Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients with the acute respiratory distress syndrome and in hypoxemic patients with chronic obstructive pulmonary disease

Objective: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). Design: Prospective clinical study. Setting: General intensive care unit in Sabadell, Spain. Patients: Nine mechanically ventilated COPD patients (mean age 72±2 years; forced expiratory volume in 1 s 0.91±0.11 l) and nine ARDS patients (mean age 57±6 years; mean lung injury score 2.8±0.1) Measurements and results: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO₂). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO₂/FIO₂ (fractional inspired oxygen) 190±18 mmHg) than in the ARDS group (PaO₂/FIO₂ 98±12 mmHg), (p<0.01). After NO-10, PaO₂/FIO₂ increased (to 141±17 mmHg, p<0.01) and Qva/Qt decreased (39±3 to 34±3%, p<0.01) in the ARDS group. There were no changes in PaO₂/FIO₂ and Qva/Qt when the NO concentration was increased to 30 ppm in the COPD group. In both groups, a correlation was found between basal MPAP and basal PVR, and between the NO-induced decrease in MPAP and in PVR. The NO-induced increase in PaO₂/FIO₂ was not correlated with basal PaO₂/FIO₂. In the ARDS group, six of the nine patients (66%) responded to NO and in the COPD group, two of nine (22%) (p=0.05). Conclusions: NO inhalation had similar effects on hemodynamics but not on gas exchange in ARDS and COPD patients, and this response probably depends on the underlying disease. Received: 19 December 1995 Accepted: 28 September 1996     

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation

Objective: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). Design: Uncontrolled prospective trial. Setting: One university hospital intensive care department. Patients and participants: 122 patients with ARDS, consecutively admitted to the ICU. Interventions: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) group (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. Measurements and results: The groups differed in both APACHE II (16 ± 5 vs 18 ± 5 points, p = 0.01) and Murray scores (3.2 ± 0.3 vs 3.4 ± 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 ± 9 vs 13 ± 9 days, p = 0.0151), and length of ICU stay in Berlin (31 ± 17 vs 50 ± 36 days, p = 0.0016). Initial PaO₂/FIO₂ was 86 ± 27 mm Hg in AT-sine-ECMO patients that improved to 165 ± 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO₂/FIO₂ of 67 ± 28 mm Hg and improvement to 160 ± 102 mm Hg was not reached until ICU day 13. Q˙_S/Q˙_T was significantly higher in the ECMO-treated group and exceeded 50 % during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75 %. Survival rates were 89 % in the AT-sine ECMO group and 55 % in the ECMO treatment group (p = 0.0000). Conclusions: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved. Received: 9 April 1997 Accepted: 13 May 1997     

The impact of respiratory variables on mortality in non-ARDS and ARDS patients requiring mechanical ventilation

Objectives: Primarily, to determine if respiratory variables, assessed on a daily basis on days 1–6 after ICU admission, were associated with mortality in non-ARDS and ARDS patients with respiratory failure requiring mechanical ventilation. Secondarily, to determine non-respiratory factors associated with mortality in ARDS and non-ARDS patients. Design: Prospective multicentre clinical study. Setting: Seventy-eight intensive care units in Sweden and Iceland. Patients: Five hundred twenty non-ARDS and 95 ARDS patients. Measurements and results: Potentially prognostic factors present at inclusion were tested against 90-day mortality using a Cox regression model. Respiratory variables (PaO₂/FIO₂, PEEP, mean airway pressure (MAP) and base excess (BE)) were tested against mortality using the model. Primary aim: in non-ARDS a low PaO₂/FIO₂ on day 1, RR (risk ratio) = 1.17, CI (95 % confidence interval) (1.00; 1.36), day 4, 1.24 (1.02; 1.50), day 5, 1.25 (1.02; 1.53) and a low MAP at baseline, 1.18 (1.00; 1.39), day 2, 1.24 (1.02; 1.52), day 3, 1.33 (1.06; 1.67), day 6, 2.38 (1.11; 5.73) were significantly associated with 90-day death. Secondary aim: in non-ARDS a low age, RR = 0.77 (0.67; 0.89), female gender, 0.85 (0.74; 0.98), and low APS (acute physiologic score), 0.85 (0.73; 0.99), were associated with survival; chronic disease, 1.31 (1.12; 1.52), and non-pulmonary origin to the respiratory failure, 1.27 (1.10; 1.47), with death. In ARDS low age, RR = 0.65 CI (0.46; 0.91), and low APS, 0.65 (0.46; 0.90), were associated with survival. Conclusions: No independent significant association was seen between 90-day mortality and degree of hypoxaemia, PEEP, MAP or BE for the first full week of ICU care in either ARDS or non-ARDS. In a sub-group of non-ARDS a lower PaO₂/FIO₂ and MAP tended to influence mortality where a significant association was seen for 3 of 7 study days. Age, gender, APS, presence of a chronic disease and a pulmonary/non-pulmonary reason for the respiratory failure were associated with mortality in non-ARDS, while only age and APS showed a similar association in ARDS. Received: 16 February 1999 Final revision received: 4 October 1999 Accepted: 24 February 2000     

