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Acute myocardial infarction associated with prostaglandin
Acute myocardial infarction associated with prostaglandin E2 WilliamJ. Meyer, MD, Steven L. Benton, MD, Timothy J. Hoon, PharmD, Daniel W. Gauthier, MD, and Valerie E. Whiteman, MD
Chicago, Illinois Prostaglandin E2 is rarely associated with serious maternal side effects when used for second· trimester pregnancy termination. Acute myocardial infarction complicating therapeutic pregnancy termination with prostaglandin E2 in a patient with chroniC glomerulosclerosis and severe hypertension is reported. (AM J OBSTET GVNECOL 1991 ;165:359·60.)
Key words: Prostaglandin E2 , myocardial infarction, pregnancy termination Prostaglandin E2 (PGE 2 ) is the preferred agent for second-trimester pregnancy termination, replacing instrumented evacuation of the uterus and intraamniotic irtiection of abortifacient agents. It is also useful for cervical ripening and induction of labor in pregnancies complicated by serious maternal illness. Side effects are usually mild and include nausea, vomiting, pyrexia, diarrhea, and occasionally hypotension. We report a case of severe hypotension and acute myocardial infarction associated with PGE 2 in a patient undergoing therapeutic termination of pregnancy. Case report A 38-year-old black woman, gravida 3, para 0-0-2-0, with chronic hypertension and renal insufficiency as a result of chronic glomerulosclerosis was seen by her physician with a 2-day history of symptoms consistent with congestive heart failure. Obstetric history was remarkable for two fetal deaths at 27 weeks' gestation because of preeclampsia. Initial evaluation revealed a blood pressure of2601140 mm Hg, bilateral rales, pretibial edema, and hyperreflexia. Electrocardiogram demonstrated normal sinus rhythm with a rate of 85 beats/min. Mild cardiomegaly and slight pulmonary edema were present on chest x-ray film. Echocardiogram revealed moderate concentric left ventricular hypertrophy with mild global hypokinesis. A gestation of 19 weeks was estimated by ultrasonography. Significant laboratory values included blood urea nitrogen, 51 gm/24 hours; creatinine, 5.0 mg/dl; hemoglobin, 6.7 gm/ dl; and uric acid, 6.1 mg! dl. Liver function test results and platelet count were normal. Magnesium sulfate was given, a nitroprusside infusion was started, and the patient was transported to our hospital with the diagnosis of possible superimposed preeclampsia. From the Division of Maternal-Fetal Medicine and the Section of Cardiology, University of Illinois at Chicago. Received for publication December 14, 1990; accepted March 1,
1991. Reprint requests: William J. Meyer, MD, Department of Obstetrics and Gynecology, University of Illinois at Chicago, 840 S. Wood St. MIC 808, Chicago,IL 60612. 611 129182
The nitroprusside was subsequently gradually withdrawn in our intensive care unit, and the patient was stabilized on a regimen of a hydralazine infusion with intermittent intravenous methyldopa and furosemide. Hemoglobin was increased to 9.4 gm/ dl after a transfusion of 2 units of packed red blood cells. Liver function test results, platelet count, and urine output remained normal, with a urine protein of 2.3 gm/24 hours. Two days after admission, a therapeutic termination of pregnancy was requested by the patient after she was counseled regarding the maternal risk of continuing the pregnancy. A 20 mg PGE 2 vaginal suppository was administered while the patient was continuously monitored in the cardiac care unit. Blood pressure was 180/98 mm Hg while she was receiving a hydralazine infusion of 8 mg/hr with no other antihypertensives (except intravenous furosemide) given within the previous 22 hours. Approximately 30 minutes after administration, the patient became hypotensive with bradycardia, and she experienced cardiovascular coliapse. Rhythm strips documented transient complete heart block followed by ventricular fibrillation. The heart was defibrillated, and she was then stabilized with vasopressors, lidocaine, an intraaortic balloon pump, and ventilatory support. A 12-1ead electrocardiogram revealed an acute inferior wall myocardial infarction, which correlated with a new inferior wall hypokinesis on repeat echocardiogram. Cardiac catheterization revealed angiographically normal coronary arteries. Hemodynamic status improved rapidly, and the patient was off assisted ventilation, balloon pump, and vasopressors within 24 hours. Spontaneous delivery of the fetus occurred 8 hours after the myocardial infarction. Urine output was maintained with only slight elevation of the· creatinine level to 7 mg / dl, and recrudescent hypertension was controlled with oral medications. The remainder of the hospital course was uncomplicated. Comment
Severe cardiovascular complications associated with PGE 2 are rare. PGE 2 is rapidly absorbed after vaginal administration and can produce hypotension as a result of direct arteriolar vasodilation. Sampson et al. ' re-
359
Meyer et al.
