Ultrasound assessment of lung consolidation and reaeration after pleural effusion drainage in patients with Acute Respiratory Distress Syndrome: a pilot study.

PURPOSE: The aim of the pilot study was to assess by ultrasound changes in dimensions of lung consolidation and reaeration after drainage of large pleural effusion in patients with acute respiratory distress syndrome (ARDS). METHODS: Lung ultrasound and blood gas were performed before, 2 hours (H2) and 24 hours (H24) after drainage of pleural effusion. Lung ultrasound aeration score was calculated. Cephalocaudal dimension and diaphragmatic transversal area of lung consolidation were measured. RESULTS: Ten patients were studied. Median volume of drained effusion was 675 ml at H2 and 895 at H24. Two hours after drainage, dimension of cephalocaudal consolidation and diaphragmatic transversal area decreased significantly. Lung reaeration after drainage occurred mainly in latero-inferior and postero-superior regions. PaO2/FiO2 increased significantly at H24. CONCLUSIONS: Ultrasound is a useful method to assess lung consolidation after pleural effusion drainage. Drainage of pleural effusion may lead to a decrease of lung consolidation and improvement of lung reaeration.

Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.

Correction to: Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: understanding nebulization of aminoglycosides and colistin.

The original version of this article unfortunately contained a mistake. There was a typographical error in Figure 1: "Nebulization time ≤ 30 min" (first light blue square) should be replaced by "Nebulization time ≤ 90 min". The authors apologize for the mistake.

Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients.

Nebulized antibiotics have an established role in patients with cystic fibrosis or bronchiectasis. Their potential benefit to treat respiratory infections in mechanically ventilated patients is receiving increasing interest. In this consensus statement of the European Society of Clinical Microbiology and Infectious Diseases, the body of evidence of the therapeutic utility of aerosolized antibiotics in mechanically ventilated patients was reviewed and resulted in the following recommendations: Vibrating-mesh nebulizers should be preferred to jet or ultrasonic nebulizers. To decrease turbulence and limit circuit and tracheobronchial deposition, we recommend: (a) the use of specifically designed respiratory circuits avoiding sharp angles and characterized by smooth inner surfaces, (b) the use of specific ventilator settings during nebulization including use of a volume controlled mode using constant inspiratory flow, tidal volume 8 mL/kg, respiratory frequency 12 to 15 bpm, inspiratory:expiratory ratio 50%, inspiratory pause 20% and positive end-expiratory pressure 5 to 10 cm H2O and (c) the administration of a short-acting sedative agent if coordination between the patient and the ventilator is not obtained, to avoid patient's flow triggering and episodes of peak decelerating inspiratory flow. A filter should be inserted on the expiratory limb to protect the ventilator flow device and changed between each nebulization to avoid expiratory flow obstruction. A heat and moisture exchanger and/or conventional heated humidifier should be stopped during the nebulization period to avoid a massive loss of aerosolized particles through trapping and condensation. If these technical requirements are not followed, there is a high risk of treatment failure and adverse events in mechanically ventilated patients receiving nebulized antibiotics for pneumonia.

Impact of graft preservation solutions for liver transplantation on early cytokine release and postoperative organ dysfunctions. A pilot study.

INTRODUCTION: During liver transplantation, graft ischemia-reperfusion injury leads to a systemic inflammatory response producing postoperative organ dysfunctions. The aim of this observational and prospective study was to compare the impact of Solution de conservation des organes et tissus (SCOT) 15 and University of Wisconsin (UW) preservation solutions on early cytokine release, postreperfusion syndrome and postoperative organ dysfunctions. METHODS: Thirty-seven liver transplantations were included: 21 in UW Group and 16 in SCOT 15 group. Five cytokines were measured in systemic blood after anesthetic induction, 30minutes after unclamping portal vein and on postoperative day 1. RESULTS: Following unclamping portal vein, cytokines were released in systemic circulation. Systemic cytokine concentrations were higher in UW than in SCOT 15 group: Interleukin-10, Interleukine-6. In SCOT 15 group, significant reduction of postreperfusion syndrome incidence and acute kidney injury were observed. Alanine and aspartate aminotransferase peak concentrations were higher in SCOT 15 group than in UW group. However, from postoperative day 1 to day 10, aminotransferase returned to normal values and did not differ between groups. CONCLUSIONS: Compared to UW, SCOT 15 decreases systemic cytokine release resulting from graft ischemia-reperfusion injury and reduces incidence of postreperfusion syndrome and postoperative renal failure.

Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases.

With an established role in cystic fibrosis and bronchiectasis, nebulized antibiotics are increasingly being used to treat respiratory infections in critically ill invasively mechanically ventilated adult patients. Although there is limited evidence describing their efficacy and safety, in an era when there is a need for new strategies to enhance antibiotic effectiveness because of a shortage of new agents and increases in antibiotic resistance, the potential of nebulization of antibiotics to optimize therapy is considered of high interest, particularly in patients infected with multidrug-resistant pathogens. This Position Paper of the European Society of Clinical Microbiology and Infectious Diseases provides recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology regarding the use of nebulized antibiotics in invasively mechanically ventilated adults, based on a systematic review and meta-analysis of the existing literature (last search July 2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in clinical practice, due to a weak level of evidence of their efficacy and the high potential for underestimated risks of adverse events (particularly, respiratory complications). Higher-quality evidence is urgently needed to inform clinical practice. Priorities of future research are detailed in the second part of the Position Paper as guidance for researchers in this field. In particular, the panel identified an urgent need for randomized clinical trials of nebulized antibiotic therapy as part of a substitution approach to treatment of pneumonia due to multidrug-resistant pathogens.

Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines.

Nebulized antimicrobial agents are increasingly administered for treatment of respiratory infections in mechanically ventilated (MV) patients. A structured online questionnaire assessing the indications, dosages and recent patterns of use for nebulized antimicrobial agents in MV patients was developed. The questionnaire was distributed worldwide and completed by 192 intensive care units. The most common indications for using nebulized antimicrobial agent were ventilator-associated tracheobronchitis (VAT; 58/87), ventilator-associated pneumonia (VAP; 56/87) and management of multidrug-resistant, Gram-negative (67/87) bacilli in the respiratory tract. The most common prescribed nebulized agents were colistin methanesulfonate and sulfate (36/87, 41.3% and 24/87, 27.5%), tobramycin (32/87, 36.7%) and amikacin (23/87, 26.4%). Colistin methanesulfonate, amikacin and tobramycin daily doses for VAP were significantly higher than for VAT (p < 0.05). Combination of parenteral and nebulized antibiotics occurred in 50 (86%) of 58 prescriptions for VAP and 36 (64.2%) of 56 of prescriptions for VAT. The use of nebulized antimicrobial agents in MV patients is common. There is marked heterogeneity in clinical practice, with significantly different in use between patients with VAP and VAT. Randomized controlled clinical trials and international guidance on indications, dosing and antibiotic combinations to improve clinical outcomes are urgently required.

Myocardial contusion in patients with blunt chest trauma as evaluated by thallium 201 myocardial scintigraphy.

Fifty five patients suffering from blunt chest trauma were studied to assess the diagnosis of myocardial contusion using thallium 201 myocardial scintigraphy. Thirty-eight patients had consistent scintigraphic defects and were considered to have a myocardial contusion. All patients with scintigraphic defects had paroxysmal arrhythmias and/or ECG abnormalities. Of 38 patients, 32 had localized ST-T segment abnormalities; 29, ST-T segment abnormalities suggesting involvement of the same cardiac area as scintigraphic defects; 21, echocardiographic abnormalities. Sixteen patients had segmental hypokinesia involving the same cardiac area as the scintigraphic defects. Fifteen patients had clinical signs suggestive of myocardial contusion and scintigraphic defects. Almost 70 percent of patients with blunt chest trauma had scintigraphic defects related to areas of myocardial contusion. When thallium 201 myocardial scintigraphy directly showed myocardial lesion, two-dimensional echocardiography and standard ECG detected related functional consequences of cardiac trauma.

Hemodynamic consequences of increasing mean airway pressure during high-frequency jet ventilation.

Six critically ill patients with acute respiratory failure were ventilated using high-frequency jet ventilation (HFJV)-frequency 100.min-1, driving pressure 35 psi, 1.8 mm inside diameter injector cannula. Hemodynamic measurements using radial artery and Swan-Ganz catheters, esophageal pressure (EP), and mean airway pressure (Paw) were measured at four different I:E ratios: 0.25, 0.43, 0.67 and 1.0. Static respiratory compliance, using the super syringe method, was measured during intermittent positive pressure ventilation (IPPV) and during HFJV. The results suggested that decreased venous return, increased right ventricular afterload, and decreased PaCO2 accounted for the decrease in cardiac index observed during HFJV using elevated I:E ratios. These variations, related to marked increases in intrathoracic pressures, are very similar to those observed during conventional ventilation with PEEP.

