Fadel et al., Respiratory alkalosis 195

J. Perinat. Med.3 (1979) 202

Original articles

Normal pregnancy: A model of sustained respiratory alkalosis

Hossam E. Fadel, Gretajo Northrop, H. Robert Misenhimer, RoUie J. Harp

Dept. of Obstetrics and Gynecology and Internal Medicine, Rush Presbyterian-St. Luke's Medical Center, Chicago

Systems and Computer Services, Medical College of Georgia, Augusta, Georgia

Hyperventilation has been known to occur inpregnancy. It is believed to result fromprogesteroneStimulation of the respiratory center [19]. Plasmabicarbonate, base excess and buffer base are allreduced in pregnancy. Most authors believe theseto be compensatory changes in response to therespiratory alkalosis, [l, 19, 20] while othersbelieve they result from an associated metabolicacidosis [15, 24].Controversy also exists in relation to maternaloxygenation during pregnancy. Some authorsreported decreased arterial oxygen tension (p02)and postulated that this was due to impairedoxygen transfer across the lungs [7, 26], whileothers reported an increased pa02 in pregnancy[1,3,23,30].The aim of the present study was to categorizethe acid-base Status in normal pregnancy. Variousacid base and blood gas parameters were s tu die din arterial blood samples obtained from normalthird trimester pregnant women and the resultsobtained form the basis of this report. The sameparameters were studied in the amniotic fluidfrom the same patients. These data and theircorrelation with the maternal blood changes arereported eisewhere [10].

l Material and methodsArterial blood gas analyses were performed on 59healthy women in their third trimester of pregnancy

Curriculum vitaeHOSSAM E. FADELborn in Egypt, 1940. Hegraduated from Ain ShamsMedical School, Egypt,1960. He specialized inObstetrics and Gynecologyand became an instructor,then a lecturer in AinShams Medical School Hemoved to U.SA, in 1970and had fellowship inPerinatal medicine, and wasappointed to thefaculty ofRush Medical College,Chicago, 1973. He is presently Associate professor, Chiefof Maternal-Fetal Medicine sectiont Medical College ofGeorgia, Augusta, Georgia, U.S.A.

who were to undergo amniocentesis. Their men-strual dates were accurate and did correlate withthe neonatal estimation of the gestational age.Prenatal Vitamins and iron Supplements were theonly medications taken by these patients. Infor-med consent was obtained. Immediately after theamniocentesis, while still supine, 20 ml of bloodwas collected anaerobically in a heparinized glasssyringe through percutaneous radial artery punctureunder local anesthesia. To a sodium fluoride con-taining tube 10 ml were added, 5 ml were deliveredinto another tube, and the heparinized syringe wasimmediately sealed and immersed in ice. Allsamples were transported immediately to the

0300-5577/79/0007-0195S02OO© by Walter de Gruyter & Co. · Berlin - New York

196 Fadel et al., Respiratory alkalosis

Tab. I. Results of the acid base determinations in normal third trimester pregnant women. Comparison with normalnon-pregnant females. ' f

Oxygen. tensionaorr)

Carbondioxidetension(Torr)

Plasma pHbicarb-onate(mEq/L)

Baseexcess(mEq/L)

Lactate(mmol/L)

Pyruvate(mmol/L)

Normal 99.3* ± 7.8 28.8 ± 3.7 19.0 ± 2.8 7.42 ± 0.03 -4.2 ± 2.2 1.316 ± 0.66 0.063 ± 0.04pregnancyNormal 95.0 ±5.72 38.1 ± 2.94 23.6 ± 0.99 7.40 ± 0.03 -1.0 ± 1.44 1.0 % ±0 .2 0.05 ±0.01

*Mean ± S.D.

laboratory. Blood gas analyses were performedwith a Radiometer BMS-3-MK-2. Arterial oxygentension (pa02), carbon dioxide tension (paC02)•and pH were measured directly. Plasma bicarbonate(HC03^ and base excess (BE) were derived fromthe SIGGARD—ANDERSEN alignment nomogram[29]. Measured amounts of blood from the fluo-ride tubes were transferred rapidly to tubes con-taining chilled trichloracetic acid and the proteinfree flltrate was used for lactic and pyruvic aciddeterminations utilizing an enzymatic method,lactic acid dehydrogenase.* All laboratory determ-inations were run in duplicate. Statistical analyses(t-test, correlation, regression line) were performedusing a Statistical package of Computer programs[17,25].

