amélioration de) la prise en charge de vos patients :
- rebrancher 1h après une épreuve de VS ?
- les médicaments (statines, beta-bloquants) à poursuivre ?
- revascularisation de lésions dans les chocs cardiogéniques ?
- vous connaissiez le mode BIPAP-APRV ?
- bonnes et nouvelles pratiques en anti-infectieux ?
- les indices de sévérité d’une anaphylaxie per-op ?
- … et j’en passe!
On vous donne même des astuces pour publier dans de belles revues… 😉
Et on en profite pour vous rappeler l’article sur les petits moyens pour profiter au mieux de la biblio : https://www.ajar-online.fr/biblio-du-mois-le-tuto-pour-se-maintenir-informe/
En espérant que vous avez passé une bonne rentrée et que ça va continuer… sinon il y aura toujours les évènements AJAR hé ! <3
Recrutement alvéolaire + titration de la PEP : Néfaste ?
ART Investigators, JAMA, 2017
https://jamanetwork.com/journals/jama/article-abstract/2654894
Importance The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain.
Objective To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy.
Design, Setting, and Participants Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS.
Interventions An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory–system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning.
Main Outcomes and Measures The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality.
Results A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95% CI, −2.1 to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.
Conclusions and Relevance In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.
Une admission systématique en Réanimation ne modifie pas la mortalité ?
Guidet et al., JAMA, 2017
https://jamanetwork.com/journals/jama/article-abstract/2654893
Importance The high mortality rate in critically ill elderly patients has led to questioning of the beneficial effect of intensive care unit (ICU) admission and to a variable ICU use among this population.
Objective To determine whether a recommendation for systematic ICU admission in critically ill elderly patients reduces 6-month mortality compared with usual practice.
Design, Setting, and Participants Multicenter, cluster-randomized clinical trial of 3037 critically ill patients aged 75 years or older, free of cancer, with preserved functional status (Index of Independence in Activities of Daily Living ≥4) and nutritional status (absence of cachexia) who arrived at the emergency department of one of 24 hospitals in France between January 2012 and April 2015 and were followed up until November 2015.
Interventions Centers were randomly assigned either to use a program to promote systematic ICU admission of patients (n=1519 participants) or to follow standard practice (n=1518 participants).
Main Outcomes and Measures The primary outcome was death at 6 months. Secondary outcomes included ICU admission rate, in-hospital death, functional status, and quality of life (12-Item Short Form Health Survey, ranging from 0 to 100, with higher score representing better self-reported health) at 6 months.
Results One patient withdrew consent, leaving 3036 patients included in the trial (median age, 85 [interquartile range, 81-89] years; 1361 [45%] men). Patients in the systematic strategy group had an increased risk of death at 6 months (45% vs 39%; relative risk [RR], 1.16; 95% CI, 1.07-1.26) despite an increased ICU admission rate (61% vs 34%; RR, 1.80; 95% CI, 1.66-1.95). After adjustments for baseline characteristics, patients in the systematic strategy group were more likely to be admitted to an ICU (RR, 1.68; 95% CI, 1.54-1.82) and had a higher risk of in-hospital death (RR, 1.18; 95% CI, 1.03-1.33) but had no significant increase in risk of death at 6 months (RR, 1.05; 95% CI, 0.96-1.14). Functional status and physical quality of life at 6 months were not significantly different between groups.
Conclusions and Relevance Among critically ill elderly patients in France, a program to promote systematic ICU admission increased ICU use but did not reduce 6-month mortality. Additional research is needed to understand the decision to admit elderly patients to the ICU.
Efficacité d’un protocole de réanimation dans les pays en voie de développement
Andrews, et al., JAMA, 2017
https://jamanetwork.com/journals/jama/article-abstract/2654854
Importance The effect of an early resuscitation protocol on sepsis outcomes in developing countries remains unknown.
Objective To determine whether an early resuscitation protocol with administration of intravenous fluids, vasopressors, and blood transfusion decreases mortality among Zambian adults with sepsis and hypotension compared with usual care.
Design, Setting, and Participants Randomized clinical trial of 212 adults with sepsis (suspected infection plus ≥2 systemic inflammatory response syndrome criteria) and hypotension (systolic blood pressure ≤90 mm Hg or mean arterial pressure ≤65 mm Hg) presenting to the emergency department at a 1500-bed referral hospital in Zambia between October 22, 2012, and November 11, 2013. Data collection concluded December 9, 2013.
Interventions Patients were randomized 1:1 to either (1) an early resuscitation protocol for sepsis (n = 107) that included intravenous fluid bolus administration with monitoring of jugular venous pressure, respiratory rate, and arterial oxygen saturation and treatment with vasopressors targeting mean arterial pressure (≥65 mm Hg) and blood transfusion (for patients with a hemoglobin level <7 g/dL) or (2) usual care (n = 105) in which treating clinicians determined hemodynamic management.
