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) groups (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. QS/QT 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.     

The antibody response to 27-, 17-, and 15-kDa Cryptosporidium antigens following experimental infection in humans

STUDY OBJECTIVE: Data concerning inhaled nitric oxide (iNO) on pediatric ARDS is rare. We investigated the effects of iNO on pediatric ARDS in order to examine the ability to predict a response to iNO, the optimal concentration of iNO, the effects of < or = 1 ppm nitric oxide (NO), and the effect of iNO on PaCO2. SETTING: ICU at Kumamoto (Japan) University Hospital. PATIENTS AND INTERVENTIONS: Seven children with ARDS. The initial responses to 16 ppm NO and the dose-response effects of 0.13 to 16 ppm NO were assessed. MEASUREMENTS AND RESULTS: Sixteen ppm of iNO improved oxygenation in all seven children. The use of iNO significantly increased the ratio of arterial oxygen tension to the fraction of inspired oxygen (PaO2/FIO2). A correlation between the NO-induced increase in PaO2/FIO2 and the baseline PaO2/FIO2 was observed (r=0.93, p<0.01). Dose-response tests showed that the optimal concentration of iNO was < or = 4 ppm, improvements in PaO2/FIO2 could be observed with concentrations of < or = 1 ppm NO, and iNO induced a slight decrease in PaCO2. CONCLUSIONS: In children with ARDS, iNO frequently improves oxygenation and induces a slight decrease in PaCO2, with the baseline PaO2/FIO2 functioning as a predictor of all NO response. Improvements of PaO2 and PaCO2 were observed with concentrations of iNO of < or = 1 ppm, a level in which the risk of a toxic reaction in children is minimal. Effects on outcome need verification in larger controlled trials.     

Effectiveness of nitric oxide inhalation in septic ARDS

STUDY OBJECTIVE: To evaluate the percentage of nitric oxide (NO) responders in septic shock patients with ARDS. Additionally, to investigate long-term NO effects on cardiac performance and oxygen kinetic patterns in NO responders vs nonresponders. DESIGN: Prospective cohort study. SETTING: ICU of a university hospital. PATIENTS: Twenty-five consecutive patients with a diagnosis of septic shock and established ARDS requiring inotropic and vasopressor support. INTERVENTIONS: After diagnosis of ARDS, NO was administered at 18 or 36 ppm. Patients demonstrating a NO-induced rise of arterial oxygen tension of 20% or more and/or a fall in mean pulmonary artery pressure of 15% or more were grouped as NO responders; others were grouped as nonresponders. MEASUREMENTS AND RESULTS: Ten patients (40%) were NO responders, while 15 patients (60%) were nonresponders. Mortality was 40% in NO responders and 67% in nonresponders (NS). NO responders developed a significantly lower mean pulmonary artery pressure (28 +/- 6 vs 33 +/- 6 mm Hg; p < 0.05), lower pulmonary vascular resistance (PVR: 258 +/- 73 vs 377 +/- 163 dyne.s.cm-5.m-2; p < 0.05), and higher PaO2/FIO2 ratio (192 +/- 85 vs 144 +/- 74 mm Hg; p < 0.05) within the study period. In responders, NO-induced afterload reduction resulted in increased right ventricular ejection fraction (RVEF: 40 +/- 7 vs 35 +/- 9%; p < 0.05), significantly higher cardiac index (CI: 4.5 +/- 1.1 vs 4.0 +/- 1.2 L.min-1.m-2; p < 0.05) and oxygen delivery (DO2: 681 +/- 141 vs 599 +/- 160 mL.min-1.m-2; p < 0.05) compared with nonresponders. In NO nonresponders, RVEF was correlated with PVR, CI, DO2, mixed venous oxygen saturation (SvO2), and oxygen extraction ratio (O2ER) (r = +/- 0.60 to +/- 0.69; p < 0.05). No significant correlation between RVEF and any of these parameters was observed in responders. SvO2 (75 +/- 7 vs 69 +/- 8%; p < 0.05) and O2ER (0.24 +/- 0.06 vs 0.27 +/- 0.06; p < 0.05) were significantly different between responders and nonresponders, while no difference in oxygen consumption was observed (161 +/- 41 vs 153 +/- 43 mL.min.m-2). CONCLUSIONS: Inhaled NO is effective in only a subgroup of septic ARDS patients, with a higher, but insignificantly different percentage of survivors in the responder group. NO responders were characterized by increased RVEF accompanied by higher CI, DO2, and lower O2ER. In nonresponders, RVEF remained depressed, with a close correlation between RVEF and CO as well as DO2 and O2ER. Thus, nonresponders seem to suffer from impaired cardiac reserves and correspondingly lower oxygen transport variables.     

