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     

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.     

Effect of inspired oxygen fraction on alveolar derecruitment in acute respiratory distress syndrome

Objective High fractions of inspired oxygen (FIO₂) used in acute lung injury (ALI) may promote resorption atelectasis. The impact of derecruitment related to high FIO₂ in ALI is debated. We evaluated derecruitment with 100% vs. 60% FIO₂ at two levels of positive end-expiratory pressure (PEEP).Patients Fourteen consecutive patients with ALI were studied.Interventions Recruited volume at two PEEP levels was computed from two pressure-volume curves, recorded from PEEP and from zero end-expiratory pressure, using the sinusoidal flow modulation method. PEEP-induced recruitment was measured during prolonged expiration as the difference between the two curves at a given pressure. PaO₂/FIO₂ was also measured. PEEP was 5 ± 1 or 14 ± 3 cmH₂O and FIO₂ was 60% or 100%, yielding four combinations. We looked for differences between the beginning and end of a 30-min period with each combination.Measurement and results With low PEEP and 100% FIO₂, recruited volume decreased significantly from 68 ± 53 to 39 ± 43 ml and PaO₂/FIO₂ from 196 ± 104 to 153 ± 83 mmHg. With the three other combinations (low PEEP and 60% FIO₂ or high PEEP and 60% or 100% FIO₂) none of the parameters decreased significantly.Conclusion In mechanically ventilated patients with ALI the breathing of pure oxygen leads to derecruitment, which is prevented by high PEEP.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.This article is discussed in the editorial available at:     

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     

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     

Terlipressin as a rescue therapy for catecholamine-resistant septic shock in children

Objective To evaluate the effect of terlipressin on oxygenation, PaO₂/FIO₂, heart rate, mean arterial pressure, and mortality in children with septic shock refractory to high doses of dopamine/dobutamine and adrenaline. Design and setting A randomized, nonblind study in the pediatric intensive care unit of a university hospital. Patients and measurements We studied 58 children with septic shock and refractory hypotension despite fluid loading and high doses of catecholamines, randomly enrolled to terlipressin (TP, n = 30) or control (n = 28). TP was administered as intravenous bolus doses of 20 μg/kg every 6 h for a maximum of 96 h. Hemodynamic changes, PaO₂/FIO₂ rates, length of stay, and mortality rate in PICU were recorded prospectively. Results Mean arterial pressure and PaO₂/FIO₂ significantly increased, and heart rate significantly decreased 30 min after each TP treatment, but mortality did not differ from control (67.3% vs. 71.4%). Mean stay in the PICU was shorter in the TP group (13.4 ± 7.9 vs. 20.2 ± 9.7 days and was longer among nonsurvivors of the TP group vs. control (10.4 ± 6.9 vs. 6.2 ± 3.4 days). Blood urea nitrogen, creatinine, AST, ALT, and urine output of patients in the TP group did not change after terlipressin. Conclusions Although terlipressin infusion had no effect on mortality, it significantly increases mean arterial pressure, PaO₂/FIO₂, and survival time in nonsurvivors. Terlipressin seems to cause no adverse effect but warrants further evaluation as a rescue therapy in refractory septic shock.     

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     

Prolonged lateral steep position impairs respiratory mechanics during continuous lateral rotation therapy in respiratory failure

Objective To establish whether prolonged lateral steep position during continuous rotation therapy leads to improvement on pulmonary gas exchange, respiratory mechanics and hemodynamics. Design Prospective observational study. Setting Intensive care unit of a university hospital. Patients Twelve consecutive patients suffering from acute lung injury or adult respiratory distress syndrome undergoing continuous rotation therapy. Interventions Blood gas analysis, static lung compliance, blood pressure, cardiac index and pulmonary shunt fraction were measured in supine as well as in left and right lateral steep position at 62° during continuous rotation therapy (phase I). Rotation was then stopped for 30 min with the patients in supine position, left and right lateral steep position, and the same measurements were performed every 10 min (phase II). Measurements and results Phase I and II revealed no significant changes in PaO₂/FiO₂ ratio, mean arterial blood pressure, pulmonary shunt fraction, or cardiac index. Significantly lower static compliance was observed in lateral steep position than in supine position (p < 0.001). Concomitantly, PaCO₂ was significantly lower in supine position than in left and right lateral steep position (p < 0.01). Conclusions Lateral steep positioning impairs the compliance of the respiratory system. Prolonged lateral steep position does not lead to benefits with respect to oxygenation or hemodynamics. Individual response to the different positions is unpredictable. The pauses in “extreme” positions should be as short as possible.     

