Fernando Frutos-Vivar

Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation

RATIONALE Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

Sepsis incidence and outcome: contrasting the intensive care unit with the hospital ward

Objective:To describe the outcome of patients with sepsis according to location on a ward or in an intensive care unit. Design:Prospective multicentered observational study. Setting:Three academic hospitals in Madrid, Spain. Patients:Consecutive patients with sepsis admitted to participating hospitals from March 1 to June 30, 2003. Interventions:None. Measurements and Main Results:During the study period, 15,852 patients >18 yrs of age were admitted. Sepsis was identified in 702 patients, giving an estimated cumulative incidence rate of 367 cases per 100,000 adult area residents per year and a cumulative incidence rate among patients admitted to the hospital of 4.4%. Most septic patients had a community-acquired infection (71%). Severe sepsis developed in 199 patients (incidence rate, 104 cases per 100,000 adult area residents per year), and 59 patients developed septic shock (incidence rate, 31 cases per 100,000 adult area residents per year). Most of the patients met the criteria for severe sepsis or septic shock on the same day that they would have qualified for the septic status one step down the scale. In the other patients, the median time between sepsis and severe sepsis was 2 days (interquartile range, 2–5) and between severe sepsis and septic shock was 3 days (interquartile range, 1–4). Only 32% of severe sepsis patients received intensive care. The hospital mortality for all septic patients was 12.8%; for severe sepsis, 20.7%; and for septic shock, 45.7%. Conclusions:This study shows the high incidence of sepsis in a general population of patients admitted to hospital. A significant proportion of patients with severe sepsis are not transferred to the intensive care unit.

Acute respiratory distress syndrome: Underrecognition by clinicians and diagnostic accuracy of three clinical definitions*

Objective:To determine and compare the diagnostic accuracy of three clinical definitions of acute respiratory distress syndrome (ARDS): (1) the American-European consensus conference definition; (2) the lung injury score; and (3) a recently developed Delphi definition. A second objective was to determine the accuracy of clinical diagnoses of ARDS made in daily practice. Design:Independent comparison of autopsy findings with the daily status of clinical definitions, constructed with data abstracted retrospectively from medical records. Setting:Tertiary intensive care unit. Patients:One hundred thirty-eight patients from the period 1995 through 2001 who were autopsied after being mechanically ventilated. Interventions:Clinical ARDS diagnoses were determined daily without knowledge of autopsy results. Charts were reviewed for any mention of ARDS in the clinical notes. Autopsies were reviewed independently by two pathologists for the presence of diffuse alveolar damage. The sensitivity and specificity of the definitions were determined with use of diffuse alveolar damage at autopsy as the reference standard. Measurements and Main Results:Diffuse alveolar damage at autopsy was documented in 42 of 138 cases (30.4%). Only 20 of these 42 patients (47.6%) had any mention of ARDS in their chart. Sensitivities and specificities (95% confidence intervals) were as follows: American-European definition, 0.83 (0.72–0.95), 0.51 (0.41–0.61); lung injury score, 0.74 (0.61–0.87), 0.77 (0.69–0.86); and Delphi definition, 0.69 (0.55–0.83), 0.82 (0.75–0.90). Specificity was significantly higher for both the lung injury score and Delphi definition than for the American-European definition (p < .001 for both), whereas comparisons of sensitivity, which was higher for the American-European definition, were not significantly different (p = .34 and p = .07, respectively). Conclusions:Acute respiratory distress syndrome appears underrecognized by clinicians in patients who die with this syndrome. In this population, the specificities of existing clinical definitions vary considerably, which may be problematic for clinical trials.

Outcome of mechanically ventilated patients who require a tracheostomy

Objective:To estimate the prevalence of, the risk factors associated with, and the outcome of tracheostomy in a heterogeneous population of mechanically ventilated patients. Design:Prospective, observational cohort study. Setting:A total of 361 intensive care units from 12 countries. Patients:A cohort of 5,081 patients mechanically ventilated for >12 hrs. Interventions:None. Measurements and Main Results:A total of 546 patients (10.7%) had a tracheostomy during their stay in the intensive care unit. Tracheostomy was performed at a median time of 12 days (interquartile range, 7–17) from the beginning of mechanical ventilation. Variables associated with the performance of tracheostomy were duration of mechanical ventilation, need for reintubation, and neurologic disease as the primary reason of mechanical ventilation. The intensive care unit stay of patients with or without tracheostomy was a median of 21 days (interquartile range, 12–32) vs. 7 days (interquartile range, 4–12; p < .001), respectively, and the hospital stay was a median 36 days (interquartile range, 23–53) vs. 15 days (interquartile range, 8–26; p < .001), respectively. Adjusting by other variables, tracheostomy was independently related with survival in the intensive care unit (odds ratio, 2.22; 95% confidence interval, 1.72–2.86). Mortality in the hospital was similar in both groups (39% vs. 40%, p = .65). Conclusions:Tracheostomy is a common surgical procedure in the intensive care unit that is associated with a lower mortality in the unit but with a longer stay and a similar mortality in the hospital than in patients without tracheostomy.