Main Outcomes and Measures The primary outcome was in-hospital mortality and the secondary outcomes included the volume of intravenous fluid received and receipt of vasopressors.
Results Among 212 patients randomized to receive either the sepsis protocol or usual care, 3 were ineligible and the remaining 209 completed the study and were included in the analysis (mean [SD] age, 36.7 [12.4] years; 117 men [56.0%]; 187 [89.5%] positive for the human immunodeficiency virus). The primary outcome of in-hospital mortality occurred in 51 of 106 patients (48.1%) in the sepsis protocol group compared with 34 of 103 patients (33.0%) in the usual care group (between-group difference, 15.1% [95% CI, 2.0%-28.3%]; relative risk, 1.46 [95% CI, 1.04-2.05]; P = .03). In the 6 hours after presentation to the emergency department, patients in the sepsis protocol group received a median of 3.5 L (interquartile range, 2.7-4.0 L) of intravenous fluid compared with 2.0 L (interquartile range, 1.0-2.5 L) in the usual care group (mean difference, 1.2 L [95% CI, 1.0-1.5 L]; P < .001). Fifteen patients (14.2%) in the sepsis protocol group and 2 patients (1.9%) in the usual care group received vasopressors (between-group difference, 12.3% [95% CI, 5.1%-19.4%]; P < .001).
Conclusions and Relevance Among adults with sepsis and hypotension, most of whom were positive for HIV, in a resource-limited setting, a protocol for early resuscitation with administration of intravenous fluids and vasopressors increased in-hospital mortality compared with usual care. Further studies are needed to understand the effects of administration of intravenous fluid boluses and vasopressors in patients with sepsis across different low- and middle-income clinical settings and patient populations.
Attention aux interactions avec AOD : d’avantage de saignements ?
Chang et al., JAMA, 2017
https://jamanetwork.com/journals/jama/article-abstract/2656168
Importance Non–vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk.
Objective To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation.
Design, Setting, and Participants Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016.
Exposures NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin.
Main Outcomes and Measures Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score.
Results Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P < .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone.
Conclusions and Relevance Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs.
Hypothermie thérapeutique pour les encéphalopathies post-anoxiques péri-natales
https://jamanetwork.com/journals/jama/article-abstract/2658322
Laptook et al., JAMA, 2017
La pharmacologie des ATB : on continue !
Vardakas et al., Lancet ID, 2017
http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30615-1.pdf
DOI: http://dx.doi.org/10.1016/S1473-3099(17)30615-1
Background
The findings of randomised controlled trials (RCT), observational studies, and meta-analyses vary regarding the effectiveness of prolonged β-lactam infusion. We aimed to identify the effectiveness of prolonged versus short-term infusion of antipseudomonal β-lactams in patients with sepsis.
Methods
We did a systematic review and meta-analysis to compare prolonged versus short-term intravenous infusion of antipseudomonal β-lactams in patients with sepsis. Two authors independently searched PubMed, Scopus, and the Cochrane Library of clinical trials until November, 2016, without date or language restrictions. Any RCT comparing mortality or clinical efficacy of prolonged (continuous or ≥3 h) versus short-term (≤60 min) infusion of antipseudomonal β-lactams for the treatment of patients with sepsis was eligible. Studies were excluded if they were not RCTs, the antibiotics in the two arms were not the same, neither mortality nor clinical efficacy was reported, only pharmacokinetic or pharmacodynamic outcomes were reported, or if ten or fewer patients were enrolled or randomised. Data were extracted in prespecified forms and we then did a meta-analysis using a Mantel-Haenszel random-effects model. The primary outcome was all-cause mortality at any timepoint. This meta-analysis is registered with the PROSPERO database, number CRD42016051678, and is reported according to PRISMA guidelines.
Findings
2196 articles were identified and screened, and 22 studies (1876 patients) were included in the meta-analysis. According to the Grading of Recommendations Assessment, Development, and Evaluation tool, the quality of evidence for mortality was high. Carbapenems, penicillins, and cephalosporins were studied. Patients with variable age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, severity of sepsis and renal function were enrolled. Prolonged infusion was associated with lower all-cause mortality than short-term infusion (risk ratio [RR] 0·70, 95% CI 0·56–0·87). Heterogeneity was not observed (p=0·93, I2=0%). The funnel plot and the Egger’s test (p=0·44) showed no evidence of publication bias.
Interpretation
Prolonged infusion of antipseudomonal β-lactams for the treatment of patients with sepsis was associated with significantly lower mortality than short-term infusion. Further studies in specific subgroups of patients according to age, sepsis severity, degree of renal dysfunction, and immunocompetence are warranted.
