Luca M. Bigatello

Inhaled nitric oxide in congenital heart disease.

BackgroundCongenital heart lesions may be complicated by pulmonary arterial smooth muscle hyperplasia, hypertrophy, and hypertension. We assessed whether inhaling low levels of nitric oxide (NO), an endothelium-derived relaxing factor, would produce selective pulmonary vasodilation in pediatric patients with congenital heart disease and pulmonary hypertension. We also compared the pulmonary vasodilator potencies of inhaled NO and oxygen in these patients. Methods and ResultsIn 10 sequentially presenting, spontaneously breathing patients, we determined whether inhaling 20-80 ppm by volume of NO at inspired oxygen concentrations (FIO2) of 0.21-0.3 and 0.9 would reduce the pulmonary vascular resistance index (Rp). We then compared breathing oxygen with inhaling NO. Inhaling 80 ppm NO at F102 0.21-0.3 reduced mean pulmonary artery pressure from 48 ± 19 to 40+14 mm Hg and Rp from 658±421 to 491±417 dyne sec cm-5 m-2 (mean±SD, both p<0.05). Increasing the F102 to 0.9 without adding NO did not reduce mean pulmonary artery pressure but reduced Rp and increased the ratio of pulmonary to systemic blood flow (Qp/Qs), primarily by increasing Qp (p<0.05). Breathing 80 ppm NO at F1O2 0.9 reduced mean pulmonary artery pressure and Rp to the lowest levels and increased Qp and Qp/Qs (all p<0.05). While breathing at F102 0.9, inhalation of 40 ppm NO reduced Rp (p<0.05); the maximum reduction of Rp occurred while breathing 80 ppm NO. Inhaling 80 ppm NO at F102 0.21-0.9 did not alter mean aortic pressure or systemic vascular resistance. Methemoglobin levels were unchanged by breathing up to 80 ppm NO for 30 minutes. ConclusionInhaled NO is a potent and selective pulmonary vasodilator in pediatric patients with congenital heart disease complicated by pulmonary artery hypertension. Inhaling low levels of NO may provide an important and safe means for evaluating the pulmonary vasodilatory capacity of patients with congenital heart disease without producing systemic vasodilation.

Prolonged inhalation of low concentrations of nitric oxide in patients with severe adult respiratory distress syndrome. Effects on pulmonary hemodynamics and oxygenation.

Background:Nitric oxide (NO) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). In this study of patients with severe ARDS, we sought to determine the effect of inhaled NO dose and time on pulmonary artery pressure and oxygen exchange and to determine which patients with ARDS are most likely to show this response. Methods:Thirteen patients with severe ARDS (hospital mortality 67%) inhaled 0-40 parts per million (ppm) NO. Seven of these patients continued to breathe 2-20 ppm NO for 2-27 days. Results:Inhaling 5-40 ppm NO decreased mean pulmonary artery pressure in a dose-related fashion (from 34 ± 7 to 30 ± 7 mmHg at 20 ppm NO). Systemic arterial pressure did not change. The ratio of arterial oxygen tension to inspired oxygen fraction increased (from 126 ± 36 to 149 ± 38 mmHg) and the venous admixture decreased (from 31.2 ± 5.5 to 28.2 ± 5.2%) without a clear dose-response effect. During prolonged NO inhalation, 2-20 ppm NO effectively reduced mean pulmonary artery pressure (38 ± 7 vs. 31 ± 6 mmHg) and increased arterial oxygen tension (79 ± 10 vs. 114 ± 27 mmHg) without evidence of tachyphylaxis. The decrease of pulmonary vascular resistance during NO inhalation correlated with the level of pulmonary vascular resistance without NO (r=-0.72). The reduction of venous admixture correlated with the level of venous admixture without NO (r=-0.78). Conclusions:Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS. The selective pulmonary vasodilation effect is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction.

Sigh improves gas exchange and lung volume in patients with acute respiratory distress syndrome undergoing pressure support ventilation.

Background The aim of our study was to assess the effect of periodic hyperinflations (sighs) during pressure support ventilation (PSV) on lung volume, gas exchange, and respiratory pattern in patients with early acute respiratory distress syndrome (ARDS). Methods Thirteen patients undergoing PSV were enrolled. The study comprised 3 steps: baseline 1, sigh, and baseline 2, of 1 h each. During baseline 1 and baseline 2, patients underwent PSV. Sighs were administered once per minute by adding to baseline PSV a 3- to 5-s continuous positive airway pressure (CPAP) period, set at a level 20% higher than the peak airway pressure of the PSV breaths or at least 35 cm H2O. Mean airway pressure was kept constant by reducing the positive end-expiratory pressure (PEEP) during the sigh period as required. At the end of each study period, arterial blood gas tensions, air flow and pressures traces, end-expiratory lung volume (EELV), compliance of respiratory system (Crs), and ventilatory parameters were recorded. Results Pao2 improved (P < 0.001) from baseline 1 (91.4 ± 27.4 mmHg) to sigh (133 ± 42.5 mmHg), without changes of Paco2. EELV increased (P < 0.01) from baseline 1 (1,242 ± 507 ml) to sigh (1,377 ± 484 ml). Crs improved (P < 0.01) from baseline 1 (40.2 ± 12.5 ml/cm H2O) to sigh (45.1 ± 15.3 ml/cm H2O). Tidal volume of pressure-supported breaths and the airway occlusion pressure (P0.1) decreased (P < 0.01) during the sigh period. There were no significant differences between baselines 1 and 2 for all parameters. Conclusions The addition of 1 sigh per minute during PSV in patients with early ARDS improved gas exchange and lung volume and decreased the respiratory drive.

