Recruitment maneuvers attenuate repeated derecruitment-associated lung injury

OBJECTIVE: Repeated derecruitments of previously recruited lungs can exacerbate lung injuries during mechanical ventilation. The aim of this study was to assess lung injury associated with repeated derecruitments and to assess whether this type of injury could be attenuated by recruitment maneuvers. DESIGN: Prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: Twenty-one rabbits were ventilated in pressure-controlled mode with constant tidal volume (10 mL/kg). After lung injury was induced by repeated saline lavage, positive end-expiratory pressure (PEEP) at a lower inflection point was applied for 3 hrs. The control group (n = 7) received ventilation with the same PEEP for 3 hrs without derecruitments. In the derecruitment group (n = 7), derecruitment was repeatedly induced by intentional disconnection of the ventilatory circuit for 1 min every 10 mins for 3 hrs. In the recruitment maneuver group (n = 7), continuous positive airway pressure of 30 cm H2O was applied for 30 secs after each derecruitment. MEASUREMENTS AND MAIN RESULTS: After PEEP levels were increased to lower the inflection point value, Pao2 increased to >500 mm Hg in all groups. Increased Pao2 persisted at >450 mm Hg in the control and recruitment maneuver groups, whereas progressive declines in arterial oxygen levels were observed in the derecruitment group (median, 381.1 mm Hg [interquartile range, 350.1-466.7 mm Hg] at 2 hrs and 318.2 mm Hg [214.3-414.9 mm Hg] at 3 hrs, p < .05 compared with other groups). Histologically, there was significantly increased hyaline membrane formation in alveolar ducts in the derecruitment group compared with the control group (p = .005). Also, significantly more membranous and respiratory bronchiolar injuries were observed in the derecruitment group compared with the control and recruitment maneuver group (p < .005). CONCLUSIONS: These findings suggest that repeated derecruitments could induce lung injuries during mechanical ventilation, and recruitment maneuvers may attenuate derecruitment-associated lung injuries.     

Recruitment maneuvers during prone positioning in patients with acute respiratory distress syndrome

OBJECTIVE: To evaluate the interaction of recruitment maneuvers and prone positioning on gas exchange and venous admixture in patients with early extrapulmonary acute respiratory distress syndrome ventilated with high levels of positive end-expiratory pressure. We hypothesized that a sustained inflation performed after 6 hrs of prone positioning would induce sustained improvement in oxygenation (Pao2/Fio2) and venous admixture. DESIGN: Prospective, interventional study. SETTING: Tertiary care, postoperative intensive care unit. PATIENTS: Fifteen patients with early extrapulmonary acute respiratory distress syndrome. INTERVENTIONS: After 6 hrs of prone positioning, a sustained inflation was performed with 50 cm H2O maintained for 30 secs. Data were recorded in supine position, after 6 hrs of prone positioning, at 3, 30, and 180 mins following the sustained inflation. MEASUREMENTS AND MAIN RESULTS: A response to prone positioning was observed in nine of 15 patients leading to an improvement of Pao2/Fio2 (147 +/- 37 torr vs. 225 +/- 77 torr, p = .005) and venous admixture (35.4 +/- 8.3% vs. 28.9 +/- 9.8%, p = .001). Six patients did not respond to prone positioning. Following the sustained inflation, the responders to prone positioning showed a further increase of Pao2/Fio2 and decrease of venous admixture at 3 mins (Pao2/Fio2, 225 +/- 77 torr vs. 368 +/- 90 torr, p = .018; venous admixture, 28.9 +/- 9.8% vs. 18.9 +/- 6.7%, p = .05). In all six nonresponders to prone positioning, an improvement of Pao2/Fio2 and venous admixture occurred at 3 mins following the sustained inflation (128 +/- 18 torr vs. 277 +/- 59 torr, p = .03; venous admixture, 34.2 +/- 6.0% vs. 23.8 +/- 6.3%, p = .05). The beneficial effects of the sustained inflation remained significantly elevated over 3 hrs in responders and nonresponders to prone positioning. CONCLUSION: In patients with early extrapulmonary acute respiratory distress syndrome, a sustained inflation performed after 6 hrs of prone positioning induced further and sustained improvement of oxygenation and venous admixture in both responders and nonresponders to prone positioning.     

Selective tracheal gas insufflation during partial liquid ventilation improves lung function in an animal model of unilateral acute lung injury.

