THE RELATIONSHIP OF THYROID HORMONES, FETAL LUNG DEVELOPMENT AND PULMONARY SUPEROXIDE DYSMUTASE (SOD) ACTIVITY IN THE OVINE FETUS

Allen Erenberg, Lee Frank, Mitchell Rhodes, Roland t$ennedy, and Robert Roberts :. a

Departments of Pediatrics, Pharmacology, Anesthesiology, and Obstetrics and Gynecology

University of Iowa, Iowa City, Iowa

Previous studies have shown that fetal lung maturation can be accelerated

by direct injection of thyroxine (T4) into the fetus, and delayed by

surgical fetal thyroidectomy. Other studies concerning the influence of

thyroid activity in modifying the development of oxygen toxicity have shown

that the toxic effects of oxygen were enhanced in the hyperthyroid animal

but delayed in the thyroidectomized animal. SOD is an enzyme which is

believed to have a protective effect against oxygen toxicity by scavenging

the toxic free radical superoxide anion (02). In order to delineate the

relationship of thyroid hormones and pulmonary SOD activity, ovine,fetuses

were surgically thyroidectomized at 95-99 days gestation. At 140 days

gestation, the thyroidectomized (TX) and control (C) fetuses were sacrificed.

In the TX, the hypothyroid state was confirmed by lack of thyroid tissue at

autopsy, and a mean serum T4 concentration of <l u%, compared to 14.2 pg% in

the C. The combined heart and lung weights were significantly reduced in

the TX. Light and electron microscopic examination of the TX lung revealed

hypercellular, thickened alveolar septae and interstitium. The alveolar

lining consisted of cuboidal cells without the characteristic lamellar

bodies and the tracheal fluid lecithin/sphingomyelin ratio was decreased,

indicative of delayed surfactant synthesis. The hypercellular histologic

appearance of the TX lung was confirmed by an increased DNA content and

reduced protein/DNA ratio per gram wet weight lung tissue indicating there

was a larger number of smaller sized cells. The SOD activity per gram wet

weight lung determined by the standard ferricytochrome-c assay was signi-

ficantly increased in the TX compared to the C. Conclusions: 1) Thyroidectomy

in the ovine fetus during the second trimester significantly delays lung

maturation and surfactant synthesis. 2) SOD activity based on per gram lung

weight, per pg protein and per ug DNA is enhanced'in the TX fetuses.

HIJMAN FETAL BREATHING MOVEMENTS -- A QUALITATIVE ANALYSIS

3

F. Manning, M.D., L. Platt, M.D., and M. Lemay, M.D.

Division of Maternal-Fetal Medicine University of Southern California School of Medicine

The presence of fetal breathing movements (FBM) as a normal component

of intrauterine development has been confirmed by direct observation in

the chronic animal model. FBM in man have been recorded indirectly

using a gated A-scan method. The advent of real time B-scanning tech-

niques makes it possible to obtain a dynamic composite, two-dimensional

image of human FBM.

A total of 250 observations of FBM were made in 75 patients using a linear

array real time B-scan method (A. D. R. , Phoenix). Longitudinal and

transverse scans of. the fetus were made using either a 2.25 or a 3.5 mHz

transducer. Selected portions were stored on videotape for analysis.

FBM were observed from as early as 18 weeks’ gestation; before this time,

FBM could not be differentiated from generalized fetal movements (FM).

FBM are episodic in nature, a burst of breathing interspersed among

periods of apnea. The proportion of time that FBM were present (9’0 FB)

over the observation period (mean 30 minutes) ranged from 0 to 95%).

FBM were paradoxical in character, inspiration associated with thoracic

indrawing and abdominal outward excursion. Thoracic indrawing was

maximal in the xiphisternal area (up to 1 cm) and minimal in the upper

thorax. Abdominal movements were maximal in the epigastric area (up to 2 cm). At times when the fetal stomach was fluid filled, the left dome

of the diaphragm could be visualized to descend with inspiration. The inspiratory/expiratory ratio ranged from 2/l to 4/l. Several patterns of

FBM were observed. The most common consisted of rapid (1 to 1.5 Hz), irregular, low amplitude FBM, usually associated with fetal limb move-

ments and rolling trunk movements. A second pattern was similar to

the first with the presence of isolated, slow (1 second), large amplitude FBM at a rate of . 1 to .3 Hz. A third pattern consisted of the isolated, slow breaths only; this pattern was associated with quick, startle-like

FM. A fourth pattern consisted of isolated, large amplitude, extremely

rapid (. 2 to .5 seconds) FBM at a rate of . 1 to .3 Hz. This type of FBM was invariably palpable per abdomen and often reported as fetal hiccups by the subject. Any one combination of those patterns could be observed in a subject during a single observation.

The possible significance of FBM and the relationship of patterns of FBM

to fetal state will be discussed.

INFLUENCE OF MATERNAL MEDICATION ON FETAL BREATHING MOVEMENTS IN THE BABOON 4

H.O. Morishima, S.N. Caritis, M-N. Yeh, and L.S. James

Departments of Anesthesiology, Obstetrics and Gynecology, and Pediatrics College of Physicians and Surgeons, Columbia University, New York, New York

In recent years, a number of studies on the use of fetal breathing movements as a more sensitive index of fetal well-being than the fetal heart response, have been reported. However, the effects of medication administered to the mother to relieve pain and anxiety have been poorly understood. Dawes and co-workers ob- served in the sheep that the fetal respiratory activity disappeared at once and did not return for approximately one hour following a minimal sedative dose of chloralose or pentobarbital administered to the ewe. The objectives of this study are: to determine whether fetal breathing movements are a more meaningful measure to assess the intrauterine condition of the fetus than monitoring fetal heart rate; and to observe the effect of anesthesia or analgesia administered to the mother during labor and delivery on fetal breathing.

Observations of fetal breathing movements have been made in 21 experiments using the semiacute preparation in the baboon. Fetal tracheal pressure was mea- sured and recorded as well as arterial pressure and heart rate. Under N O/O analgesia periodic rapid irregular breathing movements with the rates of215-$0 times per minute were observed in the more mature (gestations 159-169 days) and nonasphyxiated fetuses during and following the fetal operation. Younger fetuses (gestations 144-154 days) did not demonstrate breathing activity, regardless of their acid-base state or external stimulation. Acute fetal hypoxemia and aci- dosis produced by occlusion of the umbilical cord or administration of acetyl- choline directly to the fetus abolished the "normal pattern" of respiratory movements and replaced it with a gasping pattern. Prolonged deep and slow "gasping patterns" with 30-50 n&ig negative pressure were observed in the ma- jority of mature fetuses shortly before the death. Administration of terbuta- line, a beta increased bo h 2

adrenergic agonist, or aminophylline to the fetus significantly frequency and depth of respiration without altering fetal pHa

and Pa0 . Apnea, induced by a bolus injection of succinylcholine (4 mg/kg) to the fetus lasted for less than 2 minutes.

These observations demonstrate that rhythmic breathing movements are present in the mature baboon fetus during maternal anesthesia or analgesia. This finding is contrary to the observation in the fetal lamb where minimal maternal sedation caused respiratory arrest.

Supported in part by Grant 5POl-GkiO9069, NIGMS, NIH.

EFFECT OF INTRAUTERINE EXCHANGE TRANSFUSION ON FETAL OXYGENATION 5

Y.K. Tien, M.D.

Department of Anesthesia oston Hospital for Women and Harvard Medical School

ntrauterine exchange transfusion with adult blood (IUT) is used to A few experiments have been done on non-anemic fetal

erms of fetal oxygenation, the following remain unclear: i, e adult P50 (P5Oa) for fetus; (2) Interaction between

n of anemia and change of fetal P50 (P5of) by IUT. Fur- with a much wider separation between its P5Oa and P5Of, the sheep

? iate model for studying IUT although its other physio- ar comparable to those of humans. With a theoretical d to answer these questions.

aking into consideration hemoglobin reaction rate, Longo, et al., t steady state with constant fetal 02 uptake, end-capil- circulation would be affected little by P5Qf, hemoglobin

tion (HBc) or umbilical blood flow. Based on this and by using a set physiologic values for fetal lamb, 02 content and PO2 in various ves- derived mathematically at different levels of fetal cardiac output

Mean fetal peripheral capillary Po2 (PzQ2) was then computed At given HBc and P5of, as Q drops to a critical level

proportional changes in all flows), 02 transport may not be enough 11 venous PO2 could be zero. This CQ and the pFQ2 at higher Q were

We also tried in the human fetus the normal data from the Clinically mean HBc in normal and anemic fetus be-

, 9.9 and 12.2 gm%, respectively (4); corresponding lamb would be 12, 7.8 and 9.6.

the effects of changing normal P5Of to P5Qa alone. lower P?tlp at a given Q, both being exaggerated by This may imply a narrower margin of safety with

3 illustrates that the benefit of concomitant partial correction above disadvantage in human but not so in sheep (cQ

Obviously, IUT can improve oxygenation of anemic human fetus in comparably anemic lamb, Our results are consistent

report (4) and experiments on non-anemic lamb (1,3).

I

6 PBARMACOLOGIC ALTERATION OF BEMOGLOBIN STRUCTURE: A POSSIBLE NEW TREATMENT FOR FETAL HYPOXIA

Diane R. Riehl, Julian T. Parer, Sol M. Shnider, Judy Johnson, Berrilyn Jones, Richard G. Wright, Stephen H. Rolbin, and Gershon LeVinSOn

University of California, San Francisco

Ortho-iodo-sodium benzoate (OISB) is an organic anion which has been shown to alter the tertiary structure of the hemoglobin molecules in experimental animals and humans. This alteration results in a rightward shift of the oxyhemoglobin dissociation curve. We are currently investigating this drug to determine if a rightward shift of the maternal curve will provide more oxygen at the placental site for the fetus. Placental transfer of OISB has not hitherto been determined. The following in vitro and in vivo studies have been devised to examine both maternal and fetal effects of OISB.

In Vitro Studies: 15 ml of heparinized venous blood was drawn tram 7 healthy parturients and from the umbilical vein of doubly clamped cord segments. Likewise maternal and fetal blood samples were drawn from 6 pregnant ewes (120 days gesta- tion) from catheters in the maternal and fetal femoral arteries. Each blood sample was divided into 2 aliquots. The P50 (partial pressure of oxygen at which 50% of hemoglobin is saturated) was determined for the first aliquot. Into the second aliquot, OISB was added in a concentration of 32 mM/L. Specimens were shaken for 30 minutes and the P50 was determined in duplicate for each sample. The mean increase in P50 + standard error for the maternal and fetal samples is shoK in the following table.

P50 P50 Shift % Shift in (Control) (OISB) (mmHg) P50 n

Sheep maternal 6 42.0+2.4. 5.0.7+1.7 8.7+1.8 21% Sheep fetal 6 21.6TO.8 26.270.8 4.6TO.5 21%

Human maternal 7 29.4+1.7 38.7+2.5 9.3+3.0 32% Human fetal 7 23.2El.4 29.8EO.6 6.6El.l 28%

Based on these data, at normal hemoglobin concentration and uterine venous oxygen tension, and provided uterine blood flow remains the same, this shift to the right of the maternal sheep curve would result in an increase in uterine arterio-venous oxygen difference from 5 to 6.5 volumes percent, thus increas- ing oxygen unloading by 30 percent. Whether simultaneous changes in fetal oxygen affinity could negate this is not certain as rapid, in vivo placental transfer has not.yet been demonstrated.

A In vivo studies to determine if OISB therapy will increase fetal

'., oxygenation are currently in progress. OISB is infused intra- venously into pregnant ewes and changes in fetal ~02, oxygen saturation. content and consumntion are measured. In addition, maternal and fetal cardiovascular and uterine blood flow changes are determined. Preliminary results of these experiments and possible clinical application of QISB will be, presented.

ACUTE MATERNAL PSYCHOLOGICAL STRESS: A POSSIBLE CAUSE OF FETAL DISTRESS DURING LABOR - PRELIMINARY REPORT

H.O. Morishima, M-N. Yeh, R.E. Stark, J.M. Milliez, B.B. Gutsche, L. Indyk and L.S. James

Departments ok Anesthesiology, Obstetrics and Gynecology, and Pediatrics College of Physicians and Surgeons, Columbia University, New York, New York

The adverse effects of obstetric anesthesia on the fetus, during labor, has been extensively studied during the past decade. In contrast, little in- formation is available concerning the effects of maternal psychological stress and labor pain on the uteroplacental circulation and fetal condition. A pilot experiment was designed to investigate the effect of maternal stress and pain on the fetus and the alleviation of any adverse effects by maternal analgesia and anesthesia.

