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Effect of maternal hypercarbia on the newborn infant
Effect of maternal hypercarbia on the newborn infant ANTHONY D. IVANKOVIC, M.D. JAMES 0. ELAM, M.D. JOHN HUFFMAN, C.R.N.A. Chicago, Illinois
The effect of maternal hypercarbia on the clinical condition and biochemical status of the fetus has been studied in 45 term pregnant women divided into 3 groups. In each group, management of anesthesia was different in terms of maternal Pco, or anesthetic agent. Results of this study confirmed that maternal hypercarbia increases umbilical vein oxygen tension but does not significantly improve oxygen saturation. Higher one-minute Apgar scores and shorter times to sustained respiration were observed with higher carbon dioxide levels and could be explained by the stimulatory effect of carbon dioxide on initiation of respiration in the neonate.
T u E EFFEcT of maternal hypercarbia on the biochemical status and clinical condition of the fetus has not previously been studied. It was thought that such investigation would be of interest in view of the findings of Motoyama and associates 1 who showed that maternal hypercarbia is associated with increased oxygen tension and saturation in the lamb fetus. This is especially pertinent since previous observations in pregnant animals and parturient women have shown that the respiratory alkalosis associated with hyperventilation has a deleterious effect on the fetus. 2 • 3
minutes with the use of 8 L. of oxygen flow. Hypercarbia was then produced with endogenous C0 2 by removing the C0 2 absorber from the system; then the oxygen flow was decreased to 400 to 800 ml. per minute, depending on the extent to which the patients were hyperventilating. Within 2 to 3 minutes of rebreathing when the respiratory drive of hypercarbia was established, methoxyflurane was introduced (from an Ohio No. 8 Vaporizer on the inspiratory side of the circle) into the system at setting 3 for 30 to 60 seconds, then at setting 7 for another 30 to 90 seconds. The dial setting was then decreased in order to maintain relatively light surgical anesthesia and respiratory minute volume of 7 to 10 L. per minute. The second group of 15 patients, designated "control methoxyflurane group," was similarly anesthetized with methoxyflurane with the use of the Ohio No. 8 Vaporizer in a semiclosed C0 2 absorbing system. Anesthesia was induced with 4 to 6 L. per minute of oxygen and the vaporizer at setting Number 2 and then gradually increased until light surgical anesthesia was achieved. Ventilation was manually assisted. In the third group of 15 patients, saddleblock anesthesia with heavy dibucaine was
Methods The study was carried out in 45 healthy term pregnant women, none of whom presented signs of fetal distress during labor. The subjects were placed into 3 groups of 15 each, according to the management of anesthesia. The first group of patients, designated "hypercarbic methoxyflurane group," were essentially denitrogenated for 3 to 5 From the Department of Anesthesiology, Pritzker School of Medicine, University of Chicago. · This work was supported by Contract No. DADA-17-67-C-7052, Office of the Surgeon General, Department of the Army.
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administered after the cervix was fully dilated and the presenting part was at the +3 station. No oxygen was given to this group of patients. All mothers received a continuous intravenous infusion of lactated Ringer's solution throughout labor. Narcotics were not administered in the 3 hours prior to delivery. All cases were vertex presentation and were delivered by low forceps. Fetal blood samples were drawn from the undamped umbilical cord before the newborn infant started to breathe ..A.t the sa1ne time, a maternal arterial blood sample was obtained. Maternal and neonatal arterial blood samples were obtained 40 to 50 minutes after delivery in 8 patients who had received hypercarbic methoxyflurane anesthesia. Analysis for Po~ was done within 15 minutes with a Clark Radiometer Electrode initially standardized. The pH was determined by a Radiometer Glass Electrode. Pco 2 and base deficit were determined by the method of Astrup and the use of the Siggaard-Andersen nomogram. Arterial oxygen saturation for the newborn infant estimated from Helleger's nomogram for fetal oxygen dissociation.4 Methoxyflurane blood concentrations were analyzed with the use of a flame ionization detertor. 5 The clinical condition of the mothers was evaluated according to blood pressure and heart rate during and before anesthesia. The status of the infant was assessed by checking fetal heart rate between contractions, by
determining the time to sustained respiration, and by taking Apgar scores at 1 and 5 minutes after birth. 6 • 7
Results The mean data of all 3 groups are shown in Tables I and II. Induction, maintenance of anesthesia, and delivery were uneventful in all patients. There was no significant difference in maternal artery and umbilical artery methoxyflurane concentration between the control methoxyflurane and the hypercarbic methoxyflurane groups (p < 0.25). Umbilical vein methoxyflurane in the hypercarbic methoxyflurane group was significantly higher than in the control methoxyflurane group (p < 0.05). Induction time and induction-delivery interval was significantly shorter in the hypercarbic methoxyflurane group (p < 0.001). Mothers in ali 3 groups did not show significantly different degrees of metabolic acidosis (p for base excess values > 0.25). The mean umbilical vein Po 2 in the hypercarbic group was 49.5 mm. Hg; in the control methoxyflurane group, 39.7 mm. Hg; and in the saddle-block group, 32.9 mm. Hg. These are statistically significant different values (p < 0.001 and 0.05). There is a positive correlation between maternal Pco2 and umbilical vein Po 2 in the 30 cases that received general anesthesia (Fig. 1). There was no significant difference in oxygen saturation between the hypcrcarbic and the control methoxyflurane groups (p > 0.25). The
Table I. Mean data of induction~delivery interval, induction time, and methoxyflurane blood concentration Methoxyflurane concentration 1-D interval
IInduction
time in minutes
I
Maternal artery
Umbilical vein
Umbilical artery
7.90 3.41
3.30 2.31
< r.r.
