Previous investigations have shown that the ventilation-perfusion (VA/Q) mismatch caused by acute lung injury can be alleviated either by inducing vasodilation in ventilated lung units with inhaled nitric oxide (NO) or by inhibiting the synthesis of endogenous NO, which opposes hypoxic pulmonary vasoconstriction. To determine the effects of a combination of these interventions, we evaluated cardiopulmonary function and VA/Q distributions in 10 dogs with oleic acid-induced lung injury. Each animal received, in random order, zero or 40 ppm of NO in inspiratory gas, with and without intravenous infusion of N-G-monomethyl-L-arginine (L-NMMA) (5 mg/kg/h). The multiple inert-gas elimination technique was used to estimate VA/Q distributions. Systemic L-NMMA administration alone did not affect VA/Q inequality and gas exchange, but increased pulmonary and systemic vascular resistance. Inhaled NO improved gas exchange by redistributing blood flow from shunt units to lung units with a nearly ideal VA/Q ratio, without affecting pulmonary or systemic vascular resistance. Improved VA/Q matching and gas exchange was most pronounced when NO was inhaled in the presence of systemic L-NMMA. Inhalation of NO reversed the pulmonary but not the systemic vasoconstriction caused by L-NMMA. These results suggest that endogenous NO release is not limited to hypoxic lung regions in animals with oleic acid-induced lung injury. Inhaled NO reversed L-NMMA-induced pulmonary vasoconstriction and improved VA/Q matching by selectively dilating the pulmonary vasculature in ventilated lung units.

Fu, E. S. M.D.†; Naidu, K. A. Ph.D.*; Prockop, L. D. M.D.*; Downs, J. B. M.D.† Author Information

OBJECTIVES The present study was designed to evaluate if continuous positive airway pressure (CPAP) augments the effect of nitric oxide (NO) inhalation on matching between ventilation and perfusion (VA/Q) during acute lung injury. DESIGN Prospective, randomized study. SETTING A research laboratory at a university medical center. SUBJECTS Ten anesthetized mongrel dogs with oleic acid-induced lung injury. INTERVENTIONS Zero or 40 parts per million of NO in the inspiratory gas, with and without 10 cm H2O CPAP in random order. MEASUREMENTS AND MAIN RESULTS Gas exchange was assessed by estimating the VA/Q distributions using the multiple inert gas elimination technique. Application of CPAP decreased blood flow to shunt units by 26 +/- 2 percent (mean +/- SD) and increased the fraction of cardiac output to normal VA/Q units (VA/Q ratio of 0.1 to 10) by 26 +/- 2 percent (p < 0.05). Inhalation of NO during CPAP accounted for a further 10 +/- 2 percent decrease in the blood flow to shunt units and an 8 +/- 2 percent increase in the fraction of the cardiac output to normal VA/Q units (p < 0.05). Inhalation of NO alone had no significant effect on the VA/Q distributions. Inhalation of NO decreased mean transmural pulmonary artery pressure (Ppatm) both without (Ppatm from 30 +/- 2 to 23 +/- 2 mm Hg; PVR from 323 +/- 44 to 228 +/- 43 dynes.s .cm-5; p < 0.05) and with CPAP (Ppatm from 25 +/- 2 to 20 +/- 2 mm Hg; PVR from 255 +/- 30 to 173 +/- 31 dynes.s.cm-5; p < 0.05). CONCLUSIONS Although pulmonary vascular resistance can be lowered with NO inhalation alone, recruitment of gas exchange units with CPAP is necessary to produce a beneficial effect of NO inhalation on VA/Q matching and oxygenation. When recruitment of gas exchange units with CPAP brings gaseous NO in contact with enough pulmonary blood vessels, NO-induced vasodilation will augment VA/Q matching by a steal mechanism.

