Symposium on Pregnancy
Respiratory Disease in Pregnancy Emilio A. Leontic, M.D. *
Pregnancy represents one of the best examples of selective adaptation in terms of respiratory physiology. Alterations in respiratory physiology include not only acid base balance but also modifications of lung physiology based upon hormonal and mechanical changes. In the management of acute and chronic pathologic conditions affecting gestational pulmonary function, the clinician must not only recognize the needs of the maternal organism but also the needs of the fetus, as well as the risks attendant with providing the mother with chemotherapy. This review attempts to outline some of the more important physiologic changes occurring in the respiratory tract during pregnancy and during labor. It also represents an update on the clinical management of several common respiratory tract disorders known to occur in pregnancy. GESTATIONAL RESPIRATORY PHYSIOLOGY Anatomic Changes By the end of the third trimester, the average circumference of the maternal thoracic cage has increased by 5 to 7 cm. This includes both the transverse and anteroposterior diameters. An increase of the substernal angle from 68° to 103.5° is also noted. 6 , 33, 54, 89 These changes compensate for a diminution in the vertical diameter of the thorax which reaches approximately 4 cm because of the upward pressure exerted on the diaphragm and the rib cage by the gravid uterus. 45 ,89 This elevation is associated with a diminished height within the pleural cavities; however, the whole effect is nullified by an increase in the width of the thoracic cage. Capillary engorgement throughout the respiratory tract results in mucosal edema and hyperemia, especially in the nasopharynx and ':'Clinical Fellow, Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland Supported by NIH Grant No, NICHHD lROl HD 08061-01Al
Medical Clinics of North America- Vol. 61, No, 1, January 1977
111
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tracheobronchial tree. 6 , 33 In 75 per cent of all pregnant women, the false vocal cords and arytenoid region of the larynx appear swollen and red, occasionally producing changes in voice and making nasal breathing more difficult especially at term. Nose bleeds are also more frequent, especially when respiratory tract infection occurs concomitantly,9 Lung excursion measured under fluoroscopy appears normal throughout gestation,33,72 Roentgenograms show increased lung markings simulating a mild congestive lung failure; the most probable explanation for this is an increase in the vascular engorgement of the pulmonary tree. 9, 33, 8fJ It would seem appropriate to define the terms that apply to respiration. Vital capacity (VC): The maximal volume of gas that can be expelled from the lungs by forceful effort following a maximal inspiration. Inspiratory capacity (IC): The maximal volume of gas that can be inspired from the resting expiratory level. Expiratory reserve volume (ERV): The maximal volume of gas that can be expired from the resting expiratory level. Functional residual capacity (FRC): The volume of gas remaining in the lungs in the resting expiratory position. Residual volume (RV): The volume of gas remaining in the lungs at the end of a maximal expiration. Total lung capacity (TLC): The maximal amount of gas that can be contained in the lungs when fully expanded. Tidal volume (TV): The volume of air that moves in or out of the nose and mouth with each inspiration or expiration. Minute volume (MV): The volume of air which moves in or out of the nose and mouth per minute (tidal volume x frequency of breathing per minute). Maximal breathing capacity: The maximal volume of gas that can be breathed per minute by voluntary effort.