3.40 2.18
Group
zn minutes
Hypercarbic methoxyflurane anesthesia Mean S.D.
6.40 2.77
1.73 0.32
!3.60 6.10
Control methoxyflurane an· esthesia Mean S.D.
9.96 2.97
"en J,U\J
1.:...uu
J.::JV
0.74
6.25
3.99
!!)
0{)
Maternal hypercarbia
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est values in the saddle-block group. The calculated umbilical vein-umbilical artery oxygen saturation difference in the control methoxyflurane group was 37.3 per cent saturation, and in the hypercarbic group umbilical vein-umbilical artery oxygen saturation difference was 32.6 per cent saturation.
groups that received general anesthesia show significantly higher umbilical vein oxygen saturation than the saddle-block group (p < 0.05) . Also, there was a statistically significant difference in all 3 groups between umbilical artery Po 2 values (p < 0.05 and 0.01), with the highest values in the hypercarbic methoxyflurane group and the low-
uvpo 2 mmHg BO
!50
40
30
20
I
I
10
I
li!O
I
I
30
40
I
150
I
BO
I
70
mm Hg
Fig. 1. The relationship between individual values of maternal artery carbon dioxide tension and umbilical vein oxygen tension. The regression line indicates a significant positive correlation (y = 0.22x + 35.3, r + 0.505. t = 3.05).
Table II. Mean data of oxygen tension and saturation, carbon dioxide tension, pH, and base excess Maternal artery Po,
I Pco, I pH I BE
Umbilical vein Po,
Hypercarbic methoxyflurane anesthesia Mean 321.00 57.60 7.18 -7.30 49.50 85.40 56.60 7.21 -8.30 28.30 53.20 56.70 7.19 -8.90 S.D. 73.80 8.81 0.06 2.22 5.60 8.10 10.30 0.05 2.51 3.31 4.44 9.32 0.04 2.80 Control methoxyflurane anesthesia Mean S.D.
362.80 26.40 7.39 -7.20 39.70 81.30 34.30 7.:;!2 -8.20 22.60 44.00 40.00 7.26 -9.30 135.60 7.75 0.07 2.21 6.77 10.84 9.78 0.07 2.15 4.25 13.90 9.67 0.08 2.58
Saddle-block anesthesia Mean S.D.
103.60 30.10 7.37 -6.83 32.90 68.80 34.80 7.31 -7.98 17.90 7.13 4.22 0.04 1.75 9.33 18.80 5.70 0.04 1.59 7.88
45.70 7.22 -9.97 11.60 0.06 2.20
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-hvDercorbic Denthrone onesthesia ~p~;;thr~ne a;esthesia spinal anesthesia Apgar score '!0 9
a 7
a 5 4
one minute
five minutes time after birth
Fig. 2. Apgar scores at one and 5 minutes after delivery. The newborn infants in the hypercarbic methoxyflurane group had highest and the infants in the control methoxyflurane group had lowest mean Apgar scores.
DJo
Newborns
100 90
so 70
so so 40
Time for sustained respiration under so seconds Fig. 3. Time for sustained respiration under 60 seconds. All newborn infants in the hypercarbic methoxyflurane group but only 10 of 15 infants in the control methoxyflurane group developed respiration within 60 seconds.
There was no significant difference in the mild degree of metabolic acidosis in umbilical vessels in all 3 groups (Table II). It should be noted that actual base excess m hypercarbic group is lower as a result of
the phenomenon described by Schwartz,S consisting of a failure of bicarbonate to rise during acutely induced hypercarbia as a result of redistribution of bicarbonate into the unbuffered extravascu-
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Maternal hypercarbia 943
BE pH
po, pea,
mEq/l
mmHg 'lOCi
aa
90
45
SO
40
'7C!
35
SO
30
150
2!5
40
20
mother
newborn
Fig. 4. Mean maternal and neonatal arterial oxygen tension, carbon dioxide tension. pH, and base excess in 8 patients during recovery from hypercarbic methoxyflurane anesthesia. Within this period of time both mothers and newborn infants had corrected respiratory acidosis.
