Use, timing and factors associated with tracheal intubation in septic shock: a prospective multicentric observational study.

BACKGROUND: No recommendation exists about the timing and setting for tracheal intubation and mechanical ventilation in septic shock. PATIENTS AND METHODS: This prospective multicenter observational study was conducted in 30 ICUs in France and Spain. All consecutive patients presenting with septic shock were eligible. The use of tracheal intubation was described across the participating ICUs. A multivariate analysis was performed to identify parameters associated with early intubation (before H8 following vasopressor onset). RESULTS: Eight hundred and fifty-nine patients were enrolled. Two hundred and nine patients were intubated early (24%, range 4.5-47%), across the 18 centers with at least 20 patients included. The cumulative intubation rate during the ICU stay was 324/859 (38%, range 14-65%). In the multivariate analysis, seven parameters were significantly associated with early intubation and ranked as follows by decreasing weight: Glasgow score, center effect, use of accessory respiratory muscles, lactate level, vasopressor dose, pH and inability to clear tracheal secretions. Global R-square of the model was only 60% indicating that 40% of the variability of the intubation process was related to other parameters than those entered in this analysis. CONCLUSION: Neurological, respiratory and hemodynamic parameters only partially explained the use of tracheal intubation in septic shock patients. Center effect was important. Finally, a vast part of the variability of intubation remained unexplained by patient characteristics. Trial registration Clinical trials NCT02780466, registered on May 23, 2016. https://clinicaltrials.gov/ct2/show/NCT02780466?term=intubatic&draw=2&rank=1.

Activation of innate immunity by 14-3-3 ε, a new potential alarmin in osteoarthritis.

OBJECTIVE: The innate immune system plays a central role in osteoarthritis (OA). We identified 14-3-3ε as a novel mediator that guides chondrocytes toward an inflammatory phenotype. 14-3-3ε shares common characteristics with alarmins. These endogenous molecules, released into extracellular media, are increasingly incriminated in sustaining OA inflammation. Alarmins bind mainly to toll-like receptor 2 (TLR2) and TLR4 receptors and polarize macrophages in the synovium. We investigated the effects of 14-3-3ε in joint cells and tissues and its interactions with TLRs to define it as a new alarmin involved in OA. DESIGN: Chondrocyte, synoviocyte and macrophage cultures from murine or OA human samples were treated with 14-3-3ε. To inhibit TLR2/4 in chondrocytes, blocking antibodies were used. Moreover, chondrocytes and bone marrow macrophage (BMM) cultures from knockout (KO) TLRs mice were stimulated with 14-3-3ε. Gene expression and release of inflammatory mediators [interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNFα)] were evaluated via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and ELISA. RESULTS: In vitro, 14-3-3ε induced gene expression and release of IL6 and MCP1 in the treated cells. The inflammatory effects of 14-3-3ε were significantly reduced following TLRs inhibition or in TLRs KO chondrocytes and BMM. CONCLUSIONS: 14-3-3ε is able to induce an inflammatory phenotype in synoviocytes, macrophages and chondrocytes in addition to polarizing macrophages. These effects seem to involve TLR2 or TLR4 to trigger innate immunity. Our results designate 14-3-3ε as a novel alarmin in OA and as a new target either for therapeutic and/or prognostic purposes.

Severe atypical pneumonia in critically ill patients: a retrospective multicenter study.

BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients could require intensive care unit (ICU) admission for acute respiratory failure. METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven atypical pneumonia were retrospectively described. Patients with MP were compared to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A total of 104 patients were included, 71 men and 33 women, with a median age of 56 [44-67] years. MP was the causative agent for 76 (73%) patients and CP for 28 (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%] patients). Median number of involved quadrants on chest X-ray was 2 [1-4], with alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra-pulmonary manifestations were present in 34 (33%) patients. Mechanical ventilation was required for 75 (72%) patients and vasopressors for 41 (39%) patients. ICU length of stay was 16.5 [9.5-30.5] days, and 11 (11%) patients died in the ICU. Compared with SP patients, MP patients had more extensive interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6 (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at admission could discriminate MP and SP. MP was more often associated with hemolytic anemia, abdominal manifestations, and extensive chest radiograph abnormalities. SP-P was associated with shock, confusion, focal crackles, and focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial pneumonia requiring ICU admission, mortality was 11%. The comparison with SP pneumonia identified clinical, laboratory, and radiographic features that may suggest MP or CP pneumonia.

