死腔分数导向急性呼吸窘迫综合征呼气末正压选择的临床研究

目的 探讨早期急性呼吸窘迫综合征( ARDS)患者采用死腔分数法选择呼气末正压(PEEP)的可行性.方法 选23例机械通气的早期ARDS患者行持续肺膨胀手法充分肺复张,PEEP递减过程中分别采用最小死腔分数法、最大顺应性法、最佳氧合法选择最佳PEEP,观察不同方法选择的PEEP对患者氧合、解剖死腔容积(VD)/潮气容积(VT)、静态肺顺应性(CLst)和功能残气量(FRC)等的影响.结果 最小死腔分数法[(10.1±2.8)cm H2O(1 cm H2O =0.098 kPa)]和最大顺应性法[(11.3±2.5) cmH2O]选择的最佳PEEP间差异无统计学意义(P＞0.05),均明显低于最佳氧合法[(15.0±3.4) cm H2O,P＜0.05].最小死腔分数法选择PEEP机械通气时患者VD/VT(0.53±0.09)较基础状态(0.59±0.09)明显下降,但最大顺应性法和最佳氧合法选择的PEEP机械通气时VD/VT较基础状态未见明显变化.最小死腔分数法选择的PEEP,其氧合指数明显低于最佳氧合法[(288±123) mm Hg(1 mm Hg=0.133 kPa)比(356±119)mm Hg,P＜0.05],与最大顺应性法相比差异无统计学意义(P＞0.05),均高于基础状态.最小死腔分数法选择PEEP机械通气时气道平台压[(24±4) cm H2O]明显低于最大氧合法[(31±9) cm H2O].最佳氧合法选择的PEEP机械通气时的FRC明显高于最小死腔分数法和最大顺应性法.结论 采用最小死腔分数法选择的最佳PEEP,可改善ARDS患者氧合和CLst,减少死腔通气、降低气道平台压,是床边选择最佳PEEP的可行方法.     

Effect of posture on ventilation and breathing pattern during room air breathing at rest

We measured minute ventilation (VE), tidal volume (VT), mean inspiratory flow (VT/TI), and occlusion pressure (P.1) in 10 resting subjects breathing room air, in sitting, supine, right and left lateral positions, and compared them with corresponding data on static lung compliance [Cst(l)], dynamic lung compliance [Cdyn(l)], and pulmonary flow resistance [R(l)]. Highest values for VT, VE, VT/TI, P.1, and effective inspiratory impedance [P.1/(VT/Ti)] were observed in the supine posture. Values for P.1 and P.1/(VT/TI in lateral decubitus were intermediate to those obtained when seated and supine. While the increases in P.1 and P.1/(VT/TI) in recumbent postures were qualitatively similar to the decrease in Cdyn(l) and increase in R(l), there was no significant correlation between them, probably reflecting the complex relationship between P.1/(VT/TI) and lung compliance and resistance, as the former, in addition to lung mechanics, also depends on the shape of the inspiratory driving pressure wave, the active inspiratory impedance, the mechanics of the chest wall, and the duration of inspiration.     

Acute effects of interleukin-2 on lung mechanics and airway responsiveness in rats

