Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015. This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression. Among the 771 enrolled patients (median age 66 years, IQR [52.0–79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines. We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients. ClinicalTrial. Gov identification number: NCT01730690

Background : Need for catecholamines is frequent in COVID-19 patients, but the main echocardiographic patterns are unknown. The objective was to report the main echo patterns in critically-ill COVID-19 patients. Methods : Observational and descriptive study in consecutive COVID-19 patients admitted to the ICU between March 12 and May 8, 2020. Systematic critical care echocardiography (CCE) was performed and retrospectively analyzed off-line. Echo values are reported in the overall population and in patients who required catecholamine infusion during the first 2 days following admission (D 1-2 ) or afterwards until day 7 (D 3-7 ). Results : Of the 79 patients (78% male; median age 63 [56-71]; body mass index 29 [26-30]) included, 90% had at least 1 comorbidity. PaO 2 /FiO 2 at admission was 85 [67-162] mmHg. 53% of patients were mechanically ventilated. ICU length of stay was 9 [5-16] days and mortality 34%. 134 echocardiographic studies were performed during the first week in 65 patients. Pulmonary artery acceleration time was decreased (77 [65-97] ms), suggesting pulmonary hypertension. All 39 patients (49%) who required catecholamine infusion underwent CCE and 25.6% had left ventricular (LV) systolic dysfunction, 28.2% acute cor pulmonale (ACP), 7.7% hypovolemia, and 38.5% vasoplegia. Modification of echo patterns was observed at D 3-7 , with less LV systolic dysfunction and more ACP, which was the most frequent pattern. Computed tomography pulmonary angiography in 6 patients with ACP indicated intrapulmonary thrombus in 4. Conclusion : Different echocardiographic patterns were observed during the first week following ICU admission in COVID-19 patients. ACP was frequent and often related to thrombus in the pulmonary circulation.

