JOURNAL
OF
APPLIED
PHYSIOLOGY
Vol. 38, No. 5, May
1975.
Printed
in U.S.A.
Lung lavage using a single-lumen
endotracheal
B. ,4. MUGGENBURG AND J. L. MAUDERLY Inhalation Toxicologv , Research Institute, Lovelace Foundation
P. 0. Box
MUGGENBURG, B. A., AND J. L. MAUDERLY. Lung lavage using a single-lumen endotracheal tube. J. Appl. Physiol. 38(5): 922-926. 1975.~The physiological response of the cardiopulmonary system of the dog during and after bronchopulmonary lavage via a singlelumen endotracheal tube was evaluated. The five Beagle dogs used in the study were prepared for lavage by anesthetization, vascular cannulation, intubation with a single-lumen endotracheal tube, and hyperventilation with 100 y0 oxygen. Lavage was performed by placing a dog in lateral recumbency, slowly introducing saline to a volume approximating the total lung capacity of the dependent lung, and then draining the lung immediately by gravity. After brief ventilation the lavage sequence was repeated until five washes using a total of 2,000 ml were completed. The dog was then turned to the opposite side and the washing sequence repeated on the other lung. The heart rate slowed but pulmonary and systemic arterial mean pressures did not change. The Paoz decreased from 3 17 to 107 mmHg during but Paces did not increase and remained below the procedure, 40 mmHg. Pulmonary function tests at 24 h after lavage revealed only a few mild changes in breathing pattern and gas exchange. At 168 h after lavage pulmonary function values did not differ significantly from prelavage values.
dogs;
pulmonary
function;
blood
pressure;
gas exchange
LAVAGE or lung washing has been used in the treatment of a variety of lung diseases since the early 1960s (4, 13). It has also been used experimentally to obtain pulmonary surfactant and lung cells (10) and to remove radioactive particles from the lung (2, 11). The technique requires a functional separation of liquid-filled and ventilated lung regions. In volumecontrolled unilateral lavage (4) the lungs are functionally separated by a Carlens catheter with balloons in the trachea and one major bronchus. This method of treatment, while effective, has been limited to adults because of the large size of the Carlens catheter (4). Catheter size has also been an obstacle in the use of the procedure in experimental animals. The following study was performed to evaluate a lavage technique employing an ordinary single-lumen endotracheal tube with the functional separation of liquidand gas-filled lungs accomplished by gravity and position only. This procedure may have clinical application1 as well as providing a method for evaluating respiration from a combined air and fluid medium. AND
METHODS
Five Beagle dogs (3 males and 2 females), 35-42 months and weighing from 7.2 to 15.0 kg, were used in this study. dogs were determined to be normal by physical examination pulmonary function testing. Food was withheld from the dogs for 24 h before lavage. --* l This lung lavage procedure has been successfully used in treatment
Kylstra,
of a 9-yr-old
Duke
University
child
with
Medical
alveolar
proteinosis
by Dr.
Albuquerque,
New
Mexico
8711.5
preanesthetic agents were given. Anesthesia was induced using a face mask with a mixture of 5y0 halothane vaporized in equal parts of oxygen and nitrous oxide. A Magill-type endotracheal tube was placed in the trachea, and the balloon was inflated. The anesthetic mixture was then adjusted to l-2 y0 halothane in oxygen only. A cutdown procedure was used to isolate the left femoral artery and vein. A 4 Fr polyethylene catheter 100 cm long was inserted in the artery and passed into the thoracic aorta (about 45-50 cm). A Swan-Ganz balloon catheter, 5 Fr, (Edwards Laboratories, Santa Ana, Calif.) was inserted in the vein, the balloon was inflated, and the catheter tip was passed into the pulmonary artery. After the location was determined by the characteristics of the pressure curve, the balloon was deflated. The catheters were connected to pressure transducers (P23Db, Statham Laboratories, Inc., Hato Key, Puerto Rico) and amplifiers (Accudata 113, Honeywell, Inc., Denver, Colo.) to record systemic artery mean pressure @a) and pulmonary artery mean pressure (Hpa) during the lung washing procedure. A lead II electrocardiogram was recorded during the procedure. A 1.25-cm-diameter three-way valve was connected to the end of the endotracheal tube. One outlet of the valve was connected to the anesthetic machine and the other to tubing connected by a Y to two 2-liter saline bottles suspended from an iv rack at eye level. A saline manometer was connected to this tubing for monitoring inflow pressure of the lavage fluid. This tubing was also connected by a T to a reservoir or collecting bottle placed on the floor (Fig. 1). An infrared carbon dioxide analyzer (model LB- 1, Beckman Instruments, Fullerton, Calif.) was used to monitor breath-by-breath Fco2 through a catheter inserted in the airway just distal to the three-way valve from the dog. After the dog was stabilized in a light surgical plane of anesthesia, it was placed in either right (3 dogs) or left (2 dogs) lateral recumbency. The dog was then manually hyperventilated until At the end of the hyperventilation period the FETCO~ was 2-3%. the three-way valve was turned, and 100 ml of saline at 37’C were introduced into the lung. After a 30-s pause to allow absorption of some of the oxygen in the dependent lung, an additional 100 ml were introduced into the lung, followed by another 30-s pause and the final introduction of an additional 200 ml of saline into the lung. The fluid was then immediately drained by gravity into the reservoir on the floor, the three-way valve was turned to the breathing circuit, and the dog was manually ventilated 3 times. This washing procedure was repeated 4 times until a total volume of 2,000 ml of saline had been passed through the lung. The dog was then turned on the opposite side and the entire procedure repeated on the opposite lung. After the final wash, the dog was tilted to a head-down position and the lung was drained as completely as possible. The dog was ventilated manually every 30 s to 1 min until spontaneous respiration returned. The catheters were then removed, the vessels and cutdown site were repaired, the endotracheal tube was removed, and the dog was allowed to regain consciousness. The dog breathed ambient air at all times after removal of the endotracheal tube. The lavages were satisfactorily completed on all dogs. Arterial blood samples, taken periodically during the lavage,
BRONCHOPULMONARY
MATERIALS
5890,
tube
old The and No the
Johannes
Center. 922
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LUNG
LMMGE
IN
DOGS
923
D
FIG. 1. Diagram of the lavage procedure: A, three-way valve; B, sample port for monitoring fraction of carbon dioxide; C, tubing to anesthetic machine ; D, isotonic saline reservoir; and E, collection vessel for recovery of lavage fluid.
