Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL: ClinicalTrial. Gov identification number: NCT01730690.

Monitoring epidemic viral respiratory infections using one-step real-time triplex RT-PCR targeting influenza A and B viruses and respiratory syncytial virus.

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.

PaCO2 and alveolar dead space are more relevant than PaO2/FiO2 ratio in monitoring the respiratory response to prone position in ARDS patients: a physiological study.

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.

Actual incidence of global left ventricular hypokinesia in adult septic shock.

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 dobutamine, 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.

Prone positioning unloads the right ventricle in severe ARDS.

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.

Prone position improves mechanics and alveolar ventilation in acute respiratory distress syndrome.

OBJECTIVE: 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. DESIGN: In 11 ARDS patients treated by ventilation in the prone position because of a major oxygenation impairment (PaO(2)/FIO(2)

Early veno-venous haemodiafiltration for sepsis-related multiple organ failure.

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.

Superior vena caval collapsibility as a gauge of volume status in ventilated septic patients.

OBJECTIVE: In mechanically ventilated patients inspiratory increase in pleural pressure during lung inflation may produce complete or partial collapse of the superior vena cava. Occurrence of this collapse suggests that at this time external pressure exerted by the thoracic cavity on the superior vena cava is greater than the venous pressure required to maintain the vessel fully open. We tested the hypothesis that measurement of superior vena caval collapsibility would reveal the need for volume expansion in a given septic patient. DESIGN AND SETTING: Prospective data collection for 66 successive patients in septic shock admitted in a medical intensive care unit and mechanically ventilated for an associated acute lung injury. MEASUREMENTS AND RESULTS: We simultaneously measured superior vena caval collapsibility by echocardiography and cardiac index by the Doppler technique at baseline and after a 10 ml/kg volume expansion by 6% hydroxyethyl starch in 30 min. The threshold superior vena caval collapsibility of 36%, calculated as (maximum diameter on expiration-minimum diameter on inspiration)/maximum diameter on expiration, allowed discrimination between responders (defined by an increase in cardiac index of at least 11% induced by volume expansion) and nonresponders, with a sensitivity of 90% and a specificity of 100%. CONCLUSIONS: Superior vena cava measurement should be systematically performed during routine echocardiography in septic shock as it gives an accurate index of fluid responsiveness.

Early patterns of static pressure-volume loops in ARDS and their relations with PEEP-induced recruitment.

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.

Ability and safety of a heated humidifier to control hypercapnic acidosis in severe ARDS.

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.

Family participation in care to the critically ill: opinions of families and staff.

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.

Routine prone positioning in patients with severe ARDS: feasibility and impact on prognosis.

PURPOSE: Since 1997, we have routinely used prone positioning (PP) in patients who have a PaO(2)/FiO(2) 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). RESULTS: A total of 218 patients were admitted because of ARDS between 1997 and 2009. Of these patients, 57 (26%) were positioned prone because of a PaO(2)/FiO(2) below 100 mmHg after 24-48 h of mechanical ventilation. Age was 51 ± 16 years, PaO(2)/FiO(2) 74 ± 19, and PaCO(2) 54 ± 10 mmHg. The lung injury score was 3.13 ± 0.15. Tidal volume was 7 ± 2 mL/kg, PEEP 5.6 ± 1.2 cmH(2)O, and plateau pressure 27 ± 3 cmH(2)O. Prone sessions lasted 18 h/day and 3.4 ± 1.1 sessions were required to obtain an FiO(2) below 60%. The 60-day mortality was 19% and death occurred after 12 ± 5 days. The ratio between observed and predicted mortality was 0.43. In patients with a PaO(2)/FiO(2) below 60 mmHg, the 60-day mortality was 28%. Logistic regression analysis showed that among the 218 patients, PP appeared to be protective with an odds ratio of 0.35 [0.16-0.79]. CONCLUSION: We demonstrate the clinical feasibility of routine PP in patients with a PaO(2)/FiO(2) below 100 mmHg after 24-48 h and suggest that, when combined with a low stretch ventilation strategy, it is protective with a high survival rate.

Low stretch ventilation strategy in acute respiratory distress syndrome: eight years of clinical experience in a single center.

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.

Cyclic changes in arterial pulse during respiratory support revisited by Doppler echocardiography.