We studied the acute effects of interleukin-2 (IL-2), the principal lymphokine responsible for lymphocyte proliferation, on lung mechanics and airway responsiveness to methacholine (MCh) in rats. Lewis (n = 12) and Fisher 344 (n = 13) rats were anesthetized and intubated, and intravenous and intra-arterial lines were inserted. IL-2 (750,000 U/kg) was infused intravenously over 2 to 4 min into seven Lewis and seven Fisher rats, and vehicle alone was administered to five Lewis and six Fisher rats. Blood pressure, heart rate, respiratory frequency (f), tidal volume (VT), minute ventilation (VE), and lung resistance (RL) were measured before and every 5 min for 45 min after the infusion of IL-2. Lung compliance was measured before and 30 min after IL-2. Bronchial provocation testing with MCh was performed 45 min after the infusion of IL-2. Subsequently, the animals were exsanguinated, and the lungs were removed for histologic examination. Infused IL-2 did not alter heart rate or blood pressure, VT, f, VE, and RL increased significantly by 15 min (p less than 0.05), but they returned to baseline by 45 min. Lung compliance decreased significantly in both rat strains. IL-2 increased airway responsiveness only in Lewis rats; the concentration of MCh that caused a doubling of RL (EC200RL) was 0.6 mg/ml and 4.3 mg/ml (p = 0.003) in IL-2-treated and control rats, respectively. The airway responsiveness did not change significantly in Fisher rats; EC200RL was 0.13 and 0.35 mg/ml for IL-2-treated and control rats, respectively (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of an antiendotoxin antibody in preventing the physiologic changes of endotoxemia in awake sheep

In sheep, endotoxin (LPS) causes pulmonary hypertension, hypoxemia, leukopenia, exudation of protein-rich lung lymph, reduced dynamic compliance (Cdyn), and increased resistance to airflow (RL), changes similar to those seen in human sepsis and sepsis-induced ARDS. We used well-described methods in the awake sheep-endotoxin model to evaluate the effectiveness of a commercially manufactured antibody to prevent the physiologic changes of endotoxemia. In awake sheep with chronic lung lymph fistulas, we used a whole-body plethysmograph to measure Cdyn, RL, and FRC. Pulmonary artery, left atrial, and systemic arterial pressures were recorded continuously. Arterial blood gases (for calculating AaPO2), leukocyte counts, and lymph samples were collected every 30 min. Animals received a 30-min (2 mg/kg) infusion of antiendotoxin antibody 4 h before LPS (0.75 micrograms/kg) challenge (n = 4), or were given a mixture of LPS (0.75 micrograms/kg) and antibody (2 mg/kg) that had been incubated in vitro at 37 degrees C for 30 min before infusion (n = 6). A control group given only 2 mg/kg of antibody (n = 4) showed no change in any measured parameter, whereas control animals receiving LPS alone (n = 6) exhibited a typical endotoxin response. In all animals receiving endotoxin, Cdyn declined by approximately 50% within 30 to 60 min, and RL increased approximately sixfold over a similar time course. Accompanying the abnormalities in lung mechanics were pulmonary hypertension, leukopenia, and widening of the AaPO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory response to positive and negative inspiratory pressure in humans.

To investigate the effect of positive or negative inspiratory pressure on respiration, eight subjects breathed, either without or with added external dead space (VD, 600 ml), through either added inspiratory laminar flow resistances (RES; peak inspiratory airway pressure, Pinsp, down to -9 cmH2O) or with inspiratory pressure support (IPS; Pinsp up to +10 cmH2O). IPS, triggered by the subject's inspiratory effort, provided positive airway pressure throughout inspiration, but allowed for attainment of the subject's own respiratory pattern. The following main results were obtained with IPS or RES relative to the control (no IPS, no RES): (1) with VD, IPS led to small, but significant, increases in tidal volume (VT), respiratory frequency (fR) and ventilation (VE), with no changes in inspiratory time (TI) or duty cycle (TI/TT). Mean inspiratory flow (VT/TI) increased, and mouth occlusion pressure 0.1 sec after onset of inspiration (P0.1) decreased significantly with IPS. The changes during RES were essentially in the opposite direction; (2) without VD, similar, but smaller effects were observed, and only the changes in VT/TI and P0.1 during IPS were significant; (3) highly significant decreases were observed during IPS in end-tidal PCO2 (PETCO2); on the average from 39.6 to 29.2 Torr without VD, and from 45.7 to 39.3 Torr with VD breathing. A small, but significant decrease in PETCO2 occurred also during RES with VD. We conclude that while resistive loading is nearly completely compensated with but small changes in PETCO2, inspiratory pressure support leads to marked hyperventilation, which is not effectively counteracted by central timing commands.     