were analyzed using a glass capillary electrode for pH, a membrane-covered platinum electrode for oxygen tension and a membrane-covered electrode for carbon dioxide tension (model PHM7 1, Radiometer Corp., Copenhagen, Denmark). The measured values were corrected to the individual dog’s rectal temperature and the oxygen saturation of hemoglobin and acid-base parameters were calculated (12). Samples of lavage fluid were obtained through a small catheter placed in the lavage tubing near the three-way valve (Fig. 1). Samples (inspired and end-expired) were drawn into a syringe, air bubbles were expelled, and the syringe was capped with a mercury cap. A long small-bore catheter was used to obtain mixed expired lavage fluid samples from the bottom of the collection bottles. The tension of CO2 was measured as described for the arterial blood samples. When the dogs were ambulatory, they were placed in a cage where they remained for 24 h. Pulmonary function measurements were performed at ‘24 and 168 h after lavage. After the 24-h function evaluation, the dogs were returned to their kennels. Pulmonary function measurements were performed without the use of anesthesia or sedation by methods similar to those previously described (6). For the first series of measurements, the dogs were fitted with a face mask and esophageal balloon catheter (3) and placed in restraining stocks (8) which held them in a standing position but did not place pressure on the thorax or abdomen. Dynamic pulmonary compliance (CL) and resistance (RL) were measured by the loop-closing technique using a resistance-compliance computer (model 794444 RIC Computer, Honeywell, Denver, Colo.) and signals from a pneumotachograph and the esophageal catheter. The functional residual capacity (FRC) was measured by the open-circuit nitrogen washout method. Specific compliance was calculated by dividing CL by FRC. The respiratory frequency (f), tidal volume (VT), and minute volume (VE) during oxygen breathing were also calculated from the washout data. Nitrogen washout curves were constructed by plotting the progressive fall in FETN~,recorded during the washout, against breath number on semilog graph paper. Each curve was analyzed graphically into its individual components and the relative size and nitrogen dilution rate of each component was noted. The CO diffusing capacity (DL& and fractional uptake of CO (Fuoo) were measured by the steadystate end-tidal method previously reported (7). For a second series of measurements, the dogs were fitted with the mask and manually restrained in the supine position. Breathby-breath tensions of oxygen and CO2 were sampled at the breath-
ing valve and continuously recorded with the dogs breathing dried ambient air. After stabilization, a timed collection of the expirate was made during which a sample of blood was drawn from the femoral artery by percutaneous puncture. Analysis of the blood sample yielded arterial gas tensions (Paoe, Pacoz), pH (pHJ, hemoglobin content, and oxygen saturation of hemoglobin (Sa&. The breathing traces allowed calculation of f and the alveolar (end-tidal) gas tensions (PACT,PACT&,and gradients (PA-aoz, Pa-A co& Expired volume and gas tensions allowed calculation of VE, VT, 02 uptake (Voz), CO2 output (VCO~), and the respiratory exchange ratio (RER). The dogs were then switched to breathing 100% oxygen and, following the washout, the alveolar and arterial oxygen and CO2 tensions and gradients were again measured. Gas samples were analyzed for nitrogen, oxygen and CO2 by a mass spectrometer (model MS-8, Scientific Research Instruments, Baltimore, Md.) and CO tensions were determined by an infrared analyzer (model IR2 15, Beckman Instruments). Measurements were performed at an altitude of 1729 meters where the barometric pressure and inspired Po2 were approximately 624 and 120 mmHg, respectively. The data obtained in this study were analyzed by calculating t values for the comparison of means (16). This was a comparison of base-line means with values obtained at all subsequent times or events. Values were considered significantly different when the probability of a larger value of t at the appropriate degrees of freedom was 0.05. RESULTS
During the lung washing (which lasted from 18 to 22 min), the heart rate decreased significantly from the anesthesia base-line value but remained constant throughout the procedure (Table 1). No changes occurred in the Ppa or %a. Between the period after lavage and before spontaneous respiration returned, the heart rate increased slightly and there was a small nonsignificant fall in Psa. The pressures in the column of fluid entering the lung during the procedure varied from 25 to 35 cmH20. The Paoz increased significantly during the hyperventilation period before Iavage (Table 2). By the end of the lavage of the first side of the lung, the PaoZ had fallen significantly to about 100 mmHg and was the same at the end of the lavage of the second side of the lung. An additional fall in Pao2 occurred after the second lung was drained when the dog was allowed to breathe spontaneously. The Pace,, which decreased significantly during hyperventilation (Table 2), returned to the anesthesia base-line value during the lavage and was allowed to gradually increase after lavage to
TABLE 1. Heart rate and mean blood pressure during lung lavage with the do?c breathing oxygen and 1-2 % halothane Heart Rate, min-1
Event Anesthesia base line Period of hyperventilation Right side down FIuid in Fluid out End Left side down Fluid in Fluid out End Return of spontaneous
respiration
Ppa, mmHg
Fsa,
mmHg
107 102
zt It
8.4 15.0
14 =t 3.2 14 =t 3.4
70 5 63 zt
80* 83* 85*
zt zk =t
4.0 2.3 2.3
15 * 2.9 13 =t 4.2 13 If 4.2
72 64 69
zk 10.2 dz 18.4 AI 10.6
85* 82* 84* 88*
=t zt zt It
5.0 4.5 4.5 7.7
16 14 14 13
67 62 71 61
=t 13.6 xt 11.1 zk 8.1 zt 16.9
Values are means & 1 SD. Fpa = pulmonary systemic arterial mean pressure. * Comparison the t-test was significant at the 1 70 level, 8 df.
=t =t zt rt
3.6 4.7 3.6 4.1
artery mean pressure of this value with base
14.0 15.0
&a line
= by
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924
B. A. MUGGENBURG
TABLE 2. Blood gas tesions and acid-base balance during lung lauage _----- _-.__ --.-. - Pao2,
Event
Base line anesthesis Period of hypervent Lavage, right side down$ Lavage, left side down Return of spontaneous respiration
Paco?p
pH
mmHg
mmHg
317 rt36.6 370* zt23.1 107t jz44.6 107t zt37.2 W h33.6
41 zt2.8 17t zt2.9 36* zt3.9 36 zt4.7 56t h6.1
Sam,
7.31 zto.02 7.59t zto.07 7.37 ztO.06 7.34 zko.05 7.19t zto.05
9%
99.8 zJzo.1 99.9 zto.0 93.2 zJzlO.3 94.8 zt5.8 87.0 hl2.8
HC03, meq/l
21.3 =tl .o 16.3t ztO.6 20.9 zt2.2 20.1 ztl.9 21.7 ~2.7
me41
Base Excess mw/l
22.6 ztl.1 1s.st ztO.6 22.0 zt2.2 21.2 rt2.0 23.5 h2.8
-4.4 zto.9 --1.4* zt2.0 -3.4 zlz3.1 -4.7 zt2.1 -7.0 h2.8
Total
CO2,
_-.~-.
