Massive pulmonary embolism (PE) frequently leads to cardiac arrest (CA) which carries an extremely high mortality rate. Although available, randomized trials have not shown survival benefits from thrombolytic use. Thrombolytics however have been used successfully during resuscitation in clinical practice in multiple case reports and in retrospective studies. Recent resuscitation guidelines recommend using alteplase for PE related CA; however they do not offer a standardized treatment regimen. The most consistently applied approach is an intravenous bolus of 50 mg tissue plasminogen activator (t-PA) early during cardiopulmonary resuscitation (CPR). There is no consensus on the subsequent dosing. We present a case in which two 50 mg boluses of t-PA were administered 20 minutes apart during CPR due to persistent hemodynamic compromise guided by bedside echocardiogram. The patient had an excellent outcome with normalization of cardiac function and no neurologic sequela. This case demonstrates the benefit of utilizing bedside echocardiography to guide administration of a second bolus of alteplase when there is persistent hemodynamic compromise despite achieving return of spontaneous circulation after the initial bolus, and there is evidence of persistent right ventricle dysfunction. Future trials are warranted to help establish guidelines for thrombolytic use in cardiac arrest to maximize safety and efficacy.
Cardiac arrest due to PE is a lethal condition [
A 56-year-old, previously healthy Caucasian female presented to the emergency department (ED) with acute, severe shortness of breath and pleuritic chest pain for two hours with pulse of 140/min and respiratory rate of 30/min. She had undergone total right knee replacement surgery two weeks prior. She was taking aspirin 81 mg twice daily but no other medications and had no other medical history. She was brought in via ambulance in severe respiratory distress, diaphoretic, and a room air oxygen saturation of 70% and complained “I cannot breathe.” There was some bruising at the surgical site and a small right knee effusion, but the surgical site was well healed with no erythema or purulence. Her electrocardiogram (ECG) showed sinus tachycardia without any acute ischemic changes.
She was immediately given 5000 units of intravenous heparin due to the high suspicion of pulmonary embolism. Her oxygen saturations remained around 70–79% despite receiving 100% oxygen (15 L) via nonrebreather mask. Arterial blood gas (ABG) on 100% oxygen showed (pH 6.8, pCO2 58.6, and PaO2 188) severe acidosis with an elevated A-a gradient of 334.8 mmHg. Patient was emergently intubated due to persistent respiratory distress, increased work of breathing, continued air hunger, and worsening respiratory acidosis with hypercapnia despite being on 100% oxygen via nonrebreather mask. She was given etomidate and succinylcholine and intubated without difficulty.
Shortly after intubation, she underwent cardiac arrest with pulseless electrical activity (PEA). Immediate CPR was started. She received 50 mEq intravenous (IV) sodium bicarbonate, 1 mg of IV epinephrine, and 1 mg of IV atropine with four cycles of chest compression during first round of resuscitation. Emergent bedside echocardiogram was performed at the first pulse check and showed a severely dilated right ventricle (RV), with reduced right ventricular systolic function and normal left ventricular (LV) size and systolic function. These findings were suggestive of a massive PE (Figure
Transthoracic echocardiogram obtained before administration of t-PA: apical views showing a severely dilated right ventricle (RV) with reduced right ventricular systolic function. RV free wall is hypokinetic and RV apical wall is hypercontractile (arrow; McConnell sign). Left ventricular size and systolic function are normal.
However, despite achieving the ROSC, she was hypotensive and therefore norepinephrine infusion was started. Echocardiogram was still showing persistent evidence of RV dysfunction with normal LV function. Given her persistent hemodynamic compromise with recurrent cardiac arrest, the decision was made to administer a second bolus of 50 mg alteplase, which was given at 24 minutes into the code. She developed PEA for a third time approximately at 29 minutes into the code. During third round of resuscitation, she received 1 mg of epinephrine and had ROSC. She required CPR for a total of 32 minutes, with three rounds of resuscitation and 2 IV boluses of 50 mg alteplase, 20 minutes apart. Her chest X-ray at this point showed bilateral perihilar opacities with mild cardiomegaly, consistent with pulmonary edema. Her other laboratory findings are summarized in the table (Table
Patient characteristics.
