Permissive hypercapnia with and without expiratory washout in patients with severe acute respiratory distress syndrome

BACKGROUND: Permissive hypercapnia is a ventilatory strategy aimed at avoiding lung volutrauma in patients with severe acute respiratory distress syndrome (ARDS). Expiratory washout (EWO) is a modality of tracheal gas insufflation that enhances carbon dioxide removal during mechanical ventilation by reducing dead space. The goal of this prospective study was to determine the efficacy of EWO in reducing the partial pressure of carbon dioxide (PaCO2) in patients with severe ARDS treated using permissive hypercapnia. METHODS: Seven critically ill patients with severe ARDS (lung injury severity score, 3.1 +/- 0.3) and no contraindications for permissive hypercapnia were studied. On the first day, hemodynamic and respiratory parameters were measured and the extent of lung hyperdensities was assessed using computed tomography. A positive end-expiratory pressure equal to the opening pressure identified on the pressure-volume curve was applied. Tidal volume was reduced until a plateau airway pressure of 25 cm H2O was reached. On the second day, after implementation of permissive hypercapnia, EWO was instituted at a flow of 15 l/min administered during the entire expiratory phase into the trachea through the proximal channel of an endotracheal tube using a ventilator equipped with a special flow generator. Cardiorespiratory parameters were studied under three conditions: permissive hypercapnia, permissive hypercapnia with EWO, and permissive hypercapnia. RESULTS: During permissive hypercapnia, EWO decreased PaCO2 from 76 +/- 4 mmHg to 53 +/- 3 mmHg (-30%; P < 0.0001), increased pH from 7.20 +/- 0.03 to 7.34 +/- 0.04 (P < 0.0001), and increased PaO2 from 205 +/- 28 to 296 +/- 38 mmHg (P < 0.05). The reduction in PaCO2 was accompanied by an increase in end-inspiratory plateau pressure from 26 +/- 1 to 32 +/- 2 cm H2O (P = 0.001). Expiratory washout also decreased cardiac index from 4.6 +/- 0.4 to 3.7 +/- 0.3 l.min-1.m-2 (P < 0.01), mean pulmonary arterial pressure from 28 +/- 2 to 25 +/- 2 mmHg (P < 0.01), and true pulmonary shunt from 47 +/- 2 to 36 +/- 3% (P < 0.01). CONCLUSIONS: Expiratory washout is an effective and easy-to-use ventilatory modality to reduce PaCO2 and increase pH during permissive hypercapnia. However, it significantly increases airway pressures and lung volume through expiratory flow limitation, reexposing some patients to a risk of lung volutrauma if the extrinsic positive end-expiratory pressure is not substantially reduced.     

Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. The NO Almitrine Study Group

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.     

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 content of electrolytes (Na, K, Ca, Mg) in vertebrate otoliths and otoconia

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous low-flow tracheal gas insufflation during partial liquid ventilation in rabbits

BACKGROUND: Both partial liquid ventilation (PLV) and tracheal gas insufflation are novel techniques for mechanical ventilation. In this study we examined whether PLV superimposed by continuous low-flow tracheal gas insufflation (TGI) offers any advantage to the blood gases and lung mechanics in normal-lung rabbits compared to the use of PLV only. METHODS: Eighteen anesthetized, paralyzed and mechanically ventilated rabbits were used. After obtaining a baseline PaCO2 value between 29 and 39 mmHg (3.9 and 5.2 kPa), the animals were assigned to three equal groups according to the ventilation they received--A group: PLV superimposed by TGI; B group: PLV only; and C group: continuous mandatory ventilation (CMV) superimposed by TGI. Serial arterial blood gases, pH and lung mechanics were measured. RESULTS: The animals in each group were hemodynamically stable. In the case of the A group, PaO2 continuously increased, and PaCO2 stabilized around 40.8 +/- 5.5 mmHg (5.4 +/- 0.7 kPa, mean +/- SD, NS). In the B group, the tendency for PaO2 to increase was not as definite; PaCO2 continuously increased from 35.2 +/- 2.3 mmHg (4.7 +/- 0.3 kPa) to 56.3 +/- 12.7 mmHg (7.5 +/- 1.7 kPa, P < 0.05) at the end of the experiment. In the C group, PaO2 and PaCO2 were stable during the observation period. The superimposition of TGI on PLV did not decrease the airway pressures compared to PLV alone. CONCLUSION: In summary, continuous low-flow TGI superimposed on PLV can decrease and stabilize the PaCO2 elevation caused by the initiation of PLV.     