High-frequency jet ventilation vs continuous positive airway pressure for postoperative respiratory support.

In ten patients after recovery from general anesthesia for major vascular surgery, we compared continuous positive airway pressure (CPAP) and high-frequency jet ventilation (HFJV) at the same fractional concentration of oxygen in the inspired gas, both being superimposed on spontaneous breathing. The HFJV was delivered by a ventilator ( Acutronic VS-600) through the lateral lumen of a three-lumen endotracheal tube. Mean airway pressure was increased (3, 8, and 11 mm Hg) by adjusting the driving pressure during HFJV and by the setting of the expiratory valve during CPAP. During HFJV, the frequency (10 Hz) and inspiratory-expiratory ratio (0.25) were kept constant. Control values were measured when patients breathed spontaneously without positive end-expiratory pressure. Cardiac output and transmural filling pressures remained unchanged throughout the study. Neither the arterial oxygen pressure (PaO2) nor intrapulmonary shunt (Qs/Qt) changed significantly during CPAP. The 20- to 30-percent increase in PaO2 and the 5- to 10-percent decrease in Qs/Qt during HFJV when compared to control reflected a slightly but significantly (p less than 0.05) better oxygenation. The increase in arterial carbon dioxide tension was significantly greater during CPAP than during HFJV.

Three mixed venous saturation catheters in patients with circulatory shock and respiratory failure.

Thirty-one critically ill patients with acute respiratory failure and circulatory shock were divided into three groups. Group 1 included 11 patients with an inserted mixed venous saturation (SvO2) catheter using three-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament (Oximetrix opticath catheter); group 2 included eight patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament; (Edwards sat-one catheter); group 3 included 12 patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and two detecting fiberoptic filaments. Once calibration procedures were performed, SvO2 measured by the catheter and by an hemoximeter OSM 3 (reference value) were compared following each therapeutic intervention. Over a period of 1.5 to 6 hours during which the hematocrit value remained unchanged, 119 measurements were obtained in group 1, 91 in group 2 and 181 in group 3. The dispersion of SvO2 values was much more pronounced with the two-reference wavelength systems using either one or two detecting fiber optic filaments, and the correlation coefficient was significantly higher with the three-reference wavelength system (r = 0.970 for the Oximetrix catheter vs r = 0.855 for the Edwards catheter and r = 0.826 for the Spectramed catheter, p less than 0.001). After 24 hours, the spontaneous drifts in the two-reference wavelength systems, using either one or two detecting fiber optic filaments (expressed as the SvO2 value measured by the catheter minus the reference SvO2 value) were significantly higher than the spontaneous drift in the three-reference wavelength system (9.3 +/- 7 percent for the Edwards catheter and +/- 6 +/- 4.1 percent for the Spectramed catheter vs 3.3 +/- 3.1 percent for the Oximetrix catheter, p less than 0.05). This study shows that a three-wavelength system is more accurate than a two-wavelength system for measuring acute changes in SvO2. The addition of a second detecting fiber optic filament does not seem to improve the accuracy of the system when SvO2 changes occur in conditions of stable hematocrit.

Assessment of PEEP-induced reopening of collapsed lung regions in acute lung injury: are one or three CT sections representative of the entire lung?

OBJECTIVES: To study whether PEEP-induced reopening of collapsed lung regions--defined as the decrease in nonaerated lung volume measured on a single or three computerized tomographic (CT) sections--is representative of the decrease in overall nonaerated lung volume. DESIGN: Review of 39 CT scans obtained in consecutive patients with Acute Lung Injury. SETTINGS: Fourteen-bed surgical intensive care unit of a University Hospital. MEASUREMENTS AND RESULTS: PEEP-induced decrease in nonaerated lung volume was measured in 39 patients with ALI on a single juxtadiaphragmatic CT section, on three CT sections--apical, hilar, and juxtadiaphragmatic--and on contiguous apex-to-diaphragm CT sections. The percentage of decrease in nonaerated lung volume following PEEP, was compared between one, three and all CT sections using a linear regression analysis and Bland and Altman's method. The decrease in nonaerated lung volume measured on a single and three CT sections was significantly correlated with the decrease in nonaerated lung volume measured on all CT sections: R=0.83, P<0.0001 for one CT section and R=0.92, P<0.0001 for three CT sections. However, measurements performed on a single CT section were poorly representative of the overall lung: bias -6%, limits of agreement ranging between -37% and +25%. Measurements performed on three CT sections overestimated by 11% the overall decrease in nonaerated lung volume: bias -11%, limits of agreement ranging between -29% and +7%. CONCLUSIONS: PEEP-induced reopening of collapsed lung regions measured on a single or three CT sections sensibly differs from the reopening of collapsed lung regions measured on the overall lung. The inhomogeneous distribution of PEEP-induced reopening of collapsed lung regions along the cephalocaudal axis probably explains these discrepancies.