Pulmonary Ventilation An increased minute ventilation is one of the earliest and most obvious respiratory changes in pregnancy. It is apparent during the first trimester and at term is between 48 to 57 per cent above the normal nonpregnant level. 11, 20, 54, 68, 74 This change is the result of a progressive rise in tidal volume throughout gestation which reaches as much as 25 to 40 per cent above the nonpregnant level,2°' 54, 68, 71 These changes are accompanied by a slight increase in the respiratory rate and an increase in the alveolar ventilation at term of about 70 per cent,fJ, 11, 20, 68 as shown in Figure 1. Oxygen utilization, as indicated by the basal metabolic rate, remains unchanged until the second month, but rises progressively thereafter, reaching a peak at term, Oxygen consumption increases about 20 per cent and basal metabolic rate about 15 to 20 per cent. 3 , 9 The elevation in basal metabolic rate can probably be accounted for by the addition of fetal and placental metabolism, The 50 per cent increase in minute ventilation as well as the increase in oxygen consumption and basal met-
113
RESPIRATORY DISEASE IN PREGNANCY
70 60 50 Figure 1. Changes in respiratory parameters during pregnancy. The curves for rate, tidal volume, and minute ventilation were developed from data of Cugell et al.'o
10 O~~r-'--~-r-,~~~--r+-r~~
04567
8
Months of Pregnancy
9
~
6 months post parIum
abolic rate results in an elevation of the ventilation equivalent (ventilation expressed as liters of air required for each 100 ml of oxygen consumed)9 (Figure 2). Oxygen uptake increases in order to compensate the higher oxygen consumption. As a result of the augmented minute volume, the rate of carbon dioxide expired increases and thus plasma carbon dioxide is diminished. g • 11 Plasma pH remains normal because of a compensatory loss of bicarbonate into the urine. 60. 71 Studies have shown that the maximum breathing capacity, timed vital capacity, and air velocity index remain within normallimits.9 ,11 On the other hand, the functional residual capacity is decreased at term by 17 to 20 per cent as compared to the nonpregnant female. 9 ,11,2o This is brought about by a decrease in the expiratory reserve volume of about 150 cc and the residual volume of about 200 cc at term. 14 • 20 ,74,95 The reduction in functional residual capacity is principally a result of the elevation of the diaphragm and, to a lesser degree, an increase in the pulmonary blood volume.9.13 Under conditions of obesity, re cum-
Figure 2. Per cent change of minute ventilation, oxygen uptake, basal metabolism and the ventilation equivalent for oxygen at monthly intervals throughout pregnancy. (Redrawn from Prowse, C. M., and Gaensler, E. A.: Anesthesiology 26:381, 1965).
50
50
40
40
~ 30
30
~
~ 20 ~
~ 10
et o
80so1 metabolism
o
-10 -L-.---.-__.--.-__.---.---,.---.--+ -10 5 6 7 8 9 234 Months of Pregnancy
114
EMILIO
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bency, or labor, a further reduction in functional residual capacity and expiratory reserve volume is noted. 9 • 17 The volumetric loss of expiratory reserve is compensated for by a corresponding increase in the inspiratory capacity and inspiratory reserve volume. 20 . 54. 60. 71 Consequently, the vital capacity remains essentially unchanged. However, Cugell has reported that the total lung capacity is diminished by 4 per cent at term, since the smaller residual volume and expiratory reserve volume are not quite compensated for by an increase in the inspiratory capacity.20 Changes found by different investigators in pulmonary volumes during pregnancy, labor, and the postpartum period are summarized in Figure 3. Vital capacity remains relatively stable throughout pregnancy.2. 20. 40. 54.71. 74,Rf! Therefore, a decrease in vital capacity measured on a serial basis might be of value in the early detection of pulmonary congestion. It is important to point out that there are discrepancies in the data available on gestational pulmonary physiology, especially in the case of vital capacity, but these may be due to technical differences in measuring techniques and the timing of measurements,9, 40 Similar inconsistencies exist with respect to airway resistance and transpulmonic compliance. 44 • 54. 74 There are a number of changes occurring during pregnancy which would tend to increase the total pulmonary resistance. Included among these is the upward displacement of the diaphragm causing compression of the basal lung tissue and increased angulation of the bronchi. Restriction of the downward movement of the diaphragm and an increase in pulmonary blood volume can also affect resistance. This increase in pulmonary resistance would account for the decrease in functional residual capacity. On the other hand, two changes would account for a decrease in pulmonary resistance: (1) smooth muscle relaxation of the tracheobronchial tree which would permit an easier flow of air, and (2) the hyperventilation which would increase complianceY The lessened resistance to air flow would tend to offset the increased breathing effort caused by the physical
InspLtory reser ...e volume
2050
"" ''>"
" .~ ~
~
i}
\..)
'" ~ ~
-.J
)2 ~
2050
""~
Inspiratory capacity
2500
",,, "~~ ,:::~~
'"
Inspiratory copaclty
2650
'0
~
iN
Figure 3. Pulmonary volumes and capacities during pregnancy, labor, and pos tpartum period.