Study of the use of noninvasive ventilation of the lungs in acute respiratory insufficiency due exacerbation of chronic obstructive pulmonary disease

Noninvasive positive pressure ventilation (NPPV) is a life-saving procedure in acute respiratory failure (ARF), but its technique is not yet in routine use in many respiratory centers. We carried out a prospective randomized study comparing the combination of NPPV with conventional therapy (oxygen, bronchodilators, steroids, and theophylline) with conventional therapy alone in patients with acute respiratory failure caused by exacerbation of chronic obstructive pulmonary disease (COPD). A total of 58 patients were recruited from a large group of patients admitted to our hospital between September 1995 and March 1997. Twenty-nine patients were randomly assigned to the NPPV group and 29 to the conventional (non-NPPV) group. The patients were matched for demographic and physiological norm values (mean age 63.4 +/- 5.5 vs. 66.2 +/- 7.1 years, mean FEV1 0.68 +/- 0.15 vs. 0.74 +/- 0.16 L, PaO2 51.4 +/- 6.8 vs. 52.3 +/- 6.5 mm Hg, PaCO2 63.4 +/- 10.9 vs. 64.9 +/- 9.7 mm Hg, and pH 7.28 +/- 0.07 vs. 7.26 +/- 0.06). The outcome end points were needed for endotracheal intubation, length of hospital stay, and incidence of complications. NPPV was administered using BiPAP ventilatory device (Respironics, Inc.) by spontaneous and spontaneous/timed modes via nasal and facial masks. The mean time of NPPV was 29 +/- 25 h. Three patients refused from NPPV because of intolerance of mask or ventilation procedure. Two of them were eventually intubated and one of them died. In patients administered NPPV, we observed a significant rise of pH and fall of PaCO2 after 1 h of ventilation, in contrast to the non-NPPV group (7.34 +/ 0.09 vs. 7.21 +/- 0.08, p < 0.05; 53.2 +/- 10.7 vs. 71.4 +/- 10.2 mm Hg, p < 0.01, respectively). The need in intubation was lower in the NPPV group as compared to the reference group (12 vs. 28%, p = 0.18), mortality rate was higher in the non-NPPV group (31 vs. 8%, p = 0.03), and hospital stay was shorter in NPPV patients (26 +/- 7 vs. 34 +/- 10 days). The incidence of complications was lower in the NPPV group, they were less significant, and did not involve discontinuation of ventilation. Hence, NPPV is a first-line therapy in patients with ARF caused by COPD exacerbation, due to obvious advantages over conventional methods of treatment.     

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.     

Assessment of insulin sensitivity in glucokinase-deficient subjects

Mechanical ventilation using a modified endotracheal tube, allowing bypass and washout of the endotracheal dead space (McETV), was compared with conventional controlled mechanical ventilation (CMV) in healthy and in surfactant-depleted rabbits. In healthy animals, shifting from CMV to McETV led to an increase in PaO2 (89 +/- 16 versus 104 +/- 13 mm Hg; p < 0.05) and a decrease in PaCO2 (41.5 +/- 3 versus 30 +/- 3 mm Hg; p < 0.05). As a result of reducing the peak inspiratory pressure (PIP) from 21 +/- 2 to 12 +/- 2 cm H2O (p < 0.05), it was possible in McETV mode to maintain comparable ventilation to that achieved by CMV. In surfactant-depleted animals, compared with CMV, McETV produced a rise in PaO2 without change in thoracic volume (from 100 +/- 40 to 150 +/- 60 mm Hg, p < 0.05) and a fall in PaCO2 (from 46 +/- 5 to 37 +/- 4 mm Hg, p < 0.05). After 4 h of ventilation, the surfactant-depleted animals from the CMV group developed thoracic overdistension quicker (at hour 1, p < 0.05) and, consequently, more animals died from pneumothorax compared with the McETV group (five versus two). We concluded that McETV ensured adequate gas exchanges with lower insufflation pressures and could diminish positive pressure ventilation-induced injury.     

