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Influence of maternal hyperventilation on the newborn infant
Influence of maternal hyperventilation
on the
newborn infant FRANK
MOYA,
HISAYO
0.
SOL L. New
M.
M.D.* MORISHIMA,
SHNIDER,
STANLEY York,
New
M.D. M.D.
JAMES,
M.D.**
York
Material
H Y P E R V E N T I L A T I 0 N occurs spontaneously in many women during labor; it is an integral part of Lamaze’s technique for painless childbirth’; it may also be performed by anesthesiologists during general anesthesia for delivery. Recently we have shown that severe hypocapnea, induced by forced hyperventilation in the pregnant guinea pig, causes maternal hypotension and profound metabolic acidosis in the fetus.” At birth the piglets were limp and unresponsive. Th e present study was undertaken to determine whether moderate degrees of hyperventilation as used in clinical practice influence the clinical condition or acid-base state of the infant at birth.
address: Miami
methods
Observations were made on 85 healthy mothers and babies. Sixty-one infants were delivered at or near term by elective cesarean section and 24 were born at term per vaginam (Table I). Cesarean
section
group
None were in labor. Premeditation of meperidine hydrochloride (50 mg.) and scopolamine hydrobromide (0.4 mg.) by intramuscular injection was administered 1 to Iv* hours before induction of anesthesia. Thirty mothers received spinal anesthesia, with the use of 6 to 8 mg. of 0.3 per cent tetracaine hydrochloride in 6 per cent glucose, and breathed room air unless they became nauseated and started to retch, at which time 100 per cent oxygen was administered by mask. Thirty-one received light general anesthesia consisting of sodium thiopental induction followed by a small dose of succinylcholine chloride and 75 per cent nitrous oxide in oxygen. Thirteen of these patients underwent induction of anesthesia with 80 per cent nitrous oxide in oxygen only.3 Thereafter anesthesia was maintained by a slow infusion of succinylcholine chloride and 50 per cent nitrous oxide in oxygen. The type of anesthesia was selected at random. Thirteen of 30 patients who received
From the Departments of Anesthesiology, Obstetrics and Gynecology, and Pediatrics of the College of Physicians and Surgeons, Columbia University and from the Division of Anesthesiology, Obstetrics and Gynecology (Sloane Hospital) and Pediatrics (Babies Hospital) of the Presbyterian Hosgital. This work was supported by United States Public Health Grant H-5877 (RI). *Present Hospital,
and
Jackson Memorial 36, Florida
**Recipient of investigatorship of the Health Research Council of the City of New York under Contract I-148. **Present address: 662 West 168th Street, New York, New York 10032.
76
Vohlc Numhcr
91 1
Maternal
spinal anesthesia were urged to hyperventilate. Of those receiving general anesthesia with controlled ventilation, 19 were hyperventilated by the anesthesiologist while every effort was made to maintain ventilation at a normal level in the remaining 12.
Table I. Summary
Deliuerv
Cesarean section
of mode
newborn
77
of delivery
vertex
Maternal anesthesia
General Spinal Analgesia* Cadal
group
All received light premeditation (50 to 100 mg. meperidine hydrochloride intramuscularly) late in the first stage or early in the second stage of labor. Cyclopropane analgesia4 was administered to 20 mothers during the second stage of labor and continued to delivery of the infant. Four mothers received caudal anesthesia (1.5 per cent mepivacaine hydroxide). These patients breathed spontaneously and no attempt was made to induce voluntary hyperventilation. In all mothers who received anesthesia or analgesia through a face mask or endotracheal tube high flows of anesthetic gases and oxygen were employed (more than 6 L. per minute). This assured against CO, accumulation in the apparatus dead space. Serial blood samples were withdrawn from the maternal brachial artery. In the cesarean section group these were taken prior to and after induction of anesthesia and at the moment of birth of the baby. In the vaginal group the samples were taken earIy during the second stage of labor prior to cyclopropane analgesia and at birth of infant while cyclopropane analgesia was being administered. The umbilical cord was clamped before the first breath, and samples were collected immediateIy from a segment of the cord. All samples were withdrawn anaerobically in greased, heparinized syringes and stored in ice water. AI1 determinations were done within 1 hour after taking the sample. The pH of whole blood was determined with the radiometer microglass electrode at 38O C.” PCO~ buffer base (BB) and base excess (BE) values were calculated according to the method described by AstrupG and Siggaard Andersen7 after equilibration of the sample with two gas mixtures of known Pco~. The blood oxygen saturation was determined
and
and
type of anesthesia
Vaginal Vaginal
hyperventilation
*Analgesia was achieved with approximately cyclopropane in oxygen, the mother remaining operative, and well oriented.
Patients fNo.) 31 30 20 4 5 per awake,
cent co-
by means of the Beckman spectrophotometer.’ The clinical status of the infant was evaluated 1 minute after birth with the Apgar score.s Another method of evaluation was the “time to sustained respiration” (T.S.R.) .I0 This is the time which elapses from birth until the infant establishes and maintains rhythmical spontaneous respirations. Results
Cesarean section group. Hyperventilation, whether spontaneous or artificial, was not always accompanied by maternal alkalosis. On the other hand, alkalosis was present in some of the patients who were not being urged to hyperventilate or in whom the anesthesiologist was attempting to maintain a normal level of ventilation under succinylcholine chloride. Therefore, the patients have been subdivided according to the degree of alkalosis as reflected in arterial pH measurements at time of delivery of the infant rather than according to method of ventilation. There are four groups (Tables II and III). Group I is comprised of mothers in whom the pH was within normal range at the time of delivery. It will be referred to as the Control Group and contains some mothers who were urged to hyperventilate spontaneously, as well as some in whom the attempted hyperventilation by the anesthesiologist failed to produce alkalosis. Groups II through IV consist of mothers with varying degrees of alkalosis, the result of spontaneous or artificial hyperventilation. In Group I, the maternal acid-base state was similar irrespective of whether they re-
Maya et al.
