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CRITICAL CARE AND TRAUMA

The Effects of Nebulized Salbutamol, External Positive End-Expiratory Pressure, and Their Combination on Respiratory Mechanics, Hemodynamics, and Gas Exchange in Mechanically Ventilated Chronic Obstructive Pulmonary Disease Patients

Maria Tzoufi, MD, DEAA^*, Spyros D. Mentzelopoulos, MD, PhD, DEAA^*, Charis Roussos, MD, PhD, and Apostolos Armaganidis, MD, PhD^*

*Department of Intensive Care Medicine, Attikon University Hospital; and Department of Intensive Care Medicine, Evaggelismos General Hospital, Athens, Greece

Address correspondence and reprint requests to Maria Tzoufi, MD, DEAA, 12 Ioustinianou St., GR-11473, Athens, Greece. Address e-mail to sdm{at}hol.gr.

	Abstract

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We hypothesized that combined salbutamol and external positive end-expiratory pressure (PEEPe) may present additive benefits in chronic obstructive pulmonary disease (COPD) exacerbation. In 10 anesthetized, mechanically ventilated, and bronchodilator-responsive COPD patients exhibiting moderate intrinsic PEEP (PEEPi), we assessed respiratory system (rs) mechanics, hemodynamics, and gas exchange at (a) baseline (zero PEEPe [ZEEPe]), (b) 30 min after 5 mg of nebulized salbutamol administration (ZEEPe-S), (c) 30 min after setting PEEPe at baseline PEEPi level (PEEPe), and (d) 30 min after 5 mg of nebulized salbutamol administration with PEEPe maintained unchanged (PEEPe-S). Return of determined variable values to baseline values was confirmed before PEEPe application. Relative to ZEEPe, (a) at ZEEP-S, PEEPi (4.8 ± 0.7 versus 7.0 ± 1.1 cm H₂O), functional residual capacity change (115.6 ± 23.1 versus 202.1 ± 46.0 mL), minimal rs (airway) resistance (9.3 ± 1.4 versus 11.8 ± 2.2 cm H₂O·L^–1·s^–1), and additional rs resistance (5.2 ± 1.4 versus 7.2 ± 1.3 cm H₂O·L^–1·s^–1) were reduced (P < 0.01), and hemodynamics were improved; (b) at PEEPe, PEEPi (3.7 ± 1.3 cm H₂O) was reduced (P < 0.01), and gas exchange was improved; and (c) at PEEPe-S, PEEPi (2.0 ± 1.2 cm H₂O) was minimized, and rs mechanics (static rs elastance included), hemodynamics, and gas exchange were improved. Conclusively, in carefully preselected COPD patients, bronchodilation/PEEPe exhibits additive benefits.

	Introduction

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Expiratory airflow limitation is the cardinal feature of chronic obstructive pulmonary disease (COPD). The lungs cannot deflate to elastic equilibrium volume, and dynamic hyperinflation ensues. Thus, airway pressure remains positive throughout expiration, and intrinsic positive end-expiratory pressure (PEEPi) develops. During mechanical ventilation, adverse effects of PEEPi comprise barotrauma risk, hemodynamic compromise, increased inspiratory muscle workload, and weaning failure (1–3). Several measures have been shown to attenuate the deleterious effects of PEEPi, i.e., helium/O₂ mixture administration (4), bronchodilation (5), external PEEP (PEEPe) application (4,6,7), and ventilatory settings optimization (8).

In mechanically ventilated COPD patients, the rationale for the use of ß₂-adrenergic agonists focuses on airway secretion mobilization, airway resistance reduction, dynamic hyperinflation attenuation, and work-of-breathing improvement. Inhalation via a small-volume nebulizer or a metered dose inhaler is the preferred method of administration. Several studies have shown that nebulizers enhance drug deposition into the lungs (9,10).

Counterbalancing of PEEPi by PEEPe (3,6,11–13) may attenuate dynamic hyperinflation and inspiratory breathing work (3,7) and improve arterial oxygenation (6), without significant changes in inspiratory airway resistance or hemodynamics (6,11–13).