* Comparison of this value with base line by the Values are means =t 1 SD. t Comparison of this value with base t-test was significant at the 5% level, 8 df. $ Arterial blood sample line by the l-test was significant at the 1 To level, 8 df. drawn at end of lavage before the lung was ventilated. TABLE 3. Gas exchange of dogs breathing room air before and after lung lavage .- - -_____ ---- ~ .- _.- ~~--_~____~_.___ _~-.. .-._---~________ --Before Lav age Base Line
Lavage
Diffusing
capacity,
Fractional
uptake
Alveolar
ml srPn/min of CO,
per mmHg
decimal
fraction
Poe, mmHg
Arterial
Paz, mmHg
Alveolar-arterial
PO’L gradient,
Arterial
Pco2,
mmHg
Alveolar
Pcoz,
mmHg
Arterial-alveolar Arterial
pH,
O:! saturation 02 uptake, outpttt,
Respiratory
mmHg
Pco:! gradient, pH
mmHg
units
of hemoglobin,
‘x,
ml srPn/min ml srPn/min exchange
Specific ventilation, 02 uptake Values are means * Comparison of this level, 8 df.
ratio,
decimal
ml minute
fraction
volume/ml
9.2 zt3.2 0.497 &O. 044 76 zlz5.1 71 zt5.1 5 2t2.2 39 zt5.2 37 zt4.2 2 &I .l 7.39 zlzo.02 90.1 zt2.3 102 ztl7.3 87 ztl8.8 0.85 zto.07 32 ~3.6
---.---~-.. & 1 SD. srpn value with base
6.2 zt2.0 0.334* *o. 033 82 &lo. 1 68 zt9.8 14 ztl6.7 38 rt3.3 32 zt7.5 6 zt5.3 7.36 ztu.03 86.9 xt5.9 77 ztl8.6 73 zt20.4 0.96 *o. 14 w zt7.2
DISCUSSION
Bronchopulmonary lavage has been used for a number of years both as a valuable research method and as a therapeutic procedure to treat lung diseases (4). The procedure has generally TABLE 4. Lung ventilation and mechanics of dogs before and after lung lavage
168 h 8.3 ztz4.6 0.468
rto.097 78 zt5.9 72 It7.7 6 rt3.7 37 zt3.2 35 zt2.1 2 zt2.1 7.39 zJzo.02 90.4 zt2.6 81 zt29.7 77 ~26.6 0.96 &O. 13 38 rtlO.1
Before Lavage Base Line Frequency Tidal
(room
volume
Minute Frequency Tidal
air),
(room
volume
Minute
air),
ml
air),
02),
(100
volume
Functional
breaths/min
(room
(100%
volume
BTPS
ml
(100%
BTPS
breaths/min OZ), ml
s
19 ~3.8 181 zt38.3 3350 &850 14 Al.9 184 zt48.6
02),
BTPS
ml
2970
BTPS
residual
capacity,
ml
Functional residual body wt Dynamic pulmonary cmHz0 Specific compliance,
capacity,
ml B-rPs/kg
BTPS
compliance,
ml/
ml/cm
per
Hz0
FRC Values are means * Comparison of this level, 8 df TABLE
100%
= standard temperature and pressure, dry. line by the t-test was significant at the 1 ‘To
aid in the return of spontaneous respiration. No other significant changes were observed in the arterial blood except for the decrease in bicarbonate and total CO2 during hyperventilation. The saline introduced into the lung totaled 4 liters, about 95% of which was recovered. Samples of the fluid were obtained as it drained from the lung (end-tidal) and the Pco2 was measured at 30 mmHg. Samples obtained from the collection bottles at the end of the procedure (expired) had PCOS values of near 20 mmHg. All of the dogs appeared clinically normal several hours after the lung lavage procedure except one. That dog had an increased respiratory frequency, moist rales were heard during auscultation of the chest, and the dog was less active than the others. At 1 wk after lavage, all of the dogs were active, and no abnormal sounds were heard during auscultation of their chests.
J. L. MAUDERLY
The only statistically significant functional alterations at 24 h after lavage were a reduced Fuco, an increased ~E/~oz, and a reduced VT while breathing ambient air (Tables 3-5). At that time, all dogs also had a higher f and lower VT (Table 4). Both base-line and postlavage nitrogen washout curves had three rapidly clearing component, a major components : an initial component with an intermediate washout rate, and a small slowly clearing component. At 24 h after lavage, the slopes of the intermediate components were reduced to a mean of 30% of base line (range = 13-60 %), indicating a slower rate of nitrogen dilution. By 168 h after lavage, all functional parameters had returned to their base line values. All of the dogs in this study are active and clinically normal at more than 30 days after lavage.
_..__ _-
- ~--
CO2
After 24 h
AND
zt
value
1 SD. with
ml
=tlOOO 471 ztl44.9 42 *lo. 3 53 ztl4.1 0.116 zlzo.021
= body temperature base line by the t-test
BTPS
5. Gas exchange of dogs breathing oxygen before and after lung lavage - -.--~~_ - -~---~-.~---.--- - .~______._ Before Lavage Base Line
--
.--
Alveolar Arterial
--.-. Po2, mmHg Paz, mmHg
Alveolar-arterial Arterial Alveolar
PO:! gradient,
Pco2, Pco2,
Values
pH,
mmHg
mmHg
Arterial-alveolar Arterial
. __~~~.___
mmHg Pc02
pH
gradient,
units
are means
mmHg
519 &7.8 485 ztlO.3 34 zt13.5 40 A4.3 38 zt5.0 2 zlzl.2 7.38 *0.03
After
Lavage
24 h 48 rt39.2 101* zt57.1 3300 ztll20 38 zt25.2 103 zt64.0 3330 *1400 396 &Ill.6 37 zt9.6 40.1 zt20.0 0.103 *0.070 and pressure, was significant
-II---.------
.--168 h ----
19 zt4.0 167 zt60.6 3010 ZtllOO 17 zt3.9 180 zh84.4 2780 zJz800 479 rt138.3 44 =tlO.O 51 ztl4.7 0.106 zko. 007 saturated. at the l y0
---After Lavage
-
24 h
168 h
531 ztl4.9 374 zJzl32.0 157 ztl44.9 41 zt4.4 32 rtlO.0 9 rt8.0 7.34 zto.04
522 zt8.1 485 Al6.4 37 zt25.5 40 zt2.2 35 zt2.9 5 zt4.2 7.38 ho. 03
rt 1 SD.