2 Results

The average age of the study patients was 23.3 ±4.8, and their average parity was 2.2 ±2.1. Thegestational age ranged from 30 to 42 with anaverage of 37.5 ± 2.9 weeks. The results of thevarious laboratory determinations in the studypatients and the corresponding values fromhealthy nongravid adult females are given in Tab. I.As compared to the non-pregnant state, pa02(99.3 ± 7.8 Torr), is slightly increased, whilepaC02 (28;8 ± 3.7 Torr), HCO3- (19.0 ± 2.8mEq/L), and BE (-4.2 ± 2.2 mEq/L) are mar-kedly reduced in normal third trimester pregnancy.The pH is in the high ränge of normal (7.42 ±

*Sigma Technical Bulletin 627/826-UV, Sigma ChemicalCompany, St. Louis, MO. U.S.A.

0.03). The blood lactate and pyruvate are slightlyincreased (1.316 ± 0.66, and 0.063 ± 0.04 mmol/Lrespectively). Correlations between the differentmeasurements were calculated. Within the gesta-tion period studied (30—42 weeks) there were nosignificant correlations of any of the parametersevaluated with gestational age. The pH was ne-gatively correlated with blood pyruvate (r- -0.367,P=0.021), but not with blood lactate, (r=0.228,P-0.094). There was a significant negative corre-lation between paCO2 and blood lactate (r=-0.497,P= 0.001).

3 Discussion

Many studies of acid base balance in pregnancyhave been published. However, many discrepantresults and questions remain. At least some ofthese discrepancies are due to differences in bloodsampling methods and laboratory techniques. Insome studies, the blood specimens were eithervenous or capillary [7, 15, 24], while in.others[l, 3, 6], äs in this study, arterial blood specimenswere utilized. The control non-pregnant valuesare in close agreement with those cited in previousreports [14, 29].Maternal pa02 was reported to be reduced inpregnancy [7, 26]. Other investigators reportedhigher pa02 levels in pregnancy but stated thatpa02'did not increase äs much äs expected fromhyperventilation [23, 30]. We found that themean pa02 is increased in normal pregnancyover nonpregnant values (99.3 vs 95.0 Torr), inagreement with the more recent reports [l, 3, 28].The higher paQ2 values obtained in our study, äs

J. Perinat. Med. 7 (1979)

Fadel et al, Respiiatory alkalosis 197

well äs the latter studies, compared to the previous hyperventilation) stimulates the enzyme phospho-studies, are probably due to the use of the sen- fructo-kinase that results in increased glycolyticsitive direct polarographic technique for the production of pyruvate and consequently lactatemeasurement of the oxygen tension. The in- in both tissues and red blood cells [9, 22]. Thecreased pa02 in pregnancy is presumably due to increased pyruvate and lactate levels observed inthe increased alveolar oxygen tension (pA02) normal pregnancy may result from the same[l, 23]. The latter is caused by a significant mechanism. This is supported by our finding of areduction in alveolar carbon dioxide tension, statistically significant negative correlation be-resulting from a significant increase of the alveolar tween paC02, and blood lactate (r = -0.497,Ventilation [4], and unaltered alveolar tensions of P= 0.001), and between the pH and blood pyruvatenitrogen and water vapor. In a recent report, there (r= -0.367, P= 0.021). Other possible sourceswas noevidenceofincreased arteriovenous shunting for increased maternal lactate levels are the fetusor alveolar-arterial p02 differences in normal and/or the placenta. However, the studies thatpregnancy [28]. were conducted during cesarean section toThe mean paC02 in this study was 28.8 ± 3.7 Torr, determine the directional transfer of lactate andOthers reported the same [3] or alowervalue [7], pynwate across the placenta are conflicting andbut mostly a slightly higher paC02 [1,4, 6, 15, 24]. non-conclusive [8,13,18].Thisissignificantlylowerthaninadultnon-pregnant Significance bands relating appropriate physio-females, in agreement with the previously cited logic responses of pH (or H4), HCO3~- and/or BEstudies. The reduced paC02 presumably facilitates to varying levels of paC02 under well-controlled

