Otavio T. Ranzani

Community-acquired pneumonia

Summary Community-acquired pneumonia causes great mortality and morbidity and high costs worldwide. Empirical selection of antibiotic treatment is the cornerstone of management of patients with pneumonia. To reduce the misuse of antibiotics, antibiotic resistance, and side-effects, an empirical, effective, and individualised antibiotic treatment is needed. Follow-up after the start of antibiotic treatment is also important, and management should include early shifts to oral antibiotics, stewardship according to the microbiological results, and short-duration antibiotic treatment that accounts for the clinical stability criteria. New approaches for fast clinical (lung ultrasound) and microbiological (molecular biology) diagnoses are promising. Community-acquired pneumonia is associated with early and late mortality and increased rates of cardiovascular events. Studies are needed that focus on the long-term management of pneumonia.

C-Reactive Protein/Albumin Ratio Predicts 90-Day Mortality of Septic Patients

Introduction Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone. Methods We evaluated 334 patients admitted to the ICU as a result of severe sepsis or septic shock who were discharged alive after a minimum of 72 hours in the ICU. We evaluated the performance of both CRP and CRP/albumin to predict mortality at 90 days after ICU discharge. Two multivariate logistic models were generated based on measurements at discharge: one model included CRP (Model-CRP), and the other included the CRP/albumin ratio (Model-CRP/albumin). Results There were 229 (67%) and 111 (33%) patients with severe sepsis and septic shock, respectively. During the 90 days of follow-up, 73 (22%) patients died. CRP/albumin ratios at admission and at discharge were associated with a poor outcome and showed greater accuracy than CRP alone at these time points (p = 0.0455 and p = 0.0438, respectively). CRP levels and the CRP/albumin ratio were independent predictors of mortality at 90 days (Model-CRP: adjusted OR 2.34, 95% CI 1.14–4.83, p = 0.021; Model-CRP/albumin: adjusted OR 2.18, 95% CI 1.10–4.67, p = 0.035). Both models showed similar accuracy (p = 0.2483). However, Model-CRP was not calibrated. Conclusions Residual inflammation at ICU discharge assessed using the CRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients. The use of the CRP/albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.

An in vitro study to assess determinant features associated with fluid sealing in the design of endotracheal tube cuffs and exerted tracheal pressures.

Objective:To assess the structural characteristics involved in the design of high-volume low-pressure endotracheal tube cuffs that are associated with fluid sealing effectiveness and to determine the extent of transmitted tracheal pressures upon cuff inflation. Design:In vitro study. Settings:Pneumology laboratories. Interventions:Eight high-volume low-pressure cuffs of cylindrical or tapered shape, made of polyvinylchloride or polyurethane, were studied. Cuffs were tested within a tracheal model, oriented 30° above horizontal to assess 1 hr leakage of oropharyngeal secretions simulant at cuff internal pressures of 15–30 cm H2O. The four best performing cuffs were evaluated for 24 hrs using an internal pressure of 30 cm H2O. The extent of transmitted tracheal wall pressure throughout the cuff–trachea contact area was determined using an internal pressure sensor within a tracheal model upon cuff inflation up to 30 cm H2O. Measurements and Main Results:Outer diameter, length, and compliance of each cuff were assessed. Multivariate regression analysis was performed to identify the main determinants of simulant leakage rate. The cuff–trachea contact area and the percentage of tracheal wall pressure measurements greater than 50 cm H2O were computed. Cuff design characteristics significantly differ among tubes. The cuffs made of polyurethane showed the best short- and long-term sealing efficacy. Nevertheless, in the multivariate analysis, the cuff outer diameter (n: 288, p = 0.003) and length (n: 288, p < 0.001), along with the internal pressure (n: 288, p < 0.001), were the only predictors of simulant leakage rate. The tapered cuffs showed the lowest tracheal wall contact area (n: 96, p < 0.001). The tracheal wall pressure distribution pattern was heterogeneous, and the percentage of high tracheal wall pressure significantly differs among the cuffs (n: 96, p < 0.001). Conclusions:The high-volume low-pressure cuffs’ outer diameter, length, material, and internal pressure are the main determinants of sealing efficacy. Despite internal pressure within the safe range, transmitted tracheal pressure is extremely heterogeneous and differs among cuffs, occasionally reaching localized, very high, unsafe levels.