FAT embolism syndrome (FES) is a combination of respiratory, neurologic, cutaneous, and hematologic symptoms associated with physical trauma to fat tissue secondary to bone fracture or to medical or surgical soft-tissue injury.1–4The incidence in patients with bone fractures is usually reported as low (0.5–10%),4but can reach more than 30%.2,5Diagnosis is based on major or minor criteria historically described by Gurd and Wilson.6We report the case of a 67-yr-old female polytrauma patient who developed FES secondary to unusual bone fractures.A 67-yr-old woman was admitted to our intensive care unit because of polytrauma after high-speed injury. Despite an initial loss of consciousness, neurologic findings were normal on arrival. First clinical findings revealed left thoracic trauma and clavicle fracture. Heart rate was 81 beats/min, respiratory rate was 25 per min, vesicular breathing was abolished in the left lung field, oxygen saturation was 98% with oxygen therapy of 6 l/min, and Glasgow Coma Scale score was 14. Auscultation was consistent with the diagnosis of pneumothorax. There was no external bleeding or circulatory instability. Chest radiograph revealed a left hemopneumothorax due to five rib fractures without thoracic outlet, and a left clavicle fracture (fig. 1). Body scan showed a left pulmonary contusion and a right piriform muscle hematoma. No other visceral or vascular lesion was noted. Brain computed tomography scan was normal. Hemoglobin concentration at admission was 11.8 g/dL. Coagulation was normal and platelet count was 202,000/mm3. Otherwise, the patient presented with minor liver cytolysis (twice normal) and a moderate increase in creatine kinase (277 U/L). The hemopneumothorax was safely drained with a 24 French tube in the intensive care unit where the patient was then followed up. Six hours after admission, she suddenly lost consciousness (Glasgow Coma Scale score 3) and became hypoxemic, requiring mechanical ventilation with a high amount of oxygen. The patient's hemodynamics remained normal. Her chest radiograph showed diffuse alveolar-interstitial infiltrates. Bronchoalveolar lavage fluid revealed a high amount of lipid-laden macrophage-like cells (47%) showing Oil red O staining with red intracellular lipid droplets (fig. 2). At the same time, the patient's platelet count fell to 62,000/mm3. Body temperature was 38.4°C in the 4 h after the neurologic degradation. Brain magnetic resonance imaging showed multiple cerebral emboli on a diffusion-weighted sequence without abnormality on a T2 gradient echo sequence, attesting to the absence of hemorrhagic axonal injury (fig. 3). Transesophageal echocardiography with bubble contrast demonstrated no evidence of a patent foramen ovale. No left atrial thrombosis was found. Ocular fundus findings were normal. Despite the initial severe neurologic presentation, the patient started to recover progressively 1 month after admission and was transferred to a rehabilitation center. Two months after transfer the patient had recovered the ability to walk with a cane. The patient was oriented to time and location when last examined.The combination of neurologic signs confirmed by imaging, respiratory symptoms with alveolar-interstitial infiltrate and hypoxemia, thrombocytopenia, and a high amount of lipid-laden macrophages in bronchoalveolar lavage fluid7led us to the diagnosis of FES. The only missing symptom was petechiae, which are absent in more than 40% of cases of FES.1–3FES is a rare complication of bone fractures and soft tissue injury, generally associated with long bone fractures1–4and sometimes also caused by multiple fractures.2,3In our case, FES was a quite unexpected complication of isolated rib and clavicle fractures. The absence of patent foramen ovale in the current case, as well as in most published studies,8raises the key issue of the pathophysiology of FES. Explanations described thus far remain controversial and include the infloating theory, which holds that high pressure on fat tissue leads to lipid embolism in the systemic circulation via a transient patent foramen ovale; the lipase theory, according to which lipid stores could be saponified before embolizing; the free fatty acid theory, in which these toxic molecules create vasculitis; the coagulation theory, in which a procoagulant state is generated by the contact of bone marrow fat with platelets; and the systemic embolization theory, which argues that the combination of the deformability of fat emboli with the rise in pulmonary arterial blood pressure forces the fat globules through the pulmonary capillary bed.3In the current case, one possible mechanism could be the passage of fat droplets directly from bone marrow to injured pulmonary veins. The clinical improvement of our patient despite the severe initial presentation illustrates the potentially good prognosis of cerebrovascular accidents caused by fat embolism.FES without long bone fracture is an authentic clinical entity that should be considered in patients with polytrauma and soft-tissue injury or multiple fractures. This case report highlights an unexpected complication of rib and clavicle fractures. It also reemphasizes the value of complementary examinations, such as magnetic resonance imaging, bronchoalveolar lavage, and ocular fundus examination, in typical presentations or in sudden neurologic or respiratory distress without clear explanation. Physicians ought to be aware of such a complication even in the absence of patent foramen ovale and of its potential resolution even if the presentation is initially severe.

Since 1997, we have routinely used prone positioning (PP) in patients who have a PaO2/FiO2 below 100 mmHg after 24–48 h of mechanical ventilation and who are ventilated using a low stretch ventilation strategy. We report here the characteristics and prognosis of this subgroup of patients with severe lung injury to illustrate the feasibility, role, and impact of routine PP in acute respiratory distress syndrome (ARDS).

