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Perinatal aspiration syndrome: Its association with intrapartum events and anesthesia
Perinatal aspiration syndrome: Its association with intrapartum events and anesthesia ROSEMARY D. LEAKE, M.D. RONALD GUNTHER, M.D. PHILIP SUNSHINE, M.D. Stanford, California Intrapartum records of mothers delivering babies with perinatal aspiration syndrome (PAS) at Stanford University Medical Center over a 22 month period were compared to those of control groups. In this series, 50 babies, or 1.5 per cent of live-born babies, developed PAS. Intrapartum complications, fetal distress, use of mid forceps, and breech presentations were found with significantly increased frequency ( p 0.001) among the mothers delivering babies affected with PAS undar caudal anesthesia. The mean quantity of caudal anesthetic agent administered to the 32 mothers delivering infants with PAS and the length of their labors were not significantly different from those of the control group of 1,914 deliveries under caudal anesthesia. There was a significant increase ( p 0.001) in PAS among infants delivered from mothers receiving epidural anesthesia. Our data would suggest that further investigations of the effects of epidural anesthesia are indicated.
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P E R. 1 N A T A L aspiration syndrome (PAS) is a relatively common cause of neonatal respiratory distress, yet its exact pathogenesis remains obscure. Hallmarks of the condition appearing soon after birth include tachypnea, dyspnea, and cyanosis while breathing room air. Physical examination reveals respiratory rates greater than 60 per minute,
flaring of the alae nasi, intercostal retractions, and expiratory grunting. There may be an increase in the anteroposterior diameter of the chest, indicating air trapping. This may progress to interstitial emphysema, bleb formation, and complicating pneumothorax. Rales and rhonchi are present and there are areas of decreased breath sounds. Abnormal neurologic signs, varying from lethargy to convulsions, are sometimes noted. One of the most striking clinical findings, when present, is the mild to severe meconium staining of the newborn infant's skin, nails, and cord. This staining is often associated with signs of postmaturity such as long nails, desquamating epithelium, alert facies, and increased birth length. When such signs are present, the entity is usually termed meconium aspiration syndrome. A syndrome with similar clinical features and identical x-ray findings occurs in non-meconium-stained infants. Radiographs of the chest are most helpful in distinguishing this entity from other causes of respiratory distress in the newborn in-
From the Departments of Pediatrics and Obstetrics, Stanford University Medical Center. Supported in part by funds contributed by Sterling Winthrop Research Institute, by a United States Public Health Service Training Grant 5 TO! HD00049-09, and by a grant (RR-81) from the General Clinical Research Centers Program of the Divisions of Research Resources, National Institute of Health. Received for publication December 29, 1972. Revised May 31, 1973. Accepted July 6, 1973. Reprint requests: Rosemary D. Leake, M.D., Department of Pediatrics, Harbor General Hospital, 1000 W. Carson St., Torrance, California 90509.
271
272 Leake, Gunther, and Sunshine
Fig. 1. Chest x-ray of non-meconium-stained infant with perinatal aspiration pneumonia.
fant, 1 • 2 such as the respiratory distress syndrome, where there is a diffuse ground-glass appearance representing collapsed alveoli. Characteristic radiographic features of PAS are areas of patchy irregular opacification in the lungs. The degree of opacification tends to parallel the severity of clinical disease. When air trapping is present the lungs and thorax appear hyperexpanded. In order to define PAS more clearly, a retrospective chart review of the 3,344 liveborn deliveries at Stanford University Medical Center over a 22 month period was undertaken to determine the incidence of perinatal aspiration syndrome in one institution and to correlate intrapartum events and anesthesia with eventual perinatal outcome. Materials and methods
Neonatal records and chest x-rays of all babies exhibiting signs of respiratory distress, born at Stanford University Medical Center between July 1, 1966, and May 1, 1968, were examined. A group of 50 babies with PAS was identified and their maternal records reviewed. The diagnosis of PAS was based on the following criteria: ( 1) cyanosis, dyspnea, grunting, flaring of the alae nasi, and intercostal retractions within the first several hours of life, ( 2) respiratory rate of more than 60 for at least 24 hours, (3) a
Am .
J.