Current definitions of acute lung injury and the acute respiratory distress syndrome do not reflect their true severity and outcome

Background: Despite intensive research, there are no universally accepted clinical definitions for acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). A recent joint American-European Consensus Conference on ARDS formally defined the difference between ALI and ARDS based on the degree of oxygenation impairment. However, this definition may not reflect the true prevalence, severity and prognosis of these syndromes. Methods: During a 22-month period, 56 consecutive mechanically ventilated patients who met the American-European Consensus definition for ARDS [arterial oxygen tension/fractional inspired oxygen (PaO₂/FIO₂≤ 200 mmHg regardless of the level of positive end-expiratory pressure (PEEP), bilateral pulmonary infiltrates, and no evidence of left heart failure] were admitted into the intensive care units (ICU) of the Hospital del Pino, Las Palmas, Spain, and prospectively studied. The diagnosis of ALI and ARDS was made by a PEEP-FIO₂ trial, 24 h after patients met the Consensus inclusion criteria. Patients were classified as having ALI_{–24 h} if the PaO₂/FIO₂ was > 150 mmHg with PEEP = 5 cmH₂O, and ARDS_{–24 h} if the PaO₂ /FIO₂ was ≤ 150 mmHg with PEEP ≥ 5 cmH₂O. Results: Overall mortality was 43 % (24 of 56). However, 24 h after inclusion, PaO₂ response to PEEP 5 cmH₂O allowed the separation of our patients into two different groups: 31 patients met our ALI_{–24 h} criteria (PaO₂/FIO₂ > 150 mmHg) and their mortality was 22.6 %; 25 patients met our ARDS_{–24 h} criteria (PaO₂/FIO₂≤ 150 mmHg) and their mortality was 68 % (p = 0.0016). The differences in the respiratory severity index during the first 24 h of inclusion, PaO₂/FIO₂ ratio at baseline and at 24 h, maximum plateau airway pressure, maximum level of PEEP, and number of organ system failures during the ICU stay were statistically significant. Conclusions: Since the use of PEEP in the American-European Consensus criteria for ARDS is not mandatory, that definition does not reflect the true severity of lung damage and outcome. Our data support the need for guidelines based on a specific method of evaluating oxygenation status before the American-European Consensus definition is adopted. Received: 18 April 1999 Final revision received: 30 June 1999 Accepted: 9 July 1999     

Improvement in oxygenation by prone position and nitric oxide in patients with acute respiratory distress syndrome

Objective: Inhaled nitric oxide (NO) and prone position improve arterial oxygenation in patients with the acute respiratory distress syndrome. This study was undertaken to assess the combined effects of NO and prone position in these patients. Design: Prospective clinical study. Setting: General intensive care service in a community teaching hospital. Patients: 14 mechanically ventilated adult patients with the acute respiratory distress syndrome (mean lung injury score 3.23 ± 0.27). Measurements and results: We measured hemodynamic and oxygenation parameters in the supine position and 2 h later in the prone position, before and during inhalation of 10 ppm NO. A positive response in oxygenation was defined as a ≥ 20 % increment in the arterial oxygen tension/fractional inspired oxygen ratio (PaO₂/FIO₂). In the prone position PaO₂/FIO₂ increased significantly (from 110 ± 55 to 161 ± 89 mmHg, p < 0.01) and venous admixture decreased (from 38 ± 12 to 30 ± 7 %, p < 0.01) compared to the supine position. Ten of the 14 patients were responders in the prone position. In the supine position, inhalation of NO improved oxygenation to a lesser extent, increasing PaO₂/FIO₂ to 134 ± 64 mmHg (p < 0.01) and decreasing venous admixture to 35 ± 12 %, (p < 0.01). Five of the 14 patients responded to NO inhalation supine and 8 of 14 responded prone (p = 0.22). The combination of NO therapy and prone positioning was additive in increasing PaO₂/FIO₂ (197 ± 92 mmHg) and decreasing venous admixture (27 ± 8 %) (p < 0.01). This combination also showed a positive oxygenation response on compared to the supine value without NO in 13 of the 14 patients (93 %). NO-induced changes in PaO₂/FIO₂ were correlated to changes in pulmonary vascular resistance only in the prone position. Conclusions: In patients with the acute respiratory distress syndrome, the combination of NO and prone position is a valuable adjunct to mechanical ventilation. Received: 15 June 1998 Final revision received: 13 October 1998 Accepted: 30 October 1998     