INTRODUCTION:Our aims in this study were to report changes in the ratio of alveolar dead space to tidal volume (VDalv/VT) in the prone position (PP) and to test whether changes in partial pressure of arterial CO2 (PaCO2) may be more relevant than changes in the ratio of partial pressure of arterial O2 to fraction of inspired O2 (PaO2/FiO2) in defining the respiratory response to PP. We also aimed to validate a recently proposed method of estimation of the physiological dead space (VDphysiol/VT) without measurement of expired CO2. METHODS:Thirteen patients with a PaO2/FiO2 ratio < 100 mmHg were included in the study. Plateau pressure (Pplat), positive end-expiratory pressure (PEEP), blood gas analysis and expiratory CO2 were recorded with patients in the supine position and after 3, 6, 9, 12 and 15 hours in the PP. Responders to PP were defined after 15 hours of PP either by an increase in PaO2/FiO2 ratio > 20 mmHg or by a decrease in PaCO2 > 2 mmHg. Estimated and measured VDphysiol/VT ratios were compared. RESULTS:PP induced a decrease in Pplat, PaCO2 and VDalv/VT ratio and increases in PaO2/FiO2 ratios and compliance of the respiratory system (Crs). Maximal changes were observed after six to nine hours. Changes in VDalv/VT were correlated with changes in Crs, but not with changes in PaO2/FiO2 ratios. When the response was defined by PaO2/FiO2 ratio, no significant differences in Pplat, PaCO2 or VDalv/VT alterations between responders (n = 7) and nonresponders (n = 6) were observed. When the response was defined by PaCO2, four patients were differently classified, and responders (n = 7) had a greater decrease in VDalv/VT ratio and in Pplat and a greater increase in PaO2/FiO2 ratio and in Crs than nonresponders (n = 6). Estimated VDphysiol/VT ratios significantly underestimated measured VDphysiol/VT ratios (concordance correlation coefficient 0.19 (interquartile ranges 0.091 to 0.28)), whereas changes during PP were more reliable (concordance correlation coefficient 0.51 (0.32 to 0.66)). CONCLUSIONS:PP induced a decrease in VDalv/VT ratio and an improvement in respiratory mechanics. The respiratory response to PP appeared more relevant when PaCO2 rather than the PaO2/FiO2 ratio was used. Estimated VDphysiol/VT ratios systematically underestimated measured VDphysiol/VT ratios.

Rapid and specific diagnosis of influenza A/B and respiratory syncytial virus (RSV) viruses is needed for optimal management of patients with acute respiratory infections. In this study, a one‐step triplex real‐time RT‐PCR assay was developed for rapid diagnosis of influenza A/B and RSV infections to optimize diagnosis efficiency of acute respiratory infections. Cell‐culture supernatants and clinical samples were used to evaluate specificity and sensitivity of the assay. The assay was used routinely during two winter epidemics for testing respiratory specimens from 2,417 patients. The limit of detection in cell‐culture supernatant was 1–10 plaque forming units/input (influenza A/B) and 2 × 10−2 50% tissue culture infectious dose/input (RSV). In clinical samples, the assay was as sensitive as commercial molecular assays for the detection of each influenza A/B and RSV (Flu‐A/B and RSV‐A/B r‐gene™) individually, and far more sensitive than antigen detection. During the winter 2008–2009, the assay identified 145 RSV, 42 influenza A, and one mixed RSV‐influenza A infections among 298 patients. The next winter, the assay was used in two independent hospital laboratory settings. 776 patients were tested in one hospital and 1,343 in the other, resulting in 184 and 501 RSV, 133 and 150 influenza A, and 1 and 11 mixed RSV‐influenza A infections, respectively, being detected. This new user‐friendly assay allows rapid (within hours), effective molecular diagnosis of single or mixed infections involving influenza A (including seasonal A H1N1 and H3N2, and A(H1N1) 2009), influenza B, and RSV(A/B). The assay is very valuable for managing patients during winter epidemics when influenza and respiratory syncytial viruses co‐circulate. J. Med. Virol. 83:695–701, 2011. © 2011 Wiley‐Liss, Inc.

L’abord vasculaire, le drainage urinaire ou la ventilation assistée sont indispensables à la médecine actuelle et, durant leur prise en charge, la plupart des malades hospitalisés sont exposés à l’un ou l’autre de ces actes. Cependant, l’implantation temporaire d’un cathéter vasculaire, d’une sonde vésicale ou d’une sonde endotrachéale est associée à un risque infectieux non négligeable puisqu’on estime que 60 % des infections associées aux soins auraient pour origine un dispositif invasif. La physiopathologie de ces infections est étroitement liée à la constitution d’un biofilm sur ces corps étrangers.

