Pulmonary Function after R·ecovery from the Adult Respiratory Distress Syndrome* /. ]. Klein, M.D.; ]. R. van Haeringen, M.D.;•• H. ]. Sluiter•. M.D.; R. Holloway, M.D.;t and R. Peset, M.D.
Eight adult patients with acute respiratory distress syndrome were treated with positive end-expiratory pressure (PEEP) ventilation. The results of detailed examinations of pulmonary function in these eight patients obtained after dHferent periods of time foDowiDg discharge from the respiratory care unit were analyzed to determine the degree of disturbances in pulmonary function. For comparison, eDIIIinations of pulmonary function were also performed on two patients who were treated with zero end-expiratory pressure ventilation. This fol-
Jn 1967, Ashbaugh et aP described some adult
patients with the acute respiratory distress syndrome who were successfully treated with positive end-expiratory pressure (PEEP) ventilation. Up to that time, mortality from the adult respiratory distress syndrome was practically 100 percent. The good therapeutic results were confirmed in later publications of the same group2.3 and also by other authors.4-7 In this paper the definition of the adult respiratory distress syndrome as proposed by Ashbaugh et al8 is used, ie, acute respiratory failure and distress associated with a specific incident or illness with the exclusion of exacerbation of chronic pulmonary disease or primary cardiogenic pulmonary edema. Apart from case reports,B.l 0 there have been no detailed studies in which pulmonary function after PEEP treatment of the adult respiratory distress syndrome was investigated. We, therefore, decided to study pulmonary function in a group of eight patients who survived the adult respiratory distress syndrome after treatment with PEEP. PATIENTS
From August 1968 until March 1973, some 36 patients with the adult respiratory distress syndrome were treated °From the Lung Function Laboratory and Respiratory Care Unit, University Hospital, Groningen, the Netherlands. 0 0 Presently at Roman Catholic Hospital, Groningen, the Netherlands. tPresently at Derby Chest Clinic, Derby, England. Manuscript received December 23, 1974; revision accepted September 23.
Reprint requests: Dr. Klein, Interne Kliniek, Academisch Ziekenhuis, Groningen, The Netherlands
350 KLEIN ET AL
low-up study showed remarkably few abnormalities. When present, restrictive disturbances in pulmonary function, especiaDy decreased static compliance and dUfusing capadty, were found. No correlation was found between the pulmonary-function results of the eight patients and the duration of the PEEP treatment, nor between the results and the time interval between treatment at the respiratory care unit and the moment of the pulmonary function studies.
with PEEP in the respiratory care unit of the University Hospital of Groningen, the Netherlands. In 16 patients the cause of the adult respiratory ·distress syndrome was pulmonary trauma (direct pulmonary injury), and in 20 the syndrome was of different origin (indirect pulmonary injury). The adult respiratory distress syndrome of all these patients did not react favorably to positive-pressure ventilation with a high inspiratory oxygen concentration. Addition of PEEP often resulted in a dramatic rise in the arterial oxygen pressure ( Pa~) and immediate relief of the distress. The further treatment of these patients consisted of other measures, such as bronchial toilet, physiotherapy, and therapy with antibiotics, corticosteroids, and anticoagulants.ll Of this series of 36 patients, 15 died, and 21 patients survived the acute episode. The studies of pulmonary function were performed between March and May 1973. To allow a certain stabilization of the pulmonary function, only patients who were treated at the respiratory care unit before November 1972 were included in these studies. As a result of this selection, seven patients were excluded. Two additional patients died because of e«trathoracic diseases after discharge from the respiratory care unit, and four patients were unable to cooperate. Ultimately, eight patients were available. For comparison, two other patients were also examined; they had been treated with only zero end-expiratory pressure at a time when we were only partly familiar with PEEP. At present, ventiljltion with PEEP would undoubtedly have been applied. Tables 1 and 2 give the data on diagnosis, treatment, and complications of these ten patients. With the exception of patient 4, who had a mild form of chronic obstructive pulmonary disease (chronic cough and sinusitis in the past), all these patients were healthy before the adult respiratory distress syndrome. METHODS
Since very little is known about the character and degree of the disturbances of pulmonary function in persons who survived the adult respiratory distress syndrome, many tech-
CHEST, 69: 3, MARCH, 1976
Table 1-DiCIJ'RO- o/ Palien,. Diagnosis Patient Elapsed No., Age Time (yr) (mo)* 1, 19
5
2, 25
16
3, 28
12
4,'l!l
34
5,9
6
6,23
7
7, 9
34
8, 22 22
Cause of Pulmonary Injury Direct
Indirect
Traffic accident Traffic accident Traffic accident Traffic accident
29
10,40
14
Aspiration
Left
Rib Fractures
Hemothorax
Extrathoracic Lesions** +
+
Left and right Left and right Left and right
+
Neardrowning Neardrowning Traffic accident Traffic accident
9, 13
Lung Edema
Lung Contusion
++
+
++
+
++
+
+ ++
+
+
++
Left and right
+
+
Traffic accident Suicidal attempt via drug ingestion
Right
Right
++ ++
+ +
*Time elapsed between treatment at respiratory care unit and assessment of pulmonary function. **+,Few extrathoracic lesions; and ++,many extrathoracic lesions. niques to measure pulmonary function have been applied to detect any possible disorders. A survey of the techniques with standard values and the apparatus which were employed is given in Table 3. Because of patient's age and technical reasons, the total program was not completed in all patients, as is shown in Tables 4 to 6.
REsULTS
The results of pulmonary function studies are summarized in Tables 4 to 6.t tMore detailed information on the actual values measured with the different techniques is available from the authors on request. Table 2--DaiG Patient No. 1 2 3 4 5 6 7 8 9
10
PaOt (mm Hg) Before PEEP 50
51* 51 36 34 48 51 30
42 36
PEEP (hr)
24 72 72 120 48 24 42 72
Lung Volumes
The total lung capacity ( TLC) and vital capacity ( VC) were decreased in four patients and in five patients, respectively. Only in patient 9 were these decreases more than 30 percent. In patient 8, the VC was larger than the predicted value. In all other patients, the TLC and VC were normal. The residual volume (RV), RV/TLC, functional residual capacity ( FRC ), forced expiratocy volume in one second ( FEV t.o), FEV t.o/VC, and maximum ·voluntary ventilation ( MVV) did not show any constant change.
Treatment and Compliearion.