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LUNG
L;iVAGE
IN
DOGS
been based on the assumption that it was necessary to separate the lung into two functional compartments: the region to be lavaged, and the region for ventilation and maintenance of anesthesia. In an earlier study, however, Winternitz and Smith (17), demonstrated that the entire lung of the dog could be washed with a normal saline solution with reasonable safety. Their procedure did not provide for repeated washings nor did it include any assessment of the physiological changes that may be associated with the rapid change from air to fluid to air in the lung. Blenkarn and Hayes (1) successfully demonstrated bilateral or total lung lavage under hyperbaric conditions in the dog. They reported that pulmonary arterial mean pressure, which was stable in our dogs, rose about 4 mmHg during lavage under hyperbaric conditions. In two human patients, a small rise in Fpa was noted with the introduction of fluid during unilateral lavage (14). Increased Fpa has also been reported during unilateral lavage in dogs (9) probably due to the positive pressure in the chest. Systemic arterial pressure did not change and was not changed in other reports (9, 14). The dogs were hyperventilated for 3-4 min before the first wash to render them apneic. Although the Pao, fell during lavage of the first lung it remained adequate for normal saturation of the arterial blood. The 400 ml of fluid introduced in each wash was intended to be approximately the TLC of the dependent lung. Oxygen-halothane gas in the upper lung provided continuous gas exchange during the procedure. Manual ventilation between each wash renewed the supply of oxygen-halothane in the upper lung and removed COZ, resulting in a stable Paoe and Pacoa during the lavage. Each wash of the lung lasted no more than 2 min during which time approximately 100 ml of oxygen would have been absorbed (002 = 50 ml). Assuming the lung contained a volume of 02 equal to FRC (450 ml), approximately 8- to 9-min supply of oxygen was in the lung at the beginning of each wash. That volume provided an adequate safety factor, as verified by the consistent Paoz of 100 mmHg at the end of the lavage of each side of the lung. In the unilateral lung lavage, the one lung is ventilated throughout the procedure; however, the lavaged side of the lung is a functional shunt during the entire lavage, whereas it is only a periodic shunt in the “single-lumen endotracheal tube” lavage. Some gas exchange also occurred with the saline wash solution as reflected by the Pc02 of the end tidal (30 mmHg) and mixed expired (20 mmHg) saline samples. The exchange of CO2 into the lavage solution probably aided in preventing a rise in Paco2. Similar findings were reported by
925 Kylstra et al. (5) d uring unilateral lavage in man. The dog that had a significant decrease in PaOz was the smallest dog in this study and the 400-ml wash volume exceeded its measured baseline FRC by 150 ml. The residual gas may have been inadequate for exchange of 02. The decrease in Pao2 and the increase in PacOz following the lavage was expected as this was a period of reduced ventilation aiding the return of spontaneous respiration. The mild functional alterations present at 24 h after lavage probably resulted from a combination of postanesthetic atelectasis and the retention of small amounts of fluid in the lungs. These effects combined to reduce the overall efficiency of ventilation and gas exchange during the early postlavage period but were not sufficient to raise VE significantly or to present a hazard to the subjects. Previous studies (9), in which unilateral lavages were performed using a Carlens catheter, produced similar results both in lavaged dogs and in anesthetized sham-lavaged controls. The functional alterations, therefore, were probably related primarily to anesthesia. Bronchopulmonary lavage, using a single-lumen endotracheal tube, appears to be a reasonably safe and simple procedure. No serious physiologic alterations were found in the cardiopulmonary system during the procedure and mild pulmonary function alterations returned to base line by 1 wk after lavage. A single-lumen tube greatly increases the potential for using the procedure in small subjects over the Carlens double-lumen tube and might obviate the need for cardiopulmonary bypass during lung lavage in small children (15). Because this procedure washes the entire lung in a single anesthetic experience, the number of treatment sessions required may be less. It also may be useful in obtaining pulmonary cells and surfactant from experimental animals for research. The authors thank Dro. J. A. Kylstra, U. C. Luft, and Waneta Tuttle for their advice and criticisms; Phyllis B. Beckley, Sharon A. Felicetti, Goldie A. Morrison, W. C. Nenno, and S. A. Silbaugh for technical assistance; R. Crain for advice on statistical analysis; and F. C. Rupprecht for technical editing. Research was performed under Contract AT (29-2) - 10 13 between the Energy Research and Development Administration and the Lovelace Foundation for Medical Education and Research and in facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care. Received
for publication
15 July
1974.
REFERENCES G. D., AND J. A. HAYES. Bilateral lung lavage with hyperbarically oxygenated saline in dogs. J. A#. physiol. 29: 786-793, 1970. BOECKER, B. B., B. A. MUGGENBURG, K. 0. MCCLELLAN, S. P. CLARKSON, F. J. MARES, AND S. A. BENJAMIN. Removal of 14Ce in fused clay particles from the Beagle dog lung by bronchopulmonary lavage. Health Phys. 26: 505-5 18, 1974. DUBIN, S. E., AND G. A. MORRISON. A face mask and mouthpiece for respiratory studies in unanesthetized Beagle dogs. J. A@Z. Physiol. 27: 104-105, 1969. KYLSTRA, J. A., D. C. RAUSCH, K. D. HALL, AND A. SPOCK. Volume-controlled lung lavage in the treatment of asthma, bronchiectasis, and mucoviscidosis. Am. Rev. Respirat. Diseases 103: 651-665, 1971. KYLSTRA, J . A., W. H. SCHOENFISCH, J. M. HERRON, AND G. D. BLENKARN. Gas exchange in saline-filled lungs of man. J. A/$. Physiol. 35 : 136-142. 1973. MAUDERLY, J. L. Influence of sex and age on the pulmonary function of the unanesthetized beagle dogs. J. Gelontol. 29: 282-289, 1974.
1. BLENKARN,
2.
3.
4.
5.
6.
7. MA~DERL~, ,J. L Steady state carbon monoxide diffusing capacity of unanesthetized beagle dogs. Am. J. Vet. Res. 33: 14851491, 1972. 8. MAUDERLY, J. L., W. C. NENNO, AND G. A. MORRISON. Stocks for holding unanesthetized dogs in the standing position. Lab. Animal Sci. 2 1 : 263-266, 197 1. 9. MUGGENBURG, B. A., J. IA. MAUDERLY, J. A. PICKRELL, T. I,. CHIFFELLE, R. K. JONES, U. C. LuFrr, R. 0. MCCLELLAN, AND R. L. PFLEGER. Pathophysiologic sequelae of bronchopulmonary lavage in the dog. Am. Rev. Respirat. Diseases 106 : 2 19-232, 1972. 10. PFLEGER, R. C., R. F. HENDERSON, AND J. WAIDE. Phosphatidyl glycerol-a major component of pulmonary surfactant. Chem. Phys. Lipids 9 : 5 l-68, 1972. 11. PFLEGER, R. C., A. J. WILSON, R. G. CUDDIHY, AND R. 0. McCLELLAN. Bronchopulmonary lavage for removal of inhaled insoluble materials from the lung. Diseases CheJt 56 : 524-530, 1969. 12. PICKRELL, J. A., AND S. J. SCHLUTER. The rapid processing of canine blood gas tension and pH measurements. Am. J. Vet. Res. 34: 95-100, 1973.
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926 13. ROGERS, R. M., M. S. BROWNSTEIN, AND J. F. SHERMAN. Role of bronchopulmonary lavage in the treatment of respiratory failure: a review. Chest 62: 95S-106S, 1972. 14. ROGERS, R. M., J. P. SZIDON, J. SHELBURNE, J. L. NEIGH, J. F. SLUMAN, AND K. R. TANTIJM. Hemodynamic response of the pulmonary circulation to bronchopulmonary lavage in man. New Engl. J. Med. 286: 1230-1233, 1972. 15. SEARD, C., K. WASSERMAN, J. R. BENFIELD, A. J. CLEVELAND,
B. A. MUGGENBURG
AND
J. L. MAUDERLY
D. 0. COSTLEY, AND E. M. HEIMLICH. Simultaneous bilateral lung lavage (alveolar washing) using partial cardiopulmonary bypass. Am. Rev. Respirat. Diseases 101: 877-884, 1970. 16. STEEL, R. G. D., AND J. H. TORRIE. Principles and Procedures of Statistics. New York: McGraw, 1960, p. 67. 17. WINTERNITZ, M. C., AND G. H. SMITH. Preliminary Studies in Intratracheal Therapy, Pathology of War Gas Poisoning. New Haven, Conn. : Yale Univ. Press, 1920, p. 145-l 60.
