Effect of maternal oxygen administration on fetal oxygenation during graded reduction of umbilical or uterine blood flow in fetal sheep Rene P. Paulick, MD,' Rebecka L. Meyers, MD,",c,d and Abraham M. Rudolph, MD"b San Francisco, California OBJECTIVE: Effects of maternal oxygen administration on fetal blood gases and on oxygen delivery and consumption during reduced uterine and reduced umbilical blood flows were examined, STUDY DESIGN: In eight pregnant sheep (gestational age 133 ± 4 days) flow transducers were applied to a uterine and the common umbilical artery, Graded reductions in uterine and umbilical blood flows were achieved by a hypogastric artery snare and a balloon cuff encircling the umbilical cord, Fetal femoral arterial and umbilical venous oxygen contents and flows were measured at varying flow reductions with the ewe breathing air or oxygen, RESULTS: During 75% reduction in umbilical blood flow maternal oxygen administration significantly increased fetal oxygen delivery (6,4 ± 2,5 to 7,7 ± 2,3 ml/min/kg) and oxygen consumption (4,3 ± 1,2 to 5,0 ± 0,8 ml/min/kg), With similar reduction of uterine flow oxygen administration increased oxygen delivery from 8,3 ± 2,4 to 12,3 ± 3.6 and oxygen consumption from 3.3 ± 0,8 to 4.7 ± 1,6 ml/min/kg. CONCLUSION: Maternal oxygen inhalation improves fetal oxygenation during umbilical but especially during uterine blood flow reduction. (AM J OBSTET GVNECOL 1992;167:233'9.)
Key words: Umbilical blood flow, fetal oxygen delivery, fetal oxygen consumption The effect of maternal oxygen administration during labor on fetal oxygenation is controversiaL In one clinical study maternal oxygen administration increased fetal arterial P0 2 from 15 to 21 mm Hg,l In long-term, growth-retarded human fetuses maternal oxygen administration increased umbilical venous P0 2 ,2 On the other hand, it has been argued that maternal oxygen administration will have no major effect on fetal oxygenation because maternal arterial blood is almost completely saturated with oxygen; therefore, increasing the maternal arterial P0 2 above 100 mm Hg will increase only the amount of oxygen physically dissolved, which is relatively small compared with that attached to hemoglobin,3 During labor fetal oxygenation may need to be improved for reduction of uterine or umbilical blood flow, In fetal sheep maternal oxygen administration during reduction of umbilical blood flow improved fetal oxygenation by a modest degree.' Uterine blood flow may
From the Cardiovascular Research Institute" and the Departments of Pediatrics/ Surgery,' and Obstetrics, Gynecology and Reproductive Sciences," The University of California, San Francisco. Supported by National Heart, Lung, and Blood Institute Program Project Grant No. HL-24056 and a Deutsche Forschungsgemeinschaft Research Fellowship (DFG Pa 34211-2) awarded to R. P. Received for publication September 30, 1991; revised January 17, 1992; accepted January 27,1992. Reprint requests; AbrahamM. Rudolph, MD, Box 0544, HSE 1403, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-0544. 611136687
be markedly reduced in long-term, growth-retarded sheep fetuses, and maternal oxygen administration resulted in a significant improvement of fetal oxygenation,' However, the effect of maternal oxygen administration on fetal oxygenation during reductions of uterine blood flow has not been investigated systematically. The aim of the present study was to assess the effect of maternal oxygen administration on fetal blood gases, oxygen delivery, and oxygen consumption during graded reductions of uterine blood flow, Furthermore, the effect of maternal oxygen administration during reduction of uterine blood flow was compared with that during reduction of umbilical blood flow of similar degree.
Material and methods Animal preparation. Animal care and experimental procedures were approved by the Committee on Animal Research at the University of California, San Francisco. Eight mixed-breed Western ewes with time-dated singleton gestations of 133 ± 4 days at the time of study (term 145 days) were fasted 24 hours, given spinal anesthesia with 4 ml I % tetracaine hydrochloride (Pontocaine, Winthrop Laboratories, Murray Hill Station, N,Y.), and placea supine on the operating table, Polyvinyl catheters (inner diameter 0.05 inches) were inserted into pedal branches of a maternal femoral artery and vein and advanced to the descending aorta and
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Table I. Effect of maternal oxygen administration on fetal blood gases during graded reductions in umbilical blood flow Umbilical blood flow reduction Variable
Fetal descending aorta Hemoglobin (gm/dl) Oxygen saturation (%) Umbilical vein Hemoglobin (gm/dl) Oxygen saturation (%) pH Peo, (mm Hg) Po, (mm Hg)
Condition
30%
Baseline
Room air Oxygen Room air Oxygen
12.0 11.6 54.7 72.5
± ± ± ±
1.5 1.5 5.6 3.5
12.4 12.1 45.9 61.9
:t ± ± :t
1.9 1.7 9.0 12.5
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen
11.7 11.3 79.1 98.2 7.41 7.37 45.0 51.2 31.3 57.3
± ± ± ± ± ± ± ± ± ±
1.5 1.4 6.8 3.9 0.06 0.06 5.0 8.8 4.1 9.7
12.1 11.9 79.0 96.6 7.39 7.36 47.4 51.3 32.0 53.9
:t 1.8
± 1.6 :t 8.0 :t 4.5 :t 0.08 :t 0.07 :t 5.7 ± 5.0 :t 2.0 :t 8.2
I
50%
13.0 12.6 33.7 44.4 12.6 12.3 74.9 91.9 7.38 7.34 48.8 53.0 29.8 45.2
I
75%
± 1.8
13.7 13.7 20.7 28.2
± ± ± ±
± 1.7
13.4 13.4 70.9 88.4 7.34 7.27 51.4 54.4 32.1 45.8
± 2.0
± 1.6 ± 9.9 ± 14.8
± ± ± ±
±
± ± ±
±
1.6 4.6 2.7 0.06 0.07 3.4 6.7 1.0 6.9
2.0 1.9* 9.3 13.0*t:j:
± 1.8* ± 7.0 ± 2.2t ± 0.07 ± 0.09*t ± 4.5 ± 7.3*t ± 9.5 ± 10.7t:j:
Data are mean ± SD from five experiments. *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen.