78
Am.
ceived spinal or general anesthesia (Table II). Furthermore this acid-base picture was similar in all mothers prior to anesthesia and at birth of their infant (Table IV), indicating that normal ventilation had been maintained during cesarean section.
Table IT. Distribution cesarean section
of maternal
In Group II mothers (Table II) there was mild alkalosis, with the pH ranging from 7.46 to 7.55 (mean 7.52), Pco, 17.4 to 29.5 mm. Hg (mean 23.4 mm. Hg), and BE -7.5 to +2.2 mEq. per liter (mean -2.2 mEq. per liter). In Group III mothers
arterial
pH
at time
I
SpinaE
Mean
of pH
7.36
anesthesia pH
N General N
II
I
to 7.45
7.46
III
to 7.55
III.
Biochemical
pH at 38”
7.66
and
7.61 4
-_ 0
7.42 12
7.52 9
7.59 8
7.67 2
above
analysis
of maternal
arterial
and umbilical
cord
at time of delivery
Vessel
---
--Umbilical vein
blood
Umbilical artery
Maternal artery
Umbilical vein
Umbilical artery
C.
Mean SE N mm.
7.42 0.010 28
7.29 0.002 28
7.23 0.018 28
7.52* 0.001 19
7.35* 0.005 19
7.27* 0.013 18
29.6 1.46 27
45.6 1.86 27
58.6 2.51 26
23.4' 0.87 17
38.3Y 1.73 19
57.7 2.31 16
19.3 0.76 27
22.6 1.65 27
25.4 1.13 26
18.7 0.51 17
21.6.f 0.72 19
26.1 0.63 16
41.9 0.89 26
40.6 1.12 26
40.7 1.43 25
43.8 0.56 17
42.1t 0.68 18
42.3+ 0.82 16
-3.2 0.52 26
-4.6 0.87 26
-5.2 1.52 25
-1.8+ 0.91 17
-4.2 1.22 18
-3.9 1.14 16
Hg
Mean SE N CO2 content per liter
mEq.
Mean SE N base mEq. liter Mean SE
N Base
IV
to 7.65
7.51 10
Vessel
BuJer per
7.56
7.42 16
Maternal artery
Pco:
by
anesthesia
Mean pH
Table
of delivery
Group
__Range
January 1, 1965 J. Obst. & Gynec.
excess
Mean SE N ‘Vahes
significantly
different
irom
control
tValues
significantly
different
from
control
values values
at at
the the
1 per 3.5
cent per
level cent
and level
better. and
better.
-
Volume Number
91 1
Maternal
hyperventilation
and newborn
79
there was more alkalosis, with the pH 7.56 -7.65 (mean 7.6), Pcoz 15.9 to 20.9 mm. Hg (mean 19 mm. Hg), and BE +2.6 to -2.2 mEq. per liter (mean -0.25 mEq. per liter). Group IV consisted only of 2 patients in whom alkalosis was severe. In one there was a pH of 7.66, Pcoz of 16.5 mm. Hg, CO, content of 18.4 mEq. per liter, and BE of +l.O mEq. per liter. In the other there was a pH of 7.68, Pcoz of 11.7 mm. Hg, COz content of 13.5 mEq. per liter, and BE of -4.5 mEq. per liter. When maternal arterial pH was plotted against Pco2, the distribution followed a predictive exponential curve as anticipated in alkalosis of respiratory origin (Fig. 1). No correlation was found between maternal systolic blood pressure and Pcoz in Groups I through III. Both mothers in
by cesarean
a l
I 7.3
1
1 1
I
I
I
IO
20
30
40
MATERNAL
J 50
PCo2(mm
Hg)
Fig. 1. The relationship between maternal pH and maternal Pco? at time of delivery. The values are fitted best on an exponential curve indicating the respiratory origin of alkalosis.
section
Group III
IV
Vessel
Vessel
Umbilical vein
Umbilical artery
7.60* 0.011 12
7.38* 0.013 12
7.29s 0.018 12
19.0* 0.60 11
38.9* 1.23 11
la.5 0.40 11
Maternal artery
-
Maternal artery
Umbilical vein
Umbilical artery
7.67
7.10
7.04
2
2
2
53.5.f 2.66 10
14.1
73.5
88.8
2
2
2
23.2 0.56 11
26.8f 0.52 10
16.0
23.5
26.2
2
2
2
45.8* 0.72 11
43.71 0.94 11
43.1* 1.10 10
44.0
35.5
34.6
2
2
2
-0.3* 0.38 11
-2.3+ 1.05 11
-4.0 1.15 10
-1.7
-8.1
-9.3
2
2
2
80
January I. 1965 Am. J. Obst. & Gynec.
Moya et al.
Group IV were relatively hypotensive after hyperventilation, but the changes were not greater than those seen in some mothers in Groups II and III.
Table IV. Comparison of maternal cesarean section and at delivery
acid-base
PH (mean)
Group I Prior to anesthesia At time of delivery Groups
II
through
(mm.
In all infants delivered by cesarean section the pH and BE were lower and Pcoz and CO, content were higher in both cord vessels than that in maternal arterial blood
state
PCO? He.)
prior
CO* (mEq.
to anesthesia
20.0 19.3
43.0 41.9
-2.3 -2.8
7.42
32.0
22.0
45.0
-0.6
Umbilical
~~-___I_Vein
Table
VI.
Mean 58.3 59.6 58.5 14.5
Apgar
1
--
Range 24.5-99.0 24.5-92.7 37.6-77.3 7.2-21.7
/
score in 61 infants
delivered
Score
/
Spinal
15
/
____----.~
-.__ Artery
Mean
1
Range
23.5 29.5 24.3 10.3
II
)
Spinal
1
28 16 12 2
/
13 1
34.8 30.1 34.2 4.2
section
in group.r and
Mean V-A diference
No.
