W.D. Whybrew

Metabolites of meperidine related to fetal depression.

Abstract Three specific patterns of meperidine metabolism were observed in the maternal serum of 52 patients studied. These patterns appear to be related to the rate of formation of certain metabolites of the compound. No observable signs of infant depression were detectable when delivery was performed during the first 60 minutes following the administration of the analgesic agent regardless of the type of pattern. However, when greater than 60 minutes had elapsed following intravenous injection of meperidine the incidence of depressed infants was directly related to the more rapid metabolic patterns. Therefore, the most significant factors relating infant depression to meperidine are the maternal metabolic pattern and the length of time the patient is in labor following the administration of the compound. These observations presumably reflect the increased toxicity of certain metabolites of meperidine transferred to the fetus from the mother. Thus, if delivery takes place within 60 minutes after injection, the level of metabolites of meperidine in the fetus should be low and the chance of a depressed infant reduced.

The lecithin/sphingomyelin ratio in cases associated with fetomaternal disease

The efficacy of correlating the L/S ratio in the amniotic fluid with fetal lung maturity has been substantiated in normal pregnancies. In gestations complicated by fetomaternal diseases, however, the assay is less reliable. This study involves 555 pregnancies in which there was a significant maternal, fetal, or placental disorder. The L/S ratio was related to fetal respiratory maturity as measured by Dubowitz criteria and the occurrence of RDS. The results show that pre-eclampsia, chronic hypertension, diabetes (Class D, E, F), significant cardiovascular disease, severe hemoglobinopathies, various congenital anomalies, chronic placental insufficiency, and prolonged ruptured membranes accelerated the L/S ration. Conversely, mild diabetes (Class B, C), intrinsic renal disease, hepatitis, collagen disease, hydrops fetalis, syphilis, and toxoplasmosis were associated with a delay in the L/S ratio. A significant increase in erroneous responses was noted in these patients when the L/S ratio was correlated to infant maturity and to the incidence of RDS. Possible mechanisms for these findings are discussed.

Metabolites of meperidine in the fetal and maternal serum

Although meperidine appears to be the safest obstetric analgesic agent, it has been associated with infant respiratory depression in certain situations. It would appear that the incidence of fetal depression related to meperidine is dependent on the time of injection prior to delivery, the quantity of drug administered, and the rate of maternal metabolism of the analgesic. Previous work showed that meperidine is metabolized in the maternal system by one of three patterns. The present study demonstrates that the particular maternal serum pattern is characteristic for the individual, regardless of whether the patient is pregnant or not, and that the fetal depression, although usually mild, can be correlated with fetal pH data as well as Apgar scores. In addition, this study supports indirectly the contention that metabolites of meperidine rather than the parent compound cause fetal depression. It would appear, therefore, that in certain obstetric cases with a higher probability for infant depression, other analgesic agents might be considered, especially if the serum pattern indicates meperidine is being metabolized.

Use of partial exchange transfusion preoperatively in patients with sickle cell hemoglobinopathies

Sickle cell anemia and other severe sickle cell disorders (hemoglobin SC and hemoglobin S-thalassemia) are known to complicate surgical procedures in susceptible patients. Although transfusions have been used preoperatively to increase the packed cell volume, we have recently used the method of partial exchange transfusion in the treatment of patients with these disorders in the preoperative period. Forty-two patients with significant sickle cell hemoglobinopathies underwent operative procedures on various surgical services. The goal was to obtain a hemoglobin A percentage of 40 or above in each case, and this required 480 to 1,150 c.c. of buffy coat poor washed red cells (mean 820 c.c.). The number of complications in the intraoperative and postoperative period in this study was compared to those found in the literature. There was a significant decrease in morbidity and mortality rates noted with the use of these transfusions. There appeared to be a great advantage on a cost-benefit ratio, as well as an improvement in the physiologic state of the patient. Although the results of this study show significant improvement over previous investigations, there are many facets unknown concerning the use of this modality under these and other conditions. Therefore, further investigation of this method and restriction of the method of Level III referral centers is advocated until enough patients have been studied to assess the long- and short-term complications of the procedure.

