Didier Dreyfuss

Acute kidney injury in critical care: Experience of a conservative strategy

PURPOSEnRenal replacement therapy (RRT) is a major supportive treatment of acute kidney injury (AKI) in intensive care unit (ICU), but the timing of its initiation remains open to debate.nnnMATERIALS AND METHODSnWe retrospectively analyzed ICU patients who had AKI associated with at least one usual RRT criteria: serum creatinine concentration greater than 300 μmol/L, serum urea concentration greater than 25 mmol/L, serum potassium concentration greater than 6.5 mmol/L, severe metabolic acidosis (arterial blood pH<7.2), oliguria (urine output<135 mL/8 hours or <400 mL/24 hours), overload pulmonary edema. To estimate the risk of death associated with RRT adjusted for risk factors, we performed a marginal structural Cox model with inverse-probability-of-treatment-weighted estimator.nnnRESULTSnAmong 4173 patients admitted to the ICU, 203 patients fulfilled potential RRT criteria. Ninety-one patients (44.8%) received RRT and 112 (55.2%) did not. Non-RRT and RRT patients differed in terms of severity of illness: Simplified Acute Physiology Score II (55±17 vs 60±19, respectively; P<.05) and Sequential Organ Failure Assessment score (8 [5-10] vs 9 [7-11], respectively; P=.01). Crude analysis indicated a lower ICU mortality for non-RRT compared with RRT patients (18% vs 45%; P<.001). In the marginal structural Cox model, RRT was associated with increased mortality (P<.01).nnnCONCLUSIONnA conservative approach of AKI was not associated with increased mortality.

Risks of nonsteroidal antiinflammatory drugs in undiagnosed intensive care unit pneumococcal pneumonia: younger and more severely affected patients.

PURPOSEnThe purpose of this study is to investigate whether exposure to nonsteroidal antiinflammatory drugs (NSAIDs) at the early stage of severe pneumococcal community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission may affect its presentation and outcome.nnnMATERIAL AND METHODSnMedical records of ICU adult patients (12-year period) with a pneumococcal CAP diagnosis were retrospectively analyzed according to previous NSAID exposure.nnnRESULTSnOne hundred six confirmed pneumococcal CAP were identified, 20 received NSAIDs within 4 (2-6) days before admission. Nonsteroidal antiinflammatory drug-exposed patients were younger (43.3 vs 62.2 years; P < .0001), had less frequently at least one chronic comorbid condition (40% vs 75%; P = .003), had more often complicated pleural effusions (20% vs 2.3%; P = .01), and more frequent pleuropulmonary complications (odds ratio: 5.75 [1.97-16.76]). Nonsteroidal antiinflammatory drug patients required more often noninvasive ventilatory support (25% vs 4.6%; P = .003). Intensive care unit length of stay and mortality were similar.nnnCONCLUSIONSnWe report as severe pneumococcal pneumonia in young and healthy patients exposed to NSAIDs as in older, more comorbid, and nonexposed ones. Nonsteroidal antiinflammatory drug use may mask initial symptoms and delay antimicrobial therapy, thus predisposing to worse outcomes.

Pathophysiology of Escherichia coli ventilator-associated pneumonia: implication of highly virulent extraintestinal pathogenic strains

PurposeTo characterize Escherichia coli ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients by determining antibioresistance and genotypic characteristics of E.xa0coli isolates responsible for VAP or lung colonization, by comparing them with their oropharyngeal and rectal counterparts and by assessing representative isolates’ virulence in a pneumonia mouse model.MethodsPatients under mechanical ventilation for more than 72xa0h were screened for simultaneous presence of E.xa0coli in rectal, oropharyngeal, and respiratory samples (colonization or VAP). If present, E.xa0coli isolates were characterized by antimicrobial susceptibility, phylogenetic grouping, and virulence factor (VF) gene content determination. BALB/c mice were challenged intranasally with 3.6xa0×xa0108 colony-forming units (CFU) of patients’ E.xa0coli isolates.ResultsMultisite E.xa0coli colonization was observed in 19xa0% of patients (25 patients, 12 with E.xa0coli VAP). One hundred fifteen distinct E.xa0coli isolates were analyzed. B2 phylogenetic group was predominant, with high VF gene content and low antimicrobial resistance. Antimicrobial resistance diversity was observed in four patients with VAP. E.xa0coli isolates from VAP patients were more frequently B2 isolates, with significantly greater VF gene content than lung colonization isolates. Among screened VF genes, iroN and sfa appeared important for lung infection. A very strong correlation (R2xa0=xa00.99) was found between VF gene content and mortality in the mouse model.ConclusionsThis is the first study establishing antibioresistance and genotypic characteristics of E.xa0coli isolates responsible for VAP in adult ICU patients. These isolates are highly virulent specific extraintestinal pathogenic E.xa0coli strains expressing virulence factors, representing potential targets for new therapies.