Efficacité du traitement guidé par la PCT dans les infections respiratoires aigues : méta-analyse
Schuetz et al., Lancet, 2017
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(17)30592-3/fulltext
DOI: http://dx.doi.org/10.1016/S1473-3099(17)30592-3
Recommandations sur la prise en charge des patients Ebola
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31795-6/fulltext
Coronarographie et traitement des lésions coupables chez les patients en choc cardiogénique sur IDM : on revascularise ?
Thiele et al., NEJM, 2017
http://www.nejm.org/doi/full/10.1056/NEJMoa1710261#t=article
DOI: 10.1056/NEJMoa1710261
Background
In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial.
Methods
In this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke.
Results
At 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07). The time to hemodynamic stabilization, the risk of catecholamine therapy and the duration of such therapy, the levels of troponin T and creatine kinase, and the rates of bleeding and stroke did not differ significantly between the two groups.
Conclusions
Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI.
Revue sur les troubles hydro-électrolytiques de l’alcoolique chronique
Palmer et al., NEJM, 2017
http://www.nejm.org/doi/full/10.1056/NEJMra1704724
DOI: 10.1056/NEJMra1704724
En route vers la microbiologie moléculaire !
Cambau et al., ICM, 2017
Purpose
Microbiological diagnosis (MD) of infections remains insufficient. The resulting empirical antimicrobial therapy leads to multidrug resistance and inappropriate treatments. We therefore evaluated the cost-effectiveness of direct molecular detection of pathogens in blood for patients with severe sepsis (SES), febrile neutropenia (FN) and suspected infective endocarditis (SIE).
Methods
Patients were enrolled in a multicentre, open-label, cluster-randomised crossover trial conducted during two consecutive periods, randomly assigned as control period (CP; standard diagnostic workup) or intervention period (IP; additional testing with LightCycler®SeptiFast). Multilevel models used to account for clustering were stratified by clinical setting (SES, FN, SIE).
Results
A total of 1416 patients (907 SES, 440 FN, 69 SIE) were evaluated for the primary endpoint (rate of blood MD). For SES patients, the MD rate was higher during IP than during CP [42.6% (198/465) vs. 28.1% (125/442), odds ratio (OR) 1.89, 95% confidence interval (CI) 1.43–2.50; P < 0.001], with an absolute increase of 14.5% (95% CI 8.4–20.7). A trend towards an association was observed for SIE [35.4% (17/48) vs. 9.5% (2/21); OR 6.22 (0.98–39.6)], but not for FN [32.1% (70/218) vs. 30.2% (67/222), P = 0.66]. Overall, turn-around time was shorter during IP than during CP (22.9 vs. 49.5 h, P < 0.001) and hospital costs were similar (median, mean ± SD: IP €14,826, €18,118 ± 17,775; CP €17,828, €18,653 ± 15,966). Bootstrap analysis of the incremental cost-effectiveness ratio showed weak dominance of intervention in SES patients.
Conclusion
Addition of molecular detection to standard care improves MD and thus efficiency of healthcare resource usage in patients with SES.
Intérêt de la VNI post-extubation chez les BPCO ?
Vargas et al., ICM, 2017
Purpose
Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders.
Methods
A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852).
Results
Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2–6) versus 4 days (IQR 2–7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59–14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07–13.31); p = 0.04].
Conclusions
Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.
Evaluation de l’Early Goal-Directed Nutrition
Allingstrup et al., ICM, 2017
Purpose
We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients.
Methods
We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders.
Results
We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were reasonably balanced between the two groups. The EGDN group had less negative energy (p < 0.001) and protein (p < 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ between the two groups (mean difference 0.0, 95% CI −5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days.
Conclusions
EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients.
Repos d’1h après une épreuve de VS avant extubation ?
Fernandez et al., ICM, 2017
Background
Spontaneous breathing trials (SBT) can be exhausting, but the preventive role of rest has never been studied. This study aimed to evaluate whether reconnection to mechanical ventilation (MV) for 1 h after the effort of a successful SBT could reduce the need for reintubation in critically ill patients.
Methods
Randomized multicenter trial conducted in 17 Spanish medical-surgical intensive care units (Oct 2013–Jan 2015). Patients under MV for longer than 12 h who fulfilled criteria for planned extubation were randomly allocated after a successful SBT to direct extubation (control group) or reconnection to the ventilator for a 1-h rest before extubation (rest group). The primary outcome was reintubation within 48 h. Analysis was by intention to treat.