Variable | Value | Target range |
---|---|---|
Pulse | 140/minute | 60–100/minute |
Respiratory rate | 34–50/minute | 12–14/minute |
Blood pressure | 109/67 mmHg | 120/80 mmHg |
Temperature | 97°F | 97–99°F |
Oxygen saturation | ||
Room air | 70% | 88–100% |
100% oxygen | 70–79% | 88–100% |
ABG on 15 L oxygen nonrebreather (NRB) | ||
Ph | 6.8 | 7.4 |
pO2 | 188 mmHg | 100 mmHg |
pCO2 | 58.6 mmHg | 40 mmHg |
HCO3 | 9.2 mmol/L | 25 mmHg |
Laboratory data | ||
WBC | 4.5 × 109/L | 4–10 × 109/L |
Neutrophil | 73% | 50–60% |
Hemoglobin | 7.2 g/dl | 12–14 g/dl |
Hematocrit | 22.83% | 35–45% |
Platelets | 133 × 109/L | 130–450 × 109/L |
Sodium | 140 mEq/L | 135–145 mEq/L |
Potassium | 4.5 mEq/L | 3.6–5 mEq/L |
Chloride | 96 mEq/L | 98–110 mEq/L |
CO2 | 19 mEq/L | 25 mEq/L |
BUN | 17 mg/dL | 25 mg/dL |
Creatinine | 0.96 mg/dL | 1.0 mg/dL |
Anion gap | 15 mEq/L | 10–12 mEq/L |
Lactic acid | 4.4 mmol/L | <2.0 mmol/L |
Troponin | 4.2 ng/mL | <0.03 ng/mL |
Calcium | 6.6 mg/dL | 8 mg/dL |
Ionized calcium | <1.0 mmol/L | 1.1 mmol/L |
AST | 372 U/L | 45 U/L |
ALT | 214 U/L | 40 U/L |
ALP | 156 U/L | 100 U/L |
T. bilirubin | 1.0 mg/dL | 1.0 mg/dL |
CPK | 203 IU/L | 50 IU/L |
ABG: arterial blood gas.
After the third round of CPR, she also received a transfusion of two units of packed red blood cells via Belmont rapid infuser due to anemia. Bicarbonate infusion was initiated due to severe acidosis. Full dose heparin anticoagulation was started per postthrombolytics protocol. Some ecchymosis and swelling were noticed at the recent knee surgical site but she did not develop any significant bleeding complications after thrombolytic therapy. Venous Doppler ultrasound was done later which was positive for deep venous thrombosis in the gastrocnemius and popliteal veins of the right lower extremity. She was then transferred to the intensive care unit where bronchoscopy showed small pink frothy septum consistent with pulmonary edema but no evidence of aspiration.
Repeat echocardiogram the next day showed improvement in RV size and function (Figure
Transthoracic echocardiogram 24 hours after t-PA administration: showing improvement in RV size (arrow) and function but still dilated.
Subsequent computed tomography angiogram of the chest performed eighty-four hours after CA showed segmental PE in right middle and left lower lobe with scattered air space opacities, atelectasis, and pleural effusions (Figure
CT angiogram showing pulmonary embolism (arrow).