.the elimination of carbon dioxide from fetal blood experimental conditions have been constructedacross the placenta [19]. The mean pH wasfound [29]. These bands show, with 95% confidence,to be 7.42 ± 0.03, in close agreement with others these relationships in simple acid-base disturb-[1, 3, 6, 15, 24]. Thisvalue, which corresponds to ances. Values lying outside these bands stronglyhydrogen ion (H+) concentration of 38 nmoles/L, suggest the existence of a second independentis in the upper ränge of normal in non-pregnant primary i.e. a mixed acid base disturbance [16,females [l5, 29]. Our results confirm the previously 21, 29]. Such bands have been constructed inreported reduced HCO3" levels in normal pregnancy humans for acute and chronic hypercapnia [5][1,7, 14, 15, 24]. The mean blood BE was found m^ acute hypocapnia [2]. Comparable data in manto be -4.22 ± 2.22 mEq/L which is less than in with chronically adapted respiratoiy alkalosis arenormal adult women [29], in agreement with not available, the longest period of observationpreviousreports[l,6,7, 14, 24]. under controlled conditions was 26 hours [12].Blood lactic acid level in the normal pregnant However, such significance bands were generatedwomen was 1.316 ± 0.66 mmol/L. This agrees from observations on 10 dogs exposed tohypoxe-with the average of reported values by different mic hypocapnia for 1-2 weeks [11]. A steadyinvestigators i.e. 1.25 mmol/L, [14] and represents state was obtained after 4-5 days of stepwisean increase over non-pregnant females, in agreement decrease in atmospheric oxygen from 21% to 9%.with the previously cited report [14]. Our value The mean values of H+ and HCO3" äs they relatefor blood pyruvic acid (0.063 ± 0.04 mmol/L) is to paC02 in the normal pregnant women in thislower than the average reported in pregnancy study were found to be within the limits of these(0.19 mmol/L) [14] but higher than nonpregnant confidence bands. This suggests that changes ofcontrols both in our study, and in the latter report acid base balance in pregnancy are simple and[14]. not mixed i.e. sustained respiratory alkalosisIn man, increase of blood lactic acid was noted to without an added metabolic acidosis. When in-occur during either active (voluntary) or passive dividual values were plotted, some of the pHhyperventilation while awake or during anesthesia values were below the band (Fig. 1) and some[27]. It has been postulated that the decrease of of the HC03" values were above the band (Fig. 2).intracellular H"1" concentration (consequent to These particular values may represent the effect

J. Perinat. Med. 7(1979)

198 Fadel et al., Respiratory alkalosis

50-

10 15 20 25Ρα <χ>2·

-*r

7.30

7.40

7.50

Torr

Fig. 1. Arteiial carbon dioxide tension (paCOs) asrelatedto hydrogen ion concentration (H4") in normal third tri-mester pregnancy. The results are superimposed on thesignificance band calculated by GENNARI et al 1972[11] for chronic hypocapnia in dogs.

7.317357397.43iex748

7.547.60

15 18 2l 24 27 30 33 36 39 42 %

Po cc>2, Torr 7

Fig. 3. Significance band showing the anticipated responseof hydrogen ion activity (H*") to changes of arterial carbondioxide tension, (paCO2> (within 95% confidence limits)in normal third trimester pregnant women.

25

20

ι ΓΟο15

io

10 15 20 25 30 35 40Ρα co2. Torr

Fig. 2. Arterial carbon dioxide tension (paC 2) s relatedto plasma bicarbonate (HCOa") in normal third trimesterpregnant women. The results are superimposed on the sig-nificance band calculated by GENNARI et al. 1972 (11)for chronic hypocapnia in dogs.

of temporary increased hyperventilation andfurther decrease in paC02 due to anxiety at thetime of obtaining the blood sample. However, itis possible that these bands are not quite applic-able. The experimental design used in their gene-ration is obviously very different from the physio-logic changes that occuf in normal pregnantwomen. Therefore, we proceeded to constructfrom our data confidence bands correlating theH+ concentration (pH) and HC03" to paC02levels. Regression lines were calculated from 43cases of paired data:

H+= 28.3 + 0.335 paC02HC03' = 4.63 + 0.499 paC02

The Standard error of these regression lines at the95 % level was then calculated and the bands plotted[25] (Figs. 3 and 4).

30

26

22

O"o14

10

15 18 2l 24 27 30 33 36 39 42Ρα c<>2 Torr

Fig. 4. Significance band showing the anticipated responseof bicarbonate (HCOa-) to changes of arterial carbondioxide tension, (paCO2) (within 95% confidence limits)in normal third trimester pregnancy.