Results
We recruited 243 patients randomized to the control group and 227 to the rest group. Median time from intubation to SBT did not differ between groups [5.5 (2.7, 9.6) days in the control group vs. 5.7 (2.7, 10.6) in the rest group; p = 0.85]. Reintubation within 48 h after extubation was more common in the control than in the rest group [35 (14%) vs. 12 (5%) patients; OR 0.33; 95% CI 0.16–0.65; p < 0.001]. A multivariable regression model demonstrated that the variables independently associated with reintubation were rest [OR 0.34 (95%CI 0.17–0.68)], APACHE II [OR 1.04 (1.002–1.077)], and days of MV before SBT [OR 1.04 (1.001–1.073)], whereas age, reason for admission, and type and duration of SBT were not.
Conclusion
One-hour rest after a successful SBT reduced the rates of reintubation within 48 h after extubation in critically ill patients.
Biomarqueurs pour diminuer la durée sous antifongiques en empirique ?
Rouzé et al., ICM, 2017
Purpose
The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment.
Methods
Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β–glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14 days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7.
Results
A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.001, OR (95% CI) 62.6 (8.1–486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4–13) vs 13 (12–14) days, p < 0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups.
Conclusions
The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy.
Ventiler les patients avec un SDRA en BIPAP-APRV ?
Zhou et al., ICM, 2017
Purpose
Experimental animal models of acute respiratory distress syndrome (ARDS) have shown that the updated airway pressure release ventilation (APRV) methodologies may significantly improve oxygenation, maximize lung recruitment, and attenuate lung injury, without circulatory depression. This led us to hypothesize that early application of APRV in patients with ARDS would allow pulmonary function to recover faster and would reduce the duration of mechanical ventilation as compared with low tidal volume lung protective ventilation (LTV).
Methods
A total of 138 patients with ARDS who received mechanical ventilation for <48 h between May 2015 to October 2016 while in the critical care medicine unit (ICU) of the West China Hospital of Sichuan University were enrolled in the study. Patients were randomly assigned to receive APRV (n = 71) or LTV (n = 67). The settings for APRV were: high airway pressure (Phigh) set at the last plateau airway pressure (Pplat), not to exceed 30 cmH2O) and low airway pressure ( Plow) set at 5 cmH2O; the release phase (Tlow) setting adjusted to terminate the peak expiratory flow rate to ≥ 50%; release frequency of 10–14 cycles/min. The settings for LTV were: target tidal volume of 6 mL/kg of predicted body weight; Pplat not exceeding 30 cmH2O; positive end-expiratory pressure (PEEP) guided by the PEEP–FiO2 table according to the ARDSnet protocol. The primary outcome was the number of days without mechanical ventilation from enrollment to day 28. The secondary endpoints included oxygenation, Pplat, respiratory system compliance, and patient outcomes.
Results
Compared with the LTV group, patients in the APRV group had a higher median number of ventilator-free days {19 [interquartile range (IQR) 8–22] vs. 2 (IQR 0–15); P < 0.001}. This finding was independent of the coexisting differences in chronic disease. The APRV group had a shorter stay in the ICU (P = 0.003). The ICU mortality rate was 19.7% in the APRV group versus 34.3% in the LTV group (P = 0.053) and was associated with better oxygenation and respiratory system compliance, lower Pplat, and less sedation requirement during the first week following enrollment (P < 0.05, repeated-measures analysis of variance).
Conclusions
Compared with LTV, early application of APRV in patients with ARDS improved oxygenation and respiratory system compliance, decreased Pplat and reduced the duration of both mechanical ventilation and ICU stay.
Evaluation des effets du haut débit sous Optiflow
Mauri et al., ICM, 2017
Purpose
Limited data exist on the correlation between higher flow rates of high-flow nasal cannula (HFNC) and its physiologic effects in patients with acute hypoxemic respiratory failure (AHRF). We assessed the effects of HFNC delivered at increasing flow rate on inspiratory effort, work of breathing, minute ventilation, lung volumes, dynamic compliance and oxygenation in AHRF patients.
Methods
A prospective randomized cross-over study was performed in non-intubated patients with patients AHRF and a PaO2/FiO2 (arterial partial pressure of oxygen/fraction of inspired oxygen) ratio of ≤300 mmHg. A standard non-occlusive facial mask and HFNC at different flow rates (30, 45 and 60 l/min) were randomly applied, while maintaining constant FiO2 (20 min/step). At the end of each phase, we measured arterial blood gases, inspiratory effort, based on swings in esophageal pressure (ΔPes) and on the esophageal pressure–time product (PTPPes), and lung volume, by electrical impedance tomography.
