Download Thrombolytic Therapy for Cardiac Arrest due to Pulmonary

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CASE REPORT
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Thrombolytic Therapy for Cardiac Arrest due to
Pulmonary Embolism after Varicose Vein Surgery
Bing Wu, Guang-ju Zhao, Huan Liang, Zhong-qiu Lu, Qiao-meng Qiu and Ying-ru Lu
Abstract
Anticoagulant therapy is the mainstay in the management of venous thromboembolism. Nevertheless, the
situation is entirely different in the patients with submassive or massive pulmonary embolism (PE) and cardiac arrest, and the diagnosis and therapy strategy for such conditions are lacking. This patient, who presented with a cardiac arrest event after varicose vein surgery, was diagnosed as acute pulmonary embolism.
She survived after administration of 50 mg recombinant tissue plasminogen activator (rt-PA) for over half an
hour, along with continued anticoagulant therapy. Unfortunately, gastrointestinal and cerebral hemorrhaging
occurred during the process.
Key words: cardiac arrest, pulmonary embolism, thrombolytic therapy, varicose vein surgery, recombinant
tissue plasminogen activator
(Intern Med 51: 1899-1902, 2012)
(DOI: 10.2169/internalmedicine.51.7149)
Introduction
Surgery is one of the recognized risk factors for deep venous thrombosis and pulmonary embolism. Several series
have demonstrated pulmonary embolism after varicose vein
surgery is low (1). However, if the embolism is massive and
not recognized and treated timely, it may be rapidly fatal.
Here we present a patient with early postoperative cardiac
arrest who was diagnosed as acute pulmonary embolism after varicose vein surgery. The patient survived after administration of 50 mg recombinant tissue plasminogen activator
(rt-PA) over half an hour, along with continuous anticoagulant therapy. Unfortunately, gastrointestinal and cerebral
hemorrhaging occurred during the process. The diagnosis
and therapy strategy of this condition are discussed.
Case Report
A 68-year-old woman (63 kg) was admitted to our hospital for treatment of primary varicose vein of the left lower
extremity. In early March, partial stripping and high ligation
of the left long saphenous vein were performed under general anesthesia. The surgery went well, and she was posi-
tioned in bed postoperatively with both legs elevated and
with an elastic bandage applied overnight. Low-molecularweight heparin (5,000 IU/day) was used to avoid deep vein
thrombosis.
Four days after admission, at 9:50 AM, after her morning
walk, the patient suddenly lost consciousness. She was cyanotic, had mydriasis, and papillary light reflex was lost. Her
heart rate decreased to 30-40 beats/min, cardio-pulmonary
resuscitation (CPR) was started immediately. Endotracheal
intubation was performed and mechanical ventilation was instituted. Epinephrine was given intravenously. No upper motor neuron signs, such as hyperreflexia, the Hoffmann sign
and the Babinski sign, were noted during the process. Immediate ECG revealed sinus bradycardia with the typical
S1-Q3-T3 pattern (Fig. 1). There were no significant
changes in ST-T waves compared with previous ECG. Additionally, her troponin level was normal (0.03 μg/L) as well
as CK-MB level (11 U/L). Bedside transthoracic echocardiography was performed by a technician from the echocardiography unit and it was interpreted in real-time by a senior cardiologist with experience in echocardiography. This
revealed a significant dilated right atrium and ventricle, and
left ventricular contractility was significantly reduced
(Fig. 2). Coronary heart disease and cerebrovascular acci-
Emergency Department, The First Affiliated Hospital of Wenzhou Medical College, P.R.China
Received for publication December 19, 2011; Accepted for publication April 2, 2012
Correspondence to Dr. Zhong-qiu Lu, [email protected]
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Intern Med 51: 1899-1902, 2012
DOI: 10.2169/internalmedicine.51.7149
ter admission, her right upper limb muscle strength recovery
was very good. Head computerized tomography (CT)
showed that the hemorrhage was absorbed. She was discharged from the hospital two weeks later on warfarin, with
return to premorbid condition.
Discussion
Figure 1. Electrocardiogram revealed sinus bradycardia
with the typical S1-Q3-T3 pattern.
dents were excluded and a diagnosis of acute pulmonary
thromboembolism was made; rtPA (50 mg) was administered as an intravenous drip over half an hour for thrombolysis, along with continuous heparin therapy according to
activated partial thromboplastin time (APTT, 50-70s). After
40 minutes of CPR, the patient resumed normal sinus
rhythm, blood pressure was 127/65 mmHg, pulse was 120130 beats/min. We observed an improvement in oxygen
saturation (>95%), an increase in blood pressure, absence of
cyanotic and mydriasis. And then, she was admitted to the
emergency intensive care unit at 13:00.
After admission to EICU, The patient was placed on IV
dobutamine and norepinephrine. However, the patient could
not maintain hemodynamic stability. Her blood pressure was
70-90/40-50 mmHg, arterial blood gas values were pH=
7.040; PaO2=48.5 mmHg; PaCO2=72.5 mmHg; HCO3=-19.6
mmol/L; BE=-12.3 mmol/L. A spiral computerized tomographic angiography (CTA) of the chest was obtained as
well as coronary angiography to exclude thrombolysis failure and coronary heart disease. CTA showed that the blood
flow of the right pulmonary artery slowed down while coronary angiography was negative. A femoral arterial catheter
was positioned and her blood pressure was measured as of
160/80 mmHg. Subsequently, the patient’s hemodynamic
status continued to improve and achieved stability on decreasing doses of dobutamine and norepinephrine.
