V. Marco Ranieri

The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material

PurposeOur objective was to revise the definition of acute respiratory distress syndrome (ARDS) using a conceptual model incorporating reliability and validity, and a novel iterative approach with formal evaluation of the definition.MethodsThe European Society of Intensive Care Medicine identified three chairs with broad expertise in ARDS who selected the participants and created the agenda. After 2xa0days of consensus discussions a draft definition was developed, which then underwent empiric evaluation followed by consensus revision.ResultsThe Berlin Definition of ARDS maintains a link to prior definitions with diagnostic criteria of timing, chest imaging, origin of edema, and hypoxemia. Patients may have ARDS if the onset is within 1xa0week of a known clinical insult or new/worsening respiratory symptoms. For the bilateral opacities on chest radiograph criterion, a reference set of chest radiographs has been developed to enhance inter-observer reliability. The pulmonary artery wedge pressure criterion for hydrostatic edema was removed, and illustrative vignettes were created to guide judgments about the primary cause of respiratory failure. If no risk factor for ARDS is apparent, however, objective evaluation (e.g., echocardiography) is required to help rule out hydrostatic edema. A minimum level of positive end-expiratory pressure and mutually exclusive PaO2/FiO2 thresholds were chosen for the different levels of ARDS severity (mild, moderate, severe) to better categorize patients with different outcomes and potential responses to therapy.ConclusionsThis panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice.

The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks

PurposeIn view of the expected 2009 influenza A(H1N1) pandemic, the Italian Health Authorities set up a national referral network of selected intensive care units (ICU) able to provide advanced respiratory care up to extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS). We describe the organization and results of the network, known as ECMOnet.MethodsThe network consisted of 14 ICUs with ECMO capability and a national call center. The network was set up to centralize all severe patients to the ECMOnet centers assuring safe transfer. An ad hoc committee defined criteria for both patient transfer and ECMO institutions.ResultsBetween August 2009 and March 2010, 153 critically ill patients (53% referred from other hospitals) were admitted to the ECMOnet ICU with suspected H1N1. Sixty patients (48 of the referred patients, 49 with confirmed H1N1 diagnosis) received ECMO according to ECMOnet criteria. All referred patients were successfully transferred to the ECMOnet centers; 28 were transferred while on ECMO. Survival to hospital discharge in patients receiving ECMO was 68%. Survival of patients receiving ECMO within 7xa0days from the onset of mechanical ventilation was 77%. The length of mechanical ventilation prior to ECMO was an independent predictor of mortality.ConclusionsA network organization based on preemptive patient centralization allowed a high survival rate and provided effective and safe referral of patients with severe H1N1-suspected ARDS.

Patient-ventilator interaction and sleep in mechanically ventilated patients: pressure support versus proportional assist ventilation.

Objectives:To understand the role of patient-ventilator asynchrony in the etiology of sleep disruption and determine whether optimizing patient-ventilator interactions by using proportional assist ventilation improves sleep. Design:Randomized crossover clinical trial. Setting:A tertiary university medical-surgical intensive care unit. Patients:Thirteen patients during weaning from mechanical ventilation. Interventions:Patients were randomized to receive pressure support ventilation or proportional assist ventilation on the first night and then crossed over to the alternative mode for the second night. Polysomnography and measurement of light, noise, esophageal pressure, airway pressure, and flow were performed from 10 pm to 8 am. Ventilator settings (pressure level during pressure support ventilation and resistive and elastic proportionality factors during proportional assist ventilation) were set to obtain a 50% reduction of the inspiratory work (pressure time product per minute) performed during a spontaneous breathing trial. Measurements and Main Results:Arousals per hour of sleep time during pressure support ventilation were 16 (range 2–74) and 9 (range 1–41) during proportional assist ventilation (p = .02). Overall sleep quality was significantly improved on proportional assist ventilation (p < .05) due to the combined effect of fewer arousals per hour, fewer awakenings per hour (3.5 [0–24] vs. 5.5 [1–24]), and greater rapid eye movement (9% [0–31] vs. 4% [0–23]), and slow wave (3% [0–16] vs. 1% [0–10]) sleep. Tidal volume and minute ventilation were lower on proportional assist ventilation, allowing for a greater increase in Paco2 during the night. Patient-ventilator asynchronies per hour were lower with proportional assist ventilation than with pressure support ventilation (24 ± 15 vs. 53 ± 59; p = .02) and correlated with the number of arousals per hour (R2 = .65, p = .0001). Conclusions:Patient ventilator discordance causes sleep disruption. Proportional assist ventilation seems more efficacious than pressure support ventilation in matching ventilatory requirements with ventilator assistance, therefore resulting in fewer patient-ventilator asynchronies and better quality of sleep.