Did studies on HFOV fail to improve ARDS survival because they did not decrease VILI? On the potential validity of a physiological concept enounced several decades ago

High frequency oscillatory ventilation (HFOV) has been the subject of extensive physiological research for 30xa0years and even more so of an intense debate on its potential usefulness in the treatment of acute respiratory distress syndrome (ARDS). This technique has been enthusiastically promoted by some teams until two high-quality randomized clinical trials in adults with ARDS showed that HFOV did not decrease and might have even increased mortality. As a consequence of these results, physiological concepts such as atelectrauma and biotrauma on which ARDS management with HFOV were based should be reexamined. In contrast, the concept of volutrauma, i.e., end-inspiratory overdistension, as the cause for ventilator-induced lung injury might help explain excess mortality during mechanical ventilation of ARDS when inspiratory volumes are too high. This is what might have happened during one of the recent studies on HFOV. Failure of this complex technique must be put in perspective with the dramatic improvement of ARDS prognosis with very simple interventions such as tidal volume reduction, early pharmacological paralysis, and prone positioning which all limited end-inspiratory volume.

High-flow nasal oxygen for bronchoalveolar lavage in acute respiratory failure patients

Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) holds significant risks of oxygenation deterioration [1]. Among various means to improve oxygenation during BAL, noninvasive positive pressure ventilation (NPPV) has received the greatest attention [2, 3]. However, NPPV is a time-consuming and very demanding technique. High-flow nasal cannula oxygen therapy (HFNC) has emerged as a technique for noninvasive respiratory management of hypoxaemic patients [4]. In patients with acute respiratory failure (ARF), its beneficial effects have been shown in various populations [5], and its effectiveness and superiority over NPPV and conventional oxygenation recently demonstrated [6]. Its use has also been described during bronchoscopy in non-hypoxaemic [7] and in hypoxaemic patients in comparison with NPPV [8]. However, bronchoscopy was performed with an open mouth in both studies, which considerably reduces HFNC efficacy [9]. Thus, we aimed to determine HFNCs effectiveness during nasal bronchoscopy with BAL in patients with ARF along with BALs feasibility and yield. HFNC is an effective and safe method of oxygenation during nasal bronchoscopy with BAL in hypoxaemic ARF patients http://ow.ly/XAmtZ

The Case | A crystal-clear diagnosis: acute kidney injury in a patient with suspected meningoencephalitis

A 66-year-old man with no remarkable past history was referred to our department for suspected meningoencephalitis. Upon admission, prominent clinical features consisted of fever 38.3u2009°C, coma, and rhombencephalitis; his other vital signs and the remainder of the clinical examination were unremarkable. The serum creatinine and urea nitrogen levels were normal.

