Oxygen uptake (V o 2 ) at the alveolar-capillary membrane

ably help us to find the real mechanisms for this rare illness. For ethical reasons, such a test has not been performed. In conclusion, such cases of patients with pericarditis after influenza vaccination are rare, but the true incidences of the illness are probably underestimated. However, this complication does not outweigh the beneficial effects of the influenza vaccination in patients at risk. References 1 Margolis KL, Poland GA, Nichol KL, et al. Frequency of adverse reactions after influenza vaccination. Am J Med 1990; 88:27 30 2 Nicholson KG. Clinical features of influenza. Semin Respir Infect 1992; 7:26 37 3 Ray CG, Icenogle TB, Minnich LL, et al. The use of intravenous ribavirin to treat influenza virus-associated acute myocarditis. J Infect Dis 1989; 159:829 836 4 Fairley CK, Ryan M, Wall PG, et al. The organism reported to cause infective myocarditis and pericarditis in England and Wales. J Infect 1996; 32:223 225 5 Streifler JJ, Dux S, Garty M, et al. Recurrent pericarditis: a rare complication of influenza vaccination. BMJ 1981; 283: 526 527 6 Desson JF, Leprevost M, Vabret F, et al. Péricardite aigue bénigne après vaccination antigrippale. Presse Med 1997; 26:415 7 Robinson J, Brigden W. Recurrent pericarditis. BMJ 1968; 2:272 275 8 Bensaid J, Denis F. Péricardite aigue benigne après vaccination contre l hépatite B. Presse Med 1993; 22:269 9 Peyrière H, Hillaire-Buys D, Pons M, et al. Acute pericarditis after vaccination against hepatitis B: a rare effect to be known. Rev Med Interne 1997; 18:675 676 10 Bloth B, Lundman T. Pleuroperimyocarditis caused by immunization with anticatarrh vaccine. Acta Med Scand 1977; 201:137 140 Single-Breath Measurements of Pulmonary Oxygen Uptake and Gas Flow Rates for Ventilator Management in ARDS* James E. Szalados, MD, MBA, FCCP; Frances E. Noe, MD; Michael G. Busby, PhD; and Philip G. Boysen, MD, FCCP Monitoring data in critical care and anesthesiology should be displayed to present a rapid and easily comprehensible definition of the patient s clinical status. A graphic computer display of the analog output of gas flow rates and the O 2 and CO 2 concentrations of respiratory gases profiles the expired breath for an estimation of pulmonary function and gas exchange. An estimate of pulmonary perfusion, cardiac output, and the general adequacy of cardiovascular circulation is obtained from the computer calculation of O 2 uptake and CO 2 elimination, dead space, and alveolar ventilation. Adjunctive data from the spirometric measurements of airway pressures, volumes, and compliance, supplemented by hemodynamic monitoring, aids in the diagnosis of physiologic changes. For > 10 years, we have used this system to monitor patients who are anesthetized, sedated, and receiving mechanical ventilation during anesthesia and surgery, and recently have extended the technique to intensive care areas. Our experience has shown good correlation of changes in the computer-assisted expired breath analysis with coinciding clinical events, including upper airway obstruction, bronchospasm, and alveolar volume/pulmonary capillary blood flow impairment. To demonstrate the use of this system, we describe the ventilator management for a patient with severe ARDS. In this patient, changes in ventilator management, including pressure control ventilation, improved pulmonary O 2 uptake (mean, 18.7 vs 8.5 ml/breath), CO 2 elimination (mean, 17 vs 13 ml/ breath), and compliance (mean, 29.7 vs 19.0 ml/cm H 2 O), were compared with intermittent mandatory ventilation. (CHEST 2000; 117:1805 1809) Abbreviations: ABG arterial blood gas; Feo 2 fraction of expired oxygen; Fio 2 fraction of inspired oxygen; Fio 2 Feo 2 inverted oxygen concentration; IMV intermittent mandatory ventilation; pressure-controlled ventilation; PEEP positive end-expiratory pressure; PIP peak inspiratory pressure; Qc pulmonary capillary perfusion; V a alveolar ventilation; V co 2 carbon dioxide output; Vd dead space; V o 2 oxygen uptake; Vt tidal volume Oxygen uptake (V o 2 ) at the alveolar-capillary membrane is a function of alveolar ventilation (V a), diffusion, and pulmonary capillary perfusion ( Qc). The application of positive end-expiratory pressure (PEEP) in the treatment of ARDS is thought to recruit and splint alveoli at end-expiration and increase both the area and duration of alveolar gas exchange, thereby potentially improving V a/ Qc matching. 