Rationale and Objective: To evaluate the actual incidence of global left ventricular hypokinesia in septic shock.Method: All mechanically ventilated patients treated for an episode of septic shock in our unit were studied by transesophageal echocardiography, at least once a day, during the first 3 days of hemodynamic support. In patients who recovered, echocardiography was repeated after weaning from vasoactive agents. Main measurements were obtained from the software of the apparatus. Global left ventricular hypokinesia was defined as a left ventricular ejection fraction of < 45%.Measurements and Main Results: During a 3-yr period (January 2004 through December 2006), 67 patients free from previous cardiac disease, and who survived for > 48 hrs, were repeatedly studied. Global left ventricular hypokinesia was observed in 26 of these 67 patients at admission (primary hypokinesia) and in 14 after 24 or 48 hrs of hemodynamic support by norepinephrine (secondary hypokinesia), leading to an overall hypokinesia rate of 60%. Left ventricular hypokinesia was partially corrected by do-butamine, added to a reduced dosage of norepinephrine, or by epinephrine. This reversible acute left ventricular dysfunction was not associated with a worse prognosis.Conclusion: Global left ventricular hypokinesia is very frequent in adult septic shock and could be unmasked, in some patients, by norepinephrine treatment. Left ventricular hypokinesia is usually corrected by addition of an inotropic agent to the hemodynamic support.

BACKGROUND:Despite airway pressure limitation, acute cor pulmonale persists in a minority of ARDS patients. Insufficient airway pressure limitation, hypercapnia, or both may be responsible. Because prone positioning (PP) has been shown to be a safe way to reduce airway pressure and to improve alveolar ventilation, we decided to assess its effect on right ventricular (RV) pressure overload in ARDS patients.METHODS:Between January 1998 and December 2006, we studied 42 ARDS patients treated by PP to correct severe oxygenation impairment (Pao2/fraction of inspired oxygen ratio, <100 mm Hg). RV function was evaluated by bedside transesophageal echocardiography, before and after 18 h of prone-position ventilation. RV enlargement was measured by RV/left ventricular (LV) end-diastolic area ratio in the long axis. Septal dyskinesia was quantified by measuring short-axis systolic eccentricity of the LV.RESULTS:Before PP, 21 patients (50%) had acute cor pulmonale, defined by RV enlargement associated with septal dyskinesia (group 1), whereas 21 patients had a normal RV (group 2). PP was accompanied by a significant decrease in airway pressure and Paco2. In group 1, this produced a significant decrease in mean (+/-SD) RV enlargement (from 0.91+/-0.22 to 0.61+/-0.21) after 18 h of PP (p=0.000) and a significant reduction in mean septal dyskinesia (from 1.5+/-0.2 to 1.1+/-0.1) after 18 h of PP (p=0.000).CONCLUSION:In the most severe forms of ARDS, PP was an efficient means of controlling RV pressure overload.

We tested the hypothesis that ventilation in the prone position might improve homogenization of tidal ventilation by reducing time-constant inequalities, and thus improving alveolar ventilation. We have recently reported in ARDS patients that these inequalities are responsible for the presence of a “slow compartment,” excluded from tidal ventilation at supportive respiratory rate.

Introduction We conducted a prospective observational study from January 1995 to December 2004 to evaluate the impact on recovery of a major advance in renal replacement therapy, namely continuous veno-venous haemodiafiltration (CVVHDF), in patients with refractory septic shock.Method CVVHDF was implemented after 6 - 12 hours of maximal haemodynamic support, and base excess monitoring was used to evaluate the improvement achieved. Of the 60 patients studied, 40 had improved metabolic acidosis after 12 hours of CVVHDF, with a progressive improvement in all failing organs; the final mortality rate in this subgroup was 30%. In contrast, metabolic acidosis did not improve in the remaining 20 patients after 12 hours of CVVHDF, and the mortality rate in this subgroup was 100%. The crude mortality rate for the whole group was 53%, which is significantly lower than the predicted mortality using Simplified Acute Physiology Score II (79%).Conclusion Early CVVHDF may improve the prognosis of sepsis-related multiple organ failure. Failure to correct metabolic acidosis rapidly during the procedure was a strong predictor of mortality.

