cambios respiratorios
TRANSCRIPT
-
7/29/2019 cambios respiratorios
1/12
Respiratory Physiologic Changes in Pregnancy
Robert A. Wise, MDT, Albert J. Polito, MD,Vidya Krishnan, MD, MHS
Department of Medicine (Pulmonary and Critical Care Medicine),
Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle,
Baltimore, MD 21224, USA
This article reviews the respiratory functional changes that accompany preg-
nancy. Pregnancy is associated with enormous hormonal, circulatory, and mechani-
cal alterations. The pregnant state is accompanied by increases in progesterone
and estrogen with vascular and central nervous system effects, alterations in the
balance of bronchoconstrictor and bronchodilator prostanoids, and increased
levels of peptide hormones that alter connective tissue characteristics. Cardiac out-
put and pulmonary blood flow are increased because of the metabolic demands
of the products of conception, the increase in blood volume, and the decrease in
hemoglobin concentration. The plasma oncotic pressure is decreased because of
the increase in blood volume and decrease in albumin concentration. The com-
bination of increased pulmonary blood flow, increased pulmonary capillary blood
volume, and decreased oncotic pressure all promote the formation of edema in the
periphery and in the lung. The course of pregnancy is accompanied by structural
changes to the ribcage and abdominal compartments as a consequence of the
hormonal changes and the enlarged uterus. Given the dramatic physical and hor-
monal alterations of pregnancy, perhaps the most remarkable aspect of respiratory
physiology is the minor impact that pregnancy has on the function of the lung.
Over the years, there have been several excellent reviews of the effects of preg-
nancy on the respiratory system in health and disease. [15]. This article is an
update of a previous paper that appeared in this journal in 2000 [6].
0889-8561/06/$ see front matterD 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.iac.2005.10.004 immunology.theclinics.com
Portions of this article were previously published in Wise RA, Polito AJ. Respiratory physiologic
changes in pregnancy. Immunol Allergy Clin North Am 2000;20(4):66372.
T Corresponding author.
E-mail address: [email protected] (R.A. Wise).
Immunol Allergy Clin N Am
26 (2006) 112
http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
2/12
Effect of pregnancy on ventilation and gas exchange
Resting minute ventilation increases during pregnancy [79]. This is primarilydue to an increase in tidal volume with a constant breathing rate and pattern.
Because the dead space/tidal volume ratio remains normal during pregnancy, the
increased tidal volume leads to increased alveolar ventilation [10]. Most studies
find that this hyperventilation occurs early in pregnancy during the first trimester,
and stays constant or increases slightly as pregnancy progresses [11]. Typically,
resting minute ventilation is increased about 30% during pregnancy compared
with the postpartum value. In part, the increase in minute ventilation is caused by
an increase in metabolic rate and carbon dioxide (CO2) production. During
pregnancy, CO2 production at rest increases by about 30% to 300 mL/minute.The increase in minute ventilation exceeds that which is required to maintain
a normal arterial carbon dioxide level. As a result, the Paco2 decreases from
40 mm Hg in the nonpregnant state to 32 to 34 mm Hg in pregnancy [12]. The
kidney excretes excess bicarbonate to compensate for the respiratory alkalosis,
and maintains a serum bicarbonate level of about 15 to 20 mEq/L to preserve
a normal arterial pH. The respiratory alkalosis causes a rightward shift in the
oxyhemoglobin dissociation curve that favors the unloading of oxygen in the
periphery, and presumably aids oxygen transfer across the placenta [13].
There is general agreement that the main cause of the increased respiratorydrive that causes the hyperpnea of pregnancy is the elevation of serum pro-
gesterone, a direct respiratory stimulant. The progesterone-induced increase in
chemosensitivity results in an increase in the slope and a leftward shift of the
CO2 ventilatory response curve. The increase in chemosensitivity occurs early in
pregnancy and remains constant up until delivery. The respiratory center output,
which integrates chemical and mechanical stimuli, is measured by the mouth
pressure 100 milliseconds after airway occlusion. This measure increases
progressively throughout pregnancy, and is compatible with the idea that the
hyperpnea of pregnancy is the result of increased chemosensitivity and the loadimposed by the gravid uterus. Shortly after delivery, the respiratory drive returns
to normal with the decrease in progesterone levels and the reduction in metabolic
and mechanical loads that were induced by pregnancy.
The evidence that progesterone is a respiratory stimulant is strong [14]. When
progesterone is administered to nonpregnant individuals, it increases minute
ventilation, CO2 chemosensitivity, and airway occlusion pressure [1517]. It has
been debated whether progesterone acts through a direct stimulatory effect on
the respiratory center or through an increase in the gain of the chemoreceptors
[18]. The most recent evidence shows that the threshold for hypercapnic venti-lation and the gain in ventilation is increased in pregnancy, which suggests that
intrinsic and chemically driven responses are more sensitive in the pregnant
hormonal milieu [19].