1 However, increased inspiratory airway pressures with PEEP may compromise pulmonary perfusion by limiting cardiac output and effective Qc. 1 Titration of ventilatory variables to optimize pulmonary V o 2 may preserve both V a and pulmonary blood flow. We describe the use of single-breath gas composition and expiratory flow data obtained with a computer-assisted multigas analysis and spirometry system to guide ventilator therapy in a patient with ARDS. Computer analysis and graphical display of superimposed gas flow rates and single-breath O 2 and CO 2 concentrations were *From the Department of Anesthesiology, Division of Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. Presented in part at the American Society of Anesthesiologists Annual Meeting, October 20 22, 1996, New Orleans, LA. Manuscript received February 10, 1998; revision accepted September, 29, 1999. Correspondence to: Frances E. Noe, MD, Research Associate Professor, Department of Anesthesiology, 223 Burnett-Womack Building, CB #7010, University of North Carolina, Chapel Hill, NC, 27599-7010; e-mail: fnoe@aims.unc.edu CHEST / 117 / 6/ JUNE, 2000 1805

used to compare a patient s response to ventilator management with intermittent mechanical ventilation (IMV) and pressure-controlled ventilation () with PEEP. Materials and Methods Data for this monitoring system were obtained using a multigas analyzer (Ultima; Datex Engstrom; Helsinki, Finland) with a spirometry module that measures airway gas flow rates and pressures. 2 A fast paramagnetic sensor measures O 2 concentration, an infrared sensor gives CO 2 concentration, and a flow sensor based on the Pitot principle with electronic linearization is used to obtain flow and airway pressure measurement. The time-based analyzer analog outputs for gas flow rate, O 2, and CO 2 concentrations are introduced into the computer (model 486; IBM; Armonk, NY) through an analog-to-digital conversion board (Cyberresearch; Danbury, CT). The computer display of pulmonary data, the spirometric data including expiratory flow and volume, compliance, and airway pressures from the analyzer, plus adjunctive data from hemodynamic monitors indicate the physiologic response of the patient to a specific mode of ventilation. Our most recent work has included the use of a laser spectroscopy O 2 analyzer (Oxigraf; Mountain View, CA) to provide a more accurate output for O 2 concentration. Online cross-product integration of expired gas flow rate and either inverted O 2 concentration (fraction of inspired oxygen [Fio 2 ] fraction of expired oxygen [Feo 2 ]) or CO 2 concentration at a sampling rate of 40 Hz are used to calculate the oxygen uptake and carbon dioxide output for each breath. 3,4 Predetermined delays due to gas transport through sampling tubing and sensor response time are entered into the computer. Assayed tank gas is used to calibrate both the analyzer and the values for O 2 and CO 2 concentrations transmitted to the computer prior to monitoring. Flow volume is calibrated with a 1-L volumetric syringe. Superimposing the Fio 2 Feo 2 and CO 2 concentration curves on the expired gas flow rate curve for the breath on the computer monitor display divides the area under the flow curve into two areas directly proportional to the dead space (Vd) and the Va as shown in Figure 1, which shows a typical single-breath configuration for a patient receiving mechanical ventilation during anesthesia and muscle relaxation. The area proportional to Va delimited by the gas flow curve and the Fio 2 Feo 2 curve is equivalent to the oxygen uptake for the breath and, by computer cross-integration, provides the numerical value for oxygen uptake. With continuous monitoring of sedated patients receiving mechanical ventilation, when the single-breath value for oxygen uptake is observed to be essentially constant during 1-min periods, the