Seven pregnant baboons and four rhesus monkeys near term with semiacute preparation have been studied. Four animals were subjected to stress of noise or bright light with the mother breathing room air (group I), while 7 animals (group II) were given painful stimulation by clamping the skin of the toes during air or N20/02 breathing.

During the maternal stress in group I maternal arterial pressure and heart rate increased from the initial values of 95 to 120 mMg, and 170 to 200 beats/ min respectively. These were accompanied by fetal bradycardia, acidosis (mean pHa fell from 7.28 to 7.18), and hypoxemia (Sa02 fell from 46 to 22%). When maternal agitation subsided with administration of pentobarbital or removal of stress, fetal heart rate and acid-base state returned to the control level. Three fetuses in group II were in good condition with an average pHa of 7.35 and Sa02 57%; heart rate decreased from 173 to 159 beats/min, pHa and SaO de- creased from 7.35 to 7.33, and 57 to 42% respectively, while maternal re tless- E ness was induced by painful stimulation during air breathing. The other four fetuses in group II were moderately acidotic with a mean pHa of 7.23 and SaO of 36%. Fetal bradycardia and hypoxemia were more profound during the pet-lo *B of painful stimulation; one of the mothers developed a sinus arrhythmia which was followed by a conduction defect (2:l block) in her fetus. A marked re- duction in uterine blood flow was also observed during painful stress of the mother. All changes were partially or completely abolished following adminis- tration of N 0 or pentobarbital to the mother.

It has 2 een shown that fetal death was attributed to chronic stress in pregnant mice, in a study which also demonstrated that following stress fetal mortality was reduced if the mother had been adrenalectonized. Direct mea- surement of catecholamines could be expected to provide a more definitive ap- praisal of adrenergic activity under rapidly changing environmental circum- stances, such as occurring during labor. We plan to determine catecholamine levels in plasma to correlate with maternal and fetal effects of maternal stress.

Supported in part by Grant 5POl-GM09069, NIGMS, NIH.

8

RENAL EFFECTS OF TRANSPLACENTALLY ACQUIRED INDOMETUACIN

B.R. Parks, B.H. Douglas, and J.E. Rawson

Departments of Pediatrics and Medicine University of Mississippi Medical Center, Jackson, Mississippi

This study was designed to determine the effect of indomethacin on the offsprings of mongrel dogs which received 1.5 mgfkg of the potent prostaglandin synthesis inhibitor orally for 7 to 10 days prior to delivery. The pregnant animals were given standard laboratory chow. Water was available ad lib. The offsprings of animals which were treated

with indomethacin (Group I> and of untreated control animals (Group II) weighed 300 to 500 g. Serum analysis on the offsprings of both groups included blood urea nitrogen (BUN), creatinine, sodium (Na), potassium (K),

and osmolality (Osm). Urinary creatinine, Na, K, Osm as well as bilirubin, ketones, glucose, protein and pH were also determined. The urine was negative for bilirubin, ketones and glucose. Proteinuria was present and varied from 10 to 300 mg/dl but there was no significant difference between the two groups. Urinary creatinine was 23.5 2 4.9 mg/dl (Mean 2 SEM) in Group II and 10.4 f 3.1 mg/dl in Group I (pc6.05). Urine osmolality

was 580 + 42 mOsm/l in Group I and 793 + 103 mOsm/l in Group II (difference not significant). There was no difference in urinary Na and K concentrations between the two groups. Serum analysis revealed the following: The BUN was 18 + 3 mg/dl in the control group and 35 + 3 mg/dl in the treated group (p<O.O5). Serum creatinine levels were not significantly different (0.27 2 0.08 mg/dl in Group 1 and 0.36 + 0.02 mg/dl in Group II). There was no significant difference in serum Na, K or Osm between the two groups.

4

9

PULMONARY PATHOLOGY IN FETAL LAMBS VENTILATED WITH 15% AND 40% O2

D.C. Zavala, A. Erenberg, and M.L. Rhodes

Departments of Medicine and Pediatrics University of Iowa, Iowa City, Iowa

Because of the continuing controversy in RDS over the role played by oxygen in the development of pulmonary pathology, a control study of the effects of 15% and 40% 02 was carried out on 22 twin fetal lambs of 11 pasture-bred ewes. The ewes were anesthetized by pontocaine spinal anesthesia and delivered by cesarean section. The fetal head was exposed and covered with a saline filled glove. The fetal trachea was isolated, a specimen of tracheal fluid obtained for lecithin/sphingomyelin ratio determination, and a tracheostomy performed. Pa02, PaC02 and pH were monitored through an umbilical arterial line. One twin neonate from each ewe was ventilated with 15% 02 and the other with 40% 02 against a continuous positive airway pressure (CPAP) of 2-4 mm H20.

The lambs were divided into two groups according to gestational age (normal ovine gestation is 148-150 days). Group I consisted of 6 sets of twins (N=12) with ages of 130-134 days. Of the neonatal lambs in Group I, all had L/S ratios of 0.7-1.2 and died in severe metabolic acidosis (pH 6.67- 6.95) within 6 hours except for one animal 134 days gestation who survived and was sacrificed at 8 hours. Of the 10 neonates in Group II, all had L/S ratios of 1.4-2.3 and survived the acute experiment before being sacrificed at 8 hours. using 15%

The mean values for Pa02 and A-a gradients in Groups I and II and 40% 02 were as follows:

f FIOs 0.15 FIOs 0.40

.i

.

tGROUP I

Pa02 A-a Pa02 A-a

Initial 18 37 31 184

(130-134 days) Final (2.5-8 hrs) 22 4 31 157

GROUP II Initial 21 37 40 177

(135-145 days) Final (8 hrs) II 41 22 I 57 176

In Group I, histologic examination of the lungs revealed extensive atelectasis, moderate edema, capillary congestion, focal hemorrhage and sparse hyaline mem- branes in both the 15% and 40% oxygen exposed animals. In Group II, there was a significant difference: the animals exposed to 40% 02 showed widespread, severe atelectasis compared to mild, focal atelectasis in animals breathing 15% 02.

Conclusions: The susceptibility of the preterm neonatal lamb lung to oxygen toxicity is related to the stage of lung maturation. When exposed to hyper- oxia, neonates with L/S ratios between 1.4-2.3 (Group II) have evidence of increased oxygen toxicity acutely manifested by atelectasis. When the L/S ratios are less than 1.2 (Group I), a hyperoxic environment is necessary for survival. In this premature group there is no difference in the pulmonary histopathology of lambs exposed to a hypoxic or hyperoxic environment.

THE CONTINUING NEED FOR EXTRAPERITONEAL CESAREAN SECTION

R. P. Perkins, M.D., FACOG

University of Colorado

The continuing experience with extraperitoneal cesarean section at this institution is reviewed. The first 50 cases performed are reviewed and compared with equal numbers of two control groups as previously presented. Despite our liberalization of indications for the procedure, a persistent advantage in the use of the procedure is demonstrated. Earlier optimism regarding the use of the procedure in selected patients is vindicated. Despite the extraperitoneal group's appearing more at risk before the pro- cedure , postoperative courses were comparable. In the three years of the study, no patient required re-operation for infectious complications, a triumph over past experience.

Per cent >24 hours Per cent ruptured Mean hours Per cent febrile preoperative membranes of labor before surgery antibiotics

Group I* 48 17.4 66 76

Group II** 6+ 7.ot 12+ 24+

Group III*** 52 11.3+ 24+ 44-+

Mean anesthesia Mean Mean decrease Mean Apgars induction to operative in hematocrit (one and five delivery time time (min) (per cent) minutes)

(min)

Group I* 12.2 69.8 5.8 4.2 - 7.6

Group II** 11.2+ 61.3 5.2 6.0-b- 7.8

Group III** 11.6 70.8 6.5 5.0+- 8.9

Per cent positive endometrial cultures Per cent febrile Per cent hospitalized Pathogens Anaerobes 3 days or more 8 days or more

Group I* 66 40 46 20

Group II** 2&l- 14+ 42 16

Group III** 4ot 26 48 28

10

* Extraperitoneal * Next case

*** Transperitoneal

+ = differs from Group I (p( 0.05)

with possible infection

11

SURVEY OF SOAP MEMBERSHIP

RE REGIONAL ANESTHESIA BY NURSE ANESTHETISTS

Marcelle Willock, MD

Department of Anesthesiology Roosevelt Hospital, New York, New York

A survey was made of the SOAP membership regarding the administration of regional anesthesia by nurse anesthetists. The presidents of the state anesthesiology societies were also requested to state the position of their re- spective associations.

68 replies were received from 25 states. The majority of respondents were anesthesiologists and worked in volun- tary hospitals. Almost all had previously worked with CRNAs or were associated with them presently. 48% have taught regional anesthesia to nurse anesthetists. 58% indicated they would be willing to do so if permitted by law, 25% were unwilling and 17% were undecided. 72% felt that CRNAs can safely manage regional anesthesia, 10% felt that they would not and 18% were undecided. The consensus seemed to be that CRNAs can be taught to administer and manage regional anesthesia safely and most anesthesiologists would not be adverse to providing that instruction.

Most state societies had no official policy except to en- dorse the state law or health code in this regard. A few state societies were opposed to any alteration in their state laws to allow CRNAs to give regional anesthesia.

4

12 EARLY HYPERNATREMIA OF THESLOW BIRTHWEIGHT (VLBW) INFANT

i i 1: : 4

I

,

! I 4

Kenneth L. Harkavy, M.D., and John W. Scanlon, M.D.

Columbia Hospital for Women and Georgetown University School of Medicine

Neonatal hypernatremia is a cause of significant morbidity and mortality. Recently it has been related to excess NaHC03 administration.

The Hospital course of all infants who were born during a six month period, had a birthweight (BW) c 1250 grams and survived 24 hours or more, were reviewed. Six of 12 pa:ients (Group I) had a serum sodium greater than 149 meq/L at least once during the first 72 hours'of life. The following table summarizes this group and the six infants without hypernatremia (Group II),

Table I

kOR/I* &&?A Group I Group II

(Mean +_ S.D.)

Birth Weight

Gestational Age

Artificial Ventilation

Subarachnoid Hemorrhage

Early Na+ intake

Total Na+ intake

Early Hz0 intake

it:zgt ~~$to~~:rly intake

Urine S.G. at peak Na+

Peak serum Na+ (range)

* PC.05

826 2 219 grams*

26 +_ 2.7 weeks*

616

315

4.72 +_ 2.63 meq/Kg/24h

18.65 + 6.47 meqJKgf72h

121 5 40 ml/Kg/24h

6.5 + 3.5**

40.7-t 21.0 meq/L

1.016 +_ .005*

161.5 (150-182) meq/L

** p <.02

1072 +_ 133

29 t 1.0

3/6

l/l

3.32 f 1.38

11.89 +_ 4.05

95 2 11

1.8 f 1.7

35.0 f 13.7

1.010 +, .004

140.2 (131-148)

Conceptually, hypernatremia may result from an intake of Na in excess of H20 or from a loss of water which exceeds that of Na+. Current information suggests that immature infants tend to have a high urine Na+ loss, commonly leading to hyponatremia. This physiology, plus similar Na+ intakes in the two patient

groups, suggest that a positive Na' balance was not a primary cause of hyper- natremia.

The early water intake of 120 ml/Kg/d is consistent with current estimates of basal and insensible water needs of prematures. Nevertheless, as evidenced by weight loss and high urine specific gravities, the hypernatremic VIEW infants were dehydrated. Since abnormal stool, respiratory and oral losses were absent, insensible water loss probably exceeded published values of SO-75 ml/Kg/d.

We postulate that because the thin, permeable skin of the VLBW infant covers more surface area relative to mass than in larger neonates, larger fluid losses will occur. Free water intakes of 150-200 ml/Kg/d, guided by frequent weighings, urine specific gravities and outputs, and serum electrolytes may help avoid electrolyte imbalance and possibly some of the morbidity and mortality of the VLBW infant.

13

MATERNAL MORTALITY IN INDIANA AS RELATED TO ANFSTHESLA

Virginia K. Bond, M.D. and William D. Ragan, M.D.

Indiana University School of Medicine

All of the maternal deaths which have been reported in Indiana are studied by a staff obstetrician. This individual interviews the physician responsible, summarizes the medical records, and requests pathological findings. The case is then presented before a review committee consisting of obstetricians from various areas in the state, internists, anesthesiologists, and pathologists.