In mid-March, five days after her loss of consciousness,
mechanical ventilation was stopped. In addition, the patient’s prothrombin time (PT) was 16.6 seconds and APTT
was 60.4 seconds. One day later, bloody stool was detected
and repeat (complete blood count) CBC showed hemoglobin
of 73 g/L, the diagnosis of gastrointestinal bleeding was
made and she was treated with omeprazole while fasting. At
this time, a PT of 16.2 seconds and an APTT of 40.2 seconds were detected. After five days, her clotting profile was
retested and showed a PT of 17.5 seconds and an APTT of
54.3 seconds. The following day, the patient’s mouth became askew and the right upper limb muscle strength declined. A coagulation screen was taken. This revealed a PT
of 18.3 seconds and an APTT of 43.7 seconds. Head computerized tomography (CT) showed intracranial bleeding
(Fig. 3), and thus heparin was discontinued. At 2 months af-
Pulmonary embolism is a well-known complication of
major surgery but it is not always appreciated that it can occur even after minor interventions such as varicose vein surgery. In general, suspicion of PE is raised by clinical symptoms such as dyspnea, chest pain, or sustained hypotension
without an alternative obvious cause. However, in the case
of PE associated with unconsciousness and cardiac arrest/
PEA, the decision-making is difficult. Electrocardiographic
signs of RV strain, such as inversion of T waves in leads V1
to V4, a QR pattern in lead V1, the classic S1Q3T3 type
and incomplete or complete right bundle-branch block, may
be helpful, particularly when of new onset (2, 3). Nevertheless, such changes are generally associated with the more
severe forms of PE and may be found in right ventricular
strain of any cause (4, 5). Bedside echocardiography is particularly helpful in emergency management decisions when
computed tomography (CT) scan is not immediately available. Trans-esophageal echocardiography can provide high
sensitivity (92%) and high specificity for the diagnosis of
PE (near 100%) in the setting of CPR (6). In a patient with
suspected PE who is in a critical condition (shock or hypotension), the absence of echocardiographic signs of RV
overload or dysfunction practically excludes PE as a cause
of hemodynamic compromise (4).
Anticoagulant therapy is the mainstay in the management
of venous thromboembolism. However, the situation is entirely different in those patients with submassive or massive
PE and cardiac arrest. The European Society of Cardiology
(ESC) Guidelines and other clinical practice guidelines of
the American College of Chest physicians (ACCP) suggest
that absolute indications for thrombolytic therapy are MPE
with persistent hypotension or shock (4, 5). Drugs, such as
streptokinase, urokinase and rtPA used for therapeutic
thrombolysis have shown to lyse thrombi, resulting in salvaging of myocardium and improvement in patient outcome.
rtPA is currently the recommended drug which can achieve
a faster clot lysis with improved safety and better tolerance.
In recent randomized trials, the 2 hours infusion of rtPA has
led to faster angiographic and hemodynamic improvement
compared with 24 hours infusion of urokinase, although
lung scans obtained 24 hours after treatment were no different between the two groups (7). A more recent metaanalysis revealed no significant difference between the three
regimens and crude analysis of summated data from all
studies revealed that rtPA infusion had a lower mortality due
to the initial PE than streptokinase (8).
Considering the short duration of action, with a plasma
half-life of 4-5minutes, rtPA should be given as a continu-
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Intern Med 51: 1899-1902, 2012
DOI: 10.2169/internalmedicine.51.7149
Figure 2. Bedside transthoracic echocardiography revealed a significant dilated right atrium and
ventricle, and left ventricular contractility was significantly reduced.
Figure 3. Head computerized tomography (CT) showed intracranial bleeding.
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Intern Med 51: 1899-1902, 2012
DOI: 10.2169/internalmedicine.51.7149
ous infusion in order to main adequate plasma concentrations at the site of the thrombus in order to cause lysis of
the clot. In treatment of PE, the initial studies of rtPA generally used 2 hours of infusion (9). Nevertheless, the dose and
infusion time of rtPA in management of PE-induced cardiac
arrest is lacking evidence. Some reports in the literature, primarily case reports, state that rtPA 100 mg of over 15 minutes or intravenous bolus tenecteplase 0.5 mg/kg (50 mg
maximum) can be considered. The present case showed that
the 50 mg/30min infusion was also effective for this course
of action. In fact, rapid administration of low dose rtPA (50
mg/30min) has been successfully used in management of
acute myocardial infarction (10). Therefore, randomized
multicenter trials will be needed for assessing the efficacy
and safety of rapid administration of low dose rtPA in PE
patients with cardiac arrest.
The major complication of thrombolytic treatment is an
increased incidence of bleeding compared with the use of
heparin. A retrospective analysis found a significantly increased risk of intracranial hemorrhage in patients with hypertension and advancing age (11). Some other risk factors
for bleeding include invasive procedures, an increased body
mass index as well as dose and length of time of thrombolytic therapy (12). In the present case, 50 mg rtPA was
used for thrombolysis, along with continuous heparin therapy according to APTT. Unfortunately, gastrointestinal and
cerebral hemorrhaging occurred during the process. Moreover, a recent study revealed that the 50 mg/2h rt-PA regimen exhibits similar efficacy and less bleeding tendency
than the 100 mg/2h regimen, especially in patients with a
body weight of less than 65 kg (13). This evidence combined with our report prompt that optimizing rt-PA dosing is
worthwhile when treating patients with cardiac arrest due to
PE and should be adjunct to the guidelines.
The authors state that they have no Conflict of Interest (COI).
Acknowledgement
This work was supported, in part, by the grant of key construction academic subject (medical innovation) of Zhejiang
Province (11-CX26)
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Bing Wu and Guang-ju Zhao contributed equally
Ⓒ 2012 The Japanese Society of Internal Medicine
http://www.naika.or.jp/imindex.html
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