O-41.8 10.5-53.3 9.0-44.5 6.1-14.5
by cesarean
I
General 10 3
vessels in 60
vessels
Anesthesia
7 and above 6 and below
cord
---.
No. 28 18 12 2
I
Table
excess
per liter)
31.0 29.6
__.-
I II III IV
Base (mEq.
7.42 7.42
Table V. Per cent of oxygen saturations in the umbilical newborn infants delivered by cesarean section ___-. __-__.
I-----
Buffer base (mEq. per liter)
content per liter)
IV
Prior to anesthesia
Group
for
III
General
16 1 --_I -~-
----IV
(
/
Spinal
)
General
-.L’
--
VII 0,
saturation
(%)
croup
Score
I
4 4 5
7.29 7.30 7.32
7.24 7.23 7.26
53.0 45.0 36.5
64.0 61.0 - .-
-1.0 -3.8 -5.7
-0.3 -2.9 ---
47.5 65.0 38.7
26.3 40.0 8.1
II
4
7.35
7.“4 w
37.9
61.8
-5.9
-6.9
82.8
38.2
5
7.41
7.36
34 8
40.9
--I.:!
-1.0
47.2
21.6
4 6
7.12 7.08
7.05 7.02
65.0 82.0
91.5 86.U
-8.1 -
-9.3 -
21.7 7.2
14.5 6.1
IV
Volume Number
91 1
Maternal
(Table III). However, in infants in Groups II and III there was significantly less acidosis than in those in the control group. In contrast the 2 infants in Group IV (born from mothers with the most alkalosis) had more acidosis than did the infants in the control group. The oxygen saturation in the cord vessels and the vein-artery difference were similar in Groups I, II, and III, but were less in Group IV (Table V) . The clinical condition of the infants as evaluated by the Apgar score and T.S.R. was similar for the Control Group and combined Groups II and III (Tables VI and VIII). Three of 28 in the Control Group scored 6 or less compared with 2 of 31 in the moderately hyperventilated group. Both infants in Group IV were clinically depressed, scoring 4 and 6, respectively, and took over 2 minutes to establish spontaneous respiration. All but 1 of the lower scoring infants were born from mothers who received general anesthesia (Table VII) and this probably contributed to their depression. Vaginal group. MaternaI PcoB during labor and prior to analgesia was lower than that observed in mothers at or near term and not in labor (Table IX). However, after analgesia it was similar to that observed prior to labor (Table X) . In the infants delivered vaginally there was more acidosis than in their mothers (Table X). The cord blood pH, Pcoz, BE, and oxygen saturation were similar
hyperventilation
and newborn
to values in control infants delivered by cesarean section (Group I, Tables III and V). Twenty-one infants scored 7 or more, and 3 scored 6 or less. The distributions of scores and T.S.R. were similar to those in the cesarean section group. Comment These observations indicate that maternal hyperventilation during elective cesarean section can modify the infant’s acid-base state at birth. Maternal alkalosis occurring as a result of moderate hyperventilation was reflected in both umbilical artery and vein, the pH in the vesseIs being significantIy higher than in cord blood of infants in the control group. There was, however, no observable difference in the clinical condition between infants in the control group and those in Groups II and III combined, the distribution of scores being similar (p > 0.9). On the other hand, in the infants delivered from mothers with the most alkalosis there was marked acidosis, the pH and BE being lower than any observed in the control infants. This finding is in agreement with our experimental observations in pregnant guinea pigs and is most likely caused by a reduction in uterine blood flow occurring when maternal Pco2 falls below a critical level. For the human this level appears to be in the region of 17 mm. Hg. Acidosis in the infant was associated with clinical depression. This depression was transient
Maternal
blood pressure (mm. ffd
Admission
Birth
Maternal Pcol at birth (mm. Hd
1 lo/76 13d/70 110/62
120/70 155/100 100/56
34.0 27.5 20.8
General General General
No complications No complications Difficult breech
124/60
130/70
17.4
Spinal
120/80
114/70
20.4
General
Cord compression, difficult extraction Borderline anthropoid-android
1 lo/80 110/74
88/58 90/60
16.5 11.7
General General
No No
1
81
Maternal anesthesia
Comment
complications complications
extraction breech pelvis
January 1, 1965 Am. J. Obst. & Gynec.
82 Moya et al.
and both infants were breathing normally within 3 minutes after birth. From these data alone it is not possible to implicate
Table VIII. section
Time
to sustained
_______-
respiration
maternal hyperventilation as the sole cause of depression. However, our experimental observation in guinea pigs” indicates that
in 61 infants
___-
____-___-
Spinal 11 2 2 1
(seconds) 0 to 29 30 to 59 60 to 89 90 to 119 120 to 149 150 plus
I
(
Table IX. Biochemical analyses of anesthesia or analgesia
Not
in
labor* N
Mean Range In
labort N Mean Range “Samples from +Samples
from
mothers mothers
__
General 6 3 1 1 1
of maternal
in
groups
--
and III Spinal / General 11 4 1 8 2 2 1 1 I .._____..~
IV
II
arterial
blood
prior
Spinal
1
General
2 __
to administration
Buffer base (mEq. per liter)
Base excess (mEq. per liter)
PH
PCOP (mm. Hd
46 7.42 7.35-7.48
33 3’ 24.3-42.0
33 21 15.5-25.4
33 44 38.6-48.4
31 -1.6 -4.4-+2.0
46 100 98.6-100
24 7.45 7.25-7.57
24 27 18.1-33.5
24 19 11.9-22.1
33 43 31.3-47.0
21 -1.9 -5.5--0.2
23 100 98-100
prior to cesarean admitted in labor
Table X. Biochemical analysis time of vaginal delivery
PH Maternal
by cesarean
-_ Anesthesia
T.S.R.
delivered
section. and who
were
of maternal
Pcor (mm. Hs)
delivered
O2 saturation (%I
vaginally.