OBJECTIVE: During unilateral lung injury, we hypothesized that we can improve global lung function by applying selective tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) to the injured lung. DESIGN: Prospective, interventional animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Adult mixed-breed dogs. INTERVENTIONS: In six anesthetized dogs, left saline lung lavage was performed until PaO(2)/FiO(2) fell below 100 torr (13.3 kPa). The dogs were then reintubated with a Univent single-lumen endotracheal tube, which incorporates an internal catheter to provide TGI. In a consecutive manner, we studied 1) the application of 10 cm H(2)O of positive end-expiratory pressure (PEEP); 2) instillation of 10 mL/kg of perflubron (Liquivent) to the left lung at a PEEP level of 10 cm H(2)O (PLV+PEEP 10 initial); 3) application of selective TGI (PLV+TGI) while maintaining end-expiratory lung volume (EELV) constant; 4) PLV+TGI at reduced tidal volume (VT); and 5) PLV+PEEP 10 final. MEASUREMENTS AND MAIN RESULTS: Application of PLV+PEEP 10 initial did not change gas exchange, lung mechanics, or hemodynamics. PLV+TGI improved PaO(2)/FiO(2) from 189 +/- 13 torr (25.2 +/- 1.7 kPa) to 383 +/- 44 torr (51.1 +/- 5.9 kPa) (p <.01) and decreased PaCO(2) from 55 +/- 5 torr (7.3 +/- 0.7 kPa) to 30 +/- 2 torr (4.0 +/- 0.3 kPa) (p <.01). During ventilation with PLV+TGI, reducing VT from 15 mL/kg to 3.5 mL/kg while keeping EELV constant decreased PaO(2)/FiO(2) to 288 +/- 49 torr (38.4 +/- 6.5 kPa) (not significant) and normalized PaCO(2). At this stage, end-inspiratory plateau pressure decreased from 19.2 +/- 0.7 cm H(2)O to 13.6 +/- 0.7 cm H(2)O (p <.01). At PLV+PEEP 10 final, measurements returned to those observed at previous baseline stage (PLV+PEEP 10 initial). CONCLUSIONS: During unilateral lung injury, PLV with a moderate PEEP did not improve oxygenation, TGI superimposed on PLV improved gas exchange, and combination of TGI and PLV allowed a 77% reduction in VT without any adverse effect on PaCO(2).     

Effect of alveolar recruitment maneuver in early acute respiratory distress syndrome according to antiderecruitment strategy,etiological category of diffuse lung injury,and body position of the patient

OBJECTIVE: To assess how the level of positive end-expiratory pressure (PEEP) (antiderecruitment strategy), etiological category of diffuse lung injury, and body position of the patient modify the effect of the alveolar recruitment maneuver (ARM) in acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical trial. SETTING: Medical intensive care unit at a tertiary hospital. PATIENTS: Forty-seven patients with early ARDS, including 19 patients from our preliminary study. INTERVENTION: From baseline ventilation at a tidal volume of 8 mL/kg and PEEP of 10 cm H2O, the ARM (a stepwise increase in the level of PEEP up to 30 cm H2O with a concomitant decrease in the magnitude of tidal volume down to 2 mL/kg) was given with (ARM + PEEP, n = 20) or without (ARM only, n = 19) subsequent increase of PEEP to 15 cm H2O. In eight other patients, PEEP was increased to 15 cm H2O without a preceding ARM (PEEP only). MEASUREMENTS AND RESULTS: In all three groups, Pao2 was increased by the respective intervention (all p<.05). In the ARM-only group, Pao2 at 15 mins after intervention was lower than Pao2 immediate after intervention (p =.046). In the ARM + PEEP group, no such decrease in Pao2 was observed, and Pao2 at 15, 30, 45, and 60 mins after intervention was higher than in the ARM-only group (all p<.05). Compared with the PEEP-only group, Pao2 of the ARM + PEEP group was higher immediately after intervention and at the later time points (all p <.05). Compared with patients with ARDS associated with direct lung injury (pulmonary ARDS), patients with ARDS associated with indirect lung injury (extrapulmonary ARDS) showed a greater increase in Pao2 (27 +/- 21% vs. 130 +/- 112%; p=.002) and a greater decrease in radiologic scores (1.0 +/- 2.4 vs. 3.4 +/- 1.5; p=.005) after the ARM. The increase in Pao2 induced by the ARM was greater for patients in the supine position than for patients in the prone position (61 +/- 82% vs. 21 +/- 14%; p=.028). Consequently, Pao immediately after the ARM was similar in the two groups of patients in different positions. CONCLUSIONS: After the ARM, a sufficient level of PEEP is required as an antiderecruitment strategy. Pulmonary ARDS and extrapulmonary ARDS may be different pathophysiologic entities. An effective ARM may obviate the need for the prone position in ARDS at least in terms of oxygenation.     

Recruitment maneuver: does it promote bacterial translocation?

OBJECTIVE: High peak airway opening pressures (Pao) are used routinely during recruitment maneuvers to open collapsed lung units. High peak Pao, however, can cause lung injury as evidenced by translocation of intratracheally inoculated bacteria. In this study we explored whether recruitment maneuvers that used high Pao could cause translocation of the intratracheally inoculated from the alveoli into the systemic circulation. DESIGN: Prospective, randomized, animal study. SETTING: Experimental animal care laboratory. SUBJECTS: Eighteen male Sprague Dawley rats.INTERVENTIONS Rats were anesthetized, tracheostomized, and ventilated with 14 cm H2O peak Pao and 0 cm H2O positive end-expiratory pressure (PEEP) in pressure-controlled ventilation (frequency, 30 bpm; inspiratory/expiratory ratio, 1:2; Fio, 1). Intratracheal inoculation of 500 microL of saline containing 1 x 10 colony forming units/mL was performed before randomization into three groups (n = 6 in each): a low-pressure group (14 cm H2O peak Pao, 0 cm H2O PEEP), a high-pressure group (45 cm H2O peak Pao, 0 cm H2O PEEP), and a recruitment maneuver group (14 cm H2O peak Pao, 0 cm H2O PEEP, and a recruitment maneuver sustained inflation of 45 cm H2O continuous positive airway pressure for 30 secs every 15 mins). Blood samples for blood gas analysis were obtained before intratracheal instillation of bacteria and at the end of the experimental protocol (2 hrs). Blood cultures were obtained before and after bacterial instillation at 30-min intervals during the experiment. Blood samples were cultured directly in sheep blood, MacConkey, and Iso-Sensitest agars and were observed on the second day. Bacteremia was defined as the presence of one or more colonies of in 1 mL of blood. MEASUREMENTS AND MAIN RESULTS: The blood cultures were positive for in only six rats in the high-pressure group and remained negative throughout the study period in the low-pressure and recruitment maneuver groups. Oxygenation deteriorated in all groups after intratracheal instillation of bacteria. In the high-pressure group, oxygenation decreased from 417 +/- 67 mm Hg to 79 +/- 20 mm Hg ( p=.004), whereas in the low-pressure and recruitment maneuver groups PaO2 decreased from 410 +/- 98 mm Hg and 383 +/- 78 mm Hg to 287 +/- 105 mm Hg ( p=.031) and 249 +/- 59 mm Hg (p =.11), respectively. CONCLUSION: Intermittent recruitment maneuvers applied as a sustained inflation superimposed on low-pressure ventilation with 0 cm H2O PEEP did not cause translocation of intratracheally inoculated.     

