Whole-Lung Lavage Under Hyperbaric Oxygen Conditions for Alveolar Proteinosis with Respiratory Failure

Whole-Lung Lavage Under Hyperbaric Oxygen Conditions for Alveolar Proteinosis with Respiratory Failure* HenkM.]ansen, M.D.; Wouter~ A Zuurmond, M.D.;CarelM. Boos, M.D.; ]ohan]. Schreuder, M.D.; and DirkJ Bakker, M.D.

Whole-lung lavage under hyperbaric oxygen conditions was performed in two patients suffering from severe respiratory insufficiency in pulmonary alveolar proteinosis. Under these conditions, gas exchange was maintained and the mixed venous partial pressure of oxygen and oxygen saturation showed increases to acceptable levels. This enabled us

to limit the FIo. in order to extend the oxygen tolerance and to perform lavage procedures more effectively. Both patients showed a very signi6cant improvement of their clinical eourse, and we conclude that elective use of hyperbaric oxygen in unilateral lung lavages should be considered in these severe cases.

pulmonary alveolar proteinosis is characterized by the accumulation of lipid- and protein-rich insoluble material in the alveoli of the lungs. 1 At present, unilateral whole-lung lavage is the most effective treatment for the disease.Y although its clinical application is limited in the presence of severe respiratory failure because adequate oxygenation of the blood can then not be maintained by ventilation of only one lung. Therefore, alternative approaches have been described in the literature, such as extracorporal oxy.genation during lavage procedures (ECMO),··5 partial cardiopulmonary bypass," and sequential lobar lavage via a fiberoptic bronchoscope under topical anesthesia." However, these methods are either very invasive or ineffective. We report the use of hyperbaric oxygen ventilation during whole-lung lavage procedures to achieve improved blood oxygenation. Severely-ill patients were treated effectively, and their overall disease status improved significantly.

fonned using a ventilator. Besides arterial blood pressure, ECG, heart rate (HR), central venous pressure, pulmonary artery pressure (PAP), expired carbon dioxide, and body temperature were measured. The mixed venous oxygen saturation was continuously monitored using a 6beroptic Swan-Ganz catheter inserted via the right jugular vein in the pulmonary artery. Arterial and mixed venous blood gas levels and pulmonary artery wedge pressure were measured intermittently. After the patients were placed in the lateral decubitus position, the position of the tube in the bronchus was rechecked. Initially, both lungs were ventilated separately with pure oxygen for 6ve minutes. The tube to the depending lung, to be lavaged, was then blocked and rapid absorption of the oxygen caused subsequent collapse of this lung. A sump drain was then inserted through this part of the tube into the collapsed lung, and lavage started. The lavaged lung was gravity filled, first with 750 ml of saline solution, to FRC volume from a reservoir placed 50 em above the chest. Each following lavage-eycle consisted ofSOO to 750 ml. Lung drainage was performed by slight suction through the sump drain. During the first two lavage-eycles, initial studies on arterial and mixed venous blood gas values were performed under normal ambient pressure. Thereafter, ambient pressure in the pressure chamber was raised to 2 ATA (202.6 kPa). The ventilator settings were then left unchanged during the following lavage sequences. 'Ireatment was considered complete when the recovered fluid became clear. The entire procedure under hyperbaric conditions never lasted longer than 240 minutes. Following the lavage, gradual decompression to normal ambient pressure took place. Immediately afterwards, both lungs were ventilated with Flo, at 1.0 for the first few minutes. This was rapidly tapered to 0.5 and 10 cm PEEP which was further tapered to zero over about 60 minutes. When blood gas values remained satisfactory,

METHODS

Bronchopulmonary Lavage Under Hyperbaric Oxygen Conditions Unilateral whole-lung lavage was performed under hyperbaric oxygen conditions at 2 ATA (atmosphere absolute), in a large multiplace hyper-pressure walk-in chamber. Patients were pretreated with hydrocortisone (250 mg slow IV), starting 12 hours before the procedure. Each patient was lavaged 6rst in the left lung (LLL) with, in total, 20 L of normal saline solution at 3rc. The right lung supported as much gas exchange as possible. After two to three weeks' recovery time, right lung lavage (RLL) was performed using about 25 L of saline solution. Under general IV anesthesia, a left No. 41double lumen tube was inserted. Controlled ventilation with oxygen, and subsequently oxygen in air was per-

*From the Department of Pulmonology, Anesthesiology, and Hyperbaric Medicine, University Hospital of Amsterdani, Academic Medical Centre, Amsterdam, The Netherlands. Manuscript received July 30; revision accepted December 2.

ofPoOl in Blood Sample. After Decornpreaion and Storage on Ice

Table I-Spontaneous Decrease

PaD! (mm Hg) Sample No. Storage after decompression o minutes 5 minutes 10 minutes