Comparison of the Berlin Definition for Acute Respiratory Distress Syndrome with Autopsy

RATIONALE A revised definition of clinical criteria for acute respiratory distress syndrome (ARDS), the Berlin definition, was recently established to classify patients according to their severity. OBJECTIVE To evaluate the accuracy of these clinical criteria using diffuse alveolar damage (DAD) at autopsy as the reference standard. METHODS All patients who died and had a clinical autopsy in our intensive care unit over a 20-year period (1991-2010) were included. Patients with clinical criteria for ARDS were identified from the medical charts and were classified as mild, moderate, or severe according to the Berlin definition using PaO2/FiO2 oxygenation criteria. Microscopic analysis from each pulmonary lobe was performed by two pathologists. MEASUREMENTS AND MAIN RESULTS Among 712 autopsies analyzed, 356 patients had clinical criteria for ARDS at time of death, classified as mild (n = 49, 14%), moderate (n = 141, 40%), and severe (n = 166, 46%). Sensitivity was 89% and specificity 63% to identify ARDS using the Berlin definition. DAD was found in 159 of 356 (45%) patients with clinical criteria for ARDS (in 12, 40, and 58% of patients with mild, moderate, and severe ARDS, respectively). DAD was more frequent in patients who met clinical criteria for ARDS during more than 72 hours and was found in 69% of those with severe ARDS for 72 hours or longer. CONCLUSIONS Histopathological findings were correlated to severity and duration of ARDS. Using clinical criteria the revised Berlin definition for ARDS allowed the identification of severe ARDS of more than 72 hours as a homogeneous group of patients characterized by a high proportion of DAD.

Airway pressures, tidal volumes, and mortality in patients with acute respiratory distress syndrome

Objective:To determine the usual practice for setting tidal volume and other ventilatory parameters in patients with acute respiratory distress syndrome (ARDS) in the late 1990s and to determine the independent effects of these practices on intensive care unit mortality. Design:Subanalysis of a prospective observational study. Multivariable logistic regression was used to analyze the effects of ventilatory management on mortality. Setting:A total of 361 intensive care units in 20 countries in March 1998. Patients:A total of 467 mechanically ventilated patients with ARDS. Interventions:None. Measurements and Main Results:The mean tidal volume used in the first week of ARDS was 8.8 mL/kg measured body weight, and there was great variability in these tidal volumes (sd = 2.0). Tidal volumes were significantly lower in patients with (n = 265) than without (n = 202) a recorded plateau pressure (8.6 vs. 9.1 mL/kg, p = .01). The overall intensive care unit mortality rate was 60.2%. In addition to the strong influence of organ failures and higher levels of inspired oxygen, late-onset ARDS (onset after >48 hrs of mechanical ventilation; odds ratio, 2.09) was independently associated with mortality. In addition, lower levels of positive end-expiratory pressure were independently associated with higher mortality (odds ratio, 0.91; 1 cm of H2O increments). Neither inspiratory pressures nor tidal volumes were independently associated with mortality, and there was no evidence of increased mortality with the use of lower inspiratory pressures. Conclusions:This descriptive study demonstrated considerable interpatient variability in tidal volumes during the study period. In addition to traditional prognostic indicators, timing of ARDS onset and the use of low levels of positive end-expiratory pressure or no positive end-expiratory pressure during the first week may adversely influence outcome in ARDS patients.

Characteristics and Outcomes of Ventilated Patients According to Time to Liberation from Mechanical Ventilation

RATIONALE A new classification of patients based on the duration of liberation of mechanical ventilation has been proposed. OBJECTIVES To analyze outcomes based on the new weaning classification in a cohort of mechanically ventilated patients. METHODS Secondary analysis included 2,714 patients who were weaned and underwent scheduled extubation from a cohort of 4,968 adult patients mechanically ventilated for more than 12 hours. MEASUREMENTS AND MAIN RESULTS Patients were classified according to a new weaning classification: 1,502 patients (55%) as simple weaning,1,058 patients (39%) as difficult weaning, and 154 (6%) as prolonged weaning.Variables associated with prolonged weaning(.7d)were: severity at admission (odds ratio [OR] per unit of Simplified Acute Physiology Score II, 1.01; 95% confidence interval [CI], 1.001–1.02), duration of mechanical ventilation before first attempt of weaning (OR per day, 1.10; 95% CI, 1.06–1.13), chronic pulmonary disease other than chronic obstructive pulmonary disease (OR,13.23; 95% CI, 3.44–51.05), pneumonia as the reason to start mechanical ventilation (OR, 1.82; 95% CI, 1.07–3.08), and level of positive end-expiratory pressure applied before weaning (OR per unit,1.09; 95% CI, 1.04–1.14). The prolonged weaning group had a nonsignificant trend toward a higher rate of reintubation (P ¼ 0.08),tracheostomy (P ¼ 0.15), and significantly longer length of stay and higher mortality in the intensive care unit (OR for death, 1.97;95%CI, 1.17–3.31). The adjusted probability of death remained constant until Day 7, at which point it increased to 12.1%.