Measurement of lung volume and DLCO in acute respiratory failure

We have undertaken rebreathing measurements of functional residual capacity (FRC), carbon monoxide diffusing capacity (DLCO), and diffusing coefficient (KCO) during positive pressure ventilation in 15 patients with adult respiratory distress syndrome (ARDS). Measurements of oxygenation (PaO2:FIO2 ratio) and lung injury score (LIS) were also recorded. Eight patients subsequently died (mortality of 53%). There was no significant difference in mean FRC, PaO2:FIO2, or LIS at presentation between survivors and nonsurvivors. However, both DLCO and KCO at presentation were significantly greater in survivors than nonsurvivors. In a separate study of nine patients with less severe lung injury, pulmonary capillary blood volume, derived from values of DLCO measured at two different values of FIO2, correlated with invasive pulmonary vascular resistance (PVR) measurements (r = 0.84, p < 0.01). DLCO measurements can be successfully undertaken in patients being ventilated with acute lung injury and may be a useful, noninvasive method of assessing the pulmonary circulation. The lowest values of DLCO were recorded in patients who subsequently did not survive.     

Effects of magnesium sulphate and nitric oxide in pulmonary hypertension induced by hypoxia in newborn piglets

AIM: To examine the haemodynamic effects of intravenous magnesium sulphate on an animal model of neonatal pulmonary hypertension induced by hypoxia. METHODS: The cardiac index (Q), pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were measured in nine newborn piglets (including three controls). Pulmonary hypertension was induced by lowering the FIO2 to 0.12-0.14, after which there was a significant increase in PAP and PVRI (37% and 142%, respectively; p < 0.01) and a significant fall in SAP and Q (30% and 33%, respectively; p < 0.01). RESULTS: Magnesium sulphate was infused intravenously as four doses of 25 mg/kg, 15 minutes apart, which resulted in a significant mean (SD) increase in serum magnesium (0.83 (0.07) mmol/l to 1.82 (0.19) mmol/l; p < 0.01). After the initial dose SAP, SVRI, PAP and PVRI decreased, but not significantly. Each subsequent dose of (50, 75, 100 mg/kg) was accompanied by further significant reductions in these variables from control baseline (p < 0.05). The PVRI:SVRI ratio remained unchanged throughout. Inhaled nitric oxide (NO) 40 ppm was administered after the last dose of magnesium sulphate. The PVRI:SVRI significantly decreased (p < 0.05), indicating that reversible pulmonary hypertension remained after a maximum dose of magnesium sulphate. CONCLUSIONS: Unlike NO, magnesium sulphate is not a selective pulmonary vasodilator and may lead to deleterious effects on systemic pressures in critically ill newborns.     

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 oxygen 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%).     

Polygraphic validation of distraction tasks in clinical differential tremor diagnosis

We studied the effect of inhaled nitric oxide (NO) on 80 patients who had undergone cardiac surgery in our center. The indications for receiving NO inhalation and the number of patients were as follows: Pp/Ps > 0.5 for pulmonary hypertension (PH) (n = 32; 21 children and 11 adults), severe PH crisis (n = 9), high pulmonary vascular tone (Glenn pressure more than 18 mm Hg after bidirectional Glenn operation) or arterial oxygen saturation (SaO2) less than 70% despite an FiO2 of 1.0 after Blalock-Taussig shunt (n = 6), mean pulmonary artery pressure (PAP) > 15 mm Hg and transpulmonary gradient (TPG) (mean PAP - left atrial pressure [LAP]) > 8 mm Hg after Fontan-type operation (n = 18), elevated pulmonary vascular tone (mean PAP > 30 mm Hg and left ventricular assist system [LVAS] flow rate < 2.5 L/min/m2) in patients with LVAS (n = 3), and impaired oxygenation (PaO2/FiO2 < 100 under positive end-expiratory pressure [PEEP] > 5 cm H2O) (n = 12). Low dose inhaled NO (10 ppm) had the following effects. In adult PH patients, it significantly reduced the mean PAP (from 37.3 to 27.0 mm Hg; average values are given) and increased the mean systemic arterial pressure (SAP) (64.7 to 75.3 mm Hg). In infant PH patients, it increased the mean SAP (51.8 to 56.1 mm Hg). In patients with a PH crisis, it significantly reduced the central venous pressure (CVP) (13.3 to 8.8 mm Hg) while increasing both the mean SAP (49.4 to 57.9 mm Hg) and PaO2/FiO2 (135 to 206). In patients after a Fontan-type operation, it significantly reduced the mean PAP (16.8 to 13.8 mm Hg) and TPG (9.5 to 5.8 mm Hg). In patients under LVAS, it reduced the CVP (11.7 to 8.0 mm Hg) and mean PAP (32.0 to 24.7 mm Hg). In impaired oxygenation patients, PaO2/FiO2 was increased (75 to 106). Sixty-five patients were all followed for 2.0-4.3 years (average, 3.1 years). All 65 patients remained free from oxygen requirement, and possible chronic adverse effects including the occurrence of malignant tumors or chronic inflammation in the respiratory tract were not observed.     