2 719.4 696.4

3

436.2 344.1 421.8 331.8 407.8

CHEST I 91 I 6 I JUNE, 1987

829

Table 2-Data on PulmontJry Function and Blood Gas Levels Before and After Bronchoolveolar Lavage TIme period from first evaluation Case 1 Normal values Start 2 wks 3 wks 4 wks 5 wks 22 wks Case 2 Normal values Start 2 wks 3 wks 5 wks 8 wks 18 wks

R-L shunt PaC02 ai-sat P(A-a)02 %of Pa02 mmHg mm Hg % mmHg CO

Dco* FEV 1 Procedure TLC,L RVrrLC VC,L Usec 7.05 3.40

0.23 0.20

5.45 2.71

4.23 2.46

%

Pred

KCO

pH

100 23

100 30

7.38-7.44 7.46

18

32

7.43

>75 44

38-42 29

>90 83.3

<15 67

46

30

85.6

68

62 76

34 33

92.0 96.0

34

38-42 28

>90 89

<15 57

<5 22

<5 26

LLU: RLL§ 6.27

0.19

4.09 5.07

3.55 3.84

28 58

41 66

7.47 7.45

6.83 4.66

0.28 0.30

4.92 3.24

3.52 2.61

100 39

100 56

7.38-7.44 7.43

37

57

7.46

51

33

87

56

17

46 61

61 78

7.45 7.42

64 77

29 32

94 96

48 34

12 6.7

>75 57

14

LLL RLL 4.95 5.80

0.27 0.33

3.62 3.88

2.83 2.81

*Dco, carbon monoxide transfer factor; KCO, transfer factor per alveolar volume; R-L shunt, right-to-left shunt in percentage of cardiac output (CO); LLL, left lung lavage; and RLL, right lung lavage. anesthesia was stopped, the patients extubated and treated with oxygen (5 Umin) by double nasal prongs.

Blood Samplingand Analysis The arterial (Pa0J and mixed-venous (PVOJ oxygen partial pressures were measured immediately after decompression of the sample on ice through a small lock using an ABL-2 placed directly outside the hyperpressure chamber. In order to exclude the possibility of inflated partial pressure measurements due to oxygen hypersaturation on decompression, we performed storage experiments on the samples. The spontaneous decrease of PaOs was very slow and linear (Iable 1).The calculated VOl-sat compared well with the continuously recorded value from the oximeter placed inside the hyperpressure chamber.

giving a calculated alveolar-arterial oxygen difference of 544 mm Hg equivalent to a right-to-left shunt of26 percent of the cardiacoutput (CO).8 Further studies of pulmonary function (Table 2) showed a restric-

0)

J:

830

I 179'

E

I I

N

o

I

~ 400

I

lATA lATA S-lOC PEEP OCl PEEP

1 I I

I I I 245 1 I

200

1

A 29-year-old man was referred to another hospital with progressive severe shortness of breath. A six-week trial of high-dose corticosteroid therapy was unsuccessful and a subsequent left-sided open-lung biopsy showed pulmonary alveolar proteinosis. The patient was then referred to us for further evaluation. He smoked up to 40 cigarettes a day for more than ten years. He worked as a roadmaker and lived in a rural area. Physical examination revealed a persistent unproductive cough, peripheral cyanosis at rest, and digit clubbing. °Blood pressure was 120/80 mm Hg, pulse, 100 beats per minute; temperature, 36.6°C; respiratory rate, 20 per minute at rest, with some use of accessory muscles. Except for some fine bibasilar crackles present over the lungs, no other abnormal physical signs were present. Laboratory studies revealed the following values; hemoglobulin (Hb), 9.7 mmollL and a normal WBC count; ESR, 3 mm in one hour; serum lactic acid dehydrogenase (LDH); 327 U/L; and antinuclear antibody and rheumatoid factor were negative. The chest roentgenogram showed a diffuse, bilateral, alveolar nodular pattern, with coalescence in the center to the butterfly shadowed picture. The ECG was normal except for a regular sinus tachycardia. First gated blood pool measurements showed a normal right heart ventricle with a normal contractility pattern. Arterial pH was 7.46; PaCO Il, 29 mm Hg, and Pa0ll , 44 mm Hg, breathing room air at rest (Table 2). The Pa0ll was 109 mm Hg breathing pure oxygen,

I

E 600

CASE REPORTS CASE

l l

lATA 2ATA

325'

100

80

C)

J:

E E

80 305'

~ I>

a.