Mechanics of breathing during strenuous exercise in Thoroughbred horses

The changes induced by exercise on the mechanics of breathing, as well as the simultaneous changes occurring in arterial blood gas tensions and in respiratory gas exchange were investigated in 6 healthy thoroughbred horses, performing a treadmill exercise of increasing intensity. Respiratory airflow and tidal volume (VT) were measured with ultrasonic flowmeters. Pleural pressure changes were measured by an oesophageal balloon catheter. Gas concentration of the expired air was analysed with a mass spectrometer; the oxygen consumption (VO2) and the carbon dioxide output (VCO2) were computed breath-by-breath. Arterial blood gas values were obtained by sampling from the carotid artery. Between rest and fast gallop VT, respiratory frequency, expired minute ventilation (VE), VO2, VCO2, total pulmonary resistance (RL), mechanical work of breathing (Wrm) and PaCO2 increased significantly while PaO2 decreased significantly. The Wrm.VO2(-1) ratio in galloping horses increased exponentially with VE. This, together with the relationship between the changes in PaO2 and in PaCO2 and the increase in the ventilatory mechanics parameters, suggests that the mechanics of breathing may be one of the factors constraining further increase in ventilation in exercising healthy horses.     

Effects of leukotriene E on pulmonary mechanics in the guinea pig

The effects of intravenously infused 5(S)hydroxy-6(R)-S-cysteinyl-7,9,-trans,11,14,-cis eicosatetraenoic acid (leukotriene E) (LTE), one of the leukotriene constituents of slow-reacting substance of anaphylaxis (SRS-A), on pulmonary resistance (RL) and dynamic compliance (Cdyn), breathing frequency, and mean systemic arterial pressure were determined in both anesthetized and unanesthetized guinea pigs. The LTE caused a dose-dependent increase of RL and decrease in Cdyn over the range of doses from 100 to 10,000 ng/kg with significance effects at the highest doses. The onset of effect after a significant dose occurred within 30 s and was maximal 1 to 3 min after infusion. The LTE elicits a significantly greater effect on RL for a given change in Cdyn than occurs with LTC or LTD indicating that LTE is a less selective peripheral airway agonist than LTC or LTD. The LTD infusion resembled LTC or LTD in evoking a systemic arterial hypotension that was preceded by a brief initial period of hypertension in unanesthetized animals.     

无创通气对清醒状态慢性阻塞性肺疾病患者呼吸动力的影响

目的 探讨无创正压通气(NIPPV)对清醒状态慢性阻塞性肺疾病(COPD)患者呼吸动力的影响.方法 选择19例COPD急性加重期住院患者,治疗后病情稳定,通过食道-胃囊管法,检测气道开口压、食道压和胃内压,层流速仪测呼吸流速和容量改变.监测患者在清醒状态下自主呼吸及NIPPV时呼吸动力的变化.结果 ①对呼吸流速和肺通气的影响:吸气峰流速(PIF)、平均吸气流速(VT/Ti)、潮气量(VT)、分钟通气量(VE)在自主呼吸及NIPPV时,两组间变化差异无统计学意义.②对上气道阻力(Rua)和动态肺顺应性(CLdyn)的影响:自主呼吸时Rua(15.07±3.62)cm H2O·L-1·s-1、CLdyn(0.052±0.012)L/cm H2O,与自主呼吸比较,NIPPV时Rua减少6.91%(P＞0.05)、CLdyn增加44.23%(P＞0.05).③对呼吸肌肉活动和呼吸努力的影响:自主呼吸时跨膈压(Pdi)(19.85±4.00)cm H2O、食道负压(Pes)(-13.37±3.77)cm H2O,压力时间乘积(PTP)(287.79±95.14)cm H2O·s/min,与自主呼吸比较,NIPPV时Pdi下降61.96%(P＜0.001),Pes负压减少67.83%(P＜0.001),PTP下降58.80%(P＜0.01).结论 NIPPV对清醒状态COPD患者吸气流速、肺通气量及上气道阻力无明显影响;NIPPV有效的降低了呼吸肌肉活动,减少呼吸努力,改善呼吸肌疲劳.     