Immediate application of positive-end expiratory pressure is more effective than delayed positive-end expiratory pressure to reduce extravascular lung water

OBJECTIVE: To determine by the measurement of extravascular lung water (EVLW) whether the timing of positive-end expiratory pressure (PEEP) application influences the intensity of lung injury. DESIGN: Animal experimental study. SETTING: Animal experimental laboratory. SUBJECTS: Mixed-breed pigs (n = 18), aged 4 to 5 mos, weighing 25 to 30 kg. INTERVENTIONS: The animals were anesthetized and tracheotomized, after which a permeability pulmonary edema was instigated by infusing oleic acid (0.1/kg) into the central vein. All animals were then randomly divided into three groups. In group 1 (n = 5), 10 cm H2O of PEEP was applied immediately after the oleic acid infusion and maintained throughout the 6 hrs of the experiment. Group 2 (n = 7) received the same level of PEEP 120 mins after the insult for 4 hrs. Group 3 (n = 6), the control group, was ventilated without PEEP for the six hrs of the experiment. MEASUREMENTS AND MAIN RESULTS: At the end of the experiment, EVLW was calculated by gravimetric method. EVLW in group 1 (11.46+/-2.00 mL/kg) was significantly less than in group 2 (19.12+/-2.62 mL/kg) and group 3 (25.81+/-1.57 mL/kg), (p<.0001). Oxygenation also showed important differences by the end of the experiment when the Pao2/Fio2 ratio was significantly better in group 1 (467+/-73) than in group 2 (180+/-82) and group 3 (39+/-9), (p<.0001). CONCLUSIONS: The application of 10 cm H2O of PEEP reduces EVLW in a time-dependent manner and maximum protective effect is achieved if it is applied immediately after lung injury production.     

A comparison of intratracheal pulmonary ventilation to conventional ventilation in a surfactant deficient animal model

OBJECTIVE: To compare intratracheal pulmonary ventilation (ITPV) with conventional ventilation in a rabbit model of surfactant deficiency. DESIGN: A prospective randomized animal study. SETTING: The Children's National Medical Center Research Animal Facility in Washington, DC. SUBJECTS: Adult male New Zealand white rabbits (n = 20), weighing 1.4-4.2 kg. INTERVENTIONS: After anesthesia and catheter placement, rabbits were tracheotomized, paralyzed, and placed on the conventional ventilator. We determined pulmonary functions at baseline. We washed surfactant out of the lungs by using serial bronchoalveolar lavages. Pulmonary function studies were determined after completion of the bronchoalveolar lavages and were used as an indication of severity of lung injury. Animals were randomized into two groups: We placed ten animals on ITPV, using the ITPV reverse thruster catheter designed by Kolobow and a prototype ITPV ventilator designed at Children's National Medical Center; we placed ten animals on conventional ventilation using the Sechrist iv-100 ventilator. Arterial blood gases were drawn every 15 mins, and the ventilator settings were adjusted to the minimal level that would maintain arterial blood gases in the following ranges: pH 7.35-7.45, PaCO2 30-40 torr (3.995.33 kPa), PaO2 50-70 torr (6.66-9.33 kPa). Animals were ventilated with the randomized ventilation techniques for 4 hrs. MEASUREMENTS AND MAIN RESULTS: Peak inspiratory pressure, mean airway pressure, and positive end-expiratory pressure were measured at the distal end of the endotracheal tube. We recorded these variables plus respiratory rate at baseline and every 30 mins for a total of 4 hrs of ventilation. Lung compliance did not differ between groups at the postlavage study period (ITPV, 0.56+/-0.13 mL/cm H2O/kg; conventional 0.49+/-0.15 mL/cm H2O/kg). At the end of the 4 hr study period, peak inspiratory pressure (ITPV, 26.2+/-4.6 cm H2O; conventional, 32.4+/-5.04 cm H2O, p = .007) and positive end-expiratory pressure (ITPV, 3.9+/-1.96 cm H2O; conventional, 6.3+/-1.42 cm H2O, p = .005) were lower in the ITPV ventilation group. Peak inspiratory pressure was significantly lower in the ITPV group by 2 hrs into the study. CONCLUSION: In this model of surfactant deficiency lung injury, ventilation and oxygenation were achieved at significantly lower ventilator settings using ITPV compared with conventional ventilation. Long-term studies are needed to determine whether this reduction in ventilation is maintained, and if so, if lung injury is reduced.     

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.     