Diagnosis of ventilator-associated pneumonia: a systematic review of the literature

IntroductionEarly, accurate diagnosis is fundamental in the management of patients with ventilator-associated pneumonia (VAP). The aim of this qualitative review was to compare various criteria of diagnosing VAP in the intensive care unit (ICU) with a special emphasis on the value of clinical diagnosis, microbiological culture techniques, and biomarkers of host response.MethodsA MEDLINE search was performed using the keyword ventilator associated pneumonia AND diagnosis. Our search was limited to human studies published between January 1966 and June 2007. Only studies of at least 25 adult patients were included. Predefined variables were collected, including year of publication, study design (prospective/retrospective), number of patients included, and disease group.ResultsOf 572 articles fulfilling the initial search criteria, 159 articles were chosen for detailed review of the full text. A total of 64 articles fulfilled the inclusion criteria and were included in our review. Clinical criteria, used in combination, may be helpful in diagnosing VAP, however, the considerable inter-observer variability and the moderate performance should be taken in account. Bacteriologic data do not increase the accuracy of diagnosis as compared to clinical diagnosis. Quantitative cultures obtained by different methods seem to be rather equivalent in diagnosing VAP. Blood cultures are relatively insensitive to diagnose pneumonia. The rapid availability of cytological data, including inflammatory cells and Gram stains, may be useful in initial therapeutic decisions in patients with suspected VAP. C-reactive protein, procalcitonin, and soluble triggering receptor expressed on myeloid cells are promising biomarkers in diagnosing VAP.ConclusionAn integrated approach should be followed in diagnosing and treating patients with VAP, including early antibiotic therapy and subsequent rectification according to clinical response and results of bacteriologic cultures.

ECMO criteria for influenza A (H1N1)-associated ARDS: role of transpulmonary pressure.

PurposeTo assess whether partitioning the elastance of the respiratory system (ERS) between lung (EL) and chest wall (ECW) elastance in order to target values of end-inspiratory transpulmonary pressure (PPLATL) close to its upper physiological limit (25xa0cmH2O) may optimize oxygenation allowing conventional treatment in patients with influenza A (H1N1)-associated ARDS referred for extracorporeal membrane oxygenation (ECMO).MethodsProspective data collection of patients with influenza A (H1N1)-associated ARDS referred for ECMO (October 2009–January 2010). Esophageal pressure was used to (a) partition respiratory mechanics between lung and chest wall, (b) titrate positive end-expiratory pressure (PEEP) to target the upper physiological limit of PPLATL (25xa0cmH2O).ResultsFourteen patients were referred for ECMO. In seven patients PPLATL was 27.2xa0±xa01.2xa0cmH2O; all these patients underwent ECMO. In the other seven patients, PPLATL was 16.6xa0±xa02.9xa0cmH2O. Raising PEEP (from 17.9xa0±xa01.2 to 22.3xa0±xa01.4xa0cmH2O, Pxa0=xa00.0001) to approach the upper physiological limit of transpulmonary pressure (PPLATLxa0=xa025.3xa0±xa01.7xa0cm H2O) improved oxygenation index (from 37.4xa0±xa03.7 to 16.5xa0±xa01.4, Pxa0=xa00.0001) allowing patients to be treated with conventional ventilation.ConclusionsAbnormalities of chest wall mechanics may be present in some patients with influenza A (H1N1)-associated ARDS. These abnormalities may not be inferred from measurements of end-inspiratory plateau pressure of the respiratory system (PPLATRS). In these patients, titrating PEEP to PPLATRS may overestimate the incidence of hypoxemia refractory to conventional ventilation leading to inappropriate use of ECMO.

Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to influenza A (H1N1) pneumonia: the ECMOnet score

PurposeThe decision to start venovenous extracorporeal membrane oxygenation (VV ECMO) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. The aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of VV ECMO initiation.MethodsThis was a prospective multicenter cohort study on 60 patients with influenza A (H1N1)-associated respiratory distress syndrome participating in the Italian ECMOnet data set in the 2009 pandemic. Criteria for ECMO institution were standardized according to national guidelines.ResultsThe survival rate in patients treated with ECMO was 68xa0%. Significant predictors of death before ECMO institution by multivariate analysis were hospital length of stay before ECMO institution (ORxa0=xa01.52, 95xa0% CI 1.12–2.07, pxa0=xa00.008); bilirubin (ORxa0=xa02.32, 95xa0% CI 1.52–3.52, pxa0<xa00.001), creatinine (ORxa0=xa07.38, 95xa0% CI 1.43–38.11, pxa0=xa00.02) and hematocrit values (ORxa0=xa00.82, 95xa0% CI 0.72–0.94, pxa0=xa00.006); and mean arterial pressure (ORxa0=xa00.92, 95xa0% CI 0.88–0.97, pxa0<xa00.001). The ECMOnet score was developed based on these variables, with a score of 4.5 being the most appropriate cutoff for mortality risk prediction. The high accuracy of the ECMOnet score was further confirmed by ROC analysis (cxa0=xa00.857, 95xa0% CI 0.754–0.959, pxa0<xa00.001) and by an independent external validation analysis (cxa0=xa00.694, 95xa0% CI 0.562–0.826, pxa0=xa00.004).ConclusionsMortality risk for patients receiving VV ECMO is correlated to the extrapulmonary organ function at the time of ECMO initiation. The ECMOnet score is a tool for the evaluation of the appropriateness and timing of VV ECMO in acute lung failure.

Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy.