The hypoxic ventilatory response is increased in pregnancy to about twice
the normal level [20]. This occurs despite the blood and cerebrospinal fluid
alkalosis that tends to suppress hypoxic drive. In contrast to the response to
wise et al2
http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
3/12
CO2, the hypoxic ventilatory response in pregnancy does not correlate well with
progesterone levels. It is believed that the increased sensitivity to hypoxia is due
to the increases in estrogen and progesterone [21,22].Arterial oxygen tensions are increased slightly in pregnancy as a result of the
pregnancy-induced hyperpnea, with a normal pregnant level of 100 to 105 mm Hg
[10]. This higher level of oxygen tension may facilitate oxygen transfer across
the placenta by diffusion; however, the increased metabolic rate and the low
oxygen reservoir in the lung at end expiration make the pregnant woman par-
ticularly susceptible to develop hypoxemia in the presence of respiratory depres-
sion or apnea [23,24]. In some women, the low end-expiratory lung volume may
predispose them to decreasing oxygen tensions in the supine position [25].
The overall effect of pregnancy on the diffusing capacity for carbon mon-oxide (Dco) is determined by the relative contributions of opposing physiologic
changes. Pulmonary blood volume and cardiac output are increased in pregnancy,
which should recruit capillary surface area, and thereby, increase Dco. This is
offset by the dilutional reduction in hemoglobin concentration that occurs, and
leads to a constant or slightly diminished Dco in most pregnant patients [26].
The normal increase in Dco that occurs in the supine position is absent in
pregnancy, which might indicate that the gravid uterus prevents the normal
increase in systemic venous return, or that the pulmonary capillary bed is already
fully recruited [27]. The latter explanation is less plausible because exercisecauses a normal increase in Dco in pregnant women [28]. One study suggests that
there are different effects of pregnancy on Dco in high-altitude dwellers. Pregnant
women who dwell at high altitude have a higher Dco than those who live at sea
level; however, during the third trimester they have a lower Dco than non-
pregnant women who live at high altitude. At sea level, the Dco is similar
throughout pregnancy compared with nonpregnant controls [29].
Physiologic dyspnea of pregnancy
The increase in minute ventilation that accompanies pregnancy often is per-
ceived as shortness of breath. Approximately 75% of pregnant women have
exertional dyspnea by 30 weeks of gestation [3033]. Shortness of breath at rest
or with mild exertion is so common that it often is referred to as physiologic
dyspnea. The proposed causes of dyspnea are the increased drive to breath
and the increased respiratory load. The increase in minute ventilation and the
load that is imposed by the enlarging uterus cause an increase in the work of
breathing. Other factors that are believed to contribute to the sensation of dys-pnea include increased pulmonary blood volume, anemia, and nasal congestion.
Studies of the psycho-physiology of dyspnea in pregnancy indicate that the
dyspnea can be accounted for by the increased effort of breathing, rather than
an increased sensitivity to mechanical loads [34].
The cardiovascular response to endurance exercise in late pregnancy is un-
changed compared with the postpartum state [35]. Similarly, exercise efficiency
respiratory physiologic changes in pregnancy 3
http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
4/12
(change in oxygen consumption per change in work load) is unchanged [36];
however, ventilation at any level of oxygen consumption or CO2 production is
increased in pregnancy, which leads to increased perception of respiratory effort.This excess exercise ventilation and sensation of breathlessness can be reduced
by aerobic training [37].
It can be challenging for a physician to differentiate the normal dyspnea
of pregnancy from that which is due to disease pathology. Findings that raise
the question of pathologic dyspnea include increased respiratory rate greater
than 20 breaths per minute, Paco2 that is less than 30 mm Hg or greater than
35 mm Hg, or abnormal measures on forced expiratory spirometry or cardiac
echocardiography. The time course of symptoms also is helpful in differentiating
pathologic conditions. Abrupt or paroxysmal episodes of dyspnea suggest an ab-normal condition.
Lung and chest wall mechanics in pregnancy
Lung volumes have been measured in several case series of pregnant women,
in comparison with nonpregnant women or with the postpartum state. At term,
helium dilution lung volumes may underestimate the true lung volume by 0.2 to0.5 L because the low end-expiratory lung volume may impinge upon the closing
volume, and thereby, prevent equilibration with the helium. If accurate measures
of lung volume are required in term pregnancy, then body plethysmography is the
preferred technique [38]. The consensus of many studies is that lung volumes
mostly are well preserved in pregnancy. The total lung capacity usually is pre-
served or is decreased minimally. The residual volume tends to decrease slightly,
which leads to a small increase or stability of the vital capacity [3946]. The most
consistent change in static lung volumes with pregnancy is the reduction in
functional residual capacity (FRC) and the expiratory reserve volume. As theuterus enlarges, FRC decreases by 10% to 25% of the previous value, starting
about the twelfth week of pregnancy [39]. The normal reduction in FRC in the
supine position is accentuated further in pregnancy [47,48]. The reduction in
FRC is due to a decrease in chest wall compliance, which decreases about 35%
to 40% [49]. The lung compliance remains normal during pregnancy, whereas
expiratory muscle strength is in the low-normal range [40].
