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.     

The Geriatric Concentration Test. Results of a study of patients over 65 years of age in Mannheim

In a clinical trial, the influence of repeated intermittent prone position on pulmonary gas exchange was investigated in 6 patients with severe ARDS. Despite various intra- and interindividual differences, oxygenation index (calculated by the paO2:FiO2 ratio) was improved significantly by change from supine to prone position in the first two days of treatment, whereas paCO2 remained unchanged. Later on, a significant improvement of oxygenation could not be verified. In patients with proven or presumed densities of dorsal lung regions, body position changes from supine to prone position in the early phase of treatment may improve arterial oxygenation and may be regarded as a therapeutic principle in conventional ARDS treatment.     

Improved oxygenation utilizing a prone positioner in patients with acute respiratory distress syndrome

OBJECTIVES: (a) To determine whether placing patients with acute respiratory distress syndrome in the prone position by a light-weight portable support frame improves oxygenation, (b) whether one can determine which patients benefit from prone positioning, and (c) to determine an effective technique for prone positioning of patients. DESIGN: Prospective, controlled trial without blinding. SETTING: Medical intensive care units in two urban university-affiliated hospitals. PATIENTS: Fifteen patients meeting a standard definition for acute respiratory distress syndrome were studied prospectively. Each patient acted as his own control for purposes of comparison. INTERVENTION: Patients were assigned randomly to begin in either supine or prone positions. The positioning frame was used to turn patients from one position to the other, and oxygenation, ventilation, respiratory mechanics, and hemodynamics were measured. RESULTS: Significantly better oxygenation was seen in the prone positions than in the supine (P < 0.05). In the overall population there was a decrease in AaDO2 of 21 mmHg when the patients were placed prone. The groups were then divided into responders (n = 9) and nonresponders (n = 6). There were significant differences between the groups (but not between positions) regarding PaO2, baseline, PaCO2, pulmonary artery pressures, and peak inspiratory pressures on the ventilator and in ICU length of stay and time on mechanical ventilatory support. CONCLUSION: Prone positioning improves oxygenation in the majority of patients studied and can be achieved relatively easily.     

Artificial ventilation in acute respiratory distress syndrome in adults. Towards an individual optimization

Artificial ventilation plays a key role in the treatment of acute respiratory distress syndrome (ARDS). Initially, the goal is to normalize gas exchange compromised by the lung disease. Positive pressure ventilation can however aggravate prior lesions of the pulmonary parenchyma, at least in areas of the lung accessible to ventilation. Computed tomography of the lung has given us a better understanding of the pathogenesis of these ventilation-induced lesions, leading to new ventilatory strategies aimed at assuring adequate oxygenation without damaging the parenchyma. These ventilatory modes may tolerate a certain degree of hypercapnia to avoid lung injury. Improved oxygenation relies on optimizing the ventilation/perfusion ratio, either with inhaled nitric oxide or a supine position to improve alveolar recruitment. In the most severe cases, extra-corporal gas exchange systems have shown their efficacy for patients whose lungs cannot be ventilated. Thus ventilation should be carefully adapted to each patient based on the severity of the ARDS and its clinical course. We present a practical protocol based on a hierarchy rationale for each ventilation mode and indicate the explorations required to adapt each mode to a specific patient.     

Adaptive lung ventilation (AVL). Evaluation of new closed loop regulated respiration algorithm for operation in the hyperextended lateral position

