There is no cephalocaudal gradient of computed tomography densities or lung behavior in supine patients with acute respiratory distress syndrome.

BACKGROUND: There is debate whether pressure transmission within the lungs and alveolar collapse follow a hydrostatic pattern or the compression exerted by the weight of the heart and the diaphragm causes collapse localized in the areas adjacent to these structures. The second hypothesis proposes the existence of a cephalocaudal gradient in alveolar collapse. We aimed to define whether or not lung density and collapse follow a 'liquid-like' pattern with homogeneous isogravitational layers along the cephalocaudal axis in acute respiratory distress syndrome lungs. METHODS: Acute respiratory distress syndrome patients were submitted to full lung computed tomography scans at positive end-expiratory pressure (PEEP) zero (before) and 25 cmH2 O after a maximum-recruitment maneuver. PEEP was then decreased by 2 cmH2 O every 4 min, and a semi-complete scan performed at the end of each PEEP step. RESULTS: Lung densities were homogeneous within each lung layer. Lung density increased along the ventrodorsal axis toward the dorsal region (ß = 0.49, P < 0.001), while there was no increase, but rather a slight decrease, toward the diaphragm along the cephalocaudal axis and toward the heart. Higher PEEP attenuated density gradients. At PEEP 18 cmH2 O, dependent lung regions started to collapse massively, while best compliance was only reached at a lower PEEP. CONCLUSIONS: We could not detect cephalocaudal gradients in lung densities or in alveolar collapse. Likely, external pressures applied on the lung by the chest wall, organs, and effusions are transmitted throughout the lung in a hydrostatic pattern with homogeneous consequences at each isogravitational layer. A single cross-sectional image of the lung could fully represent the heterogeneous mechanical properties of dependent and non-dependent lung regions.

Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax.

BACKGROUND: Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting. METHODS: Five anesthetized, muscle-relaxed piglets were subjected to first right and then left capnothorax with an intra-pleural pressure of 19 cm H2 O. The contra-lateral lung was mechanically ventilated with a double-lumen tube at positive end-expiratory pressure 5 and subsequently 10 cm H2 O. Regional lung perfusion and ventilation were assessed by EIT. Hemodynamics, cerebral tissue oxygenation and lung gas exchange were also measured. RESULTS: During right-sided capnothorax, mixed venous oxygen saturation (P = 0.018), as well as a tissue oxygenation index (P = 0.038) decreased. There was also an increase in central venous pressure (P = 0.006), and a decrease in mean arterial pressure (P = 0.045) and cardiac output (P = 0.017). During the left-sided capnothorax, the hemodynamic impairment was less than during the right side. EIT revealed that during the first period of OLV/capnothorax, no or very minor ventilation on the right side could be seen (3 ± 3% vs. 97 ± 3%, right vs. left, P = 0.007), perfusion decreased in the non-ventilated and increased in the ventilated lung (18 ± 2% vs. 82 ± 2%, right vs. left, P = 0.03). During the second OLV/capnothorax period, a similar distribution of perfusion was seen in the animals with successful separation (84 ± 4% vs. 16 ± 4%, right vs. left). CONCLUSION: EIT detected in real-time dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation.

Extrapolation from ten sections can make CT-based quantification of lung aeration more practicable.

PURPOSE: Clinical applications of quantitative computed tomography (qCT) in patients with pulmonary opacifications are hindered by the radiation exposure and by the arduous manual image processing. We hypothesized that extrapolation from only ten thoracic CT sections will provide reliable information on the aeration of the entire lung. METHODS: CTs of 72 patients with normal and 85 patients with opacified lungs were studied retrospectively. Volumes and masses of the lung and its differently aerated compartments were obtained from all CT sections. Then only the most cranial and caudal sections and a further eight evenly spaced sections between them were selected. The results from these ten sections were extrapolated to the entire lung. The agreement between both methods was assessed with Bland-Altman plots. RESULTS: Median (range) total lung volume and mass were 3,738 (1,311-6,768) ml and 957 (545-3,019) g, the corresponding bias (limits of agreement) were 26 (-42 to 95) ml and 8 (-21 to 38) g, respectively. The median volumes (range) of differently aerated compartments (percentage of total lung volume) were 1 (0-54)% for the nonaerated, 5 (1-44)% for the poorly aerated, 85 (28-98)% for the normally aerated, and 4 (0-48)% for the hyperaerated subvolume. The agreement between the extrapolated results and those from all CT sections was excellent. All bias values were below 1% of the total lung volume or mass, the limits of agreement never exceeded ± 2%. CONCLUSION: The extrapolation method can reduce radiation exposure and shorten the time required for qCT analysis of lung aeration.