inferior vena cava, respectively. A continuous intravenous infusion of 0.9% saline solution (500 to 1000 ml) was administered to the ewe throughout the surgical procedure. Ketamine hydrochloride, 50 to 100 mg, was injected intravenously as necessary to maintain sedation. The ewe's abdomen was opened in the midline, and a snare was placed around the common segment of the uterine artery so that uterine blood flow could be controlled. In addition, a precalibrated electromagnetic flow transducer of appropriate size was placed around the main uterine artery supplying the pregnant horn. The fetal hind limbs were exposed through a small uterine incision. Anesthesia for the placement of all fetal catheters was provided locally with 0.5% lidocaine hydrochloride and systemically with 15 to 25 mg intramuscular ketamine hydrochloride given to the fetus. Polyvinyl catheters (inner diameter 0.03 inches) were inserted through pedal branches into the descending aorta and the inferior vena cava. A 3.5 Fr multiple sidehole catheter was inserted through a cotyledonary tributary into one of the two main umbilical veins. After placing an inflatable cuff occluder around the umbilical cord, an amniotic catheter was inserted to lie adjacent to the fetal trunk. Through a separate uterine incision, the common umbilical artery was isolated by a retroperitoneal approach as described previously.6 The diameter of the common umbilical artery was measured, ranging from 4.5 to 5.5 mm, and a precalibrated electromagnetic flow transducer of appropriate size was placed around it. The fetal and uterine incisions were closed, and am-
niotic fluid lost during surgery was replaced with warm saline solution. All catheters were filled with heparin (1000 IU Iml) and plugged. Together with the transducer cables of the flow probes and the snare, they were then directed subcutaneously to the ewe's flank, exteriorized, and stored in a vinyl pouch. On the day of surgery and each day afterward the ewe received 2 million IU penicillin G and 100 mg gentamicin, half intravenously and half into the amniotic cavity. Catheters were flushed daily and refilled with heparin. Experimental protocol and measurements. Experiments were performed 1 to 3 days after surgery while the ewe stood quietly in a study cage. Pressures in the fetal descending aorta, umbilical vein, inferior vena cava, and amniotic cavity were measured with carefully calibrated Statham P23Db pressure transducers (Gould Inc., Oxnard, Calif.). Amniotic pressure was used as the zero pressure reference. Fetal heart rate was measured with a cardiotrachometer triggered by the arterial pulse pressure. Readings of uterine and umbilical blood flow were made on Statham SP 2202 electromagnetic blood flow meters. Mean blood flows, fetal heart rate, and pressures were recorded continuously on an Astro-Med MT-8800 direct writing recorder (West Warwick, R.I.). Baseline blood samples were withdrawn simultaneously from the fetal descending aorta and the umbilical vein while the ewe was breathing room air or 100% oxygen for at least 15 minutes. The oxygen was administered to the ewe through a loosely fitting plastic bag at a rate of 15 L/min. Blood gases and pH were
Effect of maternal oxygen on fetal oxygenation
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235
Table II. The effect of maternal oxygen administration on fetal oxygenation during graded reductions in umbilical blood flow Umbilical blood flow reduction Variable
Umbilical blood flow (% of control) Umbilical blood flow (ml/min/kg) Umbilical vein oxygen (ml oxygen/dl) Descending aorta oxygen (ml oxygen/dl) Oxygen delivery (ml oxygen/min/kg) Increase in oxygen delivery (mloxygen/min/kg) Oxygen consumption (ml oxygen/min/kg) Increase in .oxygen consumption (mloxygen/min/kg)
Condition
Baseline
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen
100 100 194 ± 19 190 ± 19 12.4 ± 1.5 15.0 ± 1.3 8.8 ± 1.2 11.3±1.4 24.2 ± 4.6 28.6 ± 5.0 4.4 ± 1.1
Room air Oxygen
7.0 ± 1.6 6.9 ± 0.8 -0.1 ± 0.9
30%
71 71 137 135 12.8 15.5 7.7 10.2 17.7 21.1 3.4
± ± ± ± ± ± ± ± ± ± ±
6 7 10 14 2.0 2.3 1.7 2.7 4.0 5.1 1.4
7.1 ± 1.8 7.1 ± 1.4 0.0 ± 0.8
I
50%
48 50 94 95 12.7 15.3 6.0 7.8 12.0 14.8 2.7
± ± ± ± ± ± ± ± ±
± ±
5 8 15 18 1.6 2.2 2.3 3.3 3.2 4.9 1.7
6.2 ± l.l 7.0 ± 1.2 0.8 ± 0.6
I
75% 25 25 49 48 12.7 15.9 4.0 5.5 6.4 7.7 1.3
± ± ± ± ± ± ± ± ± ± ±
6 5* 14 10* 1.4 1.9t 2.2 3.0*t+ 2.5 2.3*t+ 0.3§
4.3 ± 1.2 5.0 ± 0.8* 0.7 ± 0.6
Data are mean ± SD from five experiments. *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen. §p < 0.05 compared with baseline.
measured by a Corning 175 Blood Gas Analyzer (Medfield, Mass.). Hemoglobin concentration and oxygen saturation were measured photometrically in duplicate (Hemoximeter OSM 2, Radiometer, Copenhagen). After baseline blood samples were obtained, either umbilical or uterine blood flow was reduced in a stepwise fashion. We aimed for 30%, 50%, and 75% reductions of blood flow. At least 10 minutes after the flow remained stable at each grade of reduction. a 0.6 ml blood sample was obtained from the descending aorta and umbilical vein, and fetal heart rate, blood pressures, and blood flows were measured. Measurements were then repeated while the ewe breathed 100% oxygen for 15 minutes. Between each grade of reduction we waited at least 20 to 30 minutes or until pressures and blood flows had returned to baseline values. On each day only one type of blood flow reduction was performed; each type of blood flow reduction was performed only once per animal. At the end of the studies the ewe was killed with an overdose of pentobarbital sodium (Euthanasia-6. Veterinary Laboratories, Lexena, Kan.) followed by an intravenous injection of 10 ml saturated potassium chloride solution. The fetus was weighed and the correct positions of the catheters, flow probes, and snare were confirmed. Calculations. The oxygen content in the umbilical vein and the descending aorta, fetal oxygen delivery, and fetal oxygen consumption were calculated as follows: Oxygen content (mlldl) = 0.0134 x Hemoglobin (gm/dl) X Oxygen saturation (%)
Oxygen delivery (mil min) = Oxygen content uv (mlldl) x Placental blood flow (mllmin)1100 Oxygen consumption (mllmin) = Oxygen content uv _ DA (mlldl) x Placental blood flow (mllmin)1100 where UV is umbilical vein and DA is descending aorta. Statistical analysis. Data analysis was performed with a computerized statistical program (SuperANOVA, Abacus Concepts, Berkeley, Calif.). Data are expressed as mean ± SD. The effect of blood flow reduction and maternal oxygen administration was analyzed by an analysis of variance for repeated measurements with two within factors. Furthermore, the program tested whether a significant interaction between the two within factors (blood flow reduction and maternal oxygen administration) was present. No post hoc multiple comparison testing was performed because only within-factors and no between-factors variations were present. For all tests, after degree of freedom adjustment, p < 0.05 was considered statistically significant. Results
Fetal weight averaged 3.6 kg (range 3.0 to 4.5 kg). At baseline, while the ewe was breathing room air, fetal blood gases, umbilical blood flow, oxygen delivery, and oxygen consumption were within the normal range of values measured in our laboratory (Tables I to IV). At baseline maternal oxygen administration increased umbilical venous oxygen saturation to nearly 100%. Because umbilical blood flow did not change, maternal oxygen administration increased fetal oxygen delivery by about 4.5 mllmin/kg, representing a 20%
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Table III. The effect of maternal oxygen administration on fetal blood gases during graded reductions in uterine blood flow Uterine blood flow reduction Variable
Fetal descending aorta Hemoglobin (gm/ dl) Oxygen saturation (%) Umbilical vein Hemoglobin (gm/ dl) Oxygen saturation (%) pH
PC02 (mm Hg) Po, (mm Hg)
Condition
I
30%
Baseline
I
50%
70%
Room air Oxygen Room air Oxygen
11.3 11.0 54.7 69.7
± ± ± ±
2.2 2.1 12.9 5.1
ILl 11.0 46.8 59.7
± ± ± ±
2.3 2.2 15.1 13.5
11.5 ± 2.5 1l.I±2.2 31.0 ± 13.1 49.5 ± 15.3
11.9 12.0 14.8 21.4
± ± ± ±
2.3 2.5* 6.4 9.1*' t
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen
10.9 10.6 79.9 95.7 7.41 7.36 45.5 51.0 30.8 50.7
± ± ± ± ± ± ± ± ± ±
2.3 2.0 12.9 3.3 0.02 0.02 3.0 5.4 7.8 10.4
10.9 10.8 71.0 85.0 7.39 7.33 47.7 55.1 26.6 38.3
± ± ± ± ± ± ± ± ± ±
2.2 2.1 15.5 12.6 0.02 0.03 3.1 4.3 7.3 12.3
11.2±2.5 10.8 ± 2.2 50.9 ± 16.3 72.0 ± 14.4 7.36 ± 0.02 7.31 ± 0.01 51.9 ± 4.8 56.6 ± 5.7 19.8 ± 4.1 32.0 ± 7.1
11.7 11.7 25.0 35.1 7.29 7.24 61.0 67.1 14.8 18.9
± ± ± ± ± ± ± ± ± ±
2.5 2.5* 9.3 12.8*t 0.05 0.03*' t 6.9 6.2*' t 2.8 2.2* t' :j:
Data are mean ± SD from six experiments, *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen.
