Comparative pharmacokinetics of cefoxitin in postpartum normotensive and pregnancy-induced hypertensive patients

Limited pharmacokinetic data exist on cefoxitin, a semisynthetic cephamycin antibiotic, in the obstetric patient. Thirteen normotensive and five subjects with severe pregnancy-induced hypertension were identified within the first two postpartum days after cesarean section. After a 2 gm intravenous infusion, serial samples of blood were obtained and analyzed for cefoxitin by high-pressure liquid chromatography. Peak cefoxitin concentrations after infusion were 53.3 ± 18.6 and 50.8 ± 25.2 μg/ml for the normotensive and pregnancy-induced hypertensive groups, respectively. The only significant difference in pharmacokinetic parameters between these groups was a higher serum trough concentration of cefoxitin in the patients with pregnancy-induced hypertension as compared to the normotensive group. Because of diminished trough levels in our study patients, attention may need to be given to the adjustment of dosages in postpartum women with serious infections.     

The use of ultrasound in the expectant management of abruptio placentae

The use of real-time ultrasound and antepartum nonstress testing in the management of abruptio placentae is discussed. In one patient, fetal distress developed when the retroplacental clot volume reached 480 ml. Two cases in which retroplacental clot was less than 480 ml were managed expectantly with the use of ultrasound and antepartum fetal testing, with excellent results.     

Premature rupture of membranes and surface energy: possible role of surfactant

Thirty-one human placental membranes of various gestational ages (24 1/2 to 42 weeks) have been studied for their surface properties by use of a goniometer to observe drops of saline and olive oil applied at regular intervals to the amniotic and chorionic surfaces as they dried in air. Results show that the epithelial surfaces of the chorion and amnion and their interface are all appreciably hydrophobic. Surface energy decreased on the amniotic surface with fetal maturity while the surface energy of the chorion was significantly (137%) higher in those displaying premature rupture of the membranes than in others of comparable gestational age. This is explained on the basis that low-energy surfaces (for instance, Teflon) do not stick and provide boundary lubrication which facilitates movement. These properties are needed to avoid the buildup of local mechanical stress which could initiate rupture. It is speculated that the release agent-lubricant is surfactant derived from amniotic fluid and directly adsorbed onto the epithelial walls. On other tissues, the same surfactants have been shown to reduce surface energy, rendering them hydrophobic and imparting many desirable properties such as release, lubrication, and resistance to erosion.     

Responses of the growth-retarded fetus to acute hypoxemia

Growth retardation in the human fetus associated with maternal cardiovascular disease is frequently accompanied by birth asphyxia and perinatal mortality. We have investigated the cardiovascular responses to acute hypoxemia in the fetal lamb with growth retardation secondary to embolization of the uteroplacental vascular bed. In the basal period, fetal arterial P_O2 and umbilical perfusion were significantly lower, and perfusion of the adrenal glands, brain, and heart was significantly higher, in embolized than in control fetal lambs. During imposed acute hypoxemia there was preferential perfusion of vital organs, the adrenal glands, brain, and heart in control and embolized fetuses. This preferential perfusion to the vital organs during hypoxemia was significantly more pronounced in embolized animals. Because of the increased compensation during acute hypoxemia, as reflected by the increased preferential perfusion of vital organs, the growth-retarded fetuses would probably decompensate sooner if the hypoxemia was prolonged.     

Preterm delivery is not predicted by serial plasma estradiol or progesterone concentration measurements

Previous studies suggest that plasma estradiol-17 beta and progesterone concentration values differ between patients who deliver before term and those who deliver at term. To determine if these values would aid in preterm delivery risk prediction, we measured plasma estradiol-17 beta and progesterone concentrations serially in 90 patients at high risk for preterm delivery. Measurements from 17 patients who developed documented preterm labor and/or were delivered before term were compared to the tenth and ninetieth percentiles of 42 patients who were delivered at term. The sensitivity of these measurements to predict preterm delivery was very low. Also, the mean plasma estradiol-17 beta and progesterone concentrations in patients with preterm labor who had term deliveries and in patients with preterm labor that progressed to preterm delivery were not different from each other or from patients delivering at term. No change in plasma estradiol-17 beta or progesterone concentration was noted preceding labor. We conclude that serial measurements of plasma estradiol-17 beta and progesterone concentrations do not improve preterm delivery risk prediction.     