Major traumatic complications after out-of-hospital cardiac arrest: Insights from the Parisian registry.

AIM: Due to collapse and cardiopulmonary resuscitation (CPR) maneuvers, major traumatic injuries may complicate the course of resuscitation for out-of-hospital cardiac arrest patients (OHCA). Our goals were to assess the prevalence of these injuries, to describe their characteristics and to identify predictive factors. METHODS: We conducted an observational study over a 9-year period (2007-2015) in a French cardiac arrest (CA) center. All non-traumatic OHCA patients admitted alive in the ICU were studied. Major injuries identified were ranked using a functional two-level scale of severity (life-threatening or consequential) and were classified as CPR-related injuries or collapse-related injuries, depending of the predominant mechanism. Factors associated with occurrence of a CPR-related injury and ICU survival were identified using multivariable logistic regression. RESULTS: A major traumatic injury following OHCA was observed in 91/1310 patients (6.9%, 95%CI: 5.6, 8.3%), and was classified as a life-threatening injury in 36% of cases. The traumatic injury was considered as contributing to the death in 19 (21%) cases. Injuries were related to CPR maneuvers in 65 patients (5.0%, (95%CI: 3.8, 6.1%)). In multivariable analysis, age [OR 1.02; 95%CI (1.00, 1.04); p = 0.01], male gender [OR 0.53; 95%CI (0.31, 0.91); p = 0.02] and CA occurring at home [OR 0.54; 95%CI (0.31, 0.92); p = 0.02] were significantly associated with the occurrence of a CPR-related injury. CPR-related injuries were not associated with the ICU survival [OR 0.69; 95%CI (0.36, 1.33); p = 0.27]. CONCLUSIONS: Major traumatic injuries are common after cardiopulmonary resuscitation. Further studies are necessary to evaluate the interest of a systematic traumatic check-up in resuscitated OHCA patients in order to detect these injuries.

Noninvasive ventilation during acute respiratory distress syndrome in patients with cancer: Trends in use and outcome.

PURPOSE: The objectives of our study were to describe the outcome of patients with malignancies treated for acute respiratory distress syndrome (ARDS) with noninvasive ventilation (NIV) and to evaluate factors associated with NIV failure. METHODS: Post hoc analysis of a multicenter database within 20 years was performed. All patients with malignancies and Berlin ARDS definition were included. Noninvasive ventilation use was defined as NIV lasting more than 1 hour, whereas failure was defined as a subsequent requirement of invasive ventilation. Conditional backward logistic regression analyses were conducted. RESULTS: A total of 1004 met the Berlin definition of ARDS. Noninvasive ventilation was used in 387 patients (38.6%) and NIV failure occurred in 71%, with an in-hospital mortality of 62.7%. Severity of ARDS defined by the partial pressure arterial oxygen and fraction of inspired oxygen ratio (odds ratio [OR], 2.20; 95% confidence interval [CI], 1.15-4.19), pulmonary infection (OR, 1.81; 95% CI, 1.08-3.03), and modified Sequential Organ Failure Assessment (SOFA) score (OR, 1.13; 95% CI, 1.06-1.21) were associated with NIV failure. Factors associated with hospital mortality were NIV failure (OR, 2.52; 95% CI, 1.56-4.07), severe ARDS as compared with mild ARDS (OR, 1.89; 95% CI, 1.05-1.19), and modified SOFA score (OR, 1.12; 95% CI, 1.05-1.19). CONCLUSION: Noninvasive ventilation failure in ARDS patients with malignancies is frequent and related to ARDS severity, SOFA score, and pulmonary infection-related ARDS. Noninvasive ventilation failure is associated with in-hospital mortality.

Hypoxic hepatitis after out-of-hospital cardiac arrest: Incidence, determinants and prognosis.