Epidemiology of acute lung injury and acute respiratory distress syndrome.

Purpose of reviewAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are diseases with a significant influence in the public health. A better knowledge of their epidemiology could help to improve the outcome of these diseases. Recent findingsAlthough the clinical criteria of the American-European Consensus Conference definitions for ALI and ARDS are simple, there is a risk of misclassification due to a poor reliability. Except for new emerging infectious diseases, such as severe acute respiratory syndrome, the etiology of ALI/ARDS has remained the same for several years. The only recent innovation is the hypothesis that pulmonary ARDS and extrapulmonary ARDS could be different clinical entities. In recent years, there has been a special interest in the study of genetic predisposition to development ALI/ARDS. Recent studies have estimated the incidence of these diseases to be between 15 and 34 cases per 100,000 inhabitants per year. This wide range could stem from differences in the methodology used to calculate the incidence or could be a true variation due to regional differences. Mortality rate of ALI/ARDS have remained steady for several years. Respiratory failure is the cause of the death in less than 20% of the patients. SummaryThe epidemiology of ALI and ARDS has some issues to improve, such as the accuracy of the clinical criteria of ALI/ARDS. Future research must to include study of genetic polymorphisms of the mediators involve in the development of ALI/ARDS. Studies to define better the population at risk are necessary to estimate better their true incidence.

Clinical risk conditions for acute lung injury in the intensive care unit and hospital ward: a prospective observational study

BackgroundLittle is known about the development of acute lung injury outside the intensive care unit. We set out to document the following: the association between predefined clinical conditions and the development of acute lung injury by using the American–European consensus definition; the frequency of lung injury development outside the intensive care unit; and the temporal relationship between antecedent clinical risk conditions, intensive care admission, and diagnosis of lung injury.MethodsWe conducted a 4-month prospective observational study in three Spanish teaching hospitals, enrolling consecutive patients who developed clinical conditions previously linked to lung injury, both inside and outside the intensive care unit. Patients were followed prospectively for outcomes, including the diagnosis of acute lung injury or acute respiratory distress syndrome.ResultsA total 815 patients were identified with at least one clinical insult; the most common were sepsis, pneumonia, and pancreatitis. Pulmonary risk conditions were observed in 30% of cases. Fifty-three patients (6.5%) developed acute lung injury; 33 of these (4.0%) met criteria for acute respiratory distress syndrome. Lung injury occurred most commonly in the setting of sepsis (46/53; 86.7%), but shock (21/59; 36%) and pneumonia (20/211; 9.5%) portended the highest proportional risk; this risk was higher in patients with increasing numbers of clinical risk conditions (2.2%, 14%, and 21% (P < 0.001) in patients with one, two, and three conditions, respectively). Median days (interquartile range) from risk condition to diagnosis of lung injury was shorter with pulmonary (0 (0 to 2)) versus extrapulmonary (3 (1 to 5)) (P = 0.029) risk conditions. Admission to the intensive care unit was provided to 9/20 (45%) patients with acute lung injury and to 29/33 (88%) of those with acute respiratory distress syndrome. Lung injury patients had higher mortality than others (acute lung injury 25.0%; acute respiratory distress syndrome 45.5%; others 10.3%; P < 0.001).ConclusionThe time course from clinical insult to diagnosis of lung injury was rapid, but may be longer for extrapulmonary cases. Some patients with lung injury receive care and die outside the intensive care unit; this observation needs further study.

Outcome of reintubated patients after scheduled extubation

PURPOSE The main objective of study was to evaluate the outcome of patients who require reintubation after elective extubation. MATERIALS AND METHODS This is an observational, prospective cohort study including mechanically ventilated patients who passed successfully a spontaneous breathing trial. Patients were observed for 48 hours after extubation. During this time, reintubation or use of noninvasive positive pressure ventilation was considered as a failure. Reintubated patients were followed after the reintubation to register complications and outcome. RESULTS A total of 1,152 extubated patients were included in the analysis. Three hundred thirty-six patients (29%) met the criteria for extubation failure. Extubation failure was independently associated with mortality (odds ratio, 3.29; 95% confidence interval, 2.19-4.93). One hundred eighty patients (16% of overall cohort) required reintubation within 48 hours after extubation. Median time from extubation to reintubation was 13 hours (interquartile range, 6-24 hours). Reintubation was independently associated with mortality (odds ratio, 5.18; 95% confidence interval, 3.38-7.94; P < .001). Higher mortality of reintubated patients was due to the development of complications after the reintubation. CONCLUSIONS In a large cohort of scheduled extubated patients, one third of patients developed extubation failure, of whom half needed reintubation. Reintubation was associated with increased mortality due to the development of new complications after reintubation.