Mechanical Ventilation (Days) 3 36 28 21 6 10 2 28 14 2
Shock
Pneumothorax
+
Left Right and left
Pulmonary Gram-Negative Infection
+ + +**
+ +
Right and left
+ + +
*With oxygen. **Also gram-negative septicemia.
CHEST, 69: 3, MARCH, 1976
PULMONARY FUNCnON AFTER RECOVERY FROM ARDS 351
Table S--Method•
Determination
Technique
Equipment
Standard Values
Spirometry
Inspiratory vital capacity
Adults 11 and children 18
Spirometer (Lode 53-R)
Lung volumes
Helium dilution
Tammeling 14
Spirometer (Lode 53-R); helium analyzer (Mijnhardt)
Lung mechanics
Esophageal-balloon technique 1•·11
Hilvering 11 and Turner et al 17
Spirometer (Lode 53-R); manometer (Godart); recorder (Bryans X-Y)
Body plethysmography
Spontaneous-breathing method 18
Quanjer 11
Volume-constant body plethysmograph constructed to our specifications (by Lode)
Blood gases
pH glass electrode; PaO, and PaCO, membrane electrodeslll
Radiometer: pH microelectrode E5021, PaO, membrane electrode E5046, PaCO, membrane electrode E5036, PaO, module 932, and· PaCO, module 933
Ergometry
75-100 w, with frequency of 60 to 70 per minute
Bicycle ergometer (Lode)
Shunt
Berggren21 modified by Chiang22
::5 8 percent of cardiac output
Dead space
Bohr equationu
::5 45 percent of tidal volume
Diffusing capacity
Breath-holding method of Krogh2•·n modified by Oglivie et al21
Washout curves
7-min N2 washout28 N 2 single-breath washoutz• CO, washout•
Lung scan
Human serum albumin microspheres labeled with llmtechnetium 1 L 12
uaxenon, regional
Open spirometric system
Constructed to our specifications (by Lode cooperating with Department of Electronics, University of Groningen) FaNs ::5 2 percent• N2 slope ::5 5 percent/sec CO, slope ::5 13 percent/sec
Nitrogen meter (SeBIDa); capnograph (Godart) Gamma camera (Nuclear Chicago)
Right lung/left lung, 55/45 percent for volume, ventilation, and perfusion
Constructed to our specifications (by Lode)
*FaN2, Nitrogen concentration of alveolar sample after breathing oxygen for seven minutes.
Lung Mechanics Work of breathing ( W) was normal in four patients and was increased in the other four patients. Static compliance ( Cst) was lower than the standard value in five patients and normal in two. Patient 8 was the only one with a larger than predicted Cst. Body plethysmographic studies failed to show abnormalities, except in patient 4, who had an increased airway resistance (Raw). Gas Exchange At rest, three out of seven patients showed a slightly decreased Pa02. During exercise, a fall in pH and Pa02, along with an increase of arterial carbon dioxide tension ( PaC02), appeared in pa352 KLEIN ET AL
tient 3 and also in patient 8 ( at rest, he was hyperventilating). In all cases the right-left shunt was increased, although in none of the patients was it over 11 percent. The dead-space ventilation ( Vo) was increased in three out of six patients. The diffusing capacity (D) was decreased, except in two patients. Washout Curves
The curves for carbon-dioxide washout in the three youngest patients were abnormal. All the other results of the washout curves were normal. Ventilation and Perfusion
Lung scanning with
99
mtechnetium failed to
CHEST, 69: 3, MARCH, 1976
Table 4--Lunl' J'oluma and Meelaanie•* Patient No. 1NN 2 3 4 5 6 7N 8NN 9 10
TLC
RV/TLC
74 84 N N 74
114 81 82 59 124 133
68 N
200 88
vc
FRC 117 N 72 N N N 86 115 84 NN
FEV1.0
FEV1.0/VC
N 69 N
N N 113
82 77 77 118 37 123
81 N N N 74 120
N 80 85 NNN N 71 82 111 51
MVV
50 70 N 112 112 58 68 128 128
w
Cst
Raw
N 120 170
N 85 50 N
138
76
N N N
135 67 64
N N N 135 N N N N N N
*Table values are percents of predicted values. N, Predicted value ± 10 percent. For abbreviations, see text.
nary disease in her medical history, was the only one with an increased Raw. Apart from the increased W, she has no other signs of chronic obstructive pulmonary disease in the pulmonary function results. The abnormal values for curves of carbon dioxide washout in the younger patients (No. 5, 7, and 9) may be explained by their higher frequency of breathing. Patient 8 had the best results on pulmonary function tests. Only Cst (which was larger than predicted, the only one of the group with this finding), the Pa02 (decreased), and the PaC02 (elevated) during exercise were abnormal. Of the two patients not treated with PEEP, patient 9 had very extensive disturbances in pulmonary function. These disturbances were both restrictive and obstructive; there were no signs of chronic obstructive pulmonary disease in her medical history. It is quite notable that the xenon studies in these two patients show not only a disturbed right-left ventilation percentage (as in patients 3 and 6) but also disturbed volume and perfusion percentages. It is open for discussion whether ventilation with PEEP in these patients would have resulted in better pulmonary function. The Pa02 on admission showed no correlation with ultimate results of pulmonary function tests. Longer treatment with PEEP and a short-
show any abnormality. Studies with 133xenon gave abnormal values of the right-left ventilation percentage in six patients, while in two (No. 9 and 10) of these six patients, the volume and perfusion percentage was also disturbed. DISCUSSION
Interpretation of the results is difficult because of the complexity of the problem, which virtually precludes prospective controlled studies; however, the data give a good picture of the disturbances in pulmonary function after the adult respiratory distress syndrome because all patients (except No. 4) were healthy before treatment at the respiratory care unit. Consequently, it may be assumed that their pulmonary function before the adult respiratory distress syndrome was normal. The results of the different techniques for measuring pulmonary function proved to be of very different significance in respect to the detection of abnormal function. Although there was no constant pattern, restrictive sequelae (defined as decreased TLC, RV, RV /TLC, Cst, and D, with an increased FEV1.o/VC) were found fairly often in these patients. In four patients, W was increased. Patient 4, who had a mild form of chronic obstructive pulmoTable 5-Data /rom ..4rterial Blood Patient No. 1 2 3 4 5 6 7 8 9 10
pH
,.----A--,
Pa02 (mm Hg)
,.----A--,
w• ..4naly•~,
PaCOt (mm Hg) ,--~Right-Left
Rest
Exercise
Rest
Exercise
Rest
7.40 7.39 7.40 7.43
7.40 7.35 7.35 7.38
95 86 92 83
98 90 74 91
38 41 41 38
7.39
7.39
85
88
45 49
7.45 7.46
7.40
113 120
88
33 33
*N, Predicted value ± 10 percent. • *Shunt, Percentage of cardiac output.