Table IV. The effect of maternal oxygen administration on fetal oxygenation during graded reductions in uterine blood flow Uterine blood flow reduction Variable
Uterine blood flow (% of control) Umbilical blood flow (ml/min/kg) Umbilical vein oxygen (ml oxygen/dl) Descending aorta oxygen (ml oxygen/dl) Oxygen delivery (ml oxygen/min/kg) Increase in oxygen delivery (mloxygen/min/kg) Oxygen consumption (ml oxygen/min/kg)
Condition
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oyxgen Room air Oxygen Room air Oxygen
Increase in oxygen consumption (mloxygen/min/kg)
Baseline
100 100 202 ± 14 201 ± 12 11.4 ± 0.9 13.7 ± 2.2 8.0 ± 1.0 10.2 ± 1.6 23.0 ± 2.0 27.4 ± 3.7 4.4 ± 3.9 6.8 ± 1.6 6.9 ± 1.3 0.1 ± 0.7
30%
73 71 205 207 10.1 12.1 6.7 8.6 20.8 25.0 4.2
± ± ± ± ± ± ± ±
± ± ±
4 5 13 19 Ll 1.4 1.5 1.2 2.2 3.0 2.1
7.0 ± 1.4 7.3 ± 1.9 0.3 ± 1.0
I
50%
50 50 211 212 7.3 10.3 4.5 7.2 15.4 21.9 6.5
± ± ± ± ± ± ± ± ± ± ±
8 7 20 24 1.5 2.1 1.3 1.7 3.0 4.4 2.6
5.9 ± 1.2 6.6 ± 1.7 0.7 ± 1.2
I
70%
30 31 219 233 3.8 5.4 2.3 3.3 8.3 12.3 4.0
± ± ± ± ±
± ± ± ± ±
±
3 3* 29 26* 1.2 2.1*' t 0.8 1.3* t 2.4 3.6*' t 2.6
3.3 ± 0.8 4.7 ± 1.6*':j: 1.4 ± 1.3§
Data are mean ± SD from six experiments. *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen. §p < 0.05 compared with baseline.
increase compared with room air (Tables II, IV). Fetal oxygen consumption remained unchanged. Graded reductions of umbilical blood flow resulted in a significant increase in fetal hemoglobin concentration (Table I). Fetal descending aortic oxygen saturation decreased significantly, whereas umbilical venous oxygen saturation remained unchanged. Fetal oxygen delivery decreased in proportion to the grade of um-
bilical blood flow reduction (Table II). With a reduction of fetal oxygen delivery below 12 ml/min/kg, fetal oxygen consumption began to decrease. Maternal oxygen administration during graded reductions of umbilical blood flow decreased umbilical venous pH and increased umbilical venous Pco 2 significantly (Table I), probably due to maternal hypercapnia. Umbilical venous Pco2 and oxygen saturation
Volume 167 Number 1
Effect of maternal oxygen on fetal oxygenation
40
Oxygen delivery at 100% oxygen 0.4 + 0.29 blood flow reduction r =0.92
237
=
30
•
• 20
• •o
o • Oxygen o Room air
o 10
Oxygen delivery at room air = 0.5 + 0.24 blood flow reduction r = 0.91
o
O+-----_,,------r------~----_,------_,
o
20
40
60
80
100
Reduction of umbilical blood flow (%) Fig. 1. Effect of maternal oxygen administration on fetal oxygen delivery during graded reductions of umbilical blood flow.
increased significantly. As a result, umbilical venous oxygen content increased to about 15.5 mllmin/kg at all grades of blood flow reduction (Table II). Thus matenlal oxygen administration increased fetal oxygen delivery by 20% compared with the corresponding room air values. There was a significant interaction between the effect of maternal oxygen administration and blood flow reduction; although oxygen administration increased fetal oxygen delivery by 4.4 mllmin/kg at baseline, increases were 3.4, 2.7, and 1.3 mllmin/kg with a 30%, 50%, and 75% reduction of umbilical blood flow. Thus the beneficial effect of maternal oxygen administration on fetal oxygen delivery diminished with the severity of blood flow reduction. Maternal oxygen administration did not increase fetal oxygen consumption significantly. Fig. I illustrates the relationship of fetal oxygen delivery to umbilical blood flow. In both room air- and oxygen-treated fetuses oxygen delivery was linearly related to umbilical blood flow. Fetal oxygen delivery was significantly greater in fetuses treated with oxygen. However, this increase was related to umbilical blood flow and diminished with the severity of blood flow reduction. Graded reductions of uterine blood flow resulted in a significant increase in fetal hemoglobin concentration (Table III). Fetal arterial and umbilical venous oxygen saturation decreased significantly; umbilical blood flow increased by a modest degree. Fetal oxygen delivery decreased when uterine blood flow fell below 60% of baseline values (Table IV). With a reduction of fetal
oxygen delivery below 15 mllmin/kg, fetal oxygen consumption began to decrease. Maternal oxygen administration during reductions of uterine blood flow decreased umbilical venous pH and increased umbilical venous Pco 2 significantly (Table Ill), indicating maternal hypercapnia. Umbilical venous Pco. and oxygen saturation increased significantly. As a result, maternal oxygen administration increased umbilical venous oxygen content by about 2 mil dl at all grades of blood flow reduction (Table IV). Because umbilical blood flow remained unchanged, maternal oxygen administration increased fetal oxygen delivery by about 4 mllmin/kg at all grades of uterine blood flow reduction. There was no significant interaction between the effect of maternal oxygen administration and blood flow reduction; thus the beneficial effect of maternal oxygen administration on fetal oxygen delivery was about the same at baseline and at 30%, 50%, and 70% reductions of uterine blood flow. Maternal oxygen administration increased fetal oxygen consumption significantly by 1.4 ± 1.3 mllmin/kg when uterine blood flow was reduced to 30% at baseline. Fig. 2 illustrates the relationship of fetal oxygen delivery to uterine blood flow reduction. In room airand oxygen-treated fetuses, oxygen delivery was logarithmically related to uterine blood flow. Fetal oxygen delivery was significantly greater in fetuses treated with oxygen. The increase in fetal oxygen delivery by maternal oxygen administration was not related to the grade of uterine blood flow reduction, even when
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Paulick, Meyers, and Rudolph
40
July 1992 Am J Obstet Gynecol
Oxygen delivery at 100% oxygen ;: • 29 + 28.6 log (blood flow reduction) f= 0.82
30
••
20
• Oxygen o Roomair 10 Oxygen delivery at room air = - 32 + 27.7 log (blood flow reduction) r = 0.91
o +-------~------~------~------._----~ 100 60 80 20 40 o Reduction of uterine blood flow (%)
Fig. 2. Effect of maternal oxygen administration on fetal oxygen delivery during graded reductions of uterine blood flow.