Results
Seventeen patients with AHRF were enrolled in the study. At increasing flow rate, HFNC reduced ΔPes (p < 0.001) and PTPPes (p < 0.001), while end-expiratory lung volume (ΔEELV), tidal volume to ΔPes ratio (VT/ΔPes, which corresponds to dynamic lung compliance) and oxygenation improved (p < 0.01 for all factors). Higher HFNC flow rate also progressively reduced minute ventilation (p < 0.05) without any change in arterial CO2 tension (p = 0.909). The decrease in ΔPes, PTPPes and minute ventilation at increasing flow rates was better described by exponential fitting, while ΔEELV, VT/ΔPes and oxygenation improved linearly.
Conclusions
In this cohort of patients with AHRF, an increasing HFNC flow rate progressively decreased inspiratory effort and improved lung aeration, dynamic compliance and oxygenation. Most of the effect on inspiratory workload and CO2 clearance was already obtained at the lowest flow rate.
Le Trendelenburg latéral contre les PAVM ?
Li Bassi et al., ICM, 2017
https://link.springer.com/content/pdf/10.1007%2Fs00134-017-4858-1.pdf
DOI 10.1007/s00134-017-4858-1
Purpose
The lateral Trendelenburg position (LTP) may hinder the primary pathophysiologic mechanism of ventilator-associated pneumonia (VAP). We investigated whether placing patients in the LTP would reduce the incidence of VAP in comparison with the semirecumbent position (SRP).
Methods
This was a randomized, multicenter, controlled study in invasively ventilated critically ill patients. Two preplanned interim analyses were performed. Patients were randomized to be placed in the LTP or the SRP. The primary outcome, assessed by intention-to-treat analysis, was incidence of microbiologically confirmed VAP. Major secondary outcomes included mortality, duration of mechanical ventilation, and intensive care unit length of stay.
Results
At the second interim analysis, the trial was stopped because of low incidence of VAP, lack of benefit in secondary outcomes, and occurrence of adverse events. A total of 194 patients in the LTP group and 201 in the SRP group were included in the final intention-to-treat analysis. The incidence of microbiologically confirmed VAP was 0.5% (1/194) and 4.0% (8/201) in LTP and SRP patients, respectively (relative risk 0.13, 95% CI 0.02–1.03, p = 0.04). The 28-day mortality was 30.9% (60/194) and 26.4% (53/201) in LTP and SRP patients, respectively (relative risk 1.17, 95% CI 0.86–1.60, p = 0.32). Likewise, no differences were found in other secondary outcomes. Six serious adverse events were described in LTP patients (p = 0.01 vs. SRP).
Conclusions
The LTP slightly decreased the incidence of microbiologically confirmed VAP. Nevertheless, given the early termination of the trial, the low incidence of VAP, and the adverse events associated with the LTP, the study failed to prove any significant benefit. Further clinical investigation is strongly warranted; however, at this time, the LTP cannot be recommended as a VAP preventive measure.
Recommandations sur la prise en charge de paludisme et de dengue sévère en conditions dégradées
Dondorp et al., ICM, 2017
L’EtCO2 comme marqueur de sévérité d’une anaphylaxie per-opératoire ?
de Almeida et al., BJA, 2017
https://academic.oup.com/bja/article-abstract/119/5/900/4157879?redirectedFrom=fulltext
Prompt diagnosis of intra-anaesthetic acute hypersensitivity reactions (AHR) is challenging because of the possible absence and/or difficulty in detecting the usual clinical signs and because of the higher prevalence of alternative diagnoses. Delayed epinephrine administration during AHR, because of incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal CO2 (etCO2) is known to be linked to low cardiac output. Yet, its clinical utility during suspected intra-anaesthetic AHR is not well documented.
Clinical data from the 86 patients of the Neutrophil Activation in Systemic Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking agent were included. Severe AHR was defined as a Grade 3–4 of the Ring and Messmer classification. Causes of AHR were explored following recommended guidelines.
Among the 86 patients, 50% had severe AHR and 69% had a confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial hypotension, hypocapnia and hypoxaemia increased significantly with the severity of AHR. Low etCO2 was the only factor able to distinguish mild [median 3.5 (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in inter-quartile range values, with an area under the receiver operator characteristic curve of 0.92 [95% confidence interval: 0.79–1.00]. Among the 41% of patients who received epinephrine, only half received it as first-line therapy despite international guidelines.
An etCO2 value below 2.6 kPa (20 mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and could facilitate early treatment with titrated doses of epinephrine.
Sevoflurane > Propofol pour la chirurgie pulmonaire ?
de la Gala et al., BJA, 2017
https://academic.oup.com/bja/article-abstract/119/4/655/4100575?redirectedFrom=fulltext
Recent studies report the immunomodulatory lung-protective role of halogenated anaesthetics during lung resection surgery (LRS) but have not investigated differences in clinical postoperative pulmonary complications (PPCs). The main goal of the present study was to compare the effect of sevoflurane and propofol on the incidence of PPCs in patients undergoing LRS. The second aim was to compare pulmonary and systemic inflammatory responses to LRS.
