Effects of positive end-expiratory pressure alone or an open-lung approach on recruited lung volumes and respiratory mechanics of mechanically ventilated horses.

OBJECTIVE: To evaluate the effects of positive end-expiratory pressure (PEEP) alone and PEEP preceded by lung recruitment manoeuvre (LRM) on lung volumes and respiratory system mechanics in healthy horses undergoing general anaesthesia. STUDY DESIGN: Controlled, prospective clinical study. ANIMALS: A group of 15 horses undergoing arthroscopy. METHODS: Following anaesthetic induction, initial ventilatory settings were: tidal volume 15 mL kg-1, inspiratory:expiratory ratio 1:2, respiratory rate to maintain end-tidal CO2 between 5.3-6.6 kPa (40-50 mmHg). The following settings were implemented sequentially: zero PEEP (ZEEP); PEEP 10 cmH2O (PEEP); LRM (50 cmH2O for 20 seconds) followed by 10 cmH2O of PEEP (LRM + PEEP). Static compliance (Cst), driving pressure, delta end-expiratory (ΔEELV) and recruited lung volumes (RLV) were obtained 30 minutes after initiating each ventilatory strategy. Data were analyzed with paired t test or analysis of variance followed by Tukey's post hoc test. Data are shown as mean ± standard deviation; p < 0.05 was considered significant. RESULTS: PEEP induced ΔEELV of 6.68 ± 3.36 mL kg-1; ΔEELV during LRM + PEEP was 14.28 ± 5.59 mL kg-1 (p < 0.0001). The RLV was greater during the LRM + PEEP phase (12.30 ± 5.85 mL kg-1) than during PEEP (4.47 ± 3.97 mL kg-1; p < 0.0001). The Cst was unchanged from ZEEP to PEEP (0.75 ± 0.21 and 0.85 ± 0.22 mL cmH2O-1 kg-1, respectively, p = 0.36) but increased using LRM + PEEP (1.11 ± 0.25 mL cmH2O-1 kg-1, p = 0.0004). Driving pressure was lower during LRM + PEEP than during PEEP and ZEEP (16 ± 2, 19 ± 2 and 21 ± 4 cmH2O, respectively, p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Unlike PEEP alone, PEEP preceded by LRM increased RLV and Cst and reduced driving pressure in horses under anaesthesia.

High-flow nasal cannula oxygen therapy decreases postextubation neuroventilatory drive and work of breathing in patients with chronic obstructive pulmonary disease.

BACKGROUND: The physiological effects of high-flow nasal cannula O2 therapy (HFNC) have been evaluated mainly in patients with hypoxemic respiratory failure. In this study, we compared the effects of HFNC and conventional low-flow O2 therapy on the neuroventilatory drive and work of breathing postextubation in patients with a background of chronic obstructive pulmonary disease (COPD) who had received mechanical ventilation for hypercapnic respiratory failure. METHODS: This was a single center, unblinded, cross-over study on 14 postextubation COPD patients who were recovering from an episode of acute hypercapnic respiratory failure of various etiologies. After extubation, each patient received two 1-h periods of HFNC (HFNC1 and HFNC2) alternated with 1 h of conventional low-flow O2 therapy via a face mask. The inspiratory fraction of oxygen was titrated to achieve an arterial O2 saturation target of 88-92%. Gas exchange, breathing pattern, neuroventilatory drive (electrical diaphragmatic activity (EAdi)) and work of breathing (inspiratory trans-diaphragmatic pressure-time product per minute (PTPDI/min)) were recorded. RESULTS: EAdi peak increased from a mean (±SD) of 15.4 ± 6.4 to 23.6 ± 10.5 µV switching from HFNC1 to conventional O2, and then returned to 15.2 ± 6.4 µV during HFNC2 (conventional O2: p < 0.05 versus HFNC1 and HFNC2). Similarly, the PTPDI/min increased from 135 ± 60 to 211 ± 70 cmH2O/s/min, and then decreased again during HFNC2 to 132 ± 56 (conventional O2: p < 0.05 versus HFNC1 and HFNC2). CONCLUSIONS: In patients with COPD, the application of HFNC postextubation significantly decreased the neuroventilatory drive and work of breathing compared with conventional O2 therapy.

Low respiratory rate plus minimally invasive extracorporeal Co2 removal decreases systemic and pulmonary inflammatory mediators in experimental Acute Respiratory Distress Syndrome.