uterine blood flow was reduced to 30% of baseline values.
Comment The aim of the present study was to assess the effect of maternal oxygen administration on fetal blood gases, oxygen delivery, and oxygen consumption during graded reductions of uterine blood flow. The effect of maternal oxygen administration during reductions of uterine blood flow was also compared with that during reductions of umbilical blood flow of similar degree. To reduce uterine blood flow, we used a snare placed around the common uterine artery. The effect of constricting the snare was monitored with a flow probe placed around the main uterine artery supplying the pregnant horn. Although the method is easy to use, certain limitations must be kept in mind. First, the uteroplacental circulation receives some blood supply from the ovarian arteries, which were not constricted by the snare, and second, although constriction of the snare should produce equal blood flow reduction in both uterine arteries, this may n?t always be true. 7 Because of these limitations, cha~ges in utero placental blood flow may not have been accurately reflected by measurement of flow in one uterine artery. Our results on the effect of reducing umbilical blood flow are in close agreement with previous studies.s,9 Umbilical venous oxygen content did not decrease during reduction of umbilical blood flow; thus fetal oxygen delivery was linearly related to umbilical blood flow.
Fetal oxygen consumption was maintained with reduction of umbilical blood flow to about 50% of baseline values; further reductions were associated with a progressive fall in oxygen consumption. The effect of maternal oxygen administration on fetal oxygenation during reduction of umbilical blood flow has been studied previously.' From these studies it was concluded that maternal oxygen administration increases oxygen delivery to the fetus during times of reduced umbilical perfusion. However, because umbilical venous oxygen content does not decrease and may actually increase during reduction of umbilical blood flow,9 only a small amount of oxygen can be added by maternal oxygen administration. Under these conditions umbilical blood flow is the main determinant of fetal oxygen delivery; the beneficial effect of maternal oxygen administration diminishes with the severity of blood flow reduction. Thus maternal oxygen administration has only a modest effect on fetal oxygen delivery when umbilical blood flow falls below 50% of baseline values. The effect of uterine blood flow reduction on fetal oxygenation has been studied extensively.,o-'2 In agreement with these studies our results demonstrate that the oxygen supply to the pregnant uterus exceeds the minimum necessary to maintain fetal oxygen delivery. Thus fetal oxygen delivery started to decrease only when uterine blood flow fell below 60% of baseline values. A previous study investigated the effect of maternal
Volume 167 Number 1
oxygen administration on fetal oxygenation in chronically hypoxemic, growth-retarded fetal sheep.s In this study maternal arterial oxygen content and umbilical blood flow were in the physiologic range of values. Thus it may be speculated that the underlying cause for chronic hypoxemia in these fetuses was a severe reduction in uterine blood flow. Maternal oxygen administration increased fetal oxygen delivery by about 5.5 mllmin/kg. 5 In our present study maternal oxygen administration has been shown to have a significant effect on fetal oxygen delivery, even with a short-term reduction in uterine blood flow to 30% of baseline. During reduction of uterine blood flow umbilical venous oxygen saturation decreases significantly. Thus a substantial amount of oxygen can be added to umbilical venous blood. For example, when uterine blood flow was reduced to 30% of baseline, maternal oxygen administration increased umbilical venous oxygen content from 3.8 to 5.4 mil dl. Because umbilical blood flow did not change, maternal oxygen administration increased fetal oxygen delivery from 8.3 to 12.3 mllmin/kg, representing a 50% increase. In summary, we have demonstrated that maternal oxygen administration has a significant effect on fetal oxygenation during short-term reductions of uterine or umbilical blood flow. However, the beneficial effect of maternal oxygen administration is far greater during reductions of uterine blood flow than during reductions of umbilical blood flow. If the response of the human fetus to maternal oxygen administration is similar to that of the sheep fetus, maternal oxygen administration may be beneficial to the fetus during labor, especially when the fetal heart rate pattern is suggestive of reduced uterine blood flow.
Effect of maternal oxygen on fetal oxygenation
239
We thank Christine Roman, Roger Chang, and Mario Trujillo for skillful technical and Paul Sagan for editorial assistance. REFERENCES I. Huch A, Huch R, Schneider H, Rooth G. Continuous transcutaneous monitoring of fetal oxygen tension during labour. Br] Obstet Gynaecol 1977;84:1-39. 2. Nicolaides KH, Campbell S, Bradley R], Bilardo CM, Sooth ill PW, Gibb D. Maternal oxygen therapy for intrauterine growth retardation. Lancet 1987; I :942-5. 3. Kunzel W, Wulf H. Der Einflul3 der maternen Ventilation auf die aktuellen Blutgase und den Saure-Basen-Status des Feten. Z Geburtshilfe GynakoI1970;172:1-24. 4. Edelstone DI, Peticca BB, Goldblum LJ. Effects of maternal oxygen administration on fetal oxygenation during reduction in umbilical blood flow in fetal lambs. AM] OBSTET GYNECOL 1985;152:351-8. 5. Goetzman BW, Itskovitz J, Rudolph AM. Fetal adaptations to spontaneous hypoxemia and responses to maternal oxygen breathing. Bioi Neonate 1984;46:276-84. 6. Berman W, Goodlin RC, Heymann MA, Rudolph AM. Measurement of umbilical blood flow in fetal lambs in utero.] Appl Physiol 1975;39: 1056-9. 7. Clark K, Durnwald M, Austin J. A model for studying chronic reduction in uterine blood flow in pregnant sheep. AmJ PhysioI1982;242:H297-301. 8. Edelstone DI, Rudolph AM, Heymann MA. Effects of hypoxemia and decreasing umbilical blood flow on liver and ductus venosus blood flows in fetal Iambs. Am] Physiol 1980;238:H656-63. 9. Itskovitz J, La Gamma EF, Rudolph AM. The effect of reducing umbilical blood flow on fetal oxygenation. AM ] OBSTET GYNECOL 1983;145:813-8. 10. Wilkening RB, Meschia G. Fetal oxygen uptake, oxygenation, and acid-base balance as a function of uterine blood flow. Am J Physiol 1983;244:H749-55. 11. Skillman CA, Plessinger MA, Woods JR, Clark KE. Effect of graded reductions in uteroplacental blood flow on the fetal Iamb. Am J Physiol 1985;249:HI098-1105. 12. Yaffe H, Parer ]T, Block BS, Llanos AJ. Cardiorespiratory responses to graded reductions of uterine blood flow in the sheep fetus.] Dev Physiol 1987;9:325-36.
