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L Gattinoni

Publications and source records attributed to L Gattinoni.

At least 37 records · Page 2Linked to original sources

Recruitment and derecruitment during acute respiratory failure: a clinical study.

In a model of acute lung injury, we showed that positive end-expiratory pressure (PEEP) and tidal volume (VT) are interactive variables that determine the extent of lung recruitment, that recruitment occurs across the entire range of total lung capacity, and that superimposed pressure is a key determinant of lung collapse. Aiming to verify if the same rules apply in a clinical setting, we randomly ventilated five ALI/ARDS patients with 10, 15, 20, 30, 35, and 45 cm H2O plateau pressure and 5, 10, 15, and 20 cm H2O of PEEP. For each PEEP-VT condition, we obtained computed tomography at end inspiration and end expiration. We found that recruitment occurred along the entire volume-pressure curve, independent of lower and upper inflection points, and that estimated threshold opening pressures were normally distributed (mode = 20 cm H2O). Recruitment occurred progressively from nondependent to dependent lung regions. Overstretching was not associated with hyperinflation. Derecruitment did not parallel deflation, and estimated threshold closing pressures were normally distributed (mode = 5 cm H2O). End-inspiratory and end-expiratory collapse were correlated, suggesting a plateau-PEEP interaction. When superimposed gravitational pressure exceeded PEEP, end-expiratory collapse increased. We concluded that the rules governing recruitment and derecruitment equally apply in an oleic acid model and in human ALI/ARDS.

Adult↗

Pulmonary and extrapulmonary forms of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults. However, the distinction between ARDS due to a direct (ARDSp) versus an indirect (ARDSexp) lung injury is gaining more attention as a means of better comprehending the pathophysiology of ARDS and for modifying ventilatory management. From the few published studies, we can summarize that: (1) the prevalent damage in early stages of a direct insult is intra-alveolar, whereas in indirect injury it is the interstitial edema. It is possible that the two insults may coexist (i.e., one lung with direct injury (as in pneumonia) and the other with indirect injury, through mediator release from the contralateral pneumonia); (2) the radiological pattern, by chest x-ray or computed tomography (CT), is different in ARDSp (characterized by prominent consolidation) and ARDSexp (characterized by prominent ground-glass opacification); (3) in ARDSp lung elastance is more markedly increased than in ARDSexp, where the main abnormality is the increase in chest wall elastance, due to abnormally high intra-abdominal pressure; (4) positive end-expiratory pressure (PEEP), inspiratory recruitment, and prone position are more effective to improve respiratory mechanics, alveolar recruitment, and gas-exchange in ARDSexp. Further studies are warranted to better define if the distinction between ARDS of different origins can improve clinical management and survival.

Journal Article↗

Effects of different continuous positive airway pressure devices and periodic hyperinflations on respiratory function.

OBJECTIVE: To compare the effect on respiratory function of different continuous positive airway pressure systems and periodic hyperinflations in patients with respiratory failure. DESIGN: Prospective SETTING: Hospital intensive care unit. PATIENTS: Sixteen intubated patients (eight men and eight women, age 54 +/- 18 yrs, PaO2/FiO2 277 +/- 58 torr, positive end-expiratory pressure 6.2 +/- 2.0 cm H2O). INTERVENTIONS: We evaluated continuous flow positive airway pressure systems with high or low flow plus a reservoir bag equipped with spring-loaded mechanical or underwater seal positive end-expiratory pressure valve and a continuous positive airway pressure by a Servo 300 C ventilator with or without periodic hyperinflations (three assisted breaths per minute with constant inspiratory pressure of 30 cm H2O over positive end-expiratory pressure). MEASUREMENTS AND MAIN RESULTS: We measured the respiratory pattern, work of breathing, dyspnea sensation, end-expiratory lung volume, and gas exchange. We found the following: a) Work of breathing and gas exchange were comparable between continuous flow systems; b) the ventilator continuous positive airway pressure was not different compared with continuous flow systems; and c) continuous positive airway pressure with periodic hyperinflations reduced work of breathing (10.7 +/- 9.5 vs. 6.3 +/- 5.7 J/min, p <.05) and dyspnea sensation (1.6 +/- 1.2 vs. 1.1 +/- 0.8 cm, p <.05) increased end-expiratory lung volume (1.6 +/- 0.8 vs. 2.0 +/- 0.9 L, p <.05) and PaO2 (100 +/- 21 vs. 120 +/- 25 torr, p <.05) compared with ventilator continuous positive airway pressure. CONCLUSIONS: The continuous flow positive airway pressure systems tested are equally efficient; a ventilator can provide satisfactory continuous positive airway pressure; and the use of periodic hyperinflations during continuous positive airway pressure can improve respiratory function and reduce the work of breathing.

