Massive pulmonary embolism in a pregnant woman with an excellent response to early thrombolytic therapy

Transcription

1 Hong Kong Journal of Emergency Medicine Massive pulmonary embolism in a pregnant woman with an excellent response to early thrombolytic therapy 孕婦大塊肺栓塞早期溶栓治療有優良的效果 DB Petrov, AI Peneva, MH Milanova Thrombolytic agents have been used successfully to treat patients with massive pulmonary embolism and cardiorespiratory insufficiency. Experience with these drugs in pregnancy is limited, nevertheless. We report a 32-year-old pregnant female, who was at 16 weeks of gestation, presented with acute collapse and progressive dyspnea caused by massive pulmonary embolism. The diagnosis was rapidly made in the emergency department with two dimensional-doppler echocardiography that showed signs of right ventricular dysfunction and pulmonary hypertension, as well as direct visualisation of large thrombus at the bifurcation of the main pulmonary artery. Because of significant haemodynamic instability and no improvement after intravenous heparin, the patient was successfully treated with recombinant tissue plasminogen activator and low-molecularweight heparin. The response to fibrinolytic therapy was excellent without haemorrhagic complications and a healthy child was born at term. We conclude that early thrombolytic therapy may be a reasonable treatment for pregnant patients with unstable pulmonary embolism. (Hong Kong j.emerg.med. 2014;21: ) 溶栓藥物治療大塊肺栓塞及心肺功能不全的患者已有成功的先例 不過 妊娠期使用這些藥物的經驗有 限 我們報告一例懷孕 16 週的 32 歲女性 因大塊肺栓塞出現急性昏倒和進行性呼吸困難 急診科作出 了迅速診斷 二維多普勒超聲心動圖顯示右心室功能不全和肺動脈高壓 在主肺動脈分叉處直接可見大 塊血栓 靜脈注射肝素後無改善 血流動力學顯著不穩定 因而改用重組組織型纖溶酶原激活劑和低分 子量肝素成功治療患者 溶栓治療的效果優良 沒有併發出血 孩子健康足月出生 我們的結論是肺栓 塞病情不穩的懷孕患者 早期溶栓治療可能是合理的治療方案 Keywords: Anticoagulants, fibrinolytic therapy, human, pregnancy, venous thromboembolism 關鍵詞 抗凝劑 溶栓治療 人類 懷孕 靜脈血栓栓塞 Introduction Pulmonary embolism (PE) is the leading cause of maternal mortality in the developed world. Mortality Correspondence to: Daniel Bogdanov Petrov, MD, FESC Pirogov Emergency Hospital, Department of Emergency Cardiology and Acute Internal Diseases, 21 Totleben Ave., Sofia 1606, Bulgaria dpetrov@techno-link.com Adelina Ilieva Peneva, MD Maria Hristova Milanova, MD, PhD from PE in pregnancy might be related to challenges in targeting the right population for prevention, ensuring that diagnosis is suspected and adequately investigated, and initiating timely and best possible treatment of this disease. 1 Pulmonary embolism has been reported in 15% to 20% of the patients with untrea ted deep vein thrombo sis. It occ urs in approximately 0.05% of all pregnancies. 2,3 The management of PE in pregnancy is difficult because few internists have experience of managing pregnant women; and few obstetricians have any experience of pulmonary embolism. In addition, there is confusion about the safety of maternal investigations for the fetus,

2 Petrov et al./pulmonary embolism in pregnancy particularly when these investigations involve ionising radiation, and also some confusion about the effects that any maternal therapy may have on the fetal wellbeing. 4 Treatment options for non-pregnant patients with severe, life-threatening pulmonary embolism, with haemodynamic compromise, or failure of therapy with heparin, include thrombolytic therapy, surgical embolectomy and catheter embolectomy or catheter thrombolysis. These options are considered as highrisk treatment in pregnancy and possibly harmful for mother and fetus.5 Thrombolytic agents have been used successfully to treat pregnant patients with massive PE, but the safety of this therapy has not been established. There is published information of pregnant women who received fibrinolysis, massive PE being the indication in about one third. 6 Thrombolytic agents are relatively contraindicated during pregnancy, because of the presumed risk of maternal bleeding and fetal loss. The decision to embark on a high-risk therapy of PE is difficult because of early observations that patients who do not die immediately usually do well once adequate anticoagulant therapy has been started. Treatment decisions are further complicated by pregnancy, in which the outcome of the fetus is also at stake. 7 We report a case of massive PE in a 261 p r eg n a n t wo ma n m a n a g e d s u c c es s f u l ly wi t h recombinant plasminogen activator (rt-pa), without adverse maternal or fetal side effects. Case A 32-year-old female, presented at 16 weeks of gestation with acute collapse and progressive dyspnoea over a few days. No risk factors were present in the patient's clinical history. On physical examination, she had tachypnoea with a respiratory rate of 30 per minute, hypotension (blood pressure 80/40 mmhg) and tachycardia (133 beats per minute). She was cyanotic, hypoxaemic with low oxygen saturation (80% on room air) and primary hypoxaemia and metabolic acidosis (ph-7.28, po 2-49 mmhg, CO 2-32 mmhg, HCO 3-20 mmol/l). Laborator y evaluation was remarkable for D-dimer 3250 ng/ml (normal <234 nm/ ml) and cardiac troponin 0.34 ng/ml (normal <0.06 ng/ml). The electrocardiogram was notable for sinus tachycardia with a rate of 133 per minute, right axis deviation (deep S wave in lead I), and T wave inversion in leads V1-V4 (Figure 1). The clinical presentation was highly suggestive of an acute pulmonary embolism, Figure 1. Initial electrocardiography showing sinus tachycardia with a rate of 133 per minute, right axis deviation (deep S wave in lead I), and T wave inversion in leads V1-V4.