CONTEXT:In recent years, protective ventilation with airway pressure limitation has constituted a major advance in acute respiratory distress syndrome treatment and has led to a substantial improvement in prognosis. With this therapeutic rationale, one may even question nowadays whether the severity of respiratory failure still influences mortality. OBJECTIVE:To determine whether the severity of respiratory failure, scored according to the usual criteria, still influences mortality in acute respiratory distress syndrome patients when a low stretch ventilation was used and to assess the impact on mortality of other nonpulmonary organ dysfunction, particularly circulatory failure. DESIGN AND SETTING:A retrospective study conducted in the medical intensive care unit of a French university hospital from October 1993 to December 2001. PATIENTS A total of 150 acute respiratory distress syndrome patients who were administered uniform protective ventilation with a limited plateau pressure (<30 cm H2O), a low positive end-expiratory pressure (<10 cm H2O), and the same strategy concerning hemodynamic support and dialysis when required. MAIN OUTCOME AND MEASURES:Mean age, general severity index (Simplified Acute Physiologic Score II), number of associated organ failures (Logistic Organ Dysfunction Score), respiratory severity indices (Pao2/Fio2, Lung Injury Severity Score), and severity of initial circulatory failure (circulatory failure present at admission or that developed during the first 48 hrs) were compared, according to recovery or death, and evaluated by a logistic regression model, which allows simultaneous control of multiple factors. RESULTS:The average mortality rate for the whole group was 38%, with 93 patients recovering after an average duration of mechanical ventilation of 18 +/- 13 days. The major factor significantly and independently associated with probability of dying was the severity of circulatory failure (p =.0001, odds ratio = 10.17). Patients free from initial circulatory failure (39 patients) had a 95% recovery rate. CONCLUSION:With our low stretch strategy, the severity of circulatory failure was the main determinant of acute respiratory distress syndrome prognosis. Patients with isolated respiratory failure during the first 48 hrs of respiratory support have an excellent chance of recovery when treated with protective ventilation associated with a low positive end-expiratory pressure.

Objective. Evaluation of low-flow pressure-volume loop at the bedside in ARDS, as an aid to assess recruitment produced by PEEP. Materials and methods. Low-flow pressure-volume loop at the bedside were obtained on the first day of respiratory support in 54 successive pulmonary ARDS patients (49 of whom had pneumonia) treated between April 1999 and June 2002. From the loop obtained at ZEEP, we determined manually the lower inflexion point (LIP). By superimposing the pressure-volume loop at ZEEP and at PEEP, we evaluated recruitment obtained at a constant elastic pressure of 20 cm H2O. Results. We observed two different types of loops, according to the pattern of the inflation limb. In type 1 (38 cases) the inflation limb was characterized by an inflexion zone, resulting from a progressive or a sudden improvement in compliance. In type 2 (16 patients) the inflation limb was virtually linear, without significant improvement in compliance during inflation, which remained particularly low (26+/-9 cm H2O). Use of a low PEEP (6+/-2 cm H2O) produced a substantial recruitment in type-1 patients (74+/-53 ml), which was marginally improved by a higher PEEP (89+/-54 ml). In type 2, recruitment produced by PEEP was significantly lower (48+/-26 ml, p=0.006). Conclusion. Pressure-volume loop at bedside confirmed that a low PEEP was sufficient to obtain recruitment in ARDS. This study also individualized a group of pulmonary ARDS patients exhibiting a markedly reduced compliance, in whom recruitment obtained by PEEP was limited.