OBJECTIVE: The Acute Respiratory Distress Syndrome Network protocol recommends limiting tidal volume and plateau pressure; it also recommends increasing respiratory rate to prevent hypercapnia. We tested a strategy that combines the low tidal volume with lower respiratory rates and minimally invasive CO2 removal. SUBJECTS: Ten lung-damaged pigs (instilled hydrochloride). INTERVENTIONS: Two conditions randomly applied in a crossover fashion: the Acute Respiratory Distress Syndrome Network protocol and the Acute Respiratory Distress Syndrome Network protocol plus lower respiratory rate plus minimally invasive Co2 removal. A similar arterial Co2 partial pressure was targeted in the two conditions. MEASUREMENTS AND MAIN RESULTS: Physiological parameters, computed tomography scans, plasma and bronchoalveolar lavage concentrations of interleukin-1ß, interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-α. During the lower respiratory rate condition, respiratory rate was reduced from 30.5 ± 3.8 to 14.2 ± 3.5 (p < 0.01) breaths/min and minute ventilation from 10.4 ± 1.6 to 4.9 ± 1.7 L/min (p < 0.01). The extracorporeal device removed 38.9% ± 6.1% (79.9 ± 18.4 mL/min) of CO2 production. During the lower respiratory rate condition, interleukin-6, interleukin-8, and tumor necrosis factor-α concentrations were significantly lower in plasma; interleukin-6 and tumor necrosis factor-α concentrations were lower in bronchoalveolar lavage, whereas the concentrations of the other cytokines remained unchanged. CONCLUSION: The strategy of lower respiratory rate plus minimally invasive extracorporeal CO2 removal was feasible and safe and, as compared with the Acute Respiratory Distress Syndrome Network protocol, reduced the concentrations of some, but not all, of the tested cytokines without affecting respiratory mechanics, gas exchange, and hemodynamics.

Accuracy of plateau pressure and stress index to identify injurious ventilation in patients with acute respiratory distress syndrome.

BACKGROUND: Guidelines suggest a plateau pressure (PPLAT) of 30 cm H(2)O or less for patients with acute respiratory distress syndrome, but ventilation may still be injurious despite adhering to this guideline. The shape of the curve plotting airway pressure versus time (STRESS INDEX) may identify injurious ventilation. The authors assessed accuracy of PPLAT and STRESS INDEX to identify morphological indexes of injurious ventilation. METHODS: Indexes of lung aeration (computerized tomography) associated with injurious ventilation were used as a "reference standard." Threshold values of PPLAT and STRESS INDEX were determined assessing the receiver-operating characteristics ("training set," N = 30). Accuracy of these values was assessed in a second group of patients ("validation set," N = 20). PPLAT and STRESS INDEX were partitioned between respiratory system (Pplat,Rs and STRESS INDEX,RS) and lung (PPLAT,L and STRESS INDEX,L; esophageal pressure; "physiological set," N = 50). RESULTS: Sensitivity and specificity of PPLAT of greater than 30 cm H(2)O were 0.06 (95% CI, 0.002-0.30) and 1.0 (95% CI, 0.87-1.00). PPLAT of greater than 25 cm H(2)O and a STRESS INDEX of greater than 1.05 best identified morphological markers of injurious ventilation. Sensitivity and specificity of these values were 0.75 (95% CI, 0.35-0.97) and 0.75 (95% CI, 0.43-0.95) for PPLAT greater than 25 cm H(2)O versus 0.88 (95% CI, 0.47-1.00) and 0.50 (95% CI, 0.21-0.79) for STRESS INDEX greater than 1.05. Pplat,Rs did not correlate with PPLAT,L (R(2) = 0.0099); STRESS INDEX,RS and STRESS INDEX,L were correlated (R(2) = 0.762). CONCLUSIONS: The best threshold values for discriminating morphological indexes associated with injurious ventilation were Pplat,Rs greater than 25 cm H(2)O and STRESS INDEX,RS greater than 1.05. Although a substantial discrepancy between Pplat,Rs and PPLAT,L occurs, STRESS INDEX,RS reflects STRESS INDEX,L.

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.

Inhomogeneity of lung parenchyma during the open lung strategy: a computed tomography scan study.

RATIONALE: The open lung strategy aims at reopening (recruitment) of nonaerated lung areas in patients with acute respiratory distress syndrome, avoiding tidal alveolar hyperinflation in the limited area of normally aerated tissue (baby lung). OBJECTIVES: We tested the hypothesis that recruited lung areas do not resume elastic properties of adjacent baby lung. METHODS: Twenty-five anesthetized, mechanically ventilated pigs were studied. Four lung-healthy pigs served as controls and the remaining 21 were divided into three groups (n = 7 each) in which lung injury was produced by surfactant lavage, lipopolysaccharide infusion, or hydrochloride inhalation. Computed tomography scans, respiratory mechanics, and gas exchange parameters were recorded under three conditions: at baseline, during lung recruitment maneuver, and at end-expiration and end-inspiration when ventilating after an open lung protocol. MEASUREMENTS AND MAIN RESULTS: During recruitment maneuver and open lung protocol, the gas volume entering the insufficiently aerated compartment was 96% (75-117%) and 48% (41-63%) (median [interquartile range]) of the functional residual capacity measured before and at zero end-expiratory pressure, respectively. Nonetheless, the volume of hyperinflated lung increased during both recruitment maneuver (by 1-28% of total lung volume; P < 0.01) and open lung protocol ventilation at end-inspiration (by 1-15% of total lung volume; P < 0.01). Regional elastance of recruited lung tissue was consistently higher than that of the baby lung regardless of the ARDS model (P < 0.01). CONCLUSIONS: Alveolar recruitment is not protective against hyperinflation of the baby lung because lung parenchyma is inhomogeneous during ventilation with the open lung strategy.

