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Refractory Bradycardia – a Rare Complication of Carboprost Tromethamine for Induction of Abortion

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Refractory Bradycardia – a Rare Complication of Carboprost Tromethamine for Induction of Abortion Acta Clin Croat 2016; 55:323-325 Case Report doi: 10.20471/acc.2016.55.02.21 REFRACTORY BRADYCARDIA – A RARE COMPLICATION OF CARBOPROST TROMETHAMINE FOR INDUCTION OF ABORTION Jasna Čerkez Habek1, Dubravko Habek2 and Dario Gulin1 1Department of Cardiology, Clinical Department of Internal Diseases, 2Clinical Department of Obstetrics and Gynecology, Sveti Duh University Hospital and Croatian Catholic University, Zagreb, Croatia SUMMARY – We report a fi rst case of refractory several-hour sinus bradycardia, a rare but already described side eff ect of intramuscular administration of carboprost tromethamine to induce abortion for medical indication in a patient without cardiovascular and other diseases. After administration of atropine sulfate 3x0.5 mg intravenously without eff ect, the patient‘s sinus rhythm spontaneously normalized as carboprost was eliminated from the body (it has a 3-hour half-life). It is reasonable to believe that the specifi c prostaglandin underlay the etiology of bradycardia. Key words: Prostaglandins; Carboprost tromethamine; Bradycardia; Case reports Introduction of intramuscular administration of carboprost to in- duce abortion with medical indication. Th e most common drugs in use for the induction of abortion and labor, as well as for curative obstetric hemorrhage are misoprostol, gemeprost, sulprostone, Case Report dinoprost and carboprost tromethamine. Th ese drugs A 32-year-old pregnant woman was hospitalized at can be used either intravenously, intramuscularly, per Department of Obstetrics because of preterm prema- os, vaginally or rectally. Carboprost is a synthetic pros- ture rupture of membranes (PPROM) with anhy- taglandin analogue of PGF2 that causes myometrial dramnios and intrauterine fetal death in 20th week of contractions by binding to the prostaglandin E2 re- ceptor. Th e known side eff ects of exogenous prosta- gestation. Obstetric history revealed two pregnancies glandins are irritability, nausea, vomiting, diarrhea, with two term births with normal neurocognitive de- coughing, dyspnea, asthma, hypertension, fl ushing, velopment. Th e course of the current pregnancy was and pyrexia. Contraindications include obstructive otherwise normal and microbiological cervical swabs lung disease and clinically relevant infl ammatory dis- were negative for pathogens. From the family history it ease. Cardiovascular side eff ects, albeit rare, mainly oc- was noted that her father had died from myocardial cur alongside cardiovascular collapse1-3. infarction, but her mother was healthy. Personal his- We report a fi rst case of refractory several-hour si- tory was unremarkable; she works as a trader, denied nus bradycardia, a rare but already described side eff ect drug use, and smoked 10 cigarettes per day prior to pregnancy. On admission, regular vital functions were recorded including normal temperature, pulse, and Correspondence to: Prof. Jasna Čerkez Habek, MD, PhD, Depart- blood pressure. Laboratory tests (hematologic, coagu- ment of Cardiology, Clinical Department of Internal Diseases, lation, biochemical including C-reactive protein) were Sveti Duh University Hospital, Sveti Duh 64, HR-10000 Zagreb, Croatia within the reference range. Obstetric examination E-mail: [email protected] evaluated patency of the cervical canal to 2 cm. Ultra- Received December 4, 2014, accepted November 23, 2015 sound confi rmed the initial diagnosis. Acta Clin Croat, Vol. 55, No. 2, 2016 323 Jasna Čerkez Habek et al. Refractory bradycardia – a rare complication of carboprost tromethamine Given the fi ndings, the patient was explained the continuous ECG recording and echocardiographic ex- possible risks of therapy and consent was obtained for amination, both of which were unremarkable, she was the induction of labor with a 0.25 mg intramuscular discharged with recommendation to do clinical ex- dose of the prostaglandin carboprost thromethamine amination after one month. Follow up cardiologist ex- (Prostin 15 M®, Pfi zer). Antibiotic prophylaxis was amination performed one month later showed normal achieved with ampicillin intravenous 1 g/6 h. Half an cardiac status. hour after the fi rst injection of carboprost, the patient was cold, sweaty, weak, and felt urgent need to defecate. Discussion With the help of a midwife, she went to the toilet but collapsed. Th e midwife could not palpate the pulse, Th e eff ects of prostaglandins on the cardiovascular and she lied the patient on the fl oor, put her in Tren- system are rare, but can be dramatic. Bradycardia and delenburg’s position, and called a doctor. Upon arrival, hypotension caused by exogenous prostaglandin was the doctor palpated