Key words: Umbilical blood flow, fetal oxygen delivery, fetal oxygen consumption The effect of maternal oxygen administration during labor on fetal oxygenation is controversiaL In one clinical study maternal oxygen administration increased fetal arterial P0 2 from 15 to 21 mm Hg,l In long-term, growth-retarded human fetuses maternal oxygen administration increased umbilical venous P0 2 ,2 On the other hand, it has been argued that maternal oxygen administration will have no major effect on fetal oxygenation because maternal arterial blood is almost completely saturated with oxygen; therefore, increasing the maternal arterial P0 2 above 100 mm Hg will increase only the amount of oxygen physically dissolved, which is relatively small compared with that attached to hemoglobin,3 During labor fetal oxygenation may need to be improved for reduction of uterine or umbilical blood flow, In fetal sheep maternal oxygen administration during reduction of umbilical blood flow improved fetal oxygenation by a modest degree.' Uterine blood flow may
From the Cardiovascular Research Institute" and the Departments of Pediatrics/ Surgery,' and Obstetrics, Gynecology and Reproductive Sciences," The University of California, San Francisco. Supported by National Heart, Lung, and Blood Institute Program Project Grant No. HL-24056 and a Deutsche Forschungsgemeinschaft Research Fellowship (DFG Pa 34211-2) awarded to R. P. Received for publication September 30, 1991; revised January 17, 1992; accepted January 27,1992. Reprint requests; AbrahamM. Rudolph, MD, Box 0544, HSE 1403, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-0544. 611136687
be markedly reduced in long-term, growth-retarded sheep fetuses, and maternal oxygen administration resulted in a significant improvement of fetal oxygenation,' However, the effect of maternal oxygen administration on fetal oxygenation during reductions of uterine blood flow has not been investigated systematically. The aim of the present study was to assess the effect of maternal oxygen administration on fetal blood gases, oxygen delivery, and oxygen consumption during graded reductions of uterine blood flow, Furthermore, the effect of maternal oxygen administration during reduction of uterine blood flow was compared with that during reduction of umbilical blood flow of similar degree.
Material and methods Animal preparation. Animal care and experimental procedures were approved by the Committee on Animal Research at the University of California, San Francisco. Eight mixed-breed Western ewes with time-dated singleton gestations of 133 ± 4 days at the time of study (term 145 days) were fasted 24 hours, given spinal anesthesia with 4 ml I % tetracaine hydrochloride (Pontocaine, Winthrop Laboratories, Murray Hill Station, N,Y.), and placea supine on the operating table, Polyvinyl catheters (inner diameter 0.05 inches) were inserted into pedal branches of a maternal femoral artery and vein and advanced to the descending aorta and
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July 1992 Am J Obstet Gynecol
Table I. Effect of maternal oxygen administration on fetal blood gases during graded reductions in umbilical blood flow Umbilical blood flow reduction Variable
Fetal descending aorta Hemoglobin (gm/dl) Oxygen saturation (%) Umbilical vein Hemoglobin (gm/dl) Oxygen saturation (%) pH Peo, (mm Hg) Po, (mm Hg)
Condition
30%
Baseline
Room air Oxygen Room air Oxygen
12.0 11.6 54.7 72.5
± ± ± ±
1.5 1.5 5.6 3.5
12.4 12.1 45.9 61.9
:t ± ± :t
1.9 1.7 9.0 12.5
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen
11.7 11.3 79.1 98.2 7.41 7.37 45.0 51.2 31.3 57.3
± ± ± ± ± ± ± ± ± ±
1.5 1.4 6.8 3.9 0.06 0.06 5.0 8.8 4.1 9.7
12.1 11.9 79.0 96.6 7.39 7.36 47.4 51.3 32.0 53.9
:t 1.8
± 1.6 :t 8.0 :t 4.5 :t 0.08 :t 0.07 :t 5.7 ± 5.0 :t 2.0 :t 8.2
I
50%
13.0 12.6 33.7 44.4 12.6 12.3 74.9 91.9 7.38 7.34 48.8 53.0 29.8 45.2
I
75%
± 1.8
13.7 13.7 20.7 28.2
± ± ± ±
± 1.7
13.4 13.4 70.9 88.4 7.34 7.27 51.4 54.4 32.1 45.8
± 2.0
± 1.6 ± 9.9 ± 14.8
± ± ± ±
±
± ± ±
±
1.6 4.6 2.7 0.06 0.07 3.4 6.7 1.0 6.9
2.0 1.9* 9.3 13.0*t:j:
± 1.8* ± 7.0 ± 2.2t ± 0.07 ± 0.09*t ± 4.5 ± 7.3*t ± 9.5 ± 10.7t:j:
Data are mean ± SD from five experiments. *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen.