Airway responses to aerosolized methacholine and citric acid in ponies with recurrent airway obstruction (heaves)

We measured lung function and airway reactivity in response to methacholine and citric acid administered by aerosol in 2 groups of ponies (principal and control). Principal ponies had a history of heaves, a disease characterized by recurrent airway obstruction. Control ponies had no history of respiratory disease. Both principal and control ponies were paired (principal and control), and measurements were made when principal ponies were in clinical remission (Period A), following barn exposure when principal ponies had acute airway obstruction (Period B), and 1 and 2 wk after they were returned to pasture (Periods C and D). Differences between groups were primarily found at Period B. Barn housing (Period B) decreased dynamic compliance (Cdyn) and increased pulmonary resistance (RL) of principal but not of control ponies. When compared with control ponies at Period B, principal ponies demonstrated airway hyperreactivity. The dose of methacholine required to reduce Cdyn to 65% of baseline (ED65Cdyn) was lower, the change in RL induced by an aerosol of 0.1 mg/ml methacholine (delta RL 0.1) was higher, and the percent change in Cdyn in response to an aerosol of 0.1 mg/ml methacholine (delta %Cdyn 0.1) was larger in principal than in control ponies. A 10-min inhalation of 10% citric acid aerosol did not cause changes in Cdyn in either group of ponies. Control ponies did not increase RL in response to citric acid, whereas at Period B, RL of principal ponies increased following citric acid. We conclude that ponies in clinical remission from heaves are not hyperreactive to aerosols of methacholine or citric acid. Hyperreactivity only exists during acute exacerbations of airway obstruction.     

Mechanisms of late hemodynamic and airway dynamic responses to endotoxin in awake sheep

The mechanism of sustained alterations in pulmonary hemodynamics and lung mechanics after endotoxin infusion in sheep remains unclear. We examined the effects of metaproterenol, propranolol, atropine, and ibuprofen on pulmonary artery pressure (Ppa), dynamic compliance (Cdyn), resistance to airflow across the lungs (RL), specific airway conductance (SGaw), and alveolar-arterial oxygen difference (delta AaPO2) (room air) given 2.5 h after endotoxemia (except for propranolol, which was given 1 h after metaproterenol) in awake sheep. Atropine infusion had no effect on any of the variables measured. Ibuprofen infusion immediately reduced mean Ppa from 31 +/- 2 (mean +/- SEM) to 24 +/- 2 cm H2O (p less than 0.05). Metaproterenol and ibuprofen immediately increased Cdyn and SGaw and decreased RL to near baseline (p less than 0.05). No intervention affected delta AaPO2 (p greater than 0.05). In sheep treated with metaproterenol, propranolol immediately returned lung mechanics (p less than 0.05) to premetaproterenol levels without affecting delta AaPO2 (p greater than 0.05). Ibuprofen reduced lung lymph thromboxane-B2 towards baseline levels (p less than 0.05). We conclude that endotoxemia causes prolonged bronchoconstriction and pulmonary hypertension in sheep, which is largely mediated by constrictor prostanoids rather than by cholinergic mechanisms and is reversible with ibuprofen given 2.5 h after endotoxin.     