January 15, 1974 Obstet. Gynecol.
radiograph of the chest interpreted by two independent observers as being compatible with PAS1 • 2 and (4) the diagnosis of aspiration pneumonia at the time of discharge. During the same 22 month time period, a prospective, in-depth analysis of the effects on labor and delivery of three continuous caudal obstetrical anesthetic agents was being conducted at Stanford. 3 • 4 All mothers who delivered infants with PAS under caudal anesthesia were included in this study. Thus detailed pregnancy, labor, delivery, and anesthesia records of mothers delivering infants with PAS were available to compare with mothers delivering unaffected babies under caudal anesthesia during the same time period. Mothers excluded from the caudal control group were those delivering stillborn infants or twins, those completely dilated at the time of caudal administration, those whose caudal anesthetics were ineffective, and those undergoing cesarean section before complete dilatation. Matched controls were selected for each mother delivering with anesthesia other than caudal whose infants developed PAS. This control group yielded a live-born baby of similar birth weight whose mother had received a comparable amount of an identical anesthetic agent by the same route . The maternal history and fetal outcome were not known at the time of selection of these controls. Chi-square analysis was used for the sta tistical evaluation of the data. Results
Incidence and outcome. There were 3,344 live-born and 44 stillborn infants delivered during the 22 month study period. Of these, 276 were live-born premature infants. There were 50 live-born babies with PAS, yielding an over-all incidence of 1.5 per cent. All of the affected babies survived. Over the same time period, there were 59 babies with the respiratory distress syndrome, an incidence of 1.8 per cent. Nineteen of the infants with PAS were meconium stained; 31 were not. A representative chest x-ray from one of the
Volume 118 Number 2
Perinatal aspiration syndrome
273
Table I. Obstetrical anesthesia used during the study period and the subsequent development of PAS
Number of babies with PAS Number of babeis without PAS Per cent affected
Epidural
Caudal
7
32
127
Other anesthesias (pudendal, spinal, local)
1,914
1.7
5.5*
No anesthesia
11 1,180 1.0
0
73
0
*The incidence of PAS in tbe epidural group is significantly higher than among those delivered with caudal or other forms of anesthesia (p < 0.001 by 2 x n chi-square analysis).
Table II. Perinatal complications among deliveries with various types of anesthesia during the study period Epidural
Number of records analyzed Intrapartum complications* Meconium staining Fetal bradycardia Fetal tachycardia Mid forceps deliveries Breech presentation
Caudal
Babies with PAS
IMatched controls
Babies with PAS
7
7
32
2 1
2 0
2
0
1 0 0 0 0 0
lOt 1St St 5t 6t 6t
I
Other anesthesia
Controls
1,914 52t 177t 91t
12t
69t 20t
Babies with PAS
11 1
3
0 0 0 0
IMatched controls
11 0 1 0 0
0 1
*Transverse arrest, shoulder dystocia, premature placental separation, cephalopelvic disproportion, intrapartum hemorrhage, and uterine inertia.
tThe difference between PAS groups and controls is significant (p
non-meconium-stained infants is shown in Fig. 1. Analysis of data. Statistical analysis of the following parameters failed to demonstrate a significant difference between mothers delivering babies with PAS and their controls: Maternal age, height, weight at conception and delivery, parity, mode of onset of labor (spontaneous vs. induced), timing or method of membrane rupture (artificial vs. spontaneous), use of oxytocics, length of labor, incidence of spontaneous and low-forceps deliveries, quantity of anesthesia used, dilatation and station at time of anesthesia administration, amount of supplemental anesthesia, narcotics, and barbiturates. All mothers who delivered affected babies received anesthesia of some type. Table I demonstrates that 5.5 per cent of those mothers receiving epidural anesthesia delivered babies with PAS. This represented a significantly increased use of epidural anesthesia (p < 0.001) among those delivering affected babies. It is tempting to interpret
< 0.001). the concomitant lack of increased numbers of intrapartum complications and/or signs of fetal distress over those found with the other types of anesthesia as evidence that epidural anesthesia itself was the event leading to PAS, hut the small numbers included in this portion of the study preclude our making this assumption. The data summarized in Table II demonstrate the significant association of intrapartum complications with the development of PAS in the caudal delivered group (p < 0.001). These intrapartum complications included transverse arrest, shoulder dystocia, premature placental separation, cephalopelvic disproportion, intrapartum hemorrhage ( > 500 c.c.), and uterine inertia. Unfortunately, the sample size was too small to allow any statistical conclusion about those deliveries performed with anesthesia other than caudal. Three signs of fetal distress-fetal tachycardia, fetal bradycardia, and meconiumstained amniotic fluid-were noted with sig-
274 Leake, Gunther, and Sunshine
nificant frequency (Table II) among mothers delivering affected babies with caudal anesthesia (p < 0.001). Based on these criteria, 50 per cent of the babies developing PAS had at least one sign of fetal distress compared to 13 per cent of the caudal control group. Mid-forceps deliveries and breech pres· entations occurred with significant frequency (p < 0.001) among the mothers with affected babies delivering with caudal anesthesia. Comment
