Current methods of forcing end-tidal P CO 2 (P ETCO 2 ) and P O 2 (P ETO 2 ) rely on breath-by-breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo-control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath-by-breath basis. In this paper, we introduce a low gas flow method to prospectively target and control P ETCO 2 and P ETO 2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change P ETCO 2 from control (40 mmHg for P ETCO 2 and 100 mmHg for P ETO 2 ) to two target P ETCO 2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), P ETO 2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and P ETCO 2 with P ETO 2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, P ETCO 2 and P ETO 2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for P ETCO 2 was ± 1 mmHg, and for P ETO 2 was ± 4 mmHg. P ETCO 2 varied by ± 1 mmHg and P ETO 2 by ± 5.6 mmHg (S.D.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min −1 ). We conclude that targeted end-tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed-forward, low gas flow system.

The predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.

No abstract

Cerebrovascular reactivity can be quantified by correlating blood oxygen level dependent (BOLD) signal intensity with changes in end-tidal partial pressure of carbon dioxide (PCO 2 ). Four 3-min cycles of high and low PCO 2 were induced in three subjects, each cycle containing a steady PCO 2 level lasting at least 60 sec. The BOLD signal closely followed the end-tidal PCO 2 . The mean MRI signal intensity difference between high and low PCO 2 (i.e., cerebrovascular reactivity) was 4.0 ؎ 3.4% for gray matter and 0.0 ؎ 2.0% for white matter. This is the first demonstration of the application of a controlled reproducible physiologic stimulus, i.e., alternating steady state levels of PCO 2 , to the quantification of cerebrovascular reactivity. Cerebral blood flow is generally determined by the metabolic demand of the brain tissue. The capacity for autoregulation can be assessed by measuring hemodynamic responses to a quantifiable stimulus such as a change in partial pressure of carbon dioxide (PCO 2 ). The magnitude of the hemodynamic response relative to the alteration in PCO 2 is termed "cerebrovascular reactivity"; changes in blood oxygen level-dependent (BOLD) signal intensity can be used as an indicator of this reactivity.Our aim was to induce changes in MR signal intensity with changes in end-tidal PCO 2 (PETCO 2 ) by:1. Selecting two easily tolerated levels of PETCO 2 sufficiently different from each other to improve the accuracy in estimating cerebrovascular reactivity by minimizing the effect of noise; 2. Maintaining each PETCO 2 at a steady level long enough to allow stabilization of cerebral blood flow and facilitate correlation of the BOLD signal intensity to a specific PETCO 2 ; and 3. Effecting rapid step changes between steady-state levels of PCO 2 in order to allow multiple measurements of cerebrovascular reactivity within the time available for scanning, thereby minimizing the confounding effect of baseline signal drift typically present in functional imaging data. MATERIALS AND METHODSFollowing institutional ethics approval, we studied one healthy female and two healthy male subjects. The subjects' inspired gas concentrations were supplied via the circuit depicted in schematic form in Fig. 1. Each subject breathed through a mouthpiece (No. 109-P; Vacumed, Ventura, CA) attached to a right angle connector (to enable it to fit inside the MRI head coil). This mouthpiece allows occlusion of the teeth and thus aids in the swallowing of excess saliva while supine. Airway PCO 2 was monitored continuously at the mouth (Capnomac Ultima, Datex Engstrom, Helsinki, Finland) and recorded digitally (Dataq, Akron, OH). Control of PETCO 2Our protocol involved four 3-min cycles of raising and lowering the PETCO 2 . During each cycle the high PETCO 2 level was attained by delivering into the circuit 8% CO 2 in O 2 , at 15 L/min for 10 -15 sec, and maintained at that level by delivering 100% O 2 (the fresh gas flow) at 0.5-2 L/min for the remainder of the 90 sec. The low PETCO 2 was attained by delivering 100% O 2 at ...