HA-1A in septic patients with ARDS: Results from the pivotal trial

Objective To evaluate the effects of HA-1A, a human monoclonal antiendotoxin antibody, in septic patients with ARDS.Design Substudy of a multicenter, double-blinded, placebo-controlled trial of HA-1A in septic patients.Patients 63 septic patients with ARDS at the time of study entry.Intervention A single intravenous injection of HA-1A (100 mg) or placebo.Results A quantitative radiographic score, the PaO₂/FIO₂ ratio and an index of the severity of ARDS did not show a significant difference between the treatment and placebo groups at 3, 5 and 7 days after treatment. The duration of endotracheal intubation did not differ between the two groups. 15 of 30 HA-1A treated patients (50%) and 23 of 33 placebo-treated patients (69.7%) died within 28 days. The daily mortality was always lower in the HA-1A group, but this difference was not statistically significant at 28 days. The 28-day survival curves for the two treatment groups adjusted by covariate analysis were not significantly different (p=0.07). Using logistic regression, a significant independent effect of HA-1A treatment was detected upon the early survival rate at 7 days (p=0.03) but not at 14 and 28 days.Conclusion A single injection of HA-1A in septic patients with ARDS did not reverse acute respiratory failure or improve long-term survival.This study was supported by a grant from Centocor Inc., Malvern, PA, USA     

Reduction of ventilator settings allowed by intravenous oxygenator (IVOX) in ARDS patients

Objective To evaluate the possibility of reducing ventilator settings to “safe” levels by extrapulmonary gas exchange with IVOX in ARDS patients. Design Uncontrolled open clinical study. Setting Medical Intensive Care Unit of a University Hospital. Patients 6 patients with ARDS who entered into IVOX phase II clinical trials. Interventions The end-point of this study was to reduce ventilator settings from the initial values, recorded on the day of inclusion, to the following: peak inspiratory pressure <40 cmH₂O, mean airway pressure <25 cmH₂O and tidal volume <10 ml/kg. Trials to achieve this goal were made on volume-controlled ventilation within the 24h before and after IVOX insertion. Comparison of the results achieved during these trials used wilcoxon test. Results Before IVOX implantation reduction of ventilator settings was not possible in the 6 patients, despite a non-significant increase in PaO₂/FIO₂ was achieved. IVOX permitted significant decrease in PaCO₂ (from 60.5±15 to 52±11 mmHg;p=0.02) before any modification of the ventilatory mode. After IVOX insertion, a significant decrease of the ventilator settings was performed: peak and mean airway pressures dropped from 44±10 to 36.8±6.7;p=0.02 and from 26.3±5.6 to 22.5±3.9 cmH₂O;p=0.02, respectively. Concommitantly, PaCO₂ remained unchanged and PaO₂/FIO₂ increased significantly from 93±28 to 117±52;p=0.04. The interruption of oxygen flow on IVOX was associated with a slight decrease of the oxygen variables. Tolerance of IVOX was satisfactory. However, a significant decrease both in cardiac index and in pulmonary wedge pressures (from 4.5±1.2 to 3.4±9;p=0.03 and from 16±5 to 11±2;p=0.04, respectively) was observed. Conclusion Gas exchange achieved by IVOX allowed reduction of ventilator settings in 6 ARDS patients in whom previous attempts have failed. CO₂ removal by the device, may explain these results. Efficacy of IVOX on arterial oxygenation was uncertain.     