Effect of surfactant on respiratory failure associated with thoracic aneurysm surgery

OBJECTIVE: To study the effects of surfactant administration on the left lung after surgical repair of descending aortic aneurysms on postoperative respiratory failure. DESIGN: Randomized, prospective, controlled study. SETTING: Clinical investigation. PATIENTS: Eleven patients with respiratory failure associated with thoracic aneurysm surgery. INTERVENTION: Eleven adult patients with acute respiratory failure (PaO2/FIO2 <300 torr [<40 kPa]) after surgical repair of descending aortic aneurysms. The artificial surfactant (30 mg/kg) was given to the operated side of the lung by intrabronchial instillation in six patients (surfactant group), whereas nothing was instilled in the other five patients (control group). MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, blood gas, and peak inspiratory pressure were measured at the end of surgery, before surfactant instillation, and at 2, 6, 12, 24, and 48 hrs after surfactant instillation. At the end of surgery, the mean +/- SEM values of the PaO2/FIO2 ratio were 204 +/- 25 torr (27.2 +/- 3.3 kPa) in the surfactant group and 240 +/- 26 torr (32.0 +/- 3.5 kPa) in the control group. After 2, 6, 12, and 48 hrs, improvements in the PaO2/FIO2 ratios were observed in the surfactant group, whereas the control group showed no improvement. Two hours after surfactant instillation, the mean value in the PaO2/FIO2 ratio was significantly higher in the surfactant group (318 +/- 24 torr [42.4 +/- 3.2 kPa]) (p < .05) compared with the control group values (240 +/- 34 torr [32 +/- 4.5 kPa]). CONCLUSION: Surfactant administration immediately after surgery restored gas exchange in postoperative respiratory failure associated with thoracic aneurysm surgery.     

The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome

Prone positioning improves gas exchange in some patients with adult respiratory distress syndrome (ARDS), but the effects of repeated, long-term prone positioning (20 h duration) have never been evaluated systemically. We therefore investigated 20 patients with ARDS after multiple trauma (Injury Severity Score [ISS] 27.3 +/- 10, ARDS score 2.84 +/- 0.42). Patients who fulfilled the entry criteria (bilateral diffuse infiltrates, severe hypoxemia, pulmonary artery occlusion pressure [PAOP] < 18 mm Hg, and PaO2/fraction of inspired oxygen [FIO2] < 200 mm Hg at inverse ratio ventilation with positive end-expiratory pressure [PEEP] > 8 mm Hg for more than 24 h) were turned to the prone position at noon and were turned back to the supine position at 8:00 AM on the next day. Thus only two turns per day were necessary, and the risk of disconnecting airways or medical lines was minimized. Prone positioning was repeated for another 20 h if the patients fulfilled the entry criteria. Except for FIO2, the ventilator settings remained unchanged during the study period. All patients were sedated and, if needed paralyzed to minimize patient discomfort. One hour before and after each position change, ventilator settings and pulmonary and systemic hemodynamics were recorded and blood was obtained for blood gas analysis. Derived cardiopulmonary and ventilatory variables were calculated using standard formulas. Overall mortality was 10%. Oxygenation variables improved significantly each time the patients were placed prone. Immediately after the first turn from the supine to the prone position the following changes were observed: PaO2 increased from 97 +/- 4 to 152 +/- 15 mm Hg, intrapulmonary shunt (Qva/Qt) decreased from 30.3 +/- 2.3 to 25.5 +/- 1.8, and the alveolar-arterial oxygen difference decreased from 424 +/- 24 to 339 +/- 25 mm Hg. All these changes were statistically significant. Most of these improvements were lost when the patients were turned supine, but could be reproduced when prone positioning was repeated after a short period (4 h) in the supine position. Short periods in the supine position were necessary to allow for nursing care, medical evaluation, and interventions such as placement of central lines. No position-dependent changes of systemic hemodynamic variables were observed. We conclude that, in trauma patients with ARDS undergoing long-term positioning treatment, lung function improves significantly during prone position compared to short phases of conventional supine position during which the beneficial effects are partly lost.     