Extracorporeal membrane oxygenation for severe respiratory failure in adult patients: A systematic review and meta-analysis of current evidence

BACKGROUND Extracorporeal membrane oxygenation (ECMO) for acute respiratory failure is still a matter of debate. METHODS We performed a structured search on Pubmed, EMBASE, Lilacs, and the Cochrane Library for randomized controlled trials and observational case-control studies with severity-paired patients, evaluating the use of ECMO on severe acute respiratory failure in adult patients. A random-effect model using DerSimonian and Laird method for variance estimator was performed to evaluate the effect of ECMO use on hospital mortality. Heterogeneity between studies was assessed with Cochrans Q statistic and Higgins I(2). RESULTS Three studies were included on the metanalysis, comprising 353 patients in the main analysis, in which 179 patients were ECMO supported. One study was a randomized controlled trial and two were observational studies with a propensity score matching. The most common reason for acute respiratory failure was influenza H1N1 pneumonia (45%) and pneumonia (33%). ECMO was not associated with a reduction in hospital mortality (OR = 0.71; CI 95% = 0.34 - 1.47; P = 0.358). If alternative severity-pairing method presented by the two observational studies was included, a total of 478 cases were included, in which 228 received ECMO support. In the former analysis, ECMO had a benefit on hospital mortality (OR = 0.52; CI 95% = 0.35 - 0.76; P < 0.001). CONCLUSION Extracorporeal membrane oxygenation benefit on hospital mortality is unclear. Results were sensitive to statistical analysis, and no definitive conclusion can be drawn from the available data. More studies are needed before the widespread use of ECMO can be recommended.

Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: A cohort study ☆,☆☆

PURPOSE To discharge a patient from the intensive care unit (ICU) is a complex decision-making process because in-hospital mortality after critical illness may be as high as up to 27%. Static C-reactive protein (CRP) values have been previously evaluated as a predictor of post-ICU mortality with conflicting results. Therefore, we evaluated the CRP ratio in the last 24 hours before ICU discharge as a predictor of in-hospital outcomes. METHODS A retrospective cohort study was performed in 409 patients from a 6-bed ICU of a university hospital. Data were prospectively collected during a 4-year period. Only patients discharged alive from the ICU with at least 72 hours of ICU length of stay were evaluated. RESULTS In-hospital mortality was 18.3% (75/409). Patients with reduction less than 25% in CRP concentrations at 24 hours as compared with 48 hours before ICU discharge had a worse prognosis, with increased mortality (23% vs 11%, P = .002) and post-ICU length of stay (26 [7-43] vs 11 [5-27] days, P = .036). Moreover, among hospital survivors (n = 334), patients with CRP reduction less than 25% were discharged later (hazard ratio, 0.750; 95% confidence interval, 0.602-0.935; P = .011). CONCLUSIONS In this large cohort of critically ill patients, failure to reduce CRP values more than 25% in the last 24 hours of ICU stay is a strong predictor of worse in-hospital outcomes.