Acute myocardial infarction with normal coronary arteries during septic shock from Neisseria meningitidis

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (?^·V_A/?^·Q) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and?^·V_A/?^·Qdistributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal?^·V_A/?^·Qratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal?^·V_A/?^·Qrelationships.     

Transcutaneous Pco2 and Po2: A multicenter study of accuracy

A multicentcr study used 756 samples from 251 patients in 12 institutions to compare arterial (PaO₂, PaCO₂) with transcutaneous (PsO₂, PsCO₂) oxygen and carbon dioxide tensions, measured usually at 44°C. Of these samples, 336 were obtained from 116 neonates, 27 from 25 children with cystic fibrosis, and 140 from 40 patients under general anesthesia. Ninety-one patients were between 4 weeks and 18 years of age, 32 were between 18 and 60 years, and 12 were over 60. The ratio of transcutaneous to arterial P(s/a)CO₂ was 1.01 ±0.11 with PaCO₂ less than 30 mm Hg, increasing to 1.04 ±0.08 at PaCO₂ greater than 40 mm Hg. Mean bias and its standard deviation (PsCO₂ — PaCO₂) were + 1.3 ± 3.9 mm Hg in the entire group, + 1.8 ± 4.2 mm Hg in neonates (NS). Bias was +0.2 ± 2.7 mm Hg when PaCO₂ was less than 30 mm Hg (N = 175, NS), 1.0 ± 3.4 with 30 < PaCO₂ < 40 (n = 329,p < 0.001), and +2.04 ± 4.00 mm Hg with 40 < PaCO₂ < 70 (n = 229,p < 0.001). These data suggest that, using transcutaneous PCO₂ monitors with inbuilt temperature correction of 4.5%/‡C, the skin metabolic offset should be set to 6 mm Hg. The linear regression was PsCO₂ =1.052(PaCO₂)-0.56, Sy·x = 3.92, R = 0.929 (n = 756); and PsCO₂ = 1.09(PaCO₂)-1.57, Sy·x = 4.17, R = 0.928 in neonates (n = 336). The use of vasopressors and vasodilators had no significant effect on bias or its standard deviation or on regression slope and intercept (n = 78). In cystic fibrosis patients, bias and standard deviation were 0.0 ± 1.7 mm Hg (n = 27). Under anesthesia, PsCO₂ = 1.07PaCO₂-1.58, with bias and standard deviation = 0.6 ± 3.5 (n = 140). For oxygen, at PaO₂ ≤ 80 the ratio P(s/a)O₂ = 1.05 ± 0.16 in nconates and 0.93 ± 0.21 in older patients, but when PaO₂ > 80, P(s/a)O₂ fell to 0.88 ± 0.18 in neonates and 0.74 ± 0.21 in older patients. The errors were significantly greater (p < 0.001) in older patients than in neonates above but not below 80 mm Hg, and within both groups errors were significantly greater above than below 80 mm Hg.     