A comparison of intravenous and intramuscular magnesium sulfate regimens in preeclampsia

A prospective study comparing continuous intravenous magnesium sulfate to intramuscular magnesium sulfate was performed in 32 preeclamptic patients. Eighteen patients received the intramuscular regimen for mild and severe preeclampsia as recommended by Pritchard. The remaining 14 patients received an intravenous regimen consisting of a 4 gm loading dose administered over 15 minutes followed by a maintenance dose of either 1 gm/hr (n = 7) or 2 gm/hr (n = 7). All groups were similar regarding maternal age, height, weight, fetal gestational age, and laboratory findings. The intravenous regimen with a maintenance dose of 1 gm/hr produced serum magnesium levels that were much lower than those achieved with the intramuscular regimen. There was no significant difference after 3 hours of therapy between the mean magnesium levels achieved with the intramuscular regimen and the levels achieved with the intravenous regimen with a maintenance dose of 2 gm/hr. However, during the first 3 hours of therapy the intramuscular regimen for severe preeclampsia produced mean magnesium levels that were significantly higher than those levels obtained with the intravenous regimen with a maintenance dose of 2 gm/hr (p less than 0.001). Both methods were safe. However, the intravenous regimen with a maintenance dose of 1 gm/hr is inadequate in management of preeclamptic patients.     

Maternal administration of dexamethasone in severe pregnancy-induced hypertension

Fourteen patients with severe pregnancy-induced hypertension and low lecithin/sphingomyelin (L/S) ratios were treated with 5 mg of dexamethasone phosphate intramuscularly every 12 hours for four doses to induce fetal pulmonary maturity. A comparison was made of the average gestational age, mean L/S ratio, method of delivery, Apgar scores, mean birth weight, and incidence of respiratory distress syndrome in these patients and in 16 patients with similar demographic backgrounds and clinical presentations who did not receive corticosteroid therapy. There was no significant difference between the two groups except that the time of treatment (or nontreatment) to delivery was longer in the steroid group. There were two cases of neonatal respiratory distress syndrome in the treatment group, and one of these infants died. In the control group, there were two neonatal deaths among four cases of respiratory distress syndrome. There was no clinical evidence of intraventricular hemorrhage in any neonate nor was there aggravation of hypertension in the parturient patients. The administration of corticosteroids to induce fetal pulmonary maturity in patients with severe pregnancy-induced hypertension who are carefully selected and monitored does not appear to be contraindicated.     

The role of Swan-Ganz catheterization in severe pregnancy-induced hypertension

Swan-Ganz catheterization was performed in 15 postpartum women who presented with severe pregnancy-induced hypertension at a mean gestational age of 31.5 weeks. The mean arterial pressure on presentation was 137.6 torr (range, 116 to 167 torr), and it remained at approximately 115 torr for the next 72 hours. Serial pulmonary capillary wedge pressure, cardiac output, and colloid oncotic pressure were obtained. The mean pulmonary capillary wedge pressure was 9 torr on insertion of the catheter, and it rose to 13 torr by 36 hours. Three patients whose pulmonary capillary wedge pressure was higher than the mean developed pulmonary edema. The mean colloid oncotic pressure was 14.14 torr. We found that hemodynamic monitoring and determinations of colloid oncotic pressure were useful additions to the clinical examination in the postpartum management of patients with severe pregnancy-induced hypertension. Our patients had a broad range of central volume status, cardiac output, and systemic vascular resistance, and the management was tailored accordingly. Although most patients had hyperdynamic pulmonary cardiac function, three developed edema at a lower pulmonary capillary wedge pressure because of decreased colloid oncotic pressure and possibly increased capillary permeability.     

