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Continuous positive airway pressure versus positive end-expiratory pressure in respiratory distress syndrome
Continuous positive airway pressure versus positive end-expiratory pressure in respiratory distress syndrome The hemodynamic and respiratory effects of spontaneous ventilation with continuous positive airway pressure (CPAP) and mechanical ventilation with positive end-expiratory pressure (PEEP) were compared in nine patient.s who had adult respiratory distress syndrome. These patients were capable of maintaining spontaneous ventilation (tidal volume above 300 mi. and Pac02 below 45 torr). Arterial and mixed venous blood gases, cardiac output, oxygen delivery and consumption, pulmonary artery pressure, and pulmonary wedge pressure were measured in II instances, with each patient on 5 or 10 em. H{J CPAP or PEEP, and in nine instances, with each patient on the ventilator but without PEEP (0 PEEP). During CPAP, when compared to PEEP at the same level of end-expiratory pressure, mean Pa02 increased significantly (p < 0.05) and mean physiological shunt decreased (p < 0.05). In nine of / / instances, cardiac output was higher on CPAP than on a corresponding level of PEEP. Thus CPAP was more effective than the same amount of PEEP in improving arterial oxygenation by the lung without adversely affecting cardiac output.
Dhiraj M. Shah, M.D., Jonathan C. Newell, Ph.D., Robert E. Dutton, M.D., and Samuel R. Powers, Jr., M.D., F.A.C.S., Albany, N. Y. With technical assistance from Chandler M. Ralph, B.S., Albany, N. Y.
Mechanical ventilation with increased positive end-expiratory pressure (PEEP) is a widely accepted method of treatment for the acute respiratory distress syndrome;':" Improvement of gas exchange is associated with increases in alveolar volume.": 4 Although there are advantages in increasing alveolar volume, alveolar ventilation, and arterial oxygenation, mechanical ventilation must not adversely affect cardiac outpur." 5. 6 distribution of pulmonary blood flow, or oxygen availability to the tissues." 6 All of these adverse effects may be accentuated by increased levels of PEEP.3-5 Furthermore, PEEP may not always result in an increase of functional residual capacity (FRC) or improvement in gas exchange." Concern over these possible complications of mechanical ventilation with PEEP has led to modified means for the application of From the Trauma Center and the Departments of Surgery and Physiology, Albany Medical College, Albany, N. Y. Supported by grants Nos. OM 15426 and I-MO-I-RR-00749 of the National Institutes of Health, Bethesda, Md. Received for publication March 2, 1977. Accepted for publication June 13, 1977. Address for reprints: Dhiraj M. Shah, M.D., Department of Surgery, V.A. Hospital, Albany, NY 12208.
positive-pressure ventilation.t' v' One such modification suggested by Civetta, Brons, and Gabel? is that spontaneous ventilation with continuous positive airway pressure (CPAP) may be effective for the treatment of adult respiratory distress. The present prospective study was designed to compare respiratory and hemodynamic effects of the sequential use of CPAP and PEEP in adult patients who were capable of maintaining spontaneous ventilation.
Patients and methods Nine patients were studied in the Trauma Center of Albany Medical College, Albany, New York. Eight patients sustained multiple system trauma and one patient had septic shock following operation (Table I). All patients required intubation and mechanical ventilatory assistance during their initial management. CPAP was administered to these patients when they could maintain a tidal volume above 300 ml. and arterial Pco, below 45 torr. An arterial cannula was inserted in the radial artery for the measurment of blood pressure, sampling of blood, and determination of cardiac output. A flowdirected, balloon-tipped catheter was introduced by an
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Table I. Clinical history of patients Case No.
Diagnosis 28
M
2
28
M
3
58
M
4
71
M
5
21
M
6
52
F
7
34
M
8
19
M
9
16
M
Lung problems
Skull fracture, scalp laceration, Fat embolism* liver laceration, fractured right Femur and patella, fractured dislocation left ankle, and fractured left clavicle Multiple gastrointestinal "Septic lung" fistulas, septic shock Head injury, fractured claviLung contusion cle, fractured ribs, and mesenteric hematoma Facial lacerations, fractured Fat embolism* metacarpals, laceration left hemidiaphragm, and shock Multiple long bone fractures, Fat embolism * facial bone fracture, ruptured spleen, and ruptured thoracic aorta Ruptured spleen, kidney contusion, and comminuted fractured pelvis Fracture of skull, head injury, Lung contusion fractured ribs, and liver laceration Multiple long bone fracture Fat embolism* and head injury Right hemopneumothorax, Lung contusion Fat embolism* fractured spine, C 2- 5 • laceration of colon and duodenum, and paraplegia
'Diagnosed by cryostat frozen sectioning and Oil-Red-O staining of wedged pulmonary blood.P
antecubital venous cutdown and floated into the pulmonary artery. This catheter was used to measure pulmonary artery pressure, pulmonary wedge pressure, and central venous pressure, to sample mixed venous blood, and to inject indocyanine green dye. All pressures were measured by strain gauge transducers and a polygraph. Cardiac output was computed from the dye-dilution curve obtained with indocyanine green. Arterial and mixed venous blood was analyzed for pH, Po 2 , and Pco, by an IL 313* blood gas analyzer. Oxygen saturation was calculated from the Severinghaus!' blood gas calculator. Oxygen content was calculated as 1.34 x hemoglobin x saturation + 0.0031 x P0 2 Physiological shunt (shunt) was calculated from Berggren's" shunt formula, at the therapeutic level of
inspired oxygen. Oxygen delivery was determined by multiplying cardiac output by arterial oxygen content. Oxygen consumption was obtained by multiplying cardiac output by arterial-mixed venous oxygen content difference. FRC was measured by a nitrogen washout technique which uses an argon and oxygen gas mixture in a second respirator. 13 A mass spectrometer was used to sample the expired gas continuously and to measure the nitrogen concentration. Expired gas passed to a bag-box wedge spirometer system for the measurement of expiratory gas flow and volume.v FRC was calculated by a PDP-15* digital computer, which integrated the product of expired gas flow and nitrogen content. Continuous positive pressure was maintained by a regulator valve.": 9 PEEP (5 em. H2 0 or 10 cm. H20 ) was administered with an Ohio 560t ventilator at a tidal volume of 12 to 15 mI. per kilogram of body weight. A level of CPAP identical to the level of PEEP was administered. CPAP was administered first in four instances and PEEP was administered first in seven instances. Additionally, in nine instances, patients were ventilated mechanically without PEEP (0 PEEP) between periods of CPAP and PEEP ventilation. In each instance 15 minutes were allowed to achieve a steady state. Then measurements of cardiac output, arterial blood pressure, pulmonary artery pressure, pulmonary wedge pressure, central venous pressure, and arterial and mixed venous blood gases were made. FRC was measured only during mechanical ventilation. All patients were studied at therapeutic level of inspired oxygen. During mechanical ventilation patients received adequate sedative or muscle relaxant to permit controlled ventilation. Statistical analysis for paired data was done with Student's paired t test. Results
Patients in this study had had multiple trauma requiring intubation, mechanical ventilation, and increased inspired oxygen. At the time of entrance. into the study their mean physiological shunt was 16 percent, mean FRC was 1,920 mI. (mean predicted normal FRC is 2,478 ml.), mean cardiac index was 4.2 L. per minute per square meter of body surface area, and mean Pan!:! was 32 torr on mechanical ventilation without PEEP (Tables II and III). With the change from PEEP to CPAP, mean Pa 0 2 increased from 113 to 130 torr (FI~ = 0.2 to 0.4) (p < 0.05). The increase of Pao2 was associated with a *Digital Equipment Corp., Maynard, Mass.