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.     

Efficacy of dead-space washout in mechanically ventilated premature newborns

The prosthetic dead space makes a significant contribution to the total dead space in low-birth-weight premature newborns receiving artificial ventilation in response to respiratory distress. Use of an endotracheal tube with capillaries molded into the tube wall enables washout of the dead space without insertion of a tracheal catheter. In 10 premature newborns (mean gestational age, 27.5 +/- 2.2 wk; mean weight, 890 +/- 260 g) receiving continuous positive-pressure ventilation (Paw = 12.7 +/- 1.8 cm H2O; FIO2 = 39 +/- 17%), tracheal gas insufflation (TGI) for CO2 washout was conducted using this technique. The flow of tracheal insufflation (0.5 L/min) was derived from the inspiratory line of the ventilator circuit and blown into the trachea. Intratracheal pressures showed little or no TGI-related modification ( < 1 cm H2O). A control system enabled TGI discontinuation in the event of a pressure rise. At constant ventilation pressure, PaCO2 decreased by 12.1 +/- 5.9 mm Hg (delta PaCO2 = -26 +/- 12%) under TGI, whereas PaO2 remained unchanged. While maintaining PaCO2 constant, peak inspiratory pressure (PIP) was decreased by 5.4 +/- 1.7 cm H2O (delta PIP = -22.0 +/- 8.3%). TGI showed immediate efficacy (PCO2 reduction of at least 5 mm Hg) in nine of the 10 newborns who then received chronic TGI (14 to 138 h). TGI appears to be an effective method, suitable for long-term clinical application, enabling a reduction in the aggressive nature of conventional ventilation.     

Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure

STUDY OBJECTIVE: To compare the efficacy of standard medical therapy (ST) and noninvasive mechanical ventilation additional to standard medical therapy in hypercapnic acute respiratory failure (HARF). DESIGN: Single center, prospective, randomized, controlled study. SETTING: Pulmonary medicine directed critical care unit in a university hospital. PATIENTS: Between March 1993 and November 1996, 30 HARF patients were randomized to receive ST or noninvasive positive pressure ventilation (NPPV) in addition to ST. INTERVENTIONS: NPPV was given with an air-cushioned face via a mechanical ventilator (Puritan Bennett 7200) with initial setting of 5 cm H2O continuous positive airway pressure and 15 cm H2O pressure support. RESULTS: At the time of randomization, patients in the ST group had (mean+/-SD) PaO2 of 54+/-13 mm Hg, PaCO2 of 67+/-11 mm Hg, pH of 7.28+/-0.02, and respiratory rate of 35.0+/-5.8 breaths/min. Patients in the NPPV group had PaO2 of 55+/-14, PaCO2 of 69+/-15, pH of 7.27+/-0.07, and respiratory rate of 34.0+/-8.1 breaths/min. With ST, there was significant improvement of only respiratory rate (p < 0.05). However, with NPPV, PaO2 (p < 0.001), PaCO2 (p < 0.001), pH (p < 0.001), and respiratory rate (p < 0.001) improved significantly compared with baseline. Six hours after randomization, pH (p < 0.01) and respiratory rate (p < 0.01) in NPPV patients were significantly better than with ST. Hospital stay for NPPV vs ST patients was, respectively, 11.7+/-3.5 and 14.6+/-4.7 days (p < 0.05). One patient in the NPPV group required invasive mechanical ventilation. The conditions of six patients in the ST group deteriorated and they were switched to NPPV; this was successful in four patients, two failures were invasively ventilated. CONCLUSION: This study suggests that early application of NPPV in HARF patients facilitates improvement, decreases need for invasive mechanical ventilation, and decreases the duration of hospitalization.     