These case summaries have then been examined anesthetic related factors.

carefully regarding

Maternal deaths are defined in this study as patients through the post-partum period extending -

deaths in pregnant for one year. Be-

cause of changes in personnel, the year 1969 is not included. With that exception, this study covers the years 1967 through 1974.

In this seven year period there were 154 deaths. These may be subdivided into the following groups:

(1) Deaths due to concommitant disease or accident 44 (2) Deaths due to a complication of the pregnancy S6 (3) Deaths due to anesthetic accident (4) Deaths in groups 1 and 2 which might have been tz

modified by prompt management by a trained anesthesiologists.

Fourteen deaths were directly related to anesthesia. Ten of these died of pulmonary failure due to aspiration of gastric fluid. A summary of related factors will be presented.

Four anesthetic deaths were not related to aspiration. One of these involved an overdose of lidocaine. Three were associated with the misuse of cyclopropane. Brief study of the management of these cases is instructive.

Obstetric anesthesiologists are constantly striving to eliminate the deaths in group 3. In addition in recent years .great advances have been made in the situations involved in group 4. Summaries of the problems encountered in these patients may set forth our goals for the future.

EFFECTS OF GLYCOPYRROLATE ON GASTRIC REQUIRING CESAREAN

VOLUME AND pH IN PATIENTS SECTION

William E. Marks, Jr., M.D. and J. Roger Bullard, M.D. Medical University of South Carolina

Charleston, South Carolina

During pregnancy, the combination of an increased gastric volume, a lower pH of gastric contents, and an increased intra-abdominal pressure all raise the risk of aspiration pneumonitis should general anesthesia be utilized. There is evidence to show that a pH below 2.5 and a volum7 greater than 0.4ml/kg are important in causing aspiration pneumonitis. Because of this, many recommend that oral antacids be administered to pregnant patients requiring general anesthesia. While this has been shown to increase the pH of gastric contents in a majority of patients, some remain at risk. A questjon has also been raised concerning the effect on the lung of aspirated antacid.

Glycopyrrolate is a quaternary ammonium compound with effective anti- cholinergic properties. It has been shown to significantly reduce the volume and acidity of gastric juice in adult volunteers in dose

4 that have no cardio-

vascular effect (0.2mg I.M., peak effect at 60 minutes). Glycopyrrolate has also been shown to be significantly more effective th n atropine in raising the gastric juice pH above 2.5 in pediatric patients. 4

Therefore, we designed a study to access the effect of 0.2mg of glycopyrrolate on the gastric volume and pH of pregnant patients. Forty un- selected patients scheduled for general anesthesia for Cesarean section were divided into two groups. Group I received atropine 0.4mg I.M. and Group II received glycopyrrolate 0.2mg I.M., both given approximately one hour pre- operatively. After the.induction of general anesthesia and the placement of an endotracheal tube, a nasogastric tube was placed in the stomach and the gastric contents aspirated. Measurements were made of volume and pH. Other appropriate-data was kept on each patient. --

ihe study is completed and the results are being analysed. Our findings will be presented at the Meeting.

1.

2.

3.

4.

REFERENCES

Roberts RB, Shirley MA: Reducing the Risk of Acid Aspiration During Cesarean Section. Anesth and Analg 53: 859-868, 1974.

Kuchling A, et al: The Pulmonary Lesion of Antacid Aspiration. Abstracts of Scientific Papers, American Society of Anesthesiologists Annual Meeting, p. 281, 1975.

Taylor WJR, et al: A Comparative Evaluation of Intramuscular Atropine, Decyclomine, and Glycopyrrolate Using Healthy Medical Students as Volunteer Subjects. Inter J Clin Pharmacol Ther Toxic01 3(4): 258, 1970.

Salem MR, et al: Premedicant Drugs and Gastric Juice pH and Volume in Pediatric Patients. Anesthesiology 44: 216-219, 1976.

16 PUIMONARY DAMAGE CAUSED BY ASPIRATION OF GASTRIC CONTENTS

CONTAINING SMALL FOOD PARTICLES

J.C. Reynolds, J.W. Wynne, and C-1. Hood

University of Florida College of Medicine, Gainesville, Florida

The aspiration of stomach contents during labor and delivery is an important problem in obstetric anesthesia and a major cause of obstetric mortality. It is generally held that the lung damage caused by the aspiration of stomach con- tents results either from the effects of acid at a pH < 2.5 or from obstruction of airways by large food particles. Aspirates with a pH > 2.5 and free of ob- structing food particles are felt to be of little clinical consequence. In the present study we used pathologic and radiologic parameters to compare the ef- fects on the lung of the aspiration of saline and of weakly acid gastric con- tents (pH 4.3) containing small food particles.

Anesthetized rabbits were secured in the supine position and a 119 intra- venous catheter was inserted through the trach'eal rings and advanced to the left lower lobe under fluoroscopic control. Gastric contents aspirated from the stomach of a normal volunteer 90 minutes following a meal of ground beef, vegetables and bread were injected via this catheter into 21 rabbits at a dose of 0.5 cc/kg. A second group of 21 rabbits received the same dose of saline. Seven animals in each group were sacrificed at 1, 3 and 7 days. Excised lungs were inflated with fixative and fixed for 24 hrs. Excess fixative was removed by passing air through the lungs at 25 cm H20 for 48 hrs. The lungs were cut in 5 mm thick frontal slices which were x-rayed, photographed, fixed in 80% ethanol, and stained with hematoxylin and eosin.

Except for occasional small patches of chronic inflammation,the lungs of all but two animals receiving saline were grossly, histologically and radiographi- tally normal when examined at 1, 3 and 7 days. Two animals had what appeared to be an infectious pneumonia. In contrast, the lungs of all animals receiving foodstuff revealed marked pathologic and radiographic changes. X-rays of these animals taken at 1 and 3 days all showed either patchy or confluent consolida- tion of the left lower lobe and infiltrates were also present in 5 of 6 animals sacrificed at 7 days.

Histologic examination of all animals sacrificed at one day showed marked involvement of the left lower lobe. Alveolar walls appeared to be intact but the alveolar spaces were filled with edema fluid and/or an inflammatory exu- date composed of polymorphonuclear cells and macrophages. Meat and vegetable fibers could be identified in the alveoli and the inflammatory process was most severe surrounding these particles. Many small airways were filled with a sim- ilar inflammatory exudate but there was little atelectasis and obstruction of airways by food particles was not seen.

At three days this extensive inflammatory reaction persisted and most of the inflammatory cells in the alveolar spaces were mononuclear. Alveolar septae were thickened and hyperplastic and occasional fibroblasts could be seen.

All animals examined at 7 days showed histologic abnormalities. The inflam- matory reaction was exclusively mononuclear but much less extensive, confined for the most part to areas containing food particles. These particles were surrounded by macrophages and fibroblasts forming early organizing granulomas. ,, Inflammation was still present in the small airways but was less marked. F'

Gram stains of histologic sections obtained from animals receiving the food- /

stuff aspirate showed only occasional bacteria. Aerobic and anaerobic cultures of the aspirate itself and of involved lungs yielded no significant bacterial growth.

These findings indicate that the pulmonary aspiration of gastric contents containing small food particles will cause severe persistent lung injury even if.,the pH of the aspirate is above 2.5. This lung injury is the result of an inflammatory foreign,body reaction and not airway obstruction or infection. Preventive measures;:,afmed.exclusively at the neutralization of gastric acid may not prevent lungidamage from aspiration of stomach contents. ',

17

POSTPARTUM UTERINE PRESSURES WITH DIFFERENT DOSES OF KETAMINE

Certie F. Marx, M.D., and Hyan S. Hwang, M.D.

Department of Anesthesiology Albert Einstein College of Medicine

Bronx, New York

The effect of ketamine on uterine tone and activity is in doubt. Recently, Galloon (Canad. Anaesth. Sot. .I. 20:141, 1973 - Anesthesiology 44:522, 1976) extrapolated results obtained in first and second trimester preg- nancy to the uterus at term and postulated that hazardous increases in uterine base tone could develop.

Being convinced of the beneficial effects of low-dose ketamine on the newborn infant, we measured uterine pressure and activity in the immediate postpartum period at four different doses of ketamine. As in our previous investigations (Zargham et al, Anesth. Analg. 53:568, 1974 - Marx et al, Abstracts of Scientific Papers, 1975 ASA Annual Meeting), we inserted a Csapo micro-balloon as soon as the placenta had been expelled. Our patients were primi- or secundiparae who delivered spontaneously under pudendal block anesthesia (1% chloroprocaine) with or without nitrous oxide-oxygen analgesia or under nitrous oxide-oxygen analgesia alone. Following a control period of at least 10 minutes, boluses of ketamine were injected intravenously in the following doses: 25 mg, 50 mg, 75 mg, 100 mg, to 4 to 6 patients in each group. The mgfkg ratio was calculated on the next day when the patients' postpartum weight was determined.

Our results are as follows: (a) 25 mg of ketamine did not change the uterine contractile pattern in any of the patients, (b) both 50 mg and 75 mg of ketamine led to an increase in the intensity and duration of the first contraction following the injection; this increase was similar to that obtained by the intravenous injection of 10 milliunits of pitocin, (c) 100 mg of ketamine led to an increase in intensity and duration of the following 2 to 3 contractions; agazLn, the increases were similar to those found after 10 milliunits of pitocin. In none of the 20 patients studied so far was there an elevation in base (resting) tone of the uterus after either ketamine or 10 milliunits of pitocin. This is in contra- distinction to the use of a 0.14; pitocin infusion (30 drops/minute) which was followed, without exception, by an elevation of the uterine resting tone as well as an increase in

In summary, postpartum uterine substantiate the safety of the

(Informed consent was obtained Labor Suite).

the frequency and intensity of contractions.

pressure measurements in full-term uteri commonly-employed low doses of ketamine.

from all patients on. admission to the

LEG AND ARM BLOOD PRESSURES AT CESAREAN SECTION 18

C. Kehler, T.F. Baskett, and R.J. Palahniuk

University of Manitoba, Winnipeg, Canada

Following the reports that the supine position was associated with increasing i. fetal acidosis and hypoxemia, and poorer neonatal condition, it was suggested

that one of the possible etiologies was aortic compression by the gravid uterus with the consequent reduction in uterine perfusion pressure and decreased placental blood flow. We moni ored arm and leg blood pressures using ultrasonic

L Doppler devices (arteriosonde 6 ) $n 10 patients undergoing Cesarean section with general anesthesia in the supine position and in 13 undergoing Cesarean section with epidural anesthesia (8 tilted, 5 supine). All patients were undergoing elective Cesarean section.

Results - See Table

Although mean blood pressure in the leg tended to be slightly lower than in the arm in the supine patients, there was no statistical difference between the arm and leg pressures. In the tilted patients, mean leg blood pressures were slightly higher than in the arm. Following the induction of general anesthesia there was no significant change in either arm or leg blood pressures, while following the induction of epidural anesthesia, both arm and leg blood pressures tended to fall with the leg pressures falling more than the arm especially in those patients kept supine. When hypotension occurred in the epidural group, arm and leg blood pressures tended to fall equally, and the use of intravenous ephedrine tended to raise both arm and leg pressures equally. There was no difference in the distri- bution of Apgar scores in the groups, while umbilical arterial blood gases in a small number of patients showed a tendency toward lower Pa02 and higher PaC02 in the epidural patients who were kept supine. One patient in whom there was a marked difference between arm and leg blood pressures will be presented as a case presentation.

TABLE

GROUP

GENERAL ANESTHESIA (supine)

EPIDURAL (lateral tilt)

EPIDURAL 4

(supine)

8

Mean B.P. (torr) Before A Arm

90.1

85.4

sthesia Leg

85.5

98.4

II Mean B.P. (torr) After AI Arm

96.1

96.6

1 Arter PaCOY

48.7

56.3

Gases PH

7.22

20

THE EFFECTS OF MATERNAL-FETAL pH CHANGES ON FETAL UPTAKE OF BUPIVACAINE

R.L. Kennedy, M.D., A.P. Erenberg, M.D., J.E. Robillard, M.D. A.J. Merkow, M.D., T. Turner, B.S.

Departments of Anesthesia, Obstetrics and Gynecology, and Pediatrics University of Iowa, Iowa City, Iowa

Fetal acidosis and the ccnnbination of fetal acidosis and maternal alkalosis have been shown to increase the fetal blood concentrations of lidocaine following maternal administration. Bupivacaine's acceptance in obstetrics is related to the lower fetal concentrations that result following its use for maternal anesthesia. We are, therefore, evaluating these pH changes as they may affect the fetal concentration of bupivacaine following maternal administration.