Hypervirulent Klebsiella pneumoniae, a 5-year study in a French ICU

Purpose. Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a leading cause of severe community‐acquired pneumonia, liver abscess and disseminated infection in the Far East. Data regarding the incidence, clinical features and microbiological characteristics related to hvKp infections in the Western world are scarce. Methodology. The incidence, clinical features and microbiological characteristics of hvKp infections were investigated through a 5‐year survey conducted in a single French intensive care unit. K. pneumoniae strains were screened for hypermucoviscosity based on a string test. Multilocus sequence typing and multiplex PCR analysis targeting virulence genes were performed on string test‐positive strains. Results. Over a 53‐month period, a total of 59 infections due to K. pneumoniae were identified including 26 community‐onset infections. Twelve hvKp infections were documented, accounting for 46.1 % of community‐acquired K. pneumoniae. Community‐acquired pneumonia (n=6), aspiration pneumonia (n=4) and liver abscess (n=2) represented initial sites and mode of infection. Compared to non‐hvKp infections, patients with hvKp infections displayed higher rates of multi‐organ failure (83.3 % vs 35.7 %; P=0.04), but mortality rates were not different (50 % vs 35 %; P=0.71). Strains K1/ST23 (n=5) and K2/ST86 (n=5) predominated. All hvKp strains displayed wild‐type susceptibility. Conclusion. hvKp represent a potentially underestimated cause of fatal infections in the Western world.

Hypothesis: early renal replacement therapy increases mortality in critically ill patients with acute on chronic renal failure. A post hoc analysis of the AKIKI trial

Dear Editor, The occurrence of acute kidney injury (AKI) in patients with chronic kidney disease (CKD) is frequent and associated with long-term risk of death and end-stage renal disease [1, 2]. This condition often constitutes a noninclusion criterion in studies investigating timing of renal replacement therapy (RRT) initiation. However, this fragile population may suffer from early RRT because of the frequently associated comorbidities. We performed a post hoc analysis of the AKIKI trial [3] focused on CKD patients. Prospective definition [4] of CKD consisted in preexisting creatinine clearance between 30 and 60 ml/min under stable conditions. Day60 mortality was compared in CKD patients with early and delayed RRT initiation. Of the 619 patients included in AKIKI [3], 60 (10%) had CKD (Table e1). We found significant treatment effect heterogeneity according to the CKD status (test for interaction p = 0.006). In CKD patients, the hazard ratio (HR) associated with randomization group was 0.40 (95% CI 0.20–0.81, p = 0.009), indicating that the early RRT initiation strategy was strongly associated with increased risk of death after 60 days in this population (Fig. 1). No significant effect of the randomization group was observed in patients without CKD (HR 1.13 (95% CI 0.89–1.44), p = 0.31), meaning that excluding CKD patients does not change the results of the original AKIKI trial. The number of vasopressor-free days was significantly higher in patients assigned to the delayed strategy [5.5 (0–20) vs 22 (3–26), p = 0.02]. The delayed strategy allowed avoidance of RRT in 17/38 patients with CKD. Mechanical ventilation-free days, ICU and hospital length of stay, and dependence on RRT at day 28 and day 60 did not significantly differ between strategies (see Tables e2, 3, 4 for secondary endpoints, RRT initiation criteria, and modalities). The post hoc nature of this analysis and the relatively small number (n = 60) of CKD patients urge for a careful interpretation. Indeed, post hoc subgroup analyses are usually flawed by excessive optimism and show a greater effect than is eventually demonstrated in dedicated randomized trials performed for each baseline condition. However, the high level of significance of the difference in mortality pleads in favor of a real effect in this particularly fragile population. Indeed, CKD patients had many comorbidities (chronic hypertension, diabetes, ischemic heart disease) rendering them more susceptible to RRT-associated hypotensive episodes which are more likely to occur in the initial days when hemodynamic instability may be present. In contrast, the delayed strategy can either give time for spontaneous renal function recovery (obviating the need for RRT) or allow clinical

Clinical impact of upper gastrointestinal endoscopy in critically ill patients with suspected bleeding

Background and AimsUpper gastrointestinal endoscopies’ (UGE) profitability is undisputable in patients admitted for an overt upper digestive tract bleeding. In critically ill subjects admitted for other causes, its performances have scarcely been investigated despite its broad use. We sought to question the performance of bedside UGE in intensive care unit (ICU) patients, admitted for another reason than overt bleeding.MethodsThis was a six-year (January 2007–December 2012) retrospective observational study of all UGE performed in a medico-surgical ICU. Exclusion of those performed: in patients admitted for a patent upper digestive bleeding; for a second-look gastroscopy of a known lesion; as a planned interventional procedure. Main demographic and clinical data were recorded; UGE indication and profitability were rated according to its findings and therapeutic impact. Operative values of the indications of UGE were calculated. This study received approval from the Ethics Committee of the French Society of Intensive Care (n° 12-363).ResultsEighty-four patients (74% male, mean age 61u2009±u200914xa0years) underwent a diagnostic UGE, all for a suspected upper digestive tract bleeding. The main symptoms justifying the procedure were anemia (52%), digestive bleeding (27%), vomiting (15%), hemodynamic instability (3%) and hyperuremia (3%). The profitability of UGE was rated as major (nu2009=u20095; 5.8%); minor (nu2009=u200934; 40.5%); or null (nu2009=u200945; 53.6%).ConclusionsWhen ICU admission is not warranted by a digestive bleeding, UGE has limited diagnostic and therapeutic interest, despite being often performed.