60 minutes after intubation

40 T

FIGURE 1. Arterial oxygen pressure (Pa0J and mixed venous oxygen pressure (PVOJ during unilateral lung lavage of the left lung (---) and of the right lung (0-0) in case 1, before, during and after hyperbaric oxygen treatment. WhoIe-Lung Lavageunder Hyperbaric O2 (Jansen 8t 81)

Table 3-Data on Blood Gas Levell During HyperbGric LtmtJge Procedura Blood Gases Minutes After Intubation

Ambient Pressure

Flo!

Case 1, LLL 10 10 60 74 78 177 179 182 243 245 429

1 ATA 1 ATA 1 ATA lATA 1 ATA 2ATA 2ATA 2ATA 2ATA 2ATA 1 ATA

1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 0.5 0.5 0.5

431

1 ATA

0.5

435

1 ATA

0.5

1 ATA 1 ATA 2ATA 2ATA 2ATA 2ATA 1 ATA 1 ATA

1.0 1.0 1.0 1.0 0.5 0.5 0.5 0.5

Case 2, RLL 10 10 95 96 131 135 290 291

Lavage Procedure

Blood Sample

Ventilated Ventilated Filled up + FRC+ FRC+ Filled up FRC Filled up Filled up FRC Ventilated +5cm PEEP Ventilated +5cm PEEP Ventilated PEEP-stop

art *

Ventilated Ventilated Filled up Filled up Filled up Filled up Ventilated Ventilated

pH

Pa°l (mm Hg)

PaCO 2 (mm Hg)

°2-sat (%)

86.8 44.4 133.1 85.3 45.4 571.3 507.6 57.5 369.0 344.1 135.6

29.2 38.8 33.0 33.5 29.6 27.8 31.8 30.5 36.4 38.6 32.8

94.7 77.9 98.3 95.2 so. 4

art

7.34 7.35 7.40 7.40 7.39 7.42 7.34 7.40 7.34 7.33 7.36

v

7.33

56.9

35.2

86.3

art

7.31

74.2

35.8

91.9

art

7.34 7.33 7.33 7.29 7.27 7.25 7.25 7.24

47.7 37.2 548.7 58.7 195.4 56.6 81.0 55.3

38.1 40.3 39.7 47.0 41.4 45.5 47.8 49.7

so. 1

v art art

v art

art

v art art

v art

v art

v art

v

99.9 99.9 88.3 99.8 99.7 98.2

66.7 99.9 85.4 99.0 82.8 92.4 81.4

*art, arterial blood sample; v, mixed venous blood sample; filled up, lavaged lung filled up with saline solution 600 ml above FRC volume; and FRC, lavaged lung filled up with saline solution until FRC volume. tive ventilatory disorder with severely depressed diffusing capacity for carbon monoxide (Dco) of 23 percent of the predicted value. The patient tolerated the lavage procedures well. At 2 ATA hyperbaric pressure with a Flo, of 1.0, a substantial increase ofPa02 from 60 mm Hg to 550 mm Hg (LLL) and from 60 mm Hg to 650 mm Hg (RLL) was seen (Fig 1). The PV02 also increased significantly from 44.4 mm Hg to 57.5 mm Hg (LLL) and from 40.5 mm Hg to 75 mm Hg (RLL). These findings enabled us to reduce Flo, from 1.0 to 0.5. Further data on the changes in blood gas values during the whole LLL procedure are given in 'Iable 3. The significant decrease of Pa02 during initial lavage fluid drainage at 1 ATA indicates that right-to-left shunting was maximal at this time. This agrees with findings already extensively described by others8•10 under conventional conditions. However, Table 3 shows that this shunting had relatively less consequence for the changes in PaO. and PVOI, using hyperbaric oxygen. Long term follow-up (five months) after the last lavage showed improvements in the following parameters: pulmonary volumes (Table 2), Dco corrected for Db content from 23 percent of predicted value to 58 percent achieved, blood gas values PaO! (at rest) from 44 mm Hg to 76 mm Hg, and P(A-a)OI difference decreased from 67 mm Hg to 34 mm Hg. Overall right-to-left shunt decreased from 26 to 14 percent of the cardiac output. CASE

2

A 46-year old florist had complained of slowly progressive shortness of breath without coughing or sputum production for 16 months. On admission elsewhere, his chest roentgenogram showed a diffuse, bilateral alveolar nodular pattern. The pathologic findings after an open lung biopsy were consistent with alveolar proteinosis.