Out-of-hospital ventilation: bag--valve device vs transport ventilator

OBJECTIVE: To examine the patterns of out-of-hospital airway management and to compare the efficacy of bag-valve ventilation with that of the use of a transport ventilator for intubated patients. METHODS: A prospective, nonrandomized, convenience sample of 160 patients requiring airway management in the out-of-hospital urban setting was analyzed. A survey inquiring about airway and ventilatory management was completed by emergency medical services (EMS) personnel, and arterial blood gas (ABG) samples were obtained within 5 minutes of patient arrival in the ED. The ABG parameters were compared for patients grouped by different airway techniques and presence or absence of cardiac arrest (systolic blood pressure < 50 mm Hg) upon ED presentation. RESULTS: Over a one-year period, 160 surveys were returned. The majority (62%) of the patients were men; the population mean age was 61 +/- 19 years. Presenting ABGs were obtained for 76 patients; 17% (13/76) had systemic perfusion and 83% (63/76) were in cardiac arrest. There was no difference in ABG parameters between the intubated cardiac arrest patients ventilated with a transport ventilator (pH 7.17 +/- 0.17, PaCO2 37 +/- 20 torr, and PaO2 257 +/- 142 torr) and those ventilated with a bag-valve device (pH 7.20 +/- 0.16, PaCO2 42 +/- 21 torr, and PaO2 217 +/- 138 torr). The patients ventilated via an esophageal obturator airway (EOA) device had impaired gas exchange, compared with the groups who had endotracheal (ET) intubation (pH 7.09 +/- 0.13, PaCO2 76 +/- 30 torr, and PaO2 75 +/- 35 torr). The intubated patients not in cardiac arrest had similar ABG parameters whether ventilated manually with a bag-valve device or with a transport ventilator. Endotracheal intubation was successfully accomplished in 93% (123/132) of attempted cases. CONCLUSIONS: In this sample, ET intubation was the most frequently used airway by EMS providers. When ET intubation was accomplished, adequate ventilation could be achieved using either bag-valve ventilation or a transport ventilator. Ventilation via the EOA proved inadequate.     

Response to symptom-limited exercise in patients with the hepatopulmonary syndrome

OBJECTIVE: To study the response to symptom-limited exercise in patients with the hepatopulmonary syndrome (HPS). DESIGN: The response to maximal cardiopulmonary exercise (CPX) was studied in 5 patients with HPS and compared with 10 case control (normoxemic, NC) cirrhotics (matched for age, gender, etiology and severity of liver disease, tobacco use, and beta-blocker therapy) and 9 hypoxemic control cirrhotics (HC) without clinical evidence of HPS. SETTING: Cardiopulmonary exercise physiology laboratory in a tertiary care referral center. PATIENTS: Cirrhotics referred for CPX as part of their preliver transplantation evaluation. MEASUREMENTS: Standard pulmonary function tests and echocardiography were performed to assess resting pulmonary and cardiac function. Peak oxygen consumption (VO2), minute ventilation, arterial blood gases, and dead space (VD/VT) were determined during symptom-limited maximal CPX. RESULTS: Resting spirometry and lung volumes were similar between HPS and NC subjects, while HC subjects had restrictive physiology. Differences existed in diffusing capacity corrected for hemoglobin and alveolar volume percent predicted (HPS, 45+/-2 vs NC, 68+/-3, p<0.05; vs HC, 70+/-4, p<0.05), PaO2 (HPS, 70+/-5 mm Hg; HC, 79+/-3 mm Hg, vs NC, 102+/-3 mm Hg, p<0.05) and alveolar-arterial (A-a) O2 gradient (HPS, 42+/-8 mm Hg vs HC, 27+/-2 mm Hg, p<0.05; vs NC, 6+/-2 mm Hg, p<0.05). During CPX, HPS patients achieved a lower peak VO2 percent predicted (HPS, 55+/-6 vs NC, 73+/-3, p<0.05; vs HC, 71+/-5, p<0.05) and VO2 at the ventilatory threshold as percent predicted peak VO2 (HPS, 36+/-2 vs NC, 55+/-4, p<0.05; vs HC 55+/-5, p<0.05). While no differences existed in heart rate and breathing reserve, HPS patients had significantly lower PaO2 (HPS, 50+/-5 mm Hg vs NC, 97+/-4 mm Hg, p<0.05; vs HC, 87+/-6 mm Hg, p<0.05), wider A-a O2 gradient (HPS, 73+/-5 mm Hg vs NC, 13+/-3 mm Hg, p<0.05; vs HC, 31+/-5 mm Hg, p<0.05) and higher VD/VT (HPS, 0.36+/-.03 vs NC, 0.18+/-.02, p<0.05; vs HC, 0.28+/-.02, p<0.05) at peak exercise. For HPS patients, VO2 was negatively correlated with VD/VT (r2=0.9) and positively correlated with PaO2 (r2=0.41) at peak exercise. Conclusions: Patients with HPS demonstrate a severe reduction in aerobic capacity, beyond that found in cirrhotics without syndrome. The significant hypoxemia and elevated VD/VT at peak exercise suggest that an abnormal pulmonary circulation contributes to further exercise limitation in patients with HPS.     

