PEEP, and Interrupted PEEP

Comparative Hemodynamic Consequences of Inflation Hold, PEEP, and Interrupted PEEP An Experimental Study in Normal Dogs Kenneth F. MacDonnell, M.D., Armand A. Lefemine, M.D., Hyung S. Moon, M.D., Daniel J. Donovan, A.B., and Richard P. Johnston ABSTRACT Cardiac output and airway, intrathoracic, arterial, pulmonary artery, left atrial, and central venous pressures were studied in 8 mongrel dogs. They were anesthetized and ventilated with (1) inflation hold of various duration, (2) continuous positive end-expiratory pressure (PEEP), and (3) interrupted PEEP (three breaths on positive end-expiratory pressure and one breath off). The results indicate a minimal decrease in cardiac output (of approximately 5%) with inflation hold. Diminished cardiac output was noted with increasing levels of continuous PEEP. The severity of the decrease in cardiac output was proportional to the airway pressure. The higher levels (20 cm H20) of PEEP were associated with profound decreases. Utilization of a technique of interrupted PEEP substantially reduced the adverse hemodynamic effects in the dog. T he hemodynamic effects of positive pressure have been related to the mean intrathoracic pressure of the complete respiratory cycle [7]. Cournand and associates [3] observed that the decline in cardiac output associated with intermittent positive pressure could be minimized by using a type 3 mask pressure curve (an asymmetrical curve with gradually increasing pressure during inspiration and a rapid drop to atmospheric pressure during expiration) by maintaining a peak pressure of less than 25 cm HzO and by allowing for an inspiratory/expiratory ratio of no greater than 1. Numerous reports utilizing techniques of varying sensitivities have documented these observations in man and dog [2, 4, 81. A system of mechanical ventilation that employs positive end-expiratory pressure (PEEP) may also have unfavorable effects on cardiac output. The purpose of this study was to compare changes in cardiac output in dogs during From the Pulmonary and Respiratory Units and the Department of Cardio-Thoracic Surgery, St. Elizabeth s Hospital of Boston, Brighton, and the Departments of Medicine and Surgery, Tufts University School of Medicine, Boston, Mass. Supported by National Institutes of Health General Research Support Grant No. 5587. Accepted for publication Nov. 26, 1974. Address reprint requests to Dr. MacDonnell, Pulmonary Unit, St. Elizabeth s Hospital, 736 Cambridge St., Brighton, Mass. 02135. 552 THE ANNALS OF THORACIC SURGERY

Interrupted PEEP mechanical ventilation under the following conditions: (1) various methods of inflation hold, (2) different levels of continuous PEEP, and (3) interrupted PEEP (three breaths on PEEP and one breath off). Methods Eight mongrel dogs unselected as to sex, each weighing greater than 30 kg, were anesthetized intravenously with pentobarbital, 25 mg per kilogram of body weight, and intubated with cuffed endotracheal tubes. Pentobarbital was added as needed. A left thoracotomy was made through the fourth intercostal space. The pericardium was incised anterior to the phrenic nerve and its edges were sutured to the wound. The main pulmonary artery was isolated and encircled with an 18-mm Statham Model SP220 electromagnetic flow probe. A flow-signal voltage, which was directly proportional to blood flow through the probe, was amplified, averaged, and recorded on an Electronics for Medicine DR8 recorder. Thus continuous cardiac output was determined. Left atrial pressures (LAP) were measured with a No. 16 