This paper presents the first report of the incidence of PAS among a large series of live-born infants. The finding that this condition is nearly as common as the respiratory distress syndrome ( 1.5 per cent of total live births) at Stanford University Hospital may be influenced by the high-risk obstetrical population and the liberal use of obstetrical anesthesia. Although none of the patients with PAS died, their morbidity was significant. Two patients required respiratory support; the average duration of 0 2 use was three days. The mean of the three highest consecutive hourly respiratory rates recorded for each patient was 95 per minute. Although meconium aspiration is generally held to be the most common variety of PAS, 31 of our PAS cases had no evidence of meconium staining of the amniotic fluid or infant. Data are not necessarily fully documented in retrospective studies but in this study there was a research nurse present in the delivery room to record all pertinent information, including meconium staining. Our data showed that there was no statistical difference in the mean quantity of caudal anesthetic agent used (59 vs. 47 c.c. for the primiparas; 42 vs. 38.4 c.c. for the multiparas) , and no prolongation of labor ( 604 vs. 55 7 minutes for primiparas; 390 vs. 370 minutes for multiparas) when the mothers delivering affected babies were com. pared to their controls. The only implication of anesthetic factors
January 15, 1974
Am.
J. Obstet. GynecoL
on the development of PAS was the seeming association with epidural anesthesia. The number of cases is very small, however, since this route of anesthesia was selected only to teach anesthesia residents alternate methods of providing obstetrical anesthesia. Several authors have shown the rapid absorption of drugs from the epidural space. 5 • 7 Peak maternal concentration is found at five minutes. The concentration of drugs in the maternal circulation approximates a 3: 2 ratio with that found in the fetal circulation; with repeated hourly injections to maintain analgesia, maternal blood concentration is similar to that found after the first 30 minutes. In a series of lidocaine levels from healthy patients receiving obstetrical epidurals for term vaginal deliveries without signs of fetal distress, Shnider and Way 6 reported that when umbilical venous lidocaine levels were higher than 2.5 J.tg per milliliter, four of eight infants had low Apgar scores; three of the depressed infants had lidocaine levels greater than 3.0 J.tg per milliliter. Morishima and associates 5 studied the transmission of mepivacaine across the placenta in 56 healthy women at term who received epidural analgesia during labor and delivery. Twelve infants were depressed at birth; in five, umbilical venous blood levels of the drug were significantly higher ( 3.15 to 4.28 J.tg per milliliter) than those found in vigorous babies. Similar studies subsequently undertaken by us confirm the presence of high lidocaine levels in depressed infants although we were not studying lidocaine or carbocaine levels at the time of the aspiration pneumonia study. Bonica8 lists the first contraindication to the use of epidural anesthesia as lack of skill by the administrator-not only in carrying out the procedure but also in treating complications. It may be that the increased incidence of PAS among those deliveries under epidural in part reflects the relative inexperience of the operators. There is clear-cut evidence that intrapartum complications, fetal distress, breech presentations, and mid-forceps deliveries are
Volume 118 Number 2
associated with an increased risk of PAS. The statistical correlation between intrapartum insults and the development of PAS demonstrated in this paper supports the theory that intrauterine hypoxia triggers PAS. It is well recognized that much amniotic fluid is formed from the fetal lung. 9• 11 Although the exact pathophysiology of PAS is as yet only postulated, it has been shown that with hypoxia, abnormal glottic relaxation and respiratory movements occur in utero, 12 thereby allowing movement of amniotic fluid to occur in a reverse direction, depositing meconium and/or epithelium (and, at times, polymorphonuclear leukocytes and bacteria) into the trachea. At birth, this chemically abnormal aspirated material may not pass rapidly into lung lymphatics, thereby producing decreased lung compliance, air trapping beyond plugged bronchioles, and resulting dyspnea. Moss and colleagues 13 have shown that fetal distress induces qualitative and quan-
Perinatal aspiration syndrome
275
titative alterations of fetal mucous secretions in utero, yielding amniotic fluid with high viscosity. This fluid may also be difficult to clear from the alveolar spaces and might explain the non-meconium-stained PAS infants in our series. In our series aspiration would seem to have been initiated by an interplay of intrapartum insults and complications of anesthesia resulting in fetal distress and asphyxia. With the development of fetal monitoring techniques it may be possible to anticipate and intervene in those labors identified as high risk for the perinatal aspiration syndrome. Statistical evaluation of the data was provided by Dr. Byron W. Brown, Professor of Biostatistics, Stanford University Medical School. Dr. William Northway provided invaluable help by reviewing the radiographs. We are indebted to Dr. William Oh for his encouragement in the preparation of this manuscript.