Long chain versus medium chain lipids in patients with ARDS: effects on pulmonary haemodynamics and gas exchange

Objective: To compare pulmonary haemodynamic and gas exchange alterations in septic patients with ARDS receiving long-chain triglycerides (LCT) versus medium-chain triglycerides (MCT). Design: Prospective, randomised, clinical study. Setting: Surgical ICU patients in a University Hospital. Patients: Twenty-one septic patients with ARDS were randomly assigned to receive 50 % of their non-protein caloric requirements as either 20 % LCT (group 1, n = 10) or 20 % 1 : 1 mixture of LCT/MCT (group 2, n = 11). Intervention: Intravenous infusion of LCT and LCT/MCT combinations at a rate of 12 g · h^{− 1}. Measurements and results: The LCT infusion was associated with an increase of pulmonary venous admixture (Qva/Qt) from 24 % ± 5 % to 37 % ± 6 %, an increase of mean pulmonary artery pressure (MPAP) from 25 ± 5 to 33 ± 4 mmHg and decrease of PaO₂/FIO₂ from 240 ± 30 to 180 ± 35. LCT/MCT administration was only associated with an elevation of oxygen consumption (VO₂) from 329 ± 14 to 396 ± 12 ml/min. During lipid infusion group 1 patients presented higher Qva/Qt (37 % ± 6 % vs 25 % ± 4 %), MPAP (33 ± 4 vs 27 ± 3 mmHg) and VO₂ (359 ± 11 vs 396 ± 12 ml/min) and lower PaO₂/FIO₂ (180 ± 35 vs 235 ± 30) values compared to group 2. Conclusion: In conclusion, we have shown that, in septic patients with respiratory failure, LCT administration was associated with more significant changes of Qva/Qt, MPAP and PaO₂/FIO₂ compared to infusion of an LCT/MCT 1 : 1 emulsion. Clinically, these transient alterations might cause serious problems in patients with marginal arterial oxygenation and cardio-respiratory impairment. Received: 23 July 1997 Accepted: 15 May 1998     

Additive effect on gas exchange of inhaled nitric oxide and intravenous almitrine bismesylate in the adult respiratory distress syndrome

Objective To assess the additive effect of inhaled nitric oxide (NO) and intravenous almitrine bismesylate (ALM) on gas exchange.Design Prospective self-controlled study.Setting 3 medico-surgical intensive care units.Patients 17 patients with severe hypoxemia (PaO₂/FIO₂ ratio: 88±30mmHg, venous admixture: 47±7%) and elevated mean pulmonary artery pressure (MPAP: 30±5mmHg) due to adult respiratory distress syndrome (ARDS).Interventions 5 conditions were studied: 1) baseline, 2) 5 to 10ppm of NO during 30min, 3) discontinuation of NO during 30min, 4) ALM infusion (0.5mg/kg) during 30min, 5) ALM infusion (0.5mg/kg) during 30min in combination with 5 to 10ppm of NO.Measurement and results The PaO₂/FIO₂ ratio rose from 88±30 to 98±37mmHg (NS) with NO alone, and from 92±25 to 130±56mmHg (p<0.01) with NO+ALM (p<0.05 vs NO alone). Seven patients were considered as NO-responders (rise in PaO₂/FIO₂ ratio of 10mmHg or more with NO); in this subgroup the PaO₂/FIO₂ ratio rose from 87±30 to 128±39mmHg (p<0.05) with NO alone, and from 93±20 to 169±51mmHg (p<0.01) with NO+ALM (p<0.05 versus NO alone). MPAP decreased from 30±5 to 26±5mmHg (p<0.01) with NO alone, increased slightly from 28±5 to 31±5mmHg (NS) with ALM alone and decreased to 27±5mmHg (p<0.05) with NO+ALM.Conclusions NO+ALM had additive effects on gas exchange while decreasing MPAP in patients with ARDS. The effects of NO alone were small and non significant, except in a subgroup of 7 patients in whom the combination of both therapies had the more pronounced results.     