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OF
APPLIED
PHYSIOLOGY
Vol. 38, No. 5, May
1975.
Printed
in U.S.A.
Lung lavage using a single-lumen
endotracheal
B. ,4. MUGGENBURG AND J. L. MAUDERLY Inhalation Toxicologv , Research Institute, Lovelace Foundation
P. 0. Box
MUGGENBURG, B. A., AND J. L. MAUDERLY. Lung lavage using a single-lumen endotracheal tube. J. Appl. Physiol. 38(5): 922-926. 1975.~The physiological response of the cardiopulmonary system of the dog during and after bronchopulmonary lavage via a singlelumen endotracheal tube was evaluated. The five Beagle dogs used in the study were prepared for lavage by anesthetization, vascular cannulation, intubation with a single-lumen endotracheal tube, and hyperventilation with 100 y0 oxygen. Lavage was performed by placing a dog in lateral recumbency, slowly introducing saline to a volume approximating the total lung capacity of the dependent lung, and then draining the lung immediately by gravity. After brief ventilation the lavage sequence was repeated until five washes using a total of 2,000 ml were completed. The dog was then turned to the opposite side and the washing sequence repeated on the other lung. The heart rate slowed but pulmonary and systemic arterial mean pressures did not change. The Paoz decreased from 3 17 to 107 mmHg during but Paces did not increase and remained below the procedure, 40 mmHg. Pulmonary function tests at 24 h after lavage revealed only a few mild changes in breathing pattern and gas exchange. At 168 h after lavage pulmonary function values did not differ significantly from prelavage values.
dogs;
pulmonary
function;
blood
pressure;
gas exchange
LAVAGE or lung washing has been used in the treatment of a variety of lung diseases since the early 1960s (4, 13). It has also been used experimentally to obtain pulmonary surfactant and lung cells (10) and to remove radioactive particles from the lung (2, 11). The technique requires a functional separation of liquid-filled and ventilated lung regions. In volumecontrolled unilateral lavage (4) the lungs are functionally separated by a Carlens catheter with balloons in the trachea and one major bronchus. This method of treatment, while effective, has been limited to adults because of the large size of the Carlens catheter (4). Catheter size has also been an obstacle in the use of the procedure in experimental animals. The following study was performed to evaluate a lavage technique employing an ordinary single-lumen endotracheal tube with the functional separation of liquidand gas-filled lungs accomplished by gravity and position only. This procedure may have clinical application1 as well as providing a method for evaluating respiration from a combined air and fluid medium. AND
METHODS
Five Beagle dogs (3 males and 2 females), 35-42 months and weighing from 7.2 to 15.0 kg, were used in this study. dogs were determined to be normal by physical examination pulmonary function testing. Food was withheld from the dogs for 24 h before lavage. --* l This lung lavage procedure has been successfully used in treatment
Kylstra,
of a 9-yr-old
Duke
University
child
with
Medical
alveolar
proteinosis
by Dr.
Albuquerque,
New
Mexico
8711.5
preanesthetic agents were given. Anesthesia was induced using a face mask with a mixture of 5y0 halothane vaporized in equal parts of oxygen and nitrous oxide. A Magill-type endotracheal tube was placed in the trachea, and the balloon was inflated. The anesthetic mixture was then adjusted to l-2 y0 halothane in oxygen only. A cutdown procedure was used to isolate the left femoral artery and vein. A 4 Fr polyethylene catheter 100 cm long was inserted in the artery and passed into the thoracic aorta (about 45-50 cm). A Swan-Ganz balloon catheter, 5 Fr, (Edwards Laboratories, Santa Ana, Calif.) was inserted in the vein, the balloon was inflated, and the catheter tip was passed into the pulmonary artery. After the location was determined by the characteristics of the pressure curve, the balloon was deflated. The catheters were connected to pressure transducers (P23Db, Statham Laboratories, Inc., Hato Key, Puerto Rico) and amplifiers (Accudata 113, Honeywell, Inc., Denver, Colo.) to record systemic artery mean pressure @a) and pulmonary artery mean pressure (Hpa) during the lung washing procedure. A lead II electrocardiogram was recorded during the procedure. A 1.25-cm-diameter three-way valve was connected to the end of the endotracheal tube. One outlet of the valve was connected to the anesthetic machine and the other to tubing connected by a Y to two 2-liter saline bottles suspended from an iv rack at eye level. A saline manometer was connected to this tubing for monitoring inflow pressure of the lavage fluid. This tubing was also connected by a T to a reservoir or collecting bottle placed on the floor (Fig. 1). An infrared carbon dioxide analyzer (model LB- 1, Beckman Instruments, Fullerton, Calif.) was used to monitor breath-by-breath Fco2 through a catheter inserted in the airway just distal to the three-way valve from the dog. After the dog was stabilized in a light surgical plane of anesthesia, it was placed in either right (3 dogs) or left (2 dogs) lateral recumbency. The dog was then manually hyperventilated until At the end of the hyperventilation period the FETCO~ was 2-3%. the three-way valve was turned, and 100 ml of saline at 37’C were introduced into the lung. After a 30-s pause to allow absorption of some of the oxygen in the dependent lung, an additional 100 ml were introduced into the lung, followed by another 30-s pause and the final introduction of an additional 200 ml of saline into the lung. The fluid was then immediately drained by gravity into the reservoir on the floor, the three-way valve was turned to the breathing circuit, and the dog was manually ventilated 3 times. This washing procedure was repeated 4 times until a total volume of 2,000 ml of saline had been passed through the lung. The dog was then turned on the opposite side and the entire procedure repeated on the opposite lung. After the final wash, the dog was tilted to a head-down position and the lung was drained as completely as possible. The dog was ventilated manually every 30 s to 1 min until spontaneous respiration returned. The catheters were then removed, the vessels and cutdown site were repaired, the endotracheal tube was removed, and the dog was allowed to regain consciousness. The dog breathed ambient air at all times after removal of the endotracheal tube. The lavages were satisfactorily completed on all dogs. Arterial blood samples, taken periodically during the lavage,
BRONCHOPULMONARY
MATERIALS
5890,
tube
old The and No the
Johannes
Center. 922
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LUNG
LMMGE
IN
DOGS
923
D
FIG. 1. Diagram of the lavage procedure: A, three-way valve; B, sample port for monitoring fraction of carbon dioxide; C, tubing to anesthetic machine ; D, isotonic saline reservoir; and E, collection vessel for recovery of lavage fluid.
