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Overdosage of misoprostol in pregnancy
Bond and Van Zee
Volume 171, Number 2 Am J Ob;tet Gynccol
teal mass separate from the recurrent pelvic masses (Fig. 1). Fine-needle apsiration of the gluteal lesion documented metastatic adenocarcinoma consistent with the primary tumor. Currently the patient is alive with persistent disease.
Comment Despite the large volume of skeletal muscle. which represents 50% of total body mass, both primary and metastatic tumors in skeletal muscle are rare.' Previously most striated muscle metastases were thought to represent contiguous invasion of the primary tumor. Striated muscle metastases confirmed at biopsy have been reported in cases of primary chest, head and neck, breast, eosphagus, kidney, uterus, ovary, prostate, and lymph node tumors. CT has improved detection and assessment of the extent of secondary skeletal muscle tumors in patients with pain in the area of the muscle involvement or a palpable mass." Magnetic resonance imaging has even greater soft-tissue contrast resolution
than CT and may be useful to better define extent if local palliative therapy were to be contemplated. To our knowledge only one previous example of ovarian carcinoma striated muscle metastasis (to the psoas muscle, also in the absence of contiguous spread) has been reported." The CT appearance of our patient's le~ion differed from the previously described case in which the lesion was of predominantly low attenuation with respect to muscle." The metastasis shown in Fig. 1 is of intermediate to increased attenuation with respect to muscle. Our case also illustrates the contribution of CT in documenting the presence of an unusual asymptomatic skeletal muscle metastasis of ovarian carcinoma. REFERENCES 1. Rose PG. Piver S, Tsukada Y, Lau 1'. Metastatic patterns m histologic variants of ovarIan cancer: an autopsy study. Cancer 1989;64:1508-13. 2. Schulz SR, Bree RL, Schwab RE, Raiss G. CT detection of skeletal muscle metastases.] Comput A"ist Tomogr 1986; 10:81-3.
Overdosage of misoprostol in pregnancy G. Randall Bond, MD," and Art Van Zee, MDb Charlottesvtlle and St. Charles, VirKmia We report the clinical course of a woman 31 weeks pregnant who ingested misoprostol (a prostaglandin E, analog, Cytotek, used to prevent gastric ulcer) and trifluoperazine (Stelazine). Manifestations of toxicity included hypertonic uterine contraction with fetal death, hyperthermia, rhabdomyolysis, hypoxemia, respiratory alkalosis, and metabolic aCidosis. We are concerned that misoprostol may be used as an lIicit abortifacient. (AM J OBSTET GYNECOL 1994;171:561-2.)
Key words: Misoprostol. pregnancy, overdosage
Misoprostol (Cytotek, Searle. Chicago), a prostaglandin E] analog, has been introduced in the United States for prevention of gastric ulcer in high-risk patients requiring long-term nonsteroidal antiinflammatory drug therapy. Very little experience has been reported after overdosage. We observed a woman who intentionally overdosed in the third trimester of pregnancy. Flam the DI1I!SIOII of Clulleal PharmalOlogy. Departmmt of III tt'l lIal MediCIne, UmvPrslt)' of l'/rglma Sthool of Medlllne," and the St. Chmles Commumtv Health Cmter.' ReceIved for publzctltlOrl December 3, 1993, leV/led December 20, 1993; accepted February 22, 1994. Repnnt, not avmlable from the alith0/5. CopYright © 1994 hy MOIb)'-Year Book, 11/(. ()002-9378/94 $3.00 + 0 6/1/55348
Case report A previously healthy 19-year-old woman, gravida 3. para 1, abortion 1, at 31 weeks' gestation reportedly ingested 30 tablets of 200 fLg misoprostol and four tablets of 2 mg trifluoperazine in a suicide attempt. Subsequent to ingestion she claims to have felt fetal movement. When she was seen in the emergency department 2 hours after ingestion, she complained of feeling hot, of having chills, and of shortness of breath. She was awake, alert, oriented, and coherent but restless and in obvious discomfort. Vital signs were temperature 105.8 F, heart rate 145 beats/min, hlood pressure 120/60 mm Hg, and respiratory rate 28 beats per minute. Physical examination was remarkable for a tetanic uterus. Pelvic examination revealed cervical dilation to 5 em with 80% effacement. Membranes were intact. Laboratory values obtained at admission in0