ported a mild decrease in mean arterial pressure after PGE 2 administration for mid trimester pregnancy termination in patients with severe preeclampsia receiving antihypertensive agents. None of these patients had serious complications. The time interval between PGE 2 administration and the circulatory collapse and myocardial infarction in our patient would imply a relationship between these events. Preexisting coronary artery disease did not complicate this case. We propose that PGE 2 acted synergistically with the antihypertensive therapy to cause profound hypotension, resulting in coronary hypoperfusion and myocardial infarction. PGE 2 has a short biologic half-life, and the rapid recovery from cardiovascular shock observed in this case also is compatible with
August 1991 Am J Obstet Gynecol
a causal relationship. PGE 2 -induced coronary artery spasm seems unlikely because it has been shown to possess coronary artery relaxant effects." In any case PGE 2 should be used with caution in patients receiving vasoactive antihypertensive medications, especially when preexisting cardiac disease or risk factors are present.
REFERENCES 1. Sampson MB, ThomasonJL, Tomasi AM, Work BA. Pregnancy termination in patients with pregnancy-induced hypertension or eclampsia at less than 22 weeks' gestation. AM J OBSTET GYNECOL 1982;143:474-5. 2. Schror K, Berg-Becker M, Nookhwun C. The specificity of prostaglandin E2 (PGE2) in reducing coronary vascular resistance: a comparison with adenosine. Basic Res Cardiol 1978;73:287-97.
CA 125 regression: A model for epithelial ovarian cancer response Richard E. Buller, MD, PhD, Michael L. Berman, MD, Jeffrey D. Bloss, MD, Alberto Manetta, MD, and Philip J. DiSaia, MD Orange, California, and Iowa City, Iowa The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - 8 (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas 8, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regreSSion curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case 8 = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (8 = 0.0671) is more effective than low-dose cisplatin (8 = 0.0380) (p < 0.03) in eliminating residual cancer. Because 8 can be calculated within 2 to 3 months of treatment and then compared with 8 for the ideal regression curve and with the values of 8 reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method. (AM J OSSTET GYNECOL 1991 ;165:360-7.)
Key words: CA 125, exponential regression, chemotherapy Ovarian carcinoma is the fourth most common cause of death among American women. 1 Aggressive surgical From the Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology, University of California, Irvine, Medical Center, and the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Iowa. Received for publication February 15, 1991 .. accepted February 27, 1991. Reprint requests: Richard E. Buller, MD, PhD, The University of Iowa, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Iowa City, IA 52242. 6/112921J
360
cytoreduction and subsequent cisplatin-based chemotherapy have helped prolong disease-free survival for women with advanced disease. 1.2 Our ability to monitor disease status during therapy has been facilitated by measurement of the tumor-associated antigen CA 125. Bast et al.' and others4 • 5 have shown that changes in serum CA 125 levels reflect progression or regression of epithelial ovarian cancer >90% of the time. That is to say, increases in serum CA 125 levels reflect disease progression whereas declines in serum CA 125 levels reflect a response to therapy. Thus by monitoring CA
Chicago, Illinois Prostaglandin E2 is rarely associated with serious maternal side effects when used for second· trimester pregnancy termination. Acute myocardial infarction complicating therapeutic pregnancy termination with prostaglandin E2 in a patient with chroniC glomerulosclerosis and severe hypertension is reported. (AM J OBSTET GVNECOL 1991 ;165:359·60.)