Inhaled nitric oxide for adult respiratory distress syndrome after pulmonary resection

BACKGROUND: The adult respiratory distress syndrome (ARDS) developing after pulmonary resection is usually a lethal complication. The etiology of this serious complication remains unknown despite many theories. Intubation, aspiration bronchoscopy, antibiotics, and diuresis have been the mainstays of treatment. Mortality rates from ARDS after pneumonectomy have been reported as high as 90% to 100%. METHODS: In 1991, nitric oxide became clinically available. We instituted an aggressive program to treat patients with ARDS after pulmonary resection. Patients were intubated and treated with standard supportive measures plus inhaled nitric oxide at 10 to 20 parts/million. While being ventilated, all patients had postural changes to improve ventilation/perfusion matching and management of secretions. Systemic steroids were given to half of the patients. RESULTS: Ten consecutive patients after pulmonary resection with severe ARDS (ARDS score = 3.1+/-0.04) were treated. The mean ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen at initiation of treatment was 95+/-13 mm Hg (mean +/- SEM) and improved immediately to 128+/-24 mm Hg, a 31%+/-8% improvement (p<0.05). The ratio improved steadily over the ensuing 96 hours. Chest x-rays improved in all patients and normalized in 8. No adverse reactions to nitric oxide were observed. CONCLUSIONS: We recommend the following treatment regimen for this lethal complication: intubation at the first radiographic sign of ARDS; immediate institution of inhaled nitric oxide (10 to 20 parts per million); aspiration bronchoscopy and postural changes to improve management of secretions and ventilation/perfusion matching; diuresis and antibiotics; and consideration of the addition of intravenous steroid therapy.     

Estrogen receptor alpha and beta expression in upper gastrointestinal tract with regulation of trefoil factor family 2 mRNA levels in ovariectomized rats