*Instrumentation Laboratories, Inc., Lexington, Mass.
tOhio Medical Products, Madison, Wis.
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Table II. Respiratory data under condition of continuous positive pressure (CPAP), mechanical ventilation without positive end-expiratory pressure (0 PEEP), and mechanical ventilation with positive end-expiratory pressure (PEEP) Shunt (%) Case EEP (em. No. H 2O) I 2 3 4 5 6 7a 7b 8a 8b 9 Mean S.E.
10 10 10 10 10 10 5 10 10 5 10
Fie!,
CPAP
0.4 0.4 0.4 0.3 0.35 0.3 0.3 0.3 0.3 0.3 0.2
15 16 13 12 8 14 13 15 5 9 2 11 ±I
I
0 PEEP 24 19 22 16 18 12
10 20 2 16 ±2 *p < 0.01
I
PEEP
CPAP
23 20 20 18 15 13 12 II II II 2 .14 ±2 P < 0.05
144 142 151 119 156 97 124 120 165 113 98 130 ±7
I
Pao, (torr) 0 PEEP
I
PEEP
102 138 126 88 102 115
93 140 134 97 III 108 131 128 119 114 64 93 101 100 106 113 ±8 ±5 P < 0.05 P < 0.05
CPAP 10 PEEPlpEEP 41 33 36 21 30 22 30 30 37 45 36 33 ±2
31 37 30 29 34 21
o
30 42 32 31 34 24 26 25 35 45 35 33 ±2
31 43 33 32 ±2
FRC (mi.) predicted normal PEEPlpEEP FRC (mi.)
Paco, (torr)
2,037 1,233 2,360 1,324 1,576 1,951
1,677 3,202 1,920 ±226
2,850 1,968 4,878 1,466 2,007 1,774 1,561 1,315 3,287 2,582 2,889 2,416 ±315
1,973 2,235 2,982 1,940 2,751 1,452 2,756 2,756 2,788 2,788 2,758 2,404 ±191
Legend: EEP, Level of end-expiratory pressure for CPAP and PEEP. Flo" Inspired oxygen fraction. Shunt, Physiological shunt. Plio" Arterial oxygen tension.
Paco, Arterial carbon dioxide tension. PRC, Functional residual capacity. 'ComparesCPAP with 0 PEEP and PEEP.
Table III. Hemodynamic data under condition of continuous positive airway pressure (CPAP), mechanical ventilation without positive end-expiratory pressure (0 PEEP), and mechanical ventilation with positive end-expiratory pressure (PEEP) CI (L/min/sq. M. body surface area) Case No.
CPAP
I 2 3 4 5 6 7a 7b 8a 8b 9 Mean S.E.
4.3 5.7 3.2 4.8 3.2 5.1 4.2 4.4 3.3 3.8 3.1 4.1 ±0.3
I
0 PEEP
I
3.9 6.7 2.7 3.9 4.8
4.2 3.1 4.2 ±0.5
PAP (torr)
PEEP
CPAP
3.0 5.2 3.1 4.5 4.2 4.4 4.1 3.6 5.7 3.7 2.7 4.0 ±0.3
16 21 20 24 20 20 16 12 13 17 21 18 ±1.0
I
0 PEEP 14 17 12 18 18
II 15 15 ± 1.0
I
PEEP CPAP 17 18 15 27 20 19 9 9 18 17 19 17 ±1.5
5 10 9 13 5 8 10 9 2 3 13 8 ±I
I
PWP (torr)
0 PEEP 2 5 3 5 4
-3 6 3 ±I
I
PEEP
V0 2 (ml.lmin.)
Oxygen delivery (ml.Imin.) CPAP
4 1,808 1,345 8 6 912 1,270 13 5 838 6 1,076 6 1,069 4 1,113 -4 1,115 2 956 9 839 5 1,121 ±I ±84 'P < 0.001
I
0 PEEP
I
1,629 1,341 769 1,157 1,016
1,295 849 1,150 ±113
PEEP
CPAP
1,237 1,067 887 1,177 1,157 940 1,081 935 1,705 946 724 1,078 ±77
274 290 133 320 201 304 204 213 315 264 170 244 ±19
I
0 PEEP 231 238 115 236 260
341 177 228 ±26
I
PEEP 197 194 144 257 281 237 201 193 490 248 193 240 ±28
Legend: CI, Cardiac index. PAP, Pulmonary artery pressure. PWP, Pulmonary wedge pressure. VO" Oxygen consumption.