Nouveautés thérapeutiques sur le SDRA* New therapeutic strategies in ARDS

Treatment of acute respiratory distress syndrome (ARDS) has been subject to many researches, sometimes leading to intense controversy. New findings in this field are varied. Effects on prognosis of commonly used treatments for ARDS have recently been investigated. Consistently, prone position, previously known to improve oxygenation without effect on mortality, has been shown to improve survival of the most severely hypoxemic patients. Administration of neuromuscular blocking agents in the acute phase of ARDS has been also shown to be beneficial on survival. In contrast, the exact place of extracorporeal membrane oxygenation (ECMO) in ARDS management remains to be defined despite data suggesting its possible efficiency. In addition, a new era of research has emerged with the advent of cell therapy. Mesenchymal stem cells are able to both promote alveolar epithelium repair and prevent infections. Their efficacy in animal models of ARDS still needs to be confirmed by clinical trials. Finally, other promising therapies including beta-2 adrenergic agonists and omega-3 fatty acids have shown significant limitations in large clinical studies on ARDS.RésuméLe traitement du syndrome de détresse respiratoire aiguë (SDRA) fait l’objet, depuis longtemps, de nombreux travaux de recherche, sources d’intenses controverses. L’actualité dans ce domaine est riche et très variée. Les effets sur le pronostic du SDRA de traitements couramment utilisés ont pu récemment être précisés. Par exemple, il a été démontré que le décubitus ventral, qui n’avait montré jusqu’ici qu’une amélioration de l’hématose sans effet sur la mortalité, pouvait améliorer la survie des patients les plus sévèrement hypoxémiques. L’utilisation de curares à la phase aiguë du SDRA a également montré un effet bénéfique sur la survie. La place de l’oxygénation par membrane extracorporelle (ECMO) dans la prise en charge du SDRA reste à définir, malgré des données laissant supposer une possible efficacité.Par ailleurs, une voie de recherche s’est ouverte avec l’avènement des thérapies cellulaires. En effet, les cellules souches mésenchymateuses semblent pouvoir à la fois favoriser la réparation de l’épithélium alvéolaire et prévenir des risques infectieux. Leur efficacité dans les modèles animaux de SDRA demande à être confirmée par des études chez l’homme. Enfin, certaines thérapeutiques prometteuses ont montré leurs limites. C’est le cas notamment des agonistes béta-adrénergiques et des acides gras oméga-3 qui ont montré leur inefficacité dans plusieurs grandes études cliniques sur le SDRA.AbstractTreatment of acute respiratory distress syndrome (ARDS) has been subject to many researches, sometimes leading to intense controversy. New findings in this field are varied. Effects on prognosis of commonly used treatments for ARDS have recently been investigated. Consistently, prone position, previously known to improve oxygenation without effect on mortality, has been shown to improve survival of the most severely hypoxemic patients. Administration of neuromuscular blocking agents in the acute phase of ARDS has been also shown to be beneficial on survival. In contrast, the exact place of extracorporeal membrane oxygenation (ECMO) in ARDS management remains to be defined despite data suggesting its possible efficiency. In addition, a new era of research has emerged with the advent of cell therapy. Mesenchymal stem cells are able to both promote alveolar epithelium repair and prevent infections. Their efficacy in animal models of ARDS still needs to be confirmed by clinical trials. Finally, other promising therapies including beta-2 adrenergic agonists and omega-3 fatty acids have shown significant limitations in large clinical studies on ARDS.