The decreased chest wall compliance is the result of the enlarging uterus in-
creasing the abdominal pressure, because the reduction in FRC is correlated with
the increase in end-expiratory abdominal pressure, but not end-expiratory pleuralpressure [50]. The diaphragm elevates about 4 cm and the circumference of the
lower rib cage increases about 5 cm [41]. The lower end-expiratory lung volume
leads to an increased area of apposition of the diaphragm to the chest wall, which
improves the coupling of the diaphragm and chest wall [51]. Thus, the increased
tidal volume of pregnancy is achieved without an increase in the respiratory
excursions of the diaphragm.
wise et al4
http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
5/12
The rib cage undergoes structural changes during pregnancy from the changes
in the hormonal milieu [52]. Progressive relaxation of the ligamentous attach-
ments of the ribs causes the subcostal angle of the rib cage to increase from 688
to1038 early in pregnancy, before the uterus is enlarged substantially. This change
persists for months after the end of pregnancy when the uterus returns to nor-
mal size. The increased elasticity of the rib cage probably is the result of the
same factors that induce changes in the elastic properties of the pelvis. One of
the important mediators is believed to be the polypeptide hormone, relaxin, which
is increased during pregnancy. This substance is responsible for the softening of
the cervix and the relaxation of the pelvic ligaments [53,54].
Airflow mechanics
Forced expiratory spirometry is useful to follow patients who have asthma.
Therefore, it is important that clinicians understand that pregnancy has no
significant effect on the forced expiratory volume in 1 second (FEV1) or the
FEV1/forced vital capacity (FVC) ratio [26,55,56]. Peak expiratory flow rates
have been reported to remain close to the normal range and be unchanged during
pregnancy [57]. A more recent study described a small, but statistically sig-nificant, decrease in peak expiratory flow rates with advancing pregnancy,
especially in the supine position [58]. The shape of the flow-volume curve and
absolute flow rates at low lung volumes are normal in pregnant women [27].
Thus, it is possible to use nonpregnant reference values to evaluate lung function
in pregnant women. A reduction in FEV1 or FVC should not be attributed to
pregnancy alone. Measurement of airway conductance by several methods
demonstrates normal or increased large airway conductance [40,55]. A recent
epidemiologic study raised the possibility that pregnancy may induce changes in
the lung that improve airway function and persist throughout life [59]. Smallairway function, as measured by closing volume, is normal [6062]; however,
because the FRC is low, airways may close during tidal breathing and increase
the alveolararterial oxygen gradient in the supine position.
Sleep and pregnancy
Sleep disturbances are common during pregnancy as the result of bio-chemical and physical changes. The American Academy of Sleep Medicine
defines a clinical entity of pregnancy-associated sleep disorder as the occur-
rence of insomnia or excessive sleepiness that develops in the course of preg-
nancy [63].
Estrogen causes alterations in the upper airway, including mucosal edema,
hyperemia, and mucus hypersecretion, which can increase upper airway resis-
respiratory physiologic changes in pregnancy 5
http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
6/12
tance. Progesterone has a strong sedating effect, which may be a teleologic pro-
tection during pregnancy to rest. Cortisol level is increased during pregnancy, and
is associated with clinical depression and its associated sleep changes (increasedrapid eye movement [REM] density and decreased REM latency). Physical
changes in pregnancy, including abdominal distension, fetal movement, bladder
distention, urinary frequency, backache, and heartburn, all contribute to the re-
duced sleep efficiency and increased nocturnal awakenings.
Pregnant women have increased complaints of insomnia and daytime sleepi-
ness. Sleep quality reportedly is worsened in the first and third trimesters, with
frequent nocturnal awakenings. Polysomnography reveals reduced slow wave
and REM phases of sleep, and increased total sleep time and wake after sleep
onset, all of which progress during the course of the pregnancy. Sleep efficiencyalso is reduced, and remains poor up to 3 months post partum [64,65]. Snoring is
common during pregnancy; it occurs in 14% to 23% of pregnant women by the
third trimester, as compared with 4% of nonpregnant, age-matched controls [66].
Of concern is that snoring during pregnancy may be associated with pregnancy-
induced hypertension and intrauterine growth retardation [67].
Sleep disorders may occur more frequently in the gravid female patient. Sleep
disordered breathing, a spectrum of respiratory disorders during sleep, including
obstructive and central sleep apnea, periodic breathing, and nocturnal hypo-
ventilation, is uncommon in otherwise healthy young women, but changes inpregnancy alter the risk of developing sleep disordered breathing. Weight gain
and increased upper airway resistance that are due to estrogen effects may pre-
cipitate or worsen preexisting sleep apnea; increased minute ventilation, prefer-
ence for the lateral sleep posture, and decreased REM sleep time can decrease the
risk of sleep apnea [64]. Restless leg syndrome (RLS), a sensory disorder in
which patients describe an uncontrollable urge to move the legs while in the
recumbent position at night, can disrupt sleep significantly. In one large study
from Japan, prevalence of RLS in pregnant women (who did not have RLS
before pregnancy) ranged from 15% in the first trimester to 23% by the finaltrimester [68]. This increased prevalence may reflect relative iron or folate
deficiency during pregnancy [69,70].