Of 180 patients undergoing LRS recruited, data from 174 patients were analysed. Patients were randomized to two groups (propofol or sevoflurane) and were managed otherwise using the same anaesthetic protocol. Bronchoalveolar lavage (BAL) was performed in both lungs before and after one-lung ventilation for analysis of cytokines. Arterial blood was drawn for measurement of the cytokines analysed in the BAL fluid at five time points. Intraoperative haemodynamic and respiratory parameters, PPCs (defined following the ARISCAT study), and mortality during the first month and yr were recorded.
More PPCs were detected in the propofol group (28.4% vs 14%, OR 2.44 [95% CI, 1.14–5.26]). First-yr mortality was significantly higher in the propofol group (12.5% vs 2.3%, OR 5.37 [95% CI, 1.23–23.54]). Expression of lung and systemic pro-inflammatory cytokines was greater in the propofol group than in the sevoflurane group. Pulmonary and systemic IL-10 release was less in the propofol group.
Our results suggest that administration of sevoflurane during LRS reduces the frequency of the PPCs recorded in our study and attenuates the pulmonary and systemic inflammatory response.
Poursuite des beta-bloquants chez les patients en sepsis ?
Fuchs et al., BJA, 2017
https://academic.oup.com/bja/article-abstract/119/4/616/4083348?redirectedFrom=fulltext
There is growing evidence that beta-blockade may reduce mortality in selected patients with sepsis. However, it is unclear if a pre-existing, chronic oral beta-blocker therapy should be continued or discontinued during the acute phase of severe sepsis and septic shock.
The present secondary analysis of a prospective observational single centre trial compared patient and treatment characteristics, length of stay and mortality rates between adult patients with severe sepsis or septic shock, in whom chronic beta-blocker therapy was continued or discontinued, respectively. The acute phase was defined as the period ranging from two days before to three days after disease onset. Multivariable Cox regression analysis was performed to compare survival outcomes in patients with pre-existing chronic beta-blockade.
A total of 296 patients with severe sepsis or septic shock and pre-existing, chronic oral beta-blocker therapy were included. Chronic beta-blocker medication was discontinued during the acute phase of sepsis in 129 patients and continued in 167 patients. Continuation of beta-blocker therapy was significantly associated with decreased hospital (P=0.03), 28-day (P=0.04) and 90-day mortality rates (40.7% vs 52.7%; P=0.046) in contrast to beta-blocker cessation. The differences in survival functions were validated by a Log-rank test (P=0.01). Multivariable analysis identified the continuation of chronic beta-blocker therapy as an independent predictor of improved survival rates (HR = 0.67, 95%-CI (0.48, 0.95), P=0.03).
Continuing pre-existing chronic beta-blockade might be associated with decreased mortality rates up to 90 days in septic patients.
Statines en traitement habituel associé à une meilleure survie pour les sepsis non sévères ?
Lee et al., BJA, 2017
https://academic.oup.com/bja/article-abstract/119/4/645/4237485?redirectedFrom=fulltext
Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied.
We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications.
We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78–0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78–0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission.
In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.
Moins de curares en chirurgie abdominale pour moins de réadmission ?
Thevatasan et al., BJA, 2017
https://academic.oup.com/bja/article-abstract/119/4/595/4106300?redirectedFrom=fulltext
https://doi.org/10.1093/bja/aex240
We hypothesised that intraoperative non-depolarising neuromuscular blocking agent (NMBA) dose is associated with 30-day hospital readmission.
Data from 13,122 adult patients who underwent abdominal surgery under general anaesthesia at a tertiary care hospital were analysed by multivariable regression, to examine the effects of intraoperatively administered NMBA dose on 30-day readmission (primary endpoint), hospital length of stay, and hospital costs.
Clinicians used cisatracurium (mean dose [SD] 0.19 mg kg−1 [0.12]), rocuronium (0.83 mg kg−1 [0.53]) and vecuronium (0.14 mg kg−1 [0.07]). Intraoperative administration of NMBAs was dose-dependently associated with higher risk of 30-day hospital readmission (adjusted odds ratio 1.89 [95% Confidence Interval (CI) 1.26–2.84] for 5th quintile vs 1st quintile; P for trend: P<0.001), prolonged hospital length of stay (adjusted incidence rate ratio [aIRR] 1.20 [95% CI 1.11–1.29]; P for trend: P<0.001) and increased hospital costs (aIRR 1.18 [95% CI 1.13-1.24]; P for trend: P<0.001). Admission type (same-day vs inpatient surgery) significantly modified the risk (interaction term: aOR 1.31 [95% CI 1.05–1.63], P=0.02), and the adjusted odds of readmission in patients undergoing ambulatory surgical procedures who received high-dose NMBAs vs low-dose NMBAs amounted to 2.61 [95% CI 1.11–6.17], P for trend: P<0.001. Total intraoperative neostigmine dose increased the risk of 30-day readmission (aOR 1.04 [1.0–1.08], P=0.048).