Jelco needle. Pulmonary artery pressure (PAP) was measured by means of a polyethylene cannula introduced into the pulmonary artery at the time of thoracotomy using a pursestring suture. Pulmonary arteriolar resistance (PAR) Mean PA - LA 80,000 a and pulmonary vascular resistance (PVR) Mean,PA x 80,000 Q were calculated. The chest wall was closed airtight, leaving a polyethylene line in place for measuring intrathoracic pressure. Arterial and central venous pressure (CVP) lines were placed through a femoral arterial and venous cutdown. Pressure inside the airway was measured by means of a T-connector at the joint of the endotracheal tube. The LAP, PAP, CVP, and intrathoracic pressure were zeroed at the level of the trachea. Airway and end-tidal Po2 and Pcoz were analyzed using a Statham mass spectrometer attached to the T-connector at the joint of the endotracheal tube. The dogs were placed in a supine position and ventilated with a volumecycled respirator (Bennett MA-1) with an FIO~ of 0.3 and a tidal volume of 10 to 12 mvkg. Dead space was added and respiratory rate changed as necessary to maintain an end PCOZ of 34 & 8 mm Hg, and the ph was kept between 7.30 and 7.50. Arterial Poz as well as Pcoz and ph were periodically monitored during intermittent positive-pressure ventilation at a respiratory rate of 14. Measurements of all variables were made during an inspiratory hold of 0.8, 1.6, and 2 seconds. The animal was ventilated with continuous and then interrupted PEEP, i.e., three breaths on PEEP and one breath (the fourth) off. PEEP was increased by units of 5 cm HzO up to 20 cm HzO for both continuous and interrupted PEEP, and the dog was ventilated for one-half hour at each step except at high levels of PEEP, i.e., 20 cm HzO, at which striking decreases in cardiac output were potentially life VOL. 19, NO. 5, MAY, 1975 553

MAC DONNELL ET AL. threatening. Baseline measurements with intermittent positive-pressure ventilation were obtained between each incremental elevation of PEEP. Results A significant decrease in cardiac output (p < 0.002) occurred at all levels of inflation hold (0.8, 1.6, and 2 sec) (Table 1). Cardiac output at baseline was 4.9 Umin (mean), dropping to 4.6 Umin with 0.8 sec of inflation hold and 4.4 Umin at 1.6 and 2 sec. A simultaneous increase in mean PAP was statistically significant at 1.6 and 2 sec inflation hold, though the magnitude of the change was not large (see Table 1). No change in CVP was observed during inflation hold. PEEP decreased cardiac output progressively at each level of pressure (Table 2). Cardiac output was reduced from a baseline of 4.8 Umin to 3.9 Llmin at 10 cm and 2.6 Wmin at 20 cm HzO. PAP, LAP, PVR, PAR, CVP, and intrathoracic pressure were all correspondingly significantly elevated (p < 0.002). Intrathoracic pressure rose immediately with the application of PEEP and fell to normal with discontinuance. A Bennett MA- 1 respirator was modified in the following manner to allow the end-expiratory pressure to drop to atmospheric level every fourth breath (Fig. 1). The MA-1 inspiration control valve (I), located on top of the MA- 1 bellows toward the back of the machine, is energized during inspiration. Connected in parallel with the inspiration control valve is a SPDT relay (H). When the DPST switch (G) is closed, the relay advances the stepping relay (E) one contact for each machine inspiration. During the expiration phase the relay is connected to the contact arm' on the stepping relay, which, depending upon its position, controls either the reset coil on the stepping relay or