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Alveolar-arterial oxygen gradient in acute pulmonary embolism in pregnancy
Alveolar-arterial oxygen gradient in acute pulmonary embolism in pregnancy Raymond O. Powrie, MD, Lucia Larson, MD, Karen Rosene-Montella, MD, Monica Abarca, MD, Linda Barbour, MD, MSPH, and Nelson Trujillo, MD Providence, t~ode Island OBJECTIVE: Our goal was to determine the prevalence of normal alveolar-arterial gradients in pregnant patients with documented pulmonary embolism. STUDY DESIGN: A retrospective chart review was performed on all pregnant women with pulmonary embolism at two large obstetric centers between 1990 and 1995. Alveolar-arterial gradients were calculated from room air arterial blood gas values and compared with values from patients who had been established as normal. RESULTS: Ten of 17 patients with pulmonary embolism identified had alveolar-arterial gradients that were normal. CONCLUSIONS: In our study 58% of pregnant women with documented pulmonary embolism had a normal alveolar-arterial gradient. This markedly differs from the published data in nonpregnant patients, in which the incidence of normal alveolar-arterial gradients in pulmonary embolism has ranged from 1.9% to 20%. This suggests that the alveolar-arterial gradient should not be used to determine the likelihood of pulmonary embolism in pregnant women because this could lead to the withholding of appropriate treatment for this lifethreatening condition. (Am J Obstet Gyneco11998;178:394-6.)
Key words: Blood gases, pulmonary embolism, pregnancy, alveolar-arterial oxygen gradient
Pulmonary embolism is a leading cause of maternal mortality in the Western world. It remains the leading cause of death after a live birth in the United States, 1 and it accounts for the largest number of maternal deaths in Wales, England, and Sweden.Z, 3 Untreated p u l m o n a r y embolism carries a 26% mortality rate. 4 The evaluation of patients with suspected pulmonary embolism is made difficult by the absence of a sensitive, specific, and practical diagnostic test. Investigators have explored numerous diagnostic tests and procedures by which clinicians can try to identify pulmonary embolism without resorting to the "gold standard" of pulmonary angiography. One such widely used tool is the alveolar-arterial oxygen gradient, which is a calculation of the difference between oxygen concentration in the alveoli and in the arterial blood. A normal disparity exists between alveolar and arterial blood oxygen tension because of physiologic ventilation-perfusion mismatching and a small physiologic degree of right-to-left pulmonary shunting. This disparity between alveolar and arterial oxygen is usually exaggerated by acute pulFrom the Division of Obstetric and Consultative Medicine, Department of Medicine, Women and Infants Hospital of Rhode Island and Brown University School of Medicine. Receivedfor publication December26, 1996; revisedJuly 10, 1997; acceptedJuly 23, 1997. Reprint requests: Raymond O. Powrie, M1), Women and Infants Hospital, 101 Dudley St., Providence, RI 02905-2401. Copyright 9 1998 by Mosby, Inc. 0002-9378/98 $5.00 + 0 6/1/84990 394
m o n a r y embolism both because acute p u l m o n a r y embolism increases ventilation-perfusion mismatching and also because it causes increased shunting. 5, 6 Because pulmonary embolism usually decreases perfusion and thus increases mismatching and shunting, the alveolar-arterial gradient has been advocated by many to be a simple and sensitive screening test to rule out pulm o n a r y embolism. 7 In 1988 Overton a n d Bocka 8 reviewed the alveolar-arterial gradient of 64 patients with positive pulmonary arteriograms and found only 4.7% of them h a d n o r m a l alveolar-arterial gradients. Initial Prospective Investigation of P u l m o n a r y Embolism Diagnosis9 data in 1990 (and a subsequent expanded review of the Prospective Investigation o f P u l m o n a r y Embolism Diagnosis database in 1995 by Stein et al. 10, 11) challenged this finding by showing that a normal alveolar-arterial gradient (defined by the authors as <20 m m Hg) was present in 11% to 14% of patients with acute pulmonary embolism and no preexisting cardiovascular or pulmonary disease. However, in 1994, McFarlane and Imperiale 12 published data showing that only 1.9% of pat e n t s with acute pulmonary embolism had normal alveolar-arterial gradients and reasserted that the diagnosis of pulmonary embolism is unlikely in the setting of a normal alveolar-arterial gradient. Regardless of which data are given the most scientific credence, in practice many clinicians still use a normal alveolar-arterial gradient as justification for not further investigating the possibility of pulmonary embolism.