The lateral decubitus position is the standard position for nephrectomies. There is a lack of data about the effects of this extreme position upon respiratory mechanics and gas exchange. In 20 patients undergoing surgery in the nephrectomy position, we compared a new closed-loop-controlled ventilation algorithm, adaptive lung ventilation (ALV), which adapts the breathing pattern automatically, to the respiratory mechanics with conventionally controlled mandatory ventilation (CMV). The aims of our study were (1) to describe positioning effects on respiratory mechanics and gas exchange, (2) to compare ventilatory parameters selected by the ALV controller with traditional settings of CMV, and (3) to assess the individual adaptation of the ventilatory parameters by the ALV controller. The respirator used was a modified Amadeus ventilator, which is controlled by an external computer and possesses an integrated lung function analyzer. In a first set of measurements, we compared parameters of respiratory mechanics and gas exchange in the horizontal supine position and 20 min after changing to the nephrectomy position. In a second set of measurements, patients were ventilated with ALV and CMV using a randomized crossover design. The CMV settings were a tidal volume of 10 ml/kg body weight, a respiratory rate of 10 breaths/min, an I:E ratio of 1:1.5, and an end-inspiratory pause of 30% of inspiratory time. With both ventilation modes F1O2 was set to 0.5 and PEEP to 3 cm H2O. During ALV a desired alveolar ventilation of 70 ml/ kg KG.min was preset. All other ventilatory parameters were determined by the ALV controller according to the instantaneously measured respiratory parameters. Positioning induced a reduction of compliance from 61.6 to 47.9 ml/cm H2O; the respiratory time constant shortened from 1.2 to 1.08 s, whereas physiological dead space increased from 158.9 to 207.5 ml. On average, the ventilatory parameters selected by the ALV controller resembled very closely those used with CMV. However, an adaptation to individual respiratory mechanics was clearly evident with ALV. In conclusion, we found that the effects of positioning for nephrectomy are minor and may give rise to problems only in patients with restrictive lung disease. The novel ALV controller automatically selects ventilatory parameters that are clinically sound and are better adapted to the respiratory mechanics of ventilated patients than the standardized settings of CMV are.     

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.     

Mechanical ventilation of patients with acute lung injury

Ventilatory management of patients with acute lung injury (ALI), particularly its most severe subset, acute respiratory distress syndrome (ARDS), is complex. Newer lung protective strategies emphasize measures to enhance alveolar recruitment and avoid alveolar overdistention, thus minimizing the risk of ventilator-induced lung injury (VILI). Key components of such strategies include the use of smaller-than-conventional tidal volumes which maintain peak transpulmonary pressure below the pressure associated with overdistention, and titration of positive end-expiratory pressure to promote maximal alveolar recruitment. Novel techniques, including prone positioning, inverse ratio ventilation, tracheal gas insufflation, and high frequency ventilation, are considerations in severe ARDS. No single approach is best for all patients; adjustment of ventilatory parameters to individual characteristics, such as lung mechanics and gas exchange, is required.     

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.     

Spectral properties of system I-deficient mutants of Chlamydomonas reinhardi. Possible occurrence of uphill energy transfer

The effects of end-inspiratory pause (EIP) on gas exchange were measured in 10 adult patients with acute respiratory insufficiency while maintained on mechanical ventilation. Four inspiratory patterns were studied with a constant tidal volume (10 to 15 ml/kg body weight), respiratory rate (9 to 12 breaths/min), FIO2 (0.5) and end-expiratory pressure. Inspiratory flow rate (V insp) and EIP time were varied to produce a control pattern (V insp = 60 L/min, EIP = 0), 2 EIP patterns of 0.6 and 1.2 seconds with a similar V insp and a "slow" flow pattern (V insp = 30 L/min) without EIP. The control pattern was applied before and after each study period. Arterial oxygenation was unchanged with both EIP and "slow" flow patterns when compared to control. Dead-space ventilation (VD/VT) and Paco2 were significantly decreased (p less than 0.01) as EIP was increased from 0 to 1.2 seconds, but remained unchanged with slow inspiratory flow. Thus, EIP improved the efficiency of ventilation with no apparent improvement in oxygenation in patients with acute respiratory insufficiency.     

Adjuncts to mechanical ventilation

Adjunctive ventilatory strategies have been developed to improve oxygenation and carbon dioxide (CO2) removal during mechanical ventilation of critically ill patients. These techniques allow clinicians to attain their clinical goals at lower levels of ventilatory support. In this article, the authors discuss extracorporeal CO2 removal, venovenous intravena caval oxygenator, and tracheal gas insufflation as adjuncts to CO2 removal and nitric oxide, surfactant replacement therapy, perfluorocarbon-associated gas exchange, and prone positioning as adjuncts to oxygenation.     

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.     