REFERENCES
1. Peterson, H. G., and Pendleton, M. E.: Am.
2. 3. 4. 5. 6.
J. Roentgenol. 74: 800, 1955. Gooding, C. A., and Gregory, G. A.: Radiology 100: 131, 1971. Gunther, R. E., and Bauman, J.: Anesthesiology 31: 5, 1969. Gunther, R. E., and Bellville, J. M.: Anesthesiology 37: 288, 1972. Morishima, H. W., Daniel, S. S., Finster, M., Poppers, P. J., and James, L. S.: Anesthesiology 27: 145, 1966. Shnider, S., and Way, E.: Anesthesiology 29: 951, 1968.
7. Lurie, A., and Weiss, J.: AM. J. 0BSTET. GYNECOL. 106: 850, 1970. 8. Bonica, J. J.: In Shnider, S. M., editor: Obstetrical Anesthesia, Baltimore, 1970, The Williams & Wilkins Company, chap. 8. 9. Towers, B.: Nature 183: 1140, 1959. 10. Adams, F. H., Fujiwara, T., and Rowshan, G.: ]. Pediatr. 63: 881, 1963. 11. Ross, B. B.: Nature 199: 1100, 1963. 12. Adams, F. H., Desirets, D. T., and Towers, B.: Resp. Physiol. 2: 302, 1967. 13. Moss, A. J., Rettori, 0., and Simmons, N. S.: Pediatrics, 38: 858, 1966.
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P E R. 1 N A T A L aspiration syndrome (PAS) is a relatively common cause of neonatal respiratory distress, yet its exact pathogenesis remains obscure. Hallmarks of the condition appearing soon after birth include tachypnea, dyspnea, and cyanosis while breathing room air. Physical examination reveals respiratory rates greater than 60 per minute,
flaring of the alae nasi, intercostal retractions, and expiratory grunting. There may be an increase in the anteroposterior diameter of the chest, indicating air trapping. This may progress to interstitial emphysema, bleb formation, and complicating pneumothorax. Rales and rhonchi are present and there are areas of decreased breath sounds. Abnormal neurologic signs, varying from lethargy to convulsions, are sometimes noted. One of the most striking clinical findings, when present, is the mild to severe meconium staining of the newborn infant's skin, nails, and cord. This staining is often associated with signs of postmaturity such as long nails, desquamating epithelium, alert facies, and increased birth length. When such signs are present, the entity is usually termed meconium aspiration syndrome. A syndrome with similar clinical features and identical x-ray findings occurs in non-meconium-stained infants. Radiographs of the chest are most helpful in distinguishing this entity from other causes of respiratory distress in the newborn in-
From the Departments of Pediatrics and Obstetrics, Stanford University Medical Center. Supported in part by funds contributed by Sterling Winthrop Research Institute, by a United States Public Health Service Training Grant 5 TO! HD00049-09, and by a grant (RR-81) from the General Clinical Research Centers Program of the Divisions of Research Resources, National Institute of Health. Received for publication December 29, 1972. Revised May 31, 1973. Accepted July 6, 1973. Reprint requests: Rosemary D. Leake, M.D., Department of Pediatrics, Harbor General Hospital, 1000 W. Carson St., Torrance, California 90509.