Nitric Oxide (NO) has been implicated in the pathologic vasodilation of sepsis. Because NO can be measured in the exhaled gas of animals and humans, we hypothesized that increases in exhaled NO would occur in a septic model. Using a blinded design, 10 male Sprague-Dawley rats (300 to 400 g) were anesthetized, paralyzed, tracheotomized, and randomized (5/group) to receive an intravenous injection of either lipopolysaccharide (LPS) (Salmonella typhosa, 20 mg/kg) or placebo (equal volume of saline). Thereafter, exhaled gas was collected and measurements of NO concentration were made using chemiluminescence every 20 min for 300 min during ventilation (RR 40 breaths/min, VT 3 ml; PEEP 0, FIO2 0.21). Another group of 10 animals (5 LPS; 5 control) were treated in the same fashion and then killed at 240 min and an arterial blood sample obtained for blood gas and TNF alpha determinations. Pressure volume (PV) curves were constructed and lungs removed, preserved, and submitted for histologic evaluation. LPS-treated rats had lower mean arterial pressures than the control group, p < 0.0001. No significant differences in static lung compliance and PV curves were found in the two groups. TNF alpha levels were greater in the LPS group (1.40 +/- 0.24 ng/ml) versus control group (0.09 +/- 0.04 ng/ml), p < 0.001. By contrast to the control group, exhaled NO concentration rose in all LPS-treated rats at approximately 100 min and at about 160 min reached a plateau that was 6 times greater than control levels (p < 0.0001). There was greater interstitial, airspace, and total lung injury in the LPS group (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

Several clinical conditions [1][2][3] and research protocols [4][5][6][7] require increases in minute ventilation (V 'E) at constant (or nearly constant) arterial carbon dioxide tension (Pa,CO 2 ). At a constant CO 2 production, Pa,CO 2 is inversely related to alveolar ventilation (V 'A), which is a function of V 'E. When V 'E increases, Pa,CO 2 falls unless CO 2 is added to the inspired gas. Maintaining a constant Pa,CO 2 despite an irregular breathing pattern requires continuous and proportional adjustment of the fractional concentration of inspired CO 2 (FI,CO 2 ). Manual adjustments of FI,CO 2 may be adequate if changes in V 'E are slow or if wide variations in V 'A are acceptable. Automated feedback systems provide finer control of V 'A but can result in phase delays, unstable responses or overdamping, despite the use of expensive equipment and complex algorithms. A simple breathing circuit was developed and tested that minimizes the effect of V 'E on V 'A by passively and continuously matching the inspired CO 2 to V 'E regardless of the extent or pattern of breathing. MethodsThe basic concept underlying this approach is that the flow of fresh gas (FI,CO 2 =0) contributing to alveolar CO 2 exchange is kept constant. When V 'E is less than or equal to the fresh gas flow (FGF), the subject inhales only fresh gas. Therefore:When V 'E exceeds FGF, the balance of inhaled gas is drawn from a reservoir containing a reserve gas with a carbon dioxide tension (PCO 2 ) equal to that of mixed venous blood and thus does not participate in CO 2 exchange, ensuring that V 'A is limited by FGF, as indicated by the following equation:where Pv,CO 2 is the oxygenated mixed venous PCO 2 . When the PCO 2 of the mixed venous and reserve gas are not equal, the V 'A depends on both this difference and the difference between V 'E and FGF. Circuit descriptionThe circuit ( fig. 1) A simple, passive circuit that minimizes changes in V 'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO 2 =0%) equal to the subject's minute ventilation (V 'E). During hyperpnoea, the balance of V 'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO 2 ) approximates that of mixed venous blood and therefore contributes minimally to V 'A.Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO 2 (Pet,CO 2 ) at rest, 0, 1.5 and 3.0 min were ( In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea. Eur Respir J 1998; 12: 698-701.

This study demonstrates that the mode of mechanical ventilation used in the early phase of reperfusion of the transplanted lung can influence ischemia-reperfusion injury, and a protective ventilatory strategy on the basis of minimizing pulmonary mechanical stress can lead to improved lung function after lung transplantation.