F. Gary Cunningham

The Parkland Memorial Hospital protocol for treatment of eclampsia: Evaluation of 245 cases☆

Since 1955, a standardized treatment regimen has been used to manage 245 cases of eclampsia at Parkland Memorial Hospital. Magnesium sulfate alone effectively controlled controlled convulsions in the great majority of cases. The only maternal death among the 245 cases reemphasizes the risk of respiratory arrest that is inherent in the administration of magnesium sulfate when given in large doses intravenously. Hydralazine to lower the diastolic blood pressure somewhat, when it was 110 mm Hg or higher, prevented intracranial hemorrhage. Avoidance of diuretics and hyperosmotic agents and limitation of fluid intake were not associated with severe renal failure. Pulmonary edema was rare. Vaginal delivery was achieved in the majority of cases. Oxytocin often proved effective for initiating and maintaining labor even remote from term. The results obtained with this regimen justify its continued clinical application.

Pulmonary injury complicating antepartum pyelonephritis

Over a 7-year period, 15 pregnant women admitted to Parkland Memorial Hospital for acute pyelonephritis developed respiratory insufficiency characterized by dyspnea, tachypnea, hypoxemia, and radiographic evidence of pulmonary infiltrates. Clinical manifestations usually appeared 24 to 48 hours after the patient was admitted and varied from mild respiratory distress to pulmonary failure in three; these three required tracheal intubation and mechanical ventilation. We found no evidence that pulmonary edema was caused by intravenous fluid overload. Oxygen therapy and ventilation were given to maintain the arterial PO2 at 80 mm Hg or greater, and erythrocyte transfusions were given to six women to correct anemia. Women with pulmonary injury were more likely to have multisystem derangement than a control group without respiratory involvement, but there were no clinical risk factors that were predictive at admission. This syndrome was probably caused by permeability pulmonary edema, likely mediated by endotoxin-induced alveolar-capillary membrane injury since other evidence of endotoxemia was common. Thrombocytopenia, hemolysis, intravascular coagulation, renal dysfunction, and transient cardiomegaly concomitant with hyperdynamic ventricular function are all explicable from endotoxin effects.

Renal infection and pregnancy outcome

To evaluate the impact of renal infection on pregnancy outcome, we studied a group of pregnant women with asymptomatic renal bacteriuria and another group who had acute pyelonephritis. In 248 women with asymptomatic bacteriuria, infection was localized by the antibody-coated bacteria method. These women were prospectively matched with abacteriuric control subjects and we found no adverse effects of treated renal or bladder infection. Specifically, the number of women with hypertension and anemia in each group was similar, and infants born to these women were comparable regarding perinatal mortality, mean gestational age, and birth weight, as well as indices of maturity. A total of 487 women with acute pyelonephritis were evaluated in a case-control study and observations of the correlation of maternal anemia and pyelonephritis were confirmed. Women with antepartum infection had no increased adverse perinatal outcome; however, in some women with intrapartum infection, pyelonephritis appeared to have initiated premature labor. We concluded that treated renal infection, whether symptomatic or asymptomatic, does not significantly modify pregnancy outcome.

Bacteremia and Septic Shock

Regardless of the site of infection, pathogenic microbes may enter the bloodstream and cause septic shock, which is a life-threatening syndrome characterized by hypotension, inadequate tissue perfusion, hypoxia, and metabolic acidosis. Circulatory insufficiency is initiated by bacteremia or by by-products of killed bacteria that cause cellular injury, activation of complement and coagulation, and release of vasoactive compounds. A presumptive diagnosis of septic shock is made when hypotension is preceded by chills and fever in association with tachycardia, tachypnea, oliguria, or mental obtundation.

Moxalactam for obstetric and gynecologic infections: In vitro and dose-finding studies

Moxalactam (LY 127935), a third-generation beta-lactam antimicrobial, has been shown to have promising in vitro activity against a wide spectrum of pathogens similar to those isolated from women with pelvic infections. Pharmacodynamic studies have shown that its serum half life is longer than 2 hours, which permits less frequent dosing. The current investigation was carried out in two parts: In the first phase, the minimal inhibitory concentration of moxalactam against 519 clinical isolates was determined and compared to antimicrobials used in infections caused by these microbes. In vitro activity of moxalactam comparable to that of clindamycin was demonstrated against B. fragilis and other Bacteroides species. There was similar activity to penicillin G and clindamycin against anaerobic gram-positive cocci and activity superior to amikacin was demonstrated against Enterobacteriaceae. The second part of this investigation was a clinical one and 100 women with pelvic infections were given treatment with moxalactam. With an initial dose of 3 gm/day, women with posthysterectomy cellulitis and pelvic inflammatory disease did well. Women with pelvic infections following cesarean section responded less readily to this dose; however, when the initial dose was increased to 6 gm/day, a 91% cure rate was effected. The results of these investigations indicate that moxalactam is useful as a single-agent antimicrobial for treatment of polymicrobial female pelvic infection.