Using halothane anesthesia, we prepare pregnant ewes of 115 to 130 days gestation by surgical placement of catheters in an artery and vein of the fetal hind limb and a maternal branch of the femoral artery. The animal is allowed to recover 48 hours before any experimentation.

The study is performed during two acid-base states: a control state and a state wherein maternal respiratory alkalosis and simulated fetal metabolic acidosis (acidemia) are produced. We hyperventilate the ewe with ambient air via a tracheostomy to produce respiratory alkalosis and infuse lactic acid 0.25 M via the fetal vein to produce fetal acidemia. We attempt to maintain ; E gradient of 0.5 by reaching a matemal_pH of 7.70 and a fetal pH of

. . In both the control and the ccnnbmation pH state, we infuse bupivi- caine 1.5 mg/kg over one minute into the maternal jugular vein. Maternal and fetal blood samples are taken at 0, 1, 5, 15, 30, and 60 seconds. Each sample is analyzed for pH, PO2, PCO2, and base excess; and the remainder of the sample is analyzed for bupivacaine concentration by gas chromatography.

Preliminary results indicate that the combination of respiratory alkalosis and metabolic acidosis increase the fetal concentrations of bupivacaine at each saarpling time except at 60 minutes where the mean levels areapproxi- mately equal. The fetal-to-maternal ratios are low and approximate those previously reported. In addition, the ratios are increasedapproximately 50% by the induced pH changes except at the 60 minute sampling time.

21

PROPHYLACTIC BLOOD PATCH DOES NOT PREVENT SPINAL HEADACHE

R. 3. Palahniuk

Department of Anesthesiology University of Manitoba, Winnipeg, Canada

Epidural blood patch has become an accepted technique of treatment

for post-lumbar puncture headache over the past five years. With the high success rate and the absence of short or long term complications of epidural blood patch, it has occurred to obstetrical anesthetists that inject-

ing blood through the epidural catheter might prevent the headache when an accidental lumbar puncture (wet tap) has been performed prior to insertion of the epidural catheter. Over a period of three years, 86 wet taps were recorded on our obstetric anesthesia service. In eleven of these

cases, 10 ml. of the patient’s blood was injected through the epidural

catheter at the completion of the delivery in an attempt to prevent the development of a headache. Of the 75 patients who did not have a pro-

phylactic blood patch attempted, 31 or 41% never developed a headache,

while of the 11 with the attempted prophylactic blood patch, 5 or 46% did not develop a headache. Of the 6 patients who developed a headache

following the prophylactic blood patch, 5 required a repeat blood patch to treat the headache. There were no complications noted following prophylactic blood patching.

Conclusion

Prophylactic blood patch appeared to have no value in preventing a post lumbar puncture headache following wet tap. Because of the increased possibility of intr0ducin.g infection by injecting blood through the epidural catheter,, this procedure does not appear warranted.

/

22

BUPIVACAINE FOR CESAREAN SECTION UNDER EPIDURAL ANALGESIA

M. J. Sakowski, M.D.

Parkland Memorial Hospital and University of Texas Southwestern Medical School, Dallas

Bupivacaine 0. 75% hos been recommended for epidural analgesia for cesarean section. Many authorities advise that epinepprine should be omitted from the local anesthesic solutions used in obstetrics. The onset and intensity of bupivacaine 0.75% pith and without epinephrine 5 pg/ml for epidural analgesia is said to be similar. My preliminary bias suggests that the bupivacaine with epinephrine has a more rapid onset of action, produces a higher level and a more intense block than bupivacaine alone in the obstetrical patient. The purpose of this double-blind study is (a) to determine whether a significant difference exists in the onset and intensity of bupivacaine 0.75% with and without epinephrine 5 pg/ml in the patient for elective cesarean section under epidural; and (b) to determine a suggested dose for initial epidural injection of bupivacaine 0. 75% for cesarean section. Coded syringes containing either bupivacaine 0. 75% with epinephrine 5 pglrnl or bupivacaine 0.75% were provided to the investigator. The se uence was determined by coin toss prior to the onset of the investigation. coded solution were injected via a lumbar epidural catheter.

e Stxteen ml.. of the

The trme of onset of reliable surgical anesthesia was determined. and the extent of blockade was evaluated. At the conclusion of the study, the code was broken and comparisons were made.

1. Gutche BB: Epidural anesthesia in OB: techniques, results and complications.

ASA Annual Refresher Course Lectures #204, 1976.

2. Moore DC, et al: ,Bupivacaine hydrochloride, a summary of investigational use in 3,274 cases. Anesth and Analg 50:856, 1971

;i i

d I

~_

INCREASED FETAL HEART RATE AND VARIABILITY FOLLOWING EPHEDRINE ADMINISTRATION

23

Richard G. Wright, Stephen H. Rolbin, Sol M. Shnider, Gershon Levinson, and Julian T. Parer

University of California, San Francisco

Observations of continuous fetal heart rate (FHR) tracings in patients who receive ephedrine during labor frequently revealed an obvious increase in FHR and beat-to-beat variability follow- ing pressor administration. This current study was undertaken to determine if this clinical observation was valid and if so whether the tachycardia was due to direct fetal effects of ephedrine or to changes in uterine blood flow resulting from epidural anesthesia alone or in combination with ephedrine.

Randomly selected FHR tracings of parturients who had received ephedrine were reviewed and compared to a control group of normal parturients who did not receive the vasopressor. The control group was divided into subgroups of a) patients without epidural anesthesia, b) patients with epidural anesthesia and no hypoten- sion, and c) patients with epidural anesthesia with hypotension successfully treated by fluid administration and left uterine displacement. The ephedrine group was divided into subgroups of a) patients given the drug for treatment of epidural induced hypotension and b) those receiving prophylactic ephedrine and monitored prior to epidural anesthesia.

Of thirty patients given ephedrine for the treatment of hypoten- sion 27 per cent displayed elevation in baseline FHR of 10 to 25 beats per minute during the first ten minutes after ephedrine administration. Despite successful treatment of the hypotension 47 per cent of the fetuses displayed increased heart rate 10 to 20 minutes after the drug and 64 per cent displayed increased heart rate of up to 40 beats per minute, 40 to 50 minutes after ephedrine administration. These results differ from those found in the control group.

In addition to the increase in baseline FHR, beat-to-beat vari- ability increased in 37 per cent of the fetuses following ephedrine administration. In 27 per cent of the fetuses we observed markedly increased variability and often a saltatory pattern.

In one-third of the fetuses developing increased FHR a fetal scalp sample was taken during the period of tachycardia and the pH ranged between 7.23 and 7.33.

Work now in progress suggest that these phenomena of fetal tachycardia and increased beat-to-beat variability are primari- ly a function of ephedrine therapy, 'are dose related and independent of labor, epidural anesthesia and corrected hypo- tension. Possible mechanisms and clinical significance of these results will be discussed.

24

AN EVALUATION OF LOW DOSE BUPNACAINE PARACERVICAL BLOCK ON THE FETUS AND NEWBORN

Paul Meis, M.D., Laurence Reisner, M.D., Calvin Hobel, M.D., and Terrence Payne, C.H.A.

Departments of Anesthesia, Obstetrics and Gynecology, and Pediatrics University of California, Los Angeles, School of Medicine

Harbor General Hospital Campus

The use of paracervical block for analgesia in the first stage of labor is controversial at the present time due to reports of adverse effects on the fetus and newborn. This prospective study was designed to evaluate the effects of paracervica block on the fetus and neonate when reasonable precautions are exercised in a group of low risk obstetrical patients. The efficacy and long duration of low-dose bupivacaine paracervical block is established in the literature, however, isolated reports have related bupivacaine paracervical blocks with fetal distress and demise. The evaluation of bupivacaine paracervical block was conducted in the following manner.

The study group consisted of forty term pregnant patients in labor identified at low risk by a problem oriented risk assessment system. Continuous fetal heart rate monitoring was instituted and showed no patterns consistent with fetal distress prior to administering the block. Upon entering the active phase of labor the patients received paracervical blockade at a controlled depth of approximately 3mm to minimize exposure of the drug to the uterine vessels. All blocks were administered by one of the investigators (P.M.) and total dosage in labor restricted to 1OOmgm of bupivacaine. All patients labored in the lateral position under constant surveillance. Fetal scalp sampling facilities were readily available to further evaluate signs of fetal distress. Anesthesia for vaginal delivery was accomplished with either saddle block or local infil- tration.

Methods of evaluating the newborn included Apgar scores at one and five minutes, pH determinations of umbilical arterial and venous blood obtained from an isolated segment of cord, and neurobehavioral examination at two, six, and twenty-four hours of age. The neurobehavioral scores were compared with those of a group of twenty infants delivered of low risk mothers who received other forms of analgesia.

Preliminary results: (31 patients) 1. No fetus in our study group developed the typical bradycardia

associated with paracervical block anesthesia 2. The median Apgar scores were eight at one minute and nine at five

minutes, pH determinations of umbilical cord arterial and venous blood were not significantly different from normal infants delivered at our institution.

3. The mean scores of the neurobehavioral examinations performed at two, six and twenty-four hours were similar for both the study and control groups.

25

HYPERBARIC BUPIVACAINE PERIDURAL ANESTHESIA IN OBSTETRICS

J. Roger Bullard, M.D. and Frances M. Houghton, M.D. Medical University of South Carolina

Charleston, South Carolina

The skillful use of peridural anesthesia has been shown to be of great benefit to both mother and baby.

By adding 10% Dextrose to 0.5% solution of Bupivacaine we produce a hyperbaric solution (specific gravity 1.016) of .33X Bupivacaine. Should an inadvertent-subarachnoid administration occur the hyperbaricity would tend to produce a saddle block-type of blockade rather than a high or total spinal.

Our technique and management of epidural block will be presented in detail.

REFERENCES

Barker AE: Clinical Experiences with Spinal Analgesia in 100 Cases. Br Med J I: 665-674, 1907.

Bonica JJ: Principles and Practice of Obstetric Analgesia and Anesthesia. Vol I: 611-641, 1967.

Bromage PR: Mechanism of Action of Epidural Anesthesia. 1974, ASA Refresher Course Vol 2: l-10.

Belfrage P, et al: Lumbar Epidural Analgesia with Bupivacaine in labor: Determination of Drug Concentration and pH in Fetal Scalp Blood, and Continuous Fetal Heart Rate Monitoring. 1975.

Am J Obstet Gynecol 121: 360-365,

Scanlon JW, et al: Neurobehavioral Responses and Drug Concentrations in Newborn after Maternal Epidural Anesthesia with Bupivacaine. Anesthesiology 45: 400-405, 1976.

c

DOUBLE BLIND ASSESSMENT OF THE EFFECT OF THE MATERNAL ADMINISTRATION 26 OF MEPERIDINE WITH AND WITHOUT NALOXONE ON NEONATAL NEUROBEHAVIOR IN

THE FIRST 48 HOURS OF LIFE

R. Hodgkinson, G. Grewall, M. Bhatt, and G.F. Marx

Department of Anesthesiology, University of Texas Health San Antonio, Texas

Department of Anesthesiology, Albert Einstein College of

Bronx, New York

Sciences Center

Medicine,

One hundred women in labor who had received 75 mg or more of meperidine within 4 hours of delivery were randomly assigned to two equal treatment groups. Group I patients were given naloxone 0.4 mg intravenously 15 or more minutes before delivery. Group I I were untreated. A further group (Group Ill) of 50 patients received neither meperidine nor naloxone.

et al(‘) The Neonatal Neurobehavioral Tests first described by Scanlon were performed on th 150 neonates at 2, 4 and between 24-36

hours of age. All babies wer examined under standardised conditions and all babies with any abnor weighing less than 2500 grams or with an Apgar of less and 10 at 5 minutes were

a normal pregnancy and delivery. mg/kg or thiopental 3.0 mg/kg

receiving meperidine alone response, tone, rooting,

sucking, Moro response, alert ess and overall assessment at 2, 4 and 24-36 hours of age compared wtth neonates whose mothers did not receive meperidine (Group III meperidine and naloxone (Grou difference from Group Ill

babies whose mothers I

. Neonates whose mothers received II) showed no statistically significant

neo ates (no meperidine) at 2 hours but the depression at 4 and 24-36 hou s was equivalent to that seen in the

received meperidine along (Group II).

i P

RE ERENCE

1) Scanlon J.W., Brown, W.U. Weiss J.B. et al: Neurobehavioral responses I- of newborn infants after aternal epidural anesthesia. Anesthesiology 40: 121-128, 1975.