Effect of pregnancy on chronic pulmonary diseases
Clinicians who care for pregnant women who have underlying pulmonary
disorders should understand that deviations from normal values of arterial oxy-genation, FEV1, FVC, diffusing capacity, and respiratory rate indicate patho-
logic conditions. In contrast, a normal nongravid value of 40 mm Hg for the
Paco2 in a pregnant patient should be considered evidence of respiratory fail-
ure and be treated accordingly. The effect of pregnancy on asthma and allergic
diseases is treated extensively elsewhere in this issue. Other chronic respiratory
diseases also may be affectedbeneficially and adverselyby pregnancy.
wise et al6
http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
7/12
Sarcoidosis is the classic example of a disease that tends to stabilize or im-
prove during pregnancy [7176]. It is the most common of the interstitial lung
diseases to complicate pregnancy. The observed increase in circulating free cor-tisol in pregnant women has been postulated as the explanation for the im-
provement that is seen in some patients [77]. This also may explain why
patients who have autoimmune disorders, including rheumatoid arthritis and
systemic lupus erythematosus with their attendant pulmonary involvement,
frequently stabilize during pregnancy [7779]. Cytotoxic agents that might be
used for autoimmune disorders are contraindicated in pregnancy because of their
teratologic and abortifacient effects. Corticosteroids have been used in pregnancy,
although they may lead to preterm delivery or intrauterine growth retardation
[79]. As with asthma, however, the effect of the use of higher doses of cortico-steroids cannot be separated clearly from the impact of increased disease activity
that prompts the use of these agents.
In contrast to the immune-mediated interstitial lung diseases, lymphangio-
leiomyomatosis (LAM), an uncommon interstitial lung disease that occurs ex-
clusively in fertile women, typically is worsened by pregnancy [8084]. This is
not surprising given the hypothesis that disease progression in LAM is estrogen-
mediated. Consequently, most women who have LAM are advised to avoid
pregnancy [85].
The mean age of survival of patients who have cystic fibrosis has increasedprogressively over the last several decades. With this change, an increasing num-
ber of women who have cystic fibrosis are choosing to become pregnant. With
careful management, such patients are generally able to tolerate pregnancy well
[8688]. An FVC of more than 50% of predicted has been offered as a safe
threshold for pregnancy; however, other factors, including frequency of pulmo-
nary exacerbations, nutritional status, and presence of pulmonary hypertension,
must be taken into account [89,90].
The physiologic changes in the cardiovascular and respiratory systems during
pregnancy are tolerated poorly by certain groups of patients. A large body ofliterature has described the problems that are induced by the increased cardiac
output demands of pregnancy in patients who have primary and secondary pul-
monary hypertension [9194]. Chronic obstructive pulmonary disease [95,96]
and neuromuscular disease [97] also generally predispose to poor outcomes
because they add to the increased work of breathing that is imposed by preg-
nancy. Among the neuromuscular disorders, myasthenia gravis presents a special
case. Two thirds of myasthenic women remain the same or show improvement in
their disease during pregnancy, whereas one third worsen [76].
Although pregnancy generally is not considered to be an immunocompro-mised state, several chronic infections, most notably tuberculosis [98,99] and coc-
cidioidomycosis [100,101], may reactivate or worsen in the gravid setting. This
may be due, in part, to changes in the number and function of T and B lympho-
cytes [102104], but hormonal alterations also may play a role. For example, es-
trogen was demonstrated to enhance the growth of Coccidioides immitis in vitro
[105]. Antituberculous and antifungal chemotherapy are useful in these settings.
respiratory physiologic changes in pregnancy 7
http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
8/12
Pulmonary embolic disease in pregnancy
The two leading causes of unexpected maternal deaths are thromboembolicdisease and amniotic fluid embolism [106]. Pregnancy increases the risk of ve-
nous thromboembolism formation by the hypercoagulable effects of estrogen
and venous stasis that are due to increased intra-abdominal pressure [107]. Am-
niotic fluid embolism may result in acute lung injury by causing pulmonary vas-
cular endothelial damage, complement activation, and direct platelet aggregation
effects of amniotic fluid [108110]. Air embolism is an uncommon complication
of pregnancy in which air enters the venous circulation through the subplacental
myometrial veins, and results in endothelial damage and mechanical obstruction.