lar-extracellular space. However, correction of the base excess for this effect was not estimated but would have yielded a lower mean base excess for the hypercarbic methoxyflurane group. The Apgar scores of all 3 groups are shown in Fig. 2. The lowest Apgar score at one minute was in the control methoxyflurane group and the highest in the hypercarbic group. This difference is statistically significant with p value < 0.01. Mean Apgar scores at 5 minutes for all groups were over 9.5. The interval from delivery until spontaneous respiration was within 60 seconds for all newborn infants in the hypercarbic group, 14 of 15 infants in the saddle-block group, but for only 10 of 15 newborn infants in the control methoxyflurane group (Fig. 3). All neonates and mothers had uneventful postpartun1 courses. Acid-base values of 8 mothers and newborn infants who received hypercarbic methoxyflurane anesthesia were determined within an hour after delivery (Fig. 4) and showed no respiratory acidosis. Comment
The results obtained from this study indicate that maternal hypercarbia increases urn-
bilical vein oxygen tension during methoxyflurane anesthesia. This is in agreement with the work of Motoyama and associates1 who showed in the lamb fetus that changes in Po 2 correlate positively with changes in maternal Pco 2 • However, we did not find the increase in fetal oxygen saturation, as reported by Motoyama and associates, to be significant. The increase in fetal oxygen tension due to maternal hypercarbia cay be explained by several different mechanisms. Alkalosis increases the affinity of blood for oxygen due to the shift to the left of the oxygen dissociation curve. Therefore, the available oxygen for the tissues and placenta will be decreased un~ess there is a decrease in the oxygen tension in the tissue. On the other hand, acidosis shifts the dissociation curve to the right so that oxygen is released from hemoglobin at higher oxygen tension levels. Increase in maternal cardiac output and uterine blood flow due to respiratory acidosis may also produce an increase in fetal oxygenation.9 • 10 It has been shown that maternal hypercarbia increases umbilical blood flow in sheep. 1 This effect would be expected in view of the lack of innervation of the umbilical blood vessels which would
944
lvankovic, Elam, and Huffman
respond to increased carbon dioxide tension by dilatation as the cerebral blood vessels respond. During the sampling of cord blood, it was noted that the umbilical vessels in the hypercarbic group were engorged and pulsatin2" vi2"orouslv. Blood samules from such vessels, therefore, were much easier to obtain than from the cords in the other groups. The umbilical vessels in some patients with low Pcoe were usually so constricted that the blood sample could not be obtained. Therefore, these patients could not be ineluded in this study. The increase in umbilical blood flow due to hypercarbia should improve fetal oxyg·en tension. It has been postulated that maternal alkalosis increases interplaccntal shunting and that maternal acidosis and hypoxia exert opposite effects.11• 1" The decrease in interplacental shunting due to respiratory acidosis will logically increase umbilical vein oxygen tension. Uterine contractions can diminish or completely arrest blood flow through the uterus/ 3 which produces an intermittent fetal hypoxia. 14 Methoxyflurane, as a general anesthetic agent, decreases uterine contractility and at a concentration of about 15 mg. per cent almost abolishes uterine contractions.15 In addition, hypercarbia can also diminish uterine contractility. 16 Decrease in or cessation of uterine contractions \vould improve uterine and umbilical blood flow and thus increase fetal tension during delivery. The decrease of intensity of uterine contractions due to a general anesthetic agent can explain why umbilical vein oxygen tension was significantly lower in patients who received saddle-block anesthesia. Voluntary breath holding and straining during regional anesthesia could also tend to produce lower fetal oxygen tension. Maternal arterial oxygen saturations were near maximal and could not explain the observed differences in fetal oxygen tensions. Perhaps a higher maternal Po 2 during general anesthesia may slightly influence umbilical vein Po 2 , since it has been reported that inhalation of oxygen may decrease fetal oxygen saturationY However, in these studies an elevated maternal Po 2 appeared to be advantageous. U
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July 15, 1970 Amer. J. Obstet. Gynec.
Most infants in the methoxyflurane groups had umbilical vein oxygen tension and oxygen saturation values higher than generally reported in the literature. As a matter of fact, the mean value of 50 mm. Hg for infants in the hypercarbic group is significantly higher than averages for any groups reported in the literature. 18 Blood sampling from the undamped cord and early estimation of blood gases eliminated lowering of Po 2 during stagnation following clamping. With the use of the saddle-block group as control subjects, the Po~ n1ean value of 32 n1n1. Hg agrees with the findings in other investigation.18 Therefore, the results of this series suggest that both methoxyflurane anesthesia and hypercarbia increase oxygen tension in the infant. The physiology of initiation of spontaneous respiration in the newborn infant is stiil not known. Hypoxia does not produce a respiratory stimulus in the newborn infant as in adults; instead it seems that hypoxia in the neonate is more likely to depress respiration.19 It has been generally accepted that hypercarbia stimulates the respiratory center in the neonate. 20 • 21 However, it has been demonstrated that severe hypercarbia in the presence of birth trauma, severe hypoxia, and ishemia depresses neonates respiration.19' 22 ~,.1ethoxyfturane, a potent anesthetic agent, produces a shift to the right of the C0 2 respiratory response curve and, consequently, a rise in the apneic threshold for carbon dioxide. 23 The increase in the C0 2 apneic threshold due to methoxyflurane can explain prolongation of onset of respiration in the newborn infant with a lower Pco 2 level and, vice versa, prolongation of onset of respiration with an increase in anesthetic concentration at a similar C0 2 level. This would explain the longer time for sustained respiration and the lower Apgar scores at one minute in the control methoxyflurane group. On the other hand, although Pco 2 was considerably lower in the saddleblock group than in the hypercarbic group, there was no significant difference in the time for sustained respiration between hypercarbic methoxyflurane and saddle-block
Volume 107 Number 6
groups. This could be explained by the absence of a C0 2 threshold or apnea in unanesthetized subjects even at extremely low Pco 2 • 2 ·> This would suggest that carbon dioxide has little or no effect on initiation of respiration in the unanesthetized neonate, and the infants born with low C0 2 values in the absence of anesthesia breathe in response to other stimuli. These studies failed to demonstrate a correlation between oxygen saturation and the clinical condition of the newborn infant. This is in agreement \\ith the work of James and colleagues 6 and somewhat in disagreement with Rorke and co-workers.~ 5 Metabolic status has been considered a useful aid in the clinical evaluation of the infant. 26 However, we encountered no instances of fetal depression despite base-excess values in newborn infants as low as -14. Although we found no correlation between anesthetic concentration and Apgar score, in agreement with Sikt~r and associates, 27 it still would seem that increased time of anesthetic exposure should influence the clinical condition of the newborn infant. Apart from the effect of lowered C0 2 tension, longer exposure of the fetus to anesthetic in the control methoxyflurane group could explain differ-
REFERENCES
1. Motoyama, E. K., Rivard, G., Acheson, F., and Cook, C. D.: Anesthesiology 28:891, 1967. 2. Moya, F., Morishima, H. 0., Shnider, S. M., and James, L. S.: AMER. J. 0BSTET. GYNEc. 91: 76, 1965. 3. Morishima, H. 0., Moya, F., Bossers, A. C., and Daniel, S. S.: AMER. J. 0BSTET. GYNEc. 88: 524, 1964. 4. Hellegers, A. E., and Schruefer, J. P.: AMER. ]. 0BSTET. GYNEC. 81: 377, 1961. 5. Lowe, H. ].: Anesthesiology 25: 808, 1964. 6. James, L. S., Weisbrot, I. M., Prince, C. E., Holaday, D. A., and Apgar, V.: ]. Pediat. 52: 379, 1958. 7. Apgar, V., Holaday, D. A., James, L. S., Weisbrot, I. M., and Berrien, C.: ]. A. M. A. 168: 1985, 1958. 8. Schwartz, W. B.: Ann. N. Y. Acad. Sci. 133: 125, 1966. 9. Richardson, D. W., Wasserman, A. ]., and Patterson, ]. L.: J. Clin. Invest. 40: 31, 1961.