'Compares CPAPwithPEEP.
decrease of mean shunt from 14 percent on PEEP to 11 percent on CPAP (p < 0.05). Although the mean decrease of shunt was only 3 percent, five patients having a physiological shunt above 14 percent all showed a decrease of shunt ranging from 4 to 8 percent. In the remaining six instances
where shunt was below 14 percent, the change of shunt was smaller and variable (-4 to 6 percent) (Table II). In nine instances where CPAP was compared to 0 PEEP, mean Pa 0 2 on CPAP was 132 torr and on 0 PEEP was 105 torr (p < 0.05). Mean shunt decreased from 16 percent on 0 PEEP to 10 percent on CPAP
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560 Shah et al.
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Table IV. Hemodynamic and respiratory data of Case 1
Pao, * (torr) Paco, (torr) Shunt (%) FRC(ml.) CO/CI PWP (torr)
Day 1 o PEEP
o PEEP
140 33 18 1,340 8.1/3.7 4
94 36 34 2,052 8.9/4.0 -4
I
Day 2 10 PEEP
I
20 PEEP
10 CPAP
86 38 29 3,636 6.6/3.0 5
144 41 15
87 35 28 2,160 7.5/3.4 -I
9.4/4.3 5
I
Day 3 OPEEP 102 31 24 2,037 8.6/3.9 2
I
10 PEEP 90 30 23 2,850 6.6/3.0 4
I
20 PEEP 97 32 25 3,888 4.9/2.2 7
Legend: PEEP, Positive end-expiratory pressure. Pa"" Arterial oxygen tension. Pac"" Arterial carbon dioxide tension. FRC. Functional residual capacity. CO/C!. Cardiac output (L./min.)/cardiac index (L./min./sq.M. of body surface area). PWP, Pulmonary wedge pressure. CPAP. Continuous positive airway pressure. 'Flo., = 0.4.
(p < 0.01). There was no change of mean arterial PC02 on CPAP, PEEP, or 0 PEEP, indicating that adequate alveolar ventilation was maintained. Cardiac index increased on CPAP in nine instances but increased on PEEP only in two instances. However, there was no change of mean cardiac index. CPAP produced an increase of oxygen delivery in eight instances and an increase of oxygen consumption in seven instances. Mean oxygen delivery and mean oxygen consumption were not different with either CPAP or PEEP (Table III). There was no change of mean pulmonary artery pressure, but mean pulmonary wedge pressure increased from 5 torr on PEEP to 8 torr on CPAP (p < 0.001) (Table III). FRC increased in seven of nine patients from a mean of 1,920 m!. on 0 PEEP to a mean of 2,416 m!. on 10 PEEP. This change was not satistically significant (Table II). The following case exemplifies the successful use of CPAP for the treatment of respiratory distress which was refractory to graded levels of PEEP.
Case report A 28-year-old white man sustained multiple trauma in an automobile accident (Case I, Table I). At the time of admission to the Trauma Center the patient was stable hemodynamically and had manifestations of mild respiratory distress (day I, Table IV). Despite treatment by a mechanical ventilator at 0 PEEP, the patient's respiratory status deteriorated on the next day. To determine the optimum level of PEEP for the treatment of his RDS, the patient was studied at graded increased levels of PEEP from 0 to 20 em. H20 . Although FRC increased, arterial oxygenation did not improve. Cardiac output decreased, associated with a decrease in oxygen delivery from 1,687 to 1,254 m!. per minute (day 2, Table IV). Since PEEP had an adverse effect on this patient, it was discontinued. The patient was continued on mechanical ventilation at 0 PEEP and an inspired oxygen concentration of 40 percent. The following day the patient was entered into the study and was selected to receive CPAP before PEEP. At the end of 15 minutes of CPAP at 10 em.
H 20 the Pall:! increased and shunt decreased. Then the patient was studied at 0 PEEP and 10 em. H20 PEEP. As on the previous occasion, PEEP produced an increase in FRC without improving oxygenation by the lung. Cardiac output and oxygen delivery decreased (day 3, Table IV). When 10 em. H20 PEEP did not result in improvement, PEEP was increased to 20 em. H20, and still there was no improvement. The patient then was placed on 10 em. H 20 CPAP as a therapeutic measure and he improved so that CPAP could be discontinued after 12 hours.
Discussion
The application of any type of positive-pressure ventilation to patients suffering from respiratory distress syndrome has effects on alveolar volume and on both the systemic and pulmonary circulations.v" Increased transpulmonary pressure may increase lung volume, inflate previously closed alveoli, and thereby increase arterial oxygenation." In addition increased airway pressure may reduce cardiac output and may redistribute pulmonary blood flow. 4, 6. 15 The net effect of positive-pressure ventilation on over-all oxygen transport will depend on the relative magnitude of each of these changes. The relative effects of CPAP and PEEP ventilation in the treatment of respiratory distress syndrome were reviewed recently.!" Prolonged mechanical ventilation was reported to cause increased pulmonary interstitial water.!" Caldini, Leith, and Brennan!" also reported that positive-pressure ventilation resulted in an increase of interstitial water in dog lungs. Furthermore, Stocks and Godfrey'? suggested that infants receiving mechanical ventilation may develop increased airway resistance subsequently, whereas those treated with CPAP all were normal. They postulated that higher airway pressure during mechanical ventilation may have damaged the airways. CPAP also appeared to be effective in reducing intrapulmonary shunts in adults. 20 However, none of the above-mentioned clinical studies compared the same levels of CPAP and PEEP .16. 19. 20
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In our present study CPAP appears to be more effective than the same level of PEEP in improving oxygenation of blood by the lung. Also when patients were changed from PEEP to CPAP, cardiac output increased in nine of II instances. However, there was no significant increase in oxygen comsumption with CPAP. Although one may assume that increased respiratory effort with CPAP is associated with an increased oxygen consumption, the added work of the respiratory muscles was not sufficient to increase oxygen consumption significantly. Oxygen consumption was correlated positively with oxygen delivery (r = 0.65, P < 0.001), as we reported in trauma patients." The level of end-expiratory pressure is not the only determinant of these effects. If the factor responsible for these changes was the end-expiratory pressure, then both spontaneous breathing and mechanical ventilation at the same levels of end-expiratory pressure would have similar effects. One basic difference between spontaneous breathing and mechanical ventilation is that of mean airway pressure. Whereas the endexpiratory pressure during spontaneous ventilation with CP AP is the highest airway pressure of the ventilatory cycle, the mean airway pressure is always lower. In contrast the end-expiratory pressure during mechanical ventilation with PEEP is the lowest airway pressure of the cycle and the mean airway pressure is always higher. An increase in transpulmonary pressure may overdistend already open alveoli. 4, 6 The variation of compliance in different regions of the lung will determine the number and distribution of these overdistended alveoli." 15 These alveolar units may become underperfused if an elevated alveolar pressure is transmitted to the alveolar capillaries. 6, 21 The addition of PEEP in respiratory distress syndrome may cause a decrease in shunt and an increase in the fraction of ventilation delivered to lung units with very high V /Q ratios." However, we have observed an increase in physiological shunt in some patients under similar circumstances.v 6 It appears that an increased shunt may result from a diversion of blood flow from well-ventilated areas to poorly ventilated areas of the lung owing to increased alveolar pressure. Baeza and co-workers" observed a fall in PaO:! after addition of 10 ern. H 20 PEEP in acid-induced respiratory distress syndrome in dogs. They also suggest that PEEP causes hyperinflation of the remaining normal lung with diversion of blood flow to the abnormal lung. Thus the potential beneficial effect of increased mean airway pressure on gas exchange may be negated by the effect of a greater perfusion inequality.