Adult↗

Estimation of end-expiratory lung volume variations by optoelectronic plethysmography.

OBJECTIVE: To test the capability of optoelectronic plethysmography (OEP) to monitor positive end-expiratory pressure (PEEP)-induced changes of end-expiratory lung volume (EELV) changes in mechanically ventilated paralyzed patients. DESIGN: Laboratory and clinical investigation. SETTING: Intensive care unit of the Ospedale Maggiore Policlinico di Milano. PATIENTS: A total of eight patients with respiratory failure of various degrees, sedated and paralyzed. INTERVENTIONS: PEEP variations (+/-5 cm H2O) relative to the baseline PEEP of 10 cm H2O. MEASUREMENTS AND MAIN RESULTS: In the model protocol, we tested the reproducibility of the OEP by repeating volume measurements of a plastic torso model over a 21-hr period, every 30 mins. The variations of OEP measurements of the torso model (9337 mL value) were encountered in a range of 16 mL (sd = 4 mL). In the patient protocol, we measured the end-expiratory volume of the chest wall (EEVCW) breath-by-breath by OEP before, during, and after the PEEP increase/decrease and we compared its variations with the corresponding variations of EELV measured by helium dilution technique. The regression line between EELV changes measured by helium and EEVCW changes measured by OEP resulted very close to the identity line (slope 1.06, intercept -0.02 L, r(2) = 0.89) and their difference was not related to their absolute magnitude. After PEEP increase, the new steady state of EEVCW was reached approximately in 15 breaths; and, after PEEP decrease, in 3-4 breaths. The slow increase in EEVCW was mainly because of the abdominal compartment. CONCLUSION: OEP measurements of EEVCW accurately reflect the changes of EELV. Furthermore, OEP allows a continuous compartmental analysis, even during unsteady conditions.

Adult↗

The effects of pressurization rate on breathing pattern, work of breathing, gas exchange and patient comfort in pressure support ventilation.

The aim of this study was to investigate the effects of different pressurization rates during pressure support ventilation on breathing pattern, work of breathing, gas exchange and patient comfort in patients with acute lung injury. The pressurization rate modifies the initial pressure ramp by changing the initial peak flow rate: the increase in pressurization rate is associated with a decrease in the time to reach the level of pressure support ventilation by increasing the peak flow rate. Ten intubated patients (age 64+/-17 yrs, body mass index 24+/-17 Kg x m(-2), arterial oxygen tension/inspired oxygen fraction 214+/-59) were studied in random order varying the pressurization rate at 5 and 15 cmH2O of pressure support ventilation. Breathing comfort was evaluated by a visual analogue scale. Increasing the pressurization rate caused an increase of peak flow rate from 473+/-141 mL x s(-1) to 758+/-302 mL x s(-1) at pressure support ventilation 5 (p<0.05) and from 481+/-126 mL x s(-1) to 1,121+/-175 mL x s(-1) at pressure support ventilation 15 (p<0.05). At the lowest pressurization rate the tidal volume was the lowest, the respiratory rate and the work of breathing were the highest (p<0.05) compared with other pressurization rates. Excluding the lowest pressurization rate, in all the other pressurization rates tested the breathing pattern and the work of breathing did not change. The lowest and the highest pressurization rates caused the worst patient comfort (p<0.05). The gas exchange was stable throughout the study. The presented results suggest: 1) the lowest pressurization rate caused the lowest tidal volume, highest respiratory rate and highest work of breathing; 2) at the other pressurization rates no differences in breathing pattern and work of breathing were observed; and 3) the patient's comfort was worse at the lowest and highest pressurization rates.