Maternal hypercarbia 945
ences m the clinical condition of the neonate. However, the results suggest that the carbon dioxide levels were the more important factor in determining the early clinical condition of the newborn infant delivered with general anesthesia. As a matter of fact, James and colleagues6 in 1958 expressed a clinical impression that the highest PC0 2 values are found in the most Yigorous newborn infants. It is generally accepted that hypercarbia does not depress the cardiovascular system 28 and that up to 90 mm. Hg does not show anesthetic properties. 29 Brief hypercarbia is compatible with methoxyflurane anesthesia; Pco 2 of even 150 mm. Hg has been reported not to produce any arrhythmias. 30 Inkster 31 reported 250,000 cases of hypercarbic induction of anesthesia by mask without serious complication. We did not observe any adverse effect of hypercarbia in our group of patients, and in our opinion, elevation of Pco 2 and, in our opinion, moderate elevation of Pco 2 can improve the clinical status of the newborn infant. Moreover, hypercarbic induction of anesthesia, considering the experience of Inkster, 31 may increase the maternal safety during general anesthesia by preventing vomiting and possible aspiration.
10. Assali, N. S., Holm, L. W., and Sehgal, N.: Circ. Res. 11: 423, 1962. ll. Boe, F.: Sympos. Quant. Bioi. 19: 29, 195+. 12. Motoyama, E. K., Rivard, G., Acheson, F. M., and Cook, C. D.: Unpublished data. 13. Caldeyro-Barcia, R.: Effect of Labor and Delivery on Fetus and Newborn, New York, 1967, Pergamon Press, Inc. 14. Howard, W. F., Hunter, C. A., Jr., and Huber, C. P.: Surg. Gynec. Obstet. 112: -135, 1961. 15. Elam, J. 0.: Unpublished data. 16. Woods, J. W.: Midwest Anesthesiology Residents Meeting, Madison, Wisconsin, May 10, 1969. 17. Sahling, H.: Geburtsh. Frauenheilk. 23: .5213, 1963. 18. Bonica, ]. ].: Principles and Practice of Obstetric Analgesia and Anesthesia, in Analgesia and Anesthesia, Philadelphia, 1965, F. A. Davis Company, pp. 162-173. 19. Miller, H. C., and Behrle, F. C.: Pediatrics 14: 93, 19.54.
July 15, 1970
946 lvankovic, Elam, and Huffman
Am cr.
T?
"'I AT
Tl
'•
"11. lr _
1
T'lo
1 1
'I ,_,
1
J., and Fitting, G. Ni., Jr.: Brit. J. Anaesth. 40: 588, 1968. Symposium on Carbon Dioxide and Man, Anesthesiology 21: 585, 1960. Eisele, J. H., Eger, E. I., II, and Muallem, M.: Anesthesiology 28: 856, 1967. Black, G. VV.: Acta Anaesth. Scand. ii: 103, 1966. Inkster, J. S.: Brit. J. Anaesth. 25: 160, 1963.
27. Siker, E. S., Wolfson, B., Dubansky,
20. Miller, H. C.: Pediatrics 14: 104, 1954. ro""' r 1:101. 2i. \..ifOSS, 1'... VV .: DrH. lV~eo. DUll. ~ 1: lOV, 22. Cross, K. W., Hooper, J. M. D., and Oppe, 1""'11
J. Obstet. Gynec.
1 ....
11
T. E.: J. Physiol. (London) 22: 264, 1953. 23. Dunbar, B. S., Ovassapian, A., and Smith, T. C.: Anesthesiology 28: 1020, 1967. 24. Comroe, J. H.: Physiology of Respiration, Chicago, 1965, )rear Book Niedicai Pubiishers, Inc., p. 68. 25. Rorke, M. ]., Davey, D. A., and DuToit, H. J.: Anesthesia 23: 585, 1968. 26, Saling, E., and Schneider, D.: J. Obstet. Gynaec. Brit. Comm. 73: 562, 1967.