The present study suggests that, in patients who are able to maintain spontaneous ventilation, CPAP is more effective than is the same level of PEEP in improving arterial oxygenation by the lung without adverse effects on cardiac output.
2
3 4
5
REFERENCES Ashbaugh, D. G., Petty, T. L., Bigelow, D. B., and Harris, T. M.: Continuous Positive-Pressure Breathing (CPPB) in Acute Respiratory Distress Syndrome, 1. THORAe. CARDIOVASC. SURG. 57: 31,1969. Kumar, A., Falke, K. J., Geffin, B., Aldredge, C. F., Laver, M. B., Lowenstein, E., and Pontoppidan, H.: Continuous Positive-Pressure Ventilation in Acute Respiratory Failure, N. Eng!. J. Med. 283: 1430, 1970. Pontoppidan, H., Geffin, B., and Lowenstein, E.: Acute Respiratory Failure in the Adult, N. Eng!. J. Med. 287: 690,743, and 799, 1972. Powers, S. R., Jr., Mannal, R., Neclerio, M., English, M., Marr, C., Leather, R., Ueda, H., Williams, G., Custead, W., and Dutton, R.: Physiologic Consequences of Positive End-Expiratory Pressure (PEEP) Ventilation, Ann. Surg. 178: 265, 1973. Ashbaugh, D. G., and Petty, T. L.: Positive EndExpiratory Pressure: Physiology, Indications, and Contraindications, J. THoRAe. CARDIOVASe. SURG. 65: 165, 1973.
6 Powers, S. R., Jr., and Dutton, R. E.: Correlation of Positive End-Expiratory Pressure With Cardiovascular Performance, Crit. Care Med. 3: 64,1975. 7 Civetta, J. M., Brons, R., and Gabel, J. c. A Simple and Effective Method of Employing Spontaneous PositivePressure Ventilation, J. THORAC. CARDIOVASC. SURG. 63: 312, 1972.
8 Glasser, K. L., Civetta, J. M., and Fior, R. J.: The Use of Spontaneous Ventilation With Constant-Positive Airway Pressure in the Treatment of Salt Water Near Drowning, Chest 67: 355, 1975. 9 Gregory, G. A., Kitterman, J. A., Phibbs, R. H., Tooley, W. H., and Hamilton, W. K.: Treatment of the Idiopathic Respiratory Distress Syndrome with Continuous Positive Airway Pressure, N. Eng!. J. Med. 284: 1333, 1971.
10 Weisel, R. D., Vito, L., Staunton, H. P. B., and Hechtman, H. B.: Treatment of Acute Respiratory Insufficiency With Cyclic Expiratory Pressure, Surg. Forum 24: 234, 1973. II Severinghaus, 1. W.: Blood Gas Calculator, J. App!. Physio!. 21: 1108, 1966. 12 Berggren, S.: The Oxygen Deficit of Arterial Blood Caused by Non-ventilating Parts of the Lung, Acta Physio!. Scand. 4: I, 1942 (Supp!. II). 13 Monaco, V., Burdge, R., Newell, J., Leather, R. P., and Powers, S. R., Jr.: Clinical Significance of Functional Residual Capacity in the Post-injury State, Surg. Forum 22: 42, 1971.
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14 Gisser, D., Newell, J., and Powers, S. R., Jr.: A Refined Bag-Box Spirometer, J. A. A. M. I. 6: 167, 1972. 15 Baeza, O. R., Wagner, R. B., Lowery, B. D., and Gott, V. L.: Pulmonary Hyperinflation: A Form of Barotrauma During Mechanical Ventilation, J. THoRAc. CARDIOVASC. SURG. 70: 790, 1975. 16 Downes, J. J.: CPAP and PEEP-A Perspective, Anesthesiology 44: I, 1976. 17 Siaden, A., Laver, M. B., and Pontoppidan, H.: Pulmonary Complications and Water Retention in Prolonged Mechanical Ventilation, N. Eng!. 1. Med. 279: 448, 1968. 18 Caldini, P., Leith, J. D., and Brennan, M. 1.: Effect of Continuous Positive-Pressure Ventilation (CPPV) on Edema Formation in Dog Lung, J. App!. Physio!. 39: 672, 1975. 19 Stocks, J., and Godfrey, S.: The Role of Artificial
20
21
22 23
Ventilation, Oxygen and CPAP in the Pathogenesis of Lung Damage in Neonates: Assessment by Serial Measurements of Lung Function, Pediatrics 57: 352, 1976. Garg, G. P., and Hill, G. E.: The Use of Spontaneous Continuous Airway Pressure (CPAP) for Reduction of Intrapulmonary Shunting in Adults With Acute Respiratory Failure, Can. Anaesth. Soc. J. 22: 284, 1975. Assimacopoulos, A., Guggenheim, R., and Kapanci, Y.: Changes in Alveolar Capillary Configuration at Different Levels of Lung Inflation in the Rat: An Ultrastructural and Morphometric Study, Lab. Invest. 34: 10, 1976. West, J. B.: New Advances in Pulmonary Gas Exchange, Anesth. Analg. 54: 409,1975. Dutton, R. E., Shah, D. M., Newell, 1. C., and Powers, S. R., Jr.: Pulmonary Fat Embolism in Acute Respiratory Distress Syndrome, Am. Rev. Respir. Dis. 115: 102, 1977.
