Physiological effects of an open lung ventilatory strategy titrated on elastance-derived end-inspiratory transpulmonary pressure: study in a pig model*.

RATIONALE: In the presence of increased chest wall elastance, the airway pressure does not reflect the lung-distending (transpulmonary) pressure. OBJECTIVE: To compare the physiological effects of a conventional open lung approach titrated for an end-inspiratory airway opening plateau pressure (30 cm H2O) with a transpulmonary open lung approach titrated for a elastance-derived end-inspiratory plateau transpulmonary pressure (26 cm H2O), in a pig model of acute respiratory distress syndrome (HCl inhalation) and reversible chest wall mechanical impairment (chest wall and abdomen restriction). METHODS: In eight pigs, physiological parameters and computed tomography were recorded under three conditions: 1) conventional open lung approach, normal chest wall; 2) conventional open lung approach, stiff chest wall; and 3) transpulmonary open lung approach, stiff chest wall. MEASUREMENTS AND MAIN RESULTS: As compared with the normal chest wall condition, at end-expiration non aerated lung tissue weight was increased by 116 ± 68 % during the conventional open lung approach and by 28 ± 41 % during the transpulmonary open lung approach (p < .01), whereas cardiac output was decreased by 27 ± 19 % and 22 ± 14 %, respectively (p = not significant). CONCLUSION: In this model, the end-inspiratory transpulmonary open lung approach minimized the impact of chest wall stiffening on alveolar recruitment without causing hemodynamic impairment.

Advances in targeting signal transduction pathways.

Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being discovered which may allow the creation of alternative therapies to overcome resistance. This review will discuss some of the highlights over the past few years on the roles of key signaling pathways in various diseases, the targeting of signal transduction pathways and the genetic mechanisms governing sensitivity and resistance to targeted therapies.

ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure.

RATIONALE: In patients with acute respiratory distress syndrome (ARDS), a focal distribution of loss of aeration in lung computed tomography predicts low potential for alveolar recruitment and susceptibility to alveolar hyperinflation with high levels of positive end-expiratory pressure (PEEP). OBJECTIVES: We tested the hypothesis that, in this cohort of patients, the table-based PEEP setting criteria of the National Heart, Lung, and Blood Institute's ARDS Network (ARDSnet) low tidal volume ventilatory protocol could induce tidal alveolar hyperinflation. METHODS: In 15 patients, physiologic parameters and plasma inflammatory mediators were measured during two ventilatory strategies, applied randomly: the ARDSnet and the stress index strategy. The latter used the same ARDSnet ventilatory pattern except for the PEEP level, which was adjusted based on the stress index, a monitoring tool intended to quantify tidal alveolar hyperinflation and/or recruiting/derecruiting that occurs during constant-flow ventilation, on a breath-by-breath basis. MEASUREMENTS AND MAIN RESULTS: In all patients, the stress index revealed alveolar hyperinflation during application of the ARDSnet strategy, and consequently, PEEP was significantly decreased (P < 0.01) to normalize the stress index value. Static lung elastance (P = 0.01), plasma concentrations of interleukin-6 (P < 0.01), interleukin-8 (P = 0.031), and soluble tumor necrosis factor receptor I (P = 0.013) were significantly lower during the stress index as compared with the ARDSnet strategy-guided ventilation. CONCLUSIONS: Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement.

Use of N-terminal pro-brain natriuretic peptide to detect acute cardiac dysfunction during weaning failure in difficult-to-wean patients with chronic obstructive pulmonary disease.

OBJECTIVE: To evaluate the utility of serial measurements of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to detect acute cardiac dysfunction during weaning failure in difficult to wean patients with chronic obstructive pulmonary disease. DESIGN: Prospective observational cohort study. SETTING: A 14-bed general intensive care unit in a university hospital. PATIENTS: Nineteen patients mechanically ventilated for chronic obstructive pulmonary disease exacerbation who were difficult to wean. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac and hemodynamic variables, arterial and central venous blood gas, breathing pattern, respiratory mechanics, indexes of oxygen cost of breathing, and plasma levels of NT-proBNP were measured and analyzed immediately before (baseline) and at the end of a spontaneous breathing trial. Eight of 19 patients (42%) were identified with acute cardiac dysfunction at the end of the weaning trial. Baseline NT-proBNP levels were significantly higher (median 5000, interquartile range 4218 pg/mL) in these patients than in patients without evidence of acute cardiac dysfunction (median 1705, interquartile range 3491 pg/mL). Plasma levels of NT-proBNP increased significantly at the end of the spontaneous breathing trial only in patients with acute cardiac dysfunction (median 12,733, interquartile range 16,456 pg/mL, p < .05). The elevation in NT-proBNP at the end of the weaning trial had a good diagnostic performance in detecting acute cardiac dysfunction, as estimated by area under the receiver operating characteristic curve analysis (area under the curve 0.909, se 0.077, 95% confidence interval 0.69-0.98; p < .0001, cutoff = 184.7 pg/mL). CONCLUSIONS: Serial measurements of NT-proBNP plasma levels provided a noninvasive manner to detect acute cardiac dysfunction during an unsuccessful weaning trial in difficult to wean patients with chronic obstructive pulmonary disease. The utility of this test as a complement of the standard clinical monitoring of the weaning trial deserves further investigation.

Measurement of PEEP-induced alveolar recruitment: just a research tool?

For positive end-expiratory pressure (PEEP) to have lung protective efficacy in patients with acute respiratory distress syndrome, it must increase the end-expiratory lung volume through alveolar recruitment while avoiding lung over-inflation. PEEP may increase the end-expiratory lung volume either by increasing the proportion of aerated alveoli at end-expiration or by further inflating already ventilated lung regions. The optimal PEEP regimen is still a matter of debate. In theory, the ability to measure of PEEP-induced alveolar recruitment would be extremely useful in titrating PEEP at the bedside. However, until now this measurement has been confined to clinical research settings. Interesting work by Lu and coworkers, published in the previous issue of this journal, deals with the problem of measuring PEEP-induced alveolar recruitment. The 'gold standard' technique (i.e. the computed tomography method) is compared with the pressure-volume curve method. Because implementation of the latter method at the bedside would be relatively simple, that report, in addition to its intrinsic scientific value, may have important clinical implications.