~
\N
Ex.plratory
reserve volume
7~O
Functional
residual
ResLua' volume lOrD
COpoclty
1700
I
Nonpregnant
,
Residual
i i
Elevotlon of diaphragm
Gravida at Term
t
RESPIRATORY DISEASE IN PREGNANCY
115
handicaps of late pregnancy. The cause of this relaxation still remains obscure. Neither estrogens nor gonadotropic hormones seem to be responsible. Progesterone, corticosteroids, and relaxin have been thought to play a role. 30 , 74 Many factors may account for hyperventilation during pregnancy. It is apparent that local changes of the lungs, such as augmented dead space, unsatisfactory intrapulmonary distribution of gases, defective diffusion across the alveolocapillary membrane, or a combination of these are conditions not usually found during pregnancy.13, 20, 48 The repeated findings of a low plasma and alveolar CO 2 content and combining power, an increased concentration of hydrogen ions, and a reduced alkaline reserve resulting from a diminution of fixed base and equal reduction of anion content of the plasma have led to the conclusion that hyperpnea is due to central stimulation. 20 There is some evidence that hyperventilation during pregnancy may be due to an altered threshold of the respiratory center. Progesterone is the only hormone that seemingly affects the respiratory cent er by lowering the threshold and acting as a mild respiratory stimulant. The result is a mild hyperventilation with resulting diminished CO 2 tension.71
Dyspnea Dyspnea is perhaps the single most common complaint associated with the respiratory tract during the first 28 weeks of gestation. As many as 60 to 70 per cent of pregnant women complain of mild dyspnea without interference with physical activity.9, 28, 71 Although altered respiratory sensitivity might explain the symptoms of dyspnea, psychological, environmental, and sociological factors may play a major role in this complaint. 20 Cugell et apo suggest that dyspnea at rest is not seen until the resting breathing reserve is less than 60 to 70 per cent; however, in pregnancy an adequate breathing reserve is maintained throughout and the walking index never reaches the level of 35 per cent.20
Respiration and Labor During the first stage of labor, which involves cervical dilatation, anxiety and the pain of contraction cause an increase in respiration. Alveolar ventilation is also increased but a reduction in the functional residual capacity caused by a redistribution of uterine blood flow into the central venous pool results in decreased dilution of the inspired air within the alveolus.1O With descent of the presenting fetal part, as in the second stage of labor, the relative increase in the intensity and frequency of uterine contractions combined with the urge to bear down, bring about further alterations in respiratory functions. 72 A decrease in oxygen saturation has been observed during labor with a full recovery 24 hours following delivery2 (as shown in Figure 4). Decreased oxygen saturation occurring during a uterine contraction is as transient as the contraction itself.22 ,72 Fetal hypoxia is known to occur when the maternal Pco z falls below
116
EMILIO
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99 98
Respiratory Disease in Pregnancy Emilio A. Leontic, M.D. *
Pregnancy represents one of the best examples of selective adaptation in terms of respiratory physiology. Alterations in respiratory physiology include not only acid base balance but also modifications of lung physiology based upon hormonal and mechanical changes. In the management of acute and chronic pathologic conditions affecting gestational pulmonary function, the clinician must not only recognize the needs of the maternal organism but also the needs of the fetus, as well as the risks attendant with providing the mother with chemotherapy. This review attempts to outline some of the more important physiologic changes occurring in the respiratory tract during pregnancy and during labor. It also represents an update on the clinical management of several common respiratory tract disorders known to occur in pregnancy. GESTATIONAL RESPIRATORY PHYSIOLOGY Anatomic Changes By the end of the third trimester, the average circumference of the maternal thoracic cage has increased by 5 to 7 cm. This includes both the transverse and anteroposterior diameters. An increase of the substernal angle from 68° to 103.5° is also noted. 6 , 33, 54, 89 These changes compensate for a diminution in the vertical diameter of the thorax which reaches approximately 4 cm because of the upward pressure exerted on the diaphragm and the rib cage by the gravid uterus. 45 ,89 This elevation is associated with a diminished height within the pleural cavities; however, the whole effect is nullified by an increase in the width of the thoracic cage. Capillary engorgement throughout the respiratory tract results in mucosal edema and hyperemia, especially in the nasopharynx and ':'Clinical Fellow, Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland Supported by NIH Grant No, NICHHD lROl HD 08061-01Al
Medical Clinics of North America- Vol. 61, No, 1, January 1977
111
112
EMILIO
A.