Pulse oximetry in severe carbon monoxide poisoning

STUDY OBJECTIVES: To evaluate the accuracy and quantitate the error of pulse oximetry measurements of arterial oxygenation in patients with severe carbon monoxide (CO) poisoning. DESIGN: Retrospective review of patient clinical records. SETTING: Regional referral center for hyperbaric oxygen therapy. PATIENTS: Thirty patients referred for treatment of acute severe CO poisoning who demonstrated carboxyhemoglobin (COHb) levels >25%, with simultaneous determinations of arterial hemoglobin oxygen saturation by pulse oximetry (SpO2) and arterial blood gas (ABG) techniques. MEASUREMENTS AND RESULTS: COHb levels and measurements of arterial oxygenation from pulse oximetry, ABG analysis, and laboratory CO oximetry were compared. SpO2 did not correlate with COHb levels. SpO2 consistently overestimated the fractional arterial oxygen saturation. The difference between arterial hemoglobin oxygen saturation (SaO2) calculated from ABG analysis and SpO2 increased with increasing COHb level. CONCLUSIONS: Presently available pulse oximeters overestimate arterial oxygenation in patients with severe CO poisoning. An elevated COHb level falsely elevates the SaO2 measurements from pulse oximetry, usually by an amount less than the COHb level, confirming a prior observation in an animal model. Accurate assessment of arterial oxygen content in patients with CO poisoning can currently be performed only by analysis of arterial blood with a laboratory CO-oximetry.     

Patients with acute respiratory distress syndrome mechanically ventilated in prone position

Animal experiments and human studies have shown better oxygenation in mechanically ventilated patients with ARDS when the patient is situated in the prone position. In contradiction to former theories of a gravitational gradient of lung perfusion, a number of investigators have found that lung perfusion is preferentially distributed to the dorsal lung regions regardless of body position. The basal atelectasis and oedema in ARDS are resolved and only partly distributed anteriorly in the prone position, and these areas are thereby better ventilated. The combination of better ventilation and unchanged perfusion improves the ventilation/perfusion ratio and decreases the shunt in the prone position. In two cases of prone position in mechanically ventilated patients the PaO2/FiO2 ratio increased from 7.5 to 14.3 and from 8.8 to 19.8 after one hour in the prone position, and some of the improvement was permanent. Prone position has only minor side effects and is recommended as the first choice amongst adjunct therapies in mechanical ventilation in patients with ARDS remaining hypoxic in conventional therapy in the supine position.     

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.     

Sequential use of noninvasive pressure support ventilation for acute exacerbations of COPD

OBJECTIVES: To compare the efficacy of noninvasive pressure support ventilation (NIPSV) in acute decompensation in chronic obstructive pulmonary disease (COPD) by means of a bi-level positive airway pressure support system (BiPAP) in a sequential mode with medical therapy alone; to assess the short-term physiologic effects of the device on gas exchange; and to compare patients successfully ventilated with NIPSV with those in whom NIPSV failed. DESIGN: A prospective case series with historically matched control study. SETTING: A general intensive care unit (ICU) of a university hospital. PATIENTS: We evaluated the efficacy of administration of NIPSV in 42 COPD patients and compared this with standard treatment in 42 matched historical control COPD patients. INTERVENTIONS: NIPSV was performed in a sequential mode, i.e., BiPAP in the spontaneous mode was used for at least 30 min every 3 h. Between periods of ventilation, patients could be systematically returned to BiPAP when the arterial oxygen saturation was < 0.85 or when the respiratory rate was > 30 breaths/min. MEASUREMENTS AND RESULTS: Success rate, mortality, duration of ventilatory assistance, and length of ICU stay were recorded. Eleven of the 42 patients (26%) in the NIPSV group needed tracheal intubation compared with 30 of the 42 control patients (71%). The 31 patients in whom NIPSV was successful were ventilated for a mean of 6 +/- 3 days. In-hospital mortality was not significantly different in the treated versus the control group, but the duration of ventilatory assistance (7 +/- 4 days vs 15 +/- 10 days, p < 0.01) and the length of ICU stay (9 +/- 4 days vs 21 +/- 12, p < 0.01) were both shortened by NIPSV. BiPAP was effective in correcting gas exchange abnormalities. The pH values, measured after 45 min of BiPAP with optimal settings, in the success (7.38 +/- 0.04) and failure (7.28 +/- 0.04) patients were significantly different (p < 0.05). CONCLUSIONS: NIPSV, performed with a sequential mode, may be used in the management of patients with acute exacerbations of COPD.     