Acute effects of continuous rotational therapy on ventilation-perfusion inequality in lung injury

Objective: To investigate ventilation-perfusion (V_A/Q) relationships, during continuous axial rotation and in the supine position, in patients with acute lung injury (ALI) using the multiple inert gas elimination technique. Design: Prospective investigation. Setting: Eighteen-bed intensive care unit in a university hospital. Patients and interventions: Ten patients with ALI (PaO₂/FIO₂ ratio < 300 mm Hg) were mechanically ventilated in a pressure controlled mode and placed on a kinetic treatment table. Measurements and results: Distributions of V_A/Q were determined 1) during rotation (after a period of 20 min) and 2) after a resting period of 20 min in the supine position. During axial rotation, intrapulmonary shunt (19.1 ± 15 % of cardiac output) was significantly reduced in comparison with when in the supine position (23 ± 14 %, p < 0.05), areas with “low” V_A/Q were not affected by the positioning maneuver. General V_A/Q mismatch (logarithmic distribution of pulmonary blood flow) was decreased during rotation (0.87 ± 0.37) in comparison with when the patient was in the supine position (0.93 ± 0.37, p < 0.05). Arterial oxygenation was significantly improved during continuous rotation (PaO₂/FIO₂ = 217 ± 137 mm Hg) as compared with in the supine position (PaO₂/FIO₂ = 174 ± 82 mm Hg, p < 0.05). The positive response of the continuous rotation on arterial oxygenation was only demonstrated in patients with a Murray Score of 2.5 or less, indicating a “mild to moderate” lung injury, while in patients presenting with progressive ARDS (Murray Score > 2.5), the acute positive response was limited. Conclusions: Continuous axial rotation might be a method for an acute reduction of V_A/Q mismatch in patients with mild to moderate ALI, but this technique is not effective in late or progressive ARDS. Further studies including a large data collection are needed. Received: 19 June 1997 Accepted: 6 November 1997     

Prone ventilation following witnessed pulmonary aspiration: the effect on oxygenation

Objective Pulmonary aspiration is a significant cause of admission to the ITU and is associated with significant morbidity and mortality. Aspiration in the supine position produces posterior collapse/consolidation, similar to that seen in ALI/ARDS patients. Prone positioning has been shown to improve oxygenation in ALI/ARDS, but no studies have been performed on pulmonary aspiration.Design A prospective crossover study.Setting Twelve-bed ITU.Patients and participants Eleven patients admitted to ITU with respiratory failure secondary to witnessed pulmonary aspiration requiring ventilation and an FIO₂ >0.50 after 12 h.Interventions Patients were placed in a prone position for 8 h and then turned supine for 8 h. Prone positioning was repeated if the FIO₂ remained >0.50. Ventilator settings were not altered in the study period.Measurements and results Arterial blood gas analysis was performed every 2 h. The PaO₂/FIO₂ gradient was calculated. Oxygenation improved on turning prone, with a significant increase in the PaO₂/FIO₂ ratio (P<0.01). There was a fall in this gradient on return to the supine position. There was a significant improvement in oxygenation on turning prone for the second period (P<0.01). Overall, there was a significant improvement in the PaO₂/FIO₂ ratio in the final supine position when compared to the first (P<0.05).Conclusion This study demonstrates a significant improvement in oxygenation in the prone position in pulmonary aspiration. Early prone positioning in patients with pulmonary aspiration requiring ventilation may improve oxygenation by altering V/Q relationships similarly to ARDS, but also may aid drainage of secretions, opening up alveoli and preventing progression to established pneumonitis.This paper was presented as a poster at the Intensive Care Society state-of-the-art meeting in London, December 2002.     

The acute respiratory distress syndrome: Definitions,severity and clinical outcome An analysis of 101 clinical investigations

Objective To determine possible changes in outcome from acute respiratory distress syndrome (ARDS) and to compare severity of lung injury and methods of treatment from 1967 to 1994.Data sources Computerized (Medline, Current Contents) and manual (Cumulated Index Medicus) literature search using the key word and/or title ARDS.Study selection Only clinical studies published as full papers reporting data on both patient mortality (survival) and oxygenation index (PaO₂/FIO₂) were included. Single case reports, abstracts, reviews and editorials were excluded from evaluation.Data extraction Relevant data were extracted in duplicate, followed by quality checks on approximately 80% of data extracted.Data synthesis 101 papers reporting on 3264 patients were included: 48 studies (2207 patients) were performed in the USA, 43 studies (742 patients) in Europe and 10 studies (315 patients) elsewhere. Mortality reported in these studies was 53±22% (mean±SD), with no apparent trend towards a higher survival (1994: 22 studies, mortality 51±19%). The mean PaO₂/FIO₂ ratio remained unchanged throughout the observation period (118±47 mmHg). No correlation could be established between outcome and PaO₂/FIO₂ or lung injury score. Patients who underwent pressure-limited ventilation had a significantly lower mortality (35±20%) than patients on volume-cycled ventilation (54±22%) or patients for whom there was no precise information on ventilatory support (59±19%). Significantly lower PaO₂/FIO₂ ratios (61±17 mmHg) were observed in patients prior to extracorporeal lung assist, together with mortality rates in the range of those for conventionally treated patients (55±22%).Conclusions The mortality of ARDS patients remained constant throughout the period studied. Therefore, the standard for outcome in ARDS should be a mortality in the 50% range. Neither PaO₂/FIO₂ ratio nor lung injury score was a reliable predictor for outcome in ARDS. Patients might benefit from pressure-limited ventilatory support, as well as extracorporeal lung assist. Since crucial data were missing in most clinical studies, thus preventing direct comparison, we emphasize the importance of using standardized definitions and study entry criteria.     