Summary
In summary, the major physiologic changes that occur in pregnancy are the
increased minute ventilation, which is caused by increased respiratory center
sensitivity and drive; a compensated respiratory alkalosis; and a low expiratory
reserve volume. The vital capacity and measures of forced expiration are well
preserved. Patients who have many lung diseases tolerate pregnancy well, with
the exception of those who have pulmonary hypertension or chronic respiratoryinsufficiency from parenchymal or neuromuscular disease.
References
[1] Fishburne JI. Physiology and disease of the respiratory system in pregnancy. A review. J Reprod
Med 1979;22:17789.
[2] Lapinsky SE, Kruczynski K, Slutsky AS. Critical care in the pregnant patient. Am J Respir Crit
Care Med 1995;152:42755.[3] Weinberger SE, Weiss ST, Cohen WR, et al. Pregnancy and the lung. Am Rev Respir Dis
1980;121:55981.
[4] Wise RA. Pulmonary function during pregnancy. In: Schatz M, Zeiger RS, Claman HN, editors.
Asthma and immunological diseases in pregnancy and early infancy. New York7 Marcel
Dekker; 1998. p. 57.
[5] Pereira A, Krieger BP. Pulmonary complications of pregnancy. Clin Chest Med 2004;25:
299310.
[6] Wise RA, Polito AJ. Respiratory physiologic changes in pregnancy. Immunol Allergy Clin
North Am 2000;20:663 72.
[7] Rees GB, Pipkin FB, Symonds EM, et al. A longitudinal study of respiratory changes in nor-
mal human pregnancy with cross-sectional data on subjects with pregnancy-induced hyper-tension. Am J Obstet Gynecol 1990;162:82630.
[8] Knuttgen HG, Emerson Jr K. Physiological response to pregnancy at rest and during exercise.
J Appl Physiol 1974;36:54953.
[9] Pernoll ML, Metcalfe J, Kovack PA, et al. Ventilation during rest and exercise in pregnancy and
post-partum. Respir Physiol 1975;25:295 310.
[10] Templeton A, Kelman GR. Maternal blood gases, PAO2-PaO2, physiological shunt and Vd/Vt
in normal pregnancy. Br J Anaesth 1967;48:10018.
wise et al8
http://-/?-http://-/?-http://-/?- -
7/29/2019 cambios respiratorios
9/12
[11] Liberatore SM, Pistelli R, Patalano F, et al. Respiratory function during pregnancy. Respiration
(Herrlisheim) 1984;46:145 50.
[12] Prowse CM, Gaensler EA. Respiratory acid-base changes during pregnancy. Anesthesiology
1965;26:38192.
[13] Tsai C, De Leeuw NK. Changes in 2,3-diphosphoglycerate during pregnancy and puerperium
in normal women and beta-thalassemia heterozygous women. Am J Obstet Gynecol 1982;
142:5203.
[14] Lyons HA, Antonio R. The sensitivity of the respiratory center in pregnancy and after the
administration of progesterone. Trans Assoc Am Phys 1959;72:17380.
[15] Zwillich CW, Natalino MR, Sutton FD, et al. Effects of progesterone on chemosensitivity in
normal men. J Lab Clin Med 1978;92:2629.
[16] Schoene RB, Pierson DJ, Lakshminarayan S, et al. Effect of medoxyprogesterone-1-acetate
on respiratory drives on occlusion pressure. Bull Eur Physiopathol Respir 1980;16:64553.
[17] Sutton FD, Zwillich CW, Creagh E, et al. Progesterone for outpatient treatment of Pickwickian
syndrome. Ann Intern Med 1975;83:4769.
[18] Skatrud JB, Dempsey JA, Kaiser DG. Ventilatory response to medoxyprogesterone acetate
in normal subjects: time course and mechanism. J Appl Physiol: Respirat Environ Exercise
Physiol 1978;44:93944.
[19] Jensen D, Wolfe LA, Slatkovska L, et al. Effects of human pregnancy on the ventilatory
chemoreflex response to carbon dioxide. Am J Physiol Regul Integr Comp Physiol 2005;
288(5):R136975.
[20] Moore LG, McCullough RE, Weil JV. Increased HVR in pregnancy: relationship to hormonal
and metabolic changes. J Appl Physiol 1987;62:15863.
[21] Hannhart B, Pickett CK, Moore LG. Effects of estrogen and progesterone on carotid body
neural output responsiveness to hypoxia. J Appl Physiol 1990;68:190916.[22] Bayliss DA, Cidlowski JA, Millhorn DE. The stimulation of respiration by progesterone in
ovariectomized cat is mediated by an estrogen-dependent hypothalamic mechanism requiring
gene expression. Endocrinology 1990;126:51927.
[23] Awe RJ, Nicotra B, Newton TD, et al. Arterial oxygenation and alveolar-arterial oxygen
gradients in term pregnancy. Obstet Gynecol 1979;53:182 6.
[24] Archer GW, Marx GF. Arterial oxygen tension during apnoea in parturient women. Br J
Anaesth 1974;46:358 60.