Ventilation–perfusion inequality and carbon dioxide sensitivity in hypoxaemic chronic obstructive pulmonary disease (COPD) and effects of 6 months of long‐term oxygen treatment (LTOT)

The aim of our study was to find out how blood gas disturbances in stable, eucapnic, severe chronic obstructive pulmonary disease (COPD) patients with an arterial oxygen tension (PaO₂) value of 7·7 (6·1–8·4) kPa are affected by ventilation–perfusion (V_A/Q) relationships and carbon dioxide (CO₂) sensitivity and how these parameters are influenced by 6 months of long‐term oxygen treatment (LTOT). V_A/Q ratios were measured using the multiple inert gas elimination technique (MIGET). Mouth occlusion pressure 0·1 s after onset of inspiration (Pi0·1) and minute ventilation (V_E) were measured to assess respiratory drive response (ΔPi0·1/ΔPCO₂) and hypercapnic ventilatory response (HCVR) to CO₂ rebreathing. At the start of LTOT, a normal median respiratory drive response level of 1·2 (0·2–2·3) cm H₂O/kPa and a low median HCVR as compared with healthy individuals (P<0·001) were found. However, 7·9 (0–29·8)% of the V_E, was directed towards hypoperfused lung areas. The dispersion of ventilation (log SDV; 0·47–1·76), and the dispersion of perfusion (log SDQ; 0·66–1·07) were wider than normal. The PaO₂ level correlated inversely with mean V_A/Q ratio for ventilation (V mean) and shunt. The PaCO₂ level correlated inversely with HCVR and vital capacity. After 6 months of LTOT, no significant changes in daytime blood gas levels, CO₂‐sensitivity or V_A/Q ratios were found. V_E tended to be reduced by 1·0 l min^–1. Conclusions: An elevated V mean and probably shunting are important contributing factors for the reduced PaO₂ and hypercapnic ventilatory response is a major determinant of PaCO₂ in eucapnic stable hypoxaemic COPD. Six months of LTOT does not affect blood gases, CO₂ sensitivity or ventilation–perfusion relationships.     

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     

Ventilation/perfusion ratio and right to left shunt in healthy newborn infants

Oxygenation impairment can be assessed non-invasively by determining the degree of right-to-left shunt and ventilation/perfusion (V_A/Q) inequality. These indices have been used in sick newborn infants, but normative values have not been reported which are essential to determine the magnitude of the abnormality. We, therefore, aimed to measure the shunt and V_A/Q in infants with no history of respiratory conditions and determine if there was any effect of supine or prone position and the reproducibility of the data. Data were analysed from infants who had undergone a hypoxic challenge and in a subset who had been assessed in the supine or prone position. Transcutaneous oxygen saturations (SpO₂) were recorded at fractions of inspired oxygen (F_IO₂) of 0.21 and 0.15. Two independent raters used a computer software algorithm which analysed and fitted paired data for F_IO₂ and SpO₂ and derived a curve which represented the best fit for each infant’s data and calculated the shunt and V_A/Q. The raters ability to interpret the SpO₂ value which corresponded to a given F_IO₂ was compared. The downwards displacement of the F_IO₂ versus SpO₂ curve was used to estimate the degree of right-to-left shunt and the rightwards shift of the curve was used to calculate the V_A/Q ratio. The mean (SD) gestational age of the 145 infants was 39 (1.6) weeks, their birth weight was 2990 (578) gms and median (range) postnatal age at measurement 3 (1–8) days. The mean (SD) V_A/Q ratio was 0.95 (0.21). None of the infants had a right-to-left shunt. No significant differences were found in V_A/Q in the supine compared to the prone position. The intraclass correlation coefficient of V_A/Q between two independent raters was 0.968 (95% CI 0.947–0.980), p?<?0.001. Right-to-left shunt and V_A/Q ratio in healthy newborn infants were similar in the prone compared to the supine position.     

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.     

Effects of prone position on alveolar recruitment and oxygenation in acute lung injury

Objective: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure.¶Design: Prospective physiologic study.¶Setting: Medical ICU two in a university hospital.¶Patients: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated.¶Measurements and results: We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (ΔFRC). The recruited alveolar volume was computed as the ΔFRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO₂/FIO₂ ratio improved from SP1 to PP (136 ± 17 vs 204 ± 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 ± 0.99 cmH₂O/l in SP1 to 6.26 ± 0.54 cmH₂O/l in PP (p < 0.05) without any correlation to the change in oxygenation.¶Conclusions: Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.     