Volume 178, Number 2 AmJ Obstet Gynecol
Our study was designed to answer the question of what the c o m b i n e d experience of Women and Infants Hospital of Rhode Island, in Providence, Rhode Island, and University Hospital of Denver, Colorado, has been regarding the alveolar-arterial gradient of p r e g n a n t women with acute pulmonary embolism. It was our hypothesis that the incidence of a normal alveolar-arterial gradient in pregnant patients with acute pulmonary embolism would be higher than McFarlane's 1.9% and may even be higher than Stein's 14%.
Material and methods All ventilation'-perfusion scans and p u l m o n a r y angiograms performed between J a n u a r y 1990 a n d December 1995 at Women a n d Infants Hospital (Providence) a n d University Hospital (Denver) were identified. Each of these was reviewed to identify all women between the ages of 15 and 45 years with highprobability ventilation-perfusion scans or positive pulmonary angiograms. Charts were then obtained and reviewed on all these women to identify which were either p r e g n a n t or within 8 weeks post partum. Because Women and Infants Hospital of Rhode Island is a major obstetric referral center, the additional measure of reviewing all charts with a discharge diagnosis of pulmonary embolism was carried out at this hospital to identify any patients who may have had lung scans at referring centers and were subsequently sent to this institution. Eighteen pregnant or postpartum patients with high-probability ventilation-perfusion scans or positive p u l m o n a r y angiograms were identified. Seventeen of these patients had undergone arterial blood gas determinations on room air immediately before their scans were obtained. The alveolar-arterial gradient was calculated by the following standard formula: A-a = [ (PB - PH2o) (Fi~ - (Paco2) (1.25)] - Pao 2. PB (mean barometric pressure) = 628 in Denver, 760 m m Hg in Providence. PH2o = 47 m m Hg. Fio 2 = 0.21. Paco 2 and Pao 2 were measured with room air arterial blood gas. An abnormal alveolar-arterial gradient was defined for our population as >15 m m Hg after a review of the literature on normal values of alveolar-arterial gradient. 13-15
Results Seventeen patients were identified with either highprobability ventilation-perfusion scans or positive pulmonary angiograms who were pregnant or within the 8week-postpartum period and had blood for arterial blood gas values drawn on room air. Of the 17 patients, 10 (58%) had alveolar-arterial gradients <15 m m Hg (Table I).
Comment A n o r m a l alveolar-arterial gradient was present in more than half the pregnant women we studied who had
P0wrie et al. 395
acute pulmonary embolism. This is in marked contrast to the findings in the literature regarding n o n p r e g n a n t patients, in whom a small minority of patients with docum e n t e d p u l m o n a r y embolism have n o r m a l alveolararterial gradients. Therefore normal values of an alveolar-arterial gradient do not exclude the diagnosis of acute pulmonary embolism in pregnant patients. In fact, the use of the alveolar-arterial gradient by physicians to "rule out" the diagnosis of pulmonary embolism in pregnancy could result in a significant n u m b e r of pregnant women with untreated pulmonary emboli and may contribute to the maternal deaths seen in this condition. This conclusion is consistent with that made by the original Prospective Investigation of P u l m o n a r y Embolism Diagnosis study researchers; however, it is not often consistent with current practice. Although the numbers in our study were not large, the high percentage of women with n o r m a l alveolar-arterial gradients would suggest that many pregnant women could go untreated for this life-threatening condition if a normal alveolar-arterial gradient is used to rule out the diagnosis of acute pulmonary embolism. O u r sample size makes it difficult to d e t e r m i n e whether pregnant women are truly more likely to have a n o r m a l alveolar-arterial gradient than n o n p r e g n a n t women without cardiopulmonary disease. However, the nearly fourfold difference in our percentages, compared with Stein's, certainly is suggestive that a true difference exists (95% confidence interval 0.3292 to 0.8155). Reasons why pregnant women might have a greater incidence of normal alveolar-arterial gradients in the setting of acute p u l m o n a r y embolism than n o n p r e g n a n t women is a topic for further research. Clearly, the elevated minute ventilation of pregnant patients is not an adequate explanation because previous research indicates that normal pregnancy is not associated with a lowering of the alveolar-arterial gradient. 16, 17 The possibility that pregnant women with acute pulmonary embolism have lower alveolar-arterial gradients than n o n p r e g n a n t women may be because of a combination of factors related to the care of pregnant women. Pregnant women with pulmonary embolism may be examined sooner because they are more regularly exposed to medical personnel or they may have been counseled about the increased risk of t h r o m b o e m b o l i s m d u r i n g pregnancy. Because the alveolar-arterial gradient is known to correlate with size and n u m b e r of embolisms, early presentation and treatment in pregnant women may explain our findings. Medical personnel, in turn, may investigate and treat these women earlier because of the general knowledge among physicians that pregnancy is a state at high risk for pulmonary thromboembolic disease. Dyspnea during pregnancy is very common; however, this study suggests that a normal alveolar-arterial gradient cannot be used as reassurance that a pulmonary em-