271
272 Leake, Gunther, and Sunshine
Fig. 1. Chest x-ray of non-meconium-stained infant with perinatal aspiration pneumonia.
fant, 1 • 2 such as the respiratory distress syndrome, where there is a diffuse ground-glass appearance representing collapsed alveoli. Characteristic radiographic features of PAS are areas of patchy irregular opacification in the lungs. The degree of opacification tends to parallel the severity of clinical disease. When air trapping is present the lungs and thorax appear hyperexpanded. In order to define PAS more clearly, a retrospective chart review of the 3,344 liveborn deliveries at Stanford University Medical Center over a 22 month period was undertaken to determine the incidence of perinatal aspiration syndrome in one institution and to correlate intrapartum events and anesthesia with eventual perinatal outcome. Materials and methods
Neonatal records and chest x-rays of all babies exhibiting signs of respiratory distress, born at Stanford University Medical Center between July 1, 1966, and May 1, 1968, were examined. A group of 50 babies with PAS was identified and their maternal records reviewed. The diagnosis of PAS was based on the following criteria: ( 1) cyanosis, dyspnea, grunting, flaring of the alae nasi, and intercostal retractions within the first several hours of life, ( 2) respiratory rate of more than 60 for at least 24 hours, (3) a
Am .
J.
January 15, 1974 Obstet. Gynecol.
radiograph of the chest interpreted by two independent observers as being compatible with PAS1 • 2 and (4) the diagnosis of aspiration pneumonia at the time of discharge. During the same 22 month time period, a prospective, in-depth analysis of the effects on labor and delivery of three continuous caudal obstetrical anesthetic agents was being conducted at Stanford. 3 • 4 All mothers who delivered infants with PAS under caudal anesthesia were included in this study. Thus detailed pregnancy, labor, delivery, and anesthesia records of mothers delivering infants with PAS were available to compare with mothers delivering unaffected babies under caudal anesthesia during the same time period. Mothers excluded from the caudal control group were those delivering stillborn infants or twins, those completely dilated at the time of caudal administration, those whose caudal anesthetics were ineffective, and those undergoing cesarean section before complete dilatation. Matched controls were selected for each mother delivering with anesthesia other than caudal whose infants developed PAS. This control group yielded a live-born baby of similar birth weight whose mother had received a comparable amount of an identical anesthetic agent by the same route . The maternal history and fetal outcome were not known at the time of selection of these controls. Chi-square analysis was used for the sta tistical evaluation of the data. Results
Incidence and outcome. There were 3,344 live-born and 44 stillborn infants delivered during the 22 month study period. Of these, 276 were live-born premature infants. There were 50 live-born babies with PAS, yielding an over-all incidence of 1.5 per cent. All of the affected babies survived. Over the same time period, there were 59 babies with the respiratory distress syndrome, an incidence of 1.8 per cent. Nineteen of the infants with PAS were meconium stained; 31 were not. A representative chest x-ray from one of the
Volume 118 Number 2
Perinatal aspiration syndrome
273
Table I. Obstetrical anesthesia used during the study period and the subsequent development of PAS
Number of babies with PAS Number of babeis without PAS Per cent affected
Epidural
Caudal
7
32
127
Other anesthesias (pudendal, spinal, local)
1,914
1.7
5.5*
No anesthesia
11 1,180 1.0
0
73
0
*The incidence of PAS in tbe epidural group is significantly higher than among those delivered with caudal or other forms of anesthesia (p < 0.001 by 2 x n chi-square analysis).