The potential additive benefits of combined ß₂-adrenergic agonists and PEEPe have not been elucidated. In the present study, we tested the hypothesis that such combined treatment may present additive benefits for respiratory system (rs) mechanics and gas exchange without adversely affecting hemodynamics. Study participants were mechanically ventilated COPD patients who were carefully preselected mainly according to their responsiveness to bronchodilators and the range of their PEEPi values.

	Methods

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IRB approval and informed patient or next-of-kin consent were obtained. Ten mechanically ventilated COPD patients with acute respiratory failure secondary to COPD exacerbation were enrolled. COPD diagnosis was based on medical history, clinical examination, chest roentgenograms, and recent pulmonary function tests. Table 1 displays individual patient characteristics. Spirometry confirmed airway obstruction reversibility during the preadmission period of clinical stability (at least a 15% increase in forced expiratory volume in 1 s after bronchodilator drug administration). Another major inclusion criterion was individual PEEPi values at (described below) baseline ventilation within 5–10 cm H₂O. Exclusion criteria were mechanical ventilatory mode other than volume-controlled, hemodynamic instability requiring inotrope use, theophylline administration, atelectasis, pneumonia, pulmonary edema, refractory hypoxemia, pneumothorax, sepsis, history of (or acute) myocardial ischemia, cardiac arrhythmias, and mean pulmonary arterial pressure (MPAP) >30 mm Hg or tricuspid valve regurgitation more than 13% (determined by transthoracic echocardiography) (13–15).

The study took place 48–72 h after institution of mechanical ventilation. Just before study protocol initiation, patients were placed semirecumbent (30-degree inclination), anesthesia was induced with midazolam and fentanyl, endotracheal suctioning was performed, and baseline ventilation was initiated as described below. Mechanical ventilation (via 8.0- to 8.5-mm internal diameter, 28 cm long, cuffed endotracheal tube) was performed with a Siemens 300C ventilator (Siemens AG, Berlin, Germany). The ventilator circuit comprised low compliance tubing (without water traps) connected to a Y-piece. Closed-system suction devices were omitted. Bronchodilators were withheld for at least 12 h before study initiation. All enrollees received IV steroids (3 mg/kg of methylprednisolone per day divided in four doses), which were initiated on intensive care unit admission; this regimen remained unmodified throughout the study period. Heavy sedation (midazolam and fentanyl infusion) throughout the study period abolished any respiratory muscle activity. The latter was confirmed by the absence of negative deflection in the airway pressure waveform and by waveform stabilization (14).

Electrocardiographic leads II and V5 and peripheral oxygen saturation were continuously monitored. A 20-gauge radial arterial catheter and a 3-port, balloon-tipped pulmonary artery catheter with fast-response thermistor (Arrow International, Reading, PA) were inserted. Both catheters were connected to pressure transducers and provided continuous monitoring of heart rate and mean arterial blood pressure (MAP), MPAP, and central venous pressures (CVP); the midaxillary line represented the zero reference level.

Baseline ventilator settings were as follows: mode: volume controlled, tidal volume: 8–9 mL/kg of predicted body weight (see Appendix), inspiratory flow: 0.75 ± 0.02 L/s (square-wave), inspiratory-to-total respiratory cycle length ratio: 0.25 ± 0.02, respiratory rate: 14 ± 2 bpm, fraction of inspired oxygen (Fio₂): 0.35–0.50, end-inspiratory pause: zero, and zero PEEPe (ZEEPe). After 45 min of baseline ventilation, patients received a first salbutamol dose (5 mg diluted in normal saline to 5 mL total volume) via a small-volume nebulizer (Micro Mist, Hudson, Upplands, Sweden). The device was placed in the inspiratory limb of the ventilator circuit, 30 cm from the Y-piece, and airflow through the nebulizer was set at 8 L/min (16). The device was completely dried out in approximately 25 min. After an 8 h washout period (third measurement time point; see below), measurement of respiratory mechanics, hemodynamics, and gas exchange confirmed return of variable values to corresponding baseline values (Tables 2 and 3). Subsequently, PEEPe was set at the PEEPi value determined during baseline ventilation, with the rest of the ventilatory settings maintained unchanged. Forty-five minutes thereafter (with PEEPe maintained unchanged), 5 mg of nebulized salbutamol was administered, as described above.