396 Powrie et al.
February 1998 AmJ Obstet Gynecol
Table I. Age, gestation, a n d alveolar-arterial g r a d i e n t o f 17 patients with pregnancy-associated p u l m o n a r y e m b o l u s
Patient No.
Age (yr)
Gestation (wk)
Pao2 (mm Hg)
Paco2 (mm Hg)
Alveolar-arterial gradient (mm Hg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
22 30 28 21 37 22 21 24 17 20 23 21 29 31 27 24 29
8 1 wk post partum 15 32 6 18 32 26 10 33 7 13 9 2 days after termination of pregnancy at 21 wk 1 wk post partum 10 7
83 91 84 78 107 76 78 101 97 91 64 57 82 38 77 82 68
39 39 32 33 23 33 33 39 33 25 37 32 29 30 27 28 32
18 10 26 31 14 33 31 0 12 0 12 25 4 47 12 5 14
bolism is n o t the u n d e r l y i n g cause. Given the m i n i m a l rad i a t i o n risk o f a v e n t i l a t i o n - p e r f u s i o n scan ( a p p r o x i mately 0.1 tad)18 a n d t h e l i f e - t h r e a t e n i n g c o n s e q u e n c e s o f u n t r e a t e d p u l m o n a r y e m b o l i s m , the alveolar-arterial g r a d i e n t s h o u l d n o t b e u s e d to d i r e c t t h e a p p r o p r i a t e evaluation of a pregnancy-associated p u l m o n a r y embolism.
REFERENCES
1. Atrash HK, Koonin LM, Lawson HW, Franks AL, Smith JC. Maternal mortality in the United States, 1979-1986. Obstet Gynecol 1990;76:1055-60. 2. Report on confidential enquiries into maternal deaths in England and Wales 1986-1988. London: Her Majesty's Stationery Office; 1991. 3. H6gberg U, Innala E, Sandstr6m A. Maternal mortality in Sweden. Obstet Gynecol 1994;84:240-4. 4. Barritt DW,Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960;1:309-12. 5. Dantzker DR, Bower JS. Alteradons in gas exchange following pulmonary thromboembolism. Chest 1982;81:495-501. 6. Huet Y, Lemaire F, Brun-Buisson C, Knaus WA, Teisseire B, Payen D, et al. Hypoxemia in acute pulmonary embolism. Chest 1985;88:829-36. 7. Szucs MMJr, Brooks HL, Grossman W, BanasJSJr, Meister G, Dexter L, et al. Diagnostic sensitivity of laboratory findings in acute pulmonary embolism. Ann Intern Med 1971;74:161-6. 8. Overton DT, Bocka J. The alveolar-arterial oxygen gradient in patients with documented pulmonary embolism. Arch Intern Med 1988;148:161%9.
Institution
Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital University Hospital University Hospital University Hospital University Hospital University Hospital University Hospital University Hospital University Hospital
9. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990;263:2753-9. 10. Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson BT, et al. Clinical, laboratory, roentgenographic and electroradiographic findings in patients with acute pulmonary embolism and no preexisting cardiac or pulmonary disease. Chest 1991;100:598-603. 11. Stein PD, Goldhaber SZ, HenryJW. Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism. Chest 1995;107:139-43. 12. McFarlane MJ, Imperiale TE Use of the alveolar-arterial oxygen gradient in tile diagnosis of pulmonary embolism. Am J Med 1994;96:57-62. 13. Mellemgaard K. The alveolar-arterial oxygen difference: its size and components in normal man. Acta Physiol Scand 1966;67:10-20. 14. Harris EA, Kenyon AM, Nisbet HD, Seelye ER, Whitlock RM. The normal alveolar-arterial oxygen-tension gradient in man. Clin Sci Mol Med 1974;46:89-104. 15. Filley GE Gregoire E Wright GW. Alveolar and arterial oxygen tensions and the significance of the alveolar-arterial oxygen tensions and the significance of the alveolar-arterial oxygen tension difference in normal men.J Clin Invest 1954;33:51%29. 16. Andersen GJ, James GB, Mathers NP, Smith EL, WalkerJ. The maternal oxygen tension and acid-base status during pregnancy. J Obstet Gynaecol Br Commonw 1969;76:16-9. 17. Awe RJ, Nicotra MB, Newsom TD, Viles R. Arterial oxygenation and alveolar-arterial gradients in term pregnancy. Obstet Gynecol 1979;53:182-6. 18. Bentur Y. Ionizing and nonionizing radiation in pregnancy. In: Gideon K, editor. Maternal-fetal toxicology: a clinicians' guide. NewYork: Marcel Dekker; 1990. p. 205-54.