It has long been known that there are cyclic changes in arterial pressure during mechanical ventilation. They are caused by cyclic changes in both the right and left ventricular stroke output, occurring in opposite phases. As a result, arterial pulse pressure is increased during inspiration and decreased during expiration. A cyclic improvement in left ventricular systolic function could thus be expected during mechanical lung inflation. We tested this hypothesis in 31 septic patients who were mechanically ventilated in controlled mode by combining left ventricular measurements by transesophageal echocardiography with invasive arterial pressure recordings and Doppler analysis of pulmonary venous flow and right and left ventricular stroke volume. Lung inflation by tidal ventilation significantly improved left ventricular stroke volume (26 +/- 0.4 cm3/m2 [mean +/- SEM] vs. 22.3 +/- 0.4 cm3/m2 at end deflation). Beat-to-beat analysis of pulmonary venous flow velocity illustrated the boosting effect of lung inflation on pulmonary venous return. The beneficial effect of inspiration thus appeared directly related to a significant increase in left ventricular diastolic volume (60.3 +/- 1.5 cm3/m2 vs. 53.3 +/- 1.4 cm3/m2 at end-expiration) and to a lesser extent to an improved left ventricular ejection fraction. We concluded that the transient beneficial hemodynamic effect of tidal ventilation on the left ventricular pump is essentially mediated by an improved left ventricular filling.

Increasing respiratory rate to improve CO2 clearance during mechanical ventilation is not a panacea in acute respiratory failure.

BACKGROUND: Increasing respiratory rate has recently been proposed to improve CO2 clearance in patients with acute respiratory failure who are receiving mechanical ventilation. However, the efficacy of this strategy may be limited by deadspace ventilation, and it might induce adverse hemodynamic effects related to dynamic hyperinflation. SETTING: An intensive care unit of a university hospital. PATIENTS: We studied 14 patients with acute respiratory failure during the adjustment of ventilator settings on the first day of mechanical ventilation in volume-controlled mode. MEASUREMENTS: After determining the positive end-expiratory pressure that suppresses any intrinsic positive end-expiratory pressure at a respiratory rate of 15 breaths/min, we compared blood gas analysis, respiratory measurements, and Doppler evaluation of right ventricular systolic function by using two different respiratory strategies with the same airway pressure limitation (plateau pressure, < or =25 cm H2O), a low-rate conventional respiratory strategy with a respiratory rate of 15 breaths/min, and a high-rate strategy with a respiratory rate of 30 breaths/min. RESULTS: Compared with the low-rate strategy, the high-rate strategy neither significantly reduced PaCO2 (47 +/- 8 vs. 51 +/- 7 mm Hg with the low-rate strategy) nor significantly improved PaO2 (99 +/- 40 vs. 95 +/- 35 mm Hg with the low-rate strategy). It significantly increased alveolar deadspace to tidal volume ratio (21% +/- 8%, vs. 14% +/- 6% with the low-rate strategy) and produced dynamic hyperinflation, resulting in a substantial intrinsic positive end-expiratory pressure (6.4 +/- 2.7 cm H2O). Right ventricular outflow impedance was increased, resulting in a significant drop in the cardiac index (2.9 +/- 0.6 vs. 3.3 +/- 0.7 L/min/m with the low-rate strategy). CONCLUSION: We conclude that a high respiratory rate strategy during mechanical ventilation in patients with acute respiratory failure did not improve CO2 clearance, produced dynamic hyperinflation, and impaired right ventricular ejection.

Pressure-volume curves in acute respiratory distress syndrome: clinical demonstration of the influence of expiratory flow limitation on the initial slope.

The presence of an initial segment with a low compliance on the static pressure-volume (PV) curve in patients with acute respiratory distress syndrome (ARDS) indicates that some lung compartments do not initially receive insufflated gas. We tested the hypothesis that an uneven distribution of time constants, producing a "slow compartment," was in part responsible for the change in compliance between the initial and the intermediate segment of the PV curve. In 16 patients with ARDS submitted to mechanical ventilation in volume-controlled mode with a supportive respiratory rate of 15 breaths/minute, we constructed the static PV curve on the first day of respiratory support and determined the intrinsic positive end-expiratory pressure (PEEPi4) during a prolonged end-expiratory pause (4 seconds). We also measured the volume of a "slow compartment" during a prolonged expiration (> 6 seconds), and determined an external PEEP (PEEPe) suppressing PEEPi4. Among the 16 patients studied, 11 exhibited a low inflection point, associated with a "slow compartment" of 172 +/- 83 ml, responsible for a PEEPi4 of 3 +/- 2 cm H2O. Conversely, the five remaining patients had a linear PV curve, associated with a minimal "slow compartment" of 28 +/- 10 ml, responsible for a negligible PEEPi4. We observed that individual slopes of the initial segment of the PV curve were inversely and significantly correlated with the proportion of the "slow compartment" (r = -0.85). We concluded that the shape of the inspiratory PV curve in ARDS might be dependent on the presence of a "slow compartment," and demonstrated that a low external PEEP appeared sufficient to achieve a substantial mechanical improvement in clinical practice.