A comparison of ventilation techniques in ARDS. Volume controlled vs pressure regulated volume control

OBJECTIVE: Comparison between effects of a new method of mechanical ventilation (PRVC) and Volume Controlled ventilation in the ARDS treatment. DESIGN: Prospective study from March 1995 to March 1997. PLACE: Intensive Care Unit of Sanremo Hospital. PATIENTS: Nine patients, six males and three females, average age 49.2 years, average SAPS 35.5, with moderate to severe ARDS related to various etiologies. INTERVENTIONS: Patient were first ventilated with Siemens Servo Ventilators 300 in Volume controlled. They were then ventilated with Pressure-regulated Volume Control maintaining the same ventilation parameters (TV, RR, FiO2, PEEP and I:E ratio). MEASUREMENTS: After a 60 minute stabilisation period in each method, Peak inspiratory pressure, Static Compliance, PaO2, PaCO2, AaDO2 and cardiovascular parameters were measured. RESULTS: With the PRVC ventilation an important decrease of PIP and an improvement of PaO2 and SaO2 were observed. CONCLUSIONS: Although it is not possible to draw any conclusion on morbidity and mortality in patients treated with PRVC versus VC, for gas exchange and compliance improvement and for inspiratory pressure decrease with consequent reduction of barotrauma, it may be affirm that PCRV seems to be the best ventilation methods in the ARDS treatment.     

The impact of prostanoids on pulmonary gas exchange during abdominal surgery with mesenteric traction

We investigated the effect of intravenous (iv) ibuprofen on prostanoid release and on pulmonary gas exchange after abdominal mesenteric traction (MT) during either abdominal aortic surgery or pancreas resection. In a prospective, randomized, double-blind study, 400 mg ibuprofen (pancreas n = 13, aorta n = 13) or a placebo (pancreas n = 13, aorta n = 13) was administered iv before skin incision. MT was applied uniformly. The prostanoid plasma concentrations, venous admixture (Q(va)/Q(t)), and PaO2/FIO2 ratio were determined at baseline (before MT) and 5, 15, 45, and 90 min after MT. Patients who underwent aortic surgery were older and exhibited a lower preoperative PaO2 than those who underwent pancreas resection. Placebo-treated patients revealed a 30-fold peak increase in 6-keto-prostaglandin F1alpha (stable metabolite of prostacyclin) levels after intentional MT during aortic as well as pancreatic operations. This response was accompanied by an increase in Q(va)/Q(t) (ibuprofen: pancreas 7% +/- 1%, aorta 14% +/- 2%; placebo: pancreas 16% +/- 3%, aorta 26% +/- 3%/15 min after MT [mean +/- SEM, P < 0.05, placebo vs ibuprofen]), which resulted in decreased PaO2/ FIO2 ratio only in the aortic surgery patients (ibuprofen: 310 +/- 19; placebo: 237 +/- 24 15 min after MT, [mean +/- SEM, P < 0.05]). The authors conclude that ibuprofen-pretreated patients demonstrated almost constant prostanoid levels without changes in pulmonary gas exchange after MT.     

Pressure-controlled, inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome

OBJECTIVES: To investigate physiologic and outcome data in patients switched from volume-cycled conventional ratio ventilation to pressure-controlled inverse ratio ventilation that did not produce air trapping and intrinsic positive end-expiratory pressure (PEEP). SETTING: Medical intensive care unit. DESIGN: Retrospective analysis of crossover data and outcome. PATIENTS: Fourteen patients with the adult respiratory distress syndrome who were receiving mechanical ventilation with volume-cycled, conventional ratio ventilation followed by pressure-controlled, inverse ratio ventilation. INTERVENTIONS: Our approach to pressure-controlled, inverse ratio ventilation was to use tidal volumes and applied PEEP values comparable to those volumes and values used on volume-cycled, conventional ratio ventilation, use inspiratory times to increase mean airway pressure instead of additional applied PEEP, and avoid air trapping (intrinsic PEEP). MEASUREMENTS AND MAIN RESULTS: With this approach, there was a reduction in peak airway pressure from 53 +/- 8.5 (SD) to 40 +/- 5.9 cm H2O (p < .01), and an increase in mean airway pressure from 20 +/- 3.9 to 30 +/- 5.2 cm H2O (p < .01). Tidal volume, mean inflation pressure, and compliance did not change. Oxygenation (PaO2) improved from 57 +/- 11.3 torr (7.6 +/- 1.5 kPa) to 94 +/- 40.2 torr (12.5 +/- 5.4 kPa) (p = .01) but the oxygenation index (mean airway pressure x FIO2 x 100/PaO2) did not change significantly (25.9 +/- 10.3 to 27.2 +/- 12.2). There was no significant change in PaCO2 or pH even though delivered minute ventilation decreased from 17.4 +/- 4.3 to 14.8 +/- 5.8 L/min (p = .02). Cardiac index slightly decreased, but hemodynamic values were otherwise stable. Only three of the 14 study patients survived. CONCLUSIONS: These data demonstrate that oxygenation is primarily a function of mean airway pressure, and that longer inspiratory times can be used as an alternative to applied PEEP to increase this oxygenation. If no air trapping develops, lung inflation pressures and delivered volumes remain constant with this approach. Because the technique was used only in patients refractory to conventional techniques, the poor outcome is not surprising.     