arterial
75content (mEq. per liter)
and umbilical
/ B(Y!~~;Y~
cord
blood
j yZC!ZF
at
) OPs~;jztion
artery N
Mean SE Umbilical
23 7.39 0.016
23 31 1.24
23 18.5 0.48
23 42.1 0.70
20 -3.5 0.57
23 100.0 -
23 7.31 0.016
23 43.5 1.56
ii.2 0.68
23 42.2 0.79
20 -4.4 0.81
23 60.0 4.20
22 7.24 0.015
22 57.7 2.44
22 25.6 0.67
22 41.5 0.74
19 -5.5 0.74
23 22.9 2.59
vein N
Mean SE Umbilical
artery N
Mean SE
Volume Number
91 1
more severe degrees of maternal hyperventilation would have undoubtedly resulted in a significant number of depressed infants. Holmes,” employing hyperventilation with a similar anesthetic technique for elective cesarean section, observed a delay in onset of respiration of up to 14 minutes. The lack of correlation between maternal blood pressure and Pco2 is contrary to observations in pregnant guinea pigs’ and in the anesthetized human’2 and animals.13 This difference might have been caused by a lesser degree of hypocapnea, to light anesthesia, or to vasopressor agents administered to all mothers receiving spinal anesthesia, Despite the lack of correlation it cannot be concluded that uterine circulation was unchanged. It has been shown that regional blood flow to the brain may be reduced with only moderate hyperventilation, even though the systemic blood pressure is normally maintained.14 More intense hyperventilation may even be associated with demonstrable cerebral damage.l” As we have noted previously” it seems likely that the uterine blood vesseIs react to hypocapnea and aIkalosis by vasoconstriction in a similar manner as cerebral vessels, and at a certain point uterine and placental circulation may be sufficiently disturbed to cause fetal asphyxia. The low oxygen saturation in both cord vessels and the small vein-artery difference in Group IV infants indicate that maternal perfusion of the placental site was indeed decreased. The lower Pco, observed during labor in unanesthetized mothers is most likely caused by respiratory stimulation from painful uterine contractions. This spontaneous hyperventilation ceased with analgesia. Maternal hyperventilation appears to be potentially hazardous for the fetus. Although moderate controlled hyperventilation during cesarean section can cause the fetus to have slightly less acidosis at birth, this does not appear to improve the clinical condition as judged by the Apgar score or T.S.R. If maternal PCO~ is lowered below 17 mm. Hq, the infant is likely to have severe acidosis at birth and delayed onset of respiration.
Maternal
hyperventilation
and
newborn
83
There is danger not for conscious mothers who are hyperventilating voluntarily, but for the unconscious patient who is artificially ventilated after receiving muscle relaxants. This hazard was demonstrated in the present study; 1 of the 2 mothers with the most alkalosis belonged to the group in which the anesthesiologist was attempting to maintain a normal level of ventilation under succinylcholine. It is possible that pregnant women might be more susceptible to the adverse effects of overventilation; the functional residual capacity of their lungs is less and arterial Pco2 and alkali reserve decreased. Interference with venous return as a result of uterine pressure on the inferior vena cava in the supine position might also contribute. Considerable caution should be exercised, therefore, in the ventilation of pregnant women who undergo cesarean section when muscle relaxants are being used; willful overventilation should be avoided. Summary
Moderate controlled hyperventilation during cesarean section can cause the fetus to have slightly less acidosis at birth. However, if maternal Pco2 is lowered below 17 mm. Hg, the infant is likely to have severe acidosis and delayed onset of respiration. Although hyperventilation was not always accompanied by maternal alkalosis in this study, 1 of the two mothers with the most alkalosis belonged to the group in which the anesthesiologist was attempting to maintain a normal level of ventilation. There is danger not for the conscious patient hyperventilating voluntarily, but for the unconscious patient who undergoes artificial ventilation after receiving muscle relaxants. Considerable caution should be exercised, therefore, in the ventilation of pregnant women who undergo cesarean section when muscle relaxants are being used; willful overventilation should be avoided. We wish to express our appreciation to Dr. S. S. Daniel and Mrs. L. Grann for carrying out the biochemical analyses, and Drs. A. C. Bossers, V. Thorndike, and M. Finster for assistance in collection of samples.
84
Moya
et al.
REFERENCES
1. 2.
3. 4.
5.
6. 7.
8.
Lamaze, F.: Semaine hBp. Paris 28: 301, 1952. Morishima, H. O., Moya, F., Bossers, A. C.: and Daniel, S. S.: Abr. J. OBST. & GYNEC. 88: 524, 1964. Moya, F.: New York J. Med. 62: 2169, 1962. Shnider, S. M., Moya, F., Thorndike, V.: Bosser, A. C., Morishima, H. O., and James, L. S.: Anesthesiology 24: 11, 1963. Siggaard Andersen, O., Engel, K., Jorgensen, K., and A&up, P.: Scandinav. J. Clin. & Lab. Invest. 12: 172, 1960. Astrup, P., Jsrgensen, K., Siggaard Andersen, O., and Engel, K.: Lancet 1: 1035, 1960. Siggaard Andersen, O., and Engel, K.: Scandinav. J. Clin. & Lab. Invest. 12: 177, 1960. Holling, H. E., MacDonald, I., O’HalIoran,
January
1, 1965
i\m. J. Obst. 3( Gynec.