Table II. Perinatal complications among deliveries with various types of anesthesia during the study period Epidural
Number of records analyzed Intrapartum complications* Meconium staining Fetal bradycardia Fetal tachycardia Mid forceps deliveries Breech presentation
Caudal
Babies with PAS
IMatched controls
Babies with PAS
7
7
32
2 1
2 0
2
0
1 0 0 0 0 0
lOt 1St St 5t 6t 6t
I
Other anesthesia
Controls
1,914 52t 177t 91t
12t
69t 20t
Babies with PAS
11 1
3
0 0 0 0
IMatched controls
11 0 1 0 0
0 1
*Transverse arrest, shoulder dystocia, premature placental separation, cephalopelvic disproportion, intrapartum hemorrhage, and uterine inertia.
tThe difference between PAS groups and controls is significant (p
non-meconium-stained infants is shown in Fig. 1. Analysis of data. Statistical analysis of the following parameters failed to demonstrate a significant difference between mothers delivering babies with PAS and their controls: Maternal age, height, weight at conception and delivery, parity, mode of onset of labor (spontaneous vs. induced), timing or method of membrane rupture (artificial vs. spontaneous), use of oxytocics, length of labor, incidence of spontaneous and low-forceps deliveries, quantity of anesthesia used, dilatation and station at time of anesthesia administration, amount of supplemental anesthesia, narcotics, and barbiturates. All mothers who delivered affected babies received anesthesia of some type. Table I demonstrates that 5.5 per cent of those mothers receiving epidural anesthesia delivered babies with PAS. This represented a significantly increased use of epidural anesthesia (p < 0.001) among those delivering affected babies. It is tempting to interpret
< 0.001). the concomitant lack of increased numbers of intrapartum complications and/or signs of fetal distress over those found with the other types of anesthesia as evidence that epidural anesthesia itself was the event leading to PAS, hut the small numbers included in this portion of the study preclude our making this assumption. The data summarized in Table II demonstrate the significant association of intrapartum complications with the development of PAS in the caudal delivered group (p < 0.001). These intrapartum complications included transverse arrest, shoulder dystocia, premature placental separation, cephalopelvic disproportion, intrapartum hemorrhage ( > 500 c.c.), and uterine inertia. Unfortunately, the sample size was too small to allow any statistical conclusion about those deliveries performed with anesthesia other than caudal. Three signs of fetal distress-fetal tachycardia, fetal bradycardia, and meconiumstained amniotic fluid-were noted with sig-
274 Leake, Gunther, and Sunshine
nificant frequency (Table II) among mothers delivering affected babies with caudal anesthesia (p < 0.001). Based on these criteria, 50 per cent of the babies developing PAS had at least one sign of fetal distress compared to 13 per cent of the caudal control group. Mid-forceps deliveries and breech pres· entations occurred with significant frequency (p < 0.001) among the mothers with affected babies delivering with caudal anesthesia. Comment
This paper presents the first report of the incidence of PAS among a large series of live-born infants. The finding that this condition is nearly as common as the respiratory distress syndrome ( 1.5 per cent of total live births) at Stanford University Hospital may be influenced by the high-risk obstetrical population and the liberal use of obstetrical anesthesia. Although none of the patients with PAS died, their morbidity was significant. Two patients required respiratory support; the average duration of 0 2 use was three days. The mean of the three highest consecutive hourly respiratory rates recorded for each patient was 95 per minute. Although meconium aspiration is generally held to be the most common variety of PAS, 31 of our PAS cases had no evidence of meconium staining of the amniotic fluid or infant. Data are not necessarily fully documented in retrospective studies but in this study there was a research nurse present in the delivery room to record all pertinent information, including meconium staining. Our data showed that there was no statistical difference in the mean quantity of caudal anesthetic agent used (59 vs. 47 c.c. for the primiparas; 42 vs. 38.4 c.c. for the multiparas) , and no prolongation of labor ( 604 vs. 55 7 minutes for primiparas; 390 vs. 370 minutes for multiparas) when the mothers delivering affected babies were com. pared to their controls. The only implication of anesthetic factors
January 15, 1974
Am.