Breathing pattern and neuromuscular drive during CO2 rebreathing in normal man and in patients with COPD

In 11 normal subjects and in 10 patients with chronic obstructive pulmonary disease we evaluated breathing pattern and mouth occlusion pressure (PO.1), while breathing room air and during reinhalation of a hypercapnic hyperoxic gas mixture. In the breathing pattern we analyzed the time and volume components of the respiratory cycle: tidal volume (VT), inspiratory time (Ti), expiratory time (Te), total time of respiratory cycle (Ttot); mean inspiratory flow (VT/Ti) and Ti/Ttot ratios, respiratory frequency (RF) and instantaneous ventilation (VE). In the normal subjects, increase in VE during rebreathing mainly depended on an increase in both VT and VT/Ti without significant changes in Ti. During CO2 rebreathing the patients exhibited a lesser increase in VE compared to normals, due to a lesser increase in VT. However, expressing VT in percent of resting inspiratory capacity showed that VT attained at the end of rebreathing (VTmax) was similar to that noted in the normal subjects at the same minute of rebreathing. Furthermore, percent increase in VE, VT, VT/Ti and PO.1 between resting value and that at 56 mm Hg (delta %), were significant in both groups with a major increase in the normal subjects for VE and VT/Ti. In comparison, delta % decreases in both Te and Ttot were found to be significant only in the normal subjects. VT/Ti was related to VE in a similar way in the two groups. In contrast, in the normal subjects, Ti/Ttot did not increase with increasing VE. During rebreathing increase in PO.1 was found to be similar in the normal subjects and in patients. However, for a given neuromuscular drive VE and VT/Ti were greater in the normal subjects than in the patients. These data show that in the patients as a whole no significant changes in breath intervals occur during CO2 rebreathing. Furthermore, in patients, in spite of a similar increase in neuromuscular drive, the efficiency by which inspiratory muscle output (PO.1) is converted into VT/Ti was found to be reduced.     

Dead space ventilation in critically ill children with lung injury

STUDY OBJECTIVE: In children with acute lung injury, there is an increase in minute ventilation (E) and inefficient gas exchange due to a high level of physiologic dead space ventilation (VD/VT). Mechanical ventilation with positive end-expiratory pressure, when used in critically ill patients to correct hypoxemia, may contribute to increased VD/VT. The purpose of this study was to measure metabolic parameters and VD/VT in critically ill children. DESIGN: A cross-sectional study. SETTING: Pediatric ICU of a university hospital. PATIENTS: A total of 45 mechanically intubated children (mean age, 5.5 years). INTERVENTIONS: Indirect calorimetry was used to measure metabolic parameters. VD/VT parameters were calculated using the modified Bohr-Enghoff equation. ARDS was defined based on criteria by The American-European Consensus Conference. Measurements and results: The group mean (+/- SD) ventilatory equivalent for oxygen (VeqO(2)) and ventilatory equivalent for carbon dioxide (VeqCO(2)) were 2.9 +/- 1 and 3.3 +/- 1 L per 100 mL, respectively. The group mean VD/VT was 0.48 +/- 0.2. When compared to non-ARDS patients (33 patients), the patients with ARDS (12 patients) had a significantly higher VeqO(2) (3.3 +/- 1 vs 2.8 +/- 1 L per 100 mL, respectively; p < 0.05), a significantly higher VeqCO(2) (3.7 +/- 1 L/100 vs 3.1 +/- 1 L per 100 mL, respectively; p < 0.05), and a significantly higher VD/VT (0.62 +/- 0.14 vs 0.43 +/- 0.15, respectively; p < 0.0005). CONCLUSIONS: Critically ill children with ARDS have increased VD/VT. Increased VD/VT was the main cause of the excess of E demand in these patients. Increased metabolic demands, as shown by the VeqO(2), VeqCO(2), and ventilatory support, are the major determinants of E requirements in children with ARDS.     

Single breath CO2 measurements of deadspace in ducks

We measured deadspace (VD) in ducks using CO2 expirograms (plots of expired PCO2 vs expired volume) obtained during artificial ventilation at different tidal volumes (VT) and respiratory system volumes (VRS). Conventional analysis of the expirograms for Bohr and Fowler VD indicated both were larger than anatomic VD. Most expirograms at VT less than or equal to 100 ml had terminal slopes greater than predicted for lung gas and violated the usual assumptions of the Fowler calculation. Bohr VD was not affected by VRS but increased with VT. This can be explained by expired PCO2 not reaching lung values at low VT and an expiratory mesobronchial ventilatory shunt. We propose a measure of mesobronchial shunt corresponding to a volume of gas exhaled in one breath from caudal air sacs through the mesobronchus (VM). VM/VT changes with pump vs constant flow ventilation indicating sensitivity of VM to flow pattern. We estimate mesobronchial shunting is greatest at the beginning of expiration and approaches zero only near the end of a 200 ml expiration with constant flow ventilation.     