561
562
Bond and Van Zee
cluded room air arterial blood gases, pH 7.46, Pco 2 24 mm Hg, P02 53 mm Hg, serum creatine kinase 76 U/L, serum bicarbonate 15 mmolJL, prothrombin time 11.3 seconds, and partial thromboplastin time 29.4 seconds. Treatment consisted of gastric lavage and administration of activated charcoal. One hour after her presentation to the emergency department a sonogram of the uterus revealed no fetal movement and no fetal heart motion. One hour later the patient was delivered of a dead 1800 gm fetus that was diffusely ecchymotic. By 9 hours after ingestion the patient's temperature was normal and remained so, except for an elevation to 100.8° F twice on day 3. She was otherwise without symptoms and was not treated with antibiotics. Her metabolic acidosis and hypoxemia resolved over the following several hours. Twenty-five hours after ingestion the serum creatine kinase level peaked at 5849 U/L. The medical examiner's findings on the fetus were remarkable only for the presence of diffuse head and upper body bruising.
Comment In the only other report of a misoprostol overdosage a 71-year-old woman experienced onset of symptoms (hyperthermia, tremor, tachycardia, hypertension, nausea, and abdominal cramping) within 3 hours of the ingestion of 15 200 f.Lg tablets. She also had complete resolution of symptoms by 12 hours after ingestion. I The rapid onset of symptoms and resolution over a period of < 12 hours seen in our patient is compatible with the known pharmacokinetics of misoprostol. Trifluoperazine is unlikely to have contributed to her symptoms. Hyperthermia in our patient is most likely a result of direct drug effect, although endometritis cannot be excluded. Infection was not clinically suspected, nor was specific therapy administered. Prostaglandin E] is known to cause pulmonary arterial dilation. Hypox-
August 1994 Am J Obstet Gynecol
emia may be the result of pulmonary vascular shunting or VQ mismatch. Although the patient had had intense uterine contractions, the creatine kinase elevation observed here is unlikely to be the result of myometrial damage. Uterine creatine kinase has only 2% of the activity of skeletal muscle, requiring 50 times as much muscle damage to reach the same degree of measured creatine kinase activity elevation. Because rhabdomyolysis is frequently found in association with druginduced hyperthermia, its occurrence in this patient is not surprising. Prostaglandins and prostaglandin analogs have been investigated as agents to induce labor. The dose of misoprostol has ranged from 400 f.Lg administered once to 400 f.Lg every 4 hours untillabor. 2 This dose is much lower than that ingested by this patient (6000 f.Lg). It is not surprising that tetanic uterine contraction occurred. Fetal death probably occurred as a result of hypertonic uterine contraction with compromise of placental function, but a directly fetotoxic effect of misoprostol cannot be excluded. The clinical course of this patient after misoprostol overdosage confirms the potential of misoprostol to be used as an illicit first- or second-trimester abortifacient. It is our expectation that physicians will continue to prescribe misoprostol for those who might legitimately benefit from it. Physicians should be wary of patient-initiated requests for the drug. Close monitoring should be COllsidered if misuse of misoprostol becomes a problem. REFERENCES
1. Graber Dj, Meier KH. Acute misoprostol toxicity. Ann Emerg Med 1991;20:549-51. 2. Rahe T, Basse H, Thuro H, et al. Wirkung des PGE I Methylanalogons Misoprostol auf den schwangeren Uterus im ersten Trimester. Gehurtshilfe Frauenheilkd 1987;47: 324-31.