were analyzed using a glass capillary electrode for pH, a membrane-covered platinum electrode for oxygen tension and a membrane-covered electrode for carbon dioxide tension (model PHM7 1, Radiometer Corp., Copenhagen, Denmark). The measured values were corrected to the individual dog’s rectal temperature and the oxygen saturation of hemoglobin and acid-base parameters were calculated (12). Samples of lavage fluid were obtained through a small catheter placed in the lavage tubing near the three-way valve (Fig. 1). Samples (inspired and end-expired) were drawn into a syringe, air bubbles were expelled, and the syringe was capped with a mercury cap. A long small-bore catheter was used to obtain mixed expired lavage fluid samples from the bottom of the collection bottles. The tension of CO2 was measured as described for the arterial blood samples. When the dogs were ambulatory, they were placed in a cage where they remained for 24 h. Pulmonary function measurements were performed at ‘24 and 168 h after lavage. After the 24-h function evaluation, the dogs were returned to their kennels. Pulmonary function measurements were performed without the use of anesthesia or sedation by methods similar to those previously described (6). For the first series of measurements, the dogs were fitted with a face mask and esophageal balloon catheter (3) and placed in restraining stocks (8) which held them in a standing position but did not place pressure on the thorax or abdomen. Dynamic pulmonary compliance (CL) and resistance (RL) were measured by the loop-closing technique using a resistance-compliance computer (model 794444 RIC Computer, Honeywell, Denver, Colo.) and signals from a pneumotachograph and the esophageal catheter. The functional residual capacity (FRC) was measured by the open-circuit nitrogen washout method. Specific compliance was calculated by dividing CL by FRC. The respiratory frequency (f), tidal volume (VT), and minute volume (VE) during oxygen breathing were also calculated from the washout data. Nitrogen washout curves were constructed by plotting the progressive fall in FETN~,recorded during the washout, against breath number on semilog graph paper. Each curve was analyzed graphically into its individual components and the relative size and nitrogen dilution rate of each component was noted. The CO diffusing capacity (DL& and fractional uptake of CO (Fuoo) were measured by the steadystate end-tidal method previously reported (7). For a second series of measurements, the dogs were fitted with the mask and manually restrained in the supine position. Breathby-breath tensions of oxygen and CO2 were sampled at the breath-
ing valve and continuously recorded with the dogs breathing dried ambient air. After stabilization, a timed collection of the expirate was made during which a sample of blood was drawn from the femoral artery by percutaneous puncture. Analysis of the blood sample yielded arterial gas tensions (Paoe, Pacoz), pH (pHJ, hemoglobin content, and oxygen saturation of hemoglobin (Sa&. The breathing traces allowed calculation of f and the alveolar (end-tidal) gas tensions (PACT,PACT&,and gradients (PA-aoz, Pa-A co& Expired volume and gas tensions allowed calculation of VE, VT, 02 uptake (Voz), CO2 output (VCO~), and the respiratory exchange ratio (RER). The dogs were then switched to breathing 100% oxygen and, following the washout, the alveolar and arterial oxygen and CO2 tensions and gradients were again measured. Gas samples were analyzed for nitrogen, oxygen and CO2 by a mass spectrometer (model MS-8, Scientific Research Instruments, Baltimore, Md.) and CO tensions were determined by an infrared analyzer (model IR2 15, Beckman Instruments). Measurements were performed at an altitude of 1729 meters where the barometric pressure and inspired Po2 were approximately 624 and 120 mmHg, respectively. The data obtained in this study were analyzed by calculating t values for the comparison of means (16). This was a comparison of base-line means with values obtained at all subsequent times or events. Values were considered significantly different when the probability of a larger value of t at the appropriate degrees of freedom was 0.05. RESULTS
During the lung washing (which lasted from 18 to 22 min), the heart rate decreased significantly from the anesthesia base-line value but remained constant throughout the procedure (Table 1). No changes occurred in the Ppa or %a. Between the period after lavage and before spontaneous respiration returned, the heart rate increased slightly and there was a small nonsignificant fall in Psa. The pressures in the column of fluid entering the lung during the procedure varied from 25 to 35 cmH20. The Paoz increased significantly during the hyperventilation period before Iavage (Table 2). By the end of the lavage of the first side of the lung, the PaoZ had fallen significantly to about 100 mmHg and was the same at the end of the lavage of the second side of the lung. An additional fall in Pao2 occurred after the second lung was drained when the dog was allowed to breathe spontaneously. The Pace,, which decreased significantly during hyperventilation (Table 2), returned to the anesthesia base-line value during the lavage and was allowed to gradually increase after lavage to
TABLE 1. Heart rate and mean blood pressure during lung lavage with the do?c breathing oxygen and 1-2 % halothane Heart Rate, min-1
Event Anesthesia base line Period of hyperventilation Right side down FIuid in Fluid out End Left side down Fluid in Fluid out End Return of spontaneous
respiration
Ppa, mmHg
Fsa,
mmHg
107 102
zt It
8.4 15.0
14 =t 3.2 14 =t 3.4
70 5 63 zt
80* 83* 85*
zt zk =t
4.0 2.3 2.3
15 * 2.9 13 =t 4.2 13 If 4.2
72 64 69
zk 10.2 dz 18.4 AI 10.6
85* 82* 84* 88*
=t zt zt It
5.0 4.5 4.5 7.7
16 14 14 13
67 62 71 61
=t 13.6 xt 11.1 zk 8.1 zt 16.9
Values are means & 1 SD. Fpa = pulmonary systemic arterial mean pressure. * Comparison the t-test was significant at the 1 70 level, 8 df.
=t =t zt rt
3.6 4.7 3.6 4.1
artery mean pressure of this value with base
14.0 15.0
&a line
= by
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924
B. A. MUGGENBURG
TABLE 2. Blood gas tesions and acid-base balance during lung lauage _----- _-.__ --.-. - Pao2,
Event
Base line anesthesis Period of hypervent Lavage, right side down$ Lavage, left side down Return of spontaneous respiration
Paco?p
pH
mmHg
mmHg
317 rt36.6 370* zt23.1 107t jz44.6 107t zt37.2 W h33.6
41 zt2.8 17t zt2.9 36* zt3.9 36 zt4.7 56t h6.1
Sam,
7.31 zto.02 7.59t zto.07 7.37 ztO.06 7.34 zko.05 7.19t zto.05
9%
99.8 zJzo.1 99.9 zto.0 93.2 zJzlO.3 94.8 zt5.8 87.0 hl2.8
HC03, meq/l
21.3 =tl .o 16.3t ztO.6 20.9 zt2.2 20.1 ztl.9 21.7 ~2.7
me41
Base Excess mw/l
22.6 ztl.1 1s.st ztO.6 22.0 zt2.2 21.2 rt2.0 23.5 h2.8
-4.4 zto.9 --1.4* zt2.0 -3.4 zlz3.1 -4.7 zt2.1 -7.0 h2.8
Total
CO2,
_-.~-.