Inspiratory airflow (V/s) was measured with a heated pneumotachograph (3700, 0–160 L/min; Hans Rudolph Inc, Kansas City, MO) connected to a differential pressure transducer (DP 55 ± 3.5 cm H₂O; Raytech Instruments, North Vancouver, British Columbia, Canada) and placed between the endotracheal tube and Y-piece. Tidal volume was measured by V/s-signal integration. Tracheal pressure was measured via a 1.5-mm internal diameter catheter connected to a pressure transducer (DP 55 ± 100 cm H₂O; Raytech Instruments). Care was taken to avoid gas leaks. Respiratory mechanics were assessed with rapid airway occlusion during constant flow inflation (17). End-inspiratory occlusion (5-s duration) resulted in an abrupt airway pressure decrease from a maximal value (Pmax) to a lower value (P₁), followed by a gradual decline to a plateau pressure (P₂) (Fig. 1). End-expiratory occlusion (EEO) (5-s duration) resulted in an airway pressure increase to a plateau value representing PEEPi (Fig. 1). Whenever PEEPe was applied, EEO plateau pressure represented the sum of PEEPi and PEEPe, i.e., total PEEP (PEEPtot).

View larger version (18K): [in this window] [in a new window]   Figure 1. Methodology of assessment of respiratory system mechanics with the rapid airway occlusion technique. Printout of computer-stored data display at the baseline study time point (zero positive end-expiratory pressure [ZEEPe] before salbutamol administration). Data originated from a representative patient of the present study (patient No. 8 of Table 1 and Fig. 2). Vt = tidal volume; Pmax = maximal airway pressure; P1 = pressure immediately after end-inspiratory airway occlusion; P2 = plateau airway pressure; PEEPtot = total positive end-expiratory pressure, which coincides with intrinsic positive end-expiratory pressure (PEEPi) at this particular time point.

View larger version (25K): [in this window] [in a new window]   Figure 2. Individual intrinsic positive end-expiratory pressure (PEEPi) values at four study time points. As in Table 1, patient numbers correspond to the order of enrollment in the study. The continuous decline of PEEPi along the four time points is evident in all patients. At PEEPe-S, PEEPi is practically abolished in four patients (patients 1, 2, 7, and 10). PEEPi values at the ZEEP-II time point (see also Methods and Tables 2 and 3) are not presented because at ZEEP-II, PEEPi values were virtually identical to values at ZEEP-I. PEEP = positive end-expiratory pressure; ZEEP = zero PEEP (ZEEP-I time point; see also Methods and Tables 2 and 3); S = salbutamol; PEEPe = external PEEP.

Functional residual capacity change (FRC) was assessed as follows: after a (brief 1 s) end-inspiratory occlusion, the patient was temporarily disconnected from the ventilator and allowed to exhale to respiratory system relaxation volume (15,17). FRC was then computed as expired-to-tidal volume difference. After analog-to-digital conversion (sample rate = 200 Hz), respiratory mechanics data were analyzed, as previously described (15). At each study time point, respiratory mechanics were assessed in triplicate, and only mean values of the measurement sets were analyzed.

Maximal (Rmax,rs), ohmic (Rmin,rs), and additional (R,rs) rs resistances were computed as corresponding Pmax – P₂, Pmax – P₁, and P₁ – P₂ differences divided by the preceding airflow. Static rs elastance (Estat,rs) was computed as P₂ – PEEPi or P₂ – PEEPtot (whenever PEEPe was applied), with the difference divided by the preceding tidal volume.

Heart rate, MAP, and MPAP were recorded (and averaged) over a 3-min period. Immediately thereafter, pulmonary capillary wedge pressure (PCWP) and CVP were measured at end expiration and averaged over three consecutive respiratory cycles. Subsequently, thermodilution cardiac output (CO) was determined in triplicate; injections of 10 mL of cold saline were performed during expiration. At all study time points, the variance of individual CO measurements was always <10%; thus, CO measurement repetition was never necessary (11). After CO determination, mixed venous and arterial blood gas samples were simultaneously collected and immediately analyzed. Only blood gas analysis-derived mixed venous oxygen saturation (SvO₂) values were included in the subsequent data analysis (15). Systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), oxygen delivery (DO₂), oxygen consumption, and shunt fraction (Qs/Qt) were calculated according to standard formulas (see Appendix).