minute volume (V o 2 ) is obtained by multiplying this value by the respiratory rate per minute. The accuracy of the computer-derived numerical data with clinical conditions of changing volumes and gas flow rates requires further study, which is in progress using the mannequin simulator (Medical Education Technologies; Sarasota, FL). In the laboratory, the comparison of V o 2 calculated from assayed gas sample breaths and the computer-derived V o 2 values yielded a correlation coefficient of 0.996. Correlation of computerderived V o 2 of normal conscious human subjects and the V o 2 obtained from 3-min bag collections of expired gas was 0.990, and the calculation of the difference using Student s t test was 0.71. Our previously reported work 4 indicates that our present system measures V o 2 and V co 2 with clinical accuracy. Comparison of Fick calculation of cardiac output using both computer V o 2 and V co 2 with arterial and venous blood data and dye dilution determinations of cardiac output gave correlation coefficients of 0.83 SE 0.15 for the O 2 Fick, and 0.85 SE 0.15 (p 0.001 for both) for the CO 2 Fick data and dye dilution values. 4 The shape of the curve of expired gas flow rate is essential to the monitoring protocol as an indication of the condition of the pulmonary airways. Changes in this curve occur with obstruction of the upper airway with secretions and position or manipulation Figure 1. Pulmonary single-breath Fio 2 Feo 2 and CO 2 concentrations in percent, and expired gas flow rate in L/min are shown as a function of time in seconds in a normal intubated anesthetized patient with muscle relaxation. Bisection of the expired flow rate curve by the gas concentration curves provides a rapid estimation of the Vd and alveolar ventilation for the single breath. 1806 Selected Reports

of the endotracheal tube, and will usually give early warning for bronchospastic constriction of lower airways. 5 Patients in the ICU are monitored to ensure that their respiratory requirements have not changed or for adequate ventilation during weaning. The selection of an optimal ventilator mode is based on flow and gas data following the stabilization of the respiratory curves, usually a period of 5 to 10 min, and the response to this selection is verified with subsequent hemodynamic and arterial blood gas (ABG) data. Case Report An 88-kg, obese 36-year-old black woman presented in septic shock. Her vital signs were as follows: BP, 77/43 mm Hg; heart rate, 136 beats/min; temperature, 39.4 C; and respiratory rate, 36 beats/min. Her medical and surgical history were significant only for mild hypertension. Admission laboratory values included an ABG on 2 L/min via nasal cannulae, which revealed ph of 7.39; Paco 2,38mmHg;Pao 2, 41 mm Hg; HCO - 3, 22.5 mmol/l; and arterial O 2 saturation, 79%. Serum chemistry showed Na of 133 meq/l; K, 3.3 meq/l; HCO - 3, 20 mmol/l; creatinine, 2.3 mmol/l, and CBC count showed WBC count of 8.4 10 3 / L, hematocrit 30%, and platelets, 282 10 3 / L. A chest radiograph revealed diffuse bilateral infiltrates, and a pelvic ultrasound showed a 10-cm pelvic abscess. She was taken to the operating room for emergent exploratory laparotomy, abscess drainage, and total abdominal hysterectomy-bilateral salpingectomy. The operative course was uneventful except for vigorous hydration (7.5-L crystalloid, 3 U packed RBCs) and she was transferred to the surgical ICU. On admission to the surgical ICU, the patient remained chemically paralyzed and sedated, and was placed on mechanical ventilation (Siemens Servo 900C; Siemens Medical Systems; Danvers, MA): IMV 10/min, tidal volume (Vt), 850 ml; Fio 2, 1.0; and PEEP, 5 cm H 2 O. Her heart rate was 112 beats/min, BP was 160/92 mm Hg, and temperature was 37 C. Chest radiography was consistent with evolving ARDS. ABG analysis revealed the following: ph, 7.31; Pao 2, 143 mm Hg; Paco 2,40mmHg, HCO - 3, 19.0 mmol/l; and lactate, 1.7 mmol/l. Laboratory values also revealed WBC count of 10.1 10 3 / L; hemoglobin, 9.5 g/dl; platelets, 240 103; and Na, 141 meq/l, K, 3.9 meq/l; Cl -, 108 meq/l; HCO - 3, 19 mmol/l. Hemodynamics from a pulmonary catheter showed