CHEST, 69: 3, MARCH, 1976
Ca• Esehan,.e, and JJ'a•hout
Exercise Shunt•• 39 39 43 36
42
Vnt
Dt
7-min FaN,
9.5 10.5 11.0 9.0
57
11.0
62
NNNN 63 85 77 85 61
10.0
34
NNNN
58
42 38
79
Curt~e•
NNN N NN N NN NN NNN
* Nt Slope
co,
Slope
NN N
(19.5) N (32) (19.5)
tVn, Percentage of tidal volume. tD, Percentage of predicted value.
PULMONARY FUNCnON AFTER RECOVERY FROM ARDS 353
Table 6--Ruult•/or Luq J'olume, J'entilation, arul Per/uaon /rom 138Xenon Seudie•• Lung Volume Patient ,......----J'-No. Right Left 1NNNNNN NNNN 2 NN 3 4NN NN 5 6NN 7 NNNNNN 8 9 29 71 42 10 58
Lung Ventilation ~
Lung Perfusion
,......----J'--
Right
Left
Right
Left
46 48 40 47
54 52 60 53
N N NN NN N
N N
26 39
74 61
38 61
62 39
N
•N, Predicted value ± 10 percent.
er interval between admission into the respiratory care unit and pulmonary function assessment did not tend to produce more disturbed pulmonary function (Tables 1, 2, 4, 5, 6). In conclusion, the assessment of pulmonary function in adults, after recovery from the acute respiratory distress syndrome should preferably include the measurements of TLC, RV, VC, FEV1.0, W, Cst, and D, which may clearly show restrictive disturbances. Additional measurements, such as blood gas analyses at rest and during exercise and studies with 133xenon, do not give substantial additional information. ACKNOWLEDGMENT: We wish to thank the Department of Nuclear MedicineJ University Hospital, Groningen, the Netherlands, for penorming the technetium scans and for providing the facilities for the xenon studies and all the other co-workers of the Lung Function Laboratory for their technical assistance. Calculations of the xenon studies were performed in the Computer Centre of the University of Groningen. REFERENCES
1 Ashbaugh DG, Bigelow DB, Petty TL, et al: Acute respiratory distress in adults. Lancet 2:319, 1967 2 Ashbaugh DG, Petty TL, Bigelow DB, et al: Continuous positive-pressure breathing ( CPPB) in adult respiratory distress syndrome. J Thorac Cardiovasc Surg 57: 31, 1969 3 Petty TL, Ashbaugh DG: The adult respiratory distress syndrome: Clinical features, factors influencing prognosis, and principles of management. Chest 60:233-239, 1971 4 Pontoppidan H, Geffin B, Lowenstein E: Acute respiratory failure in the adult. N Eng) J Med 2a7:690, 743, 799, 1972 5 Bachofen-Ponchet M, Bachofen H: Lungenveranderungen nach Trauma und Shock: Das "respiratory distress syndrome" des Erwachsenen. Schweiz Med Wochenschr 103:1, 1973 6 van Haeringen JR, Blokzijl EJ, le Coultre R, et al: Het "respiratory distress syndrome" van de volwassene: Een reactiepatroon van de long op schadelijke invloeden van zeer uiteenlopende aard. Ned Tijdschr Geneesk 118: 748, 1974
354 KLEIN ET AL
7 van Haeringen JR, Blolczijl EJ, van Dijl W, et al: Treatment of the respiratory distress syndrome following nondirect puhnonary trauma with positive end-expiratory pressure with special emphasis on near-drowning. Chest 66(suppi):30S-34S, 1974 8 Ashbaugh DG, et al: Respiratory distress syndromes in respiratory diseases. In Task Force Report on Problems, Research Approaches and Needs. Bethesda, Md, National Heart and Lung Institute, 1972, p 165 9 Downs JB, Olsen GN: Puhnonary function following adult respiratory distress syndrome. Chest 65:92-93, 1974 10 Llamas R: Adult respiratory distress syndrome: Report of survival after two episodes. Chest 65:468-469, 1974 11 Sluiter HJ, Blokzijl EJ, van Dijl W, et al: Conservative and respirator treatment of acute respiratory insufficiency in patients with chronic obstructive lung disease. Am Rev Respir Dis 105:932, 1972 12 Tammeling GJ: Standard values for lung volumes and ventilatory capacity of sanatorium patients. Selected Papers 1:65, 1961 13 Polar G, Promadhat V: Puhnonary Function Testing in Children. Philadelphia, WB Saunders Co, 1971 14 Tammeling GJ: Het Residuaalvolume en de Functionele Residuaal Capaciteit, thesis. Groningen, the Netherlands, 1958 15 Buytendijk HJ: Oesophagusdruk en Longelasticiteit, thesis. Groningen, the Netherlands, 1949 16 Hilvering C: Longmechanische Onderzoekingen bij Patienten met Longtuberculose, thesis. Groningen, the Netherlands, 1963 17 Turner JM, Mead J, Wohl ME: Elasticity of human lungs in relation to age. J Appl Physiol25:664, 1968 18 Peset R, Quanjer PH, Tammeling GJ: Bronchodilation estimated by body plethysmography. In Progress in Respiration Research: Body Plethysmography ( vol 4) DuBois AB, van de Woestijne KP, eds). Basel, Switzerland, S Karger, 1969, p 215 19 Quanjer PH: Plethysmographic Evaluation of Airway Obstruction, thesis. Groningen, the Netherlands, 1971 20 Gimeno Ortega F: Clinical Blood Gas Analysis, thesis. Groningen, the Netherlands, 1969 21 Berggren SM: The oxygen deficit of arterial blood caused by nonventilated parts of the lungs. Acta Physiol Scand (suppl)4:11, 1942 22 Chiang ST: A nomogram for venous shunt ( Q./Q,) calculation. Thorax 23:563, 1968 23 Bohr C: Ueber die Lungenathmung. Scand Arch Physiol 2:236, 1891 24 Krogh A, Krogh M: On the rate of diffusion of carbonic oxide into the lungs of man. Scand Arch Physiol 23:236, 1909 25 Krogh M: Diffusion of gases through the lungs of man. J Physiol (Lond) 49:271, 1914 26 Ogilvie CM, Foster RE, Blakemore WS, et al: A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest 36:1, 1957 27 Cotes JE: Lung Function. Oxford, England, Blackwell Scientific Publications, 1965 28 Darling RC, Cournand A, Richards OW Jr: Studies on intrapuhnonary mixture of gases. J Clin Invest 23:55, 1944 29 Comroe JH Jr, Fowler WS: Lung function studies: 6. Detection of uneven alveolar ventilation during single breath of oxygen. Am J Med 10:408, 1951
CHEST, 69: 3, MARCH, 1976