A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial

OBJECTIVE: It has been shown in a two-center study that high positive end-expiratory pressure (PEEP) and low tidal volume (LTV) improved outcome in ARDS. However, that study involved patients with underlying diseases unique to the study area, was conducted at only two centers, and enrolled a small number of patients. We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system (Pflex) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome (ARDS). DESIGN: Randomized, controlled clinical trial. SETTING: Network of eight Spanish multidisciplinary intensive care units (ICUs) under the acronym of ARIES (Acute Respiratory Insufficiency: Espa?a Study). PATIENTS: All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study. If 24 hrs after meeting ARDS criteria, the Pao2/Fio2 remained < or =200 mm Hg on standard ventilator settings, patients were randomized into two groups: control and Pflex/LTV. INTERVENTIONS: In the control group, tidal volume was 9-11 mL/kg of predicted body weight (PBW) and PEEP > or =5 cm H2O. In the Pflex/LTV group, tidal volume was 5-8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O. In both groups, Fio2 was set to maintain arterial oxygen saturation >90% and Pao2 70-100 mm Hg, and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg. MEASUREMENTS AND MAIN RESULTS: The study was stopped early based on an efficacy stopping rule as described in the methods. Of 103 patients who were enrolled (50 control and 53 Pflex), eight patients (five in control, three in Pflex) were excluded from the final evaluation because the random group assignment was not performed in one center according to protocol. Main outcome measures were ICU and hospital mortality, ventilator-free days, and nonpulmonary organ dysfunction. ICU mortality (24 of 45 [53.3%] vs. 16 of 50 [32%], p = .040), hospital mortality (25 of 45 [55.5%] vs. 17 of 50 [34%], p = .041), and ventilator-free days at day 28 (6.02 +/- 7.95 in control and 10.90 +/- 9.45 in Pflex/LTV, p = .008) all favored Pflex/LTV. The mean difference in the number of additional organ failures postrandomization was higher in the control group (p < .001). CONCLUSIONS: A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS.     

The effect of positive end-expiratory pressure during partial liquid ventilation in acute lung injury in piglets.

OBJECTIVES: To investigate the effects of positive end-expiratory pressure (PEEP) application during partial liquid ventilation (PLV) on gas exchange, lung mechanics, and hemodynamics in acute lung injury. DESIGN: Prospective, randomized, experimental study. SETTING: University research laboratory. SUBJECTS: Six piglets weighing 7 to 12 kg. INTERVENTIONS: After induction of anesthesia, tracheostomy, and controlled mechanical ventilation, animals were instrumented with two central venous catheters, a pulmonary artery catheter and two arterial catheters, and an ultrasonic flow probe around the pulmonary artery. Acute lung injury was induced by the infusion of oleic acid (0.08 mL/kg) and repeated lung lavage procedures with 0.9% sodium chloride (20 mL/kg). The protocol consisted of four different PEEP levels (0, 5, 10, and 15 cm H2O) randomly applied during PLV. The oxygenated and warmed perfluorocarbon liquid (30 mL/kg) was instilled into the trachea over 5 mins without changing the ventilator settings. MEASUREMENTS AND MAIN RESULTS: Airway pressures, tidal volumes, dynamic and static pulmonary compliance, mean and expiratory airway resistances, and arterial blood gases were measured. In addition, dynamic pressure/volume loops were recorded. Hemodynamic monitoring included right atrial, mean pulmonary artery, pulmonary capillary wedge, and mean systemic arterial pressures and continuous flow recording at the pulmonary artery. The infusion of oleic acid combined with two to five lung lavage procedures induced a significant reduction in PaO2/FI(O2) from 485 +/- 28 torr (64 +/- 3.6 kPa) to 68 +/- 3.2 torr (9.0 +/- 0.4 kPa) (p < .01) and in static pulmonary compliance from 1.3 +/- 0.06 to 0.67 +/- 0.04 mL/cm H2O/kg (p < .01). During PLV, PaO2/FI(O2) increased significantly from 68 +/- 3.2 torr (8.9 +/- 0.4 kPa) to >200 torr (>26 kPa) (p < .01). The highest PaO2 values were observed during PLV with PEEP of 15 cm H2O. Deadspace ventilation was lower during PLV when PEEP levels of 10 to 15 cm H2O were applied. There were no differences in hemodynamic data during PLV with PEEP levels up to 10 cm H2O. However, PEEP levels of 15 cm H2O resulted in a significant decrease in cardiac output. Dynamic pressure/volume loops showed early inspiratory pressure spikes during PLV with PEEP levels of 0 and 5 cm H2O. CONCLUSIONS: Partial liquid ventilation is a useful technique to improve oxygenation in severe acute lung injury. The application of PEEP during PLV further improves oxygenation and lung mechanics. PEEP levels of 10 cm H2O seem to be optimal to improve oxygenation and lung mechanics.     