28. 29. 30.
31.
The effect of maternal hypercarbia on the clinical condition and biochemical status of the fetus has been studied in 45 term pregnant women divided into 3 groups. In each group, management of anesthesia was different in terms of maternal Pco, or anesthetic agent. Results of this study confirmed that maternal hypercarbia increases umbilical vein oxygen tension but does not significantly improve oxygen saturation. Higher one-minute Apgar scores and shorter times to sustained respiration were observed with higher carbon dioxide levels and could be explained by the stimulatory effect of carbon dioxide on initiation of respiration in the neonate.
T u E EFFEcT of maternal hypercarbia on the biochemical status and clinical condition of the fetus has not previously been studied. It was thought that such investigation would be of interest in view of the findings of Motoyama and associates 1 who showed that maternal hypercarbia is associated with increased oxygen tension and saturation in the lamb fetus. This is especially pertinent since previous observations in pregnant animals and parturient women have shown that the respiratory alkalosis associated with hyperventilation has a deleterious effect on the fetus. 2 • 3
minutes with the use of 8 L. of oxygen flow. Hypercarbia was then produced with endogenous C0 2 by removing the C0 2 absorber from the system; then the oxygen flow was decreased to 400 to 800 ml. per minute, depending on the extent to which the patients were hyperventilating. Within 2 to 3 minutes of rebreathing when the respiratory drive of hypercarbia was established, methoxyflurane was introduced (from an Ohio No. 8 Vaporizer on the inspiratory side of the circle) into the system at setting 3 for 30 to 60 seconds, then at setting 7 for another 30 to 90 seconds. The dial setting was then decreased in order to maintain relatively light surgical anesthesia and respiratory minute volume of 7 to 10 L. per minute. The second group of 15 patients, designated "control methoxyflurane group," was similarly anesthetized with methoxyflurane with the use of the Ohio No. 8 Vaporizer in a semiclosed C0 2 absorbing system. Anesthesia was induced with 4 to 6 L. per minute of oxygen and the vaporizer at setting Number 2 and then gradually increased until light surgical anesthesia was achieved. Ventilation was manually assisted. In the third group of 15 patients, saddleblock anesthesia with heavy dibucaine was
Methods The study was carried out in 45 healthy term pregnant women, none of whom presented signs of fetal distress during labor. The subjects were placed into 3 groups of 15 each, according to the management of anesthesia. The first group of patients, designated "hypercarbic methoxyflurane group," were essentially denitrogenated for 3 to 5 From the Department of Anesthesiology, Pritzker School of Medicine, University of Chicago. · This work was supported by Contract No. DADA-17-67-C-7052, Office of the Surgeon General, Department of the Army.
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administered after the cervix was fully dilated and the presenting part was at the +3 station. No oxygen was given to this group of patients. All mothers received a continuous intravenous infusion of lactated Ringer's solution throughout labor. Narcotics were not administered in the 3 hours prior to delivery. All cases were vertex presentation and were delivered by low forceps. Fetal blood samples were drawn from the undamped umbilical cord before the newborn infant started to breathe ..A.t the sa1ne time, a maternal arterial blood sample was obtained. Maternal and neonatal arterial blood samples were obtained 40 to 50 minutes after delivery in 8 patients who had received hypercarbic methoxyflurane anesthesia. Analysis for Po~ was done within 15 minutes with a Clark Radiometer Electrode initially standardized. The pH was determined by a Radiometer Glass Electrode. Pco 2 and base deficit were determined by the method of Astrup and the use of the Siggaard-Andersen nomogram. Arterial oxygen saturation for the newborn infant estimated from Helleger's nomogram for fetal oxygen dissociation.4 Methoxyflurane blood concentrations were analyzed with the use of a flame ionization detertor. 5 The clinical condition of the mothers was evaluated according to blood pressure and heart rate during and before anesthesia. The status of the infant was assessed by checking fetal heart rate between contractions, by
determining the time to sustained respiration, and by taking Apgar scores at 1 and 5 minutes after birth. 6 • 7
Results The mean data of all 3 groups are shown in Tables I and II. Induction, maintenance of anesthesia, and delivery were uneventful in all patients. There was no significant difference in maternal artery and umbilical artery methoxyflurane concentration between the control methoxyflurane and the hypercarbic methoxyflurane groups (p < 0.25). Umbilical vein methoxyflurane in the hypercarbic methoxyflurane group was significantly higher than in the control methoxyflurane group (p < 0.05). Induction time and induction-delivery interval was significantly shorter in the hypercarbic methoxyflurane group (p < 0.001). Mothers in ali 3 groups did not show significantly different degrees of metabolic acidosis (p for base excess values > 0.25). The mean umbilical vein Po 2 in the hypercarbic group was 49.5 mm. Hg; in the control methoxyflurane group, 39.7 mm. Hg; and in the saddle-block group, 32.9 mm. Hg. These are statistically significant different values (p < 0.001 and 0.05). There is a positive correlation between maternal Pco2 and umbilical vein Po 2 in the 30 cases that received general anesthesia (Fig. 1). There was no significant difference in oxygen saturation between the hypcrcarbic and the control methoxyflurane groups (p > 0.25). The
Table I. Mean data of induction~delivery interval, induction time, and methoxyflurane blood concentration Methoxyflurane concentration 1-D interval
IInduction
time in minutes
I
Maternal artery
Umbilical vein
Umbilical artery
7.90 3.41
3.30 2.31
< r.r.