Key words: Blood gases, pulmonary embolism, pregnancy, alveolar-arterial oxygen gradient
Pulmonary embolism is a leading cause of maternal mortality in the Western world. It remains the leading cause of death after a live birth in the United States, 1 and it accounts for the largest number of maternal deaths in Wales, England, and Sweden.Z, 3 Untreated p u l m o n a r y embolism carries a 26% mortality rate. 4 The evaluation of patients with suspected pulmonary embolism is made difficult by the absence of a sensitive, specific, and practical diagnostic test. Investigators have explored numerous diagnostic tests and procedures by which clinicians can try to identify pulmonary embolism without resorting to the "gold standard" of pulmonary angiography. One such widely used tool is the alveolar-arterial oxygen gradient, which is a calculation of the difference between oxygen concentration in the alveoli and in the arterial blood. A normal disparity exists between alveolar and arterial blood oxygen tension because of physiologic ventilation-perfusion mismatching and a small physiologic degree of right-to-left pulmonary shunting. This disparity between alveolar and arterial oxygen is usually exaggerated by acute pulFrom the Division of Obstetric and Consultative Medicine, Department of Medicine, Women and Infants Hospital of Rhode Island and Brown University School of Medicine. Receivedfor publication December26, 1996; revisedJuly 10, 1997; acceptedJuly 23, 1997. Reprint requests: Raymond O. Powrie, M1), Women and Infants Hospital, 101 Dudley St., Providence, RI 02905-2401. Copyright 9 1998 by Mosby, Inc. 0002-9378/98 $5.00 + 0 6/1/84990 394
m o n a r y embolism both because acute p u l m o n a r y embolism increases ventilation-perfusion mismatching and also because it causes increased shunting. 5, 6 Because pulmonary embolism usually decreases perfusion and thus increases mismatching and shunting, the alveolar-arterial gradient has been advocated by many to be a simple and sensitive screening test to rule out pulm o n a r y embolism. 7 In 1988 Overton a n d Bocka 8 reviewed the alveolar-arterial gradient of 64 patients with positive pulmonary arteriograms and found only 4.7% of them h a d n o r m a l alveolar-arterial gradients. Initial Prospective Investigation of P u l m o n a r y Embolism Diagnosis9 data in 1990 (and a subsequent expanded review of the Prospective Investigation o f P u l m o n a r y Embolism Diagnosis database in 1995 by Stein et al. 10, 11) challenged this finding by showing that a normal alveolar-arterial gradient (defined by the authors as <20 m m Hg) was present in 11% to 14% of patients with acute pulmonary embolism and no preexisting cardiovascular or pulmonary disease. However, in 1994, McFarlane and Imperiale 12 published data showing that only 1.9% of pat e n t s with acute pulmonary embolism had normal alveolar-arterial gradients and reasserted that the diagnosis of pulmonary embolism is unlikely in the setting of a normal alveolar-arterial gradient. Regardless of which data are given the most scientific credence, in practice many clinicians still use a normal alveolar-arterial gradient as justification for not further investigating the possibility of pulmonary embolism.
Volume 178, Number 2 AmJ Obstet Gynecol
Our study was designed to answer the question of what the c o m b i n e d experience of Women and Infants Hospital of Rhode Island, in Providence, Rhode Island, and University Hospital of Denver, Colorado, has been regarding the alveolar-arterial gradient of p r e g n a n t women with acute pulmonary embolism. It was our hypothesis that the incidence of a normal alveolar-arterial gradient in pregnant patients with acute pulmonary embolism would be higher than McFarlane's 1.9% and may even be higher than Stein's 14%.