RH:OH

27

:

THE NEONAT& EFFECTS OF BUPIVICAINE FOLLOWING EPIIXJRAL ANESTHESIA FGR CESARIAN SECTION

Gail A. McGuinness, M.D.*, Alan J. Merkow, M.D.+, Allen Erenberg, M.D.*, Roland L. Kennedy, M.D.+5

University of Iowa Hospitals Departments of Pediatrics*, Anesthesia+, 4 Obstetrics/Gynecology§

Bupivicaine is used commonly for epidural analgesia for labor and delivery because of its lack of neurobehavioral effects on the neonate. The dose of bupivicaine required when epidural anesthesia is employed for cesarian section greatly exceeds that required for labor and delivery and is most often administered as a single dose. We are therefore evaluating the neonatal neurobehavioral effects following cesarian section to determine if the associated higher drug dosage produces neonatal effects. We also wish to determine the blood concentrations at which these effects might occur.

Patients selected are those undergoing elective cesarian section who we classify as physical status I and with no obstetrical complications. Patients receive no medications prior to delivery other than a non- absorbable antacid. The patients are randomly divided into a group re- ceiving a lumbar epidural with 22 ml bupivicaine 0.75% (165 mg) without added epinephrine, and a control group receiving subarachnoid block using tetracaine 10 mg. Both groups receive approximately one liter lactated Ringer's solution prior to delivery. Hypotension is treated with ephedrine 10 rag when it occurs. All patients receive oxygen 100% prior to delivery. At the time of delivery, blood samples are obtained from the maternal artery, umbilical artery, and umbilical vein. After blood gas analysis, the remaining sample is prepared for bupivicaine analysis by gas chromatography. A combined one- and five-minute Apgar score equal to 15 is required for inclusion in the study. A neurobehavioral examination as described by Scanlon is performed on the neonate at 4 hours and at 24 hours; and, at the same time, a one-half ml capillary blood sample is ob- tained from t:_le heel for further bupivicaine analysis. No pontocaine analysis is performed on those receiving subarachnoid block because of the presumed non-detectable levels.

Preliminary results suggest that bupivicaine employed for cesarian section does not produce neonatal neurobehavioral effects. Preliminary blood levels of bupivicaine are approximately SO% higher than those found by Scanlon. This is reasonable since the dose used in this study is 50% higher than Scanlon's dose of bupivicaine.

28

n

A COMPARISON OF THE NEONATAL NEUROBEHAVIORAL EFFECI. OF BLJPIVICAINE, MEPIVICAINE, OR Z-CHLOROPROCAINE

USED FOR PUDENDAL BLOCK

Alan J. Merkow, M.D.+, Gail A. McGuinness, M.D.*, Roland L. Kennedy, M.D.t§, Allen Erenberg, M.D.*

University of Iowa Hospitals Departments of Anesthesia?, Pediatrics*, 6 Obstetrics/Gynecology§

Large doses of local anesthetic are commonly given by pudendal and local block just prior to delivery. Mepivicaine and lidocaine, when used for lumbar epidural anesthesia, have been shown to cause neurobehavioral changes in the neonate, while bupivicaine is devoid of these effects. Because comparable doses may be used for pudendal block, we are evaluating the neonatal neurobehavioral effects of mepivicaine, bupivicaine, or 2- chloroprocaine following this block. 2-chloroprocaine is chosen for com- parison because its rapid hydrolysis prevents detectable concentrations in the mother or the neonate. The half-life of 2-chloroprocaine in the cir- culation is 21 seconds. Because of this, there presumably are no neonatal neurobehavioral effects.

Patients selected are those parturients having normal vaginal deliveries resulting in babies with Apgar scores totalling 15 at one and five minutes and exhibiting no later signs of distress. Bilateral pudendal block, combined with local infiltration of the episiotomy site, is performed at least five minutes prior to delivery. The choice of anesthetic is randomly assigned to form three groups: mepivicaine, bupivicaine, and 2-chloropro- Caine. The total dose in each case is approximately 30 ml. Blood samples are taken at the time of delivery from the maternal artery, the umbilical vein, and the umbilical artery. After a blood gas analysis! the remaining samples are prepared for bupivicaine and mepivicaine analysis. No chloro- procaine analysis is done because of the presumed non-detectable levels. A neurobehavioral examination as described by Scar&n is performed on each infant at 4 and 24 hours. At these times, one-half ml of capillary blood is obtained from each infant’s heel for bupivicaine and mepivicaine analysis.

Preliminary results suggest no neonatal neurobehavioral changes in any of the three groups. Blood levels of the bupivicaine samples are approximately one and one-half times the levels reported by Scanlon. Mepivicaine levels, however, are approximately one-fourth the level found by Scanlon.

29

4

:i ._.

EFFECT OF OBSTETRIC ANESTHESIA AND ANALGESIA ON THE NEONATAL GROWTH DURING THE FIRST WEEK OF LIFE

E. Abouleish, A. Van der Don&, H. Meeuwis, and F. Taylor

Magee Womens' Hospital, Pittsburgh, Pennsylvania

Rational: Epidural or general anesthesia analgesia can result in decreased Apgar scores and/or neurobehavioral responses. The baby may have diminished muscle tone and decreased alertness, even in spite of a good Apgar score. This effect was found to occur when either mepivacaine or lidocaine had been used but not with bupivacaine.

Owing to the low mfcrosomal enzymatic activity of its liver, the neonate metabolizes anesthetic drugs at a slower rate than adults.

The Purpose of the Study: The purpose is to answer the following question: I

Would these neonatal effects secondary to anesthetic or analgesic techniques modify the feeding ability and/or the metabolic functions of the neonate in such a way to change its growth rate during the first week of life?

The Material: This study consists of 400 consecutive full-term neonates who were vaoinallv delivered. There was no maternal disease or fetal groups:

I. 63-

11. 111 -

III. 186 -

IV. 40 - General Anesthesia.

distress.- They are divided into the following

No Anesthetic or Analgesic Techniques (control group). Spinal block using 5% lidocaine.

Epidurals, consisting of:

A. 37 Epidural using Lidocaine 8. 74 Epidural using Mepivacaine C. 75 Epidural using Bupivacaine

Each group is subdivided into breast and bottle-feU subgroups.

The rate as well as the absolute change in weight of the neonates are compared in the different groups and subgroups. The data are in the process of being analyzed by computer for statistical significance.

The Results: will be presented at the Meeting.

30

NEWBORN TEMPERATURE FOLLOWING ELECTIVE, REPEAT CESAREAN SECTION

Walter U. Brown, Jr., M.D. -

Department of Anesthesia, Harvard Medical School and Boston Hospital for Women

Labor is usually associated with a rise in maternal temperature related to increased muscular activity. The maternal-fetal temperature gradient during labor appears to be about O.S'C., the fetus having the higher temperature. In the case of elective, repeat cesarean section, the parturient does not experience labor and the baby might be expected to have a lower temperature at birth in comparison to infants delivered vaginally or by cesarean section in the course of labor.

Twentyfive neonates at or near term were studied. Sixteen were delivered by cesarean section on an elective, repeat basis, and nine were delivered vaginally or by cesarean section because of failure to progress in labor. Following birth, two temperature probes consisting of thermistor transducers* were applied to the baby, one to the skin of the right upper abdomen and one inserted rectally. Ambient temperature was also measured with a thermistor transducer. Temperatures were displayed digitally and recorded on the strip chart at minute intervals.

Room temperature at delivery averaged 23.5OC. The babies were placed in bassinets under infrared heat lamps where the mean ambient temperature was 31OC. Newborn temperatures at 2 and 15 minutes of age are presented in the following table:

Neonatal Temperature oC. Mean + SE

Site No Labor Labor n=16 n=9

2 min 15 min 2 min 15 min

Skin 33.2+0.36 35.6+0.21 35.7+0.36 36.7~0.15

Rectum35.7+0.14 35.8+0.12 36.8tO.10 36.9zO.14

The neonates whose mothers had undergone repeat cesarean sections had significantly lower temperatures than the infants whose mothers had had labor (p<O.OOl). This suggests that these babies may be subject to greater cold stress. Newborn temperature should be managed carefully, especially, in high risk cases undergoing elective cesarean section.

*Corometrics 512 Neonatal Monitor

31

PREVENTION OF NEONATAL HYPOGLYCEMIA

Luis B. Curet, M.D.

University of Wisconsin Center for Health Sciences and Wisconsin Perinatal Center, Madison, Wisconsin

In spite of the excellent perinatal mortality achieved with intensive management of the pregnant diabetic patient most investigators report a high incidence of neonatal hypoglycemia requirinq intravenous glucose administration via tiilical catheters. As umbilical catheterization carries with it significant morbidity and it is generally accepted that hypoglycemia is not in the best interest of the neonate the following protocol was followed at the Wisconsin Perinatal Center in an attempt to prevent neonatal hypoglycemia.

1. Upon admission the patient received an intravenous infusion of 10% invert sugar with regular insulin added to maintain the maternal blood sugar between 70 - gC mgm% for 10 hours prior to delivery.

2. Upon delivery the blood sugar was monitored in the baby and intravenous DlOW was aiven at a rate to raise blood sugar greater than 30 mgm% if:

apart were less than

a. Blood sugar was less than 20 mgm%.

b. Two blood sugars taken one-half hour 30 mgm%.

c. Baby showed symptoms of hypoglycemia less than 30 mgm%.

73 mothers and their babies were studied and neonates required umbilical catheterization.

and a blood sugar of

only 17% of the

TEE EFFECT OF MATERNAL CONVULSIONS ON THE FETUS FOLLOWING INTRAVENOUS ADMINISTRATION OF LIDOCAINE TO THE PREGNANT EWE

32

B.B. Gutsche, H.O. Morishima, J.B. Keenaghan and B.G. Covino

Department of Anesthesiology College of Physicians and Surgeons, Columbia University, New York, New York

and the Research Department, Astra Pharmaceutical Products, Inc., Framingham, Massachusetts

Maternal and fetal cardiovascular responses to lidocaine-induced maternal convulsions were studied in five chronically instrumented ewes at 125-128 days gestation. Arterial blood pressure and heart rate of the mother and fetus as well as uterine blood flow (UBF), were measured. Lidocaine was infused intra- venously to the mother at the rate of 0.65 mg/kg/min. At the onset of maternal convulsions the infusion was either discontinued (2 experiments) or reduced to 0.2 mg/kg/min (3 animals). Arterial blood samples were withdrawn from the mother and fetus and following convulsions for determination of lidocaine con- centration, as well as pH and blood gases.

Convulsions began in ewes at 7-15 (average 11) minutes after the initia- tion of the infusion and lasted for 1-5 minutes (average 1 min. 36 sec.). Mean lidocaine concentrations in maternal and fetal blood during convulsions were 6.41 and 2.52 pg/ml respectively. These values fell to 2.03 and 1.56 ug/ml respectively at 30 minutes. The mean UBF prior to the infusion was 415 ml/min. A significant reduction (35%) of UBF occurred at the onset of convulsions, then with further decrease of 51% by 2 minutes. UBF had begun to recover by 5 min- utes after convulsions had ceased and at 10 minutes it had returned to prein- fusion value. Maternal mean blood pressure and heart rate rose significantly during convulsions from preinfusion values of 86 to 146 tnnHg, and 94 to 138 beats/min respectively. Recovery of these changes were slower than with UBF; complete recovery occurred by 25 minutes after convulsions had stopped. In the fetus there was a significant fall in heart rate (164 to 142 beats/min) during maternal convulsions. This was accompanied by a fall in fetal Pa02 A[ie;e;9 Wig), but no alteration in fetal blood pressure, pHa or PaCO&_was

. Fetal bradycardla was only transient; recovenng completely lthln 45 minutes of the end of convulsions. However, decreased Pa02 lasted for 10 minutes and even at 30 minutes it was still 21.tnnHg.

It is concluded that a brief period of maternal convulsions induced by lidocaine may produce fetal distress secondary to maternal hemodynamic changes, leading to reduction of intervillous-space perfusion rather than to direct effect of lidocaine on the fetal myocardium.

Supported in part by Grant 5POl-GM09069, NIGMS, NIH.