N-terminal-pro-brain natriuretic peptide as a haemodynamic marker in idiopathic pulmonary arterial hypertension.

Patients with idiopathic pulmonary arterial hypertension usually undergo acute vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and therapeutical planning. The aim of this study was to evaluate the link between the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and haemodynamic parameters during the acute vasodilator test. A total of 22 idiopathic pulmonary arterial hypertension patients who underwent acute vasodilator tests were studied. Blood samples were collected at baseline and after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each sample. A receiver-operating characteristic curve was used to evaluate the capability of the NT-pro-BNP level variation during NO inhalation in recognising nonresponders. To distinguish responders from nonresponders, the increase of the NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100% sensitivity (positive predictive value of 38% and a negative predictive value of 100%). These results suggest that N-terminal-pro-brain natriuretic peptide was able to distinguish nonresponder patients with the acute vasodilator test. N-terminal-pro-brain natriuretic peptide may be an interesting additional biological tool in the evaluation of idiopathic pulmonary arterial hypertension patients.

Effects of tracheotomy on respiratory mechanics in spontaneously breathing patients.

Tracheotomy is a method of intubating the trachea, which is employed in several clinical settings, including the treatment of head and neck neoplasms. Tracheotomy is believed to facilitate weaning through changes in respiratory mechanics. Existing information concerning functional changes associated with tracheotomy are limited to comparisons with orotracheal intubation. In this study, respiratory mechanics were monitored in seven spontaneously breathing patients, before and after an elective tracheotomy was performed for surgical treatment of cancer. Campbell diagrams were constructed by plotting pressure, obtained with an oesophageal balloon catheter, against volume, obtained from a pneumotachograph placed at the airway opening. Work of breathing was calculated as the internal area of the Campbell diagram and was partitioned into its elastic and inspiratory and expiratory resistive components. Oesophageal pressure was also used to quantify intrinsic positive end-expiratory pressure (PEEPi) and the pressure-time product (PTP), which is considered to be proportional to the oxygen cost of breathing. PTP was divided into its resistive and elastic components. Inspiratory resistive work, PEEPi, inspiratory PTP, as well as its resistive and elastic components were significantly reduced by tracheotomy. Tracheotomy significantly reduces work of breathing and pressure-time product in spontaneously breathing patients.

Repetitive high-pressure recruitment maneuvers required to maximally recruit lung in a sheep model of acute respiratory distress syndrome.