Differential contribution of dead space ventilation and low arterial pCO2 to exercise hyperpnea in patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

In chronic heart failure (CHF), the abnormally large ventilatory response to exercise (VE/VCO(2) slope) has 2 conceptual elements: the requirement of restraining arterial partial pressure of carbon dioxide (pCO(2)) from increasing (because of an increased ratio between increased physiologic dead space and tidal volume [VD/VT]) and the depression of arterial pCO(2) by further increased ventilation, which necessarily implies an important non-carbon dioxide stimulus to ventilation. We aimed to assess the contribution of these 2 factors in determining the elevated VE/VCO(2) slope in CHF. Thirty patients with CHF underwent cardiopulmonary exercise testing (age 65 +/- 11 years, left ventricular ejection fraction 34 +/- 15%, peak oxygen uptake 15.2 +/- 4 ml/kg/min, VE/VCO(2) slope 36.4). At rest and during exercise, arterial pCO(2) was measured and VD was calculated and separated into serial and alveolar components. VD/VT decreased from 0.57 at rest to 0.44 at peak exercise (p <0.01). VE/VCO(2) slope was correlated with peak exercise VD/VT (r = 0.67), the serial VD/VT ratio (r = 0.64), and alveolar VD/VT ratio (r = 0.51) at peak exercise (all p <0.01). VE/VCO(2) slope was also correlated with arterial pCO(2) (r = -0.75, p <0.001). Despite this, arterial pCO(2) was not related to peak oxygen uptake (r = 0.2) or to arterial lactate (r = -0.25) and only weakly to New York Heart Association functional class (F = 3.7). First, the increased VE/VCO(2) slope was caused by both the high VD/VT ratio and by other mechanisms, as shown by low arterial pCO(2) during exercise. Second, this latter component (depression of arterial pCO(2)) was not related to conventional measures of heart failure severity.     

Volumetric capnography in patients with acute lung injury: effects of positive end-expiratory pressure.

The aim of the study was to analyse the effects of positive end-expiratory pressure (PEEP) on volumetric capnography and respiratory system mechanics in mechanically ventilated patients. Eight normal subjects (control group), nine patients with moderate acute lung injury (ALI group) and eight patients with acute respiratory distress syndrome (ARDS group) were studied. Respiratory system mechanics, alveolar ejection volume as a fraction of tidal volume (VAE/VT), phase III slopes of expired CO2 beyond VAE and Bohr's dead space (VD/VT(Bohr)) at different levels of PEEP were measured. No differences in respiratory system resistances were found between the ALI and ARDS groups. VD/VT(Bohr) and expired CO2 slope beyond VAE were higher in ALI patients (0.52+/-0.01 and 13.9+/-0.7 mmHg x L(-1), respectively) compared with control patients (0.46+/-0.01 and 7.7+/-0.4 mmHg x L(-1), p<0.01, respectively) and in ARDS patients (0.61+/-0.02 and 24.9+/-1.6 mmHg x L(-1), p<0.01, respectively) compared with ALI patients. VAE/VT differed similarly (0.6+/-0.01 in control group, 0.43+/-0.01 in ALI group and 0.31+/-0.01 in ARDS group, p<0.01). PEEP had no effect on VAE/VT, expired CO2 slope beyond VAE and VD/VT(Bohr) in any group. A significant correlation (p<0.01) was found between VAE/VT and expired CO2 slope beyond VAE and lung injury score at zero PEEP. Indices of volumetric capnography are affected by the severity of the lung injury, but are unmodified by the application of positive end-expiratory pressure.     