3.40 2.18
Group
zn minutes
Hypercarbic methoxyflurane anesthesia Mean S.D.
6.40 2.77
1.73 0.32
!3.60 6.10
Control methoxyflurane an· esthesia Mean S.D.
9.96 2.97
"en J,U\J
1.:...uu
J.::JV
0.74
6.25
3.99
!!)
0{)
Maternal hypercarbia
Volume 107 Number6
941
est values in the saddle-block group. The calculated umbilical vein-umbilical artery oxygen saturation difference in the control methoxyflurane group was 37.3 per cent saturation, and in the hypercarbic group umbilical vein-umbilical artery oxygen saturation difference was 32.6 per cent saturation.
groups that received general anesthesia show significantly higher umbilical vein oxygen saturation than the saddle-block group (p < 0.05) . Also, there was a statistically significant difference in all 3 groups between umbilical artery Po 2 values (p < 0.05 and 0.01), with the highest values in the hypercarbic methoxyflurane group and the low-
uvpo 2 mmHg BO
!50
40
30
20
I
I
10
I
li!O
I
I
30
40
I
150
I
BO
I
70
mm Hg
Fig. 1. The relationship between individual values of maternal artery carbon dioxide tension and umbilical vein oxygen tension. The regression line indicates a significant positive correlation (y = 0.22x + 35.3, r + 0.505. t = 3.05).
Table II. Mean data of oxygen tension and saturation, carbon dioxide tension, pH, and base excess Maternal artery Po,
I Pco, I pH I BE
Umbilical vein Po,
Hypercarbic methoxyflurane anesthesia Mean 321.00 57.60 7.18 -7.30 49.50 85.40 56.60 7.21 -8.30 28.30 53.20 56.70 7.19 -8.90 S.D. 73.80 8.81 0.06 2.22 5.60 8.10 10.30 0.05 2.51 3.31 4.44 9.32 0.04 2.80 Control methoxyflurane anesthesia Mean S.D.
362.80 26.40 7.39 -7.20 39.70 81.30 34.30 7.:;!2 -8.20 22.60 44.00 40.00 7.26 -9.30 135.60 7.75 0.07 2.21 6.77 10.84 9.78 0.07 2.15 4.25 13.90 9.67 0.08 2.58
Saddle-block anesthesia Mean S.D.
103.60 30.10 7.37 -6.83 32.90 68.80 34.80 7.31 -7.98 17.90 7.13 4.22 0.04 1.75 9.33 18.80 5.70 0.04 1.59 7.88
45.70 7.22 -9.97 11.60 0.06 2.20
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July 15, 1970 Amer. ]. Obstet. Gynec.
lvankovic, Elam, and Huffman
-hvDercorbic Denthrone onesthesia ~p~;;thr~ne a;esthesia spinal anesthesia Apgar score '!0 9
a 7
a 5 4
one minute
five minutes time after birth
Fig. 2. Apgar scores at one and 5 minutes after delivery. The newborn infants in the hypercarbic methoxyflurane group had highest and the infants in the control methoxyflurane group had lowest mean Apgar scores.
DJo
Newborns
100 90
so 70
so so 40
Time for sustained respiration under so seconds Fig. 3. Time for sustained respiration under 60 seconds. All newborn infants in the hypercarbic methoxyflurane group but only 10 of 15 infants in the control methoxyflurane group developed respiration within 60 seconds.
There was no significant difference in the mild degree of metabolic acidosis in umbilical vessels in all 3 groups (Table II). It should be noted that actual base excess m hypercarbic group is lower as a result of
the phenomenon described by Schwartz,S consisting of a failure of bicarbonate to rise during acutely induced hypercarbia as a result of redistribution of bicarbonate into the unbuffered extravascu-
Volume 107 Number 6
Maternal hypercarbia 943
BE pH
po, pea,
mEq/l
mmHg 'lOCi
aa
90
45
SO
40
'7C!
35
SO
30
150
2!5
40
20
mother
newborn
Fig. 4. Mean maternal and neonatal arterial oxygen tension, carbon dioxide tension. pH, and base excess in 8 patients during recovery from hypercarbic methoxyflurane anesthesia. Within this period of time both mothers and newborn infants had corrected respiratory acidosis.
