Ray Ritz

Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury

BACKGROUND Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention. METHODS We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes. RESULTS The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of variance). CONCLUSIONS As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Esophageal and transpulmonary pressures in acute respiratory failure

Objective:Pressure inflating the lung during mechanical ventilation is the difference between pressure applied at the airway opening (Pao) and pleural pressure (Ppl). Depending on the chest walls contribution to respiratory mechanics, a given positive end-expiratory and/or end-inspiratory plateau pressure may be appropriate for one patient but inadequate or potentially injurious for another. Thus, failure to account for chest wall mechanics may affect results in clinical trials of mechanical ventilation strategies in acute respiratory distress syndrome. By measuring esophageal pressure (Pes), we sought to characterize influence of the chest wall on Ppl and transpulmonary pressure (PL) in patients with acute respiratory failure. Design:Prospective observational study. Setting:Medical and surgical intensive care units at Beth Israel Deaconess Medical Center. Patients:Seventy patients with acute respiratory failure. Interventions:Placement of esophageal balloon-catheters. Measurements and Main Results:Airway, esophageal, and gastric pressures recorded at end-exhalation and end-inflation Pes averaged 17.5 ± 5.7 cm H2O at end-expiration and 21.2 ± 7.7 cm H2O at end-inflation and were not significantly correlated with body mass index or chest wall elastance. Estimated PL was 1.5 ± 6.3 cm H2O at end-expiration, 21.4 ± 9.3 cm H2O at end-inflation, and 18.4 ± 10.2 cm H2O (n = 40) during an end-inspiratory hold (plateau). Although PL at end-expiration was significantly correlated with positive end-expiratory pressure (p < .0001), only 24% of the variance in PL was explained by Pao (R2 = .243), and 52% was due to variation in Pes. Conclusions:In patients in acute respiratory failure, elevated esophageal pressures suggest that chest wall mechanical properties often contribute substantially and unpredictably to total respiratory impedance, and therefore Pao may not adequately predict PL or lung distention. Systematic use of esophageal manometry has the potential to improve ventilator management in acute respiratory failure by providing more direct assessment of lung distending pressure.

Esophageal pressures in acute lung injury: do they represent artifact or useful information about transpulmonary pressure, chest wall mechanics, and lung stress?

Acute lung injury can be worsened by inappropriate mechanical ventilation, and numerous experimental studies suggest that ventilator-induced lung injury is increased by excessive lung inflation at end inspiration or inadequate lung inflation at end expiration. Lung inflation depends not only on airway pressures from the ventilator but, also, pleural pressure within the chest wall. Although esophageal pressure (Pes) measurements are often used to estimate pleural pressures in healthy subjects and patients, they are widely mistrusted and rarely used in critical illness. To assess the credibility of Pes as an estimate of pleural pressure in critically ill patients, we compared Pes measurements in 48 patients with acute lung injury with simultaneously measured gastric and bladder pressures (Pga and P(blad)). End-expiratory Pes, Pga, and P(blad) were high and varied widely among patients, averaging 18.6 +/- 4.7, 18.4 +/- 5.6, and 19.3 +/- 7.8 cmH(2)O, respectively (mean +/- SD). End-expiratory Pes was correlated with Pga (P = 0.0004) and P(blad) (P = 0.0104) and unrelated to chest wall compliance. Pes-Pga differences were consistent with expected gravitational pressure gradients and transdiaphragmatic pressures. Transpulmonary pressure (airway pressure - Pes) was -2.8 +/- 4.9 cmH(2)O at end exhalation and 8.3 +/- 6.2 cmH(2)O at end inflation, values consistent with effects of mediastinal weight, gravitational gradients in pleural pressure, and airway closure at end exhalation. Lung parenchymal stress measured directly as end-inspiratory transpulmonary pressure was much less than stress inferred from the plateau airway pressures and lung and chest wall compliances. We suggest that Pes can be used to estimate transpulmonary pressures that are consistent with known physiology and can provide meaningful information, otherwise unavailable, in critically ill patients.

Nitrogen Dioxide Production during Mechanical Ventilation with Nitric Oxide in Adults Effects of Ventilator Internal Volume, Air Versus Nitrogen Dilution, Minute Ventilation, and Inspired Oxygen Fraction