Volume 171, Number 2 Am J Ob;tet Gynccol
teal mass separate from the recurrent pelvic masses (Fig. 1). Fine-needle apsiration of the gluteal lesion documented metastatic adenocarcinoma consistent with the primary tumor. Currently the patient is alive with persistent disease.
Comment Despite the large volume of skeletal muscle. which represents 50% of total body mass, both primary and metastatic tumors in skeletal muscle are rare.' Previously most striated muscle metastases were thought to represent contiguous invasion of the primary tumor. Striated muscle metastases confirmed at biopsy have been reported in cases of primary chest, head and neck, breast, eosphagus, kidney, uterus, ovary, prostate, and lymph node tumors. CT has improved detection and assessment of the extent of secondary skeletal muscle tumors in patients with pain in the area of the muscle involvement or a palpable mass." Magnetic resonance imaging has even greater soft-tissue contrast resolution
than CT and may be useful to better define extent if local palliative therapy were to be contemplated. To our knowledge only one previous example of ovarian carcinoma striated muscle metastasis (to the psoas muscle, also in the absence of contiguous spread) has been reported." The CT appearance of our patient's le~ion differed from the previously described case in which the lesion was of predominantly low attenuation with respect to muscle." The metastasis shown in Fig. 1 is of intermediate to increased attenuation with respect to muscle. Our case also illustrates the contribution of CT in documenting the presence of an unusual asymptomatic skeletal muscle metastasis of ovarian carcinoma. REFERENCES 1. Rose PG. Piver S, Tsukada Y, Lau 1'. Metastatic patterns m histologic variants of ovarIan cancer: an autopsy study. Cancer 1989;64:1508-13. 2. Schulz SR, Bree RL, Schwab RE, Raiss G. CT detection of skeletal muscle metastases.] Comput A"ist Tomogr 1986; 10:81-3.
Overdosage of misoprostol in pregnancy G. Randall Bond, MD," and Art Van Zee, MDb Charlottesvtlle and St. Charles, VirKmia We report the clinical course of a woman 31 weeks pregnant who ingested misoprostol (a prostaglandin E, analog, Cytotek, used to prevent gastric ulcer) and trifluoperazine (Stelazine). Manifestations of toxicity included hypertonic uterine contraction with fetal death, hyperthermia, rhabdomyolysis, hypoxemia, respiratory alkalosis, and metabolic aCidosis. We are concerned that misoprostol may be used as an lIicit abortifacient. (AM J OBSTET GYNECOL 1994;171:561-2.)
Key words: Misoprostol. pregnancy, overdosage
Misoprostol (Cytotek, Searle. Chicago), a prostaglandin E] analog, has been introduced in the United States for prevention of gastric ulcer in high-risk patients requiring long-term nonsteroidal antiinflammatory drug therapy. Very little experience has been reported after overdosage. We observed a woman who intentionally overdosed in the third trimester of pregnancy. Flam the DI1I!SIOII of Clulleal PharmalOlogy. Departmmt of III tt'l lIal MediCIne, UmvPrslt)' of l'/rglma Sthool of Medlllne," and the St. Chmles Commumtv Health Cmter.' ReceIved for publzctltlOrl December 3, 1993, leV/led December 20, 1993; accepted February 22, 1994. Repnnt, not avmlable from the alith0/5. CopYright © 1994 hy MOIb)'-Year Book, 11/(. ()002-9378/94 $3.00 + 0 6/1/55348
Case report A previously healthy 19-year-old woman, gravida 3. para 1, abortion 1, at 31 weeks' gestation reportedly ingested 30 tablets of 200 fLg misoprostol and four tablets of 2 mg trifluoperazine in a suicide attempt. Subsequent to ingestion she claims to have felt fetal movement. When she was seen in the emergency department 2 hours after ingestion, she complained of feeling hot, of having chills, and of shortness of breath. She was awake, alert, oriented, and coherent but restless and in obvious discomfort. Vital signs were temperature 105.8 F, heart rate 145 beats/min, hlood pressure 120/60 mm Hg, and respiratory rate 28 beats per minute. Physical examination was remarkable for a tetanic uterus. Pelvic examination revealed cervical dilation to 5 em with 80% effacement. Membranes were intact. Laboratory values obtained at admission in0