30 van Meerten JH: Concentratiecurven van Expiratiegassen, thesis. Nijmegen, the Netherlands, 1966 31 Rhodes BA, Zolle J, Buchanan JW, et al: Radioactive albumin microspheres for studies of the pulmonary circulation. Radiology 92:1453, 1969 32 van de Poll MAPC, Woldring MG: Radioactief gemerkt humaan albumine "microspheres". Pharm Weekblad 108: 741, 1973 33 Peset R, Holloway R, Beekhuis H, et al: Ventilation and perfusion indices measured with xenon-133 during spontaneous breathing. In Radioaktive Isotope in Klinik
und Forschung: (vol 9) Fellinger K, HOfer R, eds. Munich, Urban and Schwartzenberg, 1970, p 266 34 Peset R, Beekhuis H, Tammeling GJ, et al: A ''bag in box" system in regional ventilation studies of the lung with xenon-133. In Radioaktive Isotope in Klinik und Forschung: (vol 10), Fellinger K, Hofer R, eds. Munich, Urban and Schwartzenberg, 1973, p 335 35 Peset R, Gimeno F, van Haeringen JR, et al: Comparison of 133xenon regional studies during spontaneous breathing and bronchospirometry. Scand J Respir Dis 55:91, 1974
Pulmonary Fat Embolism Over a hundred years ago, two reports on this subject appeared in Germany, that of Zenker (Beitriige zur Normalen und Pathologischen Anatomie der Lunge, Dresden, Braunsdorf, 1862) and that of Bergmann, EB (Berlin Med Wochenschr 10:385, 1873). Since then, the original concept of its etiology, attributing it to single or multiple skeletal fractures, has been greatly modified. Clinical and pathologic investigations revealed instances of pulmonary fat embolism in patients with extensive soft tissue injury due to severe beating, accidents, blast, or surgical transection of heavy muscle layers; also, in severe skeletal concussion, osteomyelitis, severe burns, childbirth; in patients given external cardiac massage, renal transplantation, and in those on pump oxygenator. Other pertinent conditions include liver rupture, steroidinduced fatty liver; severe infections, poisonings, snake bite, neoplasms, diabetes mellitus, alcoholism, sickle-cell crisis, and simulated high-altitude Hight. Benator, SR et al (Quart J Med 41:85, 1972) recorded, in cases of trauma, histologically proved but clinically insignificant fat embolism in over 67 percent and clinically significant fat embolism in about 6 percent. Musselman, MM et al (Arch Surg 65:551, 1952) reported the following approximate incidence of'fat embolism: in fracture of the hip, 77 percent, of Hat bones, 42 percent, in severe soft tissue injury, 25 percent, in burns up to one-third of the body, 57 percent. Rogel, Setal (New England J Med 272:732, 1965) noted multiple pulmonary fat emboli without skeletal fracture. Gauss,',H (Arch Surg 9:593, 1924) first asserted that fat particles that cause embolism originate from the 'marrow of fractured bone consequent to damage to the supportive fibrous frame work, and pass into traumatized veins. On the other hand, Lehman, EP et al (Arch Surg 14:621, 1927) expressed the view that fat embolism was brought about by trauma through changes in the emulsion of fats in the blood plasma. Normally, fats in the blood are detectable as circulating chylomicrons of 1-7 micron in diameter. In patients with pulmonary fat embolism, the chylomicrons coalesce into fat macroglobules of 10-15 micron in diameter, that may appear directly after trauma. Subsequent research studies offer valid support to this concept. In many instances, both of these mechanisms of fat embolism may have a causal role. During traumatic lipemia it is likely to find abundant fat emboli in the capillaries
CHEST, 69: 3, MARCH, 1976
of alveolar septa. Massive obstruction of pulmonary arterioles by macroglobules of fat causes acute pulmonary hypertension with consequent right heart failure. The observations of King, EG et al (Chest 59:524, 1971} are of importance. By direct viewing through a thoracic window in dogs, they confirmed the concept that fatty acids produced by the action of lipase on circulating lipids cause pulmonary tissue inflammation and destructive changes, including disruption of endothelial integrity, loss of hemorrhagic fluid into perivascular and interalveolar spaces, disappearance of or interference with the expansion of implicated alveoli. Hamilton, R et al (Surgery 56:53, 1964) ascertained that alveolar surfactant is decreased by fatty acid embolization, with resultant damage to the anatomic and functional integrity of alveoli. These changes, together with chemical pneumonitis, pulmonary capillary hemorrhages, interference with microcirculation of the lung, pulmonary edema, increased shunting, ventilation-perfusion imbalance, decreased lung compliance, increased pulmonary arterial pressure are the prelude to adult respiratory distress syndrome observed by Ashbaugh, DG et al (Quart J Med 2:319, 1967). It may ensue in less than an hour to 72 hours after trauma. Occurrence of fat droplets in the urine was reported first by Scriba, J (Deutsch Zeitschr Chir 12:118, 1880) and conglomeration of fat globules in the blood by Peltier, LF (Surgery 36:198, 1954). Petechiae in the skin, most prominent in the axillae, across the anterior chest and in the Hanks were observed first by Grondahl, NB (Deutsch Zeitschr Chir 111:56, 1911}. Also, subconjunctival petechiae and embolization in the retina may be noted. X-ray may reveal bilateral Huffy densities. Other likely findings include ECG changes, hypoxemia, anemia, thrombocytopenia, hypocalcemia, azotemia, rise in serum lipase, hyperbilirubinemia and jaundice. Sproule, BJ et al (Canad MA J 90:1243, 1964) first made arterial blood gas determinations in such cases. Since then this method has become cardinal means of correct diagnostic approach. It may be of interest to mention the article of Horne RH et al (Arch Int Med 132:288, 1974) who found that intravenous administration of hypertonic glucose solution prevented fat embolism in patients with fractures of the pelvis and long bones. Andrew L. Banyai, M.D.