THE EFFECTS OF CHLORMETHIAZOIE AND MAGNESIUM SULPHATE ON UTERINE BLOOD FLOW IN PREGNANT AND NON-PREGNANT EWES

R.B. Hopkinson, M.B.,B.S., F.F.A.R.C.S?, Frank C. Greiss, Jr., M.D.* Francis M. James, III, M.D.,* and John I. Fishburne, Jr., M.D.*,**

*Senior Registrar in Anaesthesia, Midland Area Training Scheme, Birmingham, England (at present Fellow, Bowman Gray School of Medicine), and from the Departments of t Anesthesiology and ** Obstetrics and Gyne-

cology, Bowman Gray School of Medicine

33

c

I :

‘./

:

) rJ I

Chlormethiazole (CMT) rather than Magnesium Sulphate is widely used for the treatment of eclamptogenic toxaemia in the United Kingdom. This drug, primarily an anticonvulsant but with powerful sedative, hypnotic, and anti-emetic prop- erties, Is the thiazole nucleus of Vitamin Bl and its use has been recommended for the management of the pre-eclamptic patient. (Duffus, Tunstall, and MacGillivray, Lancet 1968 i 335.)

Studies of its cardiovascular effects in man have shown it to produce only a mild tachycardia. (Wilson, Stephen, and Scott, Brit. J. Anaesth. 1969, 41,840.) Little is known about its effects on uterine blood flow or myometrial activity. In contrast, Magnesium Sulphate caused no change in ovine uterine blood flow during decreases in arterial blood pressur.e. This appeared to be the result of reduced myometrlal tonus.

In the present study, pregnant and non-pregnant ewes were prepared to enable chronic continuous recording of direct arterial pressure, intra-uterine pressure and uterine blood flow during intravenous or direct uterine artery in- fusions of CMT or Magnesium Sulphate.

Preliminary results Indicate that systemic infusion of CMT into pregnant ewes produces no significant change in either systemic blood pressure, uterine blood flow or myo- metrial tonus at doses approximating the therapeutic range for women.

Local infusion of CMT into the uterine artery of non- pregnant ewes produced an effect but at estimated blood levels substantially greater than those likely to be obtain- ed under clinical‘circumstances. There was an increase in blood flow and conductance with some supression of spontan- eous uterine activity. Similar infusions of Magnesium Sulphate increased uterine blood flow and conductance while producing marked supression of uterine activity at infusion rates estimated to produce blood levels just above those needed therapeutically.

Supported by PHS Grant Hl-03941-17 from the National Heart and Lung Institution

THE EFFECTS OF UVl'ANlNE ANLJ U'l'HEK WL’ELHUlAPllNl!sb ON UTERINE SLOOD FLOW IN THE PREGNANT SHEEP

Bradley E. Smith, M.D. and Dare1 G. Hess, Ph.D.

Department of Anesthesiology, Vanderbilt University School of Medicine

Nashville, Tennessee

The activity of most commonly available natural and synthetic cate- cholamines on the uterine vascular bed has been extensively studied in vivo in the pregnant sheep. (Greiss and Van Idilkes, Obstet. Gynec. 23: 925-930, 1964). In general catecholamines with predominantly "alpha adrenergic" character reduce uterine blood flow by constricting the vascular bed (de- crease “conductance") while predominantly "beta adrenergic" drugs appear to have no effect (neither ir.crease nor decrease "conductance"). (Greiss and Pick, Obstet. Gynec. 23: 209-213, 1964).

Dopamine increases cardiac output, splanchnic and renal blood flow in some circumstances and might, therefore be a useful vasopressor in ob- stetrics if uterine blood flow were found to be affected in a similarly favorable manner. Previous in vitro studies have indicated that dopamine displayed no effect on uterine vascular conductance, but a previous in vitro study in sheep (Callendar et al ASA Abstracts of Scientific Papers, p. 545, 1976) indicated that, under the conditions of study, uterine artery conduc- tance was decreased by infusion of dopamine at a rate of 20 mcg/min and greater.

The present study compares the vascular effects of dopamine infu- sion in pregnant sheep with that of infusion of other vasoactive catechola- mines. Eight cross-bred Dorset-Suffolk ewes from 127-138 days pregnant were studied under subarachnoid anesthesia and minimal pentobarbital sedation. Maternal cardiac output was measured by electromagnetic flow meter, maternal and fetal arterial pressure and blood gases were monitored throughout the drug administration, and arterial resistances and conductances were later mathematically derived from the observations.

Cathecholamines with well known effects were administered before and after each administration of dopamine to verify the validity of each animal preparation. Dopamine was administered 113 times, phenylephrine 61 times, isoproterenol 24 times, epinephrine 16 times, and norepinephrine 20 times. Alterations of the observed effects were studied after administra- tion of alpha blockage in 4 animals.

Dopamine infusion usually resulted in an initial increase in uter- ine blood flow at the appropriate dose (between 10 and 20 mcg/kg/min), due to an increase in maternal cardiac output, with, early on, little change in uterine artery conductance. But during constant infusion at the same rate, uterine blood flow often became gradually impaired and there was often a net decrease in conductance after 15 minutes of infusion.

Conclusion: At an appropriate dose dopamine initially improves uterine blood flow without affecting conductance, but during constant infu- sion of the same dose, uterine blood flow often diminishes due to decreased conductance. This effect may be due to gradual "loading" of receptor sites and creation of a secondary "alpha" effect by relative overdose of dopamine.

*Department of Anesthesiology, Vanderbilt University School of Medicine Nashville, Tennessee

ADMINISTRATIVE CH4NGES IN A NEONATAL INTENSIVE CARE UNIT ASSOCIATED WITH IMPROVED SURVIVAL

35

i

I

i *

:

John W. Scanlon, M.D., and Thomas Nelson, M.D.

Columbia Hospital for Women and Georgetown University School of Medicine

Over a two-year period (1974-1976), several abrupt and major changes occurred

in the personnel staffing patterns, ancillary service support systems, and financial base for our maternity hospital's Neonatal Intensive Care Unit (NICU).

These changes were associated with an improvement in neonatal survival as follow:

- Total neonatal deaths were reduced by .6 per 1000 live births (from.12.4 to 11.8 per 1000).

- Deaths in infants weighing less than 1000 grams dropped by 4%. (from 61% to 59%).

- Deaths of infants with birth weights between 1000 and 1500 grams

declined 60% (from 42% to 17%). - Deaths for infants between 1500 and 2000 grams decreased by 40%

(from 5% to 3%).

Administrative changes which occurred during these two years were as follows:

1. Primary care is provided directly in delivery room and NICU by PL-III level, or higher trained, Pediatrician.

2. A redistribution of physician time so that focus is on the seriously ill neonate.

3. Increased autonomy in decision making was emphasized among intensive care nursing personnel.

4. Secondary benefit from number 2 above was the markedly increased availability of teaching time to physicians and nurses.

5. The amount of direct budgetary support for the Neonatal Intensive Care Unit was increased by over $250,000.

6. Development of 24-hours a day, seven days a week supportive services from microchemistry lab, respiratory therapy, and radiology.

It is impossible to delineate the specific contribution of each of these changes toward improved survival. Their effect in concert is striking. -

It is not possible to provide comparative data on morbidity or outcome at this time. However, the recent literature suggests that improved survival is uniformly associated with diminished morbidity, particularly from neurological causes.

These observations support the following conclusions:

- Starting from the delivery room, intensive neonatal care must be provided by competent, trained personnel.' This is not a junior traine

- Neonatal intensive care is expensive. Hospitals must be willing and prepared to pay the price.

- Delegation of responsibility to nursing professionals in therapeutic and administrative decisions is an important positive step.

- Improvements in newborn outcome are a team effort and must be treated as such at all levels of planning and implementation for neonatal - intensive care.

- Availability of teachers and time for them to teach directly affects neonatal outcome.

EVALUATION OF HISTORICAL PARAMETERS AND LABORATORY SCREENING PROCEDURES IN NEWBORN SEPSIS

Lawrence J. Grylack, M.D. and John W. Scanlon, M.D.

Columbia Hospital for Women and Georgetown University School of Medicine

3'

Two hundred and eighteen consecutive in-born neonates were evaluated for possible bacterial sepsis during one year. Major reasons for screening include< proven or suspected maternal infection , rupture of membranes greater than 24 hours duration, or evidence of aspiration at delivery. Screening tests perform< were Gram's stains, Wright's stains for polys, and cultures done on gastric and ear canal aspirates obtained shortly after birth. Also, total and differenr white blood cell (WSC) counts and micro-erythrocyte sedimentation rates (ESR) WC done within the first 24 hours, then repeated 24 hours later. Deep cultures (blood, CSF, urine, etc.) were performed in the standard manner.

Sepsis, defined as a positive deep culture during the first 96 hours, was found

in 13 babies, or 6.0%. Of 123 mothers with prolonged rupture of membranes, 4

babies (3.3%) had sepsis. Of 30 babies with aspiration by physical and x-ray

findings, 4 (7.5%) had sepsis. Other historical factors implicated in the etiology of sepsis were prolonged labor, open wound due to birth trauma, and grossly unsterile delivery.

Mean successive total peripheral WEX counts in the septic group were 11,194 and 11,394 compared to 16,433 and 16, 145 in the non-septic group. Average suc- cessive total immature poly counts were 861 (8% of total WBC) rising to 1341 (1: in the septic group, and 1353 (8%) falling to 945 (6%) in the non-septic group. The mean ESR was 1.3 rising to 6.7 in the septic group and 2.4 rising to 3.4 in the non-septic group. Chi-square and t-test analyses of these data showed that a ESR of 5 or greater was more likely in the septic group in the first 48 hours (p< .OOl). Also, an increase in the percentage immature polys in the second count was more likely in the septic group (PC .05). Other comparison of total counts and changes were not significant at the .05 level.

Analyses of Wright's and Gram's stain findings were done using chi-square on the basis of presence of 5 or more polysfhpf or presence of detectable organism! In the gastric aspirate the findings of > 5 polys/hpf was slightly more likely in the septic group, but p was greater than .l. Ear aspirates with > 5 polysfhl were markedly scarce. The presence of organisms in Gram's stained material fror either source was not predictive; furthermore, when in agreement with the offer ing organism in some cases of sepsis , .it was obscured by the presence of 1 or more other organisms. Surface cultures that were consistent with deep cultures did not provide results soon enough to be consequential in early diagnosis and subsequent management.

Conclusions from this study suggest: a more individualized approach to any policy of routine delivery in cases of prolonged rupture of membranes; the neec for continued surveillance for sepsis in babies with respiratory symptoms after birth; and the utility of some laboratory screening procedures.

The septic baby had a significantly greater likelihood of an ESR of 5 or greatel in the first 48 hours, and an increasing percentage of total immature polys in the peripheral blood during that time. The septic baby appeared to have a lowe: total WDC count and > 5 polyslhpf in the gastric aspirate, but not at significal levels.

Disadvantages of the sepsis screen include noxious stimuli to the baby, unnec- essary costs, increased laboratory work, separation of the baby from parents an< inappropriate therapeutic management based on misinterpreted findings.

RESPONSES OF THE GRAVID UTERINE VASCULATURE TO ARTERIAL 37 LEVELS OF LOCAL ANESTHETIC AGENTS

John I. Fishburne, Jr., M.D.,*rt Rowland B. Hopkinson, M.B.,B.S., F.F.A.R.C.S.X Frank C. Greiss, Jr., M.D.+

Departments of *Anesthesiology and * Obstetrics and Gynecology, Bowman Gray School of Medicine and ""Senior Registrar in Anaesthesia, Midland Area Train- ing Scheme, Birmingham, England (at present Fellow, Bowman Gray School of Medicine)

In a previous report, (Am. J. Obstet. Gynec. 124: 889, 1976) we demonstrated that intraarterially administered local anesthetic agents stimulate ovine placental and non-placental vasoconstriction and myometrial activity. In non-pregnant ewes, the threshold for these effects approximated blood levels of local anesthetics commonly seen in clinical practice. The present experiments seek to define dose-response relationships using similar chronic preparations in conscious gravid ewes. In preliminary observations with 2-chloroprocaine, lidocaine and bupivacaine, average threshold blood levels and general vascular and myometrial responses, i.e. decreasing con- ductance and increasing tonus respectively, are similar to those observed in non-pregnant ewes. However, a singular characteristic of these changes in individual animals seems to be their degree of variation of response. More complete details of these responses will be presented.

Supported by USPHS Grant HL-03941 from the National Heart and Lung Institute.

r

EPIDURAL ANESTHESIA AND CAESAREAN SECTION: MATERNAL AND NEONATAL ACID-BASE STATUS AND BUPIVACAINE CONCENTRATIONS

Sanjay Datta, M.D., Gerard W. Ostheimer, M.D., Walter U. Brown, Jr., M.D., Jess B. Weiss, M.D., and Milton H. Alper, M.D.