Association between systemic corticosteroids and outcomes of intensive care unit-acquired pneumonia*

Objective:The use of corticosteroids is frequent in critically-ill patients. However, little information is available on their effects in patients with intensive care unit–acquired pneumonia. We assessed patients’ characteristics, microbial etiology, inflammatory response, and outcomes of previous corticosteroid use in patients with intensive care unit–acquired pneumonia. Design:Prospective observational study. Setting:Intensive care units of a university teaching hospital. Patients:Three hundred sixteen patients with intensive care unit–acquired pneumonia. Patients were divided according to previous systemic steroid use at onset of pneumonia. Interventions:None. Measurements and Main Results:Survival at 28 days was analyzed using Cox regression, with adjustment for the propensity for receiving steroid therapy. One hundred twenty-five (40%) patients were receiving steroids at onset of pneumonia. Despite similar baseline clinical severity, steroid treatment was associated with decreased 28-day survival (adjusted hazard ratio for propensity score and mortality predictors 2.503; 95% confidence interval 1.176–5.330; p = .017) and decreased systemic inflammatory response. In post hoc analyses, steroid treatment had an impact on survival in patients with nonventilator intensive care unit–acquired pneumonia, those with lower baseline severity and organ dysfunction, and those without etiologic diagnosis or bacteremia. The cumulative dosage of corticosteroids had no significant effect on the risk of death, but bacterial burden upon diagnosis was higher in patients receiving steroid therapy. Conclusions:In critically-ill patients, systemic corticosteroids should be used very cautiously because this treatment is strongly associated with increased risk of death in patients with intensive care unit–acquired pneumonia, particularly in the absence of established indications and in patients with lower baseline severity. Decreased inflammatory response may result in delayed clinical suspicion of intensive care unit–acquired pneumonia and higher bacterial count.

Emotional Disorders in Pairs of Patients and Their Family Members during and after ICU Stay

Introduction Patients and family members undergo different experiences of suffering from emotional disorders during ICU stay and after ICU discharge. The purpose of this study was to compare the incidence of anxiety, depression and post-traumatic stress disorder (PTSD) symptoms in pairs (patient and respective family member), during stay at an open visit ICU and at 30 and 90-days post-ICU discharge. We hypothesized that there was a positive correlation with the severity of symptoms among pairs and different patterns of suffering over time. Methods A prospective study was conducted in a 22-bed adult general ICU including patients with >48 hours stay. The Hospital Anxiety and Depression Scale (HADS) was completed by the pairs (patients/respective family member). Interviews were made by phone at 30 and 90-days post-ICU discharge using the Impact of Event Scale (IES) and the HADS. Multivariate models were constructed to predict IES score at 30 days for patients and family members. Results Four hundred and seventy one family members and 289 patients were interviewed in the ICU forming 184 pairs for analysis. Regarding HADS score, patients presented less symptoms than family members of patients who survived and who deceased at 30 and 90-days (p<0.001). However, family members of patients who deceased scored higher anxiety and depression symptoms (p = 0.048) at 90-days when compared with family members of patients who survived. Patients and family members at 30-days had a similar IES score, but it was higher in family members at 90-days (p = 0.019). For both family members and patients, age and symptoms of anxiety and depression during ICU were the major determinants for PTSD at 30-days. Conclusions Anxiety, depression and PTSD symptoms were higher in family members than in the patients. Furthermore, these symptoms in family members persisted at 3 months, while they decreased in patients.

Validation of predictors of adverse outcomes in hospital-acquired pneumonia in the ICU.