STUDY OBJECTIVE: To investigate the effect of short-term inhalation of nitric oxide (NO) on transpulmonary angiotensin II formation in patients with severe ARDS. DESIGN: Prospective, clinical study. SETTING: Anesthesiology ICU of a university hospital. PATIENTS: Ten ARDS patients who responded to inhalation of 100 ppm NO by decreasing their pulmonary vascular resistance (PVR) by at least 20 dyne x s x cm(-5) were included in the study. INTERVENTIONS AND MEASUREMENTS: In addition to standard treatment, the patients inhaled 0, 1, and 100 ppm NO in 20-min intervals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured and recorded online. Mixed venous (pulmonary arterial catheter) and arterial (arterial catheter) blood samples were taken simultaneously for hormonal analyses at the end of each inhalation period. RESULTS: Pulmonary arterial pressure decreased from 33+/-2 mm Hg (0 ppm NO, mean+/-SEM) to 29+/-2 mm Hg (1 ppm NO, p<0.05), and to 27+/-2 mm Hg (100 ppm NO, p<0.05, vs 0 ppm). PVR decreased from 298+/-56 (0 ppm NO) to 243+/-45 dyne x s x cm(-5) (1 ppm NO, not significant [NS]), and to 197+/-34 dyne x s x cm(-5) (100 ppm NO, p<0.05, vs 0 ppm). Arterial oxygen pressure increased from 174+/-23 mm Hg (0 ppm NO) to 205+/-26 mm Hg (1 ppm NO, NS), and to 245+/-25 mm Hg (100 ppm NO, p <0.05, vs 0 ppm). Mean plasma angiotensin II concentrations were 85+/-20 (arterial) and 57+/-13 pg/mL (mixed venous) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary plasma angiotensin II concentration gradient (=difference between arterial and mixed venous blood values) was 28+/-8 pg/mL (range, 0 to 69) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient multiplied with the cardiac index) was 117+/-39 ng/min/m2 (range, 0 to 414) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean arterial plasma cyclic guanosine monophosphate concentration was 11+/-2 pmol/mL (0 ppm NO), did not change during 1 ppm NO, and increased to 58+/-8 pmol/mL (100 ppm NO, p<0.05). Arterial plasma concentrations of aldosterone (142+/-47 pg/mL), atrial natriuretic peptide (114+/-34 pg/mL), angiotensin-converting enzyme (30+/-5 U/L), and plasma renin activity (94+/-26 ng/mL/h of angiotensin I) did not change. CONCLUSION: The decrease of PVR by short-term NO inhalation in ARDS patients was not accompanied by changes in transpulmonary angiotensin II formation. Our results do not support any relationship between transpulmonary angiotensin II formation and the decrease in PVR induced by inhaled NO.     

Genetic variation at the short tandem repeat loci HumvWA, HumFXIIIB, and HumFES/FPS in the Egyptian and Yemenian populations

Eighteen head-injured patients undergoing hyperventilation were studied for changes in jugular venous oxygen saturation (SjvO2) and arteriovenous oxygen content difference (AVDO2) in response to changes in PaO2 and PaCO2. SjvO2 decreased significantly from 66% +/- 3% to 56% +/- 3% (mean +/- SD) when PaCO2 decreased from 30 to 25 mm Hg at a PaO2 of 100-150 mm Hg. SjvO2 values returned to baseline (66% +/- 2%) when PaCO2 was restored to 30 mm Hg. Repetition of the study at a PaO2 of 200-250 mm Hg produced a similar pattern. However, SjvO2 values were significantly greater with PaO2 within the range of 200-250 mm Hg (77% +/- 4% and 64% +/- 3%) than SjvO2 measured at a PaO2 of 100-150 mm Hg at PaCO2 values of both 30 and 25 mm Hg. AVDO2 also improved with a PaO2 of 200-250 mm Hg at each PaCO2 (P < 0.001). In conclusion, decreases in SjvO2 associated with decreases in PaCO2 may be offset by increasing PaO2. IMPLICATIONS: The adequacy of cerebral oxygenation can be estimated in head-injured patients by monitoring jugular bulb oxygen saturation and the arteriovenous oxygenation content difference. Increasing the partial pressure of arterial oxygen above normal offset deleterious effects of hyperventilation on jugular bulb oxygen saturation and arteriovenous oxygenation content difference in head-injured patients.     

Hemodynamic profile in severe ARDS: results of the European Collaborative ARDS Study