Department of Anesthesia Boston Hospital for Women and Harvard Medical School

38

This study evaluates maternal and neonatal acid-base status and bu- pivacaine concentrations in two groups of ten parturients each undergoing scheduled primary or repeat Caesarean section under epidural anesthesia with 0.75% bupivacaine. The first group was placed in the supine position and the second group was placed in the left lateral position after the initial onset of bilateral sensory blockade to TlO (average time - 10 minutes). The par- turients in both groups wqre allowed 40 minutes for full onset of surgical anesthesia. During the operative procedure, left uterine displacement was accomplished with all patients by placing a blanket roll under the right hip until the baby was delivered. Three parturients in the supine position and one in the lateral position developed hypotension which was immediately cor- rected by displacing the uterus and increasing the intravenous infusion.

There were significant differences in both the acid-base status and the difference between umbilical vein and umbilical artery (UV-UA) concentra- tions of bupivacaine. All Apgar scores at 1 and 5 minutes were normal.

The important findings at delivery are:

SUPINE LATERAL SIGNIFICANCE .(N=1OJ (N=lO1

Maternal Artery (MA)

Umbilical Artery (UA) 7.39* 7.42 co.025

PH 7.20 7.30 CO.001 base excess -9.10 -3.80 CO.001

Umbilical Vein (UV) PH 7.28 7.34 <O.OOl PC02 47 40 co.005

& 0.44 0.31 NS UV-UA Cont. Difference 0.07** 0.02 co.01

*mean **bupivacaine - ug/ml

Although there is not a significant difference in the UV/MV ratio between the two groups of patients, there was a trend to a hi the supine group (0.44) when compared with the lateral group 9

her ratio in 0.31). The

most interesting observation was the significant.difference in UV-UA concen- tration difference of bupivacaine in the two groups of patients.

Possible mechanisms include: (1) Decreased tissue pH will trap more ionized drugs intracellularly. (2) Acidosis increases the binding of the more ionized local anesthetics to tissue proteins. (3) Alterations in re- gional blood flow in the fetus occur during acidosis. (4) Increased renal excretion of the drug because of the acidosis.

NITROUS OXIDE-OXYGEN ANESTHESIA FOR VAGINAL DELIVERY

::

’ i .//

Richard B. Clark, M.D.

University of Arkansas for Medical Sciences, Little Rock, Arkansas

Nitrous oxide analgesia for labor and delivery is an accepted technique. Anes- thesia for vaginal delivery, however, requires high concentrations of nitrous oxide, and its use is controversial. Husteadl cited several studies which reported that nitrous oxide anesthesia can cause hypoxia in both mother and infant. This is difficult to understand as the breathing of a mixture containing at least 21% oxygen should produce normal arterial oxygen tensions.

Seventy-seven women were studied. All delivered vaginally, and all received continuously a mixture of -/L/rain N20, and 2Llmin 0 . Induction was begun by mask several minutes before delivery, and a clampe % cord section taken at delivery for neonatal acid base values. After delivery, arterial blood was obtained from the mother for acid base determinations. The results are seen in tables 1 and 2.

Maternal Values Neonatal Values at Birth Umbilical Artery Umbilical Vein

GROUP N IDI" ISI* pH p02 pC02 BE pH p02 pC02 BE pH PO2 PC02

T A B L E 1: Data on all 77 patients receiving 78% N20 for delivery. Mean values g

Total 77 3.2 7.9 7.39 120 29.3 -5.3 7.19 22 55.9 -7.5 7.31 40 40.2

Data on patients as broken down into subgroups. Miscellaneous group T A B L E 2: includes prematures, midforceps, PRBOW, hypertension, pre-eclampsia,

Normal 25 3.0 7.7 7.39 116 31.9 -5.0 7.21 24 53.9 -6.3 7.33 38 39.9

Breech 20 2.8 6.8 7.38 117 26.9 -6.6 7.16 19 62.1 -9.3 7.31 34 38.C

Nuchal Cord 8 2.1 7.8 7.41 117 26.4 -6.4 7.24 19 46.9 -5.8 7.36 36 36.5

Twins 5 1.4 11.2 7.39 113 30.0 -6.1 7,15 22 58.6 -7.9 7.29 38 40.4

Misc. 19 4.7 8.7 7.38 122 32.6 -5.5 7.19 23 56.7 -8.2 7.27 38 45.5

*IDI-Induction Delivery Interval (min) tIS1 - Induction Sampling Interval (maternz

Table 1 summarizes findings from all 77 mothers and infants. Table 2 gives values obtained when the patients were broken down into subgroups, according to maternal c fetal complications. The normal group had normal maternal and neonatal values,2 bt some of the other groups involved obstetric complications. Maternal p02's remainec good, despite 22% O2 administration probably because of hyperventilation and diffusion hyperoxia.3

These results indicate that administration of 78% N20 and 22% oxygen is safe, especially in multigravidas, for anesthesia of short duration during vaginal del- ivery. Neonatal acid base status and Apgar scores are also good, except in obviou: cases of fetal difficulty.

1. Hustead, R.F.: Nitrous oxide in obstetrics, Ch. 8 in Eastwood, D.W. (Ed).: Nitrous Oxide, Clinical Anesthesia Series l/1964, Philadelphia, F. A. Davis Company, 1964, pp. 97-114.

2. Clark, R.B., et al: Fetal and maternal effects of bicarbonate administration during labor. Anesth. Analg. 50:713-718, 1971.

3. Markello, R., et al: Diffusion hyperoxia, a "concentrating" effect. Anesth. Analg. 53~233-238, 1974.

THE KOLE OF THE PRIVATE SECTOR IN TERTIARY PERINATAL CARE 40

Martin H. Greenberg, M.D.

Chairman, Department of Newborn Medicine St. Francis Hospital, Tulsa, Oklahoma

Spiraling costs, resistance to regionalization of perinatal services by private physicians, impersonal treatment in university hospital settings, and the need to bring high standards and newest developments in care to the bulk of patients in the Private Sector, necessitate departures from traditional means of providing tertiary care.

Large, privately funded community-based hospitals can provide tertiary perinatal care and serve as focal points for regional education and clinical research. They are more apt to render personal service and relate to the needs of the private, primary care physician.

St. Francis Hospital in Tulsa, Oklahoma, Ls a private community hospital which has developed the Eastern Oklahoma Perinatal Center, serving Eastern Oklahoma , parts of Missouri, Arkansas, and Kansas. Eighteen intensive care neonatal bassinets are available, and its staff consists of full-time Neonatology, as well as Pediatric specialists in Cardiology, Surgery, Radiology, and Hematology The unit also includes a 24-hour staff of respiratory therapists. A Child Developmentalist provides long-term patient followup and data is complied by a Research Nurse, The unit trains fellows, house officers in Pediatrics, Obstetrics and Family Practice as well as nurses in many levels of expertise, including a new program to provide nurse specialists. The region is also served by con- ferences and a hot-line telephone system for direct referrals.

The role of the Private Sector in tertiary perinatal care can significantly contribute to a reduction in morbidity and mortality while increasing interest and involvement by primary care physicians.

41

IS PRETREATMENT WITH ATROPINE OF ANY VALUE IN C-SECTION UNDER EPIDURAL ANESTHESIA?

Jay S. DeVore, M.D. Department of Anesthesiology

Northwestern University Medical School

Atropine has long been a standard drug given prior to general anesthesia in order to dry secretions and block noxious vagal effects on the heart. High levels of regional anesthesia such as epidural or spinal result in such effects as bradycardia, hypotension, nausea, and vomiting, yet the use of atropine prior to regional anesthesia is not universal practice. It is a feeling among many anesthesiologists that pretreatment with atropine will minimize many of the unpleasant vagal side effects due both to the chemical sympathectomy and peritoneal traction, yet there are no data to support this feeling.

In order to answer this question forty patients under- going elective cesarean section under epidural anesthesia are being studied. A.S.A. class I patients having been entered into the study by having informed consent obtained are randomized into two groups. Continuous lumbar epidural anesthesia will be administered by standard techniques with one group receiving 0.6 mg atropine intravenously and the other one (1) cc of saline intravenously prior to the in- jection of the local anesthetic. Pulse, blood pressure, nausea and vomiting and cardiac arrhythmias will be observed and recorded every 2 minutes for the first 10 minutes and every 5 minutes thereafter and the differences between the groups studied.

/:

42

A DOUBLE BLINDCOMPAEISONOF LILKICAINEAND ETIDOCAINE FOR VAGINAL DELIVERY

c,

Brendan T. Finucane, M.D., FFAECS(E) FECP(C), John M. McCraney, M.D. Daniel F. Bush, Ph.D.

Grady Memorial Hospital, mory School of Medicine, Dept. of Anesthesiology

A double blind comparison of 0.5 percent Etidocaine plain vs. 0.5 percent Btidocaine with Bpinephrine 1:200,000 vs. 1 percent Lidocaine with Epinephrine 1:200,000 for obstetrical epidural anesthesia was undertaken.

A total of 48 patients of ASA classification 1 - 2 participated in this study. There was no significant difference in the onset of action of the three groups.

There was a significant difference in the duration of action of Etidocaine with Bpinephrine compared to the other two groups.

The degree of motor blockade based on a simple scoring system was significantly enhanced in the Etidocaine with Epinephrine group. sensory analgesia at delivery was also significantly greater in this group.

There were no adverse effects in the mother or fetus.related to the administration of these drugs.

Table 4

Anesthetic Evaluation Parameters

Lidocaine 1% with Etidocaine 0.5% with Qinephrine Bpinephrine Btidoaine Plain 1:200,000 1;200,000

Profound motor blockade

Spontaneous Delivery

Additional Analgesia at Delivery

n = 12 n = 16 n = 15

11.7% 68.78* 6.6%

47.0% 12.5%. 40.5%

76.4% 37.sa** 73%

*Probability 0.01% (Ch.i Square Test) **Probability 0.02% (Chi Square Test)

HUMAN UMBILICAL VESSEL RESPONSES TO LIDOCAINE HCl AND 2-CHLOROPROCAINE

Charles P. Gibbs and Stephen C. Noel*

43

Department of Obstetrics and Gynecology and Anesthesiology, University of Florida, Gainesville, Florida

4 Department of Pathology, University of Arizona, Tucson, Arizona

Lccal anesthetics are commonly used for obstetric analgesia and are usually benign for both mother and fetus. There are instances, however, when they can be harmful, and the most obvious instance is represented by paracervical block bradycardia. Our in vitro studies of the vasoconstrictive action of local anesthetics on isolatsuterine arteries indicate that a decreased uterine blood flow might be part of the mechanism (Am J of Obstet & Gynec 126:313, 1976). The umbilical vessels are other vessels that, if affected in the same way, might also cause problems for the fetus. There- fore, this study investigated the in vitro responses of the umbilical arteries and veins tc lidocaine and E-chlorzrocaine. Three to four mm rings were fashioned from umbilical arterial and venous segments obtained immediately after the vaginal delivery of normal newborns. Isometric contractions produced by these rings were measured in a manner similar to that reported by Faye P, Cook (Am J Physiol 222:841, 1972). Each segment was subjected to the following concentrations of lidocaine and 2-chloroprocaine: 3, 1, 10, 20, 50, 100, lc)OI! and 2000 ug/ml. None of the 10 umbilical arteries contracted to either of the local anesthetics. Ten umbilical veins were tested with lidocaine. All responded to the 2000 ug/ml concentrations; nine of the ten responded to 1000 ug/ml; six responded to 100 ug/ml; three to 20 and 50 pg/nl and two to 10 ug/ml. The individual responses are tabu- lated in Table 1. Not one of seven umbilical veins tested responded to 2_chloroprocaine, yet each of the same segments responded to lidocaine. !lean tension developed by these seven veins to 1000 pgs/ml of lidocaine was 5017.86 mgs (+SE 1532.25).

Vein No.

Mean S.E.

-r Lidocaine ug/ml I

Tension (mgs) Developed by Umbilical Veins in Response to Lidocaine HCl

10 20 50

E 450 75

: 0

: 0

52.50 34.50 82.50 2282.50 44.82 22.66 52.75 1514.73

0

i 225

: 70 50

z

ii 475 300

: 0

50

:

100

0

7,3% 900 100

15: 14,250

0 0

1000 1 2000

4,500 3,600 4,652 550 1,650 600 11,375 9,375 5,250 5,125 400 1.050

44

FETAL DEMISE FOLLOWING A NEGATIVE CONTRACTION STRESS TEST

Joseph V. Collea, M.D., Larry Evertson, M.D., Robert Gauthier, M.D. - James R. Huey, M.D., and Richard H. Paul, M.D.

IAC-USC Medical Center Los Angeles, California

I !