Effect of inhaled nitric oxide in combination with almitrine on ventilation-perfusion distributions in experimental lung injury

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V˙._A/Q˙) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and V˙._A/Q˙ distributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal V˙._A/Q˙ ratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal V˙._A/Q˙ relationships.     

The effect of exogenous surfactant in patients with lung contusions and acute lung injury

Objective To investigate the acute effect of surfactant replacement in multiple-trauma patients with lung contusion and acute lung injury. Design and setting Prospective randomized clinical trial in the 14-bed ICU of a 750-bed university hospital. Patients and participants Sixteen ventilated trauma patients with severe refractory hypoxemia (PaO₂/FIO₂ < 150 mmHg) and lung contusions. Interventions Patients were randomly assigned to either surfactant administration (n = 8) or standard treatment (n = 8). A single dose of natural bovine surfactant was instilled bronchoscopically in the involved lung areas; each segmental bronchus received (200/19) mg/kg body weight. Measurements and results The surfactant group demonstrated an acute improvement in oxygenation after surfactant replacement compared both to control group and to baseline values. In the surfactant group PaO₂/FIO₂ increased from 100 ± 20 mmHg at baseline to 140 ± 20 (6 h), 163 ± 26 (12 h), and 187 ± 30 mmHg (24 h). Compliance increased from 30 to 36 ml/cmH₂O at 6 h after administration, and this increase remained significant at the 24, 48, and 72 h time points. The surfactant group demonstrated a higher response to recruitment maneuvers than the control group at 6 h. The mean duration of ventilatory support was 5.6 ± 2.6 days in the surfactant group and 8.1 ± 2.4 days in the control group. Conclusions Surfactant replacement was well tolerated in patients with lung contusions and severe hypoxemia and resulted in improved oxygenation and compliance.     

Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury

Objective In acute lung injury (ALI) activated protein C (APC) may reopen occluded lung vessels and minimize lung inflammation. We aimed at assessing the effect of APC on regional lung perfusion, aerated lung volume, cytokine production and oxygenation in experimental ALI. Design and setting Prospective, controlled study in an imaging facility. Participants Pigs tracheotomized and mechanically ventilated. Intervention Pigs were randomly given intravenously APC (n = 8) or saline (n = 8). Thirty minutes later, ALI was induced by injecting oleic acid. Measurements and results Lung perfusion and aerated lung volume measured with positron emission tomography, plasma cytokines and arterial blood gas were determined just before ALI and 110 and 290 min thereafter. Lung cytokines were measured at the end of the experiment. PaO₂ under F_IO₂ 1 was significantly lower in the APC group before lung injury (473 ± 129 vs. 578 ± 54 mmHg) and 110 min (342 ± 138 vs. 446 ± 103 mmHg) and 290 min (303 ± 171 vs. 547 ± 54 mmHg) thereafter (p < 0.05). Lung perfusion nonsignificantly tended to redistribute towards dorsal lung regions with APC. Total aerated lung volume was not different between APC and control before ALI (10.0 ± 1.5 vs. 11.0 ± 2.5 ml/kg) (p > 0.05) or thereafter. Plasma IL-6 and IL-8 at 110 min were greater with APC (p < 0.05). Conclusions In contrast to studies using other models, pretreatment with APC was associated with worsening oxygenation in the present investigation. This might be due to ventilation–perfusion mismatch, with more perfusion to dependent nonaerated areas. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: .     

Effects of high-frequency oscillatory ventilation on circulation in neonates with pulmonary interstitial emphysema or RDS