The respiratory neuromuscular response to hypoxia, hypercapnia, and obstruction to airflow in asthma.

In chronic obstructive pulmonary disease (COPD), the neuromuscular response to an acute increase in airflow produced by external flow resistive loads (FRL) is impaired. The present study compared the response to FRL of 15 subjects with airway obstruction due to asthma and that of 15 normal subjects. FRL were applied during progressive hypercapnia and isocapnic hypoxia produced by rebreathing techniques to permit the response to be assessed at the same degree of CO2 or O2 drive. The neuromuscular response to FRL was assessed from the airway occlusion pressure developed 100 msec after the onset of inspiration (P100), as well as ventilation. During control rebreathing, ventilatory responses to hypercapnia (ratio of change in minute ventilation to change in PCO2, delta VE/delta PCO2) and hypoxia (ratio of change in VE to the change in percentage of O2 saturation, delta VE/deltaSO2) were the same in asthmatic and normal subjects despite differences in the mechanics of breathing. The P100 response to hypercapnia delta P100/delta PCO2) and hypoxia (delta P100/delta SO2) as well as absolute P100 at any given degree of O2 and CO2 drive was greater during control rebreathing in asthmatics than in normal subjects (P less than 0.05). FRL values of 9 and 18 cm H2O per L per sec applied during either hypercapnia or hypoxia increased the occlusion pressure to a greater extent in asthmatics than in normal subjects. Methacholine-induced bronchoconstriction was used to test the effect of acute airway obstruction on the response to FRL. Bronchoconstriction was associated with an increase in the P100 response to hypercapnia and to FRL, despite increases in lung volume and decreases in inspiratory muscle force. We conclude that: (1) asthmatics with airway dysfunction have an increased nonchemical drive to breathe mediated at least in part by sensory receptors in the airways; (2) asthmatics with airway obstruction respond supernormally to acute changes in resistance to airflow, unlike subjects with COPD. The failure of COPD subjects with prolonged airway obstruction to respond to FRL may be due to adaptation of the sensory mechanisms that respond to changes in airway resistance.     

ARDSNet lower tidal volume ventilatory strategy may generate intrinsic positive end-expiratory pressure in patients with acute respiratory distress syndrome

The ARDSNet trial revealed that the use of a smaller tidal volume (VT) reduced mortality by 22%. However, three earlier studies that lowered VT did not find a decrease in mortality. We tested the hypothesis that the increased respiratory rate used in the ARDSNet lower VT strategy might have led to intrinsic positive end-expiratory pressure (PEEP(i)), raising total PEEP (PEEP(total)). Ten patients with acute respiratory distress syndrome (ARDS) were ventilated using the ARDSNet lower VT protocol. Respiratory rate was then reduced (10-15 breaths/minute) to obtain a VT of 12 ml/kg (ARDSNet traditional VT). PEEP on the ventilator (PEEP(nominal): 10.1 +/- 0.7 cm H2O), FIO2 (0.7 +/- 0.1), and minute ventilation (VE: 12.4 +/- 1.7 L/minute) were set using the ARDSNet protocol and maintained constant during the two ventilatory strategies. Values of airway pressure at end-expiration of a regular breath (PEEP(external)) and 3-5 seconds after the onset of an end-expiratory occlusion (PEEP(total)) were measured. PEEP(i) was calculated by subtracting PEEP(external) from PEEP(total). PEEP(total) and PEEP(i) were, respectively, 16.3 +/- 2.9 and 5.8 +/- 3.0 cm H2O during the lower VT strategy and 11.7 +/- 0.9 and 1.4 +/- 1.0 cm H2O during the traditional VT strategy (p < 0.01). The reduced mortality observed with the ARDSNet strategy may have been due to the protective effect of a higher PEEP(total).     

The role of cyclooxygenase products in lung injury induced by tumor necrosis factor in sheep.