Dhiraj M. Shah, M.D., Jonathan C. Newell, Ph.D., Robert E. Dutton, M.D., and Samuel R. Powers, Jr., M.D., F.A.C.S., Albany, N. Y. With technical assistance from Chandler M. Ralph, B.S., Albany, N. Y.
Mechanical ventilation with increased positive end-expiratory pressure (PEEP) is a widely accepted method of treatment for the acute respiratory distress syndrome;':" Improvement of gas exchange is associated with increases in alveolar volume.": 4 Although there are advantages in increasing alveolar volume, alveolar ventilation, and arterial oxygenation, mechanical ventilation must not adversely affect cardiac outpur." 5. 6 distribution of pulmonary blood flow, or oxygen availability to the tissues." 6 All of these adverse effects may be accentuated by increased levels of PEEP.3-5 Furthermore, PEEP may not always result in an increase of functional residual capacity (FRC) or improvement in gas exchange." Concern over these possible complications of mechanical ventilation with PEEP has led to modified means for the application of From the Trauma Center and the Departments of Surgery and Physiology, Albany Medical College, Albany, N. Y. Supported by grants Nos. OM 15426 and I-MO-I-RR-00749 of the National Institutes of Health, Bethesda, Md. Received for publication March 2, 1977. Accepted for publication June 13, 1977. Address for reprints: Dhiraj M. Shah, M.D., Department of Surgery, V.A. Hospital, Albany, NY 12208.
positive-pressure ventilation.t' v' One such modification suggested by Civetta, Brons, and Gabel? is that spontaneous ventilation with continuous positive airway pressure (CPAP) may be effective for the treatment of adult respiratory distress. The present prospective study was designed to compare respiratory and hemodynamic effects of the sequential use of CPAP and PEEP in adult patients who were capable of maintaining spontaneous ventilation.
Patients and methods Nine patients were studied in the Trauma Center of Albany Medical College, Albany, New York. Eight patients sustained multiple system trauma and one patient had septic shock following operation (Table I). All patients required intubation and mechanical ventilatory assistance during their initial management. CPAP was administered to these patients when they could maintain a tidal volume above 300 ml. and arterial Pco, below 45 torr. An arterial cannula was inserted in the radial artery for the measurment of blood pressure, sampling of blood, and determination of cardiac output. A flowdirected, balloon-tipped catheter was introduced by an
557
558
The Journal of Thoracic and Cardiovascular
Shah et al.
Surgery
Table I. Clinical history of patients Case No.
Diagnosis 28
M
2
28
M
3
58
M
4
71
M
5
21
M
6
52
F
7
34
M
8
19
M
9
16
M
Lung problems
Skull fracture, scalp laceration, Fat embolism* liver laceration, fractured right Femur and patella, fractured dislocation left ankle, and fractured left clavicle Multiple gastrointestinal "Septic lung" fistulas, septic shock Head injury, fractured claviLung contusion cle, fractured ribs, and mesenteric hematoma Facial lacerations, fractured Fat embolism* metacarpals, laceration left hemidiaphragm, and shock Multiple long bone fractures, Fat embolism * facial bone fracture, ruptured spleen, and ruptured thoracic aorta Ruptured spleen, kidney contusion, and comminuted fractured pelvis Fracture of skull, head injury, Lung contusion fractured ribs, and liver laceration Multiple long bone fracture Fat embolism* and head injury Right hemopneumothorax, Lung contusion Fat embolism* fractured spine, C 2- 5 • laceration of colon and duodenum, and paraplegia
'Diagnosed by cryostat frozen sectioning and Oil-Red-O staining of wedged pulmonary blood.P
antecubital venous cutdown and floated into the pulmonary artery. This catheter was used to measure pulmonary artery pressure, pulmonary wedge pressure, and central venous pressure, to sample mixed venous blood, and to inject indocyanine green dye. All pressures were measured by strain gauge transducers and a polygraph. Cardiac output was computed from the dye-dilution curve obtained with indocyanine green. Arterial and mixed venous blood was analyzed for pH, Po 2 , and Pco, by an IL 313* blood gas analyzer. Oxygen saturation was calculated from the Severinghaus!' blood gas calculator. Oxygen content was calculated as 1.34 x hemoglobin x saturation + 0.0031 x P0 2 Physiological shunt (shunt) was calculated from Berggren's" shunt formula, at the therapeutic level of
inspired oxygen. Oxygen delivery was determined by multiplying cardiac output by arterial oxygen content. Oxygen consumption was obtained by multiplying cardiac output by arterial-mixed venous oxygen content difference. FRC was measured by a nitrogen washout technique which uses an argon and oxygen gas mixture in a second respirator. 13 A mass spectrometer was used to sample the expired gas continuously and to measure the nitrogen concentration. Expired gas passed to a bag-box wedge spirometer system for the measurement of expiratory gas flow and volume.v FRC was calculated by a PDP-15* digital computer, which integrated the product of expired gas flow and nitrogen content. Continuous positive pressure was maintained by a regulator valve.": 9 PEEP (5 em. H2 0 or 10 cm. H20 ) was administered with an Ohio 560t ventilator at a tidal volume of 12 to 15 mI. per kilogram of body weight. A level of CPAP identical to the level of PEEP was administered. CPAP was administered first in four instances and PEEP was administered first in seven instances. Additionally, in nine instances, patients were ventilated mechanically without PEEP (0 PEEP) between periods of CPAP and PEEP ventilation. In each instance 15 minutes were allowed to achieve a steady state. Then measurements of cardiac output, arterial blood pressure, pulmonary artery pressure, pulmonary wedge pressure, central venous pressure, and arterial and mixed venous blood gases were made. FRC was measured only during mechanical ventilation. All patients were studied at therapeutic level of inspired oxygen. During mechanical ventilation patients received adequate sedative or muscle relaxant to permit controlled ventilation. Statistical analysis for paired data was done with Student's paired t test. Results
Patients in this study had had multiple trauma requiring intubation, mechanical ventilation, and increased inspired oxygen. At the time of entrance. into the study their mean physiological shunt was 16 percent, mean FRC was 1,920 mI. (mean predicted normal FRC is 2,478 ml.), mean cardiac index was 4.2 L. per minute per square meter of body surface area, and mean Pan!:! was 32 torr on mechanical ventilation without PEEP (Tables II and III). With the change from PEEP to CPAP, mean Pa 0 2 increased from 113 to 130 torr (FI~ = 0.2 to 0.4) (p < 0.05). The increase of Pao2 was associated with a *Digital Equipment Corp., Maynard, Mass.
