Salvatore Maurizio Maggiore

A multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome

Objective: In randomized studies of heterogeneous patients with hypoxemic acute respiratory failure, noninvasive positive pressure ventilation (NPPV) was associated with a significant reduction in endotracheal intubation. The role of NPPV in patients with acute respiratory distress syndrome (ARDS) is still unclear. The objective was to investigate the application of NPPV as a first‐line intervention in patients with early ARDS, describing what happens in everyday clinical practice in centers having expertise with NPPV. Design: Prospective, multiple‐center cohort study. Setting: Three European intensive care units having expertise with NPPV. Patients: Between March 2002 and April 2004, 479 patients with ARDS were admitted to the intensive care units. Three hundred and thirty‐two ARDS patients were already intubated, so 147 were eligible for the study. Interventions: Application of NPPV. Measurements and Main Results: NPPV improved gas exchange and avoided intubation in 79 patients (54%). Avoidance of intubation was associated with less ventilator‐associated pneumonia (2% vs. 20%; p < .001) and a lower intensive care unit mortality rate (6% vs. 53%; p < .001). Intubation was more likely in patients who were older (p = .02), had a higher Simplified Acute Physiology Score (SAPS) II (p < .001), or needed a higher level of positive end‐expiratory pressure (p = .03) and pressure support ventilation (p = .02). Only SAPS II >34 and a Pao2/Fio2 ≤175 after 1 hr of NPPV were independently associated with NPPV failure and need for endotracheal intubation. Conclusions: In expert centers, NPPV applied as first‐line intervention in ARDS avoided intubation in 54% of treated patients. A SAPS II >34 and the inability to improve Pao2/Fio2 after 1 hr of NPPV were predictors of failure.

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).

Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: a pilot study.

Objective:Acute respiratory distress syndrome (ARDS) is frequently associated with increased pulmonary vascular resistance and thus with systolic load of the right ventricle. We hypothesized that levosimendan, a new calcium sensitizer with potential pulmonary vasodilator properties, improves hemodynamics by unloading the right ventricle in patients with ARDS. Design:Prospective, randomized, placebo-controlled, pilot study. Setting:Twenty-two-bed multidisciplinary intensive care unit of a university hospital. Patients:Thirty-five patients with ARDS in association with septic shock. Interventions:Patients were randomly allocated to receive a 24-hr infusion of either levosimendan 0.2 &mgr;g/kg/min (n = 18) or placebo (n = 17). Data from right heart catheterization, cardiac magnetic resonance, arterial and mixed venous oxygen tensions and saturations, and carbon dioxide tensions were obtained before and 24 hrs after drug infusion. Measurements and Main Results:At a mean arterial pressure between 70 and 80 mm Hg (sustained with norepinephrine infusion), levosimendan increased cardiac index (from 3.8 ± 1.1 to 4.2 ± 1.0 L/min/m2) and decreased mean pulmonary artery pressure (from 29 ± 3 to 25 ± 3 mm Hg) and pulmonary vascular resistance index (from 290 ± 77 to 213 ± 50 dynes/s/cm5/m2; each p < .05). Levosimendan also decreased right ventricular end-systolic volume and increased right ventricular ejection fraction (p < .05). In addition, levosimendan increased mixed venous oxygen saturation (from 63 ± 8 to 70 ± 8%; p < .01). Conclusions:This study provides evidence that levosimendan improves right ventricular performance through pulmonary vasodilator effects in septic patients with ARDS. A large multiple-center trial is needed to investigate whether levosimendan is able to improve the overall prognosis of patients with sepsis and ARDS.

The application of esophageal pressure measurement in patients with respiratory failure.

This report summarizes current physiological and technical knowledge on esophageal pressure (Pes) measurements in patients receiving mechanical ventilation. The respiratory changes in Pes are representative of changes in pleural pressure. The difference between airway pressure (Paw) and Pes is a valid estimate of transpulmonary pressure. Pes helps determine what fraction of Paw is applied to overcome lung and chest wall elastance. Pes is usually measured via a catheter with an air-filled thin-walled latex balloon inserted nasally or orally. To validate Pes measurement, a dynamic occlusion test measures the ratio of change in Pes to change in Paw during inspiratory efforts against a closed airway. A ratio close to unity indicates that the system provides a valid measurement. Provided transpulmonary pressure is the lung-distending pressure, and that chest wall elastance may vary among individuals, a physiologically based ventilator strategy should take the transpulmonary pressure into account. For monitoring purposes, clinicians rely mostly on Paw and flow waveforms. However, these measurements may mask profound patient-ventilator asynchrony and do not allow respiratory muscle effort assessment. Pes also permits the measurement of transmural vascular pressures during both passive and active breathing. Pes measurements have enhanced our understanding of the pathophysiology of acute lung injury, patient-ventilator interaction, and weaning failure. The use of Pes for positive end-expiratory pressure titration may help improve oxygenation and compliance. Pes measurements make it feasible to individualize the level of muscle effort during mechanical ventilation and weaning. The time is now right to apply the knowledge obtained with Pes to improve the management of critically ill and ventilator-dependent patients.