For each of the above-mentioned time points, only the means of obtained variable value sets were analyzed. Variable comparisons among measurement time points were performed with repeated measures analysis of variance. The Scheffé test was used for post hoc analysis. Significance was set at P < 0.05. Values are presented as mean ± sd.

	Results

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Complete measurement sets were obtained from all patients; no protocol-related complications (15) occurred. Nine patients were weaned from mechanical ventilation and discharged from the intensive care unit within 8–13 days postadmission, and one patient died of sepsis 11 days postadmission.

Tables 2 and 3 display results on respiratory mechanics and hemodynamics, respectively.

Relative to baseline (ZEEPe time points), the ZEEPe-S maneuver produced decreases in Rmax,rs, Rmin,rs, R,rs, FRC, PEEPi, PCWP, and SVR and increases in heart rate, SvO₂, and DO₂.

Compared to ZEEPe, the PEEPe maneuver (a) attenuated PEEPi, (b) improved Pao₂, and (c) reduced Paco₂ and Qs/Qt.

Relative to ZEEPe, the PEEPe-S combination caused: (a) Rmax,rs, Rmin,rs, FRC, PCWP, and SVR to decrease and heart rate and DO₂ to increase, similar to that observed at ZEEP-S; (b) Pao₂ to increase and Qs/Qt to decrease, similar to that observed at PEEPe; (c) Estat,rs to decrease; and (d) the largest PEEPi attenuation among study time points. Figure 2 displays individual PEEPi values and shows that in four patients, PEEPi was almost completely abolished.

	Discussion

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The major original findings of the present study are that in mechanically ventilated, bronchodilator-responsive COPD patients who exhibit a moderate PEEPi (5–10 cm H₂O), the use of nebulized salbutamol and PEEPe equal to PEEPi at ZEEP results in (a) benefits with respect to inspiratory resistance, lung volume, hemodynamics, and oxygenation, (b) an additive effect with respect to PEEPi reduction, and (c) Estat,rs decrease.

Nebulized-Salbutamol Effects
Two studies (9,10) that accurately assessed inhaled drug mass proved that nebulizers deliver large amounts to the alveoli. Accordingly, we provided bronchodilation with nebulized salbutamol. The observed Rmin,rs reduction and dynamic hyperinflation attenuation are in accordance with previously published results (5,14,18–20). The observed R,rs reduction is in accordance with the results of Guérin et al. (21) and is probably related to a significant, nebulizer-induced alveolar deposition of salbutamol (21).

In addition to the aforementioned results, salbutamol resulted in a CO-arithmetical increase and PVR-arithmetical decrease (Table 3). In vitro ß₂-adrenoceptor stimulation similarly increased heart rate and reduced SVR but also reduced MAP without affecting CO (22). In ambulatory, stable COPD patients at rest and breathing room air, inhaled ß₂ agonists similarly increased heart rate and CO but decreased PVR significantly (23). However, the present study’s participants continuously received 0.35–0.50 Fio₂, with some probable blunting of hypoxic pulmonary vasoconstriction and PVR decrease, even at baseline ventilation.

In ambulatory, stable COPD patients, ß₂-adrenergic agonists induced pulmonary artery vasodilation and attenuated hypoxic pulmonary vasoconstriction (23). This, in conjunction with CO increase, caused preferential pulmonary blood flow deviation to poorly ventilated lung regions. Consequently, right-to-left shunt increased and oxygenation deteriorated (23). However, DO₂ was well-preserved because of CO increase (23). In general, such effects were not observed in our study. The preservation of arterial oxygenation may be attributable to the salbutamol-induced reduction in R,rs, which reflects reduced lung time-constant inequality and more homogenous ventilation distribution. A previous study (5) also evaluated bronchodilation effects on Pao₂ in mechanically ventilated COPD patients; the observed Pao₂ changes were insignificant.

PEEPe Application Effects
In COPD, applying PEEPe at the PEEPi level determined at ZEEPe may increase PEEPtot, accentuate dynamic hyperinflation, and compromise hemodynamics and gas exchange (11,12). Consequently, such a maneuver cannot be generally recommended. However, in our carefully preselected COPD group, the application of PEEPe equal to PEEPi at ZEEPe resulted mainly in favorable effects with respect to gas exchange and PEEPi. Our results are in accordance with those of Guérin et al. (7), who found that PEEPe application close to PEEPi reduces the inspiratory breathing work without further promoting hyperinflation.