OBJECTIVE: To compare the effects of two different recruitment maneuvers repeated multiple times on gas exchange lung injury, hemodynamic, and lung mechanics. DESIGN: Randomized prospective comparison. SETTINGS: Animal research laboratory. SUBJECT: Nineteen fasted Hampshire sheep. INTERVENTIONS: In 15 27-kg sheep with saline lavage lung injury, we compared the effects of two recruitment maneuvers: 40 cm H2O continuous positive airway pressure for 60 secs and 40 cm H2O positive end-expiratory pressure with 20 cm H2O pressure control, rate 10 breaths/min, inspiratory to expiratory ratio 1:1 for 2 mins. Each recruitment maneuver was repeated four times, every 30 mins after a 30-sec ventilator disconnection. An additional group received no recruitment maneuvers. Animals were assigned randomly to the three groups and ventilated with 20 cm H2O positive end-expiratory pressure, pressure control 15 cm H2O, rate 20 breaths/min, inspiratory to expiratory ratio 1:1, and Fio2 1.0 between recruitment maneuver periods. MEASUREMENTS AND MAIN RESULTS: Significant and marked increases in Pao2 were observed in the pressure control recruitment maneuver group but only after the second recruitment maneuver. In both the control group and continuous positive airway pressure groups, Pao2 did not significantly increase after any recruitment maneuver compared with baseline injury. There was a significant decrease in cardiac output immediately after some continuous positive airway pressure recruitment maneuvers and a significant increase in mean pulmonary artery pressure in both continuous positive airway pressure and pressure control groups immediately after recruitment maneuvers, but these changes resolved within 10 mins. There were no marked histologic differences between groups and no volutrauma. CONCLUSION: In this model, maximal lung recruitment was obtained with 40 cm H2O positive end-expiratory pressure and 20 cm H2O pressure control applied repetitively every 30 mins for 2 mins without physiologic or histologic harm. Multiple recruitment maneuvers in some animals were required for maximum effect.

Automation of expiratory trigger sensitivity in pressure support ventilation.

Patients under pressure support ventilation sometimes encounter patient-ventilator asynchrony in the transition from inspiration to expiration, that is, expiratory asynchrony. This problem is caused by the incompatibility of the fixed level of expiratory trigger sensitivity termination criteria (i.e., flow termination criteria) in the ICU ventilators to various patient conditions. The user-adjustable expiratory trigger sensitivity implemented in some newly released ventilators has been experienced to be difficult to use and unable to adapt ever-changing patient conditions without user intervention, although it provides more flexibility. This article elucidates the rationale for automatic control of the expiratory trigger sensitivity and evaluates the automation system with a bench setup. The evaluation data suggest that good expiratory synchronies can be achieved through automatic adjustments of expiratory trigger sensitivity.

Different low constant flows can equally determine the lower inflection point in acute respiratory distress syndrome patients.

Among the possible techniques to obtain the pressure-volume (P x V) curve at the bedside the low constant flow (CF) is the easiest and quickest one. However, the best value for CF to perform a good semi-static P x V curve is still to be determined. The purpose of this study was to evaluate the influence of 4 different CFs (1, 2, 5, and 10 L/min) on determination of lower inflection point of the P x V curve (L-Pflex) and upper inflection point of the P x V curve (U-Pflex) on the maximum slope and on the inspiratory work of breathing (up to volume of 1.35 L; inspiratory work L/cm H2O), comparing the volume estimated from the CF with the measured volume obtained by the respiratory inductive plethysmograph. The design was a prospective study, and the setting was an adult medical intensive care unit of a university hospital. There were 7 acute respiratory distress syndrome (ARDS) patients, less than 5 days of installation, after the standardization of lung volume history received sequentially from 4 different low inspiratory CFs in 2 trials. The P x V curve lasted from 73 +/- 1.6 s (1 L/min) to 8.8 +/- 0.69 s (10 L/min). The L-Pflex differed in the 2 performed trials (p = 0.04). There was no difference of L-Pflex among the 4 CFs comparing the 3 methods (p = 0.072) used for its calculation as well as comparing the estimated and the measured volume (p = 0.456). The maximum slope decreased significantly while increasing the flow from 1 to 10 L/min just in the estimated volume (p = 0.03). The inspiratory work did not increase with the increment of the flow either in the estimated volume (p = 0.217) or in the measured volume (p = 0.149). The U-Pflex differed among the trials (p = 0.003) and the methods used for its calculation (p < 0.01). Constant flows from 1 to 10 L/min can equally determine L-Pflex in ARDS patients and is an easy and quick way to obtain the L-Pflex in order to optimize positive end expiratory pressure (PEEP) in ARDS patients.

Mask mechanics and leak dynamics during noninvasive pressure support ventilation: a bench study.