a pulmonary capillary wedge pressure of 30 mm Hg and cardiac index of 3.98 L/min/m 2. On the first postoperative day, when this study was done, with peak inspiratory pressures (PIPs) of 46 to 48 cm H 2 O and plateau pressures of 41 to 42 cm H 2 O with IMV and a continuous progressive widening of the alveolar-arterial O 2 tension gradient, the ventilator settings were changed to, limiting the PIP to 35 cm H 2 O and then 30 cm H 2 O, yielding a Vt of 800 ml. The patient was ventilated with an inspiration/expiration ratio of 1:1; Fio 2, 0.8; respiratory rate, 10 breaths/min; and PEEP, 7 cm H 2 O. ABGs revealed ph of 7.40; Paco 2,34mmHg;Pao 2, 193 mm Hg; HCO - 3, 20.6 meq/l; and arterial O 2 saturation, 98.3%. Vital signs obtained during were BP of 140/70 mm Hg; heart rate, 125 beats/min; pulmonary capillary wedge pressure, 17 mm Hg; cardiac index, 5.58 L/min/m 2. Venous O 2 and pulse oximetric saturation were unchanged before and after changing ventilator modes, but with increased CO, there was greater O 2 transport. A Datex Ultima Capnomac multigas analyzer (Datex Engstrom) with a spirometry module interposed between the endotracheal tube and the ventilator circuit was used to measure the inspired and expired fractional concentrations of O 2 and CO 2, the expired gas flow rates, and the pulmonary pressures and volumes. 3,4 Using the digitally converted analog output of the analyzer downloaded to the computer, the pulmonary V o 2 and the CO 2 elimination for each of a series of breaths with repetitive consistency were obtained with IMV and PVC ventilator settings (Fig 2, top, A, and bottom, B). These graphical configurations, in conjunction with the calculated data for pulmonary V o 2 and CO 2 elimination, Vd, and static compliance, were the basis for ventilator management comparison and selection (Tables 1, 2). In this case, with continued support, the patient was stabilized and was discharged home approximately 4 weeks after admission. Discussion The primary goals of mechanical ventilation are to optimize respiratory gas exchange and to improve gas flow dynamics in patients with compromised respiratory function. Bedside single-breath monitoring of expired gas flow rates and pulmonary O 2 uptake provides an estimate of metabolic and cardiopulmonary function that is not available from standard clinical ICU monitoring. This system continuously displays a graphical depiction of the expired gas flow rate curves and the Fio 2 Feo 2 concentration curves for each breath using a computer display of the analog output of a multigas analyzer with a spirometric module. Estimates of Vd and V a are provided by the curves. Physiologic Vd will change the gas concentration curves from the analyzer because the expired gas from the high V a/ Qc regions of the lungs will decrease the Figure 2. Top, A: Single-breath monitoring (one of five recorded breaths) in IMV mode. Bottom, B: Single-breath monitoring (one of six recorded breaths) in mode (30 cm H 2 O). CHEST / 117 / 6/ JUNE, 2000 1807

Table 1 Measured and Calculated Values for Ventilatory Factors With IMV and Ventilation Ventilation Mode Breath, No. Peak Flow, L/min Duration, s Vt, ml Vd, ml Vd/Vt Ratio V a, ml Compliance, ml/cm H 2 O IMV 1 110 0.8 660 350 0.53 310 17 2 106 0.9 682 365 0.54 317 21 3 108 0.9 688 395 0.57 297 18 35 cm H 2 O 4 98 1.1 840 404 0.48 436 26 5 101 1 798 351 0.44 447 23 6 100 1 830 409 0.49 421 24 30 cm H 2 O 7 95 1 813 394 0.49 419 40 8 92 1.1 816 384 0.47 432 37 9 92 1.1 875 410 0.47 465 38 Fio 2 Feo 2 concentration by dilution. The resulting V o 2 is proportional to the effective pulmonary perfusion involved in gaseous exchange, and thus provides an estimate of V a/ Qc matching. The volume of O 2 taken up by the blood from each breath is termed O 2 uptake. If conditions allow the existence of a steady metabolic state, the V o 2 will be equivalent to the metabolic O 2 consumption. In the sedated intensive care patient under muscular relaxation, it is reasonable to assume that, with no change in the observed curves and calculated data, consistent singlebreath values for O 2 uptake multiplied by the respiratory rate will provide the metabolic O 