Lung hyperinflation compresses the intraalveolar vessels, exacerbates any preexisting tricuspid incompetence, and increases right ventricular afterload (12). Hypovolemia reduces right and left ventricular preload and alveolar vessel volume, thus further deteriorating hemodynamics. In this setting, PEEPe application decreases MAP (12) and increases intrathoracic pressure with further preload compromise.

In the present study, the PEEPe level we used did not produce any significant changes in lung volume or hemodynamics. Before entering the study, all patients underwent transthoracic echocardiography, were evidently normovolemic, and had good right ventricular function. Neither tricuspid regurgitation nor severe pulmonary hypertension was present. Furthermore, PEEPe probably recruited unaerated or poorly ventilated alveoli, thus causing a more homogenous ventilation distribution. Because CO did not change significantly, we speculated that pulmonary blood flow passed through lung regions that were better aerated overall. Thus, ventilation-perfusion mismatch was attenuated, and gas exchange was improved.

In contrast to our results (Table 3), Tuxen (2) reported that PEEPe application decreased MAP and DO₂ in mechanically ventilated asthmatics. The differences between the two studies lie in the pathophysiologic profiles of asthmatics and COPD patients. In asthmatics, airway wall progressive stiffness (caused by increased bronchial tone and inflammatory infiltration) does not result in complete airway collapse, even when airway caliber is reduced (2). However, COPD patients exhibit increased airway collapsibility secondary to progressive elastic recoil loss. Moreover, Tuxen (2) administered larger baseline tidal volumes (15 ± 3 mL/kg) that could have exacerbated hyperinflation. The studies of Rossi et al. (6), Ranieri et al. (11), and Dambrosio et al. (13) suggest that PEEPe should not exceed a critical value of 50%–91% of PEEPi, more than which FRC and Estat,rs increase and CO decreases. However, analysis of the data of the aforementioned studies shows that (a) baseline PEEPi values amounted to 9.45 ± 1.99, 9.8 ± 0.5, and 9.7 ± 0.4 cm H₂O, respectively; (b) PEEPe equal to PEEPi at ZEEPe appreciably reduced PEEPi; and (c) the rest of rs mechanics and hemodynamics remained unaffected up to PEEPtot of 10.23 ± 2.41, 11.1 ± 0.3, and 10.93 ± 0.85 cm H₂O, respectively. Our patients exhibited lower baseline PEEPi values (7.0 ± 1.1 cm H₂O), whereas inspiratory resistance, hyperinflation, and hemodynamics did not change significantly up to PEEPtot values of 10.8 ± 2.2 cm H₂O. In accordance with our results, Rossi et al. (6) showed that PEEPe resulting in PEEPtot of 10.23 ± 2.41 cm H₂O substantially improved arterial oxygenation with concomitant Paco₂ decrease; this was also attributed to perfusion redistribution to more efficient alveoli.

PEEPe and Nebulized Salbutamol Combination Effects
In the particular setting of the present study, the PEEPe/salbutamol combination resulted in additive favorable effects on most determined variables and, especially, on PEEPi (Figure 2). It seems likely that PEEPe recruitment of poorly or nonventilated alveoli resulted in distribution of inspired gas (and consequently of nebulized salbutamol particles) to a larger portion of the lung parenchyma. Furthermore, the salbutamol-induced reduction in lung time-constant inequality (i.e., R,rs) (Table 2) and more homogenous ventilation distribution could have facilitated the intratidal alveolar recruitment, whereas the applied PEEPe should have facilitated the maintenance of such recruitment. Thus, PEEPe alveolar recruitment was followed by the salbutamol-induced (arithmetical) CO increase, and salbutamol-facilitated PEEPe alveolar recruitment. This interpretation is supported by the low Qs/Qt and improved arterial oxygenation, which suggest improved ventilation-perfusion relationships. The significant reduction in Estat,rs relative to ZEEPe is consistent with the PEEPe-induced reduction in alveolar atelectasis (15) and the concomitant bronchodilation-induced attenuation of lung hyperinflation.