These bands defme the 95% confidence limits foranticipated response to sustained respiratory alka-losis in normal third trimester pregnant womQn.Based on our data, there is no evidence of metabolicacidosis in pregnancy ashas been suggested by someinvestigators [7, 15, 24]. The decreases in HC03"and BE were well within the anticipated responsefor compensation of respiratory alkalosis, andthere was no undue increase in blood lactic acid.Pregnancy, therefore, represents a state of "su-stained respiratory alkalosis", 'and because the pHis still within the normal r nge, we do not agreewith its characterization s "incompletely com-pensated" respiratory alkalosis [24]. The acid baseStatus in normal pregnaiicy can best be characterizeds "maximally compensated sustained respiratory

J. Perinat. Med. 7 (1979)

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Fadel et al., Respiratory alkalosis 199

alkalosis'4. Unlike acclimatization to high altitudes,which is the other example of such a Status,pregnancy is not associated with hypoxemia.Pregnancy, therefore, is the best and only naturalmodel for this type of acid base Status. The signif-icance bands relating the pH and HC03"" to paCÜ2

levels constructed from these data should be usefuläs reference for the evaluation of the acid baseStatus of patients with sustained respiratory alka-losis, in addition to being a useful reference forthe detection ofsuperimposed acid base distrubancesin pregnant women.

Summary

The aim of this study was to categorize the acid baseStatus in normal pregnancy. Blood gases and other acidbase parameters were determined in arterial blood samplesfrom 59 normal third trimester pregnant women.Oxygen and carbon dioxide tensions (pa02 and paCO2),and pH were measured directly u sing a Radiometer BMS-3-MK-2. Plasma bicarbonate (HCO3~), and base excess(BE) were derived from Siggard Andersen alignmentnomogram. Blood lactate and pyruvate were measuredusing an enzymatic; lactic dehydrogenase method.Compared to the non-pregnant state (Tab. I), pa02(99.3 ± 7.8 Torr), blood lactate (1.316 ± 0.66 mmol/L)and blood pyruvate (0.063 ± 0.04 mmol/L) wereslightly increased, whüe paCO2 (28.8 ± 3.7 Torr),HC03- (19.0 ± 2.8 mEq/L), and BE (-4.2 ± 2.2 mEq/L)were markedly reduced. The pH (7.42 ± 0.03) wasslightly increased but still in the normal non-pregnantränge.These changes are thought to be initiated by thestimulant action of progesterone on the respiratorycenter causing increased alveolar Ventilation. Thealveolar tension of CO2 decreases whüe that of 02increases, resulting in maternal hypocapnia, andincreased paO2. The sustained hypocapnia wouldresult in alkalosis if it were not for the compensatorymechanisms that lead to a decrease in plasma bicar-bonate and base excess. The reduced H+ concen-

tration is known to stimulate the enzyme phospho-fructokinase and cause increased glycolytic productionof pyruvate and secondarily lactate. This mechanismmay explain the slightly increased lactate and pyruvatelevels in pregnancy.Pregnancy, therefore, represents a state of sustainedrespiratory alkalosis that is compensated maximally(i.e. pH is the normal ränge) without evidence ofsuperimposed metabolic acidosis. This was furthersupported by the fact that the mean values of H+

and ( >3~ äs they relate to paC02 in the study patientswere within the limits of the confidence bands repre-senting chronic hypocapnia (in dogs). Because nocomparable bands have been generated in man, so far,and because pregnancy represented a natural modelof this unique acid base Status (sustained respiratoryalkalosis) without the effects of hypoxemia, äs in indi-viduals living at high altitudes or under experimentalconditions, we elected to construct from the datasignificance bands that correlate the H+, HCOa"concentrations to paCO2 levels. These bands definethe 95% confidence limits for anticipated response in„sustained respiratory alkalosis". These should be usefulfor the evaluation of the acid base Status of patientswith sustained respiratory alkalosis, in addition to beinga useful reference for the detection of superimposed acidbase disturbances in pregnant women.

Keywords: Acid base equüibrium, bicarbonate, carbon dioxide, hyperventilation, hypocapnia, lactate, oxygen, pyruvate,respiratory alkalosis, third trimester, pregnancy.