2 consumption per minute. With clinical conditions, the accuracy of calculated data is subject to the variations in gas flow and pressures that may affect calibrated values. A study is in progress to estimate the extent of error due to these variations. However, in the individual sedated or anesthetized patient with muscular relaxation, clinical judgment is based on the extent of change in values and, over short periods of time, the effect of such factors as ventilator circuit compression, temperature, and humidity is consistent or limited. The spirometric calculation of single-breath O 2 uptake from the integrated gas flow curve and the Fio 2 Feo 2 curve provides a rapid, noninvasive, and clinically accurate estimation of the total O 2 utilization. The continuous breath-by-breath repetition of the curves provides surveillance of rapid or sustained changes in cardiovascular or pulmonary function. Storage of the curves in computer memory permits review and comparison for characterization of the pathologic process or response to a therapeutic intervention. CO 2 curves and CO 2 output data are also generated with this monitoring system, but we do not believe that they are as sensitive as the O 2 data for detecting changes in cardiorespiratory function. Pulmonary and blood component compensation for CO 2 excretion makes CO 2 curves and CO 2 output data less responsive to physiologic changes. Karan et al 6 have reported a case in which ventilatory compensation for increased CO 2 caused a significant delay in treatment for malignant hyperthermia since only end-tidal CO 2 was monitored. Our previously reported study that involved using this system to monitor hyperthermic changes in dogs indicated that the O 2 response to the increased metabolism was faster than that of CO 2, probably due to metabolic equilibration for such factors as hyperventilation preceding visible evidence for the increased CO 2 production. 3 Discussion of the deleterious effects of positive pressure ventilation center primarily on distension and shear trauma to the alveolar lining (barotrauma or volutrauma). 7,8 The Table 2 Measured and Calculated Values for Gas Exchange Factors With IMV and Ventilation Ventilation Mode Breath, No. Fio 2, % Fio 2 - Feo 2,% O 2 Uptake, ml/breath End-Tidal CO 2,% CO 2 Output, ml/breath Respiratory Exchange IMV 1 83.8 3.8 9 4.2 13 1.4 2 83.6 3.8 9 4.1 13 1.4 3 83.6 3.6 8 4.1 12 1.5 35 cm H 2 O 4 83.2 4.5 13 3.9 17 1.3 5 83.3 4.6 13 3.8 17 1.3 6 82.9 4.5 12 3.8 16 1.3 30 cm H 2 O 7 83.2 4.8 17 4.3 18 1.1 8 83.2 4.7 17 4.4 19 1.1 9 83.4 4.8 20 4.3 20 1 1808 Selected Reports

heterogenous nature of ARDS may put noninvolved alveoli at greater risk for overdistension compared with pathologic noncompliant alveoli. 9 PEEP is thought to preferentially overdistend the compliant alveoli not involved by the ARDS process. may improve recruitment of involved segments through decelerating gas flows applied throughout a prolonged inspiratory phase. The lower airway pressures generated with decrease alveolar distending pressure and thereby increase the duration of effective alveolar gas exchange with minimal shear and distension forces. 10,11 Furthermore, and most importantly, excessive lung inflation also increases pulmonary vascular resistance and right heart afterload through the overdistension of alveoli with volume-controlled ventilation. High levels of PEEP may decrease effective alveolar capillary blood flow. 9 limits alveolar distension to a preset pressure limit, which may permit a more effective Qc and V a/ Qc matching with decreased ventilatory Vd and physiologic shunt. 