Predictors of respiratory function deterioration after transfer of critically ill patients

Objectives: Critically ill patients are often transferred due to the growing number of diagnostic procedures required to be performed outside the intensive care unit. These transfers have proved to be very critical. The aim of this study was to evaluate predictors for the deterioration of respiratory function in critically ill patients after transfer. Design: Prospective, clinical, observational study. Setting: 1800-bed university teaching hospital. Subjects: 98 mechanically ventilated patients were investigated during transfer. Measurement and main results: Before transfer, all patients were classified according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Therapeutic Intervention Scoring System (TISS). Haemodynamics and arterial blood gases were measured at 11 different times. Arterial oxgen tension (PaO₂), fractional inspired oxygen (FIO₂), PaO₂/FIO₂ ratio, lowest PaO₂/FIO₂ ratio, minimal PaO₂ and maximal FIO₂, APACHE II score, TISS before transfer, age and duration of transfer were analysed as potential predictors for deterioration of respiratory function after transfer. Variables were analysed using Classification and Regression Trees and Clustering by Response. In 54 transports (55 %) there was a decrease in the PaO₂/FIO₂ ratio, and a decrease of more than 20 % from baseline was noted in 23 of the transferred patients (24 %). Age > 43 years and FIO₂ > 0.5 were identified as predictors for respiratory deterioration. Conclusions: Our predictors were able to indicate deterioration after transfer correctly in 20 of 22 patients (91 %), combined with a false-positive rate in 17 of 49 (35 %). Received: 4 December 1997 Accepted: 14 August 1998     

Impact of positive end-expiratory pressure on the definition of acute respiratory distress syndrome

Objective We examined whether PEEP during the first hours of ARDS can induce such a change in oxygenation that could mask fulfillment of the AECC criteria of a PaO₂/FIO₂ 200 essential for ARDS diagnosis.Design and setting Observational, prospective cohort in two medical-surgical ICU in teaching hospitals.Patients 48 consecutive patients who met AECC criteria of ARDS on 0 PEEP (ZEEP) at the moment of diagnosis.Measurements and results PaO₂/FIO₂ and lung mechanics were recorded on admission (0 h) to the ICU on ZEEP, and after 6, 12, and 24 h on PEEP levels selected by attending physicians. Lung Injury Score (LIS) was calculated at 0 and 24 h. PaO₂/FIO₂ rose significantly from 121±45 on ZEEP at 0 h, to 234±85 on PEEP of 12.8±3.7 cmH₂O after 24 h. LIS did not change significantly (2.34±0.53 vs. 2.42±0.62). These variables behaved similarly in pulmonary and extrapulmonary ARDS, and in survivors and nonsurvivors. After 24 h only 18 patients (38%) still had a PaO₂/FIO₂ of 200 or lower. Their mortality was similar to that in the remaining patients (61% vs. 53%).Conclusions The use of PEEP improved oxygenation such that one-half of patients after 6 h, and most after 24 h did not fulfill AECC hypoxemia criteria of ARDS. However, LIS remained stable in the overall series. These results suggest that PEEP level should be taken into consideration for ARDS diagnosis.     

Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial

Objectives The American–European consensus conference (AECC) definition for acute respiratory distress syndrome (ARDS) requires a PaO₂/F_IO₂200 mmHg, regardless of ventilator settings. We report the results of using standardized ventilator settings to screen and enroll ARDS patients in a clinical trial of high-frequency oscillatory ventilation (HFOV), including the impact on study enrollment, and potential effects on study outcome.Design Prospective cohort study.Setting Intensive care units in two teaching hospitals.Participants A consecutive sample of 41 patients with early ARDS by AECC criteria (baseline PaO₂/F_IO₂200) who met all other inclusion/exclusion criteria for the HFOV trial.Interventions Patients were placed on standardized ventilator settings (tidal volume 7–8 ml/kg, PEEP 10 cmH₂O, F_IO₂ 1.0), and the PaO₂/F_IO₂ was reassessed after 30 min.Results Seventeen patients (41.5%) had PaO₂/F_IO₂ ratios that remained 200 mmHg [Persistent ARDS; PaO₂/F_IO₂=94±36 (mean±SD)] and went on to inclusion in the HFOV study; however, in 24 patients (58.5%) the PaO₂/F_IO₂ was >200 mmHg [Transient ARDS; PaO₂/F_IO₂=310±74] and these patients were ineligible for the HFOV study. The ICU mortality was significantly greater (52.9 vs 12.5%; p=0.01) in the Persistent ARDS patients.Conclusions The use of these standardized ventilatory significantly impacted the PaO₂/F_IO₂ ratio and therefore the ARDS prevalence and trial enrollment. These results have effects on the evaluation of the current ARDS literature and conduct of clinical trials in ARDS and hence consideration should be given to the use of standardized ventilatory settings in future ARDS trials.Electronic Supplementary Material Supplementary Material is available in the online version of this article at     

COVID-19 and non-COVID ARDS patients demonstrate a distinct response to low dose steroids- A retrospective observational study

Patients with COVID-19 ARDS have distinct physiological and immunological phenotypes compared to patients with non-COVID ARDS. Patients with COVID-19 ARDS (n = 32) had a significant improvement in PaO₂: FiO₂ ratio (p = 0.046) following low-dose steroid treatment, unlike patients with non-COVID ARDS (n = 16) (p = 0.529). Patients with COVID-19 ARDS had a greater fall in CRP compared to patients with non-COVID ARDS, albeit not statistically significant (p = 0.07). Our novel findings highlight differences in the underlying physiological and immunological phenotypes between COVID-19 and non-COVID ARDS, with implications for future ARDS studies.     

Relationship between extravascular lung water and severity categories of acute respiratory distress syndrome by the Berlin definition

Introduction

The Berlin definition divides acute respiratory distress syndrome (ARDS) into three severity categories. The relationship between these categories and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, remains to be elucidated. The aim of this study was to evaluate the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and to confirm the associated predictive validity for severity.

Methods

The extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) were measured using a transpulmonary thermodilution method for three consecutive days in 195 patients with an EVLWi of ≥10 mL/kg and who fulfilled the Berlin definition of ARDS. Collectively, these patients were seen at 23 ICUs. Using the Berlin definition, patients were classified into three categories: mild, moderate, and severe.

Results

Compared to patients with mild ARDS, patients with moderate and severe ARDS had higher acute physiology and chronic health evaluation II and sequential organ failure assessment scores on the day of enrollment. Patients with severe ARDS had higher EVLWi (mild, 16.1; moderate, 17.2; severe, 19.1; P <0.05) and PVPI (2.7; 3.0; 3.2; P <0.05). When categories were defined by the minimum PaO₂/FIO₂ ratio observed during the study period, the 28-day mortality rate increased with severity categories: moderate, odds ratio: 3.125 relative to mild; and severe, odds ratio: 4.167 relative to mild. On independent evaluation of 495 measurements from 195 patients over three days, negative and moderate correlations were observed between EVLWi and the PaO₂/FIO₂ ratio (r = -0.355, P<0.001) as well as between PVPI and the PaO₂/FIO₂ ratio (r = -0.345, P <0.001). ARDS severity was associated with an increase in EVLWi with the categories (mild, 14.7; moderate, 16.2; severe, 20.0; P <0.001) in all data sets. The value of PVPI followed the same pattern (2.6; 2.7; 3.5; P <0.001).

Conclusions

Severity categories of ARDS described by the Berlin definition have good predictive validity and may be associated with increased extravascular lung water and pulmonary vascular permeability.

