Luciano Gattinoni

A Trial of Goal-Oriented Hemodynamic Therapy in Critically Ill Patients

Background Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal levels may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. Methods A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). Results The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P<0.001). Mortality was 48.4, ...

Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries

IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02010073.

Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure.

Twenty-two patients with acute respiratory failure underwent lung computed tomography (CT) and physiological measurements at 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) to investigate the relationship between morphology and function. Lung densities were primarily concentrated in the dependent regions. From the frequency distribution of CT numbers (difference in xray attenuation between water and lung) and lung gas volume measurements the authors obtained a quantitative estimate of normally inflated, poorly inflated, and non-inflated lung tissue weight. This estimated average lung weight was increased twofold nbove normal and excess lung weight correlated with the mean pulmonary artery pressure (P < 0.01). Venous admixture correlated with the non-inflated tissue mass (P < 0.01). Increasing PEEP caused progressive clearing of radiographic densities and increased the mass of normally inflated tissue (anatomic recruitment), while reducing venous admixture. The cardiac index decreased after increasing PEEP while oxygen delivery was unchanged. The authors conclude that CT scan lung density and oxygen exchange efficiency are correlated; the main effect of augmenting PEEP is to recruit perfused alveolar units that were previously collapsed.

The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia

We investigated the effects of body mass index (BMI) on functional residual capacity (FRC), respiratory mechanics (compliance and resistance), gas exchange, and the inspiratory mechanical work done per liter of ventilation during general anesthesia.We used the esophageal balloon technique, together with rapid airway occlusion during constant inspiratory flow, to partition the mechanics of the respiratory system into its pulmonary and chest wall components. FRC was measured by using the helium dilution technique. We studied 24 consecutive and unselected patients during general anesthesia, before surgical intervention, in the supine position (8 normal subjects with a BMI <or=to25 kg/m2, 8 moderately obese patients with a BMI >25 kg/m2 and <40 kg/m2, and 8 morbidly obese patients with a BMI >or=to40 kg/m2). We found that, with increasing BMI: 1.FRC decreased exponentially (r = 0.86; P < 0.01) 2.the compliance of the total respiratory system and of the lung decreased exponentially (r = 0.86; P < 0.01 and r = 0.81; P < 0.01, respectively), whereas the compliance of the chest wall was only minimally affected (r = 0.45; P < 0.05) 3.the resistance of the total respiratory system and of the lung increased (r = 0.81; P < 0.01 and r = 0.84; P < 0.01, respectively), whereas the chest wall resistance was unaffected (r = 0.06; P = not significant) 4.the oxygenation index (PaO2/PAo2) decreased exponentially (r = 0.81; P < 0.01) and was correlated with FRC (r = 0.62; P < 0.01), whereas PaCO2 was unaffected (r = 0.06; P = not significant) 5.the work of breathing of the total respiratory system increased, mainly due to the lung component (r = 0.88; P < 0.01 and r = 0.81; P < 0.01, respectively). In conclusion, BMI is an important determinant of lung volumes, respiratory mechanics, and oxygenation during general anesthesia with patients in the supine position.Implications: The aim of this study was to investigate the influence of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia. (Anesth Analg 1998;87:654-60)

Lung Stress and Strain during Mechanical Ventilation for Acute Respiratory Distress Syndrome

RATIONALE Lung injury caused by a ventilator results from nonphysiologic lung stress (transpulmonary pressure) and strain (inflated volume to functional residual capacity ratio). OBJECTIVES To determine whether plateau pressure and tidal volume are adequate surrogates for stress and strain, and to quantify the stress to strain relationship in patients and control subjects. METHODS Nineteen postsurgical healthy patients (group 1), 11 patients with medical diseases (group 2), 26 patients with acute lung injury (group 3), and 24 patients with acute respiratory distress syndrome (group 4) underwent a positive end-expiratory pressure (PEEP) trial (5 and 15 cm H2O) with 6, 8, 10, and 12 ml/kg tidal volume. MEASUREMENTS AND MAIN RESULTS Plateau airway pressure, lung and chest wall elastances, and lung stress and strain significantly increased from groups 1 to 4 and with increasing PEEP and tidal volume. Within each group, a given applied airway pressure produced largely variable stress due to the variability of the lung elastance to respiratory system elastance ratio (range, 0.33-0.95). Analogously, for the same applied tidal volume, the strain variability within subgroups was remarkable, due to the functional residual capacity variability. Therefore, low or high tidal volume, such as 6 and 12 ml/kg, respectively, could produce similar stress and strain in a remarkable fraction of patients in each subgroup. In contrast, the stress to strain ratio-that is, specific lung elastance-was similar throughout the subgroups (13.4 +/- 3.4, 12.6 +/- 3.0, 14.4 +/- 3.6, and 13.5 +/- 4.1 cm H2O for groups 1 through 4, respectively; P = 0.58) and did not change with PEEP and tidal volume. CONCLUSIONS Plateau pressure and tidal volume are inadequate surrogates for lung stress and strain. Clinical trial registered with www.clinicaltrials.gov (NCT 00143468).