12 This hypothesis would account for the improved O 2 uptake with observed with our monitoring system. In this patient, the PIP with IMV was 47 cm H 2 O, which may have decreased effective pulmonary blood flow. Figure 2 shows both improved single-breath O 2 uptake and improved V a with and plateau pressure of 30 cm H 2 O. The improved compliance with (29.7 ml/cm H 2 O) compared with IMV (19.0 ml/cm H 2 O) is consistent with improved alveolar recruitment and splinting (Table 1). However, not all patients have improved respiratory exchange with. There are cases where computer monitoring indicates that IMV is more beneficial, and this is corroborated by Pao 2 and hemodynamic data. In conclusion, bedside use of our monitoring system has shown good correlation with clinical events and corroborates accepted hypotheses for ventilator-induced pulmonary impairment. It assists clinical judgment and may indicate a change in the physiologic state of the patient, which will give early warning for pending cardiopulmonary dysfunction. ACKNOWLEDGMENT: The authors wish to thank members of the Respiratory Care Department at the University of North Carolina at Chapel Hill for their assistance and Michael J. Banner, PhD, of the Departments of Anesthesiology and Physiology, University of Florida, Gainesville, for helpful review of the manuscript. References 1 MacIntyre NR. Clinically available new strategies for mechanical ventilatory support. Chest 1993; 104:560 565 2 Barnard JPM, Sleigh JW. Breath-by-breath analysis of oxygen uptake using the Datex Ultima. Br J Anaesth 1995; 74:155 158 3 Davies RE, Noe FE, Whitty AJ, et al. Breath-by-breath measurement of oxygen consumption and FIO 2 -FEO 2 with increased oxygen demand. Acta Anaesthesiol Scand 1991; 35:201 204 4 Noe FE, Whitty AJ, Davies KR. Simultaneous computercalculated carbon dioxide and oxygen direct Fick and dye dilution measurements of cardiac output in dogs. Acta Anaesthesiol Scand 1981; 25:12 16 5 Davies KR, Noe FE, Davies RE, et al. Expiratory flow rate curves for monitoring upper and lower airway obstruction during anesthesia [letter]. J Clin Monit 1991; 7:346 348 6 Karan SM, Crowl F, Muldoon SM. Malignant hyperthermia masked by capnographic monitoring. Anesth Analg 1994; 78:590 592 7 Mancebo J. PEEP, ARDS, and alveolar recruitment. Intensive Care Med 1992; 18:383 385 8 Lachmann B. Open up the lung and keep the lung open. Intensive Care Med 1992; 18:319 321 9 Chan K, Abraham E. Effects of inverse ratio ventilation on cardiorespiratory parameters in severe respiratory failure. Chest 1992; 102:1556 1561 10 Mercat A, Graini L, Teboul J-L. Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome. Chest 1993; 104:871 875 11 Kallas HJ, Domino KB, Glenny RW, et al. Pulmonary blood flow redistribution with low levels of positive end-expiratory pressure. Anesthesiology 1998; 88:1291 1299 12 Abraham E, Yoshihara G. Cardiorespiratory effects of pressure controlled ventilation in severe respiratory failure. Chest 1990; 98:1445 1449 Persistent Pneumomediastinum in Interstitial Fibrosis Associated With Rheumatoid Arthritis* Treatment With High-Concentration Oxygen Anshul Patel, BS; Branko Kesler, MD; and Robert A. Wise, MD, FCCP We present a case of persistent spontaneous pneumomediastinum precipitated by an upper respiratory infection in a patient with interstitial fibrosis associated with rheumatoid arthritis who was receiving chronic corticosteroid treatment. The persistent nature of the mediastinal emphysema over 2 months eventually required treatment with high concentrations of inhaled oxygen that resulted in rapid resolution of the pneumomediastinum without recurrence over 6 months of follow-up. This case, along with others in the medical literature, emphasizes the need for early use of high-concentration inhaled oxygen in the treatment of pneumomediastinum in high-risk patients, such as those with connective tissue disorders. (CHEST 2000; 117:1809 1813) Key words: oxygen therapy; pneumothorax; pulmonary fibrosis; rheumatoid arthritis; spontaneous pneumomediastinum Spontaneous pneumomediastinum is an uncommon disorder that is usually benign and self-limited. We recently observed a patient with rheumatoid lung disease *From Johns Hopkins University, School of Medicine at the Johns Hopkins Asthma and Allergy Center, Division of Pulmonary and Critical Care Medicine, Baltimore, MD. Manuscript received April 27, 1999; revision accepted December 9, 1999. Correspondence to: Robert A. Wise, MD, FCCP, Johns Hopkins University, School of Medicine at the Johns Hopkins Asthma and Allergy Center, Division of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224; e-mail: rwise@welch.jhu.edu CHEST / 117 / 6/ JUNE, 2000 1809