Evaluation of the effects of helmet continuous positive airway pressure on laryngeal size in dogs anesthetized with propofol and fentanyl using computed tomography.

OBJECTIVE: To evaluate the effect of 5 cm H2 O of continuous positive airway pressure (CPAP) on laryngeal size in spontaneously breathing anesthetized dogs via computed tomography (CT). DESIGN: Prospective, randomized, cross-over clinical study. SETTING: University teaching hospital and referral private practice. ANIMALS: Eight healthy client-owned dogs undergoing CT. INTERVENTIONS: Dogs were sedated with acepromazine 20 µg/kg IM and induced with fentanyl 2 µg/kg and propofol 3-5 mg/kg IV before being maintained on fentanyl (5 µg/kg/h) and propofol (0.3 mg/kg/min) constant rate infusion. Dogs received an air/oxygen mixture with (CPAP) and without (NO-CPAP) 5 cm H2 O of CPAP in a random order. Each study step lasted 15 minutes. MEASUREMENTS AND MAIN RESULTS: Ten minutes after the beginning of each study period, a CT scan of the laryngeal region was obtained at end-expiration. CT images were analyzed to determine the laryngeal cross-sectional area (CSA; cm2 ), total volume (VTOT ; cm3 ), and laterolateral and dorsoventral diameters (DLL and DDV , respectively; cm). Differences between the 2 treatments were analyzed with t-test for paired data (P < 0.05). Compared to the NO-CPAP, during CPAP the CSA increased by 53.3 ± 23.1% (ie, from 3.3 ± 0.8 to 5.1 ± 1.3 cm2 , P = 0.0004), VTOT increased by 52.4 ± 13.6% (from 6.2 ± 1.7 to 9.4 ± 2.4 cm3 , P < 0.0001), and DLL and DDV were 55.5 ± 13.3% (3.6 ± 0.8 vs 2.4 ± 0.5 cm, P = 0.006) and 20.3 ± 8.8% larger (3.2 ± 0.7 vs 2.7 ± 0.6 cm, P = 0.0002), respectively. CONCLUSIONS: Laryngeal volume and cross sectional area increased during the application of 5 cm H2 O of helmet CPAP in spontaneously breathing anesthetized dogs.

High-flow oxygen therapy in tracheostomized patients at high risk of weaning failure.

PURPOSE: High-flow oxygen therapy delivered through nasal cannulae improves oxygenation and decreases work of breathing in critically ill patients. Little is known of the physiological effects of high-flow oxygen therapy applied to the tracheostomy cannula (T-HF). In this study, we compared the effects of T-HF or conventional low-flow oxygen therapy (conventional O2) on neuro-ventilatory drive, work of breathing, respiratory rate (RR) and gas exchange, in a mixed population of tracheostomized patients at high risk of weaning failure. METHODS: This was a single-center, unblinded, cross-over study on fourteen patients. After disconnection from the ventilator, each patient received two 1-h periods of T-HF (T-HF1 and T-HF2) alternated with 1 h of conventional O2. The inspiratory oxygen fraction was titrated to achieve an arterial O2 saturation target of 94-98% (88-92% in COPD patients). We recorded neuro-ventilatory drive (electrical diaphragmatic activity, EAdi), work of breathing (inspiratory muscular pressure-time product per breath and per minute, PTPmusc/b and PTPmusc/min, respectively) respiratory rate and arterial blood gases. RESULTS: The EAdipeak remained unchanged (mean ± SD) in the T-HF1, conventional O2 and T-HF2 study periods (8.8 ± 4.3 µV vs 8.9 ± 4.8 µV vs 9.0 ± 4.1 µV, respectively, p = 0.99). Similarly, PTPmusc/b and PTPmusc/min, RR and gas exchange remained unchanged. CONCLUSIONS: In tracheostomized patients at high risk of weaning failure from mechanical ventilation, T-HF did not improve neuro-ventilatory drive, work of breathing, respiratory rate and gas exchange compared with conventional O2 after disconnection from the ventilator. The present findings might suggest that physiological effects of high-flow therapy through tracheostomy substantially differ from nasal high flow.

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.

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.