AIM: Hypoxic hepatitis (HH) may complicate the course of resuscitated out-of-hospital cardiac arrest (OHCA) patients admitted in intensive care unit (ICU). Aims of this study were to assess the prevalence of HH, and to describe the factors associated with HH occurrence and outcome. METHODS: We conducted an observational study over a 6-year period (2009-2014) in a cardiac arrest center. All non-traumatic OHCA patients admitted in the ICU after return of spontaneous circulation (ROSC) and who survived more than 24h were included. HH was defined as an elevation of alanine aminotransferase over 20 times the upper limit of normal during the first 72h after OHCA. Factors associated with HH and ICU mortality were picked up by multivariate logistic regression. RESULTS: Among the 632 OHCA patients included in the study, HH was observed in 72 patients (11.4% (95% CI: 9.0%, 14.1%)). In multivariate analysis, time from collapse to ROSC [OR 1.02 per additional minute; 95% CI (1.00, 1.04); p=0.01], male gender [OR 0.53; 95% CI (0.29, 0.95); p=0.03] and initial shockable rhythm [OR 0.35; 95% CI (0.19, 0.65); p<0.01] were associated with HH occurrence. After adjustment for confounding factors, HH was associated with ICU mortality [OR 4.39; 95% CI (1.71, 11.26); p<0.01] and this association persisted even if occurrence of a post-CA shock was considered in the statistical model [OR 3.63; 95% CI (1.39, 9.48); p=0.01]. CONCLUSIONS: HH is not a rare complication after OHCA. This complication is mainly triggered by the duration of resuscitation and is associated with increased ICU mortality.

Changes in intensive care for allogeneic hematopoietic stem cell transplant recipients.

Intensive care unit (ICU) admission is associated with high mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Whether mortality has decreased recently is unknown. The 497 adult allogeneic HSCT recipients admitted to three ICUs between 1997 and 2011 were evaluated retrospectively. Two hundred and nine patients admitted between 1997 and 2003 were compared with the 288 patients admitted from 2004 to 2011. Factors associated with 90-day mortality were identified. The recent cohort was characterized by older age, lower conditioning intensity, and greater use of peripheral blood or unrelated-donor graft. In the recent cohort, ICU was used more often for patients in hematological remission (67% vs 44%; P<0.0001) and without GVHD (73% vs 48%; P<0.0001) or invasive fungal infection (85% vs 73%; P=0.0003) despite a stable admission rate (21.7%). These changes were associated with significantly better 90-day survival (49% vs 31%). Independent predictors of hospital mortality were GVHD, mechanical ventilation (MV) and renal replacement therapy (RRT). Among patients who required MV or RRT, survival was 29% and 18%, respectively, but dropped to 18% and 6% in those with GVHD. The use of ICU admission has changed and translated into improved survival, but advanced life support in patients with GVHD usually provides no benefits.

Prognosis of neutropenic patients admitted to the intensive care unit.

PURPOSE: The prognosis of critically ill cancer patients has improved recently. Controversies remain as regard to the specific prognosis impact of neutropenia in critically ill cancer patients. The primary objective of this study was to assess hospital outcome of critically ill neutropenic cancer patients admitted into the ICU. The secondary objective was to assess risk factors for unfavorable outcome in this population of patients and specific impact of neutropenia. METHODS: We performed a post hoc analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centers in France and Belgium. Neutropenia was defined as a neutrophil count lower than 500/mm(3). RESULTS: Among the 1,011 patients admitted into the ICU during the study period 289 were neutropenic at the time of admission. Overall, 131 patients died during their hospital stay (hospital mortality 45.3 %). Four variables were associated with a poor outcome, namely allogeneic transplantation (OR 3.83; 95 % CI 1.75-8.35), need for mechanical ventilation (MV) (OR 6.57; 95 % CI 3.51-12.32), microbiological documentation (OR 2.33; CI 1.27-4.26), and need for renal replacement therapy (OR 2.77; 95 % CI 1.34-5.74). Two variables were associated with hospital survival, namely age younger than 70 (OR 0.22; 95 % CI 0.1-0.52) and neutropenic enterocolitis (OR 0.37; 95 % CI 0.15-0.9). A case-control analysis was also performed with patients of the initial database; after adjustment, neutropenia was not associated with hospital mortality (OR 1.27; 95 % CI 0.86-1.89). CONCLUSION: Hospital survival was closely associated with younger age and neutropenic enterocolitis. Conversely, need for conventional MV, for renal replacement therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) were associated with poor outcome.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

BACKGROUND: Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES: To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS: The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS: Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 µg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 µg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS: A CTnI level of > 0.25 µg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.

Post-infectious immune suppression: a new paradigm of severe infections.

Infectious diseases remain a major public health issue in both developing and developed countries. For instance, there is still a high rate of morbidity and mortality due to seasonal influenza outbreaks and severe bacterial sepsis, despite major advances in their prevention and treatment. It is now clear that severe influenza and bacterial infections promote susceptibility for superinfections worsening the prognosis. Various immune defects acquired during severe infection may result in complex immunosuppression and may affect both innate and adaptive components. Some animal models of these common clinical situations have demonstrated the increased susceptibility of infected hosts to secondary infectious insult and allowed assessing the regulatory mechanisms. Such pathophysiological advances may help create new immunomodulatory therapeutics for infected patients exposed to severe secondary sepsis.

