Patient demographic characteristics and clinical presentations
Twenty-one patients were identified with a mean age of 54.8 years (range, 26 to 83 years). Nineteen patients had visualized pulmonary artery thrombus by using CT scan, 1 patient had a diagnosis based on the presence of impaired gas exchange, hemodynamic instability, and right heart thrombus, and 1 patient was diagnosed based on high clinical probability and echocardiographic finding of RV dilation without other plausible cause. The baseline clinical and demographic characteristics of these patients were summarized in Table 