3 262 and intravenous heparin was begun immediately. Doppler studies of the legs showed bilateral proximal deep venous thrombosis, making the diagnosis of p u l m o n a r y e m b o l i s m l i k e l y. Tr a n s t h o r a c i c echocardiography revealed a large saddle thrombus at the bifurcation of the main pulmonary artery (Figure 2). The right ventricle was enlarged, hypokinetic and severe tricuspid regurgitation was present. Systolic pulmonary-artery pressure of up 67 mmhg was estimated on the basis of continuous wave doppler echocardiography. The condition of the fetus, assessed by ultrasound, was normal. The patient was brought to the medical intensive care unit, and despite aggressive fluid resuscitation, she remained haemodynamically tenuous with systolic blood pressures ranging from 80 to 85 mmhg. Because of massive PE with significant haemodynamic compromise, increased right ventricular pressure, and no improvement after administering heparin, the decision was made to start thrombolytic therapy with rt-pa. After informing the patient and obtaining written consent, fibrinolysis was carried-out with rt-pa (10 mg bolus; then 90 mg over 2 hours) with subsequent heparin infusion according to partial thromboplastin time for the first 48 hours, when low- Hong Kong j. emerg. med. Vol. 21(4) Jul 2014 molecular-weight heparin (LMWH) (enoxaparin twice daily) was started. The response to thrombolytic therapy was remarkable. Her respirator y status dramatically improved and the heart rate and blood pressure normalised. Serial electrocardiograms demonstrated that the main QRS axis returned to normal with reduction of the S wave amplitude in lead I (Figure 3). Repeated echocardiogram performed 24 hours later showed that the right ventricular systolic pressure decreased to 36 mmhg and right ventricular dimension and function returned to within normal limits. Ultrasound scan revealed no signs of placental or fetal bleeding. On follow-up 6 weeks later, the patient's condition was good and the echocardiogram documented normal right ventricular size and function. LMWH was continued until delivery, and a healthy child was born at term. Discussion Thromboembolic disease is among the most common causes of morbidity and mortality during pregnancy, and 11% of maternal deaths were related to pulmonary embolism.8 Pregnancy due to its physiological changes is a procoagulant state and women are at increased risk Figure 2. Transthoracic echocardiography revealed a large saddle thrombus at the bifurcation of the main pulmonary artery.

4 Petrov et al./pulmonary embolism in pregnancy 263 Figure 3. Electrocardiogram after thrombolytic therapy showing that the main QRS axis returned to normal with reduction of the S wave amplitude in lead I. for PE because fibrinogen levels are increased, and during the final trimester there is a decrease in fibrinolytic activity. In addition, the gravid uterus causes compression and stasis in the lower extremities and pelvic veins, favouring thrombosis. Finally, women with a history of thrombotic complications during pregnancy have an increased prevalence of genetic mutations related to coagulation.7 A pregnant woman with a massive, life-threatening PE is a serious obstetric and medical emergency. Massive pulmonary embolism traditionally has been defined on the basis of angiographic burden of emboli by use of the Miller index, 9 but this definition is of limited use. Massive PE may be defined as an acute pulmonary embolism with sustained hypotension (systolic blood pressure <90 mmhg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolaemia, sepsis or left ventricular dysfunction), pulselessness, or persistent profound bradycardia (heart rate <40 bpm with signs or symptoms of shock). 10 The collapsed, shocked pregnant woman requires rapid assessment by a multidisciplinary resuscitation team of experienced clinicians. However, the diagnosis of pulmonary embolism during pregnancy is challenging, because classic clinical symptoms are often absent and physiological changes during pregnancy can mimic pulmonary embolism. Given the fact that massive PE is associated with high morbidity and mortality, it is critical to recognise and treat the disorder promptly. Early diagnosis and empiric treatment depends in many cases on the clinician's ability to quickly assess the situation and decide the treatment on an individual basis taking into account the available resources and expertise. In our case, the diagnosis was based on clinical, laboratory, electrocardiographic (sinus tachycardia, right avis deviation T waves inversion in leads V1-V4), and echocardiographic (right ventricular dysfunction, as well as direct visualisation of the thrombus in the pulmon ar y ar ter y) findings. Echocardiography is a preferred option in pregnancy, because of lack of radiation and will show a variety of abnormalities, as well as excluding other causes of collapse, in particular aortic dissection. In a patient with suspected massive PE, who is in critical condition, early bedside echocardiography is particularly helpful in emergency management decisions. 11,12 Spiral computed tomograph (CT) is not performed, because