Adult↗

Identification of tumor antigen-specific cytotoxic T lymphocytes cross-recognizing allogeneic major histocompatibility class I molecules.

Adoptive immunotherapy of cancer utilizes tumor antigen-specific cytotoxic T lymphocytes (CTL) as mediators of a targeted anti-tumor effect. In this study, we show that such CTL can be able to cross-recognize allogeneic major histocompatibility complex (MHC) molecules in a phenomenon of molecular mimicry. A self histo-leukocyte antigen (HLA) A*0201-restricted CTL specific for peptide MT27-35 from the human differentiation antigen Melan-A/MART-1 was shown to cross-recognize allogeneic A*0220 molecules which differ from syngeneic A*0201 for a single amino acid substitution at position 66 of the antigen-binding groove. A*0220 molecules were recognized on a variety of human cells of different histological origin but not on COS-7 cells. A second self-A*0201-restricted CTL, specific for peptide D10/6-271 encoded by the tumor-specific DAM-gene family, was shown to cross-recognize allogeneic B*3701 molecules which differ from syngeneic A*0201 by 32 amino acids in the peptide antigen-binding cleft. B*3701 molecules were recognized on a variety of cell types including COS-7 cells. These data raise new safety issues for clinical trials of cancer immunotherapy using adoptive transfer of in vitro generated, allogeneic CTL with specific anti-tumor activity.

Antigens, Neoplasm↗

Plasma concentrations and anti-L-cytokine effects of alpha-melanocyte stimulating hormone in septic patients.

OBJECTIVES: The aim of this research was to investigate endogenous concentrations and anti-cytokine effects of the antiinflammatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) in patients with systemic inflammation. The objectives were to determine the following: changes over time of plasma alpha-MSH and relationship with patient outcome, correlation between plasma alpha-MSH and tumor necrosis factor (TNF)-alpha plasma concentration and production in whole blood samples, and influences of alpha-MSH on production of TNF-alpha and interleukin (IL)-1beta in whole blood samples stimulated with lipopolysaccharide (LPS). DESIGN: Prospective, nonrandomized, clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS: A total of 21 patients with sepsis syndrome/septic shock and an equal number of healthy volunteers. INTERVENTIONS: Circulating alpha-MSH and TNF-alpha concentrations and TNF-alpha production in supernatants of LPS (1 ng/mL)-stimulated whole blood were measured repeatedly. To determine whether alpha-MSH can modulate production of TNF-alpha and IL-1 beta, these cytokines were measured in whole blood samples stimulated with LPS (1 ng/mL) in the presence or absence of concentrations of the peptide. MEASUREMENTS AND MAIN RESULTS: Plasma alpha-MSH was low in early samples and gradually increased in patients who recovered but not in those who died. There was a negative correlation between plasma concentrations of alpha-MSH and TNF-alpha. In blood samples taken at early phases of sepsis syndrome, production of TNF-alpha was reduced relative to control values; such production increased in patients who recovered but not in those who died. Addition of alpha-MSH to LPS-stimulated whole blood samples inhibited production of TNF-alpha and IL-1beta in a concentration-dependent manner. CONCLUSIONS: In patients with systemic inflammation, there are substantial changes over time in plasma concentrations of alpha-MSH that are reduced in early phases of the disease. Reduction of this endogenous modulator of inflammation could be detrimental to the host. Addition of alpha-MSH to LPS-stimulated blood samples reduces production of cytokines involved in development of septic syndrome. This inhibition by alpha-MSH, a peptide that is beneficial in treatment of experimental models of sepsis, might therefore be useful to treat sepsis syndrome in humans.

Adult↗

An improved in vivo rat model for the study of mechanical ventilatory support effects on organs distal to the lung.