She had an excellent outcome without any neurologic sequelae or any bleeding complications. She was liberated from mechanical ventilation on hospital day 3 and supplemental oxygen was gradually weaned from high flow nasal cannula to room air by the time of discharge. Apixaban was initiated on hospital day 3. She was discharged home on hospital day 5, ambulating independently, on room air and on apixaban. On 3 months’ follow-up, she had complete normalization of right ventricular size and systolic function without any residual pulmonary hypertension (Figures
Transthoracic echocardiogram after 3 months, showing interval normalization of RV size (arrow) and function and normalization of the right ventricular systolic pressure with an estimate of 19 mmHg
Transthoracic echocardiogram after 3 months, showing interval normalization of RV size (arrow) and function and normalization of the right ventricular systolic pressure with an estimate of 19 mmHg
Pulmonary embolism is the third most frequent cardiovascular disease in the United States (US) and has an extremely high morbidity and mortality [
Massive PE causes sudden increase in pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) which is proportional to degree of obstruction in patients without preexisting pulmonary vascular disease [
Traditional ACLS and CPR have been the common practice for PE related cardiac arrest [
Unfortunately, there are no strong prospective studies to show a survival benefit for the use of fibrinolytic drugs in cardiac arrest due to massive PE. Two available randomized control trials have failed to show a statistically significant outcome [
Thrombolytic therapy also carries 9–22% risk of major bleeding, including a 1–5% risk of intracranial hemorrhage [
There have been numerous cases reported in American and European literature, where thrombolysis (various formulations and regimens) was used in confirmed PE or clinically suggestive history of PE related cardiac arrest cases. Thrombolytic therapy has showed very favorable outcomes even when administered late during the CPR and as slow infusions after a prolonged CPR [
Unfortunately, there is no consensus regarding the dosage and timing of thrombolytics during resuscitation. The American Heart Association (AHA) recommends a two-hour infusion of 100 mg of alteplase in those with hemodynamic compromise. However, they do not clearly address the issue of cardiac arrest [
However, there is no existing consensus or established guidance for subsequent approach. Surgical embolectomy or catheter guided interventions can be considered for unstable patients or those who have failed maximal medical treatment [
We used focused bedside echocardiogram in our patient, as she was hemodynamically unstable and was experiencing recurrent cardiac arrest. Based on our echocardiogram findings of persistent RV dysfunction and dilatation with persistent hemodynamic compromise, we administered second bolus of t-PA with excellent outcome. This emphasizes the potential implacability of echocardiography for decision-making in such situations.
Echocardiography has limited sensitivity and specificity for the diagnosis of acute PE [
Presence of RV strain has more than twofold increase in risk of early mortality compared with patients with no signs of RV strain [
We used focused echocardiography to guide repeat alteplase bolus administration, as our patient remained hemodynamically unstable, despite successful ROSC after initial alteplase bolus. Fortunately, despite prolonged CPR, our patient had an excellent outcome with no cardiac or neurologic sequela. At three months’ follow-up, the patient had complete normalization of right RV function without any residual pulmonary hypertension (Figures
Recent resuscitation guidelines recommend using thrombolytic therapy during resuscitation in cases of CA due to massive PE [
Consent was obtained from patient for publishing this case.
The authors declare that they have no conflicts of interest.
The authors want to thank Mokshya Sharma M.D., Charles D. Graham M.D., Ahmed Waseem M.D., and Asad Javed M.D. for their help in preparation and review of this manuscript. They would also like to thank Troy Wiedenbeck M.D. and Dirk Vandergon M.D. for their help in reviewing echocardiographic material. They would also like to acknowledge permission of patient to publish this case.
Videos 1, 2: transthoracic echocardiogram during the CPR before administration of t-PA, showing a severely dilated right ventricle (RV) with reduced systolic function. RV free wall is hypokinetic and apical wall is hypercontractile (McConnell sign). There is flattening of interventricular septum with paradoxical motion of septum in diastole towards left ventricle (D-shaped left ventricle) consistent with significant RV overload. There is a dilated right atrium and moderate tricuspid regurgitation. Left ventricular size and systolic function are normal. Video 3: transthoracic echocardiogram 24 hours after t-PA administration, showing improvement in RV size and function but still dilated. Videos 4-5: transthoracic echocardiogram after 3 months showing interval normalization of right ventricular size and function. Right ventricular systolic pressure has also normalized.