lar-extracellular space. However, correction of the base excess for this effect was not estimated but would have yielded a lower mean base excess for the hypercarbic methoxyflurane group. The Apgar scores of all 3 groups are shown in Fig. 2. The lowest Apgar score at one minute was in the control methoxyflurane group and the highest in the hypercarbic group. This difference is statistically significant with p value < 0.01. Mean Apgar scores at 5 minutes for all groups were over 9.5. The interval from delivery until spontaneous respiration was within 60 seconds for all newborn infants in the hypercarbic group, 14 of 15 infants in the saddle-block group, but for only 10 of 15 newborn infants in the control methoxyflurane group (Fig. 3). All neonates and mothers had uneventful postpartun1 courses. Acid-base values of 8 mothers and newborn infants who received hypercarbic methoxyflurane anesthesia were determined within an hour after delivery (Fig. 4) and showed no respiratory acidosis. Comment
The results obtained from this study indicate that maternal hypercarbia increases urn-
bilical vein oxygen tension during methoxyflurane anesthesia. This is in agreement with the work of Motoyama and associates1 who showed in the lamb fetus that changes in Po 2 correlate positively with changes in maternal Pco 2 • However, we did not find the increase in fetal oxygen saturation, as reported by Motoyama and associates, to be significant. The increase in fetal oxygen tension due to maternal hypercarbia cay be explained by several different mechanisms. Alkalosis increases the affinity of blood for oxygen due to the shift to the left of the oxygen dissociation curve. Therefore, the available oxygen for the tissues and placenta will be decreased un~ess there is a decrease in the oxygen tension in the tissue. On the other hand, acidosis shifts the dissociation curve to the right so that oxygen is released from hemoglobin at higher oxygen tension levels. Increase in maternal cardiac output and uterine blood flow due to respiratory acidosis may also produce an increase in fetal oxygenation.9 • 10 It has been shown that maternal hypercarbia increases umbilical blood flow in sheep. 1 This effect would be expected in view of the lack of innervation of the umbilical blood vessels which would
944
lvankovic, Elam, and Huffman
respond to increased carbon dioxide tension by dilatation as the cerebral blood vessels respond. During the sampling of cord blood, it was noted that the umbilical vessels in the hypercarbic group were engorged and pulsatin2" vi2"orouslv. Blood samules from such vessels, therefore, were much easier to obtain than from the cords in the other groups. The umbilical vessels in some patients with low Pcoe were usually so constricted that the blood sample could not be obtained. Therefore, these patients could not be ineluded in this study. The increase in umbilical blood flow due to hypercarbia should improve fetal oxyg·en tension. It has been postulated that maternal alkalosis increases interplaccntal shunting and that maternal acidosis and hypoxia exert opposite effects.11• 1" The decrease in interplacental shunting due to respiratory acidosis will logically increase umbilical vein oxygen tension. Uterine contractions can diminish or completely arrest blood flow through the uterus/ 3 which produces an intermittent fetal hypoxia. 14 Methoxyflurane, as a general anesthetic agent, decreases uterine contractility and at a concentration of about 15 mg. per cent almost abolishes uterine contractions.15 In addition, hypercarbia can also diminish uterine contractility. 16 Decrease in or cessation of uterine contractions \vould improve uterine and umbilical blood flow and thus increase fetal tension during delivery. The decrease of intensity of uterine contractions due to a general anesthetic agent can explain why umbilical vein oxygen tension was significantly lower in patients who received saddle-block anesthesia. Voluntary breath holding and straining during regional anesthesia could also tend to produce lower fetal oxygen tension. Maternal arterial oxygen saturations were near maximal and could not explain the observed differences in fetal oxygen tensions. Perhaps a higher maternal Po 2 during general anesthesia may slightly influence umbilical vein Po 2 , since it has been reported that inhalation of oxygen may decrease fetal oxygen saturationY However, in these studies an elevated maternal Po 2 appeared to be advantageous. U
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July 15, 1970 Amer. J. Obstet. Gynec.
Most infants in the methoxyflurane groups had umbilical vein oxygen tension and oxygen saturation values higher than generally reported in the literature. As a matter of fact, the mean value of 50 mm. Hg for infants in the hypercarbic group is significantly higher than averages for any groups reported in the literature. 18 Blood sampling from the undamped cord and early estimation of blood gases eliminated lowering of Po 2 during stagnation following clamping. With the use of the saddle-block group as control subjects, the Po~ n1ean value of 32 n1n1. Hg agrees with the findings in other investigation.18 Therefore, the results of this series suggest that both methoxyflurane anesthesia and hypercarbia increase oxygen tension in the infant. The physiology of initiation of spontaneous respiration in the newborn infant is stiil not known. Hypoxia does not produce a respiratory stimulus in the newborn infant as in adults; instead it seems that hypoxia in the neonate is more likely to depress respiration.19 It has been generally accepted that hypercarbia stimulates the respiratory center in the neonate. 20 • 21 However, it has been demonstrated that severe hypercarbia in the presence of birth trauma, severe hypoxia, and ishemia depresses neonates respiration.19' 22 ~,.1ethoxyfturane, a potent anesthetic agent, produces a shift to the right of the C0 2 respiratory response curve and, consequently, a rise in the apneic threshold for carbon dioxide. 23 The increase in the C0 2 apneic threshold due to methoxyflurane can explain prolongation of onset of respiration in the newborn infant with a lower Pco 2 level and, vice versa, prolongation of onset of respiration with an increase in anesthetic concentration at a similar C0 2 level. This would explain the longer time for sustained respiration and the lower Apgar scores at one minute in the control methoxyflurane group. On the other hand, although Pco 2 was considerably lower in the saddleblock group than in the hypercarbic group, there was no significant difference in the time for sustained respiration between hypercarbic methoxyflurane and saddle-block
Volume 107 Number 6
groups. This could be explained by the absence of a C0 2 threshold or apnea in unanesthetized subjects even at extremely low Pco 2 • 2 ·> This would suggest that carbon dioxide has little or no effect on initiation of respiration in the unanesthetized neonate, and the infants born with low C0 2 values in the absence of anesthesia breathe in response to other stimuli. These studies failed to demonstrate a correlation between oxygen saturation and the clinical condition of the newborn infant. This is in agreement \\ith the work of James and colleagues 6 and somewhat in disagreement with Rorke and co-workers.~ 5 Metabolic status has been considered a useful aid in the clinical evaluation of the infant. 26 However, we encountered no instances of fetal depression despite base-excess values in newborn infants as low as -14. Although we found no correlation between anesthetic concentration and Apgar score, in agreement with Sikt~r and associates, 27 it still would seem that increased time of anesthetic exposure should influence the clinical condition of the newborn infant. Apart from the effect of lowered C0 2 tension, longer exposure of the fetus to anesthetic in the control methoxyflurane group could explain differ-
REFERENCES
1. Motoyama, E. K., Rivard, G., Acheson, F., and Cook, C. D.: Anesthesiology 28:891, 1967. 2. Moya, F., Morishima, H. 0., Shnider, S. M., and James, L. S.: AMER. J. 0BSTET. GYNEc. 91: 76, 1965. 3. Morishima, H. 0., Moya, F., Bossers, A. C., and Daniel, S. S.: AMER. J. 0BSTET. GYNEc. 88: 524, 1964. 4. Hellegers, A. E., and Schruefer, J. P.: AMER. ]. 0BSTET. GYNEC. 81: 377, 1961. 5. Lowe, H. ].: Anesthesiology 25: 808, 1964. 6. James, L. S., Weisbrot, I. M., Prince, C. E., Holaday, D. A., and Apgar, V.: ]. Pediat. 52: 379, 1958. 7. Apgar, V., Holaday, D. A., James, L. S., Weisbrot, I. M., and Berrien, C.: ]. A. M. A. 168: 1985, 1958. 8. Schwartz, W. B.: Ann. N. Y. Acad. Sci. 133: 125, 1966. 9. Richardson, D. W., Wasserman, A. ]., and Patterson, ]. L.: J. Clin. Invest. 40: 31, 1961.