the solenoid valve (C). When the solenoid valve is activated, it disconnects the PEEP mechanism (B) from its pressure source (A), thereby turning the PEEP off. During the next inspiration the stepping relay advances and the solenoid valve opens, allowing PEEP to be reestablished. The rotary switch (D) decides how many breaths on PEEP are allowed before the stepping relay resets and PEEP is shut off by the solenoid valve. The initial design required that three breaths be delivered to attain the preset end-expiratory pressure (Fig. 2) The modification described above affords immediate attainment of preset PEEP. This interrupted pattern halted the progres- TABLE 1. Inflation Hold CARDIAC OUTPUT AND PULMONARY ARTERY PRESSURE DURING INFLATION HOLD Q (L/min) Baseline 0.8 sec 1.6 sec 2 sec 4.9 f 0.05 4.6 f 0.04 4.4 f 0.05 4.4f 0.06 13.7 f 0.6 14.0 f 0.5 p = 0.066 14.6f 0.6 p = 0.004 14.8 f 0.6 p = 0.004 Q = cardiac output; PAP = pulmonary artery pressure. 554 THE ANNALS OF THORACIC SURGERY

~~~ - (0 z P Ln Ln Ln ul TABLE 2. EFFECTS OF CONTINUOUS PEEP ON HEMODYNAMIC VARIABLES Continuous Y PAP LAP PVR PAR CVP PEEP (L /min) (mm Hg) (mm Hg) (X lo4 dynes sec cm") (X 105 dynes sec (cm HnO) Baseline 4.8 f 0.2 5 cm 4.4 k 0.2 p 2.6 f 0.4 3.3 f 0.2 3.9 k 0.1 = 0.002 20 cm 15 cm 10 cm 16.22 1.0 19.1 1.1 22.8-C 1.5 27.2 2 2.1 31.5k 2.2 10.32 1.0 11.85 0.9 13.1 '. 0.7 14.3 f 0.7 17.8 '. 0.8 27.1 2 1.1 38.02 1.0 44.1 2 0.9 71.42 3.7 111.72 11.8 0.8k 1.1 1.2-C 0.14 p = 0.059 1.9-C 0.13 3.03 f 0.2 5.2f 1.2 9 6.1 2 0.6 7.6 2 0.9 98 9.5 f 0.9 12.42 0.7 15.2 k 0.6 9 = cardiac output; PAP = pulmonary artery pressure; LAP = left atrial pressure; PVR = pulmonary vascular resistance; PAR = pulmonary artenolar resistance; CVP = central venous pressure.

MAC DONNELL ET AL. A- FEEPPressure Source B - PEEPMechanisrn C - Solenoid Valve D- Rotary Switch E - Stepping Relay F - Pilot Light G - DPST Switch H - 24VDC SPDT Relay I - MA1 24VDC Inspiration Control Solenoid Valve FIG. 1. Interrupted PEEP modajication for MA-1. (See text for details.) sive decline in cardiac output seen with continuous PEEP and allowed it to return to normal levels (Table 3). The same was true of PAP, LAP, and intrathoracic pressure. Even at the 20 cm H20 pressure level of interrupted PEEP, the changes, while still statistically significant, were diminished and were tolerable, whereas 0 I "1 8 r CARDIAC OUTPUT I 2 I 8Or AIRWAY PRESSURE I CONTINUOUS PEEP I INTERRUPTED PEEP FIG. 2. On the right side of the tracing are various levels of interrupted PEEP ranging from 5 to 15 cm HgO. There is a return to atmospheric pressure every fourth breath with pulmonary artery pressure and cardiac output reverting to control levels. (CO = 5.2 Llmin, PA pressure = 15 mm Hg.) The lejit side of tracing demonstrated 22 cm H,O of continuous PEEP with a resultant decrease in CO and an increase an PA pressure. 556 THE ANNALS OF THORACIC SURGERY

Interrupted PEEP PRESSURE g 20-20 B CARDIAC OUTPUT L.kmcrrrmrrccI1*cc C D FIG. 3. Relationship between (A) airway pessure, (B) intrathoracic pessure, (C) pulmonary artery pressure, and (0) cardiac output during high levels of continuous PEEP. with continuous PEEP the changes in cardiac output and other variables were severe (Fig. 3). Comment The adverse hemodynamic effects of positive-pressure ventilation have been ascribed to the resultant combination of decreased venous return and increased pulmonary vascular resistance. The time/pressure characteristics of the respiratory cycle during mechanical ventilation are the critical determinants of any observed hemodynamic