In a retrospective analysis, high doses of NMBAs given during abdominal surgery was associated with an increased risk of 30-day readmission, particularly in patients undergoing ambulatory surgery.
Effets du chewing-gum sur la vidange gastrique ?
(les études sur le chewing-gum : un bon sujet pour publier dans le BJA ? on se rappelle de l’article du chewing-gum dans la prévention des NVPO l’année dernière : https://www.ajar-online.fr/biblio-du-mois-decembre-2016/)
Bouvet et al., BJA, 2017
https://academic.oup.com/bja/article-abstract/119/5/928/4560250?redirectedFrom=fulltext
https://doi.org/10.1093/bja/aex270
Current fasting guidelines allow oral intake of water up to 2 h before induction of anaesthesia. We assessed whether gum chewing affects gastric emptying of 250 ml water and residual gastric fluid volume measured 2 h after ingestion of water.
This prospective randomized observer-blind crossover trial was performed on 20 healthy volunteers who attended two separate study sessions: Control and Chewing gum (chlorophyll flavour, with 2.1 g carbohydrate). Each session started with an ultrasound measurement of the antral area, followed by drinking 250 ml water. Then, volunteers either chewed a sugared gum for 45 min (Chewing gum) or did not (Control). Serial measurements of the antral area were performed during 120 min, and the half-time to gastric emptying (t½), total gastric emptying time, and gastric fluid volume before ingestion of water and 120 min later were calculated.
Gastric emptying of water was not different between sessions; the mean (sdsd) t½ was 23 (10) min in the Control session and 21 (7) min in the Chewing gum session (P=0.52). There was no significant difference between sessions in gastric fluid volumes measured before ingestion of water and 120 min later.
Chewing gum does not affect gastric emptying of water and does not change gastric fluid volume measured 2 h after ingestion of water.
L’Anesthésie associée à une baisse de la substance blanche ?
Block et al., Anesthesiology, 2017
http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2652465
doi:10.1097/ALN.0000000000001808
Background: Anesthetics have neurotoxic effects in neonatal animals. Relevant human evidence is limited. We sought such evidence in a structural neuroimaging study.
Methods: Two groups of children underwent structural magnetic resonance imaging: patients who, during infancy, had one of four operations commonly performed in otherwise healthy children and comparable, nonexposed control subjects. Total and regional brain tissue composition and volume, as well as regional indicators of white matter integrity (fractional anisotropy and mean diffusivity), were analyzed.
Results: Analyses included 17 patients, without potential confounding central nervous system problems or risk factors, who had general anesthesia and surgery during infancy and 17 control subjects (age ranges, 12.3 to 15.2 yr and 12.6 to 15.1 yr, respectively). Whole brain white matter volume, as a percentage of total intracranial volume, was lower for the exposed than the nonexposed group, 37.3 ± 0.4% and 38.9 ± 0.4% (least squares mean ± SE), respectively, a difference of 1.5 percentage points (95% CI, 0.3 to 2.8; P = 0.016). Corresponding decreases were statistically significant for parietal and occipital lobes, infratentorium, and brainstem separately. White matter integrity was lower for the exposed than the nonexposed group in superior cerebellar peduncle, cerebral peduncle, external capsule, cingulum (cingulate gyrus), and fornix (cres) and/or stria terminalis. The groups did not differ in total intracranial, gray matter, and cerebrospinal fluid volumes.
Conclusions: Children who had anesthesia and surgery during infancy showed broadly distributed, decreased white matter integrity and volume. Although the findings may be related to anesthesia and surgery during infancy, other explanations are possible.
Le neurontin : échec dans la réduction du delirium post-op ?
Leung et al., Anesthesiology, 2017
http://anesthesiology.pubs.asahq.org/article.aspx?articleid=2645793
doi:10.1097/ALN.0000000000001804
Background: Postoperative pain and opioid use are associated with postoperative delirium. We designed a single-center, randomized, placebo-controlled, parallel-arm, double-blinded trial to determine whether perioperative administration of gabapentin reduced postoperative delirium after noncardiac surgery.