*Instrumentation Laboratories, Inc., Lexington, Mass.
tOhio Medical Products, Madison, Wis.
Volume 74
559
Respiratory distress syndrome
Number 4 October, 1977
Table II. Respiratory data under condition of continuous positive pressure (CPAP), mechanical ventilation without positive end-expiratory pressure (0 PEEP), and mechanical ventilation with positive end-expiratory pressure (PEEP) Shunt (%) Case EEP (em. No. H 2O) I 2 3 4 5 6 7a 7b 8a 8b 9 Mean S.E.
10 10 10 10 10 10 5 10 10 5 10
Fie!,
CPAP
0.4 0.4 0.4 0.3 0.35 0.3 0.3 0.3 0.3 0.3 0.2
15 16 13 12 8 14 13 15 5 9 2 11 ±I
I
0 PEEP 24 19 22 16 18 12
10 20 2 16 ±2 *p < 0.01
I
PEEP
CPAP
23 20 20 18 15 13 12 II II II 2 .14 ±2 P < 0.05
144 142 151 119 156 97 124 120 165 113 98 130 ±7
I
Pao, (torr) 0 PEEP
I
PEEP
102 138 126 88 102 115
93 140 134 97 III 108 131 128 119 114 64 93 101 100 106 113 ±8 ±5 P < 0.05 P < 0.05
CPAP 10 PEEPlpEEP 41 33 36 21 30 22 30 30 37 45 36 33 ±2
31 37 30 29 34 21
o
30 42 32 31 34 24 26 25 35 45 35 33 ±2
31 43 33 32 ±2
FRC (mi.) predicted normal PEEPlpEEP FRC (mi.)
Paco, (torr)
2,037 1,233 2,360 1,324 1,576 1,951
1,677 3,202 1,920 ±226
2,850 1,968 4,878 1,466 2,007 1,774 1,561 1,315 3,287 2,582 2,889 2,416 ±315
1,973 2,235 2,982 1,940 2,751 1,452 2,756 2,756 2,788 2,788 2,758 2,404 ±191
Legend: EEP, Level of end-expiratory pressure for CPAP and PEEP. Flo" Inspired oxygen fraction. Shunt, Physiological shunt. Plio" Arterial oxygen tension.
Paco, Arterial carbon dioxide tension. PRC, Functional residual capacity. 'ComparesCPAP with 0 PEEP and PEEP.
Table III. Hemodynamic data under condition of continuous positive airway pressure (CPAP), mechanical ventilation without positive end-expiratory pressure (0 PEEP), and mechanical ventilation with positive end-expiratory pressure (PEEP) CI (L/min/sq. M. body surface area) Case No.
CPAP
I 2 3 4 5 6 7a 7b 8a 8b 9 Mean S.E.
4.3 5.7 3.2 4.8 3.2 5.1 4.2 4.4 3.3 3.8 3.1 4.1 ±0.3
I
0 PEEP
I
3.9 6.7 2.7 3.9 4.8
4.2 3.1 4.2 ±0.5
PAP (torr)
PEEP
CPAP
3.0 5.2 3.1 4.5 4.2 4.4 4.1 3.6 5.7 3.7 2.7 4.0 ±0.3
16 21 20 24 20 20 16 12 13 17 21 18 ±1.0
I
0 PEEP 14 17 12 18 18
II 15 15 ± 1.0
I
PEEP CPAP 17 18 15 27 20 19 9 9 18 17 19 17 ±1.5
5 10 9 13 5 8 10 9 2 3 13 8 ±I
I
PWP (torr)
0 PEEP 2 5 3 5 4
-3 6 3 ±I
I
PEEP
V0 2 (ml.lmin.)
Oxygen delivery (ml.Imin.) CPAP
4 1,808 1,345 8 6 912 1,270 13 5 838 6 1,076 6 1,069 4 1,113 -4 1,115 2 956 9 839 5 1,121 ±I ±84 'P < 0.001
I
0 PEEP
I
1,629 1,341 769 1,157 1,016
1,295 849 1,150 ±113
PEEP
CPAP
1,237 1,067 887 1,177 1,157 940 1,081 935 1,705 946 724 1,078 ±77
274 290 133 320 201 304 204 213 315 264 170 244 ±19
I
0 PEEP 231 238 115 236 260
341 177 228 ±26
I
PEEP 197 194 144 257 281 237 201 193 490 248 193 240 ±28
Legend: CI, Cardiac index. PAP, Pulmonary artery pressure. PWP, Pulmonary wedge pressure. VO" Oxygen consumption.