J. A.. and Vcnner, A.: J. Appl. Physiol. 8: 249, 1955. 9. Apgar, V., Holaday, D. A., James, I,. S., Weisbrot, I. M., and Berricn, C.: J. A. M. A. 168: 1985. 1958. 10. Apgar, T’., Holaday, D. A., James, L. S., Prince. C. E.. Weisbrot. I. M.. and Weiss. I.: J, A. ti. A. 165: 2155, i957. ’ ’ 11. Holmes, F.: Brit. J. Anaesth. 35: 433, 1963. 12. Seevcrs, M. H., Stormont, R. T., Hathaway, H. R., and Waters, R. M.: J. A. M. A. 113: 2131, 1939. 13. Seevers, M. H., Stormont, R. T., and Hathaway, H. R.: J. Pharmacol. & Exper. Therap. 68: 365, 1940. 14. Kcty, S. S.. and Schmidt, C. F.: J. Clin. Invest. 25: 107, 1946. 15. Allen, G. D., and Morris, L. E.: Brit. J. Anaesth. 34: 296, 1962.
on the
newborn infant FRANK
MOYA,
HISAYO
0.
SOL L. New
M.
M.D.* MORISHIMA,
SHNIDER,
STANLEY York,
New
M.D. M.D.
JAMES,
M.D.**
York
Material
H Y P E R V E N T I L A T I 0 N occurs spontaneously in many women during labor; it is an integral part of Lamaze’s technique for painless childbirth’; it may also be performed by anesthesiologists during general anesthesia for delivery. Recently we have shown that severe hypocapnea, induced by forced hyperventilation in the pregnant guinea pig, causes maternal hypotension and profound metabolic acidosis in the fetus.” At birth the piglets were limp and unresponsive. Th e present study was undertaken to determine whether moderate degrees of hyperventilation as used in clinical practice influence the clinical condition or acid-base state of the infant at birth.
address: Miami
methods
Observations were made on 85 healthy mothers and babies. Sixty-one infants were delivered at or near term by elective cesarean section and 24 were born at term per vaginam (Table I). Cesarean
section
group
None were in labor. Premeditation of meperidine hydrochloride (50 mg.) and scopolamine hydrobromide (0.4 mg.) by intramuscular injection was administered 1 to Iv* hours before induction of anesthesia. Thirty mothers received spinal anesthesia, with the use of 6 to 8 mg. of 0.3 per cent tetracaine hydrochloride in 6 per cent glucose, and breathed room air unless they became nauseated and started to retch, at which time 100 per cent oxygen was administered by mask. Thirty-one received light general anesthesia consisting of sodium thiopental induction followed by a small dose of succinylcholine chloride and 75 per cent nitrous oxide in oxygen. Thirteen of these patients underwent induction of anesthesia with 80 per cent nitrous oxide in oxygen only.3 Thereafter anesthesia was maintained by a slow infusion of succinylcholine chloride and 50 per cent nitrous oxide in oxygen. The type of anesthesia was selected at random. Thirteen of 30 patients who received
From the Departments of Anesthesiology, Obstetrics and Gynecology, and Pediatrics of the College of Physicians and Surgeons, Columbia University and from the Division of Anesthesiology, Obstetrics and Gynecology (Sloane Hospital) and Pediatrics (Babies Hospital) of the Presbyterian Hosgital. This work was supported by United States Public Health Grant H-5877 (RI). *Present Hospital,
and
Jackson Memorial 36, Florida
**Recipient of investigatorship of the Health Research Council of the City of New York under Contract I-148. **Present address: 662 West 168th Street, New York, New York 10032.
76
Vohlc Numhcr
91 1
Maternal
spinal anesthesia were urged to hyperventilate. Of those receiving general anesthesia with controlled ventilation, 19 were hyperventilated by the anesthesiologist while every effort was made to maintain ventilation at a normal level in the remaining 12.
Table I. Summary
Deliuerv
Cesarean section
of mode
newborn
77
of delivery
vertex
Maternal anesthesia
General Spinal Analgesia* Cadal
group
All received light premeditation (50 to 100 mg. meperidine hydrochloride intramuscularly) late in the first stage or early in the second stage of labor. Cyclopropane analgesia4 was administered to 20 mothers during the second stage of labor and continued to delivery of the infant. Four mothers received caudal anesthesia (1.5 per cent mepivacaine hydroxide). These patients breathed spontaneously and no attempt was made to induce voluntary hyperventilation. In all mothers who received anesthesia or analgesia through a face mask or endotracheal tube high flows of anesthetic gases and oxygen were employed (more than 6 L. per minute). This assured against CO, accumulation in the apparatus dead space. Serial blood samples were withdrawn from the maternal brachial artery. In the cesarean section group these were taken prior to and after induction of anesthesia and at the moment of birth of the baby. In the vaginal group the samples were taken earIy during the second stage of labor prior to cyclopropane analgesia and at birth of infant while cyclopropane analgesia was being administered. The umbilical cord was clamped before the first breath, and samples were collected immediateIy from a segment of the cord. All samples were withdrawn anaerobically in greased, heparinized syringes and stored in ice water. AI1 determinations were done within 1 hour after taking the sample. The pH of whole blood was determined with the radiometer microglass electrode at 38O C.” PCO~ buffer base (BB) and base excess (BE) values were calculated according to the method described by AstrupG and Siggaard Andersen7 after equilibration of the sample with two gas mixtures of known Pco~. The blood oxygen saturation was determined
and
and
type of anesthesia
Vaginal Vaginal
hyperventilation
*Analgesia was achieved with approximately cyclopropane in oxygen, the mother remaining operative, and well oriented.
Patients fNo.) 31 30 20 4 5 per awake,
cent co-
by means of the Beckman spectrophotometer.’ The clinical status of the infant was evaluated 1 minute after birth with the Apgar score.s Another method of evaluation was the “time to sustained respiration” (T.S.R.) .I0 This is the time which elapses from birth until the infant establishes and maintains rhythmical spontaneous respirations. Results
Cesarean section group. Hyperventilation, whether spontaneous or artificial, was not always accompanied by maternal alkalosis. On the other hand, alkalosis was present in some of the patients who were not being urged to hyperventilate or in whom the anesthesiologist was attempting to maintain a normal level of ventilation under succinylcholine chloride. Therefore, the patients have been subdivided according to the degree of alkalosis as reflected in arterial pH measurements at time of delivery of the infant rather than according to method of ventilation. There are four groups (Tables II and III). Group I is comprised of mothers in whom the pH was within normal range at the time of delivery. It will be referred to as the Control Group and contains some mothers who were urged to hyperventilate spontaneously, as well as some in whom the attempted hyperventilation by the anesthesiologist failed to produce alkalosis. Groups II through IV consist of mothers with varying degrees of alkalosis, the result of spontaneous or artificial hyperventilation. In Group I, the maternal acid-base state was similar irrespective of whether they re-
Maya et al.