The effects of pregnancy on patients with hyperprolactinemia

Seventy women with amenorrhea with or without galactorrhea associated with high serum prolactin levels and radiologic evidence of pituitary tumors were treated with transsphenoidal tumor resection. The prolactin level was measured in 29 patients before pregnancy, at 3 months post partum or cessation of lactation, and at 6-month intervals thereafter. The results were compared to those of 18 patients who had hyperprolactinemia but no demonstrable radiologic evidence of a pituitary tumor and who responded to bromocriptine and conceived. Our investigations showed that operation resulted in normalization of serum prolactin levels in 74% of patients. Forty of the 49 patients less than 36 years old conceived (80%). Five of 29 patients who were studied before and after operation as well as after delivery showed an increase in serum prolactin levels post partum and persistent amenorrhea suggesting recurrence. Six of the 18 patients who became pregnant after bromocriptine also showed a significant rise in serum prolactin levels above the treatment level. None of the patients in the two groups developed visual changes or symptoms or radiologic changes during pregnancy. These results showed that transsphenoidal operation has a high incidence of success, but some patients may show a rise of serum prolactin levels and persistent amenorrhea after pregnancy or passage of time, suggesting recurrence. Some patients who become pregnant after bromocriptine therapy may have further rises in prolactin greater than pretreatment levels. Follow-up of these patients is indicated.     

Adjunctive use of magnesium sulfate with ritodrine for preterm labor tocolysis

The purpose of the study was to determine if the adjunctive administration of magnesium sulfate with ritodrine would result in decreased dosage requirements of ritodrine, and, therefore, decrease the incidence of ritodrine-associated side effects. Candidates for tocolysis were prospectively randomized so that some received a uniform tocolytic dose of magnesium sulfate in a blinded protocol. All patients received a ritodrine infusion which was titrated in the standard manner to achieve cessation of labor. Evaluations included interval cumulative ritodrine dose, maximal ritodrine infusion rate, fluid balance, and blood chemistry studies. Contrary to our hypothesis, there were significantly more cardiovascular effects in the group that received ritodrine plus magnesium sulfate (11/24) than in the group that received ritodrine alone (1/17) (p less than or equal to 0.02). The predominant side effect was chest pain, frequently associated with electrocardiogram changes indicative of myocardial ischemia. These results are consistent with the current understanding of the regulatory mechanisms of these tocolytic agents. We conclude from the results of our prospective, randomized, blinded study that the adjunctive use of magnesium sulfate with ritodrine is associated with an unacceptable increase in serious side effects and probably does not improve efficacy.     

Cardiovascular alterations in severe pregnancy-induced hypertension: effects of intravenous nitroglycerin coupled with blood volume expansion

Control of blood pressure in severe pregnancy-induced hypertension has often relied on agents with an unpredictable onset and duration of action. Because intravenous nitroglycerin is a potent, rapidly acting agent with a hemodynamic half-life measured in minutes, we evaluated its cardiovascular effects with and without volume expansion in six patients with severe pregnancy-induced hypertension. Nitroglycerin alone reduced mean arterial pressure by 27.5% without any significant changes in heart rate, central venous pressure, or stroke volume. The pulmonary capillary wedge pressure fell from 9 +/- 3 to 4 +/- 2 mm Hg (p less than 0.05) while the cardiac index decreased from 3.51 +/- 0.67 to 2.87 +/- 0.76 L/min X m2. Oxygen delivery fell significantly (p less than 0.05), from 617 +/- 78 to 491 +/- 106 ml/min X m2. While volume expansion alone had no effect on mean arterial pressure, the combination of blood volume expansion and nitroglycerin resulted in a marked resistance to the hypotensive effect of nitroglycerin. Cardiac index, pulmonary capillary wedge pressure, and oxygen utilization were not significantly different from baseline values when volume expansion preceded nitroglycerin. We conclude that the ease with which nitroglycerin reduces blood pressure is dependent on the individual patient's volume status. Although volume expansion allows one to maintain cardiac index, pulmonary capillary wedge pressure, and oxygen utilization when used in combination with nitroglycerin, this benefit may be offset by a concomitant reduction in hypotensive capability.     