'Compares CPAPwithPEEP.
decrease of mean shunt from 14 percent on PEEP to 11 percent on CPAP (p < 0.05). Although the mean decrease of shunt was only 3 percent, five patients having a physiological shunt above 14 percent all showed a decrease of shunt ranging from 4 to 8 percent. In the remaining six instances
where shunt was below 14 percent, the change of shunt was smaller and variable (-4 to 6 percent) (Table II). In nine instances where CPAP was compared to 0 PEEP, mean Pa 0 2 on CPAP was 132 torr and on 0 PEEP was 105 torr (p < 0.05). Mean shunt decreased from 16 percent on 0 PEEP to 10 percent on CPAP
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Table IV. Hemodynamic and respiratory data of Case 1
Pao, * (torr) Paco, (torr) Shunt (%) FRC(ml.) CO/CI PWP (torr)
Day 1 o PEEP
o PEEP
140 33 18 1,340 8.1/3.7 4
94 36 34 2,052 8.9/4.0 -4
I
Day 2 10 PEEP
I
20 PEEP
10 CPAP
86 38 29 3,636 6.6/3.0 5
144 41 15
87 35 28 2,160 7.5/3.4 -I
9.4/4.3 5
I
Day 3 OPEEP 102 31 24 2,037 8.6/3.9 2
I
10 PEEP 90 30 23 2,850 6.6/3.0 4
I
20 PEEP 97 32 25 3,888 4.9/2.2 7
Legend: PEEP, Positive end-expiratory pressure. Pa"" Arterial oxygen tension. Pac"" Arterial carbon dioxide tension. FRC. Functional residual capacity. CO/C!. Cardiac output (L./min.)/cardiac index (L./min./sq.M. of body surface area). PWP, Pulmonary wedge pressure. CPAP. Continuous positive airway pressure. 'Flo., = 0.4.
(p < 0.01). There was no change of mean arterial PC02 on CPAP, PEEP, or 0 PEEP, indicating that adequate alveolar ventilation was maintained. Cardiac index increased on CPAP in nine instances but increased on PEEP only in two instances. However, there was no change of mean cardiac index. CPAP produced an increase of oxygen delivery in eight instances and an increase of oxygen consumption in seven instances. Mean oxygen delivery and mean oxygen consumption were not different with either CPAP or PEEP (Table III). There was no change of mean pulmonary artery pressure, but mean pulmonary wedge pressure increased from 5 torr on PEEP to 8 torr on CPAP (p < 0.001) (Table III). FRC increased in seven of nine patients from a mean of 1,920 m!. on 0 PEEP to a mean of 2,416 m!. on 10 PEEP. This change was not satistically significant (Table II). The following case exemplifies the successful use of CPAP for the treatment of respiratory distress which was refractory to graded levels of PEEP.
Case report A 28-year-old white man sustained multiple trauma in an automobile accident (Case I, Table I). At the time of admission to the Trauma Center the patient was stable hemodynamically and had manifestations of mild respiratory distress (day I, Table IV). Despite treatment by a mechanical ventilator at 0 PEEP, the patient's respiratory status deteriorated on the next day. To determine the optimum level of PEEP for the treatment of his RDS, the patient was studied at graded increased levels of PEEP from 0 to 20 em. H20 . Although FRC increased, arterial oxygenation did not improve. Cardiac output decreased, associated with a decrease in oxygen delivery from 1,687 to 1,254 m!. per minute (day 2, Table IV). Since PEEP had an adverse effect on this patient, it was discontinued. The patient was continued on mechanical ventilation at 0 PEEP and an inspired oxygen concentration of 40 percent. The following day the patient was entered into the study and was selected to receive CPAP before PEEP. At the end of 15 minutes of CPAP at 10 em.
H 20 the Pall:! increased and shunt decreased. Then the patient was studied at 0 PEEP and 10 em. H20 PEEP. As on the previous occasion, PEEP produced an increase in FRC without improving oxygenation by the lung. Cardiac output and oxygen delivery decreased (day 3, Table IV). When 10 em. H20 PEEP did not result in improvement, PEEP was increased to 20 em. H20, and still there was no improvement. The patient then was placed on 10 em. H 20 CPAP as a therapeutic measure and he improved so that CPAP could be discontinued after 12 hours.
Discussion
The application of any type of positive-pressure ventilation to patients suffering from respiratory distress syndrome has effects on alveolar volume and on both the systemic and pulmonary circulations.v" Increased transpulmonary pressure may increase lung volume, inflate previously closed alveoli, and thereby increase arterial oxygenation." In addition increased airway pressure may reduce cardiac output and may redistribute pulmonary blood flow. 4, 6. 15 The net effect of positive-pressure ventilation on over-all oxygen transport will depend on the relative magnitude of each of these changes. The relative effects of CPAP and PEEP ventilation in the treatment of respiratory distress syndrome were reviewed recently.!" Prolonged mechanical ventilation was reported to cause increased pulmonary interstitial water.!" Caldini, Leith, and Brennan!" also reported that positive-pressure ventilation resulted in an increase of interstitial water in dog lungs. Furthermore, Stocks and Godfrey'? suggested that infants receiving mechanical ventilation may develop increased airway resistance subsequently, whereas those treated with CPAP all were normal. They postulated that higher airway pressure during mechanical ventilation may have damaged the airways. CPAP also appeared to be effective in reducing intrapulmonary shunts in adults. 20 However, none of the above-mentioned clinical studies compared the same levels of CPAP and PEEP .16. 19. 20
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In our present study CPAP appears to be more effective than the same level of PEEP in improving oxygenation of blood by the lung. Also when patients were changed from PEEP to CPAP, cardiac output increased in nine of II instances. However, there was no significant increase in oxygen comsumption with CPAP. Although one may assume that increased respiratory effort with CPAP is associated with an increased oxygen consumption, the added work of the respiratory muscles was not sufficient to increase oxygen consumption significantly. Oxygen consumption was correlated positively with oxygen delivery (r = 0.65, P < 0.001), as we reported in trauma patients." The level of end-expiratory pressure is not the only determinant of these effects. If the factor responsible for these changes was the end-expiratory pressure, then both spontaneous breathing and mechanical ventilation at the same levels of end-expiratory pressure would have similar effects. One basic difference between spontaneous breathing and mechanical ventilation is that of mean airway pressure. Whereas the endexpiratory pressure during spontaneous ventilation with CP AP is the highest airway pressure of the ventilatory cycle, the mean airway pressure is always lower. In contrast the end-expiratory pressure during mechanical ventilation with PEEP is the lowest airway pressure of the cycle and the mean airway pressure is always higher. An increase in transpulmonary pressure may overdistend already open alveoli. 4, 6 The variation of compliance in different regions of the lung will determine the number and distribution of these overdistended alveoli." 15 These alveolar units may become underperfused if an elevated alveolar pressure is transmitted to the alveolar capillaries. 6, 21 The addition of PEEP in respiratory distress syndrome may cause a decrease in shunt and an increase in the fraction of ventilation delivered to lung units with very high V /Q ratios." However, we have observed an increase in physiological shunt in some patients under similar circumstances.v 6 It appears that an increased shunt may result from a diversion of blood flow from well-ventilated areas to poorly ventilated areas of the lung owing to increased alveolar pressure. Baeza and co-workers" observed a fall in PaO:! after addition of 10 ern. H 20 PEEP in acid-induced respiratory distress syndrome in dogs. They also suggest that PEEP causes hyperinflation of the remaining normal lung with diversion of blood flow to the abnormal lung. Thus the potential beneficial effect of increased mean airway pressure on gas exchange may be negated by the effect of a greater perfusion inequality.