Material and methods All ventilation'-perfusion scans and p u l m o n a r y angiograms performed between J a n u a r y 1990 a n d December 1995 at Women a n d Infants Hospital (Providence) a n d University Hospital (Denver) were identified. Each of these was reviewed to identify all women between the ages of 15 and 45 years with highprobability ventilation-perfusion scans or positive pulmonary angiograms. Charts were then obtained and reviewed on all these women to identify which were either p r e g n a n t or within 8 weeks post partum. Because Women and Infants Hospital of Rhode Island is a major obstetric referral center, the additional measure of reviewing all charts with a discharge diagnosis of pulmonary embolism was carried out at this hospital to identify any patients who may have had lung scans at referring centers and were subsequently sent to this institution. Eighteen pregnant or postpartum patients with high-probability ventilation-perfusion scans or positive p u l m o n a r y angiograms were identified. Seventeen of these patients had undergone arterial blood gas determinations on room air immediately before their scans were obtained. The alveolar-arterial gradient was calculated by the following standard formula: A-a = [ (PB - PH2o) (Fi~ - (Paco2) (1.25)] - Pao 2. PB (mean barometric pressure) = 628 in Denver, 760 m m Hg in Providence. PH2o = 47 m m Hg. Fio 2 = 0.21. Paco 2 and Pao 2 were measured with room air arterial blood gas. An abnormal alveolar-arterial gradient was defined for our population as >15 m m Hg after a review of the literature on normal values of alveolar-arterial gradient. 13-15
Results Seventeen patients were identified with either highprobability ventilation-perfusion scans or positive pulmonary angiograms who were pregnant or within the 8week-postpartum period and had blood for arterial blood gas values drawn on room air. Of the 17 patients, 10 (58%) had alveolar-arterial gradients <15 m m Hg (Table I).
Comment A n o r m a l alveolar-arterial gradient was present in more than half the pregnant women we studied who had
P0wrie et al. 395
acute pulmonary embolism. This is in marked contrast to the findings in the literature regarding n o n p r e g n a n t patients, in whom a small minority of patients with docum e n t e d p u l m o n a r y embolism have n o r m a l alveolararterial gradients. Therefore normal values of an alveolar-arterial gradient do not exclude the diagnosis of acute pulmonary embolism in pregnant patients. In fact, the use of the alveolar-arterial gradient by physicians to "rule out" the diagnosis of pulmonary embolism in pregnancy could result in a significant n u m b e r of pregnant women with untreated pulmonary emboli and may contribute to the maternal deaths seen in this condition. This conclusion is consistent with that made by the original Prospective Investigation of P u l m o n a r y Embolism Diagnosis study researchers; however, it is not often consistent with current practice. Although the numbers in our study were not large, the high percentage of women with n o r m a l alveolar-arterial gradients would suggest that many pregnant women could go untreated for this life-threatening condition if a normal alveolar-arterial gradient is used to rule out the diagnosis of acute pulmonary embolism. O u r sample size makes it difficult to d e t e r m i n e whether pregnant women are truly more likely to have a n o r m a l alveolar-arterial gradient than n o n p r e g n a n t women without cardiopulmonary disease. However, the nearly fourfold difference in our percentages, compared with Stein's, certainly is suggestive that a true difference exists (95% confidence interval 0.3292 to 0.8155). Reasons why pregnant women might have a greater incidence of normal alveolar-arterial gradients in the setting of acute p u l m o n a r y embolism than n o n p r e g n a n t women is a topic for further research. Clearly, the elevated minute ventilation of pregnant patients is not an adequate explanation because previous research indicates that normal pregnancy is not associated with a lowering of the alveolar-arterial gradient. 16, 17 The possibility that pregnant women with acute pulmonary embolism have lower alveolar-arterial gradients than n o n p r e g n a n t women may be because of a combination of factors related to the care of pregnant women. Pregnant women with pulmonary embolism may be examined sooner because they are more regularly exposed to medical personnel or they may have been counseled about the increased risk of t h r o m b o e m b o l i s m d u r i n g pregnancy. Because the alveolar-arterial gradient is known to correlate with size and n u m b e r of embolisms, early presentation and treatment in pregnant women may explain our findings. Medical personnel, in turn, may investigate and treat these women earlier because of the general knowledge among physicians that pregnancy is a state at high risk for pulmonary thromboembolic disease. Dyspnea during pregnancy is very common; however, this study suggests that a normal alveolar-arterial gradient cannot be used as reassurance that a pulmonary em-
396 Powrie et al.
February 1998 AmJ Obstet Gynecol
Table I. Age, gestation, a n d alveolar-arterial g r a d i e n t o f 17 patients with pregnancy-associated p u l m o n a r y e m b o l u s
Patient No.