J. Obstet. GynecoL
on the development of PAS was the seeming association with epidural anesthesia. The number of cases is very small, however, since this route of anesthesia was selected only to teach anesthesia residents alternate methods of providing obstetrical anesthesia. Several authors have shown the rapid absorption of drugs from the epidural space. 5 • 7 Peak maternal concentration is found at five minutes. The concentration of drugs in the maternal circulation approximates a 3: 2 ratio with that found in the fetal circulation; with repeated hourly injections to maintain analgesia, maternal blood concentration is similar to that found after the first 30 minutes. In a series of lidocaine levels from healthy patients receiving obstetrical epidurals for term vaginal deliveries without signs of fetal distress, Shnider and Way 6 reported that when umbilical venous lidocaine levels were higher than 2.5 J.tg per milliliter, four of eight infants had low Apgar scores; three of the depressed infants had lidocaine levels greater than 3.0 J.tg per milliliter. Morishima and associates 5 studied the transmission of mepivacaine across the placenta in 56 healthy women at term who received epidural analgesia during labor and delivery. Twelve infants were depressed at birth; in five, umbilical venous blood levels of the drug were significantly higher ( 3.15 to 4.28 J.tg per milliliter) than those found in vigorous babies. Similar studies subsequently undertaken by us confirm the presence of high lidocaine levels in depressed infants although we were not studying lidocaine or carbocaine levels at the time of the aspiration pneumonia study. Bonica8 lists the first contraindication to the use of epidural anesthesia as lack of skill by the administrator-not only in carrying out the procedure but also in treating complications. It may be that the increased incidence of PAS among those deliveries under epidural in part reflects the relative inexperience of the operators. There is clear-cut evidence that intrapartum complications, fetal distress, breech presentations, and mid-forceps deliveries are
Volume 118 Number 2
associated with an increased risk of PAS. The statistical correlation between intrapartum insults and the development of PAS demonstrated in this paper supports the theory that intrauterine hypoxia triggers PAS. It is well recognized that much amniotic fluid is formed from the fetal lung. 9• 11 Although the exact pathophysiology of PAS is as yet only postulated, it has been shown that with hypoxia, abnormal glottic relaxation and respiratory movements occur in utero, 12 thereby allowing movement of amniotic fluid to occur in a reverse direction, depositing meconium and/or epithelium (and, at times, polymorphonuclear leukocytes and bacteria) into the trachea. At birth, this chemically abnormal aspirated material may not pass rapidly into lung lymphatics, thereby producing decreased lung compliance, air trapping beyond plugged bronchioles, and resulting dyspnea. Moss and colleagues 13 have shown that fetal distress induces qualitative and quan-
Perinatal aspiration syndrome
275
titative alterations of fetal mucous secretions in utero, yielding amniotic fluid with high viscosity. This fluid may also be difficult to clear from the alveolar spaces and might explain the non-meconium-stained PAS infants in our series. In our series aspiration would seem to have been initiated by an interplay of intrapartum insults and complications of anesthesia resulting in fetal distress and asphyxia. With the development of fetal monitoring techniques it may be possible to anticipate and intervene in those labors identified as high risk for the perinatal aspiration syndrome. Statistical evaluation of the data was provided by Dr. Byron W. Brown, Professor of Biostatistics, Stanford University Medical School. Dr. William Northway provided invaluable help by reviewing the radiographs. We are indebted to Dr. William Oh for his encouragement in the preparation of this manuscript.
REFERENCES
1. Peterson, H. G., and Pendleton, M. E.: Am.
2. 3. 4. 5. 6.
J. Roentgenol. 74: 800, 1955. Gooding, C. A., and Gregory, G. A.: Radiology 100: 131, 1971. Gunther, R. E., and Bauman, J.: Anesthesiology 31: 5, 1969. Gunther, R. E., and Bellville, J. M.: Anesthesiology 37: 288, 1972. Morishima, H. W., Daniel, S. S., Finster, M., Poppers, P. J., and James, L. S.: Anesthesiology 27: 145, 1966. Shnider, S., and Way, E.: Anesthesiology 29: 951, 1968.
7. Lurie, A., and Weiss, J.: AM. J. 0BSTET. GYNECOL. 106: 850, 1970. 8. Bonica, J. J.: In Shnider, S. M., editor: Obstetrical Anesthesia, Baltimore, 1970, The Williams & Wilkins Company, chap. 8. 9. Towers, B.: Nature 183: 1140, 1959. 10. Adams, F. H., Fujiwara, T., and Rowshan, G.: ]. Pediatr. 63: 881, 1963. 11. Ross, B. B.: Nature 199: 1100, 1963. 12. Adams, F. H., Desirets, D. T., and Towers, B.: Resp. Physiol. 2: 302, 1967. 13. Moss, A. J., Rettori, 0., and Simmons, N. S.: Pediatrics, 38: 858, 1966.