Validation of a software designed for computed tomographic (CT) measurement of lung water.

OBJECTIVE: The in-vitro validation of a computed tomographic (CT) software specifically designed for quantifying the volume of water contained in the lung. DESIGN: An in-vitro, ex-vivo study. In 1993, a postmortem left pneumonectomy was performed in a patient who died from acute respiratory distress syndrome. The lung was fixed, inflated and dried according to a technique proposed by Markarian and Dailey in 1975 aimed at producing a lung specimen spongy in texture and suitable for radiography. MEASUREMENTS AND RESULTS: In 1999, 13 CT scans of this lung specimen were performed corresponding to different bronchial instillations of known volumes of water and albumin 4%. The different lung weights resulting from the successive bronchial instillations were calculated using a specially designed software, Lungview, adapted for CT measurements and compared with the actual lung weight measured by an electronic scale. The increase in lung weight measured by Lungview was closely correlated with the actual increase in lung weight resulting from bronchial instillation of water and albumin (y = 0.99x - 23, r = 1 for water and y = x - 17, r = 1 for albumin 4%) and the precision of the bias was 7 g for water and 3 g for albumin 4%. CONCLUSIONS: This study shows that the CT software Lungview accurately measured the volume of lung water present within an air-dried exsanguine human lung.

Continuous positive airway pressure (CPAP) vs. intermittent mandatory pressure release ventilation (IMPRV) in patients with acute respiratory failure.

Intermittent Mandatory Pressure Release Ventilation (IMPRV) is a positive pressure spontaneous breathing ventilatory mode in which airway pressure is released intermittently and synchronously with patient's spontaneous expiration in order to provide ventilatory assistance. Eight critically ill patients free of any factor known to alter chest wall mechanics (group 1) and 8 critically ill patients whose spontaneous respiratory activity was markedly altered by a flail chest, or by a C5 quadraplegia and/or by the administration of opioids (group 2) were studied prospectively. CPAP and IMPRV were administered to each patient in a random order during a 1 h period using a CESAR ventilator. Gas flow, tidal volume, tracheal pressure, esophageal pressure, end-expiratory lung volume and hemodynamic parameters were measured. In group 1 patients, the ventilatory assistance provided by IMPRV was associated with a significant decrease in spontaneous tidal volume whereas all other respiratory parameters remained unchanged. In group 2 patients, IMPRV increased minute ventilation from 8.0 +/- 2.61/min to 12.2 +/- 1.81/min (p less than 0.05), decreased PaCO2 from 46 +/- 7.3 mmHg to 38 +/- 6.8 mmHg (p less than 0.05) and reduced respiratory frequency from 21 +/- 10 bpm to 14 +/- 5.7 bpm (p less than 0.07). These results show that IMPRV provides significant ventilatory assistance to patients with mild acute respiratory failure either by decreasing patient's contribution to minute ventilation or by increasing alveolar ventilation in presence of respiratory depression of central or peripheral origin.

Regional distribution of gas and tissue in acute respiratory distress syndrome. I. Consequences for lung morphology. CT Scan ARDS Study Group.

OBJECTIVE: To compare the computed tomographic (CT) analysis of the distribution of gas and tissue in the lungs of patients with ARDS with that in healthy volunteers. DESIGN: Prospective study over a 53-month period. SETTING: Fourteen-bed surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Seventy-one consecutive patients with early ARDS and 11 healthy volunteers. MEASUREMENTS AND RESULTS: A lung CT was performed at end-expiration in patients with ARDS (at zero PEEP) and healthy volunteers. In patients with ARDS, end-expiratory lung volume (gas + tissue) and functional residual capacity (FRC) were reduced by 17% and 58% respectively, and an excess lung tissue of 701+/-321 ml was observed. The loss of gas was more pronounced in the lower than in the upper lobes. The lower lobes of 27% of the patients were characterized by "compression atelectasis," defined as a massive loss of aeration with no concomitant excess in lung tissue, and "inflammatory atelectasis," defined as a massive loss of aeration associated with an excess lung tissue, was observed in 73% of the patients. Three groups of patients were differentiated according to the appearance of their CT: 23% had diffuse attenuations evenly distributed in the two lungs, 36% had lobar attenuations predominating in the lower lobes, and 41% had patchy attenuations unevenly distributed in the two lungs. The three groups were similar regarding excess lung tissue in the upper and lower lobes and reduction in FRC in the lower lobes. In contrast, the FRC of the upper lobes was markedly lower in patients with diffuse or patchy attenuations than in healthy volunteers or patients with lobar attenuations. CONCLUSIONS: These results demonstrate that striking differences in lung morphology, corresponding to different distributions of gas within the lungs, are observed in patients whose respiratory condition fulfills the definition criteria of ARDS.