The patient had no symptoms or signs of superimposed airway disease. He had smoked 25 cigarettes a day for more than 20 years, until one year before admission. On physical examination, blood pressure was 135/SO mm Hg, pulse, 92 beats per minute; temperature, 37.5°C; respiratory rate, 14per minute at rest. Neithercyanosis nor digit clubbing was present. Laboratory studies revealed a Hb concentration of 10.8 mmol/L, and a normal WBC count. The ESR was 17 mm in one hour. Serum LDH was 225 U/L and ANA and RF were negative. Arterial pH was 7.43; PaCO., 29 mm Hg; and FaO., 57 mm Hg, breathing room air at rest (Table 2). The right-to-Ieft shunt was 22 percent of the CO. The Dco was 39 percent of the predicted value, and there was a restrictive ventilatory disorder. The ECG was normal, but echocardiography showed a widened right ventricle with a suboptimal contractility pattern. First gated blood pool measurements showed a decreased right ventricle ejection fraction of 33 percent Lavage procedures under hyperbaric conditions were well tolerated by the patient (Fig 2). During the lung lavage under hyperbaric oxygen therapy, PaO a increased from 47.7 to 548.7 mm Hg and the PVOI from 37.2 to 58.7 mm Hg. As with Case 1, this made a reduction of the FIOt from 1.0 to 0.5 possible (Table 3). Table 3 also shows a shift toward a lower pH together with an increase of Pa0l , although ventilatory volumes remained unchanged. These phenomena develop under hyperbaric conditions due to the presence of less reduced hemoglobulin which transports CO•. U However, both phenomena were clinically insignificant and because of the high plasma solubility of carbon dioxide, CO.-retention was of no other pathophysiologic importance. Right-to-Ieft shunting also manifested itself in this patient as shown by a decrease in the continuously computed vO.-sat (Fig 2). CHEST I 91 I 6 I JUNE, 1987

831

....- P 8ft • srat. ....---. Part, dIMt. P pa, svst. o--~ P pa , dI_t. 9---V

Go·_·-
HR

50 v-,

,,',

<, ..".""

20

~

10 0 12.00

~----~--..q.'-

---~--o-_o_--~ 13.00

t

~--~-----

14.00

12.I>

2ATA

*10

.,1

• •14. 10

_---.R----v--~_v

1 *

40--

15.00

0

- - -0... -0

18.ooh

t

1ATA

•

30

M.38h

FIGURE 2. Heart rate (8R), systolic and diastolic arterial blood pressure (P art), and pulmonary artery pressure (Ppa) during a period of hyperbaric unilateral lung lavage in case 2. At the lower panel (*), a detail of the continuous registered mixed venous oxygen saturation (% sat. v) is shown, demonstrating the slight variations due to a variable R-L shunting occurring during the lavage cycles.

However, hyperbaric pressure reduced these variations importantly. Long-term studies of pulmonary functions after lavage showed a large improvement in the lung volume, a marked. increase of Dco from 39 to 61 percent, a decrease of P(A-a)O. difference from 57 to 34 mm Hg, and marked decrease of the R-L-shunt from 22 to 6.7 percent of the CO (1llble 2). Blood gas values also showed a significant improvement. In both patients, the chest roentgenogram improved significantly during follow-up (datanot shown). DISCUSSION

Whole-lung lavage is a commonly used procedure in the treatment of pulmonary alveolar proteinosfs-" and is generally indicated when the arterial oxygen tension is less than 60 mm Hg (at rest) or when hypoxemia limits exercise." Conventional lavage is unsuitable, however, if highly afBicted patients are unable to maintain satisfactory gas exchange in the nonlavaged lung during the lavage procedure, and literature studies indicate a direct negative correlation between low initial PaO! (and subsequent high initial P[A-a]OJ and ultimate disease outcome." That oxygen exchange is further decreased during conventional lavage is a probable contributory factor; Whole-lung lavageunder hyperbaric oxygen conditions is not accompanied by further deterioration in the already diminished PaO! and PVO! parameters, and lavage is more effective because of the increased lavage fluid volume that can be used. Therefore, we consider the procedure to be a 832

potentially significant therapeutic advance. A danger of hyperbaric oxygen administration is oxygen toxicity, especially for the lung tissue. Because the degree of toxicity is determined by both the pressure and duration of exposure, 14.~ we limited pressure and Flo! to the minimum consistent with optimal results. At 2 ATA, the hyperbaric pressure was as low as possible, the oxygen tolerance was extended by reducing the Flo! from 1.0 to 0.5 as soon as it was possible, and treatment duration did not exceed four hours. The clinical course of neither patient showed deterioration due to oxygen toxicity;on the contrary, it improved very significantly. On the basis of our findings, we suggest that wholelung lavage under hyperbaric conditions should be considered in severe cases of pulmonary alveolar proteinosis. The procedure is effective, less invasive than other procedures, and free of side effects. REFERENCES

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61-77 15 Bakker DJ. The use of hyperbaric oxygen in the treabnent of certain infectious diseases, especially gas gangrene and acute dermal gangrene. Thesis, Amsterdam, 1984