78
Am.
ceived spinal or general anesthesia (Table II). Furthermore this acid-base picture was similar in all mothers prior to anesthesia and at birth of their infant (Table IV), indicating that normal ventilation had been maintained during cesarean section.
Table IT. Distribution cesarean section
of maternal
In Group II mothers (Table II) there was mild alkalosis, with the pH ranging from 7.46 to 7.55 (mean 7.52), Pco, 17.4 to 29.5 mm. Hg (mean 23.4 mm. Hg), and BE -7.5 to +2.2 mEq. per liter (mean -2.2 mEq. per liter). In Group III mothers
arterial
pH
at time
I
SpinaE
Mean
of pH
7.36
anesthesia pH
N General N
II
I
to 7.45
7.46
III
to 7.55
III.
Biochemical
pH at 38”
7.66
and
7.61 4
-_ 0
7.42 12
7.52 9
7.59 8
7.67 2
above
analysis
of maternal
arterial
and umbilical
cord
at time of delivery
Vessel
---
--Umbilical vein
blood
Umbilical artery
Maternal artery
Umbilical vein
Umbilical artery
C.
Mean SE N mm.
7.42 0.010 28
7.29 0.002 28
7.23 0.018 28
7.52* 0.001 19
7.35* 0.005 19
7.27* 0.013 18
29.6 1.46 27
45.6 1.86 27
58.6 2.51 26
23.4' 0.87 17
38.3Y 1.73 19
57.7 2.31 16
19.3 0.76 27
22.6 1.65 27
25.4 1.13 26
18.7 0.51 17
21.6.f 0.72 19
26.1 0.63 16
41.9 0.89 26
40.6 1.12 26
40.7 1.43 25
43.8 0.56 17
42.1t 0.68 18
42.3+ 0.82 16
-3.2 0.52 26
-4.6 0.87 26
-5.2 1.52 25
-1.8+ 0.91 17
-4.2 1.22 18
-3.9 1.14 16
Hg
Mean SE N CO2 content per liter
mEq.
Mean SE N base mEq. liter Mean SE
N Base
IV
to 7.65
7.51 10
Vessel
BuJer per
7.56
7.42 16
Maternal artery
Pco:
by
anesthesia
Mean pH
Table
of delivery
Group
__Range
January 1, 1965 J. Obst. & Gynec.
excess
Mean SE N ‘Vahes
significantly
different
irom
control
tValues
significantly
different
from
control
values values
at at
the the
1 per 3.5
cent per
level cent
and level
better. and
better.
-
Volume Number
91 1
Maternal
hyperventilation
and newborn
79
there was more alkalosis, with the pH 7.56 -7.65 (mean 7.6), Pcoz 15.9 to 20.9 mm. Hg (mean 19 mm. Hg), and BE +2.6 to -2.2 mEq. per liter (mean -0.25 mEq. per liter). Group IV consisted only of 2 patients in whom alkalosis was severe. In one there was a pH of 7.66, Pcoz of 16.5 mm. Hg, CO, content of 18.4 mEq. per liter, and BE of +l.O mEq. per liter. In the other there was a pH of 7.68, Pcoz of 11.7 mm. Hg, COz content of 13.5 mEq. per liter, and BE of -4.5 mEq. per liter. When maternal arterial pH was plotted against Pco2, the distribution followed a predictive exponential curve as anticipated in alkalosis of respiratory origin (Fig. 1). No correlation was found between maternal systolic blood pressure and Pcoz in Groups I through III. Both mothers in
by cesarean
a l
I 7.3
1
1 1
I
I
I
IO
20
30
40
MATERNAL
J 50
PCo2(mm
Hg)
Fig. 1. The relationship between maternal pH and maternal Pco? at time of delivery. The values are fitted best on an exponential curve indicating the respiratory origin of alkalosis.
section
Group III
IV
Vessel
Vessel
Umbilical vein
Umbilical artery
7.60* 0.011 12
7.38* 0.013 12
7.29s 0.018 12
19.0* 0.60 11
38.9* 1.23 11
la.5 0.40 11
Maternal artery
-
Maternal artery
Umbilical vein
Umbilical artery
7.67
7.10
7.04
2
2
2
53.5.f 2.66 10
14.1
73.5
88.8
2
2
2
23.2 0.56 11
26.8f 0.52 10
16.0
23.5
26.2
2
2
2
45.8* 0.72 11
43.71 0.94 11
43.1* 1.10 10
44.0
35.5
34.6
2
2
2
-0.3* 0.38 11
-2.3+ 1.05 11
-4.0 1.15 10
-1.7
-8.1
-9.3
2
2
2
80
January I. 1965 Am. J. Obst. & Gynec.
Moya et al.
Group IV were relatively hypotensive after hyperventilation, but the changes were not greater than those seen in some mothers in Groups II and III.
Table IV. Comparison of maternal cesarean section and at delivery
acid-base
PH (mean)
Group I Prior to anesthesia At time of delivery Groups
II
through
(mm.
In all infants delivered by cesarean section the pH and BE were lower and Pcoz and CO, content were higher in both cord vessels than that in maternal arterial blood
state
PCO? He.)
prior
CO* (mEq.
to anesthesia
20.0 19.3
43.0 41.9
-2.3 -2.8
7.42
32.0
22.0
45.0
-0.6
Umbilical
~~-___I_Vein
Table
VI.