Albumin Replacement in Patients with Severe Sepsis or Septic Shock

BACKGROUND Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

Tidal volume lower than 6 ml/kg enhances lung protection: role of extracorporeal carbon dioxide removal.

Background:Tidal hyperinflation may occur in patients with acute respiratory distress syndrome who are ventilated with a tidal volume (VT) of 6 ml/kg of predicted body weight develop a plateau pressure (PPLAT) of 28 ≤ PPLAT ≤ 30 cm H2O. The authors verified whether VT lower than 6 ml/kg may enhance lung protection and that consequent respiratory acidosis may be managed by extracorporeal carbon dioxide removal. Methods:PPLAT, lung morphology computed tomography, and pulmonary inflammatory cytokines (bronchoalveolar lavage) were assessed in 32 patients ventilated with a VT of 6 ml/kg. Data are provided as mean ± SD or median and interquartile (25th and 75th percentile) range. In patients with 28 ≤ PPLAT ≤ 30 cm H2O (n = 10), VT was reduced from 6.3 ± 0.2 to 4.2 ± 0.3 ml/kg, and PPLAT decreased from 29.1 ± 1.2 to 25.0 ± 1.2 cm H2O (P < 0.001); consequent respiratory acidosis (Paco2 from 48.4 ± 8.7 to 73.6 ± 11.1 mmHg and pH from 7.36 ± 0.03 to 7.20 ± 0.02; P < 0.001) was managed by extracorporeal carbon dioxide removal. Lung function, morphology, and pulmonary inflammatory cytokines were also assessed after 72 h. Results:Extracorporeal assist normalized Paco2 (50.4 ± 8.2 mmHg) and pH (7.32 ± 0.03) and allowed use of VT lower than 6 ml/kg for 144 (84–168) h. The improvement of morphological markers of lung protection and the reduction of pulmonary cytokines concentration (P < 0.01) were observed after 72 h of ventilation with VT lower than 6 ml/kg. No patient-related complications were observed. Conclusions:VT lower than 6 ml/Kg enhanced lung protection. Respiratory acidosis consequent to low VT ventilation was safely and efficiently managed by extracorporeal carbon dioxide removal.

Positive End-expiratory Pressure Improves Respiratory Function in Obese but not in Normal Subjects during Anesthesia and Paralysis

BACKGROUND Morbidly obese patients, during anesthesia and paralysis, experience more severe impairment of respiratory mechanics and gas exchange than normal subjects. The authors hypothesized that positive end-expiratory pressure (PEEP) induces different responses in normal subjects (n = 9; body mass index < 25 kg/m2) versus obese patients (n = 9; body mass index > 40 kg/m2). METHODS The authors measured lung volumes (helium technique), the elastances of the respiratory system, lung, and chest wall, the pressure-volume curves (occlusion technique and esophageal balloon), and the intraabdominal pressure (intrabladder catheter) at PEEP 0 and 10 cm H2O in paralyzed, anesthetized postoperative patients in the intensive care unit or operating room after abdominal surgery. RESULTS At PEEP 0 cm H2O, obese patients had lower lung volume (0.59 +/- 0.17 vs. 2.15 +/- 0.58 l [mean +/- SD], P < 0.01); higher elastances of the respiratory system (26.8 +/- 4.2 vs. 16.4 +/- 3.6 cm H2O/l, P < 0.01), lung (17.4 +/- 4.5 vs. 10.3 +/- 3.2 cm H2O/l, P < 0.01), and chest wall (9.4 +/- 3.0 vs. 6.1 +/- 1.4 cm H2O/l, P < 0.01); and higher intraabdominal pressure (18.8 +/-7.8 vs. 9.0 +/- 2.4 cm H2O, P < 0.01) than normal subjects. The arterial oxygen tension was significantly lower (110 +/- 30 vs. 218 +/- 47 mmHg, P < 0.01; inspired oxygen fraction = 50%), and the arterial carbon dioxide tension significantly higher (37.8 +/- 6.8 vs. 28.4 +/- 3.1, P < 0.01) in obese patients compared with normal subjects. Increasing PEEP to 10 cm H2O significantly reduced elastances of the respiratory system, lung, and chest wall in obese patients but not in normal subjects. The pressure-volume curves were shifted upward and to the left in obese patients but were unchanged in normal subjects. The oxygenation increased with PEEP in obese patients (from 110 +/-30 to 130 +/- 28 mmHg, P < 0.01) but was unchanged in normal subjects. The oxygenation changes were significantly correlated with alveolar recruitment (r = 0.81, P < 0.01). CONCLUSIONS During anesthesia and paralysis, PEEP improves respiratory function in morbidly obese patients but not in normal subjects.

Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial.

CONTEXT Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome (ARDS). OBJECTIVE To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS. DESIGN, SETTING, AND PATIENTS The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia. INTERVENTIONS Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation. MAIN OUTCOME MEASURES The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning. RESULTS Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19). CONCLUSION Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00159939.

The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling.

The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last ten years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathological features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.