BACKGROUND:Allowing family members to participate in the care of patients in intensive care units (ICUs) may improve the quality of their experience. No previous study has investigated opinions about family participation in ICUs.METHODS:Prospective multicenter survey in 78 ICUs (1,184 beds) in France involving 2,754 ICU caregivers and 544 family members of 357 consecutive patients. We determined opinions and experience about family participation in care; comprehension (of diagnosis, prognosis, and treatment) and satisfaction (Critical Care Family Needs Inventory) scores to assess the effectiveness of information to families and the Hospital Anxiety and Depression score for family members.RESULTS:Among caregivers 88.2% felt that participation in care should be offered to families. Only 33.4% of family members wanted to participate in care. Independent predictors of this desire fell into three groups: patient-related (SAPS II at ICU admission, OR 0.984); ICU stay length, OR 1.021), family-related (family member age, OR 0.97/year); family not of European descent, OR 0.294); previous ICU experience in the family, OR 1.59), and those related to emotional burden and effectiveness of information provided to family members (symptoms of depression in family members, OR 1.58); more time wanted for information, OR 1.06).CONCLUSIONS:Most ICU caregivers are willing to invite family members to participate in patient care, but most family members would decline.

OBJECTIVE:To assess the ability of a heated humidifier to improve CO(2) clearance in ARDS patients submitted to protective ventilation.DESIGN:Prospective clinical study.SETTING:University hospital intensive care unit.PATIENTS:During a 12-month period, we studied 11 ARDS patients under protective mechanical ventilation with severe hypercapnia.INTERVENTION:When PaCO(2) was above 55 mmHg, the heat and moisture exchanger (HME) was removed and patients were ventilated using a heated humidifier (HH) until their recovery or death. The heated humidifier was inserted on the inspiratory limb of the respirator and the inspirated air was saturated to achieve a temperature of 40 degrees C at the Y connector of ventilator tubing and of 37 degrees C at the outlet of the endotracheal tube.MEASUREMENTS AND RESULTS:Mechanical measurements and blood gas analysis were performed just before removal of the HME, and 30 min after mechanical ventilation using HH. Ventilator parameters were kept constant in the two conditions. Using HH instead of HME, PaCO(2) was safely decreased by 11+/-5 mmHg, without any need to change respiratory rate. No significant difference was noted in intrinsic PEEP or airway plateau pressure. Decrease in PaCO(2) after HME removal was strongly correlated with the initial value of PaCO(2).CONCLUSION:Supposing there is an interest in correcting or limiting hypercapnic acidosis in ARDS patients submitted to protective ventilation, HME removal and use of HH appears to be an efficient and safe way of increasing CO(2) clearance.

. Objective : The indications for the use of thrombolytic agents in massive pulmonary embolism (MPE) remain controversial and it has been suggested that transthoracic echocardiographic (TTE) examination, which is able to detect an associated right ventricular dysfunction, may cast light on this question. The goal of this study was to examine the incidence of acute cor pulmonale (ACP) in MPE, diagnosed on the basis of TTE criteria, its clinical implications and its resolution rate. Design : Ten-year retrospective clinical study. Setting : A medical and a coronary intensive care unit, university hospital. Patients : One hundred sixty-one patients with proven MPE. Interventions : Acute cor pulmonale was defined as right ventricular end-diastolic area / left ventricular end-diastolic area (RVEDA/LVEDA) ratio in the long axis greater than 0.6 associated with septal dyskinesia in the short axis. ACP patients were divided into three groups according to circulatory status: 32 patients without circulatory failure constituted group 1, 32 patients with circulatory failure requiring inotropic support, but free of metabolic acidosis, constituted group 2 and 34 patients in whom circulatory failure was associated with metabolic acidosis (defined by a base deficit >5 mEq/l) constituted group 3. Results : Acute cor pulmonale was present in 61% of patients with MPE and carried a 23% mortality, but this mortality was very different in stable patients (groups 1 and 2, 64 patients, 3% mortality) and in unstable patients (group 3, 34 patients, 59% mortality). A multivariate logistic regression analysis showed that the TTE results were not predictive of the risk of death. Conversely, the same analysis showed that the presence of metabolic acidosis was a powerful predictor of death. Conclusion : Because none of the TTE measurements in ACP could be used to stratify the severity of MPE, TTE was of no help in deciding on medical thrombolysis. However, depending on its severity, metabolic acidosis could justify a large cooperative study to assess the impact of thrombolytic therapy on mortality rate in this specific group.