changes. West [9] has done much to clarify the interrelationships between pulmonary blood flow and arterial, venous, and alveolar pressures. He pointed out that the distribution of blood flow in the pulmonary capillary bed is influenced by alveolar wall pressure; increases can have profound effects on pulmonary microcirculation. The interrelationship of blood flow and alveolar volume has been further elucidated by Mead and Whittenberger [5], who showed that PVR in the excised dog lung is volume (air) dependent. PVR is lowest at 50% of the maximum lung volume, with the least total resistance at functional residual capacity. West has also shown that the resistance of small vessels (below 30p in diameter) - the ones that are exposed to increasing alveolar pressure - increases with rising lung volume. Thus it is clear that whether a capillary is open, closed, or partially collapsed depends upon transmural pressure. It has also been noted that the pulmonary vascular bed functions best if exposed to pulsatile pressures [6]. A primary alteration in the microcirculation is thought to be responsible for this phenomenon and has led to the concept of a critical closing pressure in the microcirculation. The many factors involved in determining this closing pressure include not only mean capillary pressure and pulse frequency but probably also pulsatile flow. We speculate that lack of flow in the pulmonary microcirculation secondary to alveolar wall pressure may result in increasing PVR, thus suggesting an intimate interrelationship between the critical closing pressure for the pulmonary microcirculation and airway pressure. VOL. 19, NO. 5, MAY, 1975 557

4 X M 4 3: 0 TABLE 3. EFFECTS OF INTERRUPTED PEEP ON r HEMODYNAMIC VARIABLES : PEEP' (L /min) (mm Hg) (mm Hg) $ E Interrupted Q PAP LAP PVR PAR (X lo4 dynes sec ~ m-~) (X lo5 dynes sec cm4) At 5 cm z 13.3 f 0.4 Baseline 4.9 f 0.03 21.52 0.9 13.2 2 0.4 34.8f 1.3 1st breath 4.82 0.03 21.82 1.0 13.22 0.4 35.82 1.2 14.02 1.6 p = 0.1 p = 0.5 2nd breath 4.7 2 0.04 22.72 1.0 13.2 2 0.4 38.22-C 1.5 15.92 1.6 p = 0.02 p = 0.5 p = 0.2 p = 0.2 3rd breath 4.6 f 0.04 23.82 1.0 12.6 f 0.4 41.02 1.4 19.2f 1.6 p = 0.1 p = 0.5 p = 0.02 p = 0.02 4th breath 4.9 f 0.03 21.51 0.9 13.2 2 0.4 34.82 1.3 13.32 1.4 At 10cm Baseline 4.9 f 0.03 1st breath 4.8 f.0.03 p = 0.1 2nd breath 4.7 2 0.03 3rd breath 4.5 f.0.03 4th breath 4.9 2 0.03 21.5 2 0.9 21.72 1.1 23.22 1.0 p = 0.2 24.3f 0.9 p = 0.1 21.5f 0.9 13.22 0.4 13.252 0.4 12.62 1.0 p = 0.5 11.8 2 0.5 p = 0.1 13.2 2 0.4 34.82 1.3 36.01 1.6 p = 0.5 39.31 1.5 p = 0.05 42.51 1.5 34.8k 1.3 13.32 1.4 14.02 1.6 17.92 1.4 p = 0.05 21.82 1.6 13.32 1.4

~ At 15 cm Baseline 1st breath 2nd breath 3rd breath 4th breath 4.9 2 0.03. 4.8 2 0.02 4.6 2 0.03 4.5 2 0.03 4.9f 0.03 21.52 0.9 22.2 2 0.9 p = 0.5 23.82 0.8 p = 0.1 25.8+- 0.9 p = 0.02 21.5+- 0.9 13.25 2 0.4 13.2 2 0.4 12.4 f 0.4 p = 0.2 11.6 f 0.4 p = 0.05 13.25+ 0.4 34.8 f 1.3 37.22 1.5 p = 0.2 41.1 f 1.2 45.42 1.4 34.82 1.3 13.32 1.5 14.8f 1.5 19.82 1.4 24.92 1.7 13.3rt 1.4 At 20 cm Baseline 1st breath 2nd breath 3rd breath 4th breath 4.9 2 0.04 4.6 2 0.05 4.3 2 0.08 3.8f 0.16 4.92 0.04 21.52 0.9 21.62 1.1 23.02 1.3 p = 0.02 25.52 1.2 21.52 0.9 13.2 2 0.5 11.8f 0.4 11.1 +. 0.4 10.0 2 0.4 13.2 +- 0.5 35.0 f 0.9 37.5 2 1.o 42.4-C 1.8 53.6 f 3.2 p = 0.005 35.0 2 0.9 1.32 0.14 1.62 0.16 2.182 0.28 3.272 1.4 1.32 0.14 'Preset end-expiratory pressure attained by third breath. Q = cardiac output; PAP = pulmonary artery pressure; LAP = left atrial pressure; PVR = pulmonary vascular resistance; PAR = pulmonary artenolar resistance.