LEONTIC
tracheobronchial tree. 6 , 33 In 75 per cent of all pregnant women, the false vocal cords and arytenoid region of the larynx appear swollen and red, occasionally producing changes in voice and making nasal breathing more difficult especially at term. Nose bleeds are also more frequent, especially when respiratory tract infection occurs concomitantly,9 Lung excursion measured under fluoroscopy appears normal throughout gestation,33,72 Roentgenograms show increased lung markings simulating a mild congestive lung failure; the most probable explanation for this is an increase in the vascular engorgement of the pulmonary tree. 9, 33, 8fJ It would seem appropriate to define the terms that apply to respiration. Vital capacity (VC): The maximal volume of gas that can be expelled from the lungs by forceful effort following a maximal inspiration. Inspiratory capacity (IC): The maximal volume of gas that can be inspired from the resting expiratory level. Expiratory reserve volume (ERV): The maximal volume of gas that can be expired from the resting expiratory level. Functional residual capacity (FRC): The volume of gas remaining in the lungs in the resting expiratory position. Residual volume (RV): The volume of gas remaining in the lungs at the end of a maximal expiration. Total lung capacity (TLC): The maximal amount of gas that can be contained in the lungs when fully expanded. Tidal volume (TV): The volume of air that moves in or out of the nose and mouth with each inspiration or expiration. Minute volume (MV): The volume of air which moves in or out of the nose and mouth per minute (tidal volume x frequency of breathing per minute). Maximal breathing capacity: The maximal volume of gas that can be breathed per minute by voluntary effort.
Pulmonary Ventilation An increased minute ventilation is one of the earliest and most obvious respiratory changes in pregnancy. It is apparent during the first trimester and at term is between 48 to 57 per cent above the normal nonpregnant level. 11, 20, 54, 68, 74 This change is the result of a progressive rise in tidal volume throughout gestation which reaches as much as 25 to 40 per cent above the nonpregnant level,2°' 54, 68, 71 These changes are accompanied by a slight increase in the respiratory rate and an increase in the alveolar ventilation at term of about 70 per cent,fJ, 11, 20, 68 as shown in Figure 1. Oxygen utilization, as indicated by the basal metabolic rate, remains unchanged until the second month, but rises progressively thereafter, reaching a peak at term, Oxygen consumption increases about 20 per cent and basal metabolic rate about 15 to 20 per cent. 3 , 9 The elevation in basal metabolic rate can probably be accounted for by the addition of fetal and placental metabolism, The 50 per cent increase in minute ventilation as well as the increase in oxygen consumption and basal met-
113
RESPIRATORY DISEASE IN PREGNANCY
70 60 50 Figure 1. Changes in respiratory parameters during pregnancy. The curves for rate, tidal volume, and minute ventilation were developed from data of Cugell et al.'o
10 O~~r-'--~-r-,~~~--r+-r~~
04567
8
Months of Pregnancy
9
~
6 months post parIum
abolic rate results in an elevation of the ventilation equivalent (ventilation expressed as liters of air required for each 100 ml of oxygen consumed)9 (Figure 2). Oxygen uptake increases in order to compensate the higher oxygen consumption. As a result of the augmented minute volume, the rate of carbon dioxide expired increases and thus plasma carbon dioxide is diminished. g • 11 Plasma pH remains normal because of a compensatory loss of bicarbonate into the urine. 60. 71 Studies have shown that the maximum breathing capacity, timed vital capacity, and air velocity index remain within normallimits.9 ,11 On the other hand, the functional residual capacity is decreased at term by 17 to 20 per cent as compared to the nonpregnant female. 9 ,11,2o This is brought about by a decrease in the expiratory reserve volume of about 150 cc and the residual volume of about 200 cc at term. 14 • 20 ,74,95 The reduction in functional residual capacity is principally a result of the elevation of the diaphragm and, to a lesser degree, an increase in the pulmonary blood volume.9.13 Under conditions of obesity, re cum-
Figure 2. Per cent change of minute ventilation, oxygen uptake, basal metabolism and the ventilation equivalent for oxygen at monthly intervals throughout pregnancy. (Redrawn from Prowse, C. M., and Gaensler, E. A.: Anesthesiology 26:381, 1965).
50
50
40
40
~ 30
30
~
~ 20 ~
~ 10
et o
80so1 metabolism
o
-10 -L-.---.-__.--.-__.---.---,.---.--+ -10 5 6 7 8 9 234 Months of Pregnancy
114
EMILIO
A.