Physiologic Determinants of the Response to Inhaled Nitric Oxide in Patients with Acute Respiratory Distress Syndrome

Background:The response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) varies. It is unclear which patients will respond favorably and whether the initial response persists over time. The authors defined a clinically useful response to inhaled NO as an incre

Continuous positive airway pressure delivered with a "helmet": effects on carbon dioxide rebreathing.

Objective:The “helmet” has been used as a novel interface to deliver noninvasive ventilation without applying direct pressure on the face. However, due to its large volume, the helmet may predispose to Co2 rebreathing. We hypothesized that breathing with the helmet is similar to breathing in a semiclosed environment, and therefore the Pco2 inside the helmet is primarily a function of the subject’s Co2 production and the flow of fresh gas through the helmet. Design:Human volunteer study. Setting:Laboratory in a university teaching hospital. Subjects:Eight healthy volunteers. Interventions:We delivered continuous positive airway pressure (CPAP) with the helmet under a variety of ventilatory conditions in a lung model and in volunteers. Measurements and Main Results:Gas flow and Co2 concentration at the airway were measured continuously. End-tidal Pco2, Co2 production, and ventilatory variables were subsequently computed. We found that a) when CPAP was delivered with a ventilator, the inspired Co2 of the volunteers was high (12.4 ± 3.2 torr [1.7 ± 0.4 kPa]); b) when CPAP was delivered with a continuous high flow system, inspired Co2 of the volunteers was low (2.5 ± 1.2 torr [0.3 ± 0.2 kPa]); and c) the inspired Co2 calculated mathematically for a semiclosed system model of Co2 rebreathing was highly correlated with the values measured in a lung model (r2 = .97, slope = 0.92, intercept = −1.17, p < .001) and in the volunteers (r2 = .94, slope = 0.96, intercept = 0.90, p < .001). Conclusions:a) The helmet predisposes to Co2 rebreathing and should not be used to deliver CPAP with a ventilator; b) continuous high flow minimizes Co2 rebreathing during CPAP with the helmet; and c) minute ventilation and Pco2 should be monitored during CPAP with the helmet.

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 patients comfort was worse at the lowest and highest pressurization rates.

Inaccuracies of Nitric Oxide Delivery Systems during Adult Mechanical Ventilation

Background Various systems to administer inhaled nitric oxide (NO) have been used in patients and experimental animals. We used a lung model to evaluate five NO delivery systems during mechanical ventilation with various ventilatory patterns. Methods An adult mechanical ventilator was attached to a test lung configured to separate inspired and expired gases. Four injection systems were evaluated with NO injected either into the inspiratory circuit 90 cm proximal to the Y piece or directly at the Y piece and delivered either continuously or only during the inspiratory phase. Alternatively, NO was mixed with air using a blender and delivered to the high‐pressure air inlet of the ventilator. Nitric oxide concentration was measured from the inspiratory limb of the ventilator circuit and the tracheal level using rapid‐ and slow‐response chemiluminescence analyzers. The ventilator was set for constant‐flow volume control ventilation, pressure control ventilation, pressure support ventilation, or synchronized intermittent mandatory ventilation. Tidal volumes of 0.5 l and 1 l were evaluated with inspiratory times of 1 s and 2 s. Results The system that premixed NO proximal to the ventilator was the only one that maintained constant NO delivery regardless of ventilatory pattern. The other systems delivered variable NO concentration during pressure control ventilation and spontaneous breathing modes. Systems that injected a continuous flow of NO delivered peak NO concentrations greater than the calculated dose. These variations were not apparent when a slow‐response chemiluminescence analyzer was used. Conclusions NO delivery systems that inject NO at a constant rate, either continuously or during inspiration only, into the inspiratory limb of the ventilator circuit produce highly variable and unpredictable NO delivery when inspiratory flow is not constant. Such systems may deliver a very high NO concentration to the lungs, which is not accurately reflected by measurements performed with slow‐response analyzers.

Outcome of patients undergoing prolonged mechanical ventilation after critical illness.

Objective:To examine the longitudinal outcome of a cohort of mechanically ventilated patients admitted to an acute care respiratory unit after critical illness. Design, Setting, and Patients:Prospective, observational study of 210 consecutive patients admitted to a respiratory unit of an acute, tertiary care university hospital, who had an acute critical illness with respiratory failure. The study was powered to develop multivariate regression models to investigate the relationship between patient characteristics and a) liberation from mechanical ventilation and b) survival. Interventions:None. Measurements and Main Results:The median time to liberation from mechanical ventilation after respiratory unit admission was 14 days (interquartile range, 6–51). A total of 146 patients (69%) were off mechanical ventilation at 6 months, and 123 patients (61%) were alive at 1 yr. Patients who did not come off mechanical ventilation in the respiratory unit were seven times more likely to die within a year than those who did (odds ratio, 6.55; 95% confidence intervals, 4.04–10.63; p < .001). At least 75% of deaths occurred by consensual withdrawal of life support. Patient activity of daily living scores (0–100 scale) increased progressively from hospital discharge (24 ± 6) through 3 (54 ± 21) and 6 months (64 ± 22) (p < .001). The median cost of hospitalization for all study patients was

Different modes of assisted ventilation in patients with acute respiratory failure

149,624 (interquartile range,

Effect of laboratory testing guidelines on the utilization of tests and order entries in a surgical intensive care unit.

102,540–225,843). Conclusions:The majority of patients requiring prolonged mechanical ventilation in a respiratory unit after acute critical illness are liberated from mechanical ventilation, survive, and have a steady improvement in the activity of daily living during the first 6 months after discharge. However, a substantial fraction of these patients does not wean from mechanical ventilation and dies from consensual withdrawal of life support after a prolonged and costly hospital stay.