Influence of gas composition on recurrence of atelectasis after a reexpansion maneuver during general anesthesia

BACKGROUND: Atelectasis, an important cause of impaired gas exchange during general anesthesia, may be eliminated by a vital capacity maneuver. However, it is not clear whether such a maneuver will have a sustained effect. The aim of this study was to determine the impact of gas composition on reappearance of atelectasis and impairment of gas exchange after a vital capacity maneuver. METHODS: A consecutive sample of 12 adults with healthy lungs who were scheduled for elective surgery were studied. Thirty minutes after induction of anesthesia with fentanyl and propofol, the lungs were hyperinflated manually up to an airway pressure of 40 cmH2O. FIO2 was either kept at 0.4 (group 1, n = 6) or changed to 1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by computed tomography. The amount of dense areas was measured at end-expiration in a transverse plane at the base of the lungs. The ventilation-perfusion distributions (VA/Q) were estimated with the multiple inert gas elimination technique. The static compliance of the total respiratory system (Crs) was measured with the flow interruption technique. RESULTS: In group 1 (FIO2 = 0.4), the recruitment maneuver virtually eliminated atelectasis for at least 40 min, reduced shunt (VA/Q < 0.005), and increased at the same time the relative perfusion to poorly ventilated lung units (0.005 < VA/Q < 0.1; mean values are given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to 163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P = 0.028). In contrast to these findings, atelectasis recurred within 5 min after recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after recruitment, all parameters of VA/Q were unchanged. In both groups, Crs increased from 57.1/55.0 ml.cmH2O-1 (group 1/group 2) before to 70.1/67.4 ml.cmH2O-1 after the recruitment maneuver. Crs showed a slow decrease thereafter (40 min after recruitment: 61.4/60.0 ml.cmH2O-1), with no difference between the two groups. CONCLUSIONS: The composition of inspiratory gas plays an important role in the recurrence of collapse of previously reexpanded atelectatic lung tissue during general anesthesia in patients with healthy lungs. The reason for the instability of these lung units remains to be established. The change in the amount of atelectasis and shunt appears to be independent of the change in the compliance of the respiratory system.     

High-frequency partial liquid ventilation in respiratory distress syndrome: hemodynamics and gas exchange

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.     

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 lung function after intratracheal perfluorocarbon administration in healthy animals

OBJECTIVES: To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. SUBJECTS: Ten adult male New Zealand rabbits. INTERVENTIONS: Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. MEASUREMENTS AND MAIN RESULTS: Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). CONCLUSIONS: These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.     

Hyperoxia stimulates endothelin-1 secretion from endothelial cells; modulation by captopril and nifedipine

OBJECTIVE: Validation of an open-circuit multibreath nitrogen washout technique (MBNW) for measurement of functional residual capacity (FRC). The accuracy of FRC measurement with and without continuous viscosity correction of mass spectrometer delay time (TD) relative to gas flow signal and the influence of baseline FIO2 was investigated. DESIGN: Laboratory study and measurements in mechanically ventilated patients. SETTING: Experimental laboratory and anesthesiological intensive care unit of a university hospital. PATIENTS: 16 postoperative patients with normal pulmonary function (NORM), 8 patients with acute lung injury (ALI) and 6 patients with chronic obstructive pulmonary disease (COPD) were included. INTERVENTIONS: Change of FIO2 from baseline to 1.0. MEASUREMENTS AND MAIN RESULTS: FRC was determined by MBNW using continuous viscosity correction of TD(TDdyn), a constant TD based on the viscosity of a calibration gas mixture (TD0) and a constant TD referring to the mean viscosity between onset and end of MBNW (TDmean). Using TDdyn, the mean deviation between 15 measurements of three different lung model FRCs (FRCmeasured) and absolute volumes (FRCmodel) was 0.2%. For baseline FIO2 ranging from 0.21 to 0.8, the mean deviation between FRCmeasured and FRCmodel was -0.8%. However, depending on baseline FIO2, the calculation of FRC using TDmean and TD0 increased the mean deviation between FRCmeasured and FRCmodel to 2-4% and 8-12%, respectively. In patients (n = 30) the average repeatability coefficient was 6.0%. FRC determinations with TDmean and TD0 were 0.8-13.3% and 4.2-23.9% (median 2.7% and 8.7%) smaller than those calculated with TDdyn. CONCLUSION: A dynamic viscosity correction of TD improves the accuracy of FRC determinations by MBNW considerably, when gas concentrations are measured in a sidestream. If dynamic TD correction cannot be performed, the use of constant TDmean might be suitable. However, in patient measurements this can cause an FRC underestimation of up to 13%.