OBJECTIVE: To study the mask mechanics and air leak dynamics during noninvasive pressure support ventilation. SETTING: Laboratory of a university hospital. DESIGN: A facial mask was connected to a mannequin head that was part of a mechanical respiratory system model. The mask fit pressure (P(mask-fit)) measured inside the mask's pneumatic cushion was adjusted to 25 cmH(2)O using elastic straps. Pressure support (PS) was set to ensure a maximal tidal volume distal to the mask (VT(distal)) but avoiding failure to cycle to exhalation. MEASUREMENTS: Airway pressure (P(aw)), P(mask-fit), mask occlusion pressure (P(mask-occl)=P(mask-fit)-P(aw)), VT proximal (VT(prox)), distal to the mask (VT(distal)), air leak volume ( Leak=VT(prox)-VT(distal)), and inspiratory air leak flow rate (difference between inspiratory flow proximal and distal to the mask) were recorded. RESULTS: PS 15 cmH(2)O was the highest level that could be used without failure to cycle to exhalation (VT(distal) of 585+/-4 ml, leak of 32+/-1 ml or 5.2+/-0.2% of VT(prox), and a minimum P(mask-occl) of 1.7+/-0.1 cmH(2)O). During PS 16 cmH(2)O the P(mask-occl) dropped to 1.1+/-0.1 cmH(2)O, and at this point all flow delivered by the ventilator leaked around the mask, preventing the inspiratory flow delivered by the ventilator from reaching the expiratory trigger threshold. CONCLUSION: P(mask-fit) and P(mask-occl) can be easily measured in pneumatic cushioned masks and the data obtained may be useful to guide mask fit and inspiratory pressure set during noninvasive positive pressure ventilation.

Use of recruitment maneuvers and high-positive end-expiratory pressure in a patient with acute respiratory distress syndrome.

OBJECTIVE: To present the use of a novel high-pressure recruitment maneuver followed by high levels of positive end-expiratory pressure in a patient with the acute respiratory distress syndrome (ARDS). DESIGN: Observations in one patient. SETTING: The medical intensive care unit at a tertiary care university teaching hospital. PATIENT: A 32-yr-old woman with severe ARDS secondary to streptococcal sepsis. INTERVENTIONS: The patient had severe gas exchange abnormalities because of acute lung injury and marked lung collapse. Attempts to optimize recruitment based on the inflation pressure-volume (PV) curve were not sufficient to avoid dependent lung collapse. We used a recruitment maneuver using 40 cm H2O of positive end-expiratory pressure (PEEP) and 20 cm H2O of pressure controlled ventilation above PEEP for 2 mins to successfully recruit the lung. The recruitment was maintained with 25 cm H2O of PEEP, which was much higher than the PEEP predicted by the lower inflection point (P(Flex)) of the PV curve. MEASUREMENTS AND MAIN RESULTS: Recruitment was assessed by improvements in oxygenation and by computed tomography of the chest. With the recruitment maneuvers, the patient had a dramatic improvement in gas exchange and we were able to demonstrate nearly complete recruitment of the lung by computed tomography. A PV curve was measured that demonstrated a P(Flex) of 16-18 cm H2O. CONCLUSION: Accumulating data suggest that the maximization and maintenance of lung recruitment may reduce lung parenchymal injury from positive pressure ventilation in ARDS. We demonstrate that in this case PEEP alone was not adequate to recruit the injured lung and that a high-pressure recruitment maneuver was required. After recruitment, high-level PEEP was needed to prevent derecruitment and this level of PEEP was not adequately predicted by the P(Flex) of the PV curve.

Regional pressure volume curves by electrical impedance tomography in a model of acute lung injury.