The Trend,Feasibility, and Safety of Salpingectomy as a form of Permanent Sterilization

Study ObjectiveTo assess the change in the rate of laparoscopic salpingectomy for sterilization after the release of the November 2013 Society of Gynecologic Oncology Clinical Practice Statement and the January 2015 American College of Obstetricians and Gynecologists Committee Opinion: Salpingectomy for Ovarian Cancer Prevention. We hypothesized there would be an increase in salpingectomy as a percentage of total laparoscopic sterilizations performed without an increase in complications when compared with conventional bilateral tubal ligation (BTL).DesignA retrospective cohort study.SettingFour university-affiliated hospitals in Houston, TX, and New York, NY.PatientsAll women 21 years or older who underwent interval laparoscopic permanent sterilization between April 2013 and September 2016.InterventionsSterilization by bilateral salpingectomy or conventional tubal ligation.Measurements and Main ResultsThere were 454 sterilization procedures identified; 60% were BTLs, whereas 40% were salpingectomies. The rate of use of salpingectomy significantly increased from 5% to 9% in 2013 to 2014 to 78% by 2016. There was no significant difference in intraoperative or postoperative complications or estimated blood loss. The mean procedure time was 54 minutes for salpingectomy compared with 45 minutes for BTL (p <.0001). Salpingectomy was more likely to require 3 ports compared with 2 ports for BTL (p <.0001).ConclusionsThe Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists’ support of salpingectomy for ovarian cancer prevention increased its use for sterilization. Based on this study, laparoscopic bilateral salpingectomy is a safe method of sterilization without an increase in perioperative risk compared with conventional tubal ligation. Physicians should incorporate these findings and implications when counseling patients regarding contraception and permanent sterilization.     

Second trial drugs in ovarian cancer.

Three hundred forty-seven patients received a second trial of chemotherapy for progressing ovarian carcinoma. A complete or partial respond to the second trial of chemotherapy was noted in only 6.1% of patients. No change in the disease was noted in 12.6%, and resistance to second trial chemotherapy with progressing disease was noted in 81.3%.     

Prospective study of angiotensin II response to positional change in pregnancy-induced hypertension

The response of endogenous angiotensin II levels to positional change, lateral to supine recumbency, was investigated in a prospective study of 55 primigravid patients during the last half of pregnancy. Blood samples were obtained in the lateral and supine recumbent positions. The mean supine angiotensin II level was significantly higher between 29 and 34 weeks' gestation in those patients destined to develop pregnancy-induced hypertension than in those who remained normotensive (P < 0.05). As gestation advanced, the mean per cent relative change of angiotensin II from the lateral to the supine position altered from negative to positive in those patients destined to develop pregnancy-induced hypertension, whereas it remained negative in those patients who remained normotensive. These findings are discussed in relation to pathophysiologic alterations in the development of pregnancy-induced hypertension.     

Intrapartum to postpartum changes in colloid osmotic pressure

A study was undertaken to determine the effect of route of delivery on plasma colloid osmotic pressure. Plasma colloid osmotic pressure was measured on admission to the hospital and 8 to 24 hours post partum in 72 patients at term with uncomplicated prenatal histories. Thirty-six patients underwent uncomplicated vaginal deliveries (local anesthesia, 18; conduction anesthesia, 18) and 36 patients had cesarean sections (conduction anesthesia, 18; general anesthesia, 18). The mean (+/- SD) intrapartum colloid osmotic pressure of the overall group was 21.0 +/- 2.1 mm Hg, and it declined significantly (p less than 0.01) to 15.4 +/- 2.1 mm Hg post partum. A comparison of the intrapartum and postpartum reductions in colloid osmotic pressure between patients who underwent vaginal delivery and those who underwent cesarean section revealed no significant differences. Furthermore, the mean reductions in colloid osmotic pressure when all four groups were compared by type of anesthesia were not significantly different. Fifteen patients (20.8%) in the study had a postpartum colloid osmotic pressure of less than 13.6 mm Hg, and five (6.9%) had a postpartum colloid pressure of less than 12.5 mm Hg. Our results indicate that, for normal pregnancy, colloid osmotic pressure is uniformly lowered in the post partum and, in some cases, to levels that have been reported to be dangerously low.