Mean 58.3 59.6 58.5 14.5
Apgar
1
--
Range 24.5-99.0 24.5-92.7 37.6-77.3 7.2-21.7
/
score in 61 infants
delivered
Score
/
Spinal
15
/
____----.~
-.__ Artery
Mean
1
Range
23.5 29.5 24.3 10.3
II
)
Spinal
1
28 16 12 2
/
13 1
34.8 30.1 34.2 4.2
section
in group.r and
Mean V-A diference
No.
O-41.8 10.5-53.3 9.0-44.5 6.1-14.5
by cesarean
I
General 10 3
vessels in 60
vessels
Anesthesia
7 and above 6 and below
cord
---.
No. 28 18 12 2
I
Table
excess
per liter)
31.0 29.6
__.-
I II III IV
Base (mEq.
7.42 7.42
Table V. Per cent of oxygen saturations in the umbilical newborn infants delivered by cesarean section ___-. __-__.
I-----
Buffer base (mEq. per liter)
content per liter)
IV
Prior to anesthesia
Group
for
III
General
16 1 --_I -~-
----IV
(
/
Spinal
)
General
-.L’
--
VII 0,
saturation
(%)
croup
Score
I
4 4 5
7.29 7.30 7.32
7.24 7.23 7.26
53.0 45.0 36.5
64.0 61.0 - .-
-1.0 -3.8 -5.7
-0.3 -2.9 ---
47.5 65.0 38.7
26.3 40.0 8.1
II
4
7.35
7.“4 w
37.9
61.8
-5.9
-6.9
82.8
38.2
5
7.41
7.36
34 8
40.9
--I.:!
-1.0
47.2
21.6
4 6
7.12 7.08
7.05 7.02
65.0 82.0
91.5 86.U
-8.1 -
-9.3 -
21.7 7.2
14.5 6.1
IV
Volume Number
91 1
Maternal
(Table III). However, in infants in Groups II and III there was significantly less acidosis than in those in the control group. In contrast the 2 infants in Group IV (born from mothers with the most alkalosis) had more acidosis than did the infants in the control group. The oxygen saturation in the cord vessels and the vein-artery difference were similar in Groups I, II, and III, but were less in Group IV (Table V) . The clinical condition of the infants as evaluated by the Apgar score and T.S.R. was similar for the Control Group and combined Groups II and III (Tables VI and VIII). Three of 28 in the Control Group scored 6 or less compared with 2 of 31 in the moderately hyperventilated group. Both infants in Group IV were clinically depressed, scoring 4 and 6, respectively, and took over 2 minutes to establish spontaneous respiration. All but 1 of the lower scoring infants were born from mothers who received general anesthesia (Table VII) and this probably contributed to their depression. Vaginal group. MaternaI PcoB during labor and prior to analgesia was lower than that observed in mothers at or near term and not in labor (Table IX). However, after analgesia it was similar to that observed prior to labor (Table X) . In the infants delivered vaginally there was more acidosis than in their mothers (Table X). The cord blood pH, Pcoz, BE, and oxygen saturation were similar
hyperventilation
and newborn
to values in control infants delivered by cesarean section (Group I, Tables III and V). Twenty-one infants scored 7 or more, and 3 scored 6 or less. The distributions of scores and T.S.R. were similar to those in the cesarean section group. Comment These observations indicate that maternal hyperventilation during elective cesarean section can modify the infant’s acid-base state at birth. Maternal alkalosis occurring as a result of moderate hyperventilation was reflected in both umbilical artery and vein, the pH in the vesseIs being significantIy higher than in cord blood of infants in the control group. There was, however, no observable difference in the clinical condition between infants in the control group and those in Groups II and III combined, the distribution of scores being similar (p > 0.9). On the other hand, in the infants delivered from mothers with the most alkalosis there was marked acidosis, the pH and BE being lower than any observed in the control infants. This finding is in agreement with our experimental observations in pregnant guinea pigs and is most likely caused by a reduction in uterine blood flow occurring when maternal Pco2 falls below a critical level. For the human this level appears to be in the region of 17 mm. Hg. Acidosis in the infant was associated with clinical depression. This depression was transient
Maternal
blood pressure (mm. ffd
Admission
Birth
Maternal Pcol at birth (mm. Hd
1 lo/76 13d/70 110/62
120/70 155/100 100/56
34.0 27.5 20.8
General General General
No complications No complications Difficult breech
124/60
130/70
17.4
Spinal
120/80
114/70
20.4
General
Cord compression, difficult extraction Borderline anthropoid-android
1 lo/80 110/74
88/58 90/60
16.5 11.7
General General
No No
1
81
Maternal anesthesia
Comment
complications complications
extraction breech pelvis
January 1, 1965 Am. J. Obst. & Gynec.
82 Moya et al.
and both infants were breathing normally within 3 minutes after birth. From these data alone it is not possible to implicate
Table VIII. section
Time
to sustained
_______-
respiration
maternal hyperventilation as the sole cause of depression. However, our experimental observation in guinea pigs” indicates that
in 61 infants
___-
____-___-
Spinal 11 2 2 1
(seconds) 0 to 29 30 to 59 60 to 89 90 to 119 120 to 149 150 plus
I
(
Table IX. Biochemical analyses of anesthesia or analgesia
Not
in
labor* N
Mean Range In
labort N Mean Range “Samples from +Samples
from
mothers mothers
__
General 6 3 1 1 1
of maternal
in
groups
--
and III Spinal / General 11 4 1 8 2 2 1 1 I .._____..~
IV
II
arterial
blood
prior
Spinal
1
General
2 __
to administration
Buffer base (mEq. per liter)
Base excess (mEq. per liter)
PH
PCOP (mm. Hd
46 7.42 7.35-7.48
33 3’ 24.3-42.0
33 21 15.5-25.4
33 44 38.6-48.4
31 -1.6 -4.4-+2.0
46 100 98.6-100
24 7.45 7.25-7.57
24 27 18.1-33.5
24 19 11.9-22.1
33 43 31.3-47.0
21 -1.9 -5.5--0.2
23 100 98-100
prior to cesarean admitted in labor
Table X. Biochemical analysis time of vaginal delivery
PH Maternal
by cesarean
-_ Anesthesia
T.S.R.