OBJECTIVE: A new noninvasive method, electrical impedance tomography (EIT), was used to make pressure-impedance (PI) curves in a lung lavage model of acute lung injury in pigs. The lower inflection point (LIP) and the upper deflection point (UDP) were determined from these curves and from the traditional pressure-volume (PV) curves to determine whether the PI curves resemble the traditional PV curves. Furthermore, regional differences in the mentioned determinants were investigated. DESIGN: Prospective, experimental study. SETTING: Animal research laboratory. INTERVENTIONS: In nine anesthetized pigs, repeated lung lavage was performed until a Pao2 <80 torr was reached. Thereafter, an inspiratory PV curve was made using a constant flow of oxygen. During the intervention, EIT measurements were performed. MEASUREMENTS AND MAIN RESULTS: In this study, the LIP(EIT) was within 2 cm H2O of the LIP(PV). Furthermore, it was possible to visualize regional PI curves by EIT. No significant difference was found between the LIP(PV) (21.3+/-3.0 cm H2O) and the LIP(EIT) of the total lung (21.5+/-3.0 cm H2O) or the anterior parts of the lung (21.5+/-2.9 cm H2O). A significantly higher LIP (29.5+/-4.9 cm H2O) was found in the posterior parts of the lung. A UDP(PV) could be found in three animals only, whereas in all animals a UDP(EIT) could be determined from the anterior part of the lung. CONCLUSIONS: Using EIT, determination of LIP and UDP from the regional PI curves is possible. The obtained information from the regional PI curves may help in understanding alveolar recruitment. The use of this new bedside technique for clinical decision making remains to be examined.

Interação cardiopulmonar durante a ventilação mecânica / Cardiopulmonary interaction during mechanical ventilation

As interaçöes cardiopulmonares durante a ventilação mecânica são complexas e dependem do estado volêmico do paciente (hipovolemia, normovolemia e hipervolemia), das funçöes dos ventrículos direito e esquerdo, assim como de sua pós-carga, do estado funcional dos pulmöes (normal, restritivo, ou obstrutivo) e da complacência do sistema toracoabdominal. Nos estados hipovolêmicos, a adição de pressão positiva intratorácica prporciona diminuição do retorno venoso e conseqüente dominuição do débito cardíaco. Esse efeito encontr-se exacerbado nas disfunçöes do ventrículo direito presentes no tromboembolismo pulmonar e na doença pulmonar obstrutiva crônica e, em menor grau, do ventrículo esquerdo. Nos estados de hipervolemia, a pré-carga de ambos os ventrículos está aumentada. Quando a pressão capilar pulmonar ultrapassa 18 mmHg em pulmöes normais ocorre o extravasamento de líquido para o interstício pulmonar e interior dos alvéolos. Esse efeito está exacerbado nas alteraçöes de permeabilidade da membrana alveolocapilar (síndrome do desconforto respiratório agudo). Nos estados hipervolêmicos, a adição de pressão intratorácica positiva não costuma ocasionar a diminuição do débito cardíaco. Nas disfunçöes de ventrículo esquerdo com pressão capilar acima de 18 mmHg, a adição de pressão intratorácica positiva mantém os alvéolos abertos, melhorando a oxigenação e diminuição a pós-carga do ventrículo esquerdo, o que proporciona a melhora do desempenho ventricular. Assim observando-se e compreendendo-se essas complexas interaçöes cardiopulmonares, poderemos otimizar as condiçöes cardiorrespiratórias nas diferentes situaçöes clínicas.

Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.

BACKGROUND: In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. METHODS: We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve, a tidal volume of less than 6 ml per kilogram, driving pressures of less than 20 cm of water above the PEEP value, permissive hypercapnia, and preferential use of pressure-limited ventilatory modes. RESULTS: After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group (P=0.005): the rates of clinical barotrauma were 7 percent and 42 percent, respectively (P=0.02), despite the use of higher PEEP and mean airway pressures in the protective-ventilation group. The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P=0.37). CONCLUSIONS: As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge.

Temporal hemodynamic effects of permissive hypercapnia associated with ideal PEEP in ARDS.