Critique on Methods
The responses to salbutamol might have been limited by corticosteroid-induced bronchodilation (20). Also, single 0.8-mg/kg methylprednisolone-bolus administration (not preceded by steroid treatment) may acutely decrease Rmin,rs and dynamic hyperinflation (24). However, a previous randomized, controlled trial (25) demonstrated that the beneficial effects of intermittent IV methylprednisolone on forced expiratory lung volumes are maximized within 48 h of treatment initiation and are maintained virtually constant thereafter. Because the present study’s participants were enrolled at least 48 h after IV steroid initiation (see Methods), it is unlikely that such treatment has qualitatively influenced our results (20).

A randomized crossover study design might have been more appropriate because a patient’s clinical condition could have changed over the 11-hour study period. If study sequence is always the same, it may be impossible to identify residual effects of inhaled salbutamol on PEEPe application or PEEPe-S, despite allowing an eight-hour washout period. These concepts probably do not apply here because (a) Tables 2 and 3 confirm that before PEEPe application, all determined variable values had returned to ZEEPe levels, (b) individual response patterns to salbutamol washout were similar (data not shown), (c) no significant clinical events/deterioration (e.g., hypoxemia or hemodynamic instability) occurred throughout the study period in any case; such events would have caused patient exclusion (see Methods), and complete measurement sets would have not been obtained in all cases (see Results); and (d) in most cases, substantial clinical improvement allowing weaning from mechanical ventilation occurred 5–10 days after study enrollment; consequently, the 11-hour study period should have been too short for a study result affecting clinical change.

Clinical Implications and Further Research
In COPD, PEEPi is not evenly distributed throughout the lung parenchyma. EEO-measured, average PEEPi of 10 cm H₂O may correspond to a wide regional PEEPi variation. Maximal PEEPi values (which are probably substantially higher than the EEO-measured average) are encountered by alveoli that are cut off from the airway opening. However, lung regions with the highest PEEPi values may be especially prone to barotrauma. According to our results, combined bronchodilation/PEEPe minimizes PEEPi in an additive manner. Consequently, such treatment may be recommendable for mechanically ventilated COPD patients who are bronchodilator responsive and exhibit a moderate PEEPi of 5–10 cm H₂O.

It could be argued that because at PEEPe-S the inhaled salbutamol further decreased PEEPi, the setting of PEEPe at a PEEPi level determined at ZEEPe might result in a PEEPe exceeding average effective PEEPi, with consequent accentuation of dynamic hyperinflation. This is supported by the substantial arithmetical FRC difference between ZEEPe-S and PEEPe-S reported in Table 2. Thus, one could advocate PEEPe counterbalancing of the PEEPi present at ZEEPe-S (and not at ZEEPe). However, it should be noted that the PEEPi value present at ZEEP-S returned to baseline (i.e., PEEPi value at ZEEPe) approximately eight hours after inhaled salbutamol (Table 2). Consequently, an ideal PEEPe strategy could comprise intermittent (e.g., every one to two hours) determination of PEEPi after inhaled salbutamol, with concomitant "appropriate" adjustment of PEEPe.

If our results were applicable during partial ventilatory support, then combined bronchodilation/PEEPe could result in substantial unloading of inspiratory muscles by minimizing PEEPi (1,3). This would probably facilitate the weaning process. Consequently, the above speculations warrant further investigation.

	Conclusion

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In bronchodilator-responsive COPD patients exhibiting moderate PEEPi, combined PEEPe-counterbalancing of PEEPi, and nebulized salbutamol minimize PEEPi, attenuate lung hyperinflation and inspiratory resistance, and exhibit a favorable hemodynamic and gas exchange profile.