OBJECTIVE: To study the influence of different mechanical ventilatory support strategies on organs distal to the lung, we developed an in vivo rat model, in which the effects of different tidal volume values can be studied while maintaining other indexes. DESIGN: Prospective, randomized animal laboratory investigation. SETTING: University laboratory of Ospedale Maggiore di Milano-Instituto di Ricovero e Cura a Carattere Scientifico. SUBJECTS: Anesthetized, paralyzed, and mechanically ventilated male Sprague-Dawley rats. INTERVENTIONS: Two groups of seven rats each were randomized to receive tidal volumes of either 25% or 75% of inspiratory capacity (IC), calculated from a preliminary estimation of total lung capacity. Ventilation strategies for the two groups were as follows: a) 25% IC, 9.9+/-0.8 mL/kg; frequency, 59+/-4 beats/min; positive end-expiratory pressure, 3.6+/-0.8 cm H2O; and peak inspiratory airway pressure (Paw), 13.2+/-2 cm H20; and b) 75% IC, 29.8+/-2.9; frequency, 23+/-13; positive end-expiratory pressure, 0; peak inspiratory Paw, 29.0+/-3. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (invasively monitored) remained well above adequate perfusion pressure values throughout, and no significant difference was seen between the two groups. PaO2, pHa, and PaCO2 values were compared after 60 mins of ventilation and again, no significant difference was seen between the two groups (PaO2, 269+/-25 and 260+/-55 torr; pHa, 7.432+/-0.09 and 7.415+/-0.03; PaCO2, 35.4+/-8 and 32.5+/-2 torr, for the 25% IC and 75% IC groups, respectively). Mean Paws were not different (6.4+/-0.8 cm H2O in the 25% IC groups, and 6.1+/-1.2 in the 75% IC groups, respectively). At the end of the experiment, animals were killed and the liver and kidney isolated, fixed in 4% formalin, cut, and stained for optic microscopy. Kidneys from rats ventilated with 75% IC showed increased Bowman's space with collapse of the glomerular capillaries. This occurred in a greater percentage of rats ventilated with 75% IC (0.67+/-0.2 vs. 0.29+/-0.2, 75% IC vs. 25% IC, respectively; p < .05). Perivascular edema was also present in rats ventilated with 75% IC (p < .05). Morphometric determinations of the empty zones (index of edema) demonstrated a trend toward differences between 75% IC livers and 25% IC (0.14+/-0.05 vs. 0.11+/-0.02, respectively). CONCLUSION: We conclude that it is possible to study the effects of mechanical ventilatory support on organs distal to the lung by means of an in vivo rat model.

Animals↗

Optoelectronic plethysmography in intensive care patients.

We used optoelectronic plethysmography to study 11 normal subjects during quiet and deep breathing, six sedated and paralyzed patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving continuous positive pressure ventilation (CPPV) (positive end-expiratory pressure [PEEP] = 10 cm H(2)O, tidal volume [VT] = 300, 600, 900 ml), and seven ALI/ARDS patients receiving pressure support ventilation (PSV) (PEEP 10 cm H(2)O, pressure support = 5, 10, 15, 25 cm H(2)O). The volumes measured using optoelectronic plethysmography were compared with measurements taken using spirometry and pneumotachography. The three methods were highly correlated. The discrepancies found were 1.7 +/- 5.9%, -1.6 +/- 5.4%, and 4.9 +/- 6.4% when comparing optoelectronic plethysmography with spirometry, optoelectronic plethysmography with pneumotachography, and spirometry with pneumotachography, respectively. Accuracy of the compartmentalization procedure (upper thorax, lower thorax, and abdomen) was assessed by calculating compartmental volume changes during isovolume maneuvers. The discrepancy from the ideal zero line was -2.1 +/- 48.3 ml. Abdominal contribution to inspired volume was greater for normal subjects than for PSV patients (63 +/- 11% versus 43 +/- 14%, p < 0.001). It decreased with VT for normal subjects (48.5 +/- 15%, p < 0.05), whereas it increased for CPPV patients (61 +/- 10%, p < 0.05). No significant distribution differences were found between 5 and 25 cm H(2)O PSV. We conclude that optoelectronic plethysmography is a feasible technique able to provide unique data on the distribution of chest wall volume changes in intensive care patients.

Adult↗

[Positive end expiratory pressure in anesthesia].