inferior vena cava, respectively. A continuous intravenous infusion of 0.9% saline solution (500 to 1000 ml) was administered to the ewe throughout the surgical procedure. Ketamine hydrochloride, 50 to 100 mg, was injected intravenously as necessary to maintain sedation. The ewe's abdomen was opened in the midline, and a snare was placed around the common segment of the uterine artery so that uterine blood flow could be controlled. In addition, a precalibrated electromagnetic flow transducer of appropriate size was placed around the main uterine artery supplying the pregnant horn. The fetal hind limbs were exposed through a small uterine incision. Anesthesia for the placement of all fetal catheters was provided locally with 0.5% lidocaine hydrochloride and systemically with 15 to 25 mg intramuscular ketamine hydrochloride given to the fetus. Polyvinyl catheters (inner diameter 0.03 inches) were inserted through pedal branches into the descending aorta and the inferior vena cava. A 3.5 Fr multiple sidehole catheter was inserted through a cotyledonary tributary into one of the two main umbilical veins. After placing an inflatable cuff occluder around the umbilical cord, an amniotic catheter was inserted to lie adjacent to the fetal trunk. Through a separate uterine incision, the common umbilical artery was isolated by a retroperitoneal approach as described previously.6 The diameter of the common umbilical artery was measured, ranging from 4.5 to 5.5 mm, and a precalibrated electromagnetic flow transducer of appropriate size was placed around it. The fetal and uterine incisions were closed, and am-
niotic fluid lost during surgery was replaced with warm saline solution. All catheters were filled with heparin (1000 IU Iml) and plugged. Together with the transducer cables of the flow probes and the snare, they were then directed subcutaneously to the ewe's flank, exteriorized, and stored in a vinyl pouch. On the day of surgery and each day afterward the ewe received 2 million IU penicillin G and 100 mg gentamicin, half intravenously and half into the amniotic cavity. Catheters were flushed daily and refilled with heparin. Experimental protocol and measurements. Experiments were performed 1 to 3 days after surgery while the ewe stood quietly in a study cage. Pressures in the fetal descending aorta, umbilical vein, inferior vena cava, and amniotic cavity were measured with carefully calibrated Statham P23Db pressure transducers (Gould Inc., Oxnard, Calif.). Amniotic pressure was used as the zero pressure reference. Fetal heart rate was measured with a cardiotrachometer triggered by the arterial pulse pressure. Readings of uterine and umbilical blood flow were made on Statham SP 2202 electromagnetic blood flow meters. Mean blood flows, fetal heart rate, and pressures were recorded continuously on an Astro-Med MT-8800 direct writing recorder (West Warwick, R.I.). Baseline blood samples were withdrawn simultaneously from the fetal descending aorta and the umbilical vein while the ewe was breathing room air or 100% oxygen for at least 15 minutes. The oxygen was administered to the ewe through a loosely fitting plastic bag at a rate of 15 L/min. Blood gases and pH were
Effect of maternal oxygen on fetal oxygenation
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235
Table II. The effect of maternal oxygen administration on fetal oxygenation during graded reductions in umbilical blood flow Umbilical blood flow reduction Variable
Umbilical blood flow (% of control) Umbilical blood flow (ml/min/kg) Umbilical vein oxygen (ml oxygen/dl) Descending aorta oxygen (ml oxygen/dl) Oxygen delivery (ml oxygen/min/kg) Increase in oxygen delivery (mloxygen/min/kg) Oxygen consumption (ml oxygen/min/kg) Increase in .oxygen consumption (mloxygen/min/kg)
Condition
Baseline
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen
100 100 194 ± 19 190 ± 19 12.4 ± 1.5 15.0 ± 1.3 8.8 ± 1.2 11.3±1.4 24.2 ± 4.6 28.6 ± 5.0 4.4 ± 1.1
Room air Oxygen
7.0 ± 1.6 6.9 ± 0.8 -0.1 ± 0.9
30%
71 71 137 135 12.8 15.5 7.7 10.2 17.7 21.1 3.4
± ± ± ± ± ± ± ± ± ± ±
6 7 10 14 2.0 2.3 1.7 2.7 4.0 5.1 1.4
7.1 ± 1.8 7.1 ± 1.4 0.0 ± 0.8
I
50%
48 50 94 95 12.7 15.3 6.0 7.8 12.0 14.8 2.7
± ± ± ± ± ± ± ± ±
± ±
5 8 15 18 1.6 2.2 2.3 3.3 3.2 4.9 1.7
6.2 ± l.l 7.0 ± 1.2 0.8 ± 0.6
I
75% 25 25 49 48 12.7 15.9 4.0 5.5 6.4 7.7 1.3
± ± ± ± ± ± ± ± ± ± ±
6 5* 14 10* 1.4 1.9t 2.2 3.0*t+ 2.5 2.3*t+ 0.3§
4.3 ± 1.2 5.0 ± 0.8* 0.7 ± 0.6
Data are mean ± SD from five experiments. *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen. §p < 0.05 compared with baseline.
measured by a Corning 175 Blood Gas Analyzer (Medfield, Mass.). Hemoglobin concentration and oxygen saturation were measured photometrically in duplicate (Hemoximeter OSM 2, Radiometer, Copenhagen). After baseline blood samples were obtained, either umbilical or uterine blood flow was reduced in a stepwise fashion. We aimed for 30%, 50%, and 75% reductions of blood flow. At least 10 minutes after the flow remained stable at each grade of reduction. a 0.6 ml blood sample was obtained from the descending aorta and umbilical vein, and fetal heart rate, blood pressures, and blood flows were measured. Measurements were then repeated while the ewe breathed 100% oxygen for 15 minutes. Between each grade of reduction we waited at least 20 to 30 minutes or until pressures and blood flows had returned to baseline values. On each day only one type of blood flow reduction was performed; each type of blood flow reduction was performed only once per animal. At the end of the studies the ewe was killed with an overdose of pentobarbital sodium (Euthanasia-6. Veterinary Laboratories, Lexena, Kan.) followed by an intravenous injection of 10 ml saturated potassium chloride solution. The fetus was weighed and the correct positions of the catheters, flow probes, and snare were confirmed. Calculations. The oxygen content in the umbilical vein and the descending aorta, fetal oxygen delivery, and fetal oxygen consumption were calculated as follows: Oxygen content (mlldl) = 0.0134 x Hemoglobin (gm/dl) X Oxygen saturation (%)
Oxygen delivery (mil min) = Oxygen content uv (mlldl) x Placental blood flow (mllmin)1100 Oxygen consumption (mllmin) = Oxygen content uv _ DA (mlldl) x Placental blood flow (mllmin)1100 where UV is umbilical vein and DA is descending aorta. Statistical analysis. Data analysis was performed with a computerized statistical program (SuperANOVA, Abacus Concepts, Berkeley, Calif.). Data are expressed as mean ± SD. The effect of blood flow reduction and maternal oxygen administration was analyzed by an analysis of variance for repeated measurements with two within factors. Furthermore, the program tested whether a significant interaction between the two within factors (blood flow reduction and maternal oxygen administration) was present. No post hoc multiple comparison testing was performed because only within-factors and no between-factors variations were present. For all tests, after degree of freedom adjustment, p < 0.05 was considered statistically significant. Results
Fetal weight averaged 3.6 kg (range 3.0 to 4.5 kg). At baseline, while the ewe was breathing room air, fetal blood gases, umbilical blood flow, oxygen delivery, and oxygen consumption were within the normal range of values measured in our laboratory (Tables I to IV). At baseline maternal oxygen administration increased umbilical venous oxygen saturation to nearly 100%. Because umbilical blood flow did not change, maternal oxygen administration increased fetal oxygen delivery by about 4.5 mllmin/kg, representing a 20%
236
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July 1992 Am J Obstet Gynecol
Table III. The effect of maternal oxygen administration on fetal blood gases during graded reductions in uterine blood flow Uterine blood flow reduction Variable
Fetal descending aorta Hemoglobin (gm/ dl) Oxygen saturation (%) Umbilical vein Hemoglobin (gm/ dl) Oxygen saturation (%) pH
PC02 (mm Hg) Po, (mm Hg)
Condition
I
30%
Baseline
I
50%
70%
Room air Oxygen Room air Oxygen
11.3 11.0 54.7 69.7
± ± ± ±
2.2 2.1 12.9 5.1
ILl 11.0 46.8 59.7
± ± ± ±
2.3 2.2 15.1 13.5
11.5 ± 2.5 1l.I±2.2 31.0 ± 13.1 49.5 ± 15.3
11.9 12.0 14.8 21.4
± ± ± ±
2.3 2.5* 6.4 9.1*' t
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen Room air Oxygen
10.9 10.6 79.9 95.7 7.41 7.36 45.5 51.0 30.8 50.7
± ± ± ± ± ± ± ± ± ±
2.3 2.0 12.9 3.3 0.02 0.02 3.0 5.4 7.8 10.4
10.9 10.8 71.0 85.0 7.39 7.33 47.7 55.1 26.6 38.3
± ± ± ± ± ± ± ± ± ±
2.2 2.1 15.5 12.6 0.02 0.03 3.1 4.3 7.3 12.3
11.2±2.5 10.8 ± 2.2 50.9 ± 16.3 72.0 ± 14.4 7.36 ± 0.02 7.31 ± 0.01 51.9 ± 4.8 56.6 ± 5.7 19.8 ± 4.1 32.0 ± 7.1
11.7 11.7 25.0 35.1 7.29 7.24 61.0 67.1 14.8 18.9
± ± ± ± ± ± ± ± ± ±
2.5 2.5* 9.3 12.8*t 0.05 0.03*' t 6.9 6.2*' t 2.8 2.2* t' :j:
Data are mean ± SD from six experiments, *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen.