Key words: Prostaglandin E2 , myocardial infarction, pregnancy termination Prostaglandin E2 (PGE 2 ) is the preferred agent for second-trimester pregnancy termination, replacing instrumented evacuation of the uterus and intraamniotic irtiection of abortifacient agents. It is also useful for cervical ripening and induction of labor in pregnancies complicated by serious maternal illness. Side effects are usually mild and include nausea, vomiting, pyrexia, diarrhea, and occasionally hypotension. We report a case of severe hypotension and acute myocardial infarction associated with PGE 2 in a patient undergoing therapeutic termination of pregnancy. Case report A 38-year-old black woman, gravida 3, para 0-0-2-0, with chronic hypertension and renal insufficiency as a result of chronic glomerulosclerosis was seen by her physician with a 2-day history of symptoms consistent with congestive heart failure. Obstetric history was remarkable for two fetal deaths at 27 weeks' gestation because of preeclampsia. Initial evaluation revealed a blood pressure of2601140 mm Hg, bilateral rales, pretibial edema, and hyperreflexia. Electrocardiogram demonstrated normal sinus rhythm with a rate of 85 beats/min. Mild cardiomegaly and slight pulmonary edema were present on chest x-ray film. Echocardiogram revealed moderate concentric left ventricular hypertrophy with mild global hypokinesis. A gestation of 19 weeks was estimated by ultrasonography. Significant laboratory values included blood urea nitrogen, 51 gm/24 hours; creatinine, 5.0 mg/dl; hemoglobin, 6.7 gm/ dl; and uric acid, 6.1 mg! dl. Liver function test results and platelet count were normal. Magnesium sulfate was given, a nitroprusside infusion was started, and the patient was transported to our hospital with the diagnosis of possible superimposed preeclampsia. From the Division of Maternal-Fetal Medicine and the Section of Cardiology, University of Illinois at Chicago. Received for publication December 14, 1990; accepted March 1,
1991. Reprint requests: William J. Meyer, MD, Department of Obstetrics and Gynecology, University of Illinois at Chicago, 840 S. Wood St. MIC 808, Chicago,IL 60612. 611 129182
The nitroprusside was subsequently gradually withdrawn in our intensive care unit, and the patient was stabilized on a regimen of a hydralazine infusion with intermittent intravenous methyldopa and furosemide. Hemoglobin was increased to 9.4 gm/ dl after a transfusion of 2 units of packed red blood cells. Liver function test results, platelet count, and urine output remained normal, with a urine protein of 2.3 gm/24 hours. Two days after admission, a therapeutic termination of pregnancy was requested by the patient after she was counseled regarding the maternal risk of continuing the pregnancy. A 20 mg PGE 2 vaginal suppository was administered while the patient was continuously monitored in the cardiac care unit. Blood pressure was 180/98 mm Hg while she was receiving a hydralazine infusion of 8 mg/hr with no other antihypertensives (except intravenous furosemide) given within the previous 22 hours. Approximately 30 minutes after administration, the patient became hypotensive with bradycardia, and she experienced cardiovascular coliapse. Rhythm strips documented transient complete heart block followed by ventricular fibrillation. The heart was defibrillated, and she was then stabilized with vasopressors, lidocaine, an intraaortic balloon pump, and ventilatory support. A 12-1ead electrocardiogram revealed an acute inferior wall myocardial infarction, which correlated with a new inferior wall hypokinesis on repeat echocardiogram. Cardiac catheterization revealed angiographically normal coronary arteries. Hemodynamic status improved rapidly, and the patient was off assisted ventilation, balloon pump, and vasopressors within 24 hours. Spontaneous delivery of the fetus occurred 8 hours after the myocardial infarction. Urine output was maintained with only slight elevation of the· creatinine level to 7 mg / dl, and recrudescent hypertension was controlled with oral medications. The remainder of the hospital course was uncomplicated. Comment
Severe cardiovascular complications associated with PGE 2 are rare. PGE 2 is rapidly absorbed after vaginal administration and can produce hypotension as a result of direct arteriolar vasodilation. Sampson et al. ' re-
359
Meyer et al.