PULMONARY FUNCTION AFTER RECOVERY FROM ARDS 355
Eight adult patients with acute respiratory distress syndrome were treated with positive end-expiratory pressure (PEEP) ventilation. The results of detailed examinations of pulmonary function in these eight patients obtained after dHferent periods of time foDowiDg discharge from the respiratory care unit were analyzed to determine the degree of disturbances in pulmonary function. For comparison, eDIIIinations of pulmonary function were also performed on two patients who were treated with zero end-expiratory pressure ventilation. This fol-
Jn 1967, Ashbaugh et aP described some adult
patients with the acute respiratory distress syndrome who were successfully treated with positive end-expiratory pressure (PEEP) ventilation. Up to that time, mortality from the adult respiratory distress syndrome was practically 100 percent. The good therapeutic results were confirmed in later publications of the same group2.3 and also by other authors.4-7 In this paper the definition of the adult respiratory distress syndrome as proposed by Ashbaugh et al8 is used, ie, acute respiratory failure and distress associated with a specific incident or illness with the exclusion of exacerbation of chronic pulmonary disease or primary cardiogenic pulmonary edema. Apart from case reports,B.l 0 there have been no detailed studies in which pulmonary function after PEEP treatment of the adult respiratory distress syndrome was investigated. We, therefore, decided to study pulmonary function in a group of eight patients who survived the adult respiratory distress syndrome after treatment with PEEP. PATIENTS
From August 1968 until March 1973, some 36 patients with the adult respiratory distress syndrome were treated °From the Lung Function Laboratory and Respiratory Care Unit, University Hospital, Groningen, the Netherlands. 0 0 Presently at Roman Catholic Hospital, Groningen, the Netherlands. tPresently at Derby Chest Clinic, Derby, England. Manuscript received December 23, 1974; revision accepted September 23.
Reprint requests: Dr. Klein, Interne Kliniek, Academisch Ziekenhuis, Groningen, The Netherlands
350 KLEIN ET AL
low-up study showed remarkably few abnormalities. When present, restrictive disturbances in pulmonary function, especiaDy decreased static compliance and dUfusing capadty, were found. No correlation was found between the pulmonary-function results of the eight patients and the duration of the PEEP treatment, nor between the results and the time interval between treatment at the respiratory care unit and the moment of the pulmonary function studies.
with PEEP in the respiratory care unit of the University Hospital of Groningen, the Netherlands. In 16 patients the cause of the adult respiratory ·distress syndrome was pulmonary trauma (direct pulmonary injury), and in 20 the syndrome was of different origin (indirect pulmonary injury). The adult respiratory distress syndrome of all these patients did not react favorably to positive-pressure ventilation with a high inspiratory oxygen concentration. Addition of PEEP often resulted in a dramatic rise in the arterial oxygen pressure ( Pa~) and immediate relief of the distress. The further treatment of these patients consisted of other measures, such as bronchial toilet, physiotherapy, and therapy with antibiotics, corticosteroids, and anticoagulants.ll Of this series of 36 patients, 15 died, and 21 patients survived the acute episode. The studies of pulmonary function were performed between March and May 1973. To allow a certain stabilization of the pulmonary function, only patients who were treated at the respiratory care unit before November 1972 were included in these studies. As a result of this selection, seven patients were excluded. Two additional patients died because of e«trathoracic diseases after discharge from the respiratory care unit, and four patients were unable to cooperate. Ultimately, eight patients were available. For comparison, two other patients were also examined; they had been treated with only zero end-expiratory pressure at a time when we were only partly familiar with PEEP. At present, ventiljltion with PEEP would undoubtedly have been applied. Tables 1 and 2 give the data on diagnosis, treatment, and complications of these ten patients. With the exception of patient 4, who had a mild form of chronic obstructive pulmonary disease (chronic cough and sinusitis in the past), all these patients were healthy before the adult respiratory distress syndrome. METHODS
Since very little is known about the character and degree of the disturbances of pulmonary function in persons who survived the adult respiratory distress syndrome, many tech-
CHEST, 69: 3, MARCH, 1976
Table 1-DiCIJ'RO- o/ Palien,. Diagnosis Patient Elapsed No., Age Time (yr) (mo)* 1, 19
5
2, 25
16
3, 28
12
4,'l!l
34
5,9
6
6,23
7
7, 9
34
8, 22 22
Cause of Pulmonary Injury Direct
Indirect
Traffic accident Traffic accident Traffic accident Traffic accident
29
10,40
14
Aspiration
Left
Rib Fractures
Hemothorax
Extrathoracic Lesions** +
+
Left and right Left and right Left and right
+
Neardrowning Neardrowning Traffic accident Traffic accident
9, 13
Lung Edema
Lung Contusion
++
+
++
+
++
+
+ ++
+
+
++
Left and right
+
+
Traffic accident Suicidal attempt via drug ingestion
Right
Right
++ ++
+ +
*Time elapsed between treatment at respiratory care unit and assessment of pulmonary function. **+,Few extrathoracic lesions; and ++,many extrathoracic lesions. niques to measure pulmonary function have been applied to detect any possible disorders. A survey of the techniques with standard values and the apparatus which were employed is given in Table 3. Because of patient's age and technical reasons, the total program was not completed in all patients, as is shown in Tables 4 to 6.
REsULTS
The results of pulmonary function studies are summarized in Tables 4 to 6.t tMore detailed information on the actual values measured with the different techniques is available from the authors on request. Table 2--DaiG Patient No. 1 2 3 4 5 6 7 8 9
10
PaOt (mm Hg) Before PEEP 50
51* 51 36 34 48 51 30
42 36
PEEP (hr)
24 72 72 120 48 24 42 72
Lung Volumes
The total lung capacity ( TLC) and vital capacity ( VC) were decreased in four patients and in five patients, respectively. Only in patient 9 were these decreases more than 30 percent. In patient 8, the VC was larger than the predicted value. In all other patients, the TLC and VC were normal. The residual volume (RV), RV/TLC, functional residual capacity ( FRC ), forced expiratocy volume in one second ( FEV t.o), FEV t.o/VC, and maximum ·voluntary ventilation ( MVV) did not show any constant change.
Treatment and Compliearion.
Mechanical Ventilation (Days) 3 36 28 21 6 10 2 28 14 2
Shock
Pneumothorax
+
Left Right and left
Pulmonary Gram-Negative Infection
+ + +**
+ +
Right and left
+ + +
*With oxygen. **Also gram-negative septicemia.
CHEST, 69: 3, MARCH, 1976
PULMONARY FUNCnON AFTER RECOVERY FROM ARDS 351
Table S--Method•
Determination
Technique
Equipment
Standard Values
Spirometry
Inspiratory vital capacity
Adults 11 and children 18
Spirometer (Lode 53-R)
Lung volumes
Helium dilution
Tammeling 14
Spirometer (Lode 53-R); helium analyzer (Mijnhardt)
Lung mechanics
Esophageal-balloon technique 1•·11
Hilvering 11 and Turner et al 17
Spirometer (Lode 53-R); manometer (Godart); recorder (Bryans X-Y)
Body plethysmography
Spontaneous-breathing method 18
Quanjer 11
Volume-constant body plethysmograph constructed to our specifications (by Lode)
Blood gases
pH glass electrode; PaO, and PaCO, membrane electrodeslll
Radiometer: pH microelectrode E5021, PaO, membrane electrode E5046, PaCO, membrane electrode E5036, PaO, module 932, and· PaCO, module 933
Ergometry
75-100 w, with frequency of 60 to 70 per minute
Bicycle ergometer (Lode)
Shunt
Berggren21 modified by Chiang22
::5 8 percent of cardiac output
Dead space
Bohr equationu
::5 45 percent of tidal volume
Diffusing capacity
Breath-holding method of Krogh2•·n modified by Oglivie et al21
Washout curves
7-min N2 washout28 N 2 single-breath washoutz• CO, washout•
Lung scan
Human serum albumin microspheres labeled with llmtechnetium 1 L 12
uaxenon, regional
Open spirometric system
Constructed to our specifications (by Lode cooperating with Department of Electronics, University of Groningen) FaNs ::5 2 percent• N2 slope ::5 5 percent/sec CO, slope ::5 13 percent/sec
Nitrogen meter (SeBIDa); capnograph (Godart) Gamma camera (Nuclear Chicago)
Right lung/left lung, 55/45 percent for volume, ventilation, and perfusion
Constructed to our specifications (by Lode)
*FaN2, Nitrogen concentration of alveolar sample after breathing oxygen for seven minutes.
Lung Mechanics Work of breathing ( W) was normal in four patients and was increased in the other four patients. Static compliance ( Cst) was lower than the standard value in five patients and normal in two. Patient 8 was the only one with a larger than predicted Cst. Body plethysmographic studies failed to show abnormalities, except in patient 4, who had an increased airway resistance (Raw). Gas Exchange At rest, three out of seven patients showed a slightly decreased Pa02. During exercise, a fall in pH and Pa02, along with an increase of arterial carbon dioxide tension ( PaC02), appeared in pa352 KLEIN ET AL
tient 3 and also in patient 8 ( at rest, he was hyperventilating). In all cases the right-left shunt was increased, although in none of the patients was it over 11 percent. The dead-space ventilation ( Vo) was increased in three out of six patients. The diffusing capacity (D) was decreased, except in two patients. Washout Curves
The curves for carbon-dioxide washout in the three youngest patients were abnormal. All the other results of the washout curves were normal. Ventilation and Perfusion
Lung scanning with
99
mtechnetium failed to
CHEST, 69: 3, MARCH, 1976
Table 4--Lunl' J'oluma and Meelaanie•* Patient No. 1NN 2 3 4 5 6 7N 8NN 9 10
TLC
RV/TLC
74 84 N N 74
114 81 82 59 124 133
68 N
200 88
vc
FRC 117 N 72 N N N 86 115 84 NN
FEV1.0
FEV1.0/VC
N 69 N
N N 113
82 77 77 118 37 123
81 N N N 74 120
N 80 85 NNN N 71 82 111 51
MVV
50 70 N 112 112 58 68 128 128
w
Cst
Raw
N 120 170
N 85 50 N
138
76
N N N
135 67 64
N N N 135 N N N N N N
*Table values are percents of predicted values. N, Predicted value ± 10 percent. For abbreviations, see text.
nary disease in her medical history, was the only one with an increased Raw. Apart from the increased W, she has no other signs of chronic obstructive pulmonary disease in the pulmonary function results. The abnormal values for curves of carbon dioxide washout in the younger patients (No. 5, 7, and 9) may be explained by their higher frequency of breathing. Patient 8 had the best results on pulmonary function tests. Only Cst (which was larger than predicted, the only one of the group with this finding), the Pa02 (decreased), and the PaC02 (elevated) during exercise were abnormal. Of the two patients not treated with PEEP, patient 9 had very extensive disturbances in pulmonary function. These disturbances were both restrictive and obstructive; there were no signs of chronic obstructive pulmonary disease in her medical history. It is quite notable that the xenon studies in these two patients show not only a disturbed right-left ventilation percentage (as in patients 3 and 6) but also disturbed volume and perfusion percentages. It is open for discussion whether ventilation with PEEP in these patients would have resulted in better pulmonary function. The Pa02 on admission showed no correlation with ultimate results of pulmonary function tests. Longer treatment with PEEP and a short-
show any abnormality. Studies with 133xenon gave abnormal values of the right-left ventilation percentage in six patients, while in two (No. 9 and 10) of these six patients, the volume and perfusion percentage was also disturbed. DISCUSSION
Interpretation of the results is difficult because of the complexity of the problem, which virtually precludes prospective controlled studies; however, the data give a good picture of the disturbances in pulmonary function after the adult respiratory distress syndrome because all patients (except No. 4) were healthy before treatment at the respiratory care unit. Consequently, it may be assumed that their pulmonary function before the adult respiratory distress syndrome was normal. The results of the different techniques for measuring pulmonary function proved to be of very different significance in respect to the detection of abnormal function. Although there was no constant pattern, restrictive sequelae (defined as decreased TLC, RV, RV /TLC, Cst, and D, with an increased FEV1.o/VC) were found fairly often in these patients. In four patients, W was increased. Patient 4, who had a mild form of chronic obstructive pulmoTable 5-Data /rom ..4rterial Blood Patient No. 1 2 3 4 5 6 7 8 9 10
pH
,.----A--,
Pa02 (mm Hg)
,.----A--,
w• ..4naly•~,
PaCOt (mm Hg) ,--~Right-Left
Rest
Exercise
Rest
Exercise
Rest
7.40 7.39 7.40 7.43
7.40 7.35 7.35 7.38
95 86 92 83
98 90 74 91
38 41 41 38
7.39
7.39
85
88
45 49
7.45 7.46
7.40
113 120
88
33 33
*N, Predicted value ± 10 percent. • *Shunt, Percentage of cardiac output.
CHEST, 69: 3, MARCH, 1976
Ca• Esehan,.e, and JJ'a•hout
Exercise Shunt•• 39 39 43 36
42
Vnt
Dt
7-min FaN,
9.5 10.5 11.0 9.0
57
11.0
62
NNNN 63 85 77 85 61
10.0
34
NNNN
58
42 38
79
Curt~e•
NNN N NN N NN NN NNN
* Nt Slope
co,
Slope
NN N
(19.5) N (32) (19.5)
tVn, Percentage of tidal volume. tD, Percentage of predicted value.
PULMONARY FUNCnON AFTER RECOVERY FROM ARDS 353
Table 6--Ruult•/or Luq J'olume, J'entilation, arul Per/uaon /rom 138Xenon Seudie•• Lung Volume Patient ,......----J'-No. Right Left 1NNNNNN NNNN 2 NN 3 4NN NN 5 6NN 7 NNNNNN 8 9 29 71 42 10 58
Lung Ventilation ~
Lung Perfusion
,......----J'--
Right
Left
Right
Left
46 48 40 47
54 52 60 53
N N NN NN N
N N
26 39
74 61
38 61
62 39
N
•N, Predicted value ± 10 percent.
er interval between admission into the respiratory care unit and pulmonary function assessment did not tend to produce more disturbed pulmonary function (Tables 1, 2, 4, 5, 6). In conclusion, the assessment of pulmonary function in adults, after recovery from the acute respiratory distress syndrome should preferably include the measurements of TLC, RV, VC, FEV1.0, W, Cst, and D, which may clearly show restrictive disturbances. Additional measurements, such as blood gas analyses at rest and during exercise and studies with 133xenon, do not give substantial additional information. ACKNOWLEDGMENT: We wish to thank the Department of Nuclear MedicineJ University Hospital, Groningen, the Netherlands, for penorming the technetium scans and for providing the facilities for the xenon studies and all the other co-workers of the Lung Function Laboratory for their technical assistance. Calculations of the xenon studies were performed in the Computer Centre of the University of Groningen. REFERENCES
1 Ashbaugh DG, Bigelow DB, Petty TL, et al: Acute respiratory distress in adults. Lancet 2:319, 1967 2 Ashbaugh DG, Petty TL, Bigelow DB, et al: Continuous positive-pressure breathing ( CPPB) in adult respiratory distress syndrome. J Thorac Cardiovasc Surg 57: 31, 1969 3 Petty TL, Ashbaugh DG: The adult respiratory distress syndrome: Clinical features, factors influencing prognosis, and principles of management. Chest 60:233-239, 1971 4 Pontoppidan H, Geffin B, Lowenstein E: Acute respiratory failure in the adult. N Eng) J Med 2a7:690, 743, 799, 1972 5 Bachofen-Ponchet M, Bachofen H: Lungenveranderungen nach Trauma und Shock: Das "respiratory distress syndrome" des Erwachsenen. Schweiz Med Wochenschr 103:1, 1973 6 van Haeringen JR, Blokzijl EJ, le Coultre R, et al: Het "respiratory distress syndrome" van de volwassene: Een reactiepatroon van de long op schadelijke invloeden van zeer uiteenlopende aard. Ned Tijdschr Geneesk 118: 748, 1974
354 KLEIN ET AL
7 van Haeringen JR, Blolczijl EJ, van Dijl W, et al: Treatment of the respiratory distress syndrome following nondirect puhnonary trauma with positive end-expiratory pressure with special emphasis on near-drowning. Chest 66(suppi):30S-34S, 1974 8 Ashbaugh DG, et al: Respiratory distress syndromes in respiratory diseases. In Task Force Report on Problems, Research Approaches and Needs. Bethesda, Md, National Heart and Lung Institute, 1972, p 165 9 Downs JB, Olsen GN: Puhnonary function following adult respiratory distress syndrome. Chest 65:92-93, 1974 10 Llamas R: Adult respiratory distress syndrome: Report of survival after two episodes. Chest 65:468-469, 1974 11 Sluiter HJ, Blokzijl EJ, van Dijl W, et al: Conservative and respirator treatment of acute respiratory insufficiency in patients with chronic obstructive lung disease. Am Rev Respir Dis 105:932, 1972 12 Tammeling GJ: Standard values for lung volumes and ventilatory capacity of sanatorium patients. Selected Papers 1:65, 1961 13 Polar G, Promadhat V: Puhnonary Function Testing in Children. Philadelphia, WB Saunders Co, 1971 14 Tammeling GJ: Het Residuaalvolume en de Functionele Residuaal Capaciteit, thesis. Groningen, the Netherlands, 1958 15 Buytendijk HJ: Oesophagusdruk en Longelasticiteit, thesis. Groningen, the Netherlands, 1949 16 Hilvering C: Longmechanische Onderzoekingen bij Patienten met Longtuberculose, thesis. Groningen, the Netherlands, 1963 17 Turner JM, Mead J, Wohl ME: Elasticity of human lungs in relation to age. J Appl Physiol25:664, 1968 18 Peset R, Quanjer PH, Tammeling GJ: Bronchodilation estimated by body plethysmography. In Progress in Respiration Research: Body Plethysmography ( vol 4) DuBois AB, van de Woestijne KP, eds). Basel, Switzerland, S Karger, 1969, p 215 19 Quanjer PH: Plethysmographic Evaluation of Airway Obstruction, thesis. Groningen, the Netherlands, 1971 20 Gimeno Ortega F: Clinical Blood Gas Analysis, thesis. Groningen, the Netherlands, 1969 21 Berggren SM: The oxygen deficit of arterial blood caused by nonventilated parts of the lungs. Acta Physiol Scand (suppl)4:11, 1942 22 Chiang ST: A nomogram for venous shunt ( Q./Q,) calculation. Thorax 23:563, 1968 23 Bohr C: Ueber die Lungenathmung. Scand Arch Physiol 2:236, 1891 24 Krogh A, Krogh M: On the rate of diffusion of carbonic oxide into the lungs of man. Scand Arch Physiol 23:236, 1909 25 Krogh M: Diffusion of gases through the lungs of man. J Physiol (Lond) 49:271, 1914 26 Ogilvie CM, Foster RE, Blakemore WS, et al: A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest 36:1, 1957 27 Cotes JE: Lung Function. Oxford, England, Blackwell Scientific Publications, 1965 28 Darling RC, Cournand A, Richards OW Jr: Studies on intrapuhnonary mixture of gases. J Clin Invest 23:55, 1944 29 Comroe JH Jr, Fowler WS: Lung function studies: 6. Detection of uneven alveolar ventilation during single breath of oxygen. Am J Med 10:408, 1951
CHEST, 69: 3, MARCH, 1976
30 van Meerten JH: Concentratiecurven van Expiratiegassen, thesis. Nijmegen, the Netherlands, 1966 31 Rhodes BA, Zolle J, Buchanan JW, et al: Radioactive albumin microspheres for studies of the pulmonary circulation. Radiology 92:1453, 1969 32 van de Poll MAPC, Woldring MG: Radioactief gemerkt humaan albumine "microspheres". Pharm Weekblad 108: 741, 1973 33 Peset R, Holloway R, Beekhuis H, et al: Ventilation and perfusion indices measured with xenon-133 during spontaneous breathing. In Radioaktive Isotope in Klinik
und Forschung: (vol 9) Fellinger K, HOfer R, eds. Munich, Urban and Schwartzenberg, 1970, p 266 34 Peset R, Beekhuis H, Tammeling GJ, et al: A ''bag in box" system in regional ventilation studies of the lung with xenon-133. In Radioaktive Isotope in Klinik und Forschung: (vol 10), Fellinger K, Hofer R, eds. Munich, Urban and Schwartzenberg, 1973, p 335 35 Peset R, Gimeno F, van Haeringen JR, et al: Comparison of 133xenon regional studies during spontaneous breathing and bronchospirometry. Scand J Respir Dis 55:91, 1974
Pulmonary Fat Embolism Over a hundred years ago, two reports on this subject appeared in Germany, that of Zenker (Beitriige zur Normalen und Pathologischen Anatomie der Lunge, Dresden, Braunsdorf, 1862) and that of Bergmann, EB (Berlin Med Wochenschr 10:385, 1873). Since then, the original concept of its etiology, attributing it to single or multiple skeletal fractures, has been greatly modified. Clinical and pathologic investigations revealed instances of pulmonary fat embolism in patients with extensive soft tissue injury due to severe beating, accidents, blast, or surgical transection of heavy muscle layers; also, in severe skeletal concussion, osteomyelitis, severe burns, childbirth; in patients given external cardiac massage, renal transplantation, and in those on pump oxygenator. Other pertinent conditions include liver rupture, steroidinduced fatty liver; severe infections, poisonings, snake bite, neoplasms, diabetes mellitus, alcoholism, sickle-cell crisis, and simulated high-altitude Hight. Benator, SR et al (Quart J Med 41:85, 1972) recorded, in cases of trauma, histologically proved but clinically insignificant fat embolism in over 67 percent and clinically significant fat embolism in about 6 percent. Musselman, MM et al (Arch Surg 65:551, 1952) reported the following approximate incidence of'fat embolism: in fracture of the hip, 77 percent, of Hat bones, 42 percent, in severe soft tissue injury, 25 percent, in burns up to one-third of the body, 57 percent. Rogel, Setal (New England J Med 272:732, 1965) noted multiple pulmonary fat emboli without skeletal fracture. Gauss,',H (Arch Surg 9:593, 1924) first asserted that fat particles that cause embolism originate from the 'marrow of fractured bone consequent to damage to the supportive fibrous frame work, and pass into traumatized veins. On the other hand, Lehman, EP et al (Arch Surg 14:621, 1927) expressed the view that fat embolism was brought about by trauma through changes in the emulsion of fats in the blood plasma. Normally, fats in the blood are detectable as circulating chylomicrons of 1-7 micron in diameter. In patients with pulmonary fat embolism, the chylomicrons coalesce into fat macroglobules of 10-15 micron in diameter, that may appear directly after trauma. Subsequent research studies offer valid support to this concept. In many instances, both of these mechanisms of fat embolism may have a causal role. During traumatic lipemia it is likely to find abundant fat emboli in the capillaries
CHEST, 69: 3, MARCH, 1976
of alveolar septa. Massive obstruction of pulmonary arterioles by macroglobules of fat causes acute pulmonary hypertension with consequent right heart failure. The observations of King, EG et al (Chest 59:524, 1971} are of importance. By direct viewing through a thoracic window in dogs, they confirmed the concept that fatty acids produced by the action of lipase on circulating lipids cause pulmonary tissue inflammation and destructive changes, including disruption of endothelial integrity, loss of hemorrhagic fluid into perivascular and interalveolar spaces, disappearance of or interference with the expansion of implicated alveoli. Hamilton, R et al (Surgery 56:53, 1964) ascertained that alveolar surfactant is decreased by fatty acid embolization, with resultant damage to the anatomic and functional integrity of alveoli. These changes, together with chemical pneumonitis, pulmonary capillary hemorrhages, interference with microcirculation of the lung, pulmonary edema, increased shunting, ventilation-perfusion imbalance, decreased lung compliance, increased pulmonary arterial pressure are the prelude to adult respiratory distress syndrome observed by Ashbaugh, DG et al (Quart J Med 2:319, 1967). It may ensue in less than an hour to 72 hours after trauma. Occurrence of fat droplets in the urine was reported first by Scriba, J (Deutsch Zeitschr Chir 12:118, 1880) and conglomeration of fat globules in the blood by Peltier, LF (Surgery 36:198, 1954). Petechiae in the skin, most prominent in the axillae, across the anterior chest and in the Hanks were observed first by Grondahl, NB (Deutsch Zeitschr Chir 111:56, 1911}. Also, subconjunctival petechiae and embolization in the retina may be noted. X-ray may reveal bilateral Huffy densities. Other likely findings include ECG changes, hypoxemia, anemia, thrombocytopenia, hypocalcemia, azotemia, rise in serum lipase, hyperbilirubinemia and jaundice. Sproule, BJ et al (Canad MA J 90:1243, 1964) first made arterial blood gas determinations in such cases. Since then this method has become cardinal means of correct diagnostic approach. It may be of interest to mention the article of Horne RH et al (Arch Int Med 132:288, 1974) who found that intravenous administration of hypertonic glucose solution prevented fat embolism in patients with fractures of the pelvis and long bones. Andrew L. Banyai, M.D.
PULMONARY FUNCTION AFTER RECOVERY FROM ARDS 355