Treatment of obstetric and gynecologic infections with cefamandole

Cefamandole nafate is a derivative of 7-aminocephalosporanic acid which has been shown to have good in vitro activity against aerobes traditionally susceptible to cephalosporins as well as many anaerobes, including B. fragilis. One hundred women with obstetric or gynecologic infections completed treatment with cefamandole: 53 had post-cesarean section infections: 24, acute pelvic inflammatory disease: 16, posthysterectomy cuff cellulitis/abscess; and seven, vulvar or abdominal wound abscess. Almost 90% of these women had either polymicrobial aerobic/anaerobic bacterial infections or an anaerobic infection alone. Ninety women responded to cefamandole alone; in 10 cases chloramphenicol was added, but in addition five of these women required surgical therapy for eradication of infection. Mild to severe phlebitis at the infusion site that responded to conservative therapy was demonstrated in 14 women. Of 312 bacterial isolates from these women, 89% were sensitive to cefamandole at 32 microgram/ml, an easily achievable serum level; 93% of anaerobic streptococci, the most common isolates, were sensitive at 32 microgram/ml. Also, 90% of all Bacteroides species were susceptible at 32 microgram/ml; 82% of B. fragilis were susceptible at this concentration. These data indicate that cefamandole is safe and effective for treatment of women with polymicrobial pelvic infections but that approximately 5% of these women will require surgical exploration in addition to antimicrobial administration.

High pressure liquid chromatographic assay of cefamandole in serum following intravenous and intraperitoneal administration

Abstract Following cesarean section 102 women were treated with cefamandole by either perioperative intravenous administration or intraperitoneal irrigation. High-pressure liquid chromatographic (HPLC) methods for the quantitation of the low serum levels of cefamandole following intraperitoneal lavage were developed. The antibiotic was assayed in the serum using a standard microbiological assay and two types of reverse phase column technology for HPLC. The two HPLC systems were almost identical in performance. Both HPLC methods were at least 10-fold more sensitive than the microbiological assay. The correlation between the three methods was 0.9739. The half-life of cefamandole was 37 min, which was not significantly different from the half-life of the drug in serum of non-pregnant women. The peak serum levels were 47.6 ± 36.8 μg/ml and 1.98 ± 1.5 μg/ml for the intravenous and intraperitoneal methods of administration, respectively.

Chapter 20 – Clinical Management

The final chapter of the fourth edition summarizes management of gestational hypertension with a focus on the preeclampsia syndrome. The importance of preeclampsia as a multisystem disorder is emphasized, with the goal of arriving at management interventions that are based on scientific observations that describe the pathophysiology of the syndrome. Over the past three decades there has been an unprecedented accrual of high-quality evidence-based studies that underpin clinical management of the woman and her fetus in pregnancies complicated by severe preeclampsia or eclampsia. In that regard, this chapter describes management principles that are based on many of the scientific and clinical observations elucidated in the preceding 19 chapters.

Chapter 21 – Management

Publisher Summary nManagement of preeclampsia depends upon its severity as well as the gestational age at which it becomes clinically apparent. While in most cases, diagnosis is made by the appearance of new-onset gestational hypertension accompanied by proteinuria, observations over the last two decades—which are discussed in detail in other chapters— have emphasized the importance of endothelial cell injury and multiorgan dysfunction as integral parts of the preeclampsia syndrome. The basic management objectives for any pregnancy complicated by preeclampsia are: termination of pregnancy with the least possible trauma to mother and fetus, birth of an infant who subsequently thrives, and complete restoration of health to the mother. In certain women with preeclampsia, especially those at or near term, all three objectives are served equally well by induction of labor. One of the most important clinical questions for successful management is precise knowledge of the age of the fetus.