Oscar Peñuelas

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.

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.

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%.

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.

Ventilation-induced lung injury in rats is associated with organ injury and systemic inflammation that is attenuated by dexamethasone.

Objective:To determine whether mechanical ventilation using high tidal volume is associated with nonpulmonary organ dysfunction that can be attenuated by dexamethasone. Design:Prospective randomized animal intervention study. Setting:Animal care facility in a university hospital. Subjects:Sedated and tracheostomized male Sprague-Dawley rats. Interventions:Three groups of rats were ventilated with different strategies: tidal volume = 9 mL/kg, positive end-expiratory pressure = 8 cm H2O, control group (C); tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H2O, overventilated group (OV); and tidal volume = 35 mL/kg, positive end-expiratory pressure = 0 cm H2O, plus administration of 6 mg/kg dexamethasone intraperitoneally (OV + dexamethasone). All rats were ventilated for 75 mins with respiratory rate = 70 breaths/min, Fio2 = 0.35, and plateau time = 0. Measurements and Main Results:Mean arterial pressure and peak airway pressure were monitored. We measured arterial blood gases, aspartate aminotransferase, alanine aminotransferase, lactate, nitrates and nitrites, tumor necrosis factor-α, and interleukin-6 serum concentration. Lung slices were prepared for blind histologic examination. Heart tissue was analyzed for cyclooxygenase-1 and -2 expression (reverse transcription-polymerase chain reaction). Compared with the C group, the OV group showed hypotension; worsened gas exchange; increased aspartate aminotransferase, lactate, nitrates and nitrites, and interleukin-6 serum concentrations; and hyaline membrane formation in the lungs, as well as increased cyclooxygenase-1 and cyclooxygenase-2 expression in the heart. Dexamethasone prevented the pulmonary and cardiovascular injury and attenuated the increase in aspartate aminotransferase, nitrates and nitrites, interleukin-6, and cyclooxygenase-1 and cyclooxygenase-2 expression. Conclusions:High tidal volume ventilation induces cardiovascular, pulmonary, and liver injury as well as a systemic proinflammatory response. These changes are attenuated by dexamethasone, suggesting that inflammatory rather than purely hemodynamic mechanisms are involved in the changes induced by high tidal volume ventilation.

Human neutrophil peptides and phagocytic deficiency in bronchiectatic lungs.

RATIONALE A well-known clinical paradox is that severe bacterial infections persist in the lungs of patients with cystic fibrosis (CF) despite the abundance of polymorphonuclear neutrophils (PMN) and the presence of a high concentration of human neutrophil peptides (HNP), both of which are expected to kill the bacteria but fail to do so. The mechanisms remain unknown. OBJECTIVES This study examined several possible mechanisms to understand this paradox. METHODS PMN were isolated from sputum and blood of subjects with and without CF or non-CF bronchiectasis for phagocytic assays. HNP isolated from patients with CF were used to stimulate healthy PMN followed by phagocytic tests. MEASUREMENTS AND MAIN RESULTS PMN isolated from the sputum of the bronchiectatic patients display defective phagocytosis that correlated with high concentrations of HNP in the lung. When healthy PMN were incubated with HNP, decreased phagocytic capacity was observed in association with depressed surface Fc gamma RIII, actin-filament remodeling, enhanced intracellular Ca(2+), and degranulation. Treatment of PMN with an intracellular Ca(2+) blocker or alpha1-proteinase inhibitor to attenuate the activity of HNP largely prevented the HNP-induced phagocytic deficiency. Intratracheal instillation of HNP in Pallid mice (genetically deficient in alpha1-proteinase inhibitor) resulted in a greater PMN lung infiltration and phagocytic deficiency compared with wild-type mice. CONCLUSIONS HNP or PMN alone exert antimicrobial ability, which was lost as a result of their interaction. These effects of HNP may help explain the clinical paradox seen in patients with inflammatory lung diseases, suggesting HNP as a novel target for clinical therapy.

Noninvasive positive-pressure ventilation in acute respiratory failure

Noninvasive positive-pressure ventilation is a type of mechanical ventilation that does not require an artificial airway. Studies published in the 1990s that evaluated the efficacy of this technique for the treatment of diseases as chronic obstructive pulmonary disease, congestive heart failure and acute respiratory failure have generalized its use in recent years. Important issues include the selection of the ventilation interface and the type of ventilator. Currently available interfaces include nasal, oronasal and facial masks, mouthpieces and helmets. Comparisons of the available interfaces have not shown one to be clearly superior. Both critical care ventilators and portable ventilators can be used for noninvasive positive-pressure ventilation; however, the choice of ventilator type depends on the patients condition and therapeutic requirements and on the expertise of the attending staff and the location of care. The best results (decreased need for intubation and decreased mortality) have been reported among patients with exacerbations of chronic obstructive pulmonary disease and cardiogenic pulmonary edema.

Management and outcome of mechanically ventilated patients after cardiac arrest

IntroductionThe aim of this study was to describe and compare the changes in ventilator management and complications over time, as well as variables associated with 28-day hospital mortality in patients receiving mechanical ventilation (MV) after cardiac arrest.MethodsWe performed a secondary analysis of three prospective, observational multicenter studies conducted in 1998, 2004 and 2010 in 927 ICUs from 40 countries. We screened 18,302 patients receiving MV for more than 12 hours during a one-month-period. We included 812 patients receiving MV after cardiac arrest. We collected data on demographics, daily ventilator settings, complications during ventilation and outcomes. Multivariate logistic regression analysis was performed to calculate odds ratios, determining which variables within 24 hours of hospital admission were associated with 28-day hospital mortality and occurrence of acute respiratory distress syndrome (ARDS) and pneumonia acquired during ICU stay at 48 hours after admission.ResultsAmong 812 patients, 100 were included from 1998, 239 from 2004 and 473 from 2010. Ventilatory management changed over time, with decreased tidal volumes (VT) (1998: mean 8.9 (standard deviation (SD) 2) ml/kg actual body weight (ABW), 2010: 6.7 (SD 2) ml/kg ABW; 2004: 9 (SD 2.3) ml/kg predicted body weight (PBW), 2010: 7.95 (SD 1.7) ml/kg PBW) and increased positive end-expiratory pressure (PEEP) (1998: mean 3.5 (SD 3), 2010: 6.5 (SD 3); P <0.001). Patients included from 2010 had more sepsis, cardiovascular dysfunction and neurological failure, but 28-day hospital mortality was similar over time (52% in 1998, 57% in 2004 and 52% in 2010). Variables independently associated with 28-day hospital mortality were: older age, PaO2 <60 mmHg, cardiovascular dysfunction and less use of sedative agents. Higher VT, and plateau pressure with lower PEEP were associated with occurrence of ARDS and pneumonia acquired during ICU stay.ConclusionsProtective mechanical ventilation with lower VT and higher PEEP is more commonly used after cardiac arrest. The incidence of pulmonary complications decreased, while other non-respiratory organ failures increased with time. The application of protective mechanical ventilation and the prevention of single and multiple organ failure may be considered to improve outcome in patients after cardiac arrest.