BACKGROUND:Improved matching between ventilation and perfusion (VA/Q) has been proposed to be a major advantage of partial ventilatory support compared with controlled mechanical ventilation. This study was designed to determine whether a difference in gas exchange exists between partial ventilatory support techniques that allow unsupported spontaneous breathing to occur during any phase of the mechanical ventilatory cycle and those that provide mechanical support for each spontaneous inspiratory effort. METHODS:Ten anesthetized dogs with oleic acid-induced lung injury received, in random order, pressure-support ventilation (PSV) and airway pressure-release ventilation (APRV) with and without spontaneous breathing using equivalent airway pressure limits. Gas exchange was assessed by conventional blood gas analysis and by estimating the VA/Q distributions using the multiple inert-gas elimination technique. RESULTS:During APRV, spontaneous breathing accounted for 10 +/- 1% of the total expiratory minute ventilation. Breath-to-breath ventilatory support with PSV resulted in the highest total expiratory minute ventilation (P < 0.05). During spontaneous breathing with APRV, cardiac output increased from 3.9 +/- 0.3 to 4.6 +/- 0.41.min-1 (P < 0.05), arterial oxygen tension from 75 +/- 3 to 107 +/- 8 mmHg (P < 0.05), and oxygen delivery from 567 +/- 47 to 719 +/- 73 ml.kg.min-1 (P < 0.05). PSV did not increase cardiac output, arterial oxygen tension, and oxygen delivery. Spontaneous breathing did not increase oxygen consumption. During APRV spontaneous breathing accounted for a 13 +/- 2% decrease (P < 0.05) in blood flow to shunt units (VA/Q < 0.005) and a 14 +/- 2% increase (P < 0.05) in the perfusion of normal VA/Q units (0.1 < VA/Q < 10). Pulmonary blood flow distribution to shunt and normal VA/Q units was similar during PSV and APRV without spontaneous breathing. Dead space (VA/Q > 100) ventilation decreased by 6% during APRV with spontaneous breathing compared with PSV (P < 0.05). CONCLUSIONS:Spontaneous breathing superimposed on mechanical ventilation contributes to improved VA/Q matching and increased systemic blood flow. Apparently, the spontaneous contribution to a mechanically assisted breath during PSV is not sufficient to counteract the VA/Q maldistribution of positive pressure lung insufflation during acute lung injury.

VALENTINE, D. D.; HAMMOND, M. D.; DOWNS, J. B.; SEARS, N. J.; SIMS, W. R. Author Information

“Assessment” of oxygenation may entail measurement and calculation of a variety of physiologic variables. However, the oxygen tension of arterial blood (P a02) is by far the most common measurement utilized in determining the of “adequacy” of oxygenation. Because of the case of measurement, PaO2, often is used as a guide to oxygen therapy, ventilator adjustment, and other therapeutic interventions. Some clinicians have suggested a mathematical manipulation of Pa02, alone or in combination with other variables, to improve diagnostic accuracy and assessment of pulmonary function. The pereeived advantage of using the alveolararterial O2 tension difference (AAD), the arterial/alveolar oxygen tension ratio (AAI), the PaO2/FIO2 ratio (PFI), etc., rather than the PaO2 alone, often is far greater than the aetual advantage. It is apparent that the ease and effideney of measurements and calculations have played a greater role in the determination of monitoring practices than accuracy and efficacy. Because of advances in monitoring technology during the last decade, a reassessment of monitoring techniques is indicated.

ObjectiveTo evaluate the feasibility of airway pressure release ventilation (APRV) in providing ventilatory support to patients with acute lung injury of diverse etiology and mild-to-moderate severity. DesignProspective, multicenter, nonrandomized crossover trial. SettingICUs in six major referral hospitals. PatientsFifty adult patients with respiratory failure requiring mechanical ventilation and positive end-expiratory airway pressure. InterventionsAfter optimization of continuous positive airway pressure (CPAP), conventional ventilation and APRV were administered sequentially for 30 mins. During APRV, the CPAP level and airway pressure release level were adjusted to prevent hypoxemia, while the degree of ventilatory support was adjusted by altering the frequency of pressure release. Measurements and Main ResultsCirculatory and ventilatory pressures, arterial blood gases and pH, heart rate, and respiratory rate were measured. Alveolar ventilation was augmented adequately in 47 of 50 patients by APRV. Adjustment of APRV required an increase in mean CPAP from 13 ± 3 (SD) to 21 ± 9 cm H2O and a release pressure of 6 ± 5 cm H2O. This airway pressure pattern produced a mean airway pressure comparable to that pressure achieved during conventional ventilation. Failure of APRV in three patients could be attributed to an inadequate level of CPAP or an inadequate APRV rate. While maintaining oxygenation of arterial blood and circulatory function, APRV allowed a substantial (55 ± 17%; p < .0001) reduction in peak airway pressure compared with conventional positive pressure ventilation adjusted to deliver a comparable or lower level of ventilatory support. ConclusionsAPRV is a feasible alternative to conventional mechanical ventilation for augmentation of alveolar ventilation in patients with acute lung injury of mild-to-moderate severity.