Zusammenfassung

Die normale Schwangerschaft als Modell einer beständigenrespiratorischen AlkaloseZiel dieser Arbeit war die Untersuchung des Säure-Basen-Status einer normalen Schwangerschaft. Dazu wurden inarteriellen Blutproben von 59 gesunden Schwangerenim letzten Schwangerschaftsdrittel die Blutgaswerte so-wie andere Säure-Basen-Parameter bestimmt.Der O2- und CO2-Partialdruck (paO2 und paCO2) wieauch der pH wurden direkt mit einem Radiometer BMS-3-MK-2 gemessen. Die Plasmabikarbonatkonzentration(HCO3~) und den Basenüberschuß (=base excess, BE)erhielten wir aus dem Siggaard-Andersen-Nomogramm.Der Laktat- Jxr,w. Pyruvatspiegel im Blut wurde mitHilfe der enzymatischen Aktivität der Laktatdehydro-genase bestimmt. Im Vergleich mit Nichtschwangeren(Tab. I) waren der paO2 (99.3 ±7 .8 Torr), der Laktat-

spiegel (1.316 ± 0.66 mmol/1) und der Pyruvatspiegel(0.063 ± 0.04 mmol/1) leicht erhöht. Deutlich ernie-drigt dagegen waren der paCO2 (28.8 ± 3.7 Torr), dieHCO3-Konzentration (19.0 ± 2.8 mäq/1) und der BE(-4.2 ± 2.2 mäq/1). Der pH war mit 7.42 ± 0.03 leichterhöht, jedoch noch innerhalb der normalen Schwan-kungsbreite.Diese Änderungen werden als ein stimulierender Effektdes Progesterons auf das Atemzentrum gedeutet, wo-durch eine gesteigerte alveoläre Ventilation ausgelöstwird. Die Folgen sind ein verminderter alveolärer pCO2gegenüber einem erhöhten p02 in der Alveolarluft. Dasbedeutet, daß sich im mütterlichen arteriellen Blut eineHypokapnie und ein erhöhter paO2 einstellt. Diese an-dauernde Hypokapnie würde eine Alkalose zur Folgehaben, die jedoch durch die kompensatorische -

. Perinat. Med. 7 (1979)

200 Fadel et al, Respiiatory alkalosis

nähme der HCO3-Erniedrigung und damit der Herab-setzung des BE verhindert wird. Weiter ist bekannt,daß eine verminderte H+-Ionenkonzentration einenStimulus für die Aktivität der Phosphofruktokinasedarstellt und auf diesem Weg die Glykolyse gesteigertwird, d.h. mehr Pyruvat und letztlich auch Laktat pro-duziert wird. Über diesen Mechanismus könnten dieleicht erhöhten Laktat- und Pyruvatspiegel in derSchwangerschaft erklärt werden.Die Schwangerschaft stellt damit einen Zustand derbeständigen respiratorischen Alkalose dar, die jedochvoll kompensiert ist (pH = normal), ohne daß Anzeichenfür eine überlagernde metabolische Azidose erkennbarsind. Diese Interpretation ließ sich durch folgende Beob-achtung weiter stützen: wir fanden, daß die mittlerenH+- und HCO3-Konzentrationen als Funktion despaCO2 bei den untersuchten Patienten innerhalb vonVertrauensbereichen lagen, die man für chronische

Hypokapnien (bei Hunden) aufgestellt hat. Für denMenschen wurden vergleichbate Kurven nicht ent-wickelt. Da die Schwangerschaft aber ein natürlichesModell dieses abweichenden Säure-Basen-Status dar-stellt, ohne daß sich Anzeichen einer Hypoxämie wiebei Menschen in großen Höhen oder unter experimen-tellen Bedingungen einstellen, nutzten wir die gewonne-nen Daten zur Erstellung von Signifikanzbereichen, diedie H+ bzw. HCOa-Konzentrationen mit dem paCO2korrelieren. Mit diesen Bereichen definierten wir die95%- Vertrauensschranken für bestimmte Erwartungs-werte bei „beständiger respiratorischer Alkalose/' Einpraktischer Nutzen liegt in der Untersuchung des Säure-Basen-Haushalts von Patienten mit chronischer respira-torischer Alkalose. Darüberhinaus könnte dadurch eineHilfestellung bei der Aufdeckung von überlagerndenSäure-Basen-Störungen in der Schwangerschaft gegebenwerden.