OBJECTIVE: Although the acute respiratory distress syndrome (ARDS) was identified as long as 30 years ago, potential therapeutic objectives have been defined from small series rather than large trials. Moreover, relationships between ARDS and hemodynamics are unclear. The European Collaborative ARDS Study was designed to identify factors influencing the pathogenesis, severity, and prognosis of ARDS. Analysis of the hemodynamic profiles collected during this study and of their contribution to the above-mentioned facets of ARDS is the focus of the present report. DESIGN: Prospective clinical study. SETTING: 38 European intensive care units (ICUs). PATIENTS AND METHODS: We collected 2758 sets of data from 586 patients, including baseline data, data on proven or suspected causes of ARDS differentiating direct and nondirect lung injury, and data on baseline status including multiple organ dysfunction (MOD) with differentiation of primary ARDS from ARDS secondary to severe systemic disorders. Events during follow-up were also recorded, including whether the acute respiratory failure did or did not improve after 24 h (groups A and B, respectively). When available, hemodynamic data were recorded at enrollment (day 0), on days 1-3, 7, 14, and 21, and at discharge or at the time of death in the ICU. RESULTS: Although the rate of pre-existing disease and the nature and rate of complications varied widely among etiologic categories, differences in the hemodynamic profile occurred only between primary and secondary ARDS. Both at inclusion and during the course of the illness, variables that were used to investigate Va/Q mismatch [arterial oxygen tension (PaO2, arterial oxygen saturation, right-to-left shunt, and the PaO2/fractional inspired oxygen (FIO2) ratio] predicted survival. High pulmonary artery pressure (PAP) and low systemic artery pressure (SAP) were also related to the prognosis. In the logistic regression model including hemodynamic and oxygen-related variables, however, the only independent predictors of survival were the ratio of right over left ventricular stroke work (RVSW/LVSW) and the PaO2/FIO2 ratio at admission. On day 2, the best prognostic model included: age [odds ratio (OR) = 1.04, p = 0.0004], opportunistic pneumonia as the cause of ARDS (OR = 3.2, p = 0.03), existence of MOD (OR = 1.9, p = 0.03), PaO2/FIO2 (OR = 0.96, p = 0.005), and RVSW/LVSW (OR = 25, p = 0.02). A high RVSW/LVSW ratio, high systolic PAP, low diastolic SAP, and low PaO2/FIO2, and increased right atrial pressure were negative prognostic indicators during follow-up. CONCLUSION: In addition to the cause of ARDS and the early time-course of lung function, a high systolic PAP and a low diastolic SAP were strong independent indicators of survival.     

Comparison of alveolar ventilation, oxygenation, pressure support, and respiratory system resistance in response to noninvasive versus conventional mechanical ventilation in foals

OBJECTIVE: To compare the efficacy of positive pressure ventilation applied through a mask versus an endotracheal tube, using anesthetized/paralyzed foals as a model for foals with hypoventilation. ANIMALS: Six 1-month-old foals. PROCEDURE: A crossover design was used to compare the physiologic response of foals to 2 ventilatory techniques, noninvasive mask mechanical ventilation (NIMV) versus endotracheal mechanical ventilation (ETMV), during a single period of anesthesia and paralysis. Arterial pH, PaO2, PaCO2, oxygen saturation, end-tidal CO2 tension, airway pressures, total respiratory system resistance, resistance across the upper airways (proximal to the midtracheal region), and positive end-expiratory pressures (PEEP) were measured. Only tidal volume (VT; 10, 12.5, and 15 ml/kg of body weight) or PEEP (7 cm of H2O) varied. RESULTS: Compared with ETMV, use of NIMV at equivalent VT resulted in PaCO2 and pH values that were significantly higher, but PaO2 was only slightly lower. Between the 2 methods, peak airway pressure was similar, but peak expiratory flow was significantly lower and total respiratory resistance higher at each VT for NIMV. Delivery of PEEP (7 cm of H2O) was slightly better for ETMV (7.1 +/- 1.3 cm of H2O) than for NIMV (5.6 +/- 0.6 cm of H2O). CONCLUSION: These data suggest that use of NIMV induces similar physiologic effects as ETMV, but the nasal cavities and mask contribute greater dead space, manifesting in hypercapnia. Increasing the VT used on a per kilogram of body weight basis, or the use of pressure-cycled ventilation might reduce hypercapnia during NIMV. CLINICAL RELEVANCE: Use of NIMV might be applicable in selected foals, such as those with hypoventilation and minimal changes in lung compliance, during weaning from endotracheal mechanical ventilation, or for short-term ventilation in weak foals.     