5 264 radiation to the fetus carries a potential risk. This risk must be balanced against the risk to the mother/fetus if PE is not diagnosed or treated and against the risk of treatment of non-confirmed PE. 13 The use of diagnostic imaging in pregnant patients needs careful consideration because of the teratogenic and oncogenic effects of radiation. Although CT is associated with a lower dose of radiation for the fetus than a ventilation/ perfusion (V/Q) lung scan, it exposes the mother to a relatively high radiation dose: as much as 20 mgy to the thorax and particular breast tissue. It has been calculated that this is associated with a significant increase in the lifetime risk of breast cancer because breast tissue is especially sensitive to radiation exposure during pregnancy.14 In pregnancy spiral CT scanning should be limited to patients who have collapsed where there is no confirm diagnosis.15 The main therapeutic goal in the management of acute massive PE is to reverse right heart failure as rapidly as p o s s i b l e. Cu r r e n t r ec o m me n d a t i o n s s u g g es t thrombolytic therapy for patients with severe PE with haemodynamic compromise.10 The use of thrombolytic drugs should be discouraged in normotensive patients with adequate oxygenation and isolated right ventricular dysfunction, since this indication is debated even in non-pregnant patients. 16 If thrombolytic therapy is employed in pregnancy, r t-pa and streptokinase are the preferred agents. Some authors recommended rt-pa over streptokinase and urokinase, because of presumably less bleeding complications, a shorter duration of administration and no allergic complications. 5 Pregnancy is considered a relative contraindication for thrombolytic therapy, but successful outcomes with the use this therapy have been reported.17,18 The experience with thrombolytic therapy in pregnant patients is minimal and there are no prospective randomised trials to date that evaluate the efficacy and safety of this therapy. Hence data from case reports and case series are yet the best level of evidence we have. Thrombolytic therapy has been rarely used in pregnancy with only 28 cases of rt-pa thrombolysis reported in the literature so far. Indication for rt-pa thrombolysis were stroke (n=10), thrombosis of cardiac valve prosthesis (n=7), pulmonary embolism (n=7), deep venous thrombosis Hong Kong j. emerg. med. Vol. 21(4) Jul 2014 (n=3) and myocardial infarction (n=1). 19 However, Ahearn et al reviewed the available literature and found that thrombolytic therapy in pregnancy was associated w i t h a ve r y lo w m a t e r n a l m o r t a l i t y r a t e o f approximately 1%, with a 6% rate of fetal loss and a 6 % r at e o f p rema tu re d eliver y. 7 In c on t r as t, embolectomy and cardiopulmonary bypass were associated with a 20-40% rate of fetal loss despite low maternal mortality rate. These data must be interpreted carefully as they are limited to case studies or case reports; and the approach to the management of an acute massive PE should be individualised and adapted to changing circumstances. In our case, we recognised that thrombolysis can be dangerous in the early phases of pregnancy, but the urgency of the situation required a quick decision. The decision to administer a fibrinolytic agent requires individualised assessment of the balance of benefits versus risk. Potential benefits include more rapid resolution of symptoms, stabilisation of respiratory and cardiovascular function without need for mechanical ventilation or vasopressor support, reduction of right ventricular damage and increased probability of survival. Potential harm includes disabling of fatal haemorrhage and the presumed risk of maternal bleeding and fetal loss. There is concern that thrombolysis may lead to placental abruption, but this complication has not been reported. Therapy was initiated with unfractionated heparin, but because of significant haemodynamic compromise and the perceived high risk of a fatal PE, the decision was made to start thrombolytic therapy using recombinant tissue plasminogen activator. The response to fibrinolysis was remarkable. There was no haemorrhagic complication either. Further, the pregnancy was uneventful till term and a healthy child was delivered. These findings suggest that the use of fibrinolytic therapy in emergency situations may be an efficient and safe method, when applied in accordance with the standard procedure. We feel that it is not justified to withhold thrombolytic therapy from pregnant patients, if effective alternatives are lacking. Because of the risk of bleeding, thrombolysis should not be used routinely in pregnancy, but reserved for those who are haemodynamically unstable, particularly with regard to systemic hypotension.

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