Nasal High-Flow versus Venturi Mask Oxygen Therapy after Extubation. Effects on Oxygenation, Comfort, and Clinical Outcome

RATIONALE Oxygen is commonly administered after extubation. Although several devices are available, data about their clinical efficacy are scarce. OBJECTIVES To compare the effects of the Venturi mask and the nasal high-flow (NHF) therapy on PaO2/FiO2SET ratio after extubation. Secondary endpoints were to assess effects on patient discomfort, adverse events, and clinical outcomes. METHODS Randomized, controlled, open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation. The Venturi mask (n = 52) or NHF (n = 53) were applied for 48 hours postextubation. MEASUREMENTS AND MAIN RESULTS PaO2/FiO2SET, patient discomfort caused by the interface and by symptoms of airways dryness (on a 10-point numerical rating scale), interface displacements, oxygen desaturations, need for ventilator support, and reintubation were assessed up to 48 hours after extubation. From the 24th hour, PaO2/FiO2SET was higher with the NHF (287 ± 74 vs. 247 ± 81 at 24 h; P = 0.03). Discomfort related both to the interface and to airways dryness was better with NHF (respectively, 2.6 ± 2.2 vs. 5.1 ± 3.3 at 24 h, P = 0.006; 2.2 ± 1.8 vs. 3.7 ± 2.4 at 24 h, P = 0.002). Fewer patients had interface displacements (32% vs. 56%; P = 0.01), oxygen desaturations (40% vs. 75%; P < 0.001), required reintubation (4% vs. 21%; P = 0.01), or any form of ventilator support (7% vs. 35%; P < 0.001) in the NHF group. CONCLUSIONS Compared with the Venturi mask, NHF results in better oxygenation for the same set FiO2 after extubation. Use of NHF is associated with better comfort, fewer desaturations and interface displacements, and a lower reintubation rate. Clinical trial registered with www.clinicaltrials.gov (NCT 01575353).

Respective effects of end-expiratory and end-inspiratory pressures on alveolar recruitment in acute lung injury

ObjectiveA low tidal volume can induce alveolar derecruitment in patients with acute lung injury. This study was undertaken to evaluate whether this resulted mainly from the decrease in tidal volume per se or from the reduction in end-inspiratory plateau pressure and whether there is any benefit in raising the level of positive end-expiratory pressure (PEEP) while plateau pressure is kept constant. DesignProspective crossover study. SettingMedical intensive care unit of a university teaching hospital. PatientsFifteen adult patients ventilated for acute lung injury (Pao2/Fio2, 158 ± 34 mm Hg; lung injury score, 2.7 ± 0.6). InterventionsThree combinations were tested: PEEP at the lower inflection point with 6 mL/kg tidal volume, PEEP at the lower inflection point with 10 mL/kg tidal volume, and high PEEP with tidal volume at 6 mL/kg, keeping the plateau pressure similar to the preceding condition. Measurements and Main ResultsPressure-volume curves at zero PEEP and at set PEEP were recorded, and recruitment was calculated as the volume difference between both curves for pressures ranging from 15 to 30 cm H2O. Arterial blood gases were measured for all patients. For a similar PEEP at the lower inflection point (10 ± 3 cm H2O), tidal volume reduction (10 to 6 mL/kg) led to a significant derecruitment. A low tidal volume (6 mL/kg) with high PEEP (14 ± 3 cm H2O), however, induced a significantly greater recruitment and a higher Pao2 than the two other strategies. ConclusionAt a given plateau pressure (i.e., similar end-inspiratory distension), lowering tidal volume and increasing PEEP increase recruitment and Pao2.