Contribution of bronchoalveolar lavage and transbronchial biopsy to diagnosis and prognosis of drug-induced pneumopathies

OBJECTIVE: The purpose of this study was to evaluate three ventilator weaning strategies and to evaluate whether the use of continuous positive airway pressure (CPAP) via a nasopharyngeal or endotracheal tube would increase the likelihood of extubation failure in very low birth weight (VLBW) infants. STUDY DESIGN: We studied prospectively 87 preterm infants (mean +/- SD; birth weight: 1078 +/- 188 g; gestational age: 28.8 +/- 2.2 weeks) who were in the process of being weaned from intermittent mandatory ventilation (IMV). Infants were assigned by systematic sampling to one of the following three treatment groups: (1) direct extubation from IMV (D.EXT) (n = 30); (2) preextubation endotracheal CPAP (ET-CPAP) for 12-24 hr (n = 28); or (3) postextubation nasopharyngeal CPAP (NP-CPAP) for 12-24 hr (n = 29). Failure was defined as the need for resumption of mechanical ventilation within 72 hr of extubation due to frequent or severe apnea and/or respiratory failure (pH < 7.25, PaCO2 > 60 mm Hg, and/or requirement for oxygen FiO2 > 60%). RESULTS: There were no significant differences in failure rates among the three procedures. Failures were 2/30 (7%) in D.EXT; 4/28 (14%) in ET-CPAP; and 7/29 (24%) in the NP-CPAP. There were also no differences in FiO2, PaO2, and respiratory rates before and after discontinuation of IMV among the three groups. PaCO2 values were slightly higher in the NP-CPAP group 12-24 hr after weaning from IMV. CONCLUSION: We were unable to demonstrate a clear difference in extubation outcome by use of CPAP administered via an endotracheal or nasopharyngeal tube when compared to direct extubation from low-rate IMV in VLBW infants.     

Comparative physiologic effects of noninvasive assist-control and pressure support ventilation in acute hypercapnic respiratory failure

STUDY OBJECTIVE: To compare the effects of noninvasive assist-control ventilation (ACV) and pressure support ventilation (PSV) by nasal mask on respiratory physiologic parameters and comfort in acute hypercapnic respiratory failure (AHRF). DESIGN: A prospective randomized study. SETTING: A medical ICU. PATIENTS AND INTERVENTIONS: Fifteen patients with COPD and AHRF were consecutively and randomly assigned to two noninvasive ventilation (NIV) sequences with ACV and PSV mode, spontaneous breathing (SB) via nasal mask being used as control. ACV and PSV settings were always subsequently adjusted according to patient's tolerance and air leaks. Fraction of inspired oxygen did not change between the sequences. MEASUREMENTS AND RESULTS: ACV and PSV mode strongly decreased the inspiratory effort in comparison with SB. The total inspiratory work of breathing (WOBinsp) expressed as WOBinsp/tidal volume (VT) and WOBinsp/respiratory rate (RR), the pressure time product (PTP), and esophageal pressure variations (deltaPes) were the most discriminant parameters (p<0.001). ACV most reduced WOBinsp/VT (p<0.05), deltaPes (p<0.05), and PTP (0.01) compared with PSV mode. The surface diaphragmatic electromyogram activity was also decreased >32% as compared with control values (p<0.01), with no difference between the two modes. Simultaneously, NIV significantly improved breathing pattern (p<0.01) with no difference between ACV and PSV for VT, RR, minute ventilation, and total cycle duration. As compared to SB, respiratory acidosis was similarly improved by both modes. The respiratory comfort assessed by visual analog scale was less with ACV (57.23+/-30.12 mm) than with SB (75.15+/-18.25 mm) (p<0.05) and PSV mode (81.62+/-25.2 mm) (p<0.01) in our patients. CONCLUSIONS: During NIV for AHRF using settings adapted to patient's clinical tolerance and mask air leaks, both ACV and PSV mode provide respiratory muscle rest and similarly improve breathing pattern and gas exchange. However, these physiologic effects are achieved with a lower inspiratory workload but at the expense of a higher respiratory discomfort with ACV than with PSV mode.