Acute oxygenation response to inhaled nitric oxide when combined with high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome

OBJECTIVE: To prospectively evaluate the oxygenation effect of inhaled nitric oxide (INO) delivered during high-frequency oscillatory ventilation in adult patients with the acute respiratory distress syndrome and oxygenation failure. DESIGN Prospective, clinical study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: A total of 23 adults (14 women, 9 men, 44.9 +/- 17.5 yrs, Acute Physiology and Chronic Health Evaluation II score of 28.6 +/- 7.1) with acute respiratory distress syndrome (lung injury score, 3.5 +/- 0.4) with Fio2 of > or = 0.6 and mean airway pressure of >or=28 cm H2O. INTERVENTIONS: INO was initiated at a dose of 5 ppm, and subsequently titrated according to a protocol, to determine the dose (5, 10, or 20 ppm) resulting in the greatest increase in Pao2/Fio2. Blood gas measurements were obtained 10-15 mins after initiation or any increase in INO dosage to assess the effect on Pao2/Fio2. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and ventilator settings were recorded at four time points: during conventional ventilation just before initiating high-frequency oscillatory ventilation, during high-frequency oscillatory ventilation just before initiating INO, after 30 mins on the optimal dose of INO, and 8-12 hrs after starting INO. Oxygenation index ([Fio2 x mean airway pressure x 100]/Pao2) and Pao2/Fio2 ratios were calculated at the same time intervals. At 30 mins after INO initiation, 83% of patients had a significant increase in blood oxygen tension, defined as > or = 20% increase in Pao2/Fio2. The mean change in Pao2/Fio2 at 30 mins was 38%. In these 19 patients, Pao2/Fio2 was highest at 20 ppm in four patients, at 10 ppm in eight patients, and at 5 ppm in seven patients. Compared with baseline measurements, Pao2/Fio2 improved significantly at both 30 mins (112 +/- 59 vs. 75 +/- 32, p=.01) and 8-12 hrs after INO initiation (146 +/- 52 vs. 75 +/- 32, p<.0001). In addition, oxygenation index was reduced at 8-12 hrs compared with baseline measurements (26 +/- 13 vs. 40 +/- 17, p=.08). CONCLUSIONS: INO delivered at doses of 5 to 20 ppm during high-frequency oscillatory ventilation increases Pao2/Fio2 and may be a safe and effective rescue therapy for patients with severe oxygenation failure.     

Cerebral blood flow and metabolism during and after prolonged hypercapnia in newborn lambs

OBJECTIVE: To study the effects of prolonged (6 hrs) hypercapnia on cerebral blood flow and cerebral metabolism in newborn lambs and to evaluate the effects on cerebral blood flow and cerebral metabolism on return to normocapnia after prolonged hypercapnia. DESIGN: Animal studies, using the newborn lamb, with comparison to control group. SUBJECTS: Newborn lambs of mixed breed, 1-7 days of age, were used for the study. Two groups of animals were studied: a hypercapnic group (n = 10) and a normocapnic control group (n = 5). SETTING: Work was conducted in the research laboratories at Children's National Medical Center, Washington, DC. INTERVENTIONS: Animals were anesthetized with pentobarbital, intubated, paralyzed, and mechanically ventilated. After baseline measurements were made, CO2 was blended into the ventilator gas until a PaCO2 of 75-80 torr (10-10.6 kPa) was obtained. Measurements were made 1 hr after the desired PaCO2 was achieved and after 6 hrs of hypercapnia. After 6 hrs of hypercapnia, the ventilator gas was returned to the baseline value, that is, normocapnia. Measurements were made 30, 60, and 90 mins after PaCO2 returned to baseline. MEASUREMENTS: Six measurements were made during the study. For each measurement, blood samples were drawn from the sagittal sinus and brachiocephalic artery catheters and were analyzed for pH, hemoglobin concentration, oxygen saturation, and blood gas values. Cerebral blood flow (CBF) was measured by using the radiolabeled microsphere technique. Cerebral oxygen consumption, fractional oxygen extraction, and oxygen transport values were calculated at each study period. MAIN RESULTS: Increasing PaCO2 from 37 +/- 3 torr to 78 +/- 6 torr (4.9 +/- 0.4 kPa to 10.3 +/- 0.8 kPa) for 1 hr increased CBF by 355%. After 6 hrs of PaCO2 at 78 +/- 3 torr (10.3 +/- 0.4 kPa), CBF remained 195% above baseline. At 30 mins of normocapnia, CBF had returned to baseline and remained at baseline until the conclusion of the study, a total of 90 mins of normocapnia. Cerebral oxygen consumption did not change during hypercapnia or with return to normocapnia. Oxygen transport increased 331% above baseline after 1 hr of hypercapnia and stayed 180% above baseline after 6 hrs of hypercapnia. Fractional oxygen extraction decreased by 55% at 1 hr of hypercapnia and stayed 39% below baseline at 6 hrs of hypercapnia. CONCLUSIONS: Healthy lambs seem to tolerate undergoing hypercapnia for 6 hrs with a return to normocapnia. The return to baseline of CBF and cerebral metabolism at normocapnia seen in our study with lambs may explain why prolonged hypercapnia appears to be well tolerated in mechanically ventilated patients. If these results can be extrapolated to human subjects, our study in lambs supports evidence that patients who have undergone permissive hypercapnia seem to be neurologically unaffected.     