Schlüsselwörter: Bikarbonat, Kohlendioxyd, Hyperventilation, Hypokapnie, Laktat, Pyruvat, respiratorische Alkalose,Säure-Basen-Haushalt, Sauerstoff.

Resume

Grossesse normale: Un modele d'alcalose respiratoiresoutenueCette etude a eu pour but de categoriser le Statut acido-basique de la grossesse normale. Las gaz sanguins etautres parametres acido-basiques ont ete definis dansdes specimens de sang arteriel de 59 parturientes autroisieme trimestre d'une grossesse normale.Nous avons mesure directement a Faide d'un radiometreBMS-3-MK-2 les tensions d'oxygene et de dioxide decarbone (paO2 et paCO2) ainsi que le pH. Le bicarbonatedu plasma (HCO3) et Fexces basique (BE) ont ete derivesdu nomogramme d'alignement de siggard Andersen. Lesei lactique et le pyruvate sanguins ont mesures al'aide d'un enzymatique (methode de dehydrogenaselactique). Compares a Fetat de non-grossesse (Tab. I),le paO2 (99,3 ± 7,8 Torr), le sei lactique du sang(1,316 ± 0,66 mmol/L) et le pyruvate du sang (0,063± 0,04 mmol/L) ont legerement augmente, tandis quele paCO2 (28,8 ± 3,7 Torror), le HCO3- (19,0 ± 2,8 mEq/L), et le BE (-4,2 ± 2,2 mEq/L) ont nettement baisse.Le pH (7,42 ± 0,03) a legerement augmente tout enrestant dans les normes de la non-grossesse.Ces changements sont düs sans doute a Faction stimulantedu progesterone sur le centre respiratoire causant uneVentilation alveolaire accrue. La tension alveolaire deC02diminue tandis que celle de O2 augmente, causant unehypoxapnie maternelle et un Pao2 accru. L'hypocapniesoutenue causerait une alcalose sans les mocanismescompensateurs provoquant une reduction du bicarbonate

du plasma et de l'exces basique. La concentration reduitede H*", conime on sait, stimule la phosphofructocinaseenzymatique et cause une production glycolytique accruede pyruvate et de sei lactique secondaire. Ce mecanismepeut expliquer la hausse legere de sei lactique et de py-ruvate dans la grossesse. En consequence, lä grossesserepresente un etat d'alcalose respiratoire soutenue quiest compensee au maximum (c.a.d. que le pH restenormal) sans evidence d'acidose metabolique superposee.Cette hypothese a ete renforcee par le fait que les valeursmoyennes de H*" et de HCO3- dans leurs rapports avecpaCO2 chez les parturientes examinees sont restees dansles limites des bandes precises representant Fhypocapniechronique (chez les chiens). Etant donne qu.aucune bändecomparable n'a ete produite jusque la chez Fhomme etque la grossesse a constitue un modele naturel de ceStatut acidobasique unique (alcalose respiratoire soutenue)sans les effets d'hypoxemie, comme chez les individusvivant a haute altitude ou dans des conditions experimen-taies, nöus avons choisi de nous baser sur les donnees desbandes significatives qui etablissent des correlations entreles congentrations de H*" et de HCO3" et les degres depaCO2. Ces bandes definissent les limites a 95% deprecision pour la reaction anticipee d'une «alcaloserespiratoire soutenue». Celles-ci devraient etre utilespour Fevaluation du Statut acido-basique des sujets avecalcalose respiratoire soutenue et servir de reference pourle depistage des troubles acido-basiques superposes chezles femmes enceintes.

Mots-cles: Alcalose respkatoire, bicarbonate, dioxide de carbone, equilibre acido-basique, hyperventilation, hypocapnie,oxygene, pyruvate, sei lactique, troisieme trimestre de grossesse.

Acknowledgement: This work was supported in pari by a Grant Number 37133, Research Committee of Rush Pres-byterian-St. Luke's Medical Center.The authors express their appreciation to Dr. WILLIAM A. SPEIR, Jr., Pulmonary Medicine Section,Department of Medicine, Medical College of Georgia, for his review of the manuscript and bis help-ful suggestions.

J. Perinat. Med. 7(1979)

Fadel et al., Respiratory alkalosis 201

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Received August 25, 1978. Accepted February 2, 1979.

Dr. Hossam E. FadelDepartment of Obstetrics and GynecologyMedical College of GeorgiaAugusta, Georgia 30902/USA

J.Perinat. Med. 7(1979)