Objective: Mechanical ventilation may impair cardiovascular function if the transpulmonary pressure rises. Studies on the effects of high-frequency oscillatory ventilation (HFOV) on cardiovascular functions have yielded conflicting results. This study was done to compare alterations in left ventricular output and blood flow velocities in the anterior cerebral artery, internal carotid artery, and celiac artery using a Doppler ultrasound divice before and 2 h after initiating HFOV in neonates with respiratory distress syndrome (RDS) or pulmonary interstitial emphysema (PIE). Design: Prospective clinical study. Setting: Neonatal intensive care unit in a perinatal center. Patients: 18 critically ill infants (postnatal age 47 ± 12 h; mean ± SD) were studied before and during HFOV (piston oscillator). Indications for HFOV were severe respiratory failure due to PIE (n = 10) and severe surfactant deficiency (RDS, n = 8). In the RDS group, gestational age was 27 ± 6 weeks (range 26–31 weeks) and birthweight 1620 ± 380 g (range 850–1970 g). In the PIE group, gestational age was 28 ± 2 weeks (range 26–36 weeks) and birthweight 1740 ± 470 g (range 890–2760 g). Measurements and main results: During HFOV, mean airway pressure was maintained at the same level as during intermittent mandatory ventilation in both groups (RDS, 12 ± 2 cmH₂O; PIE, 10 ± 2 cmH₂O). Compared to intermittent mandatory ventilation, several of the 12 parameters studied changed significantly (p < 0.004) during HFOV. In the RDS group, the partial pressure of oxygen in arterial blood/fractional inspired oxygen (PaO₂/FIO₂) ratio increased from 56 ± 9 to 86 ± 7 and partial pressure of carbon dioxide in arterial blood (PaCO₂) decreased from 49 ± 4 to 35 ± 3 mmHg. In the PIE group, PaO₂/FIO₂ ratio increased from 63 ± 8 to 72 ± 7 and PaCO₂ decreased from 63 ± 7 to 40 ± 5 mmHg. In the PIE group, heart rate decreased (135 ± 15 before HFOV vs 115 ± 14 min^{− 1} during HFOV) and mean systolic blood pressure increased (before 43 ± 4 vs 51 ± 4 mmHg during HFOV) significantly, whereas these parameters did not change in the RDS group. Left ventricular output increased significantly in the PIE group (210 ± 34 before vs 245 ± 36 ml/kg per min during HFOV; p < 0.004), but not in the RDS group (225 ± 46 before vs 248 ± 47 ml/kg per min during HFOV; k < 0.05). Shortening fraction and systemic resistance did not change in either group. In the PIE group, mean blood flow velocities in the internal carotid artery (+ 59 %), anterior cerebral artery (+ 65 %) and celiac artery (+ 45 %) increased significantly but did not change in the RDS group. Conclusions: The results show that HFOV as used in this study, improves oxygenation, CO₂ elimination, and circulation in infants with RDS and PIE. However, systemic, cerebral, and intestinal circulation improved more in neonates with PIE than in those with RDS. This may be due to higher pulmonary compliance in infants with PIE when compared to those with RDS. Received: 15 May 1996 Accepted: 31 January 1997     

Intrapulmonary percussive ventilation in tracheostomized patients: a randomized controlled trial

Objective To investigate whether the addition of intrapulmonary percussive ventilation to the usual chest physiotherapy improves gas exchange and lung mechanics in tracheostomized patients.Design and setting Randomized multicenter trial in two weaning centers in northern Italy.Patients and participants 46 tracheostomized patients (age 70 ± 7 years, 28 men, arterial blood pH 7.436 ± 0.06, PaO₂/FIO₂ 238 ± 46) weaned from mechanical ventilation.Interventions Patients were assigned to two treatment groups performing chest physiotherapy (control), or percussive ventilation (IMP2 Breas, Sweden) 10 min twice/day in addition to chest physiotherapy (intervention).Measurements and results Arterial blood gases, PaO₂/FIO₂ ratio, and maximal expiratory pressure were assessed every 5th day for 15 day. Treatment complications that showed up in 1 month of follow-up were recorded. At 15 days the intervention group had a significantly better PaO₂/FIO₂ ratio and higher maximal expiratory pressure; after follow-up this group also had a lower incidence of pneumonia.Conclusions The addition of percussive ventilation to the usual chest physiotherapy regimen in tracheostomized patients improves gas exchange and expiratory muscle performance and reduces the incidence of pneumonia.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.This research was supported by the Italian Ministry of University and Research and Agenzia Italiana del Farmaco.