It is well established that general anesthesia, with or without paralysis, causes profound changes in respiratory function. From a clinical point of view, the more important consequence of this impairment is a decreased efficiency of gas exchange, with a decreased blood oxygenation. The main reason of this respiratory embarrassment is the intraoperative occurrence of atelectasis, mainly in the dependent lung regions. The amount of atelectasis, computed through Computerized Tomography, correlates with the amount of intrapulmonary shunt; thus, alveolar collapse and ventilation/perfusion mismatching are considered the most important factors for poor respiratory function. This deterioration seems also to play a crucial role in obese patients, who have poorer respiratory function and gas exchange than normal subjects already in physiological conditions. Different ventilatory approaches have been tried to resolve and eventually prevent the anesthesia-induced atelectasis. In normal subjects, the sole application of positive end-expiratory pressure (PEEP) seems to be an useless tool for improving gas exchange, probably because of changes in hemodynamics functions. The only effective application of PEEP seems to be in association to an alveolar recruitment manoeuvre. As the anesthesia-induced atelectasis are also present in the postoperative period, this ventilatory approach may also be used to prevent this condition. In obese patients PEEP seems to have a major effectiveness than in normal subjects, with an improvement of lung volumes, respiratory mechanics, gas exchange and an occurrence of recruitment. However, further studies are necessary to define optimal value of PEEP and tidal volume for different types of patients.

Anesthesia, General↗

Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis.

BACKGROUND: Morbidly obese patients, during anesthesia and paralysis, experience more severe impairment of respiratory mechanics and gas exchange than normal subjects. The authors hypothesized that positive end-expiratory pressure (PEEP) induces different responses in normal subjects (n = 9; body mass index < 25 kg/m2) versus obese patients (n = 9; body mass index > 40 kg/m2). METHODS: The authors measured lung volumes (helium technique), the elastances of the respiratory system, lung, and chest wall, the pressure-volume curves (occlusion technique and esophageal balloon), and the intraabdominal pressure (intrabladder catheter) at PEEP 0 and 10 cm H2O in paralyzed, anesthetized postoperative patients in the intensive care unit or operating room after abdominal surgery. RESULTS: At PEEP 0 cm H2O, obese patients had lower lung volume (0.59 +/- 0.17 vs. 2.15 +/- 0.58 l [mean +/- SD], P < 0.01); higher elastances of the respiratory system (26.8 +/- 4.2 vs. 16.4 +/- 3.6 cm H2O/l, P < 0.01), lung (17.4 +/- 4.5 vs. 10.3 +/- 3.2 cm H2O/l, P < 0.01), and chest wall (9.4 +/- 3.0 vs. 6.1 +/- 1.4 cm H2O/l, P < 0.01); and higher intraabdominal pressure (18.8 +/-7.8 vs. 9.0 +/- 2.4 cm H2O, P < 0.01) than normal subjects. The arterial oxygen tension was significantly lower (110 +/- 30 vs. 218 +/- 47 mmHg, P < 0.01; inspired oxygen fraction = 50%), and the arterial carbon dioxide tension significantly higher (37.8 +/- 6.8 vs. 28.4 +/- 3.1, P < 0.01) in obese patients compared with normal subjects. Increasing PEEP to 10 cm H2O significantly reduced elastances of the respiratory system, lung, and chest wall in obese patients but not in normal subjects. The pressure-volume curves were shifted upward and to the left in obese patients but were unchanged in normal subjects. The oxygenation increased with PEEP in obese patients (from 110 +/-30 to 130 +/- 28 mmHg, P < 0.01) but was unchanged in normal subjects. The oxygenation changes were significantly correlated with alveolar recruitment (r = 0.81, P < 0.01). CONCLUSIONS: During anesthesia and paralysis, PEEP improves respiratory function in morbidly obese patients but not in normal subjects.

Abdomen↗

Adult respiratory distress syndrome due to pulmonary and extrapulmonary causes: CT, clinical, and functional correlations.