PurposeAlthough chemotherapy and transplantation improve outcome of patients with hematological malignancy, complications of these therapies are responsible for a 20–50% mortality rate that increases when respiratory symptoms evolve into acute lung injury (ALI). The aim of this study is to determine the effectiveness of early continuous positive airway pressure (CPAP) delivered in the ward to prevent occurrence of ALI requiring intensive care unit (ICU) admission for mechanical ventilation.MethodsPatients with hematological malignancy presenting in the hematological ward with early changes in respiratory variables were randomized to receive oxygen (Nxa0=xa020) or oxygen plus CPAP (Nxa0=xa020). Primary outcome variables were need of mechanical ventilation requiring ICU admission, and intubation rate among those patients who required ICU admission.ResultsAt randomization, arterial-to-inspiratory O2 ratio in control and CPAP group was 282xa0±xa041 and 256xa0±xa052, respectively. Patients who received CPAP had less need of ICU admission for mechanical ventilation (4 versus 16 patients; Pxa0=xa00.0002). CPAP reduced the relative risk for developing need of ventilatory support to 0.25 (95% confidence interval: 0.10–0.62). Among patients admitted to ICU, intubation rate was lower in the CPAP than in the control group (2 versus 14 patients; Pxa0=xa00.0001). CPAP reduced the relative risk for intubation to 0.46 (95% confidence interval: 0.27–0.78).ConclusionsThis study suggests that early use of CPAP on the hematological ward in patients with early changes in respiratory variables prevents evolution to acute lung injury requiring mechanical ventilation and ICU admission.

Polymyxin-B hemoperfusion inactivates circulating proapoptotic factors

ObjectiveTo test the hypothesis that extracorporeal therapy with polymyxin B (PMX-B) may prevent Gram-negative sepsis-induced acute renal failure (ARF) by reducing the activity of proapoptotic circulating factors.SettingMedical-Surgical Intensive Care Units.Patients and interventionsSixteen patients with Gram-negative sepsis were randomized to receive standard care (Surviving Sepsis Campaign guidelines) or standard care plus extracorporeal therapy with PMX-B.Measurements and resultsCell viability, apoptosis, polarity, morphogenesis, and epithelial integrity were evaluated in cultured tubular cells and glomerular podocytes incubated with plasma from patients of both groups. Renal function was evaluated as SOFA and RIFLE scores, proteinuria, and tubular enzymes. A significant decrease of plasma-induced proapoptotic activity was observed after PMX-B treatment on cultured renal cells. SOFA and RIFLE scores, proteinuria, and urine tubular enzymes were all significantly reduced after PMX-B treatment. Loss of plasma-induced polarity and permeability of cell cultures was abrogated with the plasma of patients treated with PMX-B. These results were associated to a preserved expression of molecules crucial for tubular and glomerular functional integrity.ConclusionsExtracorporeal therapy with PMX-B reduces the proapoptotic activity of the plasma of septic patients on cultured renal cells. These data confirm the role of apoptosis in the development of sepsis-related ARF.

Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study.

IntroductionAlbumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome.MethodsIn a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay.ResultsOf 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001).ConclusionAlbumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients.

Circulating plasma factors induce tubular and glomerular alterations in septic burns patients

BackgroundSevere burn is a systemic illness often complicated by sepsis. Kidney is one of the organs invariably affected, and proteinuria is a constant clinical finding. We studied the relationships between proteinuria and patient outcome, severity of renal dysfunction and systemic inflammatory state in burns patients who developed sepsis-associated acute renal failure (ARF). We then tested the hypothesis that plasma in these patients induces apoptosis and functional alterations that could account for proteinuria and severity of renal dysfunction in tubular cells and podocytes.MethodsWe studied the correlation between proteinuria and indexes of systemic inflammation or renal function prospectively in 19 severe burns patients with septic shock and ARF, and we evaluated the effect of plasma on apoptosis, polarity and functional alterations in cultured human tubular cells and podocytes. As controls, we collected plasma from 10 burns patients with septic shock but without ARF, 10 burns patients with septic shock and ARF, 10 non-burns patients with septic shock without ARF, 10 chronic uremic patients and 10 healthy volunteers.ResultsSeptic burns patients with ARF presented a severe proteinuria that correlated to outcome, glomerular (creatinine/urea clearance) and tubular (fractional excretion of sodium and potassium) functional impairment and systemic inflammation (white blood cell (WBC) and platelet counts). Plasma from these patients induced a pro-apoptotic effect in tubular cells and podocytes that correlated with the extent of proteinuria. Plasma-induced apoptosis was significantly higher in septic severe burns patients with ARF with respect to those without ARF or with septic shock without burns. Moreover, plasma from septic burns patients induced an alteration of polarity in tubular cells, as well as reduced expression of the tight junction protein ZO-1 and of the endocytic receptor megalin. In podocytes, plasma from septic burns patients increased permeability to albumin and decreased the expression of the slit diaphragm protein nephrin.ConclusionPlasma from burns patients with sepsis-associated ARF contains factors that affect the function and survival of tubular cells and podocytes. These factors are likely to be involved in the pathogenesis of acute tubular injury and proteinuria, which is a negative prognostic factor and an index of renal involvement in the systemic inflammatory reaction.