Dramatic effect on oxygenation in patients with severe acute lung insufficiency treated in the prone position

OBJECTIVE: To confirm the positive effect of prone positioning on oxygenation in patients with acute lung insufficiency. DESIGN: Clinical follow-up study. SETTING: The intensive care unit at a tertiary care academic hospital. PATIENTS: Thirteen patients suffering from severe acute lung insufficiency caused by trauma, septicemia, aspiration, and burn injury. Eleven of the patients had severe hypoxia (oxygenation indices [PaO2/FIO2] < or = 80 torr [< or = 10.7 kPa]). Patients > 70 yrs of age were excluded from the study. INTERVENTIONS: Treatment in the prone position without changing other ventilatory settings than FIO2 when saturation increased. MEASUREMENTS AND MAIN RESULTS: Twelve of the 13 patients responded to treatment in the prone position. The patient that did not respond improved her gas exchange when nitric oxide was instituted. She died, however, from a Gram-negative septicemia. No patient needed extracorporeal membrane oxygenation. Apart from the settings of FIO2 when saturation increased, the ventilatory settings were unchanged. In the prone position, the oxygenation index increased (p < .0002) and the alveolar-arterial oxygen gradient, P(A-a)O2, decreased dramatically (p < .0001). CONCLUSIONS: The prone position significantly improves impaired gas exchange due to severe acute lung insufficiency. It is suggested that this treatment is used before more complex modalities.     

Experimental antitumour activity of S 16020-2 in a panel of human tumours

OBJECTIVE: To compare the effects of inhaled nitric oxide (NO) and extracorporeal membrane oxygenation (ECMO) on oxygenation, hemodynamics, and lymphatic drainage in an oleic acid lung injury model in sheep. DESIGN: Prospective, randomized study. SETTING: Animal research laboratory. ANIMALS: Thirty female sheep, weighing 35 to 40 kg. INTERVENTIONS: Acute lung injury was induced by central venous injection of oleic acid (0.5 mL/kg body weight). A chronic lymph fistula had been prepared through a right thoracotomy 3 days before the experiment. Animals were assigned randomly to the NO group (n = 14) or the ECMO group (n = 16). When a lung injury score of > 2.5 was achieved, the animals were given NO in dosage increments of 2, 5, 10, 20, and 40 parts per million (ppm), or placed on ECMO with an FIO2 of 0.21 (ECMO-21) and then 1.0 (ECMO-100) at the oxygenator. Mechanical ventilator parameters were kept constant to isolate the effects of NO and ECMO on systemic and pulmonary hemodynamics, cardiac output, oxygenation parameters, lymph/plasma protein ratio, and lymph flow. Measurements and calculations were performed after 1 hr at each individual step of NO concentration or FIO2. MEASUREMENTS AND MAIN RESULTS: In the ECMO group, PVRI and MPAP did not change and were significantly different from the NO group. In the NO group, there was a dose-dependent decrease in venous admixture, maximal at 10 ppm NO and decreasing from 40 +/- 6% to 23 +/- 10% (p < .05). This decrease was significantly different from the ECMO group, where there was no change. There was a significant increase in PaO2/FIO2 in the NO group, maximal at 10 ppm NO (84 +/- 11 to 210 +/- 90, p < .05), but a greater increase in PaO2/FIO2 on ECMO-21 (81 +/- 14 to 265 +/- 63) and a further increase on ECMO-100 (398 +/- 100) (p < .05). The lymph/plasma protein ratio remained unchanged in both groups after induction of lung injury by oleic acid. However, lymph flow decreased by 11 +/- 6% in the NO group, whereas it increased by 14 +/- 17% in the ECMO group (p < .05). CONCLUSIONS: In an oleic acid-induced sheep model of acute lung injury, there were significant differences between the effects of NO and ECMO on acute pulmonary hypertension, hypoxemia, hypercarbia, and lymph flow. NO significantly decreases pulmonary hypertension, whereas pulmonary hemodynamics were not substantially affected by ECMO. Both interventions reversed hypoxemia, but ECMO did so to a greater degree, and only ECMO improved hypercarbia. Only NO decreased lymph flow, possibly as an effect of decreased microvascular filtration pressure. This study did not attempt to evaluate the impact of these interventions on ventilatory requirements, barotrauma, or outcome. However, this model suggests that NO therapy may moderate pulmonary hypertension and improve lymph flow in acute lung injury. Clinical studies are needed to assess whether NO therapy might be beneficial in treatment of severe acute lung injury in older children and adults.     

Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS

BACKGROUND: Oxidant stress is a purported mechanism of tissue damage in patients with ARDS and acute lung injury (ALI). Isoprostanes, prostanoid compounds primarily formed nonenzymatically via lipid peroxidation, are precise markers of in vivo oxidant stress. Plasma levels of metabolites of 8-iso-prostaglandin-F2alpha (8-iso-PGF2alpha) correlate with outcome in patients with ARDS. OBJECTIVE: To examine exhaled breath condensate levels of 8-iso-PGF2alpha as a noninvasive quantification of pulmonary oxidant stress in patients with, or at risk for, ARDS/ALI. METHODS: Breath condensate was collected from 22 patients with, or at risk for, ARDS/ALI by placing Tygon tubing submerged in an ice bath in line with the expiratory limb of the ventilator circuit. Ten patients without lung disease, who were intubated while undergoing minor surgical procedures, served as control subjects. Between 1 and 3 mL of condensate was collected over a 30- to 60-min period, then immediately frozen and stored at -70 degrees C until analysis. The 8-iso-PGF2alpha was purified and derivatized, then quantified by stable isotope dilution in conjunction with gas chromatography/mass spectrometry. RESULTS: The mean level of exhaled 8-iso-PGF2alpha in the patients with ALI/ARDS, 87+/-28 pg/mL, was significantly higher than the mean in the normal group, 7+/-4 pg/mL (p = 0.007). The 8-iso-PGF2alpha levels were greater than two standard deviations above the mean of the normal group in 12 of 22 patients with or at risk for ARDS/ALI. CONCLUSIONS: These results provide further evidence that lipid peroxidation does occur in patients with ARDS/ALI. The measurement of exhaled isoprostanes provides a novel, noninvasive method to quantify oxidant stress in such patients.     

Volume-controlled versus biphasic positive airway pressure ventilation in leukopenic patients with severe respiratory failure

OBJECTIVE: To study comparatively the effects of volume-controlled vs. biphasic positive airway pressure mechanical ventilation on respiratory mechanics and oxygenation in leukopenic patients with severe respiratory failure. DESIGN: Prospective, comparative study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Leukopenic (<1000 leukocytes/microliter) patients (n=20) after cytoreductive chemotherapy requiring mechanical ventilation for severe respiratory failure (Murray score of > 2.5). INTERVENTION: Patients were assigned in a consecutive, alternating manner to receive either volume-controlled or biphasic positive airway pressure mechanical ventilation, starting within 12 to 24 hrs after endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: Tidal volume, inspiratory flow, peak inspiratory and positive end-expiratory pressures, FIO2, and arterial blood gas analyses were recorded hourly for a study period of 48 hrs. Biphasic positive airway pressure ventilation was associated with a significant reduction in peak inspiratory pressure (mean differences at 24, 36, and 48 hrs: 4.4, 3.4, and 4.2 cm H2O; p = .024, .019, and .013, respectively) and positive end-expiratory pressures (mean differences at 24, 36, and 48 hrs: 1.6, 1.4, and 1.5 cm H20; p = .023, .024, and .023, respectively) at significantly lower FIO2 (mean differences at 12, 24, 36, and 48 hrs; p = .007, .015, .016, and .011, respectively). PaO2/FIO2 ratios and CO2 removal were similar under ventilatory conditions. CONCLUSIONS: Biphasic positive airway pressure ventilation offers the advantage of significantly reduced peak inspiratory and positive end-expiratory pressures at a lower FIO2 and with at least similar oxygenation and CO2 removal as achieved by volume-controlled mechanical ventilation. Our results are in line with previous reports on nonleukopenic patients and suggest that the positive effects of pressure-limited mechanical ventilation are independent of circulating white blood cells. Further studies are mandatory to demonstrate clinical benefit in this critically ill patient population.     

Does airway pressure release ventilation alter lung function after acute lung injury?