False hyperlactatemia in life-threatening ethylene glycol poisoning.

Ethylene glycol poisoning is rare, but prompt diagnosis is crucial, in order to initiate specific treatments. Herein, we report the case of a patient who was admitted to ICU for coma and extreme metabolic acidosis with unexpected hyperlactatemia on initial ICU blood gas analyzer. Ethylene glycol poisoning was diagnosed, and hyperlactatemia was ruled out on a blood sample sent to the biochemistry department. Interference of blood gas analyzers lactate electrodes with metabolites of ethylene glycol were the source of this apparent hyperlactatemia. Symptoms gradually improved and false hyperlactatemia resolved after renal replacement therapy and fomepizole administration. Time course of ethylene glycol concentration showed similar evolution. After initial confirmation of ethylene glycol presence, this biological interference could thus be used as a surrogate of costly and highly specialised dosages.

Acute respiratory failure in neutropenic patients is associated with a high post-ICU mortality.

BACKGROUND: Few studies have evaluated outcomes of neutropenic patients admitted to the ICU at the onset of acute respiratory failure (ARF). The main objective of this study was to describe outcomes and to identify early predictors of hospital mortality in critically ill cancer patients with ARF during chemotherapy-induced neutropenia. METHODS: Retrospective analysis of prospectively collected data extracted from two recent prospective multicentre studies. We included neutropenic adults admitted to the ICU for ARF. RESULTS: Of the 123 study patients, 107 patients (87%) had haematological malignancies; 78 (64%) were male, median age was 57 years (44-62), and median LOD score at ICU admission was 6 (4-9). ICU and hospital mortality rates were 42% and 77%, respectively. Endotracheal mechanical ventilation was an independent risk factor for hospital mortality (odds ratio [OR], 7.73; 95% confidence interval [95%CI], 2.52-23.69); two factors independently protected from hospital mortality, namely, ICU admission for ARF during neutropenia recovery (OR, 0.23; 95%CI, 0.07-0.73) and steroid therapy before ICU admission (OR, 0.35; 95%CI, 0.11-0.95). CONCLUSION: Our study demonstrates a meaningful ICU survival in the studied population and identified factors associated with ICU and hospital mortality. Further work is needed to address the reasons for the high post-ICU mortality rate after ARF.

Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients.

AIMS: Gut dysfunction is suspected to play a major role in the pathophysiology of post-resuscitation disease through an increase in intestinal permeability and endotoxin release. However this dysfunction often remains occult and is poorly investigated. The aim of this pilot study was to explore intestinal failure biomarkers in post-cardiac arrest patients and to correlate them with endotoxemia. METHODS: Following resuscitation after cardiac arrest, 21 patients were prospectively studied. Urinary intestinal fatty acid-binding protein (IFABP), which marks intestinal permeability, plasma citrulline, which reflects the functional enterocyte mass, and whole blood endotoxin were measured at admission, days 1-3 and 6. We explored the kinetics of release and the relationship between IFABP, citrulline and endotoxin values. RESULTS: IFABP was extremely high at admission and normalized at D3 (6668 pg/mL vs 39 pg/mL, p=0.01). Lowest median of citrulline (N=20-40 µmol/L) was attained at D2 (11 µmol/L at D2 vs 24 µmol/L at admission, p=0.01) and tended to normalize at D6 (21 µmol/L). During ICU stay, 86% of patients presented a detectable endotoxemia. Highest endotoxin level was positively correlated with highest IFABP level (R(2)=0.31, p=0.01) and was inversely correlated with lowest plasma citrulline levels (R(2)=0.55, p<0.001). Endotoxin levels increased between admission and D2 in patients with post-resuscitation shock, whereas it decreases in patients with no shock (median +0.33 EU vs -0.19 EU, p=0.03). Highest endotoxin level was positively correlated with D3 SOFA score (R(2)=0.45, p=0.004). CONCLUSION: Biomarkers of intestinal injury are altered after cardiac arrest and are associated with endotoxemia. This could worsen post-resuscitation shock and organ failure.