Determinants of Procedural Pain Intensity in the Intensive Care Unit. The Europain® Study

RATIONALE Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. OBJECTIVES To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. METHODS Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. MEASUREMENTS AND MAIN RESULTS Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. CONCLUSIONS Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

Long-term effects of different humidification systems on endotracheal tube patency: evaluation by the acoustic reflection method

BackgroundAccumulation of mucous secretions in an endotracheal tube (ETT) increases its resistance, and the amount of deposit may be affected by the quality of humidification and heating of the inspired gas. MethodsThe authors assessed the impact of two humidification systems, a heated humidifier (HH) and a hygroscopic–hydrophobic heat and moisture exchanger (HME), on the ETT patency in patients selected to require mechanical ventilation for more than 48 h. This comparison was performed over two consecutive periods and used the acoustic reflection method, which characterizes the amount and site of ETT obstruction and allows estimating ETT inner volume and resistance. Measurements were performed three times a week over the period of mechanical ventilation. Comparisons were performed at mid duration and at the end of the mechanical ventilation period. ResultsThe HH was used in 34 patients, and the HME was used in 26 patients. The two groups had similar severity and duration of mechanical ventilation. At mid duration of mechanical ventilation (5.5 ± 3.3 vs. 4.8 ± 3.3 days; P = 0.4), no difference was observed in ETT volume and resistance between the two groups. At the end of the study period (10.5 ± 5.8 vs. 9.6 ± 6.3 days of mechanical ventilation; P = 0.4), ETT volume was reduced to a greater extent with HME than with HH (−3.3 ± 2.9 vs. −5.1 ± 2.5%; P = 0.008), and ETT resistance increased significantly more with the HME than with the HH (8.4 ± 12.2 vs. 19.4 ± 17.7%; P = 0.001). ConclusionProlonged use of humidification systems results in progressive reduction of ETT patency, and to a greater extent with HMEs than with HHs.

A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease.

Objective:To assess the effect of a helium-oxygen mixture on intubation rate and clinical outcomes during noninvasive ventilation in acute exacerbation of chronic obstructive pulmonary disease. Design:Multicenter, prospective, randomized, controlled trial. Setting:Seven intensive care units. Patients:A total of 204 patients with known or suspected chronic obstructive pulmonary disease and acute dyspnea, Paco2> 45 mm Hg and two among the following factors: pH <7.35, Paco2 <50 mm Hg, respiratory rate >25/min. Interventions:Noninvasive ventilation randomly applied with or without helium (inspired oxygen fraction 0.35) via a face mask. Measurements and Main Results:Duration and complications of NIV and mechanical ventilation, endotracheal intubation, discharge from intensive care unit and hospital, mortality at day 28, adverse and serious adverse events were recorded. Follow-up lasted until 28 days since enrollment. Intubation rate did not significantly differ between groups (24.5% vs. 30.4% with or without helium, p = .35). No difference was observed in terms of improvement of arterial blood gases, dyspnea, and respiratory rate between groups. Duration of noninvasive ventilation, length of stay, 28-day mortality, complications and adverse events were similar, although serious adverse events tended to be lower with helium (10.8% vs. 19.6%, p = .08). Conclusions:Despite small trends favoring helium, this study did not show a statistical superiority of using helium during NIV to decrease the intubation rate in acute exacerbation of chronic obstructive pulmonary disease.

Alveolar recruitment in pulmonary and extrapulmonary acute respiratory distress syndrome: comparison using pressure-volume curve or static compliance.

Background:Alveolar recruitment in response to positive end-expiratory pressure (PEEP) may differ between pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS), and alveolar recruitment values may differ when measured by pressure-volume curve compared with static compliance. Methods:The authors compared PEEP-induced alveolar recruitment in 71 consecutive patients identified in a database. Patients were classified as having pulmonary, extrapulmonary, or mixed/uncertain ARDS. Pressure-volume curves with and without PEEP were available for all patients, and pressure-volume curves with two PEEP levels were available for 44 patients. Static compliance was calculated as tidal volume divided by pressure change for tidal volumes of 400 and 700 ml. Recruited volume was measured at an elastic pressure of 15 cm H2O. Results:Volume recruited by PEEP (10 ± 3 cm H2O) was 223 ± 111 ml in the pulmonary ARDS group (29 patients), 206 ± 164 ml in the extrapulmonary group (16 patients), and 242 ± 176 ml in the mixed/uncertain group (26 patients) (P = 0.75). At high PEEP (14 ± 2 cmH2O, 44 patients), recruited volumes were also similar (P = 0.60). With static compliance, recruitment was markedly underestimated and was dependent on tidal volume (226 ± 148 ml using pressure-volume curve, 95 ± 185 ml for a tidal volume of 400 ml, and 23 ± 169 ml for 700 ml; P < 0.001). Conclusion:In a large sample of patients, classification of ARDS was uncertain in more than one third of patients, and alveolar recruitment was similar in pulmonary and extrapulmonary ARDS. PEEP levels should not be determined based on cause of ARDS.