Background Inhaled nitric oxide (NO) may be useful in the treatment of adult respiratory distress syndrome and other diseases characterized by pulmonary hypertension and hypoxemia. NO is rapidly converted to nitrogen dioxide (NO2) in oxygen (Oxygen2) environments. We hypothesized that in patients whose lungs are mechanically ventilated and in those with a long residence time for NO in the lungs, a clinically important [NO2] may be present. We therefore determined the rate constants for NO conversion in adult mechanical ventilators and in a test lung simulating prolonged intrapulmonary residence of NO. Methods NO (800 ppm) was blended with nitrogen (Nitrogen2), delivered to the high‐pressure air inlet of a Puritan‐Bennett 7200ae or Siemens Servo 900C ventilator, and used to ventilate a test lung. The ventilator settings were varied: minute ventilation (VE) from 5 to 25 l/min, inspired Oxygen2 fraction (FIO2) from 0.24 to 0.87, and [NO] from 10 to 80 ppm. The experiment was then repeated with air instead of Nitrogen2 as the dilution gas. The effect of pulmonary residence time on NO2 production was examined at test lung volumes of 0.5–4.0 l, V with dotE of 5–25 l/min, FIO2 of 0.24–0.87, and [NO] of 10–80 ppm. The inspiratory gas mixture was sampled 20 cm from the Y‐piece and from within the test lung. NO and NO sub 2 were measured by chemiluminescence. The rate constant (k) for the conversion of NO to NO2 was determined from the relation 1/[NO]1 1/[NO]0 k x [Oxygen2] x t, where t = residence time. Results No NO2 was detected during any trial with V with dot sub E 20 or 25 l/min. With Nitrogen2 dilution and the Puritan‐ Bennett 7200ae, NO2 (less or equal to 1 ppm) was detected only at a V with dotE of 5 l/min with an FIO2 of 0.87 and [NO] greater or equal to 70 ppm. In contrast, [NO2] values were greater with the Servo 900C ventilator than with the Puritan‐Bennett 7200ae at similar settings. When NO was diluted with air, clinically important [NO sub 2] values were measured with both ventilators at high [NO] and FI sub O2. Rate constants were 1.46 x 109 ppm2 *symbol* min sup ‐1 when NO was mixed with Nitrogen2, 1.17 x 108 ppm sup ‐ 2 *symbol* min sup ‐1 when NO was blended with air, and 1.44 x 109 ppm sup ‐2 *symbol* min sup ‐1 in the test lung. Conclusions [NO2] increased with increased FIO2 and [NO], decreased V with dotE, blending with air, and increased lung volumes. Higher [NO2] was produced with the Servo 900C ventilator than the Puritan‐Bennett 7200ae because of the greater residence time. With long intrapulmonary residence times for NO, there is a potential for NO2 production within the lungs. The rate constants determined can be used to estimate [NO2] in adult mechanical ventilation systems.

Low-dose inhaled nitric oxide in acutely burned children with profound respiratory failure

BACKGROUND Inhaled nitric oxide (NO) is a rapidly acting selective pulmonary vasodilator that partially reverses the pathophysiology of acute respiratory distress syndrome (ARDS). METHODS After human studies approval, we studied 11 burned children with severe ARDS in a trial of inhaled NO therapy, assessing its effect on intrapulmonary shunt as measured by the PaO2/FiO2 ratio (PFR). There were 12 episodes of administration; 1 child was treated twice. RESULTS The children had an average age of 8.3 +/- 4.8 years (mean +/- SEM, range 11 months to 14 years) and average burn size of 64% +/- 22%. At the time of enrollment, the PFR averaged 95 +/- 50 and Murray lung score 3.1 +/- 0.5. Inhaled NO was begun an average of 6.3 +/- 5.5 days after injury and was administered for an average of 7.8 +/- 7.2 days at an average dose of 6.7 +/- 2.4 parts per million. PFR improved an average of 162% +/- 214%. Eight of the 11 children (73%) survived. The 3 nonsurvivors had similar admission PFR values (100 +/- 75 versus 93 +/- 44, P = .089) but a significantly less favorable initial response to inhaled NO, with a percentage of improvement in PFR at 1 hour after enrollment of 7.3% +/- 6.4% versus 213% +/- 226% (P = .026). There were no complications related to NO administration. CONCLUSIONS Inhaled NO can be safely administered to treat ARDS in children with acute burns and appears to improve their ventilatory management. An immediate improvement in PFR with inhaled NO may correlate with survival.

Inhaled nitric oxide in burn patients with respiratory failure.

BACKGROUND Inhaled nitric oxide (NO) has the potential to improve ventilation/perfusion matching and decrease pulmonary artery pressure in patients with profound respiratory failure. METHODS Eight patients, average age of 35 years (range, 2.5-77 years) and burn size 49% (range, 19-80%), with inhalation injury and respiratory failure failing conventional management (average Pao2/FiO2 ratio (PFR) 85) were given inhaled NO at 20 ppm. RESULTS An immediate mean increase in PFR of 10% and a decrease in pulmonary artery mean pressure of 7.8% was noted. At 24 hours, the average improvement in PFR was 28% and that in pulmonary artery mean pressure was 7.7%. Although not reaching statistical significance, these changes were more pronounced in those patients who went on to survive. There was no hypotension attributed to NO administration, and maximum methemoglobin levels averaged 0.9%. CONCLUSIONS Inhaled NO can be safely administered to selected burn patients with severe respiratory failure who are perceived to be failing conventional support. Although current data are not adequate to support its general use, an immediate and sustained improvement in PFR and pulmonary artery mean pressure may correlate with eventual recovery of pulmonary function. Continued evaluation in controlled settings seems warranted and is in progress.