561
562
Bond and Van Zee
cluded room air arterial blood gases, pH 7.46, Pco 2 24 mm Hg, P02 53 mm Hg, serum creatine kinase 76 U/L, serum bicarbonate 15 mmolJL, prothrombin time 11.3 seconds, and partial thromboplastin time 29.4 seconds. Treatment consisted of gastric lavage and administration of activated charcoal. One hour after her presentation to the emergency department a sonogram of the uterus revealed no fetal movement and no fetal heart motion. One hour later the patient was delivered of a dead 1800 gm fetus that was diffusely ecchymotic. By 9 hours after ingestion the patient's temperature was normal and remained so, except for an elevation to 100.8° F twice on day 3. She was otherwise without symptoms and was not treated with antibiotics. Her metabolic acidosis and hypoxemia resolved over the following several hours. Twenty-five hours after ingestion the serum creatine kinase level peaked at 5849 U/L. The medical examiner's findings on the fetus were remarkable only for the presence of diffuse head and upper body bruising.
Comment In the only other report of a misoprostol overdosage a 71-year-old woman experienced onset of symptoms (hyperthermia, tremor, tachycardia, hypertension, nausea, and abdominal cramping) within 3 hours of the ingestion of 15 200 f.Lg tablets. She also had complete resolution of symptoms by 12 hours after ingestion. I The rapid onset of symptoms and resolution over a period of < 12 hours seen in our patient is compatible with the known pharmacokinetics of misoprostol. Trifluoperazine is unlikely to have contributed to her symptoms. Hyperthermia in our patient is most likely a result of direct drug effect, although endometritis cannot be excluded. Infection was not clinically suspected, nor was specific therapy administered. Prostaglandin E] is known to cause pulmonary arterial dilation. Hypox-
August 1994 Am J Obstet Gynecol
emia may be the result of pulmonary vascular shunting or VQ mismatch. Although the patient had had intense uterine contractions, the creatine kinase elevation observed here is unlikely to be the result of myometrial damage. Uterine creatine kinase has only 2% of the activity of skeletal muscle, requiring 50 times as much muscle damage to reach the same degree of measured creatine kinase activity elevation. Because rhabdomyolysis is frequently found in association with druginduced hyperthermia, its occurrence in this patient is not surprising. Prostaglandins and prostaglandin analogs have been investigated as agents to induce labor. The dose of misoprostol has ranged from 400 f.Lg administered once to 400 f.Lg every 4 hours untillabor. 2 This dose is much lower than that ingested by this patient (6000 f.Lg). It is not surprising that tetanic uterine contraction occurred. Fetal death probably occurred as a result of hypertonic uterine contraction with compromise of placental function, but a directly fetotoxic effect of misoprostol cannot be excluded. The clinical course of this patient after misoprostol overdosage confirms the potential of misoprostol to be used as an illicit first- or second-trimester abortifacient. It is our expectation that physicians will continue to prescribe misoprostol for those who might legitimately benefit from it. Physicians should be wary of patient-initiated requests for the drug. Close monitoring should be COllsidered if misuse of misoprostol becomes a problem. REFERENCES
1. Graber Dj, Meier KH. Acute misoprostol toxicity. Ann Emerg Med 1991;20:549-51. 2. Rahe T, Basse H, Thuro H, et al. Wirkung des PGE I Methylanalogons Misoprostol auf den schwangeren Uterus im ersten Trimester. Gehurtshilfe Frauenheilkd 1987;47: 324-31.