[25] Ang CK, Tan TH, Walters WA, et al. Postural influence on maternal capillary oxygen and
carbon dioxide tensions. BMJ 1969;4:2013.
[26] Milne JA. The respiratory response to pregnancy. Postgrad Med J 1979;55:318 24.
[27] Norregaard O, Schultz P, Ostergaard A, et al. Lung function and postural changes duringpregnancy. Respir Med 1989;83:467 70.
[28] Bedell GN, Adams RW. Pulmonary diffusing capacity during rest and exercise. A study of
normal persons and persons with atrial septal defect, pregnancy, and pulmonary disease. J Clin
Invest 1962;41:190814.
[29] McAuliffe F, Kametas N, Rafferty GF, et al. Pulmonary diffusing capacity in pregnancy at sea
level and at high altitude. Respir Physiol Neurobiol 2003;134(2):8592.
[30] Gilbert R, Auchincloss J. Dyspnea of pregnancy: clinical and physiological observations. Am J
Med Sci 1966;252:2706.
[31] Milne J, Howie A, Pack A. Dyspnea during normal pregnancy. Br J Obstet Gynaecol 1978;85:
2603.
[32] Tenholder M, South-Paul J. Dyspnea in pregnancy. Chest 1989;96:381 8.[33] Zeldis SM. Dyspnea during pregnancy. Distinguishing cardiac from pulmonary causes. Clin
Chest Med 1992;13:56785.
[34] Field SK, Bell SG, Cenaiko DF, et al. Relationship between inspiratory effort and breath-
lessness in pregnancy. J Appl Physiol 1991;71:1897902.
[35] Lotgering FK, Spinnewijn WE, Struijk PC, et al. Respiratory and metabolic responses
to endurance cycle exercise in pregnant and postpartum women. Int J Sports Med 1998;19:
1938.
respiratory physiologic changes in pregnancy 9
-
7/29/2019 cambios respiratorios
10/12
[36] Spaaij CJ, van Raaij JM, de Groot LC, et al. No changes during pregnancy in the net cost
of cycling exercise. Eur J Clin Nutr 1994;48:513 21.
[37] Ohtake PJ, Wolfe LA. Physical conditioning attenuates respiratory responses to steady-state
exercise in late gestation. Med Sci Sports Exerc 1998;30:1727.
[38] Garcia-Rio F, Pino-Garcia JM, Serrano S, et al. Comparison of helium dilution and plethys-
mographic lung volumes in pregnant women. Eur Respir J 1997;10:23715.
[39] Cugell DW, Frank NR, Gaensler EA, et al. Pulmonary function in pregnancy, 1: serial
observations in normal women. Am Rev Tuberc Pulm Dis 1953;67:56889.
[40] Gee JBL, Packer BS, Millen JE, et al. Pulmonary mechanics during pregnancy. J Clin Invest
1967;46:94552.
[41] Thomson KJ, Cohen ME. Studies in the circulation in pregnancy. II. Vital capacity observa-
tions in normal pregnant women. Surg Gynecol Obstet 1938;66:591603.
[42] Gazioglu K, Kaltreider NL, Rosen M, et al. Pulmonary function during pregnancy in normal
women and in patients with cardiopulmonary disease. Thorax 1970;25:44550.
[43] Ihrman K. A clinical and physiological study of pregnancy in a material from northern
Sweden; III. Vital capacity and maximal breathing capacity during and after pregnancy. Acta
Soc Med Upsalla 1960;65:14754.
[44] Rubin A, Russo N, Goucher D. The effect of pregnancy upon pulmonary function in normal
women. Am J Obstet Gynecol 1956;72:9639.
[45] Baldwin GR, Moorthi DS, Whelton JA, et al. New lung function and pregnancy. Am J Obstet
Gynecol 1977;127:235 9.
[46] Alaily AB, Carrol KB. Pulmonary ventilation in pregnancy. Br J Obstet Gynaecol 1978;85:
51824.
[47] Blair E, Hickham JB. The effect of change in body position on lung volume and intra-
pulmonary gas mixing in normal subjects. J Clin Invest 1955;34:383 9.[48] Schneider KT, Deckardt R. The implication of upright posture on pregnancy. J Perinat Med
1991;19:12131.
[49] Marx GF, Murthy PK, Orkin LR. Static compliance before and after vaginal delivery. Br J
Anaesth 1970;42:1100 4.
[50] Contreras G, Gutierrez M, Beroiza T, et al. Ventilatory drive and respiratory muscle function in
pregnancy. Am Rev Respir Dis 1991;144:837 41.
[51] Gilroy RJ, Mangura BT, Lavietes MH. Rib cage and abdominal volume displacements during
breathing in pregnancy. Am Rev Respir Dis 1988;137:668 72.
[52] Oddoy A, Merker G. Lung mechanics and blood gases in pregnant guinea pigs. Acta Physiol
Hung 1987;70:3115.