Regional distribution of gas and tissue in acute respiratory distress syndrome. III. Consequences for the effects of positive end-expiratory pressure. CT Scan ARDS Study Group. Adult Respiratory Distress Syndrome.

OBJECTIVE: To determine whether differences in lung morphology assessed by computed tomography (CT) affect the response to positive end-expiratory pressure (PEEP). DESIGN: Prospective study over a 53-month period. SETTING: Fourteen-bed surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Seventy-one consecutive patients with early adult respiratory distress syndrome (ARDS). MEASUREMENTS AND RESULTS: Fast spiral thoracic CT was performed at zero end-expiratory pressure (ZEEP) and after implementation of PEEP 10 cmH2O. Hemodynamic and respiratory parameters were measured in both conditions. PEEP-induced overdistension and alveolar recruitment were quantified by specifically designed software (Lungview). Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung, characterized by a CT attenuation ranging between -900 and -800 HU in ZEEP conditions. Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS. PEEP-induced alveolar recruitment of the lower lobes was significantly correlated with their lung volume (gas + tissue) at functional residual capacity. PEEP-induced alveolar recruitment was greater in the lower lobes with "inflammatory atelectasis" than in the lower lobes with "mechanical atelectasis." Lung morphology as assessed by CT markedly influenced the effects of PEEP: in patients with diffuse CT attenuations PEEP induced a marked alveolar recruitment without overdistension, whereas in patients with lobar CT attenuations PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas. These results can be explained by the uneven distribution of regional compliance characterizing patients with lobar CT attenuations (compliant upper lobes and stiff lower lobes) contrasting with a more even distribution of regional compliances observed in patients with diffuse CT attenuations. CONCLUSIONS: In patients with ARDS, the cardiorespiratory effects of PEEP are affected by lung morphology rather than by the cause of the lung injury (primary versus secondary ARDS). The regional distribution of the loss of aeration and the type of atelectasis -- "mechanical" with a massive loss of lung volume, or "inflammatory" with a preservation of lung volume-- characterizing the lower lobes are the main determinants of the cardiorespiratory effects of PEEP.

Regional distribution of gas and tissue in acute respiratory distress syndrome. II. Physiological correlations and definition of an ARDS Severity Score. CT Scan ARDS Study Group.

OBJECTIVES: (a) To assess whether differences in lung morphology observed in patients with adult respiratory distress syndrome (ARDS) are associated with differences in cardiorespiratory parameters, lung mechanics, and outcome. (b) To propose a new ARDS Severity Score to identify patients with a high mortality risk. DESIGN: Prospective study over a 53-month period. SETTING: Fourteen-bed surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Seventy-one consecutive patients with early ARDS. MEASUREMENTS AND RESULTS: Cardiorespiratory parameters were measured using a Swan-Ganz catheter, the pressure-volume (PV) curve was measured using the gross syringe method, and fast spiral computed tomography (CT) was performed. Patients with diffuse attenuations (n = 16) differed from patients with lobar attenuations (n = 26) regarding: (a) mortality rate (75% vs. 42%, p = 0.05), (b) incidence of primary ARDS (82% vs. 50%, p = 0.03), (c) respiratory compliance (47 +/- 12 vs. 64 +/- 16 ml per cmH2O(-1) p = 0.04), and (d) lower inflexion point (8.4 +/- 2.0 vs. 4.6 +/- 2.0 cmH2O, p = 0.001). A third group of patients with patchy attenuations (n = 29) had a mortality rate of 41 %, a respiratory compliance of 56 +/- 18 ml per cmH2O(-1) and a lower inflexion point of 6.3 +/- 2.7 cmH2O. The bedside chest radiograph accurately assessed lung morphology in only 42% of the patients. In contrast to the scores based on the bedside chest radiograph, a new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters identified a subgroup of patients with a high mortality rate (> or = 60%). CONCLUSIONS: In patients with ARDS, differences in lung morphology are associated with differences in outcome and lung mechanics. A new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters accurately identified patients with the most severe forms of ARDS and a mortality rate above 60%.