The present study suggests that, in patients who are able to maintain spontaneous ventilation, CPAP is more effective than is the same level of PEEP in improving arterial oxygenation by the lung without adverse effects on cardiac output.
2
3 4
5
REFERENCES Ashbaugh, D. G., Petty, T. L., Bigelow, D. B., and Harris, T. M.: Continuous Positive-Pressure Breathing (CPPB) in Acute Respiratory Distress Syndrome, 1. THORAe. CARDIOVASC. SURG. 57: 31,1969. Kumar, A., Falke, K. J., Geffin, B., Aldredge, C. F., Laver, M. B., Lowenstein, E., and Pontoppidan, H.: Continuous Positive-Pressure Ventilation in Acute Respiratory Failure, N. Eng!. J. Med. 283: 1430, 1970. Pontoppidan, H., Geffin, B., and Lowenstein, E.: Acute Respiratory Failure in the Adult, N. Eng!. J. Med. 287: 690,743, and 799, 1972. Powers, S. R., Jr., Mannal, R., Neclerio, M., English, M., Marr, C., Leather, R., Ueda, H., Williams, G., Custead, W., and Dutton, R.: Physiologic Consequences of Positive End-Expiratory Pressure (PEEP) Ventilation, Ann. Surg. 178: 265, 1973. Ashbaugh, D. G., and Petty, T. L.: Positive EndExpiratory Pressure: Physiology, Indications, and Contraindications, J. THoRAe. CARDIOVASe. SURG. 65: 165, 1973.
6 Powers, S. R., Jr., and Dutton, R. E.: Correlation of Positive End-Expiratory Pressure With Cardiovascular Performance, Crit. Care Med. 3: 64,1975. 7 Civetta, J. M., Brons, R., and Gabel, J. c. A Simple and Effective Method of Employing Spontaneous PositivePressure Ventilation, J. THORAC. CARDIOVASC. SURG. 63: 312, 1972.
8 Glasser, K. L., Civetta, J. M., and Fior, R. J.: The Use of Spontaneous Ventilation With Constant-Positive Airway Pressure in the Treatment of Salt Water Near Drowning, Chest 67: 355, 1975. 9 Gregory, G. A., Kitterman, J. A., Phibbs, R. H., Tooley, W. H., and Hamilton, W. K.: Treatment of the Idiopathic Respiratory Distress Syndrome with Continuous Positive Airway Pressure, N. Eng!. J. Med. 284: 1333, 1971.
10 Weisel, R. D., Vito, L., Staunton, H. P. B., and Hechtman, H. B.: Treatment of Acute Respiratory Insufficiency With Cyclic Expiratory Pressure, Surg. Forum 24: 234, 1973. II Severinghaus, 1. W.: Blood Gas Calculator, J. App!. Physio!. 21: 1108, 1966. 12 Berggren, S.: The Oxygen Deficit of Arterial Blood Caused by Non-ventilating Parts of the Lung, Acta Physio!. Scand. 4: I, 1942 (Supp!. II). 13 Monaco, V., Burdge, R., Newell, J., Leather, R. P., and Powers, S. R., Jr.: Clinical Significance of Functional Residual Capacity in the Post-injury State, Surg. Forum 22: 42, 1971.
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14 Gisser, D., Newell, J., and Powers, S. R., Jr.: A Refined Bag-Box Spirometer, J. A. A. M. I. 6: 167, 1972. 15 Baeza, O. R., Wagner, R. B., Lowery, B. D., and Gott, V. L.: Pulmonary Hyperinflation: A Form of Barotrauma During Mechanical Ventilation, J. THoRAc. CARDIOVASC. SURG. 70: 790, 1975. 16 Downes, J. J.: CPAP and PEEP-A Perspective, Anesthesiology 44: I, 1976. 17 Siaden, A., Laver, M. B., and Pontoppidan, H.: Pulmonary Complications and Water Retention in Prolonged Mechanical Ventilation, N. Eng!. 1. Med. 279: 448, 1968. 18 Caldini, P., Leith, J. D., and Brennan, M. 1.: Effect of Continuous Positive-Pressure Ventilation (CPPV) on Edema Formation in Dog Lung, J. App!. Physio!. 39: 672, 1975. 19 Stocks, J., and Godfrey, S.: The Role of Artificial
20
21
22 23
Ventilation, Oxygen and CPAP in the Pathogenesis of Lung Damage in Neonates: Assessment by Serial Measurements of Lung Function, Pediatrics 57: 352, 1976. Garg, G. P., and Hill, G. E.: The Use of Spontaneous Continuous Airway Pressure (CPAP) for Reduction of Intrapulmonary Shunting in Adults With Acute Respiratory Failure, Can. Anaesth. Soc. J. 22: 284, 1975. Assimacopoulos, A., Guggenheim, R., and Kapanci, Y.: Changes in Alveolar Capillary Configuration at Different Levels of Lung Inflation in the Rat: An Ultrastructural and Morphometric Study, Lab. Invest. 34: 10, 1976. West, J. B.: New Advances in Pulmonary Gas Exchange, Anesth. Analg. 54: 409,1975. Dutton, R. E., Shah, D. M., Newell, 1. C., and Powers, S. R., Jr.: Pulmonary Fat Embolism in Acute Respiratory Distress Syndrome, Am. Rev. Respir. Dis. 115: 102, 1977.