	Appendix: Formulas Used to Derive Predicted Body Weight and Hemodynamic* and Gas Exchange Variables**

Top Abstract Introduction Methods Results Discussion Conclusion Appendix: Formulas Used to... References

 
1. Predicted body weight (males) = 50 + (height [cm] – 152.4) x 0.91

2. Predicted body weight (females) = 45.5 + (height [cm] – 152.4) x 0.91

3. SVR = (MAP – CVP) x 80

4. PVR = (MPAP – PCWP) x 80

5. O₂ delivery₂ = CO x 1.36 x Hgb x Sao₂

6. O₂ consumption = CO x 1.36 x Hgb x (Sao₂ – Svo₂)

7. Respiratory quotient = (FEY of carbohydrate intake) x 1.0 + (FEY of protein intake) x 0.8 + (FEY of lipid intake) x 0.7^**

8. Alveolar Po₂ = Pio₂ – Paco₂ x (Fio₂ – [1 – Fio₂] x R^–1); Pio₂ = Fio₂ x (P_B – 47); Paco₂ Paco₂

9. O₂ content of blood = Hgb x 1.36 x So₂/10 + 0.003 x Po₂

10. Shunt fraction = (CcO₂ – CaO₂)/(CcO₂ – CvO₂)

CO = cardiac output (L/min); MAP = mean arterial blood pressure (mm Hg); CVP = central venous pressure (mm Hg); 80 = transformation factor of Wood units (mm Hg·L^–1·min^–1) to standard metric units (dynes·s^–1·cm^–5); MPAP = mean pulmonary artery pressure (mm Hg); PCWP, = pulmonary capillary wedge pressure (mm Hg); Hgb = hemoglobin concentration in g/L; 1.36 = O₂ combining power of 1 g of Hgb (mL); Sao₂ = arterial O₂ saturation determined by the blood gas analysis reported in Methods; Svo₂ = mixed venous O₂ saturation; FEY = fractional energy yield relative to the total of prescribed nutritional support; P = gas partial pressure (mm Hg); Pio₂ = inspired O₂ partial pressure (mm Hg); Paco₂ = alveolar CO₂ partial pressure (mm Hg); Fio₂ = fraction of inspired O₂; R = respiratory quotient; P_B = barometric pressure (mm Hg); 47 = water saturated vapor pressure at 37°C (mm Hg); 0.003 = O₂ solubility coefficient at 37°C (mL·dL^–1·mm Hg^–1); Po₂ = O₂ partial pressure (mm Hg); CcO₂/CaO₂/CvO₂ = O₂ content in end-capillary/arterial/mixed-venous blood, respectively.

	Footnotes

 
* Mark JB, Slaughter TF, Reves JG. Cardiovascular monitoring. In: Miller RD, ed. Anesthesia. 5th ed. New York: Churchill Livingstone, 2000:1117–30 and Moon ME, Camporesi EM. Respiratory monitoring. In: Miller RD, ed. Anesthesia. 5th ed. New York: Churchill Livingstone, 2000:1255–96.

**Marino PL. Nutrient and energy requirements. In: Marino PL, ed. The ICU book. 2nd ed. Baltimore: Williams & Wilkins, 1997:721–36.

Accepted for publication March 14, 2005.