Table IV. The effect of maternal oxygen administration on fetal oxygenation during graded reductions in uterine blood flow Uterine blood flow reduction Variable
Uterine blood flow (% of control) Umbilical blood flow (ml/min/kg) Umbilical vein oxygen (ml oxygen/dl) Descending aorta oxygen (ml oxygen/dl) Oxygen delivery (ml oxygen/min/kg) Increase in oxygen delivery (mloxygen/min/kg) Oxygen consumption (ml oxygen/min/kg)
Condition
Room air Oxygen Room air Oxygen Room air Oxygen Room air Oyxgen Room air Oxygen Room air Oxygen
Increase in oxygen consumption (mloxygen/min/kg)
Baseline
100 100 202 ± 14 201 ± 12 11.4 ± 0.9 13.7 ± 2.2 8.0 ± 1.0 10.2 ± 1.6 23.0 ± 2.0 27.4 ± 3.7 4.4 ± 3.9 6.8 ± 1.6 6.9 ± 1.3 0.1 ± 0.7
30%
73 71 205 207 10.1 12.1 6.7 8.6 20.8 25.0 4.2
± ± ± ± ± ± ± ±
± ± ±
4 5 13 19 Ll 1.4 1.5 1.2 2.2 3.0 2.1
7.0 ± 1.4 7.3 ± 1.9 0.3 ± 1.0
I
50%
50 50 211 212 7.3 10.3 4.5 7.2 15.4 21.9 6.5
± ± ± ± ± ± ± ± ± ± ±
8 7 20 24 1.5 2.1 1.3 1.7 3.0 4.4 2.6
5.9 ± 1.2 6.6 ± 1.7 0.7 ± 1.2
I
70%
30 31 219 233 3.8 5.4 2.3 3.3 8.3 12.3 4.0
± ± ± ± ±
± ± ± ± ±
±
3 3* 29 26* 1.2 2.1*' t 0.8 1.3* t 2.4 3.6*' t 2.6
3.3 ± 0.8 4.7 ± 1.6*':j: 1.4 ± 1.3§
Data are mean ± SD from six experiments. *Significant effect of blood flow reduction. tSignificant effect of oxygen. :j:Significant interaction between blood flow reduction and oxygen. §p < 0.05 compared with baseline.
increase compared with room air (Tables II, IV). Fetal oxygen consumption remained unchanged. Graded reductions of umbilical blood flow resulted in a significant increase in fetal hemoglobin concentration (Table I). Fetal descending aortic oxygen saturation decreased significantly, whereas umbilical venous oxygen saturation remained unchanged. Fetal oxygen delivery decreased in proportion to the grade of um-
bilical blood flow reduction (Table II). With a reduction of fetal oxygen delivery below 12 ml/min/kg, fetal oxygen consumption began to decrease. Maternal oxygen administration during graded reductions of umbilical blood flow decreased umbilical venous pH and increased umbilical venous Pco 2 significantly (Table I), probably due to maternal hypercapnia. Umbilical venous Pco2 and oxygen saturation
Volume 167 Number 1
Effect of maternal oxygen on fetal oxygenation
40
Oxygen delivery at 100% oxygen 0.4 + 0.29 blood flow reduction r =0.92
237
=
30
•
• 20
• •o
o • Oxygen o Room air
o 10
Oxygen delivery at room air = 0.5 + 0.24 blood flow reduction r = 0.91
o
O+-----_,,------r------~----_,------_,
o
20
40
60
80
100
Reduction of umbilical blood flow (%) Fig. 1. Effect of maternal oxygen administration on fetal oxygen delivery during graded reductions of umbilical blood flow.
increased significantly. As a result, umbilical venous oxygen content increased to about 15.5 mllmin/kg at all grades of blood flow reduction (Table II). Thus matenlal oxygen administration increased fetal oxygen delivery by 20% compared with the corresponding room air values. There was a significant interaction between the effect of maternal oxygen administration and blood flow reduction; although oxygen administration increased fetal oxygen delivery by 4.4 mllmin/kg at baseline, increases were 3.4, 2.7, and 1.3 mllmin/kg with a 30%, 50%, and 75% reduction of umbilical blood flow. Thus the beneficial effect of maternal oxygen administration on fetal oxygen delivery diminished with the severity of blood flow reduction. Maternal oxygen administration did not increase fetal oxygen consumption significantly. Fig. I illustrates the relationship of fetal oxygen delivery to umbilical blood flow. In both room air- and oxygen-treated fetuses oxygen delivery was linearly related to umbilical blood flow. Fetal oxygen delivery was significantly greater in fetuses treated with oxygen. However, this increase was related to umbilical blood flow and diminished with the severity of blood flow reduction. Graded reductions of uterine blood flow resulted in a significant increase in fetal hemoglobin concentration (Table III). Fetal arterial and umbilical venous oxygen saturation decreased significantly; umbilical blood flow increased by a modest degree. Fetal oxygen delivery decreased when uterine blood flow fell below 60% of baseline values (Table IV). With a reduction of fetal
oxygen delivery below 15 mllmin/kg, fetal oxygen consumption began to decrease. Maternal oxygen administration during reductions of uterine blood flow decreased umbilical venous pH and increased umbilical venous Pco 2 significantly (Table Ill), indicating maternal hypercapnia. Umbilical venous Pco. and oxygen saturation increased significantly. As a result, maternal oxygen administration increased umbilical venous oxygen content by about 2 mil dl at all grades of blood flow reduction (Table IV). Because umbilical blood flow remained unchanged, maternal oxygen administration increased fetal oxygen delivery by about 4 mllmin/kg at all grades of uterine blood flow reduction. There was no significant interaction between the effect of maternal oxygen administration and blood flow reduction; thus the beneficial effect of maternal oxygen administration on fetal oxygen delivery was about the same at baseline and at 30%, 50%, and 70% reductions of uterine blood flow. Maternal oxygen administration increased fetal oxygen consumption significantly by 1.4 ± 1.3 mllmin/kg when uterine blood flow was reduced to 30% at baseline. Fig. 2 illustrates the relationship of fetal oxygen delivery to uterine blood flow reduction. In room airand oxygen-treated fetuses, oxygen delivery was logarithmically related to uterine blood flow. Fetal oxygen delivery was significantly greater in fetuses treated with oxygen. The increase in fetal oxygen delivery by maternal oxygen administration was not related to the grade of uterine blood flow reduction, even when
238
Paulick, Meyers, and Rudolph
40
July 1992 Am J Obstet Gynecol
Oxygen delivery at 100% oxygen ;: • 29 + 28.6 log (blood flow reduction) f= 0.82
30
••
20
• Oxygen o Roomair 10 Oxygen delivery at room air = - 32 + 27.7 log (blood flow reduction) r = 0.91
o +-------~------~------~------._----~ 100 60 80 20 40 o Reduction of uterine blood flow (%)
Fig. 2. Effect of maternal oxygen administration on fetal oxygen delivery during graded reductions of uterine blood flow.
uterine blood flow was reduced to 30% of baseline values.