We compared pulmonary gas exchange during synchronized intermittent mandatory ventilation (SIMV), pressure support ventilation (PSV), and airway pressure release ventilation (APRV). Nine subjects aged 56 to 75 yr were studied from 4 to 19 h after cardiac operations. When subjects were ready to be weaned from mechanical ventilation their ventilation-perfusion distribution was estimated using the multiple inert gas elimination technique during SIMV. The subjects then received PSV and APRV during alternating periods on a randomized basis, and the gas-exchange measurements were repeated. Vasoactive infusions and inspired oxygen fraction were held constant throughout the investigation. The results indicated that the major characteristics of the main mode of the VA/Q distributions (mean, standard deviation, and skew) were similar during all three modes. Dead space was lower during APRV (30.1 +/- 1.7% [SEM]) than during SIMV (36.2 +/- 1.5%) and PSV (37.1 +/- 2.7%) (p less than 0.05). Right-to-left shunt was significantly greater during APRV (19.9 +/- 2.3%) than during SIMV (15.4 +/- 1.7%) (p less than 0.05). Peak airway pressure (Paw) was higher during SIMV (32.8 +/- 1.3 cm H2O) than both PSV (19.4 +/- 2.1 cm H2O) and APRV (14.3 +/- 1.0 cm H2O) (p less than 0.05). Minute ventilation was lower during APRV (7.5 +/- 0.07 L/min) than during SIMV (9.4 +/- 0.6 L/min) and PSV (9.0 +/- 0.5 L/min) (p less than 0.05). Hemodynamic variables were similar during all three modes. We conclude that all three modes provide acceptable oxygenation and ventilatory support.

As early as the 1970s, several authorities stated that further development of mechanical ventilatory techniques would not alter the outcome of patients with respiratory failure. They suggested directing research efforts toward extinguishing the process of lung injury at the cellular level. These arguments now appear more valid than ever. No evidence indicates that a particular ventilatory support modality improves the survival rate of patients with respiratory failure. Fortunately or not, these doubts have not thwarted enthusiasm for new ventilatory modalities. A well-informed intensivist could easily list two dozen acronyms describing current techniques of mechanical ventilation. Since adoption of a new modality is an intellectual, educational, and economical investment, determining whether it represents a true advancement in respiratory care is important. However, information that would help the clinician distinguish between viable and vanishing techniques is lacking. Mushin et al1Mushin WW Rendell-Baker L Thompson PW Automatic ventilation of the lungs. Blackwell, Oxford1959Google Scholar published the first classification of mechanical ventilators. This traditional classification is based primarily on technical aspects of ventilator function and is not helpful in predicting differences in the cardiopulmonary effects of individual ventilatory techniques. Therefore, we propose a new classification based on three physiologic characteristics that predict significant clinical differences between various ventilatory modalities: (1) the method by which lung volume is altered, (2) the magnitude of tidal volume relative to respiratory dead space, and (3) the mechanism by which ventilatory support modifies the patient's spontaneous breathing.2Räsänen J Downs JB Modes of mechanical ventilatory support..in: Kirby RR Banner MB Downs JB Clinical applications of ventilatory support. Churchill Livingstone, New York1990Google Scholar Lung volume for a given lung compliance is determined by the difference between airway and intrathoracic pressure. A change in lung volume follows an increase or decrease in airway pressure or an elevation or reduction in intrathoracic pressure. Ventilatory techniques that use different methods to alter lung volume are likely to produce clinically significant differences in airway and intrathoracic pressure. The magnitude of the tidal volume causes considerable physiologic differences between ventilatory techniques. Alveolar gas mixing is largely dependent on the ratio of tidal volume to respiratory dead space volume. Modalities that deliver a tidal volume significantly greater than dead space depend upon mass movement of gas for alveolar gas mixing; techniques that employ tidal volumes substantially smaller than dead space rely on other mechanisms. Although low volume, high frequency ventilation has been shown anecdotally to improve ventilation and oxygenation with a reduction in peak airway pressure, its large-scale clinical significance remains questionable. Two major strategies are used to modulate the patient's spontaneous breathing during partial ventilatory support. Pressure support ventilation modulates tidal volume and provides mechanical assistance to every inspiratory effort. No ventilatory effort is unsupported, and the degree of ventilatory support does not vary with respiratory rate. In contrast, intermittent mandatory ventilation modulates minute ventilation by adding exogenous breaths to the patient's own breathing pattern. Spontaneous breaths are unsupported, and a fixed level of mechanical ventilation is delivered, even if minute ventilation requirements change. Physiologic effects of these differences in patient-ventilator interfacing are not well known, but they may prove to be significant. In this issue (see page 460), Cane et al address the utility of airway pressure release ventilation (APRV), a recently introduced ventilatory support modality that clearly differs from others in its physiologic characteristics. During APRV, the active phase of the ventilator produces a fall in airway pressure and decreases lung volume from the equilibration volume established by continuous positive airway pressure (CPAP). The tidal volume of an APRV breath is larger than dead space, defining APRV as a high volume, low frequency technique. Adequate minute ventilation is maintained during APRV by adding mechanical cycles to the patients spontaneous breathing pattern. Cane et al describe APRV as a form of inverse ratio ventilation (IRV), a definition that is true only when APRV provides full ventilatory support. Unlike IRV, APRV can provide any degree of partial ventilatory support. The relationship between APRV and IRV is similar to that between intermittent mandatory ventilation and controlled positive pressure ventilation. This similarity holds true even for the inaccuracy with which the effects of a partial ventilatory support technique can be deduced from those of the corresponding full-support method. Therefore, it may be more accurate to describe IRV as a form of APRV than vice versa. The physiologic characteristics of APRV should produce a lower peak and mean airway pressure, lung volume, and mean intrathoracic pressure than techniques that inflate the lungs from the same level of CPAP using positive pressure. Consequently, possible advantages of APRV are a lower risk of structural lung injury, improved matching of ventilation and perfusion, and reduction in cardiovascular compromise. Some of these considerations are supported by Cane et al who observed average reductions of 40 percent in peak airway pressure and 31 percent in mean airway pressure upon changeover to APRV Results of their study verify differences between APRV and continuous positive pressure ventilation and justify large-scale evaluation of APRV Determining whether physiologic advantages of new ventilator technology translate into improved outcome will require years of scientific and clinical evaluation. In the meantime, we will do well to look for differences, rather than similarities, in ventilatory methodology.