Age (yr)
Gestation (wk)
Pao2 (mm Hg)
Paco2 (mm Hg)
Alveolar-arterial gradient (mm Hg)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
22 30 28 21 37 22 21 24 17 20 23 21 29 31 27 24 29
8 1 wk post partum 15 32 6 18 32 26 10 33 7 13 9 2 days after termination of pregnancy at 21 wk 1 wk post partum 10 7
83 91 84 78 107 76 78 101 97 91 64 57 82 38 77 82 68
39 39 32 33 23 33 33 39 33 25 37 32 29 30 27 28 32
18 10 26 31 14 33 31 0 12 0 12 25 4 47 12 5 14
bolism is n o t the u n d e r l y i n g cause. Given the m i n i m a l rad i a t i o n risk o f a v e n t i l a t i o n - p e r f u s i o n scan ( a p p r o x i mately 0.1 tad)18 a n d t h e l i f e - t h r e a t e n i n g c o n s e q u e n c e s o f u n t r e a t e d p u l m o n a r y e m b o l i s m , the alveolar-arterial g r a d i e n t s h o u l d n o t b e u s e d to d i r e c t t h e a p p r o p r i a t e evaluation of a pregnancy-associated p u l m o n a r y embolism.
REFERENCES
1. Atrash HK, Koonin LM, Lawson HW, Franks AL, Smith JC. Maternal mortality in the United States, 1979-1986. Obstet Gynecol 1990;76:1055-60. 2. Report on confidential enquiries into maternal deaths in England and Wales 1986-1988. London: Her Majesty's Stationery Office; 1991. 3. H6gberg U, Innala E, Sandstr6m A. Maternal mortality in Sweden. Obstet Gynecol 1994;84:240-4. 4. Barritt DW,Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960;1:309-12. 5. Dantzker DR, Bower JS. Alteradons in gas exchange following pulmonary thromboembolism. Chest 1982;81:495-501. 6. Huet Y, Lemaire F, Brun-Buisson C, Knaus WA, Teisseire B, Payen D, et al. Hypoxemia in acute pulmonary embolism. Chest 1985;88:829-36. 7. Szucs MMJr, Brooks HL, Grossman W, BanasJSJr, Meister G, Dexter L, et al. Diagnostic sensitivity of laboratory findings in acute pulmonary embolism. Ann Intern Med 1971;74:161-6. 8. Overton DT, Bocka J. The alveolar-arterial oxygen gradient in patients with documented pulmonary embolism. Arch Intern Med 1988;148:161%9.
Institution
Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital Women and Infants Hospital University Hospital University Hospital University Hospital University Hospital University Hospital University Hospital University Hospital University Hospital
9. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990;263:2753-9. 10. Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson BT, et al. Clinical, laboratory, roentgenographic and electroradiographic findings in patients with acute pulmonary embolism and no preexisting cardiac or pulmonary disease. Chest 1991;100:598-603. 11. Stein PD, Goldhaber SZ, HenryJW. Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism. Chest 1995;107:139-43. 12. McFarlane MJ, Imperiale TE Use of the alveolar-arterial oxygen gradient in tile diagnosis of pulmonary embolism. Am J Med 1994;96:57-62. 13. Mellemgaard K. The alveolar-arterial oxygen difference: its size and components in normal man. Acta Physiol Scand 1966;67:10-20. 14. Harris EA, Kenyon AM, Nisbet HD, Seelye ER, Whitlock RM. The normal alveolar-arterial oxygen-tension gradient in man. Clin Sci Mol Med 1974;46:89-104. 15. Filley GE Gregoire E Wright GW. Alveolar and arterial oxygen tensions and the significance of the alveolar-arterial oxygen tensions and the significance of the alveolar-arterial oxygen tension difference in normal men.J Clin Invest 1954;33:51%29. 16. Andersen GJ, James GB, Mathers NP, Smith EL, WalkerJ. The maternal oxygen tension and acid-base status during pregnancy. J Obstet Gynaecol Br Commonw 1969;76:16-9. 17. Awe RJ, Nicotra MB, Newsom TD, Viles R. Arterial oxygenation and alveolar-arterial gradients in term pregnancy. Obstet Gynecol 1979;53:182-6. 18. Bentur Y. Ionizing and nonionizing radiation in pregnancy. In: Gideon K, editor. Maternal-fetal toxicology: a clinicians' guide. NewYork: Marcel Dekker; 1990. p. 205-54.