[53] Sherwood OD, Downing SJ, Guico-Lamm ML, et al. The physiological effects of relaxinduring pregnancy: studies in rats and pigs. Oxf Rev Reprod Biol 1993;15:143 89.
[54] Goldsmith LT, Weiss G, Steinetz BG. Relaxin and its role in pregnancy. Endocrinol Metab Clin
North Am 1995;24:171 86.
[55] Milne JA, Mills RJ, Howie AD, et al. Large airways function during normal pregnancy. Br J
Obstet Gynaecol 1977;84:448 51.
[56] Mokkapatti R, Prasad EC, Venkatraman, et al. Ventilatory functions in pregnancy. Indian J
Physiol Pharmacol 1991;35:237 40.
[57] Brancazio LR, Laifer SA, Schwartz T. Peak expiratory flow rate in normal pregnancy. Obstet
Gynecol 1997;89:383 6.
[58] Harirah HM, Donia SE, Nashrallah FK, et al. Effect of gestational age and position on peak
expiratory flow rate: a longitudinal study. Obstet Gynecol 2005;105:3726.[59] Harik-Khan R, Wise RA, Lou C, et al. The effect of gestational parity on FEV1 in a group of
healthy volunteer women. Respir Med 1999;93:3828.
[60] Garrard GS, Littler WA, Redman CW. Closing volume during normal pregnancy. Thorax
1978;33:48892.
[61] Bevan DR, Holdcroft A, Loh L, et al. Closing volume and pregnancy. Br Med J 1974;1(896):
135.
[62] Russell IF, Chambers WA. Closing volume in normal pregnancy. Br J Anaesth 1981;53:1043 7.
wise et al10
-
7/29/2019 cambios respiratorios
11/12
[63] American Academy of Sleep Medicine. International classification of sleep disorders, revised:
diagnostic and coding manual. Westchester (IL)7 American Academy of Sleep Medicine; 2000.
[64] Pien GW, Schwab RJ. Sleep disorders during pregnancy. Sleep 2004;27:1405 17.
[65] Santiago JR, Nolledo MS, Kinzler W, et al. Sleep and sleep disorders in pregnancy. Ann Intern
Med 2001;134:396408.
[66] Schweiger MS. Sleep disturbance in pregnancy. A subjective survey. Am J Obstet Gynecol
1972;114:879 82.
[67] Franklin KA, Holmgren PA, Jonsson F, et al. Snoring, pregnancy-induced hypertension, and
growth retardation of the fetus. Chest 2000;117:13741.
[68] Suzuki K, Ohida T, Sone T, et al. The prevalence of restless legs syndrome among pregnant
women in Japan and the relationship between restless legs syndrome and sleep problems. Sleep
2003;26:6737.
[69] Lee KA, Zaffke ME, Baratte-Beebe K. Restless legs syndrome and sleep disturbance
during pregnancy: the role of folate and iron. J Womens Health Gend Based Med 2001;10:
33541.
[70] Manconi M, Govoni V, De Vito A, et al. Pregnancy as a risk factor for restless legs syndrome.
Sleep Med 2004;5:305 8.
[71] Dines DE, Banner EA. Sarcoidosis during pregnancy: improvement in pulmonary function.
JAMA 1967;200:726.
[72] Agha FP, Vade A, Amendola MA, et al. Effects of pregnancy on sarcoidosis. Surg Gynecol
Obstet 1982;155:817 22.
[73] Haynes de Regt R. Sarcoidosis and pregnancy. Obstet Gynecol 1987;70:369 72.
[74] Noble PW, Lavee AE, Jacobs MM. Respiratory diseases in pregnancy. Obstet Gynecol Clin
North Am 1988;15:391 428.
[75] Fortin F, Wallaert B. Interstitial pathology and pregnancy. Rev Mal Respir 1988;5:275 8.[76] King Jr TE. Restrictive lung disease in pregnancy. Clin Chest Med 1992;13:607 22.
[77] Selroos O. Sarcoidosis and pregnancy: a review with results of a retrospective survey. J Intern
Med 1990;227:2214.
[78] Lockshin MD. Pregnancy does not cause systemic lupus erythematosus to worsen. Arthritis
Rheum 1989;32:66570.
[79] Clark CA, Spitzer KA, Nadler JN, et al. Preterm deliveries in women with systemic lupus
erythematosus. J Rheumatol 2003;30(10):212732.
[80] Yockey CC, Riepe RE, Ryan K. Pulmonary lymphangioleiomyomatosis complicated by preg-
nancy. Kans Med 1986;87:2778.
[81] Hughes E, Hodder RV. Pulmonary lymphangiomyomatosis complicating pregnancy. A case
report. J Reprod Med 1987;32:5537.[82] Wahedna I, Cooper S, Williams J, et al. Relation of pulmonary lymphangio-leiomyomatosis
to use of the oral contraceptive pill and fertility in the UK: a national case-control study.
Thorax 1994;49:9104.