Protective effects of low tidal volume ventilation in a rabbit model of Pseudomonas aeruginosa-induced acute lung injury

OBJECTIVE: To determine whether low "stretch" mechanical ventilation protects animals from clinical sepsis after direct acute lung injury with Pseudomonas aeruginosa as compared with high "stretch" ventilation. DESIGN: Prospective study. SETTING: Experimental animal laboratory. SUBJECTS: Twenty-seven anesthetized and paralyzed rabbits. INTERVENTIONS: P. aeruginosa (109 colony forming units) was instilled into the right lungs of rabbits that were then ventilated at a tidal volume of either 15 mL/kg (n = 11) or 6 mL/kg (n = 7) for 8 hrs. Control animals were ventilated at a tidal volume of either 15 mL/kg (n = 4) or 6 mL/kg (n = 5) for 8 hrs, but an instillate without bacteria was used. A positive end-expiratory pressure of 3-5 cm H2O was used for all experiments. Radiolabeled albumin was used as a marker of alveolar epithelial permeability. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gas determination, alveolar permeability, wet-to-dry ratios on lungs, and time course of bacteremia were determined. When final values were compared with the values at the beginning of the experiment, there were significant decreases in mean arterial pressure (from 104 +/- 15 to 57 +/- 20 mm Hg), pH (from 7.46 +/- 0.04 to 7.24 +/- 15), Pao2 (from 528 +/- 35 to 129 +/- 104 torr [70.4 +/- 4.7 to 17.2 +/- 13.9 kPa]), and temperature (from 38.2 +/- 1 to 36.2 +/- 1.2 degrees C) in the high tidal volume group, whereas no significant differences were found in the low tidal volume group. Decreased alveolar permeability was shown in the low tidal volume group, as was decreased extravascular lung water in the uninstilled lung in the low tidal volume group (12.7 +/- 2.5 vs. 4.3 +/- 0.45 g H2O/g dry lung). No noteworthy difference was noted in the time course of bacteremia, although there was a trend toward earlier bacteremia in the high tidal volume group. CONCLUSIONS: In our animal model of P. aeruginosa-induced acute lung injury, low tidal volume ventilation was correlated with improved oxygenation, hemodynamic status, and acid-base status as well as decreased alveolar permeability and contralateral extravascular lung water.     

Respective effects of end-expiratory and end-inspiratory pressures on alveolar recruitment in acute lung injury

OBJECTIVE: A low tidal volume can induce alveolar derecruitment in patients with acute lung injury. This study was undertaken to evaluate whether this resulted mainly from the decrease in tidal volume or from the reduction in end-inspiratory plateau pressure and whether there is any benefit in raising the level of positive end-expiratory pressure (PEEP) while plateau pressure is kept constant. DESIGN: Prospective crossover study. SETTING: Medical intensive care unit of a university teaching hospital. PATIENTS: Fifteen adult patients ventilated for acute lung injury (PaO2/FiO2, 158 +/- 34 mm Hg; lung injury score, 2.7 +/- 0.6). INTERVENTIONS: Three combinations were tested: PEEP at the lower inflection point with 6 mL/kg tidal volume, PEEP at the lower inflection point with 10 mL/kg tidal volume, and high PEEP with tidal volume at 6 mL/kg, keeping the plateau pressure similar to the preceding condition. MEASUREMENTS AND MAIN RESULTS: Pressure-volume curves at zero PEEP and at set PEEP were recorded, and recruitment was calculated as the volume difference between both curves for pressures ranging from 15 to 30 cm H2O. Arterial blood gases were measured for all patients. For a similar PEEP at the lower inflection point (10 +/- 3 cm H2O), tidal volume reduction (10 to 6 mL/kg) led to a significant derecruitment. A low tidal volume (6 mL/kg) with high PEEP (14 +/- 3 cm H2O), however, induced a significantly greater recruitment and a higher Pao than the two other strategies. CONCLUSION: At a given plateau pressure (i.e., similar end-inspiratory distension), lowering tidal volume and increasing PEEP increase recruitment and PaO2.     

Gastric tonometry in patients with cardiogenic shock and intra-aortic balloon counterpulsation

OBJECTIVE: To study the course of gastric regional PCO2 (PrCO2) in patients with cardiogenic shock requiring intra-aortic balloon (IAB) counterpulsation and the prognostic value of PrCO2 in this patient population. DESIGN: A prospective, observational clinical study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Twenty-six consecutive patients with cardiogenic shock requiring mechanical support with an IAB counterpulsation undergoing mechanical ventilation INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULT: Hemodynamic variables, tonometric variables, arterial blood gases, and arterial lactate were assessed before insertion of IAB (baseline), and 1, 2, 3, 8, 16, 24, and 48 hrs thereafter. A subset of these patients (n = 14) were studied just before and 1, 8, 24, and 32 hrs after IAB removal; 12/26 patients (46.2%) died. Cardiac index increased from baseline to 1 hr after insertion of IAB (1.7 +/- 0.3 to 2.6 +/- 0.8 L/min/m2, p < .05). PrCO2 did not change between admission (47 +/- 13 torr [6.3 +/- 1.7 kPa]) and 8 hrs after placement of IAB but increased to 63 +/- 22 torr (8.4 +/- 2.9 kPa) at 16 hrs (p < .05) without any further alteration until 48 hrs. CO2 gap showed a similar pattern with 15 +/- 11 torr (2.0 +/- 1.5 kPa) at baseline and an increase to 28 +/- 22 torr (3.7 +/- 2.9 kPa) 16 hrs later. PrCO2 and CO2 gap remained at high levels (59 +/- 11 torr [7.7 +/- 1.5 kPa] and 22 +/- 10 torr [2.9 +/- 1.3 kPa], respectively), before IAB removal without further improvement or deterioration thereafter. PrCO2 values showed no difference between survivors and nonsurvivors at any time point. CONCLUSION: Patients with cardiogenic shock developed high PrCO2 within the first 24 hrs, which reflects gastric mucosal ischemia. Persistently high levels of PrCO2 were indicative for prolonged hypoperfusion of the gut. Gastric tonometry failed to discriminate between survivors and nonsurvivors.     