The associated use of permissive hypercapnia (PHY) and high PEEP levels (PEEP(IDEAL)) has been recently indicated as part of a lung-protective-approach (LPA) in acute respiratory distress syndrome (ARDS). However, the net hemodynamic effect produced by this association is not known. We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients (mean age 34 +/- 13 yr) with ARDS, focusing on its immediate (after 1 h), early (first 36 h), and late (2nd-7th d) consequences. Twenty-five patients were submitted to LPA--with the combined use of permissive hypercapnia (PHY), VT < 6 ml/kg, distending pressures above PEEP < 20 cm H2O, and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve (P(FLEX))- and 23 control patients were submitted to conventional mechanical ventilation. LPA was initiated at once, resulting in an immediate increase in heart rate (p = 0.0002), cardiac output (p = 0.0002), oxygen delivery (DO2l, p = 0.0003), and mixed venous Po2 (p = 0.0006), with a maintained systemic oxygen consumption (p = 0.52). The mean pulmonary arterial pressure markedly increased (mean increment 8.8 mm Hg; p < 0.0001), but the pulmonary vascular resistance did not change (p = 0.32). Cardiac filling pressures increased (p < 0.001) and the systemic vascular resistance fell (p = 0.003). All these alterations were progressively attenuated in the course of the first 36 h, despite persisting hypercapnia. Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients (p < 0.0001). No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved. A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis, with no depressant effects ascribed to high PEEP levels. In contrast, high plateau pressures were associated with cardiovascular depression. Thus, as long as sufficiently low distending pressures are concomitantly applied, the sudden installation of PHY plus PEEP(IDEAL) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population.

Chronic amiodarone ingestion induces pulmonary toxicity in rats.

Patients who receive amiodarone may develop interstitial pulmonary disease. The objective of the present study was to develop an experimental model of interstitial pulmonary disease in rats based on the chronic oral administration of amiodarone diluted in water ad libitum. A total of 97 three-month old male Wistar rats weighing 133-167 g (control and intoxicated) were studied after daily administration of amiodarone (about 50 mg/kg) for 3 weeks and 3, 6, and 13 months. We carried out conventional histopathologic evaluation, morphometric studies of the alveolar wall, transmission electron microscopy, measurement of pulmonary volumes and forced expiratory flows, and computed respiratory system resistance and elastance during spontaneous breath cycles. Chronic ingestion of amiodarone by rats produced pulmonary disease that started as a phospholipidosis, as early as 3 weeks after the use of the drug. After 6, and mainly after 13 months, a focal inflammatory reaction with reactive alveolar epithelium was observed. Signals of a concomitant repair process were also present, but fibrosis was visible only by electron microscopy. The physiologic dysfunction could be identified after 13 months; expiratory flow (ml/sec) limitation and an increased respiratory system elastance (cmH2O/ml) were the main functional changes, respectively 10.8 (forced expiratory mean flow between 0-25% of forced vital capacity) and 5.36 in treated animals vs 13.3 and 3.65 in controls, reported as mean +/- SD for 6 animals in each group. A body of evidence suggests that amiodarone may cause changes in lung phospholipid metabolism that may be responsible for a part of the functional derangement observed in this study.

Chronic amiodarone ingestion induces pulmonary toxicity in rats

Patients who receive amiodarone may develop interstitial pulmonary disease. The objective of the present study was to develop an experimental model of interstitial pulmonary disease in rats based on the chronic oral administration of amiodarone diluted in water ad libitum. A total of 97 three-month old male. Wistar rats weighing 133-167g (control and intoxicated) were studied after daily administration of amiodarone (about 50 mg/Kg) for 3 weeks and 3,6, and 13 months. We carried out conventional histopathologic evaluation, morphometric studies of the alveolar wall, transmission electron microscopy measurement of pulmonary volumes and forced expiratory flows, and computed respiratory system resistance and elastance during spontaneous breath cycles. Chronic ingestion of amiodarone by rats produced pulmonary disease that started as a phospholipidosis, as early 3 weeks after the use of the drug. After 6, and mainly after 13 months, a focal inflammatory reation with reactive alveolar epithelium was observed . Signals of a comcomitant repair process were also present, but fibrosis was visible only by electron microscopy. The physiologic dysfunction could be identified after 13 months; expiratory flow (ml/sec) limitation and an increased respiratory system elastance (cmH2O/ml) were the main functional changes, respectively 10.8 (forced expiratory mean flow between 0-25 per cent of forced vital capacity) and 5.36 in treated animals vs 13.3 and 3.65 in controls, reported as mean + SD for 6 animals in each group. A body of evidence suggests that amiodarone may cause changes in lung phospholipid metabolism that may be responsible for a part of the functional derangement observed in this study.

Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation.

Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals submitted to artificial ventilation. To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome (ARDS) submitted to conventional mechanical ventilation (MV), we evaluated the impact of a new ventilatory strategy directed at minimizing "cyclic parenchymal stretch." After receiving pre-established levels of hemodynamic, infectious, and general care, 28 patients with early ARDS were randomly assigned to receive either MV based on a new approach (NA, consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve, VT < 6 ml/kg, peak pressures < 40 cm H2O, permissive hypercapnia, and stepwise utilization of pressure-limited modes) or a conventional approach (C = conventional volume-cycled ventilation, VT = 12 ml/kg, minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels). Fifteen patients were selected to receive NA, exhibiting a better evolution of the PaO2/FIO2 ratio (p < 0.0001) and of compliance (p = 0.0018), requiring shorter periods under FIO2 > 50% (p = 0.001) and a lower FIO2 at the day of death (p = 0.0002). After correcting for baseline imbalances in APACHE II, we observed a higher weaning rate in NA (p = 0.014) but not a significantly improved survival (overall mortality: 5/15 in NA versus 7/13 in C, p = 0.45). We concluded that the NA ventilatory strategy can markedly improve the lung function in patients with ARDS, increasing the chances of early weaning and lung recovery during mechanical ventilation.

Volume-assured pressure support ventilation (VAPSV). A new approach for reducing muscle workload during acute respiratory failure.

This study reports the preliminary clinical evaluation of a new mode of ventilation--volume-assured pressure support ventilation (VAPSV)--which incorporates inspiratory pressure support (PSV) with conventional volume-assisted cycles (VAV). This combination optimizes the inspiratory flow during assisted/controlled cycles, reducing the patient's respiratory burden commonly observed during VAV. Different from conventional PSV, VAPSV assures precise control of tidal volume (VT) in unstable patients. Eight patients with acute respiratory failure (ARF) were submitted to assisted ventilation under VAV and VAPSV. Patient's ventilatory workload (evaluated through the pressure-time product, mechanical work per liter of ventilation, and work per minute) and patient's ventilatory drive (occlusion pressure--P0.1) were significantly reduced during VAPSV. This "relief" was more evident among the most distressed patients (p < 0.001), allowing a reduction of more than 60 percent in muscle load, without the need of increasing peak tracheal pressure. Mean inspiratory flow (VT/TI), VT, and effective dynamic compliance were significantly increased during VAPSV, whereas the effective inspiratory impedance decreased. These mechanical advantages of VAPSV allowed a reduction of intrinsic PEEP, whenever it was present. Blood gas values were similar in both periods. We concluded that VAPSV is a promising form of ventilatory support. At the same time that it was able to safely assure a minimum preset VT, VAPSV reduced patient workload and improved synchrony between the patient and the ventilator during ARF.

Estenose bronquica de etiologia tuberculosa: patogenia e tratamento / Bronchial stenosis of tuberculous etiology: pathogenesis and treatment

Descrevemos quatro casos de estenose bronquica, uma complicacao rara de tuberculose pulmonar. No primeiro caso, uma mulher de 18 anos, sem tratamento previo para tuberculose, apresentou estenose bronquica como resultado da cicatrizacao de complexo primario. Nao havia lesao de parenquima ao raio X. Nos outros tres pacientes a estenose bronquica foi atribuida a tuberculose ativa com pesquisa positiva para bacilo alcool-acido resistente em escarro. Estes receberam tratamento para tuberculose. Em um deles isto foi suficiente para a resolucao da estenose, mas nos outros dois pacientes ocorreu estenose bronquica devido a fibrose.