delivered
section. and who
were
of maternal
Pcor (mm. Hs)
delivered
O2 saturation (%I
vaginally.
arterial
75content (mEq. per liter)
and umbilical
/ B(Y!~~;Y~
cord
blood
j yZC!ZF
at
) OPs~;jztion
artery N
Mean SE Umbilical
23 7.39 0.016
23 31 1.24
23 18.5 0.48
23 42.1 0.70
20 -3.5 0.57
23 100.0 -
23 7.31 0.016
23 43.5 1.56
ii.2 0.68
23 42.2 0.79
20 -4.4 0.81
23 60.0 4.20
22 7.24 0.015
22 57.7 2.44
22 25.6 0.67
22 41.5 0.74
19 -5.5 0.74
23 22.9 2.59
vein N
Mean SE Umbilical
artery N
Mean SE
Volume Number
91 1
more severe degrees of maternal hyperventilation would have undoubtedly resulted in a significant number of depressed infants. Holmes,” employing hyperventilation with a similar anesthetic technique for elective cesarean section, observed a delay in onset of respiration of up to 14 minutes. The lack of correlation between maternal blood pressure and Pco2 is contrary to observations in pregnant guinea pigs’ and in the anesthetized human’2 and animals.13 This difference might have been caused by a lesser degree of hypocapnea, to light anesthesia, or to vasopressor agents administered to all mothers receiving spinal anesthesia, Despite the lack of correlation it cannot be concluded that uterine circulation was unchanged. It has been shown that regional blood flow to the brain may be reduced with only moderate hyperventilation, even though the systemic blood pressure is normally maintained.14 More intense hyperventilation may even be associated with demonstrable cerebral damage.l” As we have noted previously” it seems likely that the uterine blood vesseIs react to hypocapnea and aIkalosis by vasoconstriction in a similar manner as cerebral vessels, and at a certain point uterine and placental circulation may be sufficiently disturbed to cause fetal asphyxia. The low oxygen saturation in both cord vessels and the small vein-artery difference in Group IV infants indicate that maternal perfusion of the placental site was indeed decreased. The lower Pco, observed during labor in unanesthetized mothers is most likely caused by respiratory stimulation from painful uterine contractions. This spontaneous hyperventilation ceased with analgesia. Maternal hyperventilation appears to be potentially hazardous for the fetus. Although moderate controlled hyperventilation during cesarean section can cause the fetus to have slightly less acidosis at birth, this does not appear to improve the clinical condition as judged by the Apgar score or T.S.R. If maternal PCO~ is lowered below 17 mm. Hq, the infant is likely to have severe acidosis at birth and delayed onset of respiration.
Maternal
hyperventilation
and
newborn
83
There is danger not for conscious mothers who are hyperventilating voluntarily, but for the unconscious patient who is artificially ventilated after receiving muscle relaxants. This hazard was demonstrated in the present study; 1 of the 2 mothers with the most alkalosis belonged to the group in which the anesthesiologist was attempting to maintain a normal level of ventilation under succinylcholine. It is possible that pregnant women might be more susceptible to the adverse effects of overventilation; the functional residual capacity of their lungs is less and arterial Pco2 and alkali reserve decreased. Interference with venous return as a result of uterine pressure on the inferior vena cava in the supine position might also contribute. Considerable caution should be exercised, therefore, in the ventilation of pregnant women who undergo cesarean section when muscle relaxants are being used; willful overventilation should be avoided. Summary
Moderate controlled hyperventilation during cesarean section can cause the fetus to have slightly less acidosis at birth. However, if maternal Pco2 is lowered below 17 mm. Hg, the infant is likely to have severe acidosis and delayed onset of respiration. Although hyperventilation was not always accompanied by maternal alkalosis in this study, 1 of the two mothers with the most alkalosis belonged to the group in which the anesthesiologist was attempting to maintain a normal level of ventilation. There is danger not for the conscious patient hyperventilating voluntarily, but for the unconscious patient who undergoes artificial ventilation after receiving muscle relaxants. Considerable caution should be exercised, therefore, in the ventilation of pregnant women who undergo cesarean section when muscle relaxants are being used; willful overventilation should be avoided. We wish to express our appreciation to Dr. S. S. Daniel and Mrs. L. Grann for carrying out the biochemical analyses, and Drs. A. C. Bossers, V. Thorndike, and M. Finster for assistance in collection of samples.
84
Moya
et al.
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3. 4.
5.
6. 7.
8.
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i\m. J. Obst. 3( Gynec.
J. A.. and Vcnner, A.: J. Appl. Physiol. 8: 249, 1955. 9. Apgar, V., Holaday, D. A., James, I,. S., Weisbrot, I. M., and Berricn, C.: J. A. M. A. 168: 1985. 1958. 10. Apgar, T’., Holaday, D. A., James, L. S., Prince. C. E.. Weisbrot. I. M.. and Weiss. I.: J, A. ti. A. 165: 2155, i957. ’ ’ 11. Holmes, F.: Brit. J. Anaesth. 35: 433, 1963. 12. Seevcrs, M. H., Stormont, R. T., Hathaway, H. R., and Waters, R. M.: J. A. M. A. 113: 2131, 1939. 13. Seevers, M. H., Stormont, R. T., and Hathaway, H. R.: J. Pharmacol. & Exper. Therap. 68: 365, 1940. 14. Kcty, S. S.. and Schmidt, C. F.: J. Clin. Invest. 25: 107, 1946. 15. Allen, G. D., and Morris, L. E.: Brit. J. Anaesth. 34: 296, 1962.