* Comparison of this value with base line by the Values are means =t 1 SD. t Comparison of this value with base t-test was significant at the 5% level, 8 df. $ Arterial blood sample line by the l-test was significant at the 1 To level, 8 df. drawn at end of lavage before the lung was ventilated. TABLE 3. Gas exchange of dogs breathing room air before and after lung lavage .- - -_____ ---- ~ .- _.- ~~--_~____~_.___ _~-.. .-._---~________ --Before Lav age Base Line
Lavage
Diffusing
capacity,
Fractional
uptake
Alveolar
ml srPn/min of CO,
per mmHg
decimal
fraction
Poe, mmHg
Arterial
Paz, mmHg
Alveolar-arterial
PO’L gradient,
Arterial
Pco2,
mmHg
Alveolar
Pcoz,
mmHg
Arterial-alveolar Arterial
pH,
O:! saturation 02 uptake, outpttt,
Respiratory
mmHg
Pco:! gradient, pH
mmHg
units
of hemoglobin,
‘x,
ml srPn/min ml srPn/min exchange
Specific ventilation, 02 uptake Values are means * Comparison of this level, 8 df.
ratio,
decimal
ml minute
fraction
volume/ml
9.2 zt3.2 0.497 &O. 044 76 zlz5.1 71 zt5.1 5 2t2.2 39 zt5.2 37 zt4.2 2 &I .l 7.39 zlzo.02 90.1 zt2.3 102 ztl7.3 87 ztl8.8 0.85 zto.07 32 ~3.6
---.---~-.. & 1 SD. srpn value with base
6.2 zt2.0 0.334* *o. 033 82 &lo. 1 68 zt9.8 14 ztl6.7 38 rt3.3 32 zt7.5 6 zt5.3 7.36 ztu.03 86.9 xt5.9 77 ztl8.6 73 zt20.4 0.96 *o. 14 w zt7.2
DISCUSSION
Bronchopulmonary lavage has been used for a number of years both as a valuable research method and as a therapeutic procedure to treat lung diseases (4). The procedure has generally TABLE 4. Lung ventilation and mechanics of dogs before and after lung lavage
168 h 8.3 ztz4.6 0.468
rto.097 78 zt5.9 72 It7.7 6 rt3.7 37 zt3.2 35 zt2.1 2 zt2.1 7.39 zJzo.02 90.4 zt2.6 81 zt29.7 77 ~26.6 0.96 &O. 13 38 rtlO.1
Before Lavage Base Line Frequency Tidal
(room
volume
Minute Frequency Tidal
air),
(room
volume
Minute
air),
ml
air),
02),
(100
volume
Functional
breaths/min
(room
(100%
volume
BTPS
ml
(100%
BTPS
breaths/min OZ), ml
s
19 ~3.8 181 zt38.3 3350 &850 14 Al.9 184 zt48.6
02),
BTPS
ml
2970
BTPS
residual
capacity,
ml
Functional residual body wt Dynamic pulmonary cmHz0 Specific compliance,
capacity,
ml B-rPs/kg
BTPS
compliance,
ml/
ml/cm
per
Hz0
FRC Values are means * Comparison of this level, 8 df TABLE
100%
= standard temperature and pressure, dry. line by the t-test was significant at the 1 ‘To
aid in the return of spontaneous respiration. No other significant changes were observed in the arterial blood except for the decrease in bicarbonate and total CO2 during hyperventilation. The saline introduced into the lung totaled 4 liters, about 95% of which was recovered. Samples of the fluid were obtained as it drained from the lung (end-tidal) and the Pco2 was measured at 30 mmHg. Samples obtained from the collection bottles at the end of the procedure (expired) had PCOS values of near 20 mmHg. All of the dogs appeared clinically normal several hours after the lung lavage procedure except one. That dog had an increased respiratory frequency, moist rales were heard during auscultation of the chest, and the dog was less active than the others. At 1 wk after lavage, all of the dogs were active, and no abnormal sounds were heard during auscultation of their chests.
J. L. MAUDERLY
The only statistically significant functional alterations at 24 h after lavage were a reduced Fuco, an increased ~E/~oz, and a reduced VT while breathing ambient air (Tables 3-5). At that time, all dogs also had a higher f and lower VT (Table 4). Both base-line and postlavage nitrogen washout curves had three rapidly clearing component, a major components : an initial component with an intermediate washout rate, and a small slowly clearing component. At 24 h after lavage, the slopes of the intermediate components were reduced to a mean of 30% of base line (range = 13-60 %), indicating a slower rate of nitrogen dilution. By 168 h after lavage, all functional parameters had returned to their base line values. All of the dogs in this study are active and clinically normal at more than 30 days after lavage.
_..__ _-
- ~--
CO2
After 24 h
AND
zt
value
1 SD. with
ml
=tlOOO 471 ztl44.9 42 *lo. 3 53 ztl4.1 0.116 zlzo.021
= body temperature base line by the t-test
BTPS
5. Gas exchange of dogs breathing oxygen before and after lung lavage - -.--~~_ - -~---~-.~---.--- - .~______._ Before Lavage Base Line
--
.--
Alveolar Arterial
--.-. Po2, mmHg Paz, mmHg
Alveolar-arterial Arterial Alveolar
PO:! gradient,
Pco2, Pco2,
Values
pH,
mmHg
mmHg
Arterial-alveolar Arterial
. __~~~.___
mmHg Pc02
pH
gradient,
units
are means
mmHg
519 &7.8 485 ztlO.3 34 zt13.5 40 A4.3 38 zt5.0 2 zlzl.2 7.38 *0.03
After
Lavage
24 h 48 rt39.2 101* zt57.1 3300 ztll20 38 zt25.2 103 zt64.0 3330 *1400 396 &Ill.6 37 zt9.6 40.1 zt20.0 0.103 *0.070 and pressure, was significant
-II---.------
.--168 h ----
19 zt4.0 167 zt60.6 3010 ZtllOO 17 zt3.9 180 zh84.4 2780 zJz800 479 rt138.3 44 =tlO.O 51 ztl4.7 0.106 zko. 007 saturated. at the l y0
---After Lavage
-
24 h
168 h
531 ztl4.9 374 zJzl32.0 157 ztl44.9 41 zt4.4 32 rtlO.0 9 rt8.0 7.34 zto.04
522 zt8.1 485 Al6.4 37 zt25.5 40 zt2.2 35 zt2.9 5 zt4.2 7.38 ho. 03
rt 1 SD.