Over the past four years, the contraction stress test (CST), or o_xytocin challenge test (OCT), has come into widespread use in the antepartum evaluation of fetal well-being. This has come about largely because of (1) the need for a simple, accurate and predictive test for fetal reserve in high-risk patients prior to labor, (2) the clinical data that late decelerations of the fetal heart rate, associated with spontaneous or induced uterine con- tractions, are often indicative of fetal hypoxia and are a sign of the compromised respiratory function of the fetopEenta1 unit, and (3) the availability of fetal heart rate recording from the maternal abdominal wall.

Initial clinical experience with the CST demonstrated that a negative test reliably predicted fetal well-being, and proponents of the test claimed that a negative test provided assurance that the fetus at risk for uteroplacental insufficiency was unlikely to die within one week.

At the LAC-USC Medical Center, during the calendar year 1975, 542 contraction stress tests were performed on 159 patients, and for 1976, 480 tests were performed on 318 patients. Over this two- year period, 5 patients experienced a fetal demise within one week of a negative CST--a false negative CST rate of I.@& This means, however, that the CST is 99% predictive of continued fetal survival in utero for at least one more week. It is advisable, in the absence of significant maternal deterioration, to continue the pregnancy and retest within one week.

4'

SEQUENTIAL BLOOD VOLUME STUDIES FOLLOWING ALBUMIN INFUSION IN NEWBORN IAMBS WITH HYPOVOLEMIC SHOCK

Sunthorn Horpaopan, M.D., Didier Moulin, M.D., James D. Ferguson, Warner Tyree, and Maria Delivoria-Papadopoulos, M.D.

Departments of Physiology and Pediatrics University of Pennsylvania School of Pedidine

Philadelphia, Pennsylvania

The experiments were designed to investigate the time sequence in blood volume changes in 2 groups of newborn lambs: those receiving 25% salt-poor human albumin, 1 gm/kg, after removal of 20% estimated blood volume (Group A, n = 6), and those receiving albumin without blood removal (Group B, n = 8). In each group half of the animals served as controls and did not receive albumin. To calculate total blood volume, 51Cr tagged red blood cells were used to measure red blood cell volume with central hematocrits; measurements were made before and after albumin infusion in all groups at intervals of 15, 45 and 90 minutes, and 3 and 6 hours, Vital signs, blood pressure and blood gases were monitored throughout the experiments. Total blood volume expressed as % change from baseline values was 9.85 f 1.61% in Group R following albumin infusion, a signifi- cant increase from controls (n < 0.01) and remained unchanged for 6 hours. Following bleeding in Group A, total blood volume decreased by 16.61 ?1 4.26% and increased to 10.46 + 6.02% immediately after albumin infusion, and reached 14.76 f 6.11% at 45 minutes and 19.89 + 6.24% at 3 hours, significantly different from control values (p < 0.05). The bled animals that did not receive albumin remained with a decreased blood volume for 3 hours, and thereafter increased. These data indicate that since 25% albumin infusion increased total blood volume in both groups of lambs for at least 6 hours, a single dose infusion can be beneficial in newborns with hypovolemic shock.

46

RESPIRATORY DISTRESS SYNDROEIE

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: 1

H.H. Shuman, M.D. and Tiffany Field, Ph.D.

Baystate Medical Center, Springfield, Massachusetts

The recent regionalization and advances in intensive care technology have diminished the mortality rate associated with prematurity and the respiratory distress syndrome (LIDS). The purpose of this study was to follow the developmental progress of survivors of RDS to determine whether morbidity was also on the decrease. Forty premature infants (mean=32 weeks gestation, 1800 gms. birthweight) with severe RDS were treated with intermittent positive pressure ventilation for a minimum of 12 hours (mean=5 days) and hospitalized for an average of 32 days during the period June - October, 1975. These babies were then assessed over the course of their first-year. At 4 months, the growth measurements and Denver Developmental screening test scores of the RDS babies lagged significantly behind the norms, even when an age correction was made for their prematurity. Again at eight months, they received lower than average scores in motor and mental development (Bayley Developmental Scale). By one year, both their growth measurements and Bayley .Developmental scores were approaching the norm. Although their motor scores remained one standard deviation below the norm, only one of the forty babies was considered neurologically suspect at the one year examination. These results suggest that the morbidity associated with RDS has also been diminished by recent advances in intensive care.

EFFECTS OF LCCAL ANESTHETICS ON UTERINE BLOOD FLOW IN PREGNANT SHEEP 47

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Alex F. pue, M.D., Michael H. Plumer, M.D., Robert Resnik, M.D., Gary W. Brink;B.A.

Departments of Anesthesiology and Reproductive Medicine University of California Medical Center, San Diego

Local anesthetics, once regarded as vasodilating drugs, have recently been shown to act as vasoconstrictors in the uterine arteries of non-pregnant sheep and in uterine artery segments from pregnant humans. We studied changes in the uterine artery blood flow (UBF) of pregnant sheep in response to direct infusion of local anesthetics and constructed dose-response curves for bupivacaine, mepivacaine, lidocaine, and chloro-

procaine. METHODS. Five pregnant ewes at 95-110 days gestation were prepared for chronic

study by placing an electromagentic flow probe around each of the two main uterine arteries and inserting a vinyl catheter through a side branch of each artery until the catheter tip lay within the lumen of the main artery. This permitted continuous monitoring of flow during direct infusion of drugs into the artery. After a one-week recovery period, studies were begun in the standing, unstressed ewe. The local anes- thetic being studied was infused directly into one uterine artery for 10 min. using a Harvard pump. Flows were allowed to return to control for up to one hour between

infusions. Infusion rates were calculated to give initial concentrations of 1, 5, 10,

25, or 50 ug/ml in the uterine artery, using the formula

Intra-arterial concentration(ug/mlj = Infusion rate (pg'minl Arterial flow (ml/min)

The order of initial concentrations was randomized, and only one anesthetic was

studied each day. Uterine artery flows were recorded continuously during control periods and infusions. In addition, maternal arterial pressure and intrauterine

pressure (IUP) were recorded in the first two ewes studied. RESULTS. Each local anesthetic, when infused into the uterine artery, caused a

dose-related decrease in blood flow in that artery. This decrease occurred without change in maternal arterial pressure, intrauterine pressure, or contralateral uterine blood flow. After the initial decrease, blood flow tended to return toward baseline near the end of each infusion period. Since blood flow decreased while infusion rate remained constant, the intra-arterial local anesthetic concentration became progress- ively greater during an infusion period. We therefore computed local anesthetic con- centration for each minute during the infusion, then plotted UBF as percent of control against log local anesthetic concentration (Fig. I). The regression lines of these graphs have similar slopes, and eoual concentrations of different anesthetics can be seen to have nearly the same effects on blood flow (Table I).

DISCUSSION. The dose-related decrease in uterine blood flow which follows in- fusion of local anesthetics into the uterine artery appears to be due entirely to a

local increase in uterine vascular resistance, since no changes in maternal blood pressure or contralateral UBF were noted. This increase does not appear to be related

to myometrial contraction, since IUP did not change with changes in flow. The four drugs studied were nearly equipotent as uterine artery vasoconstrictors, although they are not considered eauipotent as local anesthetics. This study supports the hypothesi that the bradycardia which sometimes follows paracervical block may be related to uterine artery vasoconstriction caused by local anesthetics.

X UBF AT X UEF PT DRUG 5 ug/ml* 50 r;g/ml**

BUPIVACAIME 80 48.5 MEPIVACAISE 52.3 LIWCAINE i: 49 CHLOROPROCAINf a3 46.5

TABLE I: UBF AS f CONTROL FLOW AT LOCAL ANESiHETIC LEVELS OF l 5 ug/ml AiiD

48

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ARTERIAL BLOOD GASES IN MOTHERS AND INFANTS WITH KETAMINE FOR VAGINAL DELIVERS

Albert L. Maduska. M.D. and Mehrdokht Hajghassemali, M.D.

University of Tennessee Center for the Health Sciences Memphis, Tennessee

Ketamine has been widely used for vaginal delivery and Caesarian section in doses of 0.25-2 mg/kg/I.V. In spite of this! arterial blood gas studies have not been widely reported particularly with mothers breathing room air at delivery. After a recent report by Zsigmond that revealed serious hypoxemia when ketamine was used in non-pregnant females, we decided to inves- tigate this possibility in mothers receiving ketamine in doses of 1 mg/kg/I.V. for vaginal delivery. We found no difference between controls and the ketamine group in either mothers or infants with regard to pH, PC02, PO2 and Apgar score. We did not see hypoxemia as Zsigmond reported.

Fa02 PaC02 PH

PO2 PC02 PH

ma ma ma

uv uv uv

TABLE I

BLOOD GAS VALUES AND pH

(ROOM AIR + s. D.)

Ketamine Group Controls

96.94 + 6.97 30.60 7 4.48 7.445 T 0.066 -

32.01 + 3.19 34.91 T 3.66 7.356 - 0.058

99.58 + 3.35 32.35 + 4.20 7.433 z 0.058

32.46 + 2.34 36.16 + 3.52 7.337 E 0.042

t-test

1.079 0.901 0.427

0.359 0.777 0.829

UTERINE INCISION - DELIVERY INTERVAL AND NEONATAL OUTCOME

49

Sanjay Datta, M.D., Walter U. Brown, Jr., M.D.

Department of Anesthesia, Harvard Medical School and Boston Hospital for Women

Evidence indicates that the longer the induction of anesthe- sia to delivery interval (I-D interval) for cesarean section the higher the incidence of depressed Apgar scores and neonatal aci- dosis.A factor related to the I-D interval which may have consid- erable influence on the infant's condition is the duration of the uterine incision to delivery interval (U-D interval).

Forty-seven healthy parturients were studied during elective, repeat cesarean section. Balanced general anesthesia was used for all cases. Patients were divided into 4 groups according to the length of the I-D and U-D intervals: Group A (I-D e 8 minutes, U-D < 90 seconds), Group B (I-D < 8 minutes, U-D < 180 seconds), Group C (I-D > 8 minutes, U-D < 180 seconds), and Group D (I-D > 8 minutes, U-D > 180 seconds).

The mean pH of maternal arterial(MA) and umbilical artery (UA) blood at delivery and the per cent of babies with Apgar scores less than 7 at 1 minute are presented in the following tab1

GP A GP B n=19 n=13

GP C n=8

GP D n=7

MA PH 7.42 7.44 7.45 7.48

UA pH 7.31 7..30 7.28 7.23

& Apgar < 7 5 23 38 71

.: :

As the U-D interval increased the number of babies with low Apgar scores rose. U-D intervals exceeding 3 minutes were asso- ciated with significantly lower pH in the baby (~~0.02) and significantly higher incidence of depressed Apgar scores (~~0.01). Prolonged uterine manipulation may adversely effect uteroplacental and umbilical cord circulation.

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PROPER POSITION FOR CESAREAN SECTION AND NEONATAL OUTCOME

Gulen F. Tangoren, M.D.

Rockville, Maryland

50

Many authors have studied the effects of position during cesarean section or vaginal delivery on neonatal well-being. *We are all aware of hypotensive syndrome. In this study patients were positioned head up and ten degrees right side up.

This study includes 10 cases, six emergency and four elective section. One of the elective cesarean section patients had a All infants had Apgar scores of nine at one minute and ten at One of the twins had an Apgar score of six at one minute.

the supine twenty degrees

cesarean twin pregnancy. five minutes.

Only one case had epidural anesthesia; the others received general anes- thesia.

As a result, I recounnend this position for all cesarean sections. Since completion of this study I have been placing patients for vaginal delivery in a twenty degree head up position.

References:

1.

2.

3.

4.

5.

6.

Coleman, A.J., et al.: Ethrane anesthesia for C. section. African South J. Med. - November, 1975.

Howard, B.K., Goodson, J.H., and Mengert, W.F.: Supine hypotensive syndrome in late pregnancy. Obstet. Gynecol. 1:371-377, 1953.

Lees, M.M., Scott, D.B., Slawson, K.B., and Keer, M.G.: Eaemodynamic changes during caesarean section. 2. Obstet. Gynaecol. Br. Comm. 75: -- 546-551, 1968.

Roberts, W.A. MC.: Postural shock in pregnancy. Am. J. Obstet. Gynecol. -- 62:627, 1951.

Sprague, D.H.: Effects of position and uterine displacement,on spinal anesthesia for C. section. Anesthesiology 44:164-166, 1976.

De Vivo Pica, P.: Bromuro di pancuronio nella chirurgica de1 taglio cesareo.

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