	References

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1. Tobin MJ. Respiratory muscles in disease. Clin Chest Med 1988;9:263–86.[Web of Science][Medline]
2. Tuxen DV. Detrimental effects of positive end-expiratory pressure during controlled mechanical ventilation of patients with severe airflow obstruction. Am Rev Respir Dis 1989;140:5–9.[Web of Science][Medline]
3. Smith TC, Marini JJ. Impact of PEEP on lung mechanics and work of breathing in severe airflow obstruction. J Appl Physiol 1988;65:1488–99.[Abstract/Free Full Text]
4. Jolliet P, Watremez C, Roeseler J, et al. Comparative effects of helium-oxygen and external positive end-expiratory pressure on respiratory mechanics, gas exchange, and ventilation-perfusion relationships in mechanically ventilated patients with chronic obstructive pulmonary disease. Intensive Care Med 2003;29:1442–50.[Web of Science][Medline]
5. Bernasconi M, Brandolese R, Poggi R, et al. Dose-response effects and time course of effects of inhaled fenoterol on respiratory mechanics and arterial oxygen tension in mechanically ventilated patients with chronic airflow obstruction. Intensive Care Med 1990;16:108–14.[Web of Science][Medline]
6. Rossi A, Santos C, Roca J, et al. Effects of PEEP on VA/Q mismatching in ventilated patients with chronic airflow obstruction. Am J Respir Crit Care Med 1994;149:1077–84.[Abstract]
7. Guérin C, Milic-Emili J, Fournier G. Effect of PEEP on work of breathing in mechanically ventilated COPD patients. Intensive Care Med 2000;26:1207–14.[Web of Science][Medline]
8. Tuxen D, Lane S. The effects of ventilatory pattern on hyperinflation, airway pressures, and circulation in mechanical ventilation of patients with severe airflow obstruction. Am Rev Respir Dis 1987;136:872–9.[Web of Science][Medline]
9. Diot P, Morra L, Smaldone GC. Albuterol delivery in a model of mechanical ventilation. Am J Respir Crit Care Med 1995;152:1391–4.[Abstract]
10. Palmer LB, Smaldone GC, Simon SR, et al. Aerosolized antibiotics in mechanically ventilated patients: delivery and response. Crit Care Med 1998;26:31–9.[Web of Science][Medline]
11. Ranieri VM, Giuliani R, Cinnela G, et al. Physiologic effects of positive end-expiratory pressure in patients with chronic obstructive pulmonary disease during acute ventilatory failure and controlled mechanical ventilation. Am Rev Respir Dis 1993;147:5–13.[Web of Science][Medline]
12. Baigorri F, De Monte A, Blanch L, et al. Hemodynamic responses to external counterbalancing of auto-positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease. Crit Care Med 1994;22:1782–91.[Web of Science][Medline]
13. Dambrosio M, Cinnella G, Brienza N, et al. Effects of positive end-expiratory pressure on right ventricular function in COPD patients during acute ventilatory failure. Intensive Care Med 1996;22:923–32.[Web of Science][Medline]
14. Dhand R, Jubran A, Tobin M. Bronchodilator delivery by metered-dose inhaler in ventilator-supported patients. Am J Respir Crit Care Med 1995;151:1827–33.[Abstract]
15. Mentzelopoulos SD, Zakynthinos SG, Roussos C, et al. Prone position improves lung mechanical behavior and enhances gas exchange efficiency in mechanically ventilated chronic obstructive pulmonary disease patients. Anesth Analg 2003;96:1756–67.[Abstract/Free Full Text]
16. Gross NJ, Jenne JW, Hess D. Bronchodilator therapy. In: Tobin MJ, ed. Principles and practice of mechanical ventilation. New York: McGraw-Hill, 1994:1077–123.
17. Guérin C, Coussa ML, Elissa NT, et al. Lung and chest wall mechanics in mechanically ventilated COPD patients. J Appl Physiol 1993;74:1570–80.[Abstract/Free Full Text]
18. Fuller HD, Dolovich MB, Posmituck G, et al. Pressurized aerosol versus jet aerosol delivery to mechanically ventilated patients. Am Rev Respir Dis 1990;141:440–4.[Web of Science][Medline]
19. Fernandez A, Lazaro A, Garcia A, et al. Bronchodilators in patients with chronic obstructive pulmonary disease on mechanical ventilation. Am Rev Respir Dis 1990;141: 164–8.[Web of Science][Medline]
20. Mouloudi E, Prinianakis G, Kondili E, Georgopoulos D. Effect of inspiratory flow rate on beta2-agonist induced bronchodilation in mechanically ventilated COPD patients. Intensive Care Med 2001;27:42–6.[Web of Science][Medline]
21. Guérin C, Chevre A, Dessirier P, et al. Inhaled fenoterol-ipratropium bromide in mechanically ventilated patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;159:1036–42.[Abstract/Free Full Text]
22. Lee RW, Raya TE, Gay RG, et al. Beta-2-adrenoceptor control of the venous circulation in intact dogs. J Pharmacol Exp Ther 1987;242:1138–43.[Abstract/Free Full Text]
23. Saito S, Miyamoto K, Nishimura M, et al. Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD. Chest 1999;115:376–82.[Abstract/Free Full Text]
24. Rubini F, Rampulla C, Nava S. Acute effect of corticosteroids on respiratory mechanics in mechanically ventilated patients with chronic airflow obstruction and acute respiratory failure. Am J Respir Crit Care Med 1994;149:306–10.[Abstract]
25. Albert RK, Martin TR, Lewis SW. Controlled clinical trial of methylprednisolone in patients with chronic bronchitis and acute respiratory insufficiency. Ann Intern Med 1980;92:753–8.

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