Methods: Patients were randomly assigned to receive placebo (N = 347) or gabapentin 900 mg (N = 350) administered preoperatively and for the first 3 postoperative days. The primary outcome was postoperative delirium as measured by the Confusion Assessment Method. Secondary outcomes were postoperative pain, opioid use, and length of hospital stay.
Results: Data for 697 patients were included, with a mean ± SD age of 72 ± 6 yr. The overall incidence of postoperative delirium in any of the first 3 days was 22.4% (24.0% in the gabapentin and 20.8% in the placebo groups; the difference was 3.20%; 95% CI, 3.22% to 9.72%; P = 0.30). The incidence of delirium did not differ between the two groups when stratified by surgery type, anesthesia type, or preoperative risk status. Gabapentin was shown to be opioid sparing, with lower doses for the intervention group versus the control group. For example, the morphine equivalents for the gabapentin-treated group, median 6.7 mg (25th, 75th quartiles: 1.3, 20.0 mg), versus control group, median 6.7 mg (25th, 75th quartiles: 2.7, 24.8 mg), differed on the first postoperative day (P = 0.04).
Conclusions: Although postoperative opioid use was reduced, perioperative administration of gabapentin did not result in a reduction of postoperative delirium or hospital length of stay.
Attention aux dysnatrémies dans les hémorragies méningées ?
Okazaki et al., CCM, 2017
doi: 10.1097/SHK.0000000000000897
Introduction: Dysnatremia commonly occur in the intensive care unit (ICU) management of patients with aneurysmal subarachnoid hemorrhage (SAH). However, detailed management strategies have not been provided even by current guidelines. The purposes of this study were to examine the association of abnormal serum sodium levels with unfavorable neurologic outcomes and to identify the target range of serum sodium in patients with SAH.
Methods: We retrospectively reviewed all patients who were consecutively hospitalized with a confirmed diagnosis of SAH between January 2009 and December 2015. Univariate/multivariate analyses were performed to identify the independent predictors of an unfavorable neurologic outcome (modified Rankin scale of 3–6 upon hospital discharge).
Results: There were 131 patients included in this study. Unfavorable neurologic outcomes occurred in 45% of patients. On multiple regression analysis, age, Hunt and Kosnik grade, and serum sodium levels in the ICU at the maximum [odds ratio (OR), 1.18; 95% CI, 1.05–1.35; P < 0.01] and minimum (OR, 0.88; 95% CI, 0.77–0.99; P = 0.048) values were significantly associated with unfavorable neurologic outcomes. The receiver operating characteristic curve analysis showed that the cut-off serum sodium levels were 145 mmol/L for maximum value and 132 mmol/L for minimum value. Patients with hyponatremia and hypernatremia during the first 2 weeks in the ICU accounted for 88.2% of patients with an unfavorable neurologic outcome; whereas, those with normal sodium levels accounted for only 15.6%.
Conclusions: In patients with SAH, both hyponatremia and hypernatremia during ICU management were significantly associated with unfavorable neurologic outcomes.
Le Burn-out sévère : banal chez les réanimateurs ?
Bhatt et al., CCM, 2017
doi: 10.1097/CCM.0000000000002689
Objectives: To determine the prevalence of and risk factors for burnout among critical care medicine physician assistants.
Design: Online survey.
Settings: U.S. ICUs.
Subjects: Critical care medicine physician assistant members of the Society of Critical Care Medicine coupled with personal contacts.
Interventions: None.
Measurements and Main Results: We used SurveyMonkey to query critical care medicine physician assistants on demographics and the full 22-question Maslach Burnout Inventory, a validated tool comprised of three subscales—emotional exhaustion, depersonalization, and achievement. Multivariate regression was performed to identify factors independently associated with severe burnout on at least one subscale and higher burnout scores on each subscale and the total inventory. From 431 critical care medicine physician assistants invited, 135 (31.3%) responded to the survey. Severe burnout was seen on at least one subscale in 55.6%—10% showed evidence of severe burnout on the “exhaustion” subscale, 44% on the “depersonalization” subscale, and 26% on the “achievement” subscale. After multivariable adjustment, caring for fewer patients per shift (odds ratio [95% CI]: 0.17 [0.05–0.57] for 1–5 vs 6–10 patients; p = 0.004) and rarely providing futile care (0.26 [0.07–0.95] vs providing futile care often; p = 0.041) were independently associated with having less severe burnout on at least one subscale. Those caring for 1–5 patients per shift and those providing futile care rarely also had a lower depersonalization scores; job satisfaction was independently associated with having less exhaustion, less depersonalization, a greater sense of personal achievement, and a lower overall burnout score.
Conclusions: Severe burnout is common in critical care medicine physician assistants. Higher patient-to-critical care medicine physician assistant ratios and provision of futile care are risk factors for severe burnout.
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