MAC DONNELL ET AL. Since the adult respiratory distress syndrome with its associated alveolar collapse was identified and subsequently treated with PEEP [ 11, much interest has been directed toward the hemodynamic effects of this form of therapy. We have examined various methods of PEEP in an attempt to further define its hemodynamic effects. Inspiratory hold, which maintains full inspiratory pressure for up to 2 seconds before exhalation begins, was found to decrease cardiac output and increase PAP at all levels tested (0.8, 1.6, 2 sec). This decrease in cardiac output was statistically significant but not of great magnitude (approximately 5%). With continuous PEEP there was a substantial decrease in cardiac output. There was also an increase in PAP, PVR, and PAR that was directly related to the level of airway pressure. The changes up to 10 cni H2O pressure were not large, whereas at the 15 cm and 20 cm levels they were large and dangerous. Cardiac output was reduced 45% by continuous PEEP at the 20 cm H20 level. The changes in PAP, LAP, CVP, and intrathoracic pressure were proportional to the changes in cardiac output. We found that interrupted PEEP ventilation (intrathoracic and airway pressure returning to atmospheric every fourth breath) substantially reduced adverse effects on cardiac output. The PAP, PVR, and PAR were only mildly increased with this technique. Thus, periodic interruption of PEEP allows for a nearly normal pressurehlow relationship in the dog lung. References 1. 2. 3. 4. 5. 6. 7. 8. 9. Ashbaugh, D. G., Petty, T. L., Bigelow, D. B., and Harris, T. M. Continuous positive pressure breathing (CPPB) in adult respiratory distress syndrome. J Thorac Cardiouusc Surg 57:31, 1969. Colgan, F., and Marocco, P. Cardiac respiratory effects of constant and intermittent positive pressure breathing. Anesthesiology 36:444, 1972. Cournand, A., Motley, H., Werko, L., and Richards, D. Physiological studies of the effects of intermittent positive pressure breathing on cardiac output in man. Am J Physiol 152:162, 1948. Hubay, C. A,, Brecher, G. A., and Clement, F. L. Etiological factors affecting pulmonary artery flow with controlled respiration. Surgery 38:215, 1955. Mead, J., and Whittenberger, J. L. Lung Inflation and Hemodynamics. In W. 0. Fenn and H. Rahn (Eds), Handbook of Physiology: Section 3, Respiration, 1964. Vol I, p 477. Milnor, W. R. Physiology in medicine. N Engl J Med 287:27, 1972. Morgan, B., Martin, N., Honbein, T., Crawford, E., and Guntheroth, W. Hernodynamic effects of intermittent positive pressure respirators. Anesthesiology 27:584, 1966. 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. West, J. B. Distribution of Blood Flow and Ventilation Measurements Measured with Radioactive Gases. In M. Simon (Ed), Frontiers in Pulmonary Radiology. New York: Grune & Stratton, 1969. P 174. 560 THE ANNALS OF THORACIC SURGERY