BACKGROUND: During airway pressure release ventilation (APRV), tidal ventilation occurs between the increased lung volume established by the application of continuous positive airway pressure (CPAP) and the relaxation volume of the respiratory system. Concern has been expressed that release of CPAP may cause unstable alveoli to collapse and not reinflate when airway pressure is restored. OBJECTIVE: To compare pulmonary mechanics and oxygenation in animals with acute lung injury during CPAP with and without APRV. DESIGN: Experimental, subject-controlled, randomized crossover investigation. SETTING: Anesthesiology research laboratory, University of South Florida College of Medicine Health Sciences Center. SUBJECTS: Ten pigs of either sex. INTERVENTIONS: Acute lung injury was induced with an intravenous infusion of oleic acid (72 micrograms/kg) followed by randomly alternated 60-min trials of CPAP with and without APRV. Continuous positive airway pressure was titrated to produce an arterial oxyhemoglobin saturation of at least 95% (FIO2 = 0.21). Airway pressure release ventilation was arbitrarily cycled to atmospheric pressure 10 times per minute with a release time titrated to coincide with attainment of respiratory system relaxation volume. MEASUREMENTS: Cardiac output, arterial and mixed venous pH, blood gas tensions, hemoglobin concentration and oxyhemoglobin saturation, central venous pressure, pulmonary and systemic artery pressures, pulmonary artery occlusion pressure, airway gas flow, airway pressure, and pleural pressure were measured. Tidal volume (VT), dynamic lung compliance, intrapulmonary venous admixture, pulmonary vascular resistance, systemic vascular resistance, oxygen delivery, oxygen consumption, and oxygen extraction ratio were calculated. MAIN RESULTS: Central venous infusion of oleic acid reduced PaO2 from 94 +/- 4 mm Hg to 52 +/- 9 mm Hg (mean +/- 1 SD) (p < 0.001) and dynamic lung compliance from 40 +/- 6 mL/cm H2O to 20 +/- 6 mL/cm H2O (p = 0.002) and increased venous admixture from 13 +/- 3% to 32 +/- 7% (p < 0.001) in ten swine weighing 33.3 +/- 4.1 kg while they were spontaneously breathing room air. After induction of lung injury, the swine received CPAP (14.7 +/- 3.3 cm H2O) with or without APRV at 10 breaths per minute with a release time of 1.1 +/- 0.2 s. Although mean transpulmonary pressure was significantly greater during CPAP (11.7 +/- 3.3 cm H2O) vs APRV (9.4 +/- 3.8 cm H2O) (p < 0.001), there were no differences in hemodynamic variables. PaCO2 was decreased and pHa was increased during APRV vs CPAP (p = 0.003 and p = 0.005). PaO2 declined from 83 +/- 4 mm Hg to 79 +/- 4 mm Hg (p = 0.004) during APRV, but arterial oxyhemoglobin saturation (96.6 +/- 1.4% vs 96.9 +/- 1.3%) did not. Intrapulmonary venous admixture (9 +/- 3% vs 11 +/- 5%) and oxygen delivery (469 +/- 67 mL/min vs 479 +/- 66 mL/min) were not altered. After treatment periods and removal of CPAP for 60 min, PaO2 and intrapulmonary venous admixture returned to baseline values. DISCUSSION: Intrapulmonary venous admixture, arterial oxyhemoglobin saturation, and oxygen delivery were maintained by APRV at levels induced by CPAP despite the presence of unstable alveoli. Decrease in PaO2 was caused by increase in pHa and decrease in PaCO2, not by deterioration of pulmonary function. We conclude that periodic decrease of airway pressure created by APRV does not cause significant deterioration in oxygenation or lung mechanics.     

Evaluation of four commercial rapid diagnostic kits for identifying Staphylococcus aureus