Open lung ventilation does not increase right ventricular outflow impedance: An echo-Doppler study

OBJECTIVE: Ventilation according to the open lung concept (OLC) consists of recruitment maneuvers, followed by low tidal volume and elevated positive end-expiratory pressure (PEEP). Elevated PEEP is associated with an increased right ventricular afterload. We investigated the effect of OLC ventilation on right ventricular outflow impedance during inspiration and expiration in patients after cardiac surgery using transesophageal echo-Doppler. DESIGN: A prospective, single-center, crossover, randomized, controlled clinical study. SETTING: Cardiothoracic intensive care unit of a university hospital. PATIENTS: Twenty-eight patients scheduled for elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: In the intensive care unit, each patient was ventilated for approximately 30 mins according to both OLC and conventional ventilation. During OLC ventilation, recruitment maneuvers were applied until PaO2/FiO2 was >375 torr (50 kPa); during conventional ventilation no recruitment maneuvers were performed. MEASUREMENTS AND MAIN RESULTS: Transesophageal echo-Doppler measurements were performed at end-inspiration and end-expiration in a steady-state condition, 20 mins after initiation of a ventilation strategy. Mean acceleration of flow was determined in the long axis of the pulmonary artery in a transverse axis view. During OLC ventilation, a total PEEP of 14 +/- 4 cm H2O was applied vs. 5 cm H2O during conventional ventilation. Mean acceleration during expiration was comparable between groups. During inspiration, OLC ventilation did not cause a decrease of mean acceleration compared with expiration, whereas this did occur during conventional ventilation. CONCLUSIONS: Despite the use of elevated PEEP levels, ventilation according to OLC does not change right ventricular outflow impedance during expiration and decreases right ventricular outflow impedance during inspiration.     

Extending inspiratory time in acute respiratory distress syndrome

OBJECTIVE: To assess the short-term effects of extending inspiratory time by lengthening end-inspiratory pause (EIP) without inducing a clinically significant increase in intrinsic positive end-expiratory pressure (PEEPi) in patients with acute respiratory distress syndrome (ARDS). DESIGN: Controlled, randomized, crossover study. SETTING: Two medical intensive care units of university hospitals. PATIENTS: Sixteen patients with early (< or =48 hrs) ARDS. INTERVENTION: We applied two durations of EIP (0.2 secs and extended) each for 1 hr while keeping all the following ventilatory parameters constant: FIO2, total PEEP (PEEPtot = applied PEEP + PEEPi), tidal volume, inspiratory flow, and respiratory rate. The duration of extended EIP was titrated to avoid an increase of PEEPi of > or =1 cm H2O. MEASUREMENTS AND MAIN RESULTS: Despite an increase in mean airway pressure (20.6 +/- 2.3 vs. 17.6 +/- 2.1 cm H2O, p < .01), extended EIP did not significantly improve PaO2 (93 +/- 21 vs. 86 +/-16 torr [12.40 +/- 2.80 vs. 11.46 +/- 2.13 kPa] with 0.2 secs EIP, NS). However, although the difference in PaO2 between the two EIP durations was <20 torr (<2.66 kPa) in 14 patients, two patients exhibited a >40 torr (>5.33 kPa) increase in PaO2 with extended EIP. Extended EIP decreased PaCO2 (62 +/- 13 vs. 67 +/- 13 torr [8.26 +/- 1.73 vs. 8.93 +/- 1.73 kPa] with 0.2 secs EIP, p < .01), which resulted in a higher pH (7.22 +/- 0.10 vs. 7.19 +/- 0.09 with 0.2 secs EIP, p < .01) and contributed to a slight increase in arterial hemoglobin saturation (94 +/- 3 vs. 93 +/- 3% with 0.2 EIP, p < .01). No significant difference in hemodynamics was observed. CONCLUSION: In patients with ARDS, extending EIP without inducing a clinically significant increase in PEEPi does not consistently improve arterial oxygenation but enhances CO2 elimination.     

Mechanical ventilation with permissive hypercapnia increases intrapulmonary shunt in septic and nonseptic patients with acute respiratory distress syndrome