Comment The aim of the present study was to assess the effect of maternal oxygen administration on fetal blood gases, oxygen delivery, and oxygen consumption during graded reductions of uterine blood flow. The effect of maternal oxygen administration during reductions of uterine blood flow was also compared with that during reductions of umbilical blood flow of similar degree. To reduce uterine blood flow, we used a snare placed around the common uterine artery. The effect of constricting the snare was monitored with a flow probe placed around the main uterine artery supplying the pregnant horn. Although the method is easy to use, certain limitations must be kept in mind. First, the uteroplacental circulation receives some blood supply from the ovarian arteries, which were not constricted by the snare, and second, although constriction of the snare should produce equal blood flow reduction in both uterine arteries, this may n?t always be true. 7 Because of these limitations, cha~ges in utero placental blood flow may not have been accurately reflected by measurement of flow in one uterine artery. Our results on the effect of reducing umbilical blood flow are in close agreement with previous studies.s,9 Umbilical venous oxygen content did not decrease during reduction of umbilical blood flow; thus fetal oxygen delivery was linearly related to umbilical blood flow.
Fetal oxygen consumption was maintained with reduction of umbilical blood flow to about 50% of baseline values; further reductions were associated with a progressive fall in oxygen consumption. The effect of maternal oxygen administration on fetal oxygenation during reduction of umbilical blood flow has been studied previously.' From these studies it was concluded that maternal oxygen administration increases oxygen delivery to the fetus during times of reduced umbilical perfusion. However, because umbilical venous oxygen content does not decrease and may actually increase during reduction of umbilical blood flow,9 only a small amount of oxygen can be added by maternal oxygen administration. Under these conditions umbilical blood flow is the main determinant of fetal oxygen delivery; the beneficial effect of maternal oxygen administration diminishes with the severity of blood flow reduction. Thus maternal oxygen administration has only a modest effect on fetal oxygen delivery when umbilical blood flow falls below 50% of baseline values. The effect of uterine blood flow reduction on fetal oxygenation has been studied extensively.,o-'2 In agreement with these studies our results demonstrate that the oxygen supply to the pregnant uterus exceeds the minimum necessary to maintain fetal oxygen delivery. Thus fetal oxygen delivery started to decrease only when uterine blood flow fell below 60% of baseline values. A previous study investigated the effect of maternal
Volume 167 Number 1
oxygen administration on fetal oxygenation in chronically hypoxemic, growth-retarded fetal sheep.s In this study maternal arterial oxygen content and umbilical blood flow were in the physiologic range of values. Thus it may be speculated that the underlying cause for chronic hypoxemia in these fetuses was a severe reduction in uterine blood flow. Maternal oxygen administration increased fetal oxygen delivery by about 5.5 mllmin/kg. 5 In our present study maternal oxygen administration has been shown to have a significant effect on fetal oxygen delivery, even with a short-term reduction in uterine blood flow to 30% of baseline. During reduction of uterine blood flow umbilical venous oxygen saturation decreases significantly. Thus a substantial amount of oxygen can be added to umbilical venous blood. For example, when uterine blood flow was reduced to 30% of baseline, maternal oxygen administration increased umbilical venous oxygen content from 3.8 to 5.4 mil dl. Because umbilical blood flow did not change, maternal oxygen administration increased fetal oxygen delivery from 8.3 to 12.3 mllmin/kg, representing a 50% increase. In summary, we have demonstrated that maternal oxygen administration has a significant effect on fetal oxygenation during short-term reductions of uterine or umbilical blood flow. However, the beneficial effect of maternal oxygen administration is far greater during reductions of uterine blood flow than during reductions of umbilical blood flow. If the response of the human fetus to maternal oxygen administration is similar to that of the sheep fetus, maternal oxygen administration may be beneficial to the fetus during labor, especially when the fetal heart rate pattern is suggestive of reduced uterine blood flow.
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239
We thank Christine Roman, Roger Chang, and Mario Trujillo for skillful technical and Paul Sagan for editorial assistance. REFERENCES I. Huch A, Huch R, Schneider H, Rooth G. Continuous transcutaneous monitoring of fetal oxygen tension during labour. Br] Obstet Gynaecol 1977;84:1-39. 2. Nicolaides KH, Campbell S, Bradley R], Bilardo CM, Sooth ill PW, Gibb D. Maternal oxygen therapy for intrauterine growth retardation. Lancet 1987; I :942-5. 3. Kunzel W, Wulf H. Der Einflul3 der maternen Ventilation auf die aktuellen Blutgase und den Saure-Basen-Status des Feten. Z Geburtshilfe GynakoI1970;172:1-24. 4. Edelstone DI, Peticca BB, Goldblum LJ. Effects of maternal oxygen administration on fetal oxygenation during reduction in umbilical blood flow in fetal lambs. AM] OBSTET GYNECOL 1985;152:351-8. 5. Goetzman BW, Itskovitz J, Rudolph AM. Fetal adaptations to spontaneous hypoxemia and responses to maternal oxygen breathing. Bioi Neonate 1984;46:276-84. 6. Berman W, Goodlin RC, Heymann MA, Rudolph AM. Measurement of umbilical blood flow in fetal lambs in utero.] Appl Physiol 1975;39: 1056-9. 7. Clark K, Durnwald M, Austin J. A model for studying chronic reduction in uterine blood flow in pregnant sheep. AmJ PhysioI1982;242:H297-301. 8. Edelstone DI, Rudolph AM, Heymann MA. Effects of hypoxemia and decreasing umbilical blood flow on liver and ductus venosus blood flows in fetal Iambs. Am] Physiol 1980;238:H656-63. 9. Itskovitz J, La Gamma EF, Rudolph AM. The effect of reducing umbilical blood flow on fetal oxygenation. AM ] OBSTET GYNECOL 1983;145:813-8. 10. Wilkening RB, Meschia G. Fetal oxygen uptake, oxygenation, and acid-base balance as a function of uterine blood flow. Am J Physiol 1983;244:H749-55. 11. Skillman CA, Plessinger MA, Woods JR, Clark KE. Effect of graded reductions in uteroplacental blood flow on the fetal Iamb. Am J Physiol 1985;249:HI098-1105. 12. Yaffe H, Parer ]T, Block BS, Llanos AJ. Cardiorespiratory responses to graded reductions of uterine blood flow in the sheep fetus.] Dev Physiol 1987;9:325-36.