Inhaled nitric oxide in acute respiratory failure: dose-response curves.

OBJECTIVE: To determine the dose-response curve of inhaled nitric oxide (NO) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure. DESIGN: Prospective randomized study. SETTING: A 14-bed ICU in a teaching hospital. PATIENTS: 6 critically ill patients with severe acute respiratory failure (lung injury severity score > or = 2.5) and pulmonary hypertension. INTERVENTIONS: 8 concentrations of inhaled NO were administered at random: 100, 400, 700, 1000, 1300, 1600, 1900 and 5000 parts per billion (ppb). Control measurements were performed before NO inhalation and after the last concentration administered. After an NO exposure of 15-20 min, hemodynamic parameters obtained from a fiberoptic Swan-Ganz catheter, blood gases, methemoglobin blood concentrations and intratracheal NO and nitrogen dioxide (NO2) concentrations, continuously monitored using a bedside chemiluminescence apparatus, were recorded on a Gould ES 1000 recorder. In 2 patients end-tidal CO2 was also recorded. RESULTS: The administration of 100-2000 ppb of inhaled NO induced: i) a dose-dependent decrease in pulmonary artery pressure and in pulmonary vascular resistance (maximum decrease--25%); ii) a dose-dependent increase in PaO2 via a dose-dependent reduction in pulmonary shunt; iii) a slight but significant decrease in PaCO2 via a reduction in alveolar dead space; iv) a dose-dependent increase in mixed venous oxygen saturation (SVO2). Systemic hemodynamic variables and methemoglobin blood concentrations did not change. Maximum NO2 concentrations never exceeded 165 ppb. In 2 patients, 91% and 74% of the pulmonary vasodilation was obtained for inhaled NO concentrations of 100 ppb. CONCLUSION: In hypoxemic patients with pulmonary hypertension and severe acute respiratory failure, therapeutic inhaled NO concentrations are in the range 100-2000 ppb. The risk of toxicity related to NO inhalation is therefore markedly reduced. Continuous SVO2 monitoring appears useful at the bedside for determining optimum therapeutic inhaled NO concentrations in a given patient.

Prevention of gram negative nosocomial bronchopneumonia by intratracheal colistin in critically ill patients. Histologic and bacteriologic study.

OBJECTIVE: To evaluate the efficiency of intratracheal colistin in preventing nosocomial bronchopneumonia (BPN) in the critically ill. DESIGN: Study evaluating the clinical incidence of nosocomial BPN in 2 groups of critically ill patients who receive or did not receive intratracheal colistin. BPN was assessed clinically in survivors and histologically in non-survivors. SETTING: A 14-bed surgical intensive care unit. PATIENTS: 598 consecutive critically ill patients were studied during a prospective non-randomized study over a 40-month period. INTERVENTIONS: 251 patients--31 non-survivors and 220 survivors--did not receive intratracheal colistin and 347-42 non-survivors and 305 survivors--received intratracheal colistin for a 2-week period (1,600,000 units per 24 h). MEASUREMENTS AND RESULTS: The incidence of nosocomial BPN was evaluated clinically in survivors, using repeated protected minibronchoalveolar lavages, and histologically in non-survivors via an immediate postmortem pneumonectomy (histologic and semi-quantitative bacteriologic analysis of one lung). The clinical incidence of nosocomial BPN was of 37% in coli (-) survivors and of 27% in coli (+) survivors (p < 0.01). This result was histologically confirmed in non-survivors, where the incidence of histologic BPN was of 61% in coli (-) patients and of 36% in coli (+) patients (p < 0.001). Emergence of BPN due to colistin-resistant micro-organisms was not observed. Because colistin was successful in preventing Gram-negative BPN and did not change the absolute number of Gram-positive BPN, the proportion of BPN caused by staphylococcus species was higher in group coli (+) patients (33% vs 16%). Mortality was not significantly influenced by the administration of colistin. CONCLUSION: This study suggests that the administration of intratracheal colistin during a 2-week period significantly reduces the incidence of Gram-negative BPN without creating an increasing number of BPN due to colistin-resistant micro-organisms.