Objective:To validate a set of predictors of adverse outcomes in patients with ICU-acquired pneumonia in relation to clinically relevant assessment at 28 days. Design:Prospective, observational study. Setting:Six medical and surgical ICUs of a university hospital. Patients:Three hundred thirty-five patients with ICU-acquired pneumonia. Interventions:None. Measurements and Main Results:Development of predictors of adverse outcomes was defined when at least one of the following criteria was present at an evaluation made 72–96 hours after starting treatment: no improvement of PaO2/FIO2, need for intubation due to pneumonia, persistence of fever or hypothermia with purulent respiratory secretions, greater than or equal to 50% increase in radiographic infiltrates, or occurrence of septic shock or multiple organ dysfunction syndrome. We also assessed the inflammatory response by different serum biomarkers. The presence of predictors of adverse outcomes was related to mortality and ventilator-free days at day 28. Sequential Organ Failure Assessment score was evaluated and related to mortality at day 28.One hundred eighty-four (55%) patients had at least one predictor of adverse outcomes. The 28-day mortality was higher for those with versus those without predictors of adverse outcomes (45% vs 19%, p < 0.001), and ventilator-free days were lower (median [interquartile range], 0 [0–17] vs 22 [0–28]) for patients with versus patients without predictors of adverse outcomes (p < 0.001). The lack of improvement of PaO2/FIO2 and lack of improvement in Sequential Organ Failure Assessment score from day 1 to day 5 were independently associated with 28-day mortality and fewer ventilator-free days. The marginal structural analysis showed an odds ratio of death 2.042 (95% CI, 1.01–4.13; p = 0.047) in patients with predictors of adverse outcomes. Patients with predictors of adverse outcomes had higher serum inflammatory response accordingly to biomarkers evaluated. Conclusions:The presence of any predictors of adverse outcomes was associated with mortality and decreased ventilator-free days at day 28. The lack of improvement in the PaO2/FIO2 and Sequential Organ Failure Assessment score was independently associated with mortality in the multivariate analysis.

Thrombocytosis Is a Marker of Poor Outcome in Community-Acquired Pneumonia

BACKGROUND Thrombocytosis, often considered a marker of normal inflammatory reaction of infections, has been recently associated with increased mortality in hospitalized patients with community-acquired pneumonia (CAP). We assessed the characteristics and outcomes of patients with CAP and thrombocytosis (platelet count ≥ 4 × 105/mm3) compared with thrombocytopenia (platelet count < 105/mm3) and normal platelet count. METHODS We prospectively analyzed 2,423 consecutive, hospitalized patients with CAP. We excluded patients with immunosuppression, neoplasm, active TB, or hematologic disease. RESULTS Fifty-three patients (2%) presented with thrombocytopenia, 204 (8%) with thrombocytosis, and 2,166 (90%) had normal platelet counts. Patients with thrombocytosis were younger (P < .001); those with thrombocytopenia more frequently had chronic heart and liver disease (P < .001 for both). Patients with thrombocytosis presented more frequently with respiratory complications, such as complicated pleural effusion and empyema (P < .001), whereas those with thrombocytopenia presented more often with severe sepsis (P < .001), septic shock (P = .009), need for invasive mechanical ventilation (P < .001), and ICU admission (P = .011). Patients with thrombocytosis and patients with thrombocytopenia had longer hospital stays (P = .004), and higher 30-day mortality (P = .001) and readmission rates (P = .011) than those with normal platelet counts. Multivariate analysis confirmed a significant association between thrombocytosis and 30-day mortality (OR, 2.720; 95% CI, 1.589-4.657; P < .001). Adding thrombocytosis to the confusion, respiratory rate, and BP plus age ≥65 years score slightly improved the accuracy to predict mortality (area under the receiver operating characteristic curve increased from 0.634 to 0.654, P = .049). CONCLUSIONS Thrombocytosis in patients with CAP is associated with poor outcome, complicated pleural effusion, and empyema. The presence of thrombocytosis in CAP should encourage ruling out respiratory complication and could be considered for severity evaluation.

New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study

Rationale: The Sepsis‐3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis‐related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. Objectives: To perform a clinical decision‐making analysis of Sepsis‐3 in patients with community‐acquired pneumonia. Methods: This was a cohort study including adult patients with community‐acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB‐65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision‐curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in‐hospital mortality. Measurements and Main Results: Of 6,874 patients, 442 (6.4%) died in‐hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB‐65, and PSI. Overall, overestimation of in‐hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over‐treatment and being comparable with the “treat‐all” strategy. PSI had higher net benefit than mSOFA and CURB‐65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis‐3 flowchart resulted in better identification of patients at high risk of mortality. Conclusions: qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community‐acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision‐aid tool profile.