Inhaled corticosteroids for asthma: Are ED visits a missed opportunity for prevention?☆

Inhaled corticosteroids are effective but underused. This study evaluated the outpatient management of emergency department (ED) patients presenting with acute asthma and the relation of inhaled corticosteroid use to the patients primary care provider (PCP) status. ED patients were interviewed by the hospitals asthma education program staff about their asthma. Overall, 85% (101 of 119) of asthmatics reported having a PCP. Although patients with a PCP and patients without a PCP both were using inhaled beta-agonists (93% v 89%, respectively; P = .54), patients without a PCP were less likely to be using inhaled corticosteroids (49% v 11%, P = .003). Controlling for age, acute asthma severity, and asthma hospitalizations during the past year, PCP status remained a significant predictor of inhaled corticosteroid use (odds ratio = 5.6; 95% confidence interval 1.1 to 27). Even among ED patients with a PCP, inhaled corticosteroids appear to be underused. ED asthma visits present an opportunity to initiate preventive measures such as inhaled corticosteroid use.

Expiratory phase and volume-adjusted tracheal gas insufflation : A lung model study

OBJECTIVE To evaluate in a lung model the effects of expiratory-phase tracheal gas insufflation (expiratory-phase TGI) with both volume and pressure control ventilation, and tidal volume-adjusted continuous flow TGI (volume-adjusted TGI) on system pressures and volumes. DESIGN Single-compartment lung model. SETTING Research laboratory in a university medical center. INTERVENTIONS Expiratory-phase TGI was established, using a solenoid valve activated by the ventilator. Volume-adjusted TGI was applied by reducing tidal volume (VT) by the product of TGI flow and inspiratory time. Ventilation was provided with pressure control of 20 cm H2O or volume control ventilation with VT similar to that with pressure control ventilation. A rate of 15 breaths/min and positive end-expiratory pressure (PEEP) of 10 cm H2O were used throughout. Inspiratory time periods of 1.0, 1.5, 2.0, and 2.5 secs were used with TGI flows of 0, 4, 8, and 12 L/min. Lung model compliance (mL/cm H2O) and resistance (cm H2O/L/sec) combinations of 20/20, 20/5, and 50/20 were used. MEASUREMENTS AND MAIN RESULTS In expiratory-phase TGI with pressure control ventilation, peak alveolar pressure remained constant, PEEP increased (p < .01) and VT decreased (p < .01). In expiratory-phase TGI with volume control ventilation and volume-adjusted TGI, there were significant increases in peak alveolar pressure and PEEP (p < .01). Readjustment of VT in volume-adjusted TGI was impossible with longer inspiratory time (> or = 2 secs) and higher TGI flows (> or = 8 L/min). CONCLUSIONS The marked increases in system pressures and volumes observed with continuous-flow TGI can be avoided with expiratory-phase TGI and volume-adjusted TGI.

Measuring gas leakage from bronchopleural fistulas during high-frequency jet ventilation.

A simple volumetric system can be used to measure leakage from bronchopleural fistulas even when inspiratory volumes are unknown or when constant suction is required.

Assessment of errors when expiratory condensate PCO2 is used as a proxy for mixed expired PCO2 during mechanical ventilation

Objectives. We designed a series of experiments to determine whetherexpiratory water condensate (PconCO2) can be used as a proxyfor mixed expired gas collection. Methods. In 18 adult mechanically ventilatedpatients with ARDS (40 samples), simultaneous collections of arterial blood,expiratory water trap condensate, mixed expired gas, and minute ventilationwere used to calculate VCO2 and VD/VT. To assess theeffect of temperature, a constant gas flow (PCO2 10-30mm Hg) was bubbled through water at temperatures of 19.5-37 °C. Gasand water samples were collected, immediately analyzed forPCO2, and a temperature correction factor was calculated. Alung model was constructed using a 5 L anesthesia bag connected to amechanical ventilator with a heated humidifier. Temperature at the Y-piece wasset to ≈37 °C and CO2 was injectedinto the bag to establish an end-tidal PCO2 of 20-70 mmHg. After equilibration, condensate was collected, PCO2 wasmeasured, and the temperature-corrected PCO2 was compared toPĒCO2. The capnogram at points along the expiratory limbcircuit was used to evaluate gas mixing. Results. There was anover-estimation of PĒCO2 by PconCO2 (p <0.001) for the patient data, resulting in an underestimation of VD/VT (p <0.001) and an overestimation of VCO2 (p < 0.001). Thetemperature correction factor for PCO2 in water was−0.010 (about half of the factor used for whole blood). The bias betweentemperature-corrected PconCO2 and PĒCO2 was0.3 ± 3.2 mm Hg in the lung model. Mixing in the expiratory limb waspoor, as evaluated by the capnogram. Conclusions. Even with temperaturecorrection, we failed to precisely predict PĒCO2 fromPconCO2. For measurement of VD/VT andVCO2, we do not recommend methods that usePconCO2.