[83] Brunelli A, Catalini G, Fianchini A. Pregnancy exacerbating unsuspected mediastinal
lymphangioleiomyomatosis and chylothorax. Int J Gynaecol Obstet 1996;52:28990.
[84] Urban T, Lazor R, Lacronique J, et al. Pulmonary lymphangioleiomyomatosis. A study of
69 patients. Groupe dEtudes et de Recherche sur les Maladies Orphelines Pulmonaires
(GERMOP). Medicine 1999;78:321 37.
[85] Eliasson AH, Phillips YY, Tenholder MF. Treatment of lymphangioleiomyomatosis: a meta-
analysis. Chest 1989;196:1352 5.
[86] Palmer J, Dillon-Baker C, Tecklin JS, et al. Pregnancy in patients with cystic fibrosis. AnnIntern Med 1983;99:596600.
[87] Canny GJ, Corey M, Livingstone RA, et al. Pregnancy and cystic fibrosis. Obstet Gynecol
1991;77:8503.
[88] Kent NE, Farquharson DF. Cystic fibrosis in pregnancy. Can Med Assoc J 1993;149:809 13.
[89] Larsen Jr JW. Cystic fibrosis and pregnancy. Obstet Gynecol 1972;39:880 3.
[90] Tanoue LT. Pulmonary problems in pregnancy. Clin Pulm Med 1998;5:83 92.
[91] Baethge BA, Wolf RE. Successful pregnancy with scleroderma renal disease and pulmonary
respiratory physiologic changes in pregnancy 11
-
7/29/2019 cambios respiratorios
12/12
hypertension in a patient using angiotensin converting enzyme inhibitors. Ann Rheum Dis
1989;48:7768.
[92] Roberts NV, Keast PJ. Pulmonary hypertension and pregnancya lethal combination. Anaesth
Intensive Care 1990;18:366 74.
[93] Ray J, Sermer M. Systemic lupus erythematosus and pulmonary hypertension during preg-
nancy: report of a case fatality. Can J Cardiol 1996;12:753 6.
[94] Weiss BM, Zemp L, Seifert B, et al. Outcome of pulmonary vascular disease in pregnancy:
a systematic overview from 1978 through 1996. J Am Coll Cardiol 1998;31:16507.
[95] Geisler CF, Bulhler JH, Depp R. Alpha-1-antitrypsin deficiency: severe obstructive lung dis-
ease and pregnancy. Obstet Gynecol 1977;49:314.
[96] Kuller JA, Katz VL, McCoy MC, et al. Alpha-1-antitrypsin deficiency and pregnancy. Am J
Perinatol 1995;12:303 5.
[97] Bravo RH, Katz M, Inturrisi M, et al. Obstetric management of Landry-Guillain-Barr syn-
drome: a case report. Am J Obstet Gynecol 1982;142:7145.
[98] Jacobs RF, Abernathy RS. Management of tuberculosis in pregnancy and the newborn. Clin
Perinatol 1988;15:305 19.
[99] Margono F, Mroueh J, Garely A, et al. Resurgence of active tuberculosis among pregnant
women. Obstet Gynecol 1994;83:911 4.
[100] Barbee RA, Hicks MJ, Grosso D, et al. The maternal immune response in coccidioidomycosis.
Is pregnancy a risk factor for serious infection? Chest 1991;100:70915.
[101] Peterson CM, Schuppert K, Kelly PC, et al. Coccidioidomycosis and pregnancy. Obstet
Gynecol Surv 1993;48:14956.
[102] Sridama V, Pacini F, Yang SL, et al. Decreased levels of helper T cells. A possible cause of
immunodeficiency in pregnancy. N Engl J Med 1982;307:3526.
[103] Stahn R, Fabrikus HA, Hartleitner W. Suppression of human T-cell colony formation duringpregnancy. Nature 1978;276:831 2.
[104] Glassman AB, Bennett CE, Christopher JB, et al. Immunity during pregnancy: lymphocyte
subpopulations and mitogen responsiveness. Ann Clin Lab Sci 1985;15:35762.
[105] Catanzaro A. Pulmonary mycosis in pregnant women. Chest 1984;86:14S 9S.
[106] Clark SL, Hankins GD, Dudley DA, et al. Amniotic fluid embolism: analysis of the national
registry. Am J Obstet Gynecol 1995;172:115867.
[107] Kupferminc MJ. Thrombophilia and pregnancy. Reprod Biol Endocrinol 2003;1:111.
[108] Hammerschmidt DE, Ogburn PL, Williams JE. Amniotic fluid activates complement. A role
in amniotic fluid embolism syndrome? J Lab Clin Med 1984;104:9017.
[109] Karetzky M, Ramirez M. Acute respiratory failure in pregnancy. An analysis of 19 cases.
Medicine (Baltimore) 1998;77:41 9.[110] Walsh SW, Wang Y. Secretion of lipid peroxides by the human placenta. Am J Obstet Gynecol
1993;169:14626.
wise et al12