“Assessment” of oxygenation may entail measurement and calculation of a variety of physiologic variables. However, the oxygen tension of arterial blood (PaO2) is by far the most common measurement utilized in determining the “adequacy” of oxygenation. Because of the ease of measurement, PaO2 often is used as a guide to oxygen therapy, ventilator adjustment, and other therapeutic interventions. Some clinicians have suggested a mathematical manipulation of PaO2, alone or in combination with other variables, to improve diagnostic accuracy and assessment of pulmonary function. The perceived advantage of using the alveolar-arterial O2 tension difference (AAD), the arterial/alveolar oxygen tension ratio (AAI), the PaO2/F1O2 ratio (PFI), etc., rather than the PaO2 alone, often is far greater than the actual advantage. It is apparent that the ease and efficiency of measurements and calculations have played a greater role in the determination of monitoring practices than accuracy and efficacy. Because of advances in monitoring technology during the last decade, a reassessment of monitoring techniques is indicated.

This randomized, controlled, crossover study evaluated the effect of continuous positive airway pressure (CPAP) breathing on hepatic blood flow (HBF) and cardiac output in 10 healthy male subjects. A CPAP mask was placed on the face and the subject breathed at either CPAP 12.5 cm H2O or ambient airway pressure. The estimated HBF was calculated as the ratio of indocyanine green plasma clearance to one minus the hematocrit. Cardiac output was measured with Doppler ultrasound. CPAP caused HBF to decrease in 8 of 10 subjects (14.1% +/- 15.3%, mean +/- SD, p = 0.033) and cardiac index (CI) to decrease in all subjects (14.1% +/- 5.7%, p = 0.0001). Stroke volume and respiratory rate were significantly decreased; heart rate was unchanged. These results indicate that CPAP at 12.5 cm H2O causes a small, but significant decrease in both HBF and CI.

Clinicians frequently adopt an imperical approach to the respiratory care of patients with pulmonary failure. As a result, only the symptomatology is treated, which often fails to restore normal pulmonary function and may have deleterious side effects. Since therapeutic interventions may have significant physiologic consequences, rational application of therapies requires an understanding of the variable physiologic effects of different ventilatory patterns. The following analysis will consider some of these effects in terms of volume expansion and pressure transmission. Generally speaking, the volume related effects of positive airway pressure may be considered therapeutic and the pressure related effects as less desirable side effects. However, as we shall see, these generalizations may have exceptions.