LEONTIC
bency, or labor, a further reduction in functional residual capacity and expiratory reserve volume is noted. 9 • 17 The volumetric loss of expiratory reserve is compensated for by a corresponding increase in the inspiratory capacity and inspiratory reserve volume. 20 . 54. 60. 71 Consequently, the vital capacity remains essentially unchanged. However, Cugell has reported that the total lung capacity is diminished by 4 per cent at term, since the smaller residual volume and expiratory reserve volume are not quite compensated for by an increase in the inspiratory capacity.20 Changes found by different investigators in pulmonary volumes during pregnancy, labor, and the postpartum period are summarized in Figure 3. Vital capacity remains relatively stable throughout pregnancy.2. 20. 40. 54.71. 74,Rf! Therefore, a decrease in vital capacity measured on a serial basis might be of value in the early detection of pulmonary congestion. It is important to point out that there are discrepancies in the data available on gestational pulmonary physiology, especially in the case of vital capacity, but these may be due to technical differences in measuring techniques and the timing of measurements,9, 40 Similar inconsistencies exist with respect to airway resistance and transpulmonic compliance. 44 • 54. 74 There are a number of changes occurring during pregnancy which would tend to increase the total pulmonary resistance. Included among these is the upward displacement of the diaphragm causing compression of the basal lung tissue and increased angulation of the bronchi. Restriction of the downward movement of the diaphragm and an increase in pulmonary blood volume can also affect resistance. This increase in pulmonary resistance would account for the decrease in functional residual capacity. On the other hand, two changes would account for a decrease in pulmonary resistance: (1) smooth muscle relaxation of the tracheobronchial tree which would permit an easier flow of air, and (2) the hyperventilation which would increase complianceY The lessened resistance to air flow would tend to offset the increased breathing effort caused by the physical
InspLtory reser ...e volume
2050
"" ''>"
" .~ ~
~
i}
\..)
'" ~ ~
-.J
)2 ~
2050
""~
Inspiratory capacity
2500
",,, "~~ ,:::~~
'"
Inspiratory copaclty
2650
'0
~
iN
Figure 3. Pulmonary volumes and capacities during pregnancy, labor, and pos tpartum period.
~
\N
Ex.plratory
reserve volume
7~O
Functional
residual
ResLua' volume lOrD
COpoclty
1700
I
Nonpregnant
,
Residual
i i
Elevotlon of diaphragm
Gravida at Term
t
RESPIRATORY DISEASE IN PREGNANCY
115
handicaps of late pregnancy. The cause of this relaxation still remains obscure. Neither estrogens nor gonadotropic hormones seem to be responsible. Progesterone, corticosteroids, and relaxin have been thought to play a role. 30 , 74 Many factors may account for hyperventilation during pregnancy. It is apparent that local changes of the lungs, such as augmented dead space, unsatisfactory intrapulmonary distribution of gases, defective diffusion across the alveolocapillary membrane, or a combination of these are conditions not usually found during pregnancy.13, 20, 48 The repeated findings of a low plasma and alveolar CO 2 content and combining power, an increased concentration of hydrogen ions, and a reduced alkaline reserve resulting from a diminution of fixed base and equal reduction of anion content of the plasma have led to the conclusion that hyperpnea is due to central stimulation. 20 There is some evidence that hyperventilation during pregnancy may be due to an altered threshold of the respiratory center. Progesterone is the only hormone that seemingly affects the respiratory cent er by lowering the threshold and acting as a mild respiratory stimulant. The result is a mild hyperventilation with resulting diminished CO 2 tension.71
Dyspnea Dyspnea is perhaps the single most common complaint associated with the respiratory tract during the first 28 weeks of gestation. As many as 60 to 70 per cent of pregnant women complain of mild dyspnea without interference with physical activity.9, 28, 71 Although altered respiratory sensitivity might explain the symptoms of dyspnea, psychological, environmental, and sociological factors may play a major role in this complaint. 20 Cugell et apo suggest that dyspnea at rest is not seen until the resting breathing reserve is less than 60 to 70 per cent; however, in pregnancy an adequate breathing reserve is maintained throughout and the walking index never reaches the level of 35 per cent.20
Respiration and Labor During the first stage of labor, which involves cervical dilatation, anxiety and the pain of contraction cause an increase in respiration. Alveolar ventilation is also increased but a reduction in the functional residual capacity caused by a redistribution of uterine blood flow into the central venous pool results in decreased dilution of the inspired air within the alveolus.1O With descent of the presenting fetal part, as in the second stage of labor, the relative increase in the intensity and frequency of uterine contractions combined with the urge to bear down, bring about further alterations in respiratory functions. 72 A decrease in oxygen saturation has been observed during labor with a full recovery 24 hours following delivery2 (as shown in Figure 4). Decreased oxygen saturation occurring during a uterine contraction is as transient as the contraction itself.22 ,72 Fetal hypoxia is known to occur when the maternal Pco z falls below
116
EMILIO
A.
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99 98