pulse of 35/min on radial artery. Th e described in experimental pharmacology (e.g., on cats), patient was somnolent, complaining of painless discom- and the mentioned complications were inhibited by fort in the chest. Her vital parameters showed oxygen use of meclofenamic acid4. Hainsworth5 has described saturation of 90% and blood pressure of 90/50 mm Hg. the possible pathophysiological mechanism of brady- Immediate intravenous infusion of Ringer’s lactate cardia and hypotension on endogenous bradykinin was administered, but she was still bradycardic. After 5 and prostaglandins due to the eff ects on chemosensi- minutes, a 0.5 mg dose of atropine was administered tive ventricular mechanoreceptors and coronary baro- intravenously, successfully raising the pulse to 50/min. receptors. Hintze6 has described vasoactive eff ects of Th e elevation in heart rate was only transient, as it prostaglandin with refl ex bradycardia and hypotension dropped soon to 30/min. Th e patient was administered due to stimulation of cardiac receptors predominantly 500 mL of colloid solution (HAES) and transferred to in the inferoposterior wall of the left ventricle. the Intensive Care Unit (ICU). In the ICU, her blood Vagal bradycardia as an eff ect of prostaglandins pressure was 100/60 mm Hg and her electrocardio- due to activation of cardiac refl ex sensitivity to myo- gram (ECG) showed sinus bradycardia of 30/min. No cardial ischemia has been described by Staszewska- other abnormalities, including abnormal atrioventric- 7 ular conduction, were detected on ECG. Another 0.5 Barczak . However, only a few papers describe the mg dose of atropine was administered intravenously. negative cardiovascular eff ects of prostaglandins in ob- Th e possible embolic events and acute coronary syn- stetrics. Vasospastic angina pectoris with bradycardia drome were excluded by laboratory analysis of D-di- after induction of labor with mifepristone and ge- mer, troponin and creatine phosphokinase (MB frac- meprost in pregnant women with migraine and smok- 1 tion). One hour after arrival, repeat ECG still showed ing history has been described by Lindhardt et al. Th e sinus bradycardia without any eff ect of three repeated authors suggest taking careful history of the possible 0.5 mg doses of intravenous atropine. Blood pressure vasospastic disease in women as the prevention of seri- was maintained at 110/70 mm Hg with the adminis- ous cardiac complications. tration of colloids and crystalloids. Two works report on cardiac arrest after adminis- While in the ICU, the pregnant patient felt strong tration of sulprostone. In the fi rst one, arrest occurred contractions and quickly delivered a dead embryo with upon the intravenous use of sulprostone after cesarean the placenta en bloc. Ultrasound showed a blank empty section due to postpartum hemorrhage with successful uterine cavity and obstetric procedure ended. Prophy- resuscitation. Th e authors emphasize the potential im- lactic use of ampicillin was continued. Half an hour pact of sulprostone on coronary spasm, bradycardia, after delivery, a heart rate increase to 50/min was not- and asystole2. Th e other describes cardiac arrest in a ed, and then to 60/min after one hour. Follow up labo- 39-year-old woman in labor after the application of ratory fi ndings were normal, except for mild leukocy- sulprostone into the uterine cavity because of postpar- tosis to 12.3 (the possible side eff ect of prostaglandin). tum hemorrhage following manual removal of the pla- With continuous monitoring, the patient had no more centa. Resuscitation took a long time, but was success- episodes of bradycardia or hypotension. After 24-hour ful. Evidence in the literature suggests that sulprostone 324 Acta Clin Croat, Vol. 55, No. 2, 2016 Jasna Čerkez Habek et al. Refractory bradycardia – a rare complication of carboprost tromethamine is contraindicated in women who are older than 35 2. Lampati L, Colantonio LB, Calderini E. Cardiac arrest during years, smoke, or have other cardiovascular risk factors3. sulprostone adminisatration – a case report. Acta Anaesthesiol Scand. 2013;57:395-7. With the exception of smoking outside of preg- nancy, our patient had no major risk factors for devel- 3. Beerendonk CC, Massuger LF, Lucassen AM, Lerou JG, van den Berg PP. Circulatory arrest following sulprostone adminis- oping cardiovascular side eff ects. Considering that the tration in postpartum hemorrhage. Ned Tijdschr Geneeskd. patient’s sinus rhythm spontaneously normalized as 1998;142:195-7. carboprost was eliminated from the body (it has a 4. Koss MC, Nakano J, Rieger JA. Inhibition of prostaglandin F2 3-hour half-life), it is reasonable to believe that the alpha-induced refl ex bradycardia and hypotension by meclofe- specifi c prostaglandin underlay the etiology of brady- namic acid. Prostaglandins. 1976;11:691-8. cardia. 5. Hainsworth R. Cardiovascular
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