Cerebral spinal fluid studies in eclampsia

Abstract During the 5 year period 1966–1970, 94 eclamptic patients were delivered of infants at the City of Memphis Hospitals. The cerebrospinal fluid of the last 21 patients was studied in an attempt to clarify the various neurological manifestations of this syndrome. The results were compared with cerebral spinal fluid obtained at delivery from 25 patients with severe pre-eclampsia, 10 with chronic hypertensive vascular disease, 9 with documented seizure disorders, and 35 patients with normal term pregnancies. Nineteen of the 21 eclamptic patients had bloody spinal fluid (hematorrhachis), and this finding, in addition to others, is correlated with neurological deficits and prognosis.

Modification of the lecithin/sphingomyelin assay for fetal development

Abstract Modifications in the lecithin/sphingomyelin assay have been introduced which provide for a rapid, sensitive, reproducible, and economical procedure for the determination of fetal maturity. This procedure can be carried out easily by individuals with a minimal amount of training and equipment. The method as modified has been shown to be accurate in the assessment of fetal maturity in the 100 normal pregnancies studied. This test is recommended before delivery, particularly in complicated cases, to predict the risk of pulmonary immaturity.

Placental transfer of 14C-hexoprenaline

The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus.

Fluctuation of fetal hemoglobin in sickle-cell anemia

A reduction of morbidity and mortality rates in homozygous sickle-cell patients was found in those with high fetal hemoglobin (HbF) levels. This factor would lead one to believe that an adequate amount of this substance would be protective to a patient with this hemoglobinopathy. This study utilizing pregnant and nongravid females, as well as males, followed for long periods of time indicates that the HbF level fluctuates with crisis. Some patients had low HbF levels with many crises and others had high amounts of HbF with no crises. However, many patients with high levels on one occasion demonstrated a decrease in HbF levels when crisis occurred. More importantly, no patient had high levels of HbF during a crisis although the amount was elevated before and after the episodes. The possible explanation and ramifications of this finding are discussed.

Purification and characterization of B-Protein from human serum

B-Protein, present in the serum of individuals with cancer, has been purified to electrophoretic homogeneity. The purification procedure consisted of chromatography on Sephacryl S-200, Affi-Gel Blue, Con A--Sepharose 4B, wheat germ lectin--Sepharose and preparative polyacrylamide gel electrophoresis. The molecular weight of B-Protein is estimated to be 100 000 to 120 000. It is a glycoprotein which appears to be composed of two subunits, each with a molecular weight of approximately 52 000. Analytical polyacrylamide gel electrophoresis and analytical ultracentrifugation data indicate that purified B-Protein is homogeneous. Isoelectric focusing studies also show the purified B-Protein to be homogeneous in composition consisting of a single band of pI = 4.8. Amino acid analysis is consistent with this acidic isoelectric point. Other analyses indicate that B-Protein contains 7% carbohydrate and 7% lipid in the form of triglycerides.

Effects of hexoprenaline on the lecithin/sphingomyelin ratio and pressure-volume relationships in fetal rabbits

A placebo-controlled, double-blind trial was carried out on 74 New Zealand White rabbit fetuses from 15 does to assess the effect of a fetal injection of hexoprenaline on surfactant release. After the uterus was exposed, half the fetuses received 0.1 ml (0.25 microgram) of hexoprenaline injected intraperitoneally through the intact uterine wall; the other half received an equivalent volume of placebo. After 3 hours, the abdomen was reopened, and the fetuses were surgically delivered and killed before breathing. The lecithin/sphingomyelin (L/S) ratios, obtained from lung washings, revealed a mean of 1.59:1 for the placebo group and 1.92:1 for the hexoprenaline group (p less than 0.001). Pressure/volume curves were generated from the lungs of 24 fetuses from 10 does, and the volume of air in the lungs for each pressure was analyzed in four ways: total volume, volume per gram of fetal body weight, volume per gram of dry lung weight, and as a percentage of total lung capacity at a pressure of 40 cm H2O. A first and second inflation-deflation curve was obtained for each experiment. The lungs from the hexoprenaline-treated group retained significantly more air than those from the placebo group. The most significant comparison was obtained when lung volume was expressed per gram of dry lung weight. The possibility of administering a beta 2-sympathomimetic drug to the mother in advanced preterm labor, specifically to release surfactant in the fetal lung, is suggested.