Trial registration

UMIN-CTR ID UMIN000003627     

Hemodynamics in experimental gastric juice induced aspiration pneumonitis

Objective To characterize hemodynamic changes during experimental aspiration pneumonitis, paying special attention to echocardiographic assessment. Design and setting Animal study in a university-based research laboratory. Subjects Fourteen mechanically ventilated New Zealand white rabbits Interventions We instilled 1 ml/kg human gastric juice (mean pH: 4.1 + 0.2) intratracheally. Hemodynamic and respiratory parameters were measured every hour for 4 h, associated with a transthoracic echocardiography. Measurements and results Lung injury occurred within 1 hour with a marked decrease in PaO₂/FIO₂ and an increase in plateau pressure; after this initial drop the ratio remained stable throughout the experiment. Seven rabbits experienced only a mild to moderate alteration in lung oxygenation function as defined by a PaO₂/FIO₂ ratio above 200 (group A), while the other seven developed a severe alteration with a ratio below 200 (group B). At the end of the experiment pH and cardiac output were lower in group B than in group A. Using a PaO₂/FIO₂ threshold value of 150, pH, mean arterial pressure, and cardiac output were lower in the animals with the more severe hypoxemia. Neither left nor right ventricular dysfunction occurred during the experiment, and no animal experienced circulatory failure Conclusion Experimental aspiration pneumonitis after intratracheal infusion of human gastric juice is characterized by a stable fall in PaO₂/FIO₂. Animals with the most severe lung injury experienced a lower systemic arterial pressure, cardiac output, and metabolic acidosis without circulatory failure or cardiac dysfunction.     

Inhaled nitric oxide (NO) for the treatment of early allograft failure after lung transplantation

Objective: Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantion. Design: Prospective clinical dose- response study. Setting: Anesthesiological intensive care unit of a university hospital. Patients and participants: 8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO₂/FIO₂) of less than 13.3 kPa (100 mmHg). Interventions: Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator. Measurements and results: Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p < 0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5(5.2/6.0) kPa at control to 5.1(4.7/5.6) kPa at 1 ppm, 4.9(4.3/5.3) kPa at 4 ppm, and to 4.7(4.1/5.1) kPa at 8 ppm. PaO₂ increased from 12.7(10.4/17.1) to 19.2(12.4/26.0) kPa at 1 ppm NO, to 23.9(4.67/26.7) kPa at 4 ppm NO and to 24.5(11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO₂), all were subject to long-term inhalation (1–19 days). All were successfully weaned from NO and were discharged from the intensive care unit. Conclusion: The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation. Received: 23 February 1998 Accepted: 20 August 1998     

Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients

Objective: To evaluate the prevalence and outcome of the acute respiratory distress syndrome (ARDS) among patients requiring mechanical ventilation. Design: A prospective, multi-institutional, initial cohort study including 28-day follow-up. Settings: Thirty-six French intensive care units (ICUs) from a working group of the French Intensive Care Society (SRLF). Patients: All the patients entering the ICUs during a 14-day period were screened prospectively. Hypoxemic patients, defined as having a PaO₂/FIO₂ ratio (P/F) of 300 mmHg or less and receiving mechanical ventilation, were classified into three groups, according to the Consensus Conference on ARDS: group 1 refers to ARDS (P/F: 200 mmHg or less and bilateral infiltrates on the chest X-ray); group 2 to acute lung injury (ALI) without having criteria for ARDS (200 < P/F ≤ 300 mmHg and bilateral infiltrates) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups. Results: Nine hundred seventy-six patients entered the ICUs during the study period, 43 % of them being mechanically ventilated and 213 (22 %) meeting the criteria for one of the three groups. Among all the ICU admissions, ARDS, ALI and group 3 patients amounted, respectively, to 6.9 % (67), 1.8 % (17) and 13.3 % (129) of the patients, and represented 31.5 %, 8.1 % and 60.2 % of the hypoxemic, ventilated patients. The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others (60 % vs 31 % p < 0.01). In group 3, 42 patients had P/F less than 200 mmHg associated with unilateral lung injury; mortality was significantly lower (40.5 %) than in the ARDS group. In the whole group of hypoxemic, ventilated patients, septic shock and severity indices but not oxygenation indices were significantly associated with mortality, while the association with immunosuppression revealed only a trend (p = 0.06). Conclusions: In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high. Received: 21 September 1998 Final revision received: 3 February 1999 Accepted: 3 May 1999