PURPOSE: To assess the differences in CT appearance between adult respiratory distress syndrome due to pulmonary disease (ARDSP) and that due to extrapulmonary disease (ARDSEXP) and determine whether the variable appearances of ARDS are due, in part, to the initial pulmonary and systemic causes. MATERIALS AND METHODS: Thirty-three patients, 22 with ARDSP and 11 with ARDSEXP, underwent helical CT shortly after intubation. Two readers evaluated images for the type, extent, and distribution of pulmonary opacities; secondary findings; and correlation with survival and physiologic parameters. RESULTS: In both ARDSP and ARDSEXP, approximately 80% of the lung was abnormal. In ARDSP, ground-glass opacification and consolidation were equally prevalent, whereas in ARDSEXP ground-glass opacification was dominant. Ground-glass opacification was evenly distributed, whereas consolidation tended to be dorsal and caudal. ARDSP often caused asymmetric consolidation, whereas ARDSEXP caused symmetric ground-glass opacification. Air bronchograms were almost universal. Pleural effusions were present in one-half of the patients, and Kerley B lines and pneumatoceles were uncommon. Lung consolidation correlated with the ratio of mean partial pressure of arterial oxygen to fraction of inspired oxygen, shunt fraction, and pulmonary arterial pressure. The patients who died tended to have more consolidation and asymmetric disease. CONCLUSION: ARDSP tends to be asymmetric, with a mix of consolidation and ground-glass opacification, whereas ARDSEXP has predominantly symmetric ground-glass opacification. In both groups, pleural effusions and air bronchograms are common, and Kerley B lines and pneumatoceles are uncommon.

Adult↗

Sigh in acute respiratory distress syndrome.

Mechanical ventilation with plateau pressure lower than 35 cm H2O and high positive end-expiratory pressure (PEEP) has been recommended as lung protective strategy. Ten patients with ARDS (five from pulmonary [p] and five from extrapulmonary [exp] origin), underwent 2 h of lung protective strategy, 1 h of lung protective strategy with three consecutive sighs/min at 45 cm H2O plateau pressure, and 1 h of lung protective strategy. Total minute ventilation, PEEP (14.0 +/- 2.2 cm H2O), inspiratory oxygen fraction, and mean airway pressure were kept constant. After 1 h of sigh we found that: (1) PaO2 increased (from 92.8 +/- 18.6 to 137.6 +/- 23.9 mm Hg, p < 0.01), venous admixture and PaCO2 decreased (from 38 +/- 12 to 28 +/- 14%, p < 0.01; and from 52.7 +/- 19.4 to 49.1 +/- 18.4 mm Hg, p < 0.05, respectively); (2) end-expiratory lung volume increased (from 1.49 +/- 0.58 to 1.91 +/- 0.67 L, p < 0.01), and was significantly correlated with the oxygenation (r = 0.82, p < 0.01) and lung elastance (r = 0.76, p < 0.01) improvement. Sigh was more effective in ARDSexp than in ARDSp. After 1 h of sigh interruption, all the physiologic variables returned to baseline. The derecruitment was correlated with PaCO2 (r = 0.86, p < 0.01). We conclude that: (1) lung protective strategy alone at the PEEP level used in this study may not provide full lung recruitment and best oxygenation; (2) application of sigh during lung protective strategy may improve recruitment and oxygenation.

Adult↗

[The sigh in ARDS (acute respiratory distress syndrome)].

We studied 10 consecutive, sedated and paralyzed patients with Acute Respiratory Distress Syndrome (ARDS). The entire study lasted 4 hours, divided in 3 periods: 2 hours of recommended ventilation [lung protective strategy, LPS, i.e., ventilation with low tidal volume (< 8 mL/kg), limiting the plateau at 35 cm H2O, together with high positive end-expiratory pressure (PEEP)], 1 hour of sigh (LPS with 3 consecutive sighs/min at 45 cm H2O plateau pressure), and 1 hour of LPS. Total minute ventilation, PEEP, FiO2 and mean airway pressure were kept constant. The introduction of sighs induced a consistent recruitment and PaO2 improvement, and a decrease in venous admixture and PaCO2. Interrupting sighs and resuming LPS led to a progressive derecruitment, and all the physiological variables returned to baseline. Derecruitment was higher in patients with higher PaCO2 and lower VA/Q ratio. We conclude that: 1) LPS alone does not provide full lung recruitment and best oxygenation in ARDS; 2) application of sigh may provide pressure enough to recruit and volume enough to prevent reabsorption atelectasis.

Acute Disease↗