Tumor necrosis factor-alpha (TNF alpha) has been proposed as a mediator of endotoxin-induced lung injury. When given to sheep, TNF alpha mimics endotoxin (LPS) causing hypoxemia, pulmonary hypertension, leukopenia, reduced dynamic compliance (Cdyn), increased resistance to airflow (RL), exudation of lung lymph, and enhanced airway reactivity. TNF alpha also induces rapid release of thromboxane A2 (TxA2), prostaglandin E2 (PGE2), and prostacyclin (PGI2). We hypothesized that the inflammatory effects of TNF alpha are due at least in part to cyclooxygenase products, and therefore cyclooxygenase inhibition would have similar effects on TNF alpha-induced lung injury as has previously been demonstrated for LPS-induced lung damage. Using awake sheep with chronic lung lymph fistulas, we measured Cdyn, RL, and FRC using a whole-body plethysmograph. Pulmonary artery (Ppa), left atrial (PLA), and systemic arterial (Psa) pressures were recorded continuously. Arterial blood gases (for calculating AaPO2), leukocyte counts, and lymph samples (for prostanoid levels) were collected every 30 min. Eleven animals underwent paired random-order experiments receiving ibuprofen (14 mg/kg) 1 h before human recombinant TNF alpha (10 micrograms/kg), or an identical dose of TNF alpha alone. Within 15 min of initiating TNF alpha, Ppa doubled and remained elevated for 4 h. Ibuprofen prevented the early rise in Ppa after TNF alpha. In the group receiving TNF alpha alone, increases in Ppa were accompanied by a 60% decline in leukocyte count and a 50% increase in AaPo2 within 30 min. Ibuprofen prevented increases in AaPo2, but it had no effect on leukopenia or late increases in lymph flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altitude, the ratio of PaO2 to fraction of inspired oxygen, and shunt: impact on the assessment of acute lung injury

The ratio of PaO2 to the fraction of inspired oxygen (PaO2/FIO2) is commonly used to determine the severity of acute lung injury and acute respiratory distress syndrome (ARDS). The research presented here used computational models of the lung to analyze the effect of altitude on the PaO2/FIO2 ratio and pulmonary shunt. At a given shunt, the PaO2/FIO2 ratio is lower at higher altitudes. Therefore, when evaluating for ARDS based on a PaO2/FIO2 ratio of <200 mm Hg, patients residing at high altitudes will have less shunt and, presumably, less severe lung injury than patients at sea level. This should be taken into consideration when comparing patients from different altitudes. Shunt should more often be measured directly or be estimated assuming a constant arteriovenous oxygen content difference.     

Physiologic evaluation of pressure support ventilation by nasal mask in patients with stable COPD.

We evaluated the physiologic effects of pressure support ventilation by nasal route (NPSV) in eight patients with severe stable COPD and chronic hypercapnia who were randomly submitted to 2-h sessions of NPSV both with a portable ventilator (Respironics BIPAP device) and with a standard ventilator (Bird 6400ST device) at an inspiratory airway pressure of 22 cm H2O. Two sessions with each ventilator were performed using an FIO2 of 0.21 in each patient on two consecutive days. One patient did not tolerate either form of ventilation. Comparison of spontaneous with BIPAP ventilation showed a significant improvement in pH, PaCO2, and PaO2. Ventilatory pattern assessed by a respiratory inductive plethysmograph showed a significant increase in minute ventilation (VE), VT, and Ttot. Integrated surface diaphragmatic EMG activity measured only during BIPAP device ventilation decreased from that measured during spontaneous breathing. Similar changes in blood gases and ventilatory pattern were observed during ventilation by the Bird 6400ST except for VT/Ti ratio, which significantly increased. Comparison of baseline with measurements performed 12 h after the whole cycle of treatment showed a significant increase in pH and VE and a decrease in PaCO2. We conclude that short-term NPSV may be useful in improving respiratory pattern and blood gases in stable COPD patients with chronic hypercapnia.