Maternal hypercarbia 945
ences m the clinical condition of the neonate. However, the results suggest that the carbon dioxide levels were the more important factor in determining the early clinical condition of the newborn infant delivered with general anesthesia. As a matter of fact, James and colleagues6 in 1958 expressed a clinical impression that the highest PC0 2 values are found in the most Yigorous newborn infants. It is generally accepted that hypercarbia does not depress the cardiovascular system 28 and that up to 90 mm. Hg does not show anesthetic properties. 29 Brief hypercarbia is compatible with methoxyflurane anesthesia; Pco 2 of even 150 mm. Hg has been reported not to produce any arrhythmias. 30 Inkster 31 reported 250,000 cases of hypercarbic induction of anesthesia by mask without serious complication. We did not observe any adverse effect of hypercarbia in our group of patients, and in our opinion, elevation of Pco 2 and, in our opinion, moderate elevation of Pco 2 can improve the clinical status of the newborn infant. Moreover, hypercarbic induction of anesthesia, considering the experience of Inkster, 31 may increase the maternal safety during general anesthesia by preventing vomiting and possible aspiration.
10. Assali, N. S., Holm, L. W., and Sehgal, N.: Circ. Res. 11: 423, 1962. ll. Boe, F.: Sympos. Quant. Bioi. 19: 29, 195+. 12. Motoyama, E. K., Rivard, G., Acheson, F. M., and Cook, C. D.: Unpublished data. 13. Caldeyro-Barcia, R.: Effect of Labor and Delivery on Fetus and Newborn, New York, 1967, Pergamon Press, Inc. 14. Howard, W. F., Hunter, C. A., Jr., and Huber, C. P.: Surg. Gynec. Obstet. 112: -135, 1961. 15. Elam, J. 0.: Unpublished data. 16. Woods, J. W.: Midwest Anesthesiology Residents Meeting, Madison, Wisconsin, May 10, 1969. 17. Sahling, H.: Geburtsh. Frauenheilk. 23: .5213, 1963. 18. Bonica, ]. ].: Principles and Practice of Obstetric Analgesia and Anesthesia, in Analgesia and Anesthesia, Philadelphia, 1965, F. A. Davis Company, pp. 162-173. 19. Miller, H. C., and Behrle, F. C.: Pediatrics 14: 93, 19.54.
July 15, 1970
946 lvankovic, Elam, and Huffman
Am cr.
T?
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Tl
'•
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1
T'lo
1 1
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1
J., and Fitting, G. Ni., Jr.: Brit. J. Anaesth. 40: 588, 1968. Symposium on Carbon Dioxide and Man, Anesthesiology 21: 585, 1960. Eisele, J. H., Eger, E. I., II, and Muallem, M.: Anesthesiology 28: 856, 1967. Black, G. VV.: Acta Anaesth. Scand. ii: 103, 1966. Inkster, J. S.: Brit. J. Anaesth. 25: 160, 1963.
27. Siker, E. S., Wolfson, B., Dubansky,
20. Miller, H. C.: Pediatrics 14: 104, 1954. ro""' r 1:101. 2i. \..ifOSS, 1'... VV .: DrH. lV~eo. DUll. ~ 1: lOV, 22. Cross, K. W., Hooper, J. M. D., and Oppe, 1""'11
J. Obstet. Gynec.
1 ....
11
T. E.: J. Physiol. (London) 22: 264, 1953. 23. Dunbar, B. S., Ovassapian, A., and Smith, T. C.: Anesthesiology 28: 1020, 1967. 24. Comroe, J. H.: Physiology of Respiration, Chicago, 1965, )rear Book Niedicai Pubiishers, Inc., p. 68. 25. Rorke, M. ]., Davey, D. A., and DuToit, H. J.: Anesthesia 23: 585, 1968. 26, Saling, E., and Schneider, D.: J. Obstet. Gynaec. Brit. Comm. 73: 562, 1967.
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31.