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LUNG
L;iVAGE
IN
DOGS
been based on the assumption that it was necessary to separate the lung into two functional compartments: the region to be lavaged, and the region for ventilation and maintenance of anesthesia. In an earlier study, however, Winternitz and Smith (17), demonstrated that the entire lung of the dog could be washed with a normal saline solution with reasonable safety. Their procedure did not provide for repeated washings nor did it include any assessment of the physiological changes that may be associated with the rapid change from air to fluid to air in the lung. Blenkarn and Hayes (1) successfully demonstrated bilateral or total lung lavage under hyperbaric conditions in the dog. They reported that pulmonary arterial mean pressure, which was stable in our dogs, rose about 4 mmHg during lavage under hyperbaric conditions. In two human patients, a small rise in Fpa was noted with the introduction of fluid during unilateral lavage (14). Increased Fpa has also been reported during unilateral lavage in dogs (9) probably due to the positive pressure in the chest. Systemic arterial pressure did not change and was not changed in other reports (9, 14). The dogs were hyperventilated for 3-4 min before the first wash to render them apneic. Although the Pao, fell during lavage of the first lung it remained adequate for normal saturation of the arterial blood. The 400 ml of fluid introduced in each wash was intended to be approximately the TLC of the dependent lung. Oxygen-halothane gas in the upper lung provided continuous gas exchange during the procedure. Manual ventilation between each wash renewed the supply of oxygen-halothane in the upper lung and removed COZ, resulting in a stable Paoe and Pacoa during the lavage. Each wash of the lung lasted no more than 2 min during which time approximately 100 ml of oxygen would have been absorbed (002 = 50 ml). Assuming the lung contained a volume of 02 equal to FRC (450 ml), approximately 8- to 9-min supply of oxygen was in the lung at the beginning of each wash. That volume provided an adequate safety factor, as verified by the consistent Paoz of 100 mmHg at the end of the lavage of each side of the lung. In the unilateral lung lavage, the one lung is ventilated throughout the procedure; however, the lavaged side of the lung is a functional shunt during the entire lavage, whereas it is only a periodic shunt in the “single-lumen endotracheal tube” lavage. Some gas exchange also occurred with the saline wash solution as reflected by the Pc02 of the end tidal (30 mmHg) and mixed expired (20 mmHg) saline samples. The exchange of CO2 into the lavage solution probably aided in preventing a rise in Paco2. Similar findings were reported by
925 Kylstra et al. (5) d uring unilateral lavage in man. The dog that had a significant decrease in PaOz was the smallest dog in this study and the 400-ml wash volume exceeded its measured baseline FRC by 150 ml. The residual gas may have been inadequate for exchange of 02. The decrease in Pao2 and the increase in PacOz following the lavage was expected as this was a period of reduced ventilation aiding the return of spontaneous respiration. The mild functional alterations present at 24 h after lavage probably resulted from a combination of postanesthetic atelectasis and the retention of small amounts of fluid in the lungs. These effects combined to reduce the overall efficiency of ventilation and gas exchange during the early postlavage period but were not sufficient to raise VE significantly or to present a hazard to the subjects. Previous studies (9), in which unilateral lavages were performed using a Carlens catheter, produced similar results both in lavaged dogs and in anesthetized sham-lavaged controls. The functional alterations, therefore, were probably related primarily to anesthesia. Bronchopulmonary lavage, using a single-lumen endotracheal tube, appears to be a reasonably safe and simple procedure. No serious physiologic alterations were found in the cardiopulmonary system during the procedure and mild pulmonary function alterations returned to base line by 1 wk after lavage. A single-lumen tube greatly increases the potential for using the procedure in small subjects over the Carlens double-lumen tube and might obviate the need for cardiopulmonary bypass during lung lavage in small children (15). Because this procedure washes the entire lung in a single anesthetic experience, the number of treatment sessions required may be less. It also may be useful in obtaining pulmonary cells and surfactant from experimental animals for research. The authors thank Dro. J. A. Kylstra, U. C. Luft, and Waneta Tuttle for their advice and criticisms; Phyllis B. Beckley, Sharon A. Felicetti, Goldie A. Morrison, W. C. Nenno, and S. A. Silbaugh for technical assistance; R. Crain for advice on statistical analysis; and F. C. Rupprecht for technical editing. Research was performed under Contract AT (29-2) - 10 13 between the Energy Research and Development Administration and the Lovelace Foundation for Medical Education and Research and in facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care. Received
for publication
15 July
1974.
REFERENCES G. D., AND J. A. HAYES. Bilateral lung lavage with hyperbarically oxygenated saline in dogs. J. A#. physiol. 29: 786-793, 1970. BOECKER, B. B., B. A. MUGGENBURG, K. 0. MCCLELLAN, S. P. CLARKSON, F. J. MARES, AND S. A. BENJAMIN. Removal of 14Ce in fused clay particles from the Beagle dog lung by bronchopulmonary lavage. Health Phys. 26: 505-5 18, 1974. DUBIN, S. E., AND G. A. MORRISON. A face mask and mouthpiece for respiratory studies in unanesthetized Beagle dogs. J. A@Z. Physiol. 27: 104-105, 1969. KYLSTRA, J. A., D. C. RAUSCH, K. D. HALL, AND A. SPOCK. Volume-controlled lung lavage in the treatment of asthma, bronchiectasis, and mucoviscidosis. Am. Rev. Respirat. Diseases 103: 651-665, 1971. KYLSTRA, J . A., W. H. SCHOENFISCH, J. M. HERRON, AND G. D. BLENKARN. Gas exchange in saline-filled lungs of man. J. A/$. Physiol. 35 : 136-142. 1973. MAUDERLY, J. L. Influence of sex and age on the pulmonary function of the unanesthetized beagle dogs. J. Gelontol. 29: 282-289, 1974.
1. BLENKARN,
2.
3.
4.
5.
6.
7. MA~DERL~, ,J. L Steady state carbon monoxide diffusing capacity of unanesthetized beagle dogs. Am. J. Vet. Res. 33: 14851491, 1972. 8. MAUDERLY, J. L., W. C. NENNO, AND G. A. MORRISON. Stocks for holding unanesthetized dogs in the standing position. Lab. Animal Sci. 2 1 : 263-266, 197 1. 9. MUGGENBURG, B. A., J. IA. MAUDERLY, J. A. PICKRELL, T. I,. CHIFFELLE, R. K. JONES, U. C. LuFrr, R. 0. MCCLELLAN, AND R. L. PFLEGER. Pathophysiologic sequelae of bronchopulmonary lavage in the dog. Am. Rev. Respirat. Diseases 106 : 2 19-232, 1972. 10. PFLEGER, R. C., R. F. HENDERSON, AND J. WAIDE. Phosphatidyl glycerol-a major component of pulmonary surfactant. Chem. Phys. Lipids 9 : 5 l-68, 1972. 11. PFLEGER, R. C., A. J. WILSON, R. G. CUDDIHY, AND R. 0. McCLELLAN. Bronchopulmonary lavage for removal of inhaled insoluble materials from the lung. Diseases CheJt 56 : 524-530, 1969. 12. PICKRELL, J. A., AND S. J. SCHLUTER. The rapid processing of canine blood gas tension and pH measurements. Am. J. Vet. Res. 34: 95-100, 1973.
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926 13. ROGERS, R. M., M. S. BROWNSTEIN, AND J. F. SHERMAN. Role of bronchopulmonary lavage in the treatment of respiratory failure: a review. Chest 62: 95S-106S, 1972. 14. ROGERS, R. M., J. P. SZIDON, J. SHELBURNE, J. L. NEIGH, J. F. SLUMAN, AND K. R. TANTIJM. Hemodynamic response of the pulmonary circulation to bronchopulmonary lavage in man. New Engl. J. Med. 286: 1230-1233, 1972. 15. SEARD, C., K. WASSERMAN, J. R. BENFIELD, A. J. CLEVELAND,
B. A. MUGGENBURG
AND
J. L. MAUDERLY
D. 0. COSTLEY, AND E. M. HEIMLICH. Simultaneous bilateral lung lavage (alveolar washing) using partial cardiopulmonary bypass. Am. Rev. Respirat. Diseases 101: 877-884, 1970. 16. STEEL, R. G. D., AND J. H. TORRIE. Principles and Procedures of Statistics. New York: McGraw, 1960, p. 67. 17. WINTERNITZ, M. C., AND G. H. SMITH. Preliminary Studies in Intratracheal Therapy, Pathology of War Gas Poisoning. New Haven, Conn. : Yale Univ. Press, 1920, p. 145-l 60.
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