[Dropped Head Syndrome after whiplash injury in a patient treated for a Hodgkin's lymphoma by mantle field radiotherapy]. / Syndrome de la tête tombante après traumatisme cervical dans le cadre d'un lymphome de Hodgkin irradié en mantelet.

The authors report a case of Dropped Head Syndrome with an unusually rapid onset after an accident in a patient with a history of Hodgkin's lymphoma cured by chemotherapy and mantle field radiotherapy and compare this case to the rare published cases of chronic Dropped Head Syndrome occurring after this type of treatment. A 56-year-old man was treated at the age 36 years for supra-diaphragmatic Hodgkin's lymphoma by chemotherapy and mantle field radiotherapy according to a standard technique and standard doses (40Gy, 20 fractions, 27 days). Seventeen years after the end of treatment, he experienced a violent whiplash injury, rapidly followed by a Dropped Head Syndrome, similar to the cases of chronic Dropped Head Syndrome already described in the context of Hodgkin's lymphoma (permanent flexion of the head, only reduced in the supine position). Physical and neurophysiological examination, electromyogram, and magnetic resonance imaging confirmed the diagnosis of Dropped Head Syndrome. Very few treatment options are available for the major disability related to Dropped Head Syndrome. This type of subacute onset of Dropped Head Syndrome has not been previously described. The good results of radiation therapy after chemotherapy allow a dose reduction to 30Gy in the involved regions. This, together with recent progress in treatment planning, should allow eradication of these complications.

[Therapeutic of respiratory manifestations at the early phase of acute myeloid leukaemia]. / Prise en charge thérapeutique des manifestations pulmonaires à la phase aiguë des leucémies aiguës myéloblastiques.

The effective management of the respiratory manifestations at the early phase of acute myeloid hemopathies, especially acute myeloid leukaemia, frequently requires a close collaboration between hematologists, pulmonologists and intensivists. Dominated by infectious etiologies, there are however "specific" disease entities that should not be neglected in the diagnostic and therapeutic approach. These include lung leukostasis, leukemic lung infiltration, the cell lysis pneumopathy and the secondary alveolar proteinosis. These were the subject of a review in the Revue des Maladies Respiratoires published in 2010. We wished to review the management of these clinical situations, the severity of which mean patients frequently require intensive care unit admission. We are only able to make proposals for management here as there is little consensus, except in the metabolic care of tumour lysis syndrome. These data must therefore be reinterpreted regularly as new publications become available.

Necrotizing fasciitis and septic shock related to the uncommon gram-negative pathogen Sphingobacterium multivorum.

We report the first case of necrotizing fasciitis due to the uncommon Gram-negative pathogen Sphingobacterium multivorum in an immunocompromised patient, who presented with septic shock. This case adds necrotizing fasciitis to the spectrum of S. multivorum-related infections and highlights the emergence of Gram-negative bacteria in severe soft tissue infections.

Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock.

PURPOSE: Septic shock induces a decrease in dendritic cells (DCs) that may contribute to sepsis-induced immunosuppression. We analyzed the time course of circulating DCs in patients with septic shock and its relation to susceptibility to intensive care unit (ICU)-acquired infections. METHODS: We enrolled adult patients with septic shock (n = 43), non-septic shock (n = 29), and with sepsis without organ dysfunction (n = 16). Healthy controls (n = 16) served as reference. Blood samples were drawn on the day of shock (day 1), then after 3 and 7 days. Myeloid (mDC) and plasmacytoid (pDC) DCs were counted by flow cytometry. Cell surface HLA-DR expression was analyzed in both DC subsets. RESULTS: At day 1, median mDC and pDC counts were dramatically lower in septic shock patients as compared to healthy controls (respectively, 835 mDCs and 178 pDCs/ml vs. 19,342 mDCs and 6,169 pDCs/ml; P < 0.0001) but also to non-septic shock and sepsis patients (P < 0.0001). HLA-DR expression was decreased in both mDCs and pDCS within the septic shock group as compared to healthy controls. DC depletion was sustained for at least 7 days in septic shock patients. Among them, 10/43 developed ICU-acquired infections after a median of 9 [7.5-11] days. At day 7, mDC counts increased in patients devoid of secondary infections, whereas they remained low in those who subsequently developed ICU-acquired infections. CONCLUSION: Septic shock is associated with profound and sustained depletion of circulating DCs. The persistence of low mDC counts is associated with the development of ICU-acquired infections, suggesting that DC depletion is a functional feature of sepsis-induced immunosuppression.