ported a mild decrease in mean arterial pressure after PGE 2 administration for mid trimester pregnancy termination in patients with severe preeclampsia receiving antihypertensive agents. None of these patients had serious complications. The time interval between PGE 2 administration and the circulatory collapse and myocardial infarction in our patient would imply a relationship between these events. Preexisting coronary artery disease did not complicate this case. We propose that PGE 2 acted synergistically with the antihypertensive therapy to cause profound hypotension, resulting in coronary hypoperfusion and myocardial infarction. PGE 2 has a short biologic half-life, and the rapid recovery from cardiovascular shock observed in this case also is compatible with
August 1991 Am J Obstet Gynecol
a causal relationship. PGE 2 -induced coronary artery spasm seems unlikely because it has been shown to possess coronary artery relaxant effects." In any case PGE 2 should be used with caution in patients receiving vasoactive antihypertensive medications, especially when preexisting cardiac disease or risk factors are present.
REFERENCES 1. Sampson MB, ThomasonJL, Tomasi AM, Work BA. Pregnancy termination in patients with pregnancy-induced hypertension or eclampsia at less than 22 weeks' gestation. AM J OBSTET GYNECOL 1982;143:474-5. 2. Schror K, Berg-Becker M, Nookhwun C. The specificity of prostaglandin E2 (PGE2) in reducing coronary vascular resistance: a comparison with adenosine. Basic Res Cardiol 1978;73:287-97.
CA 125 regression: A model for epithelial ovarian cancer response Richard E. Buller, MD, PhD, Michael L. Berman, MD, Jeffrey D. Bloss, MD, Alberto Manetta, MD, and Philip J. DiSaia, MD Orange, California, and Iowa City, Iowa The rate of decline of CA 125 in effectively treated epithelial ovarian cancer is described by the exponential regression curve CA 125 = EXP [i - 8 (days after surgery)]. In this equation i, the y-axis intercept, measures initial tumor burden whereas 8, the slope of the regression curve, is determined by the extent of cytoreductive surgery and the subsequent response to chemotherapy. Departure from the regreSSion curve uniformly results in progressive disease. In patients whose cancers had been completely removed, we calculated the mean half-life of CA 125 to be 10.4 days (range 4 to 21). In this case 8 = 0.0835 and characterizes the ideal regression rate. The model predicts that high-dose cisplatin chemotherapy (8 = 0.0671) is more effective than low-dose cisplatin (8 = 0.0380) (p < 0.03) in eliminating residual cancer. Because 8 can be calculated within 2 to 3 months of treatment and then compared with 8 for the ideal regression curve and with the values of 8 reported for standard chemotherapy, evaluation of any new treatment protocol can be facilitated with this method. (AM J OSSTET GYNECOL 1991 ;165:360-7.)
Key words: CA 125, exponential regression, chemotherapy Ovarian carcinoma is the fourth most common cause of death among American women. 1 Aggressive surgical From the Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology, University of California, Irvine, Medical Center, and the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Iowa. Received for publication February 15, 1991 .. accepted February 27, 1991. Reprint requests: Richard E. Buller, MD, PhD, The University of Iowa, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Iowa City, IA 52242. 6/112921J
360
cytoreduction and subsequent cisplatin-based chemotherapy have helped prolong disease-free survival for women with advanced disease. 1.2 Our ability to monitor disease status during therapy has been facilitated by measurement of the tumor-associated antigen CA 125. Bast et al.' and others4 • 5 have shown that changes in serum CA 125 levels reflect progression or regression of epithelial ovarian cancer >90% of the time. That is to say, increases in serum CA 125 levels reflect disease progression whereas declines in serum CA 125 levels reflect a response to therapy. Thus by monitoring CA