OBJECTIVE: Regulation of circulatory homeostasis is based on several factors including various circulating vasoactive substances. Whether these regulators differ between survivors and non-survivors was investigated in critically ill patients. DESIGN: Prospective study. SETTING: Clinical investigation on a surgical intensive care unit of an university hospital. PATIENTS: 60 consecutive patients suffering from trauma (n = 21) or postoperative complications (n = 39) were studied prospectively. The patients were divided into survivors (n = 27) and non-survivors (n = 33). Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study. MEASUREMENTS AND RESULTS: Endothelin-1, atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured from arterial blood samples using radioimmunoassay (RIA) or high-pressure liquid chromatography (HPLC) technique on the day of admission to ICU and during the following 5 days. Various hemodynamic parameters were also monitored during that period. The non-survivors showed elevated pulmonary artery pressure (PAP: 34.1 +/- 5.4 mmHg) and pulmonary capillary wedge pressure (PCWP: 20.3 +/- 7.3 mmHg) already at the beginning of the study. Cardiac index (CI) did not differ among the groups, whereas right ventricular ejection fraction (RVEF) decreased in the non-survivors. PaO2/FIO2 decreased only in the non-survivors, whereas VO2 increased in the survivors (from 246 +/- 48 to 331 +/- 43 ml/min). Plasma levels of renin (from 206 +/- 40 to 595 +/- 81 pg/ml) and vasopressin (from 5.78 +/- 0.82 to 7.97 +/- 0.69 pg/ml) increased significantly in the non-survivors. Epinephrine and norepinephrine plasma concentrations were elevated in the non-survivors already at baseline and tremendously increased in these patients during the following days. ANP plasma levels significantly increased also only in the non-survivors (from 188 +/- 63 to 339 +/- 55 pg/ml) (p < 0.05). Endothelin-1 decreased in the survivors, whereas it significantly increased in the non-survivors (from 3.62 +/- 0.68 to 9.37 +/- 0.94 pg/ml) during the study period (p < 0.05). Analyses of co-variance revealed overall no significant correlation between circulating vasoactive substances and hemodynamics. CONCLUSIONS: Systemic and regional regulators of the circulation were markedly changed by critical illness. In survivors, these regulators almost normalized within the study period of 5 days, whereas in non-survivors these alterations were even aggravated. It can only be speculated whether these regulator systems were influenced by activation of various mediator systems or whether they themselves influenced the negative outcome in the non-survivors.     

Platelet activating factor and tumor necrosis factor-alpha in bronchoalveolar lavage fluid of patients with ARDS

Platelet activating factor (PAF) and tumor necrosis factor alpha (TNF-alpha) were examined in the bronchoalveolar lavage fluid (BALF) of 21 ARDS patients to clarify the role of these factors in ARDS. Neutrophil percentages and albumin concentrations in the BALF of the ARDS group were markedly elevated compared with those in the control group (p < 0.01), showing a significant correlation (r = 0.596, p < 0.01). PAF was detected in 14 of 19 ARDS patients (237.5 +/- 86.0 pg/ml) and TNF-alpha was detected in 7 of 16 ARDS patients (24.9 +/- 13.6 pg/ml), whereas these factors were not detected in control subjects. Neither PAF nor TNF-alpha showed a significant correlation with neutrophil percentage, neutrophil number or albumin concentration. They do not seem to be contributing factors to the prognosis of ARDS patients. However the existence of PAF and TNF-alpha in the BALF of some ARDS patients suggests that they might play a role in the pathogenesis of ARDS.     

Value of pulmonary hemodynamic exploration during muscular exercise in chronic bronchitis?]

The value of pulmonary haemodynamic tests during physical exercise in chronic bronchitis was shown by the comparison of two groups of patients. In the first group (n=24) the PAP during exercise is lower than 30 torr. In the second it was over 30 torr. The PAP at rest was always lower than 20 torr. The load was 40 to 50 watts, i.e. an average O2 consumption of 500-600 ml.mm-1 m-2. The cardiac output doubled on average in exercise. Both groups varied markedly in their PAP at rest: 13.6 +/- 1.7 torr for the first group and 15.8 +/- 2.4 for the second (p less than 0.001). In fact differences in pressure during exercise (I=25.0 +/- 3.4 torr; II=39.6 +/- 7.4 torr, p less than 0.001) could be explained mainly by the differences of pulmonary vascular resistances (I=0.91 +/- 0.37; II=1.47 +/- 0.61, p less than 0.005): they tended to fall during effort in the first group and increased slightly in the second; and by the much higher increase in the pulmonary "capillary" pressure during exercise in the second group (I=12.5 +/- 4.4 torr; II=19.7 +/- 72 torr, p less than 0.001). The cardiac output during rest and exercise was equal in both groups. The haemo-dynamic "recovery delay" was much higher in the second group. The spirographic shortage was on the whole identical in both groups. PaO2 on average was higher in group I (p less than 0.05) where it improved during exercise (p less than 0.01). The PaO2 of the second group did improve during exercise. The haemodynamic differences were concomitant with the differences in gas exchanges during effort, of well known prognostic significance. As the "foretelling" of PAP in effort from the PAP at rest was quite poor, it appeared that haemodynamic test in effort has a real value in contributing efficiently to the differenciation of the degree in severeness. The threshold of 30 torr for PAP in exercise (and for the load mentioned above) seemed a good discriminating factor.