OBJECTIVE: To compare the effects of conventional mechanical ventilation with low-volume, pressure-limited ventilation (LVPLV) and permissive hypercapnia on ventilation-perfusion (V/Q) distributions in patients with acute respiratory distress syndrome. We hypothesized that the advantageous cardiopulmonary effects of LVPLV would be greater in patients with sepsis than in those without sepsis. PATIENTS AND INTERVENTIONS: Twenty-two patients with acute respiratory distress syndrome were studied (group 1: 12 patients with hyperdynamic sepsis; group 2: 10 nonseptic patients). Intrapulmonary shunt (Qsp/Qt) (percentage of cardiac output), perfusion of "low" V/Q areas (percentage of cardiac output), ventilation of "high" V/Q areas (percentage of total ventilation [VE]), and deadspace ventilation (percentage of VE) were calculated from the retention/excretion data of six inert gases. Data were obtained during conventional mechanical ventilation and during LVPLV. MEASUREMENTS AND MAIN RESULTS: In group 1, LVPLV increased PaCO(0)rom 38 +/- 6 torr (5.1 +/- 0.8 kPa) to 61 +/- 12 torr (8.1 +/- 1.6 kPa). Qsp/Qt increased from 28 +/- 16% to 36 +/- 17%, whereas Pao2 (84 +/- 15 torr [11.1 +/- 2.0 kPa] vs. 86 +/- 21 torr [11.5 +/- 2.8 kPa]) and Qt (10.6 +/- 2.3 vs. 11.5 +/- 2.5 L x -1) remained unchanged and PVO(2) (40 +/- 4 [5.3 +/- 0.5 kPa] vs. 49 +/- 6 torr [6.5 +/- 0.3]) increased. In group 2, LVPLV increased PaCO(2) from 38 +/- 6 torr (5.1 +/- 0.8 kPa) to 63 +/- 11 torr (8.4 +/- 1.5 kPa). For Qsp/Qt (24 +/- 9% to 34 +/- 16%), the increase was not significant, whereas Qt (7.4 +/- 1.8 vs. 10.2 +/- 2.2 L x -1), PVO(2)(38 +/- 4 torr [5.1 +/- 0.5 kPa] vs. 50 +/- 6 mm Hg [6.7 +/- 0.8 kPa]), and PaO(2) (89 +/- 16 torr [11.9 +/- 2.1 kPa] vs. 98 +/- 19 torr [13.1 +/- 2.5 kPa]) increased. In both groups, the scatter of perfusion distribution (log SDQ) was greater than expected for normal subjects but was not different between the groups or altered by the treatments. CONCLUSIONS: In patients with acute respiratory distress syndrome, LVPLV with permissive hypercapnia, tended to increase Qsp/Qt, without a concomitant decrease of PaO(2). This occurs because, although atelectasis and increased shunt result from the low ventilatory volume, the effects on PaO(2) are offset by increased PVO(2) resulting from the hypercapnic stimulation of cardiac output. This result was independent of the presence or absence of sepsis.     

Time required for equilibration of arterial oxygen pressure after setting optimal positive end-expiratory pressure in acute respiratory distress syndrome

OBJECTIVE: To evaluate the time course of Pao2 change following the setting of optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Twenty-five consecutive patients with ARDS. INTERVENTIONS: ARDS was diagnosed during pressure-regulated volume control ventilation with tidal volume of 7 mL/kg actual body weight, respiratory rate of 12 breaths/min, inspiratory/expiratory ratio of 1:2, Fio2 of 1, and PEEP of 5 cm H2O. A critical care attending physician obtained pressure volume curves and determined the lower inflection point. Following a rest period of 30 mins with initial ventilation variables, PEEP was set at 2 cm H2O above the lower inflection point, and serial blood samples were collected during 1-hr ventilation with optimal PEEP. Arterial blood gas analyses were performed at 1, 3, 5, 7, 9, 11, 15, 20, 30, 45, and 60 mins. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were found eligible for the study. Three patients were excluded due to deterioration of oxygen saturation and hemodynamic instability following the initiation of optimal PEEP. Eight cases (36%) were considered to be of pulmonary origin and 14 cases (64%) of extrapulmonary origin. Optimal PEEP levels were 14 +/- 3 cm H2O and 14 +/- 4 cm H2O in pulmonary and extrapulmonary ARDS, respectively. Pao2 demonstrated a 130 +/- 101% increase at the end of 1-hr period in total study population. This improvement did not differ significantly between pulmonary and extrapulmonary forms of ARDS (135 +/- 118% vs. 127 +/- 95%, p = .8). Mean 90% oxygenation time was found to be 20 +/- 19 mins. In the subset of patients with ARDS of pulmonary origin, 90% oxygenation time was 25 +/- 26 mins, whereas it was 17 +/- 15 mins in patients with ARDS of extrapulmonary origin (p = .8). CONCLUSIONS: Our data showed that 20 mins would be adequate for obtaining a blood gas sample in ARDS patients with pulmonary and extrapulmonary origin after application of optimal PEEP 2 cm H2O above the lower inflection point.     

Physiologic comparison between conventional mechanical ventilation and transtracheal open ventilation in acute traumatic quadriplegic patients

OBJECTIVE: To evaluate the efficacy of mechanical ventilation administered through a small-bore, uncuffed tracheotomy tube, so-called transtracheal open ventilation (TOV), in comparison with conventional mechanical ventilation via a cuffed tracheal tube (endotracheal invasive ventilation, EIV). DESIGN: Physiologic study. SETTING: Intensive care unit of a referral trauma center. PATIENTS: Ten acute quadriplegic patients. INTERVENTIONS: In acute quadriplegic patients receiving EIV, TOV was subsequently applied via an uncuffed, small-bore tube (internal diameter of 4 or 5 mm). MEASUREMENTS AND MAIN RESULTS: Compared with EIV, arterial blood gases were not significantly different after 1 hr of TOV (Pao2/Fio2, 222.8 +/- 60.9 vs. 218.5 +/- 60.3; Paco2, 37.8 +/- 7.1 torr [5.04 +/- 0.95 kPa] vs. 35.5 +/- 6.8 torr [4.73 +/- 0.91 kPa], for EIV and TOV, respectively). Respiratory rate (19.5 +/- 4.7 vs. 19.6 +/- 5 breaths/min) and inspiratory effort (pressure-time product of esophageal pressure during a 1-min period, 125.9 +/- 48.4 vs. 112.8 +/- 36.4 cm H2O.sec.min) were also no different between the two modes. After 24 hrs of TOV, compared with EIV and TOV after 1 hr, respiratory rate and arterial blood gases remained stable, and the pressure-time product of esophageal pressure during a 1-min period was slightly, but significantly, reduced (83.5 +/- 16.6 cm H2O.sec.min, p < .05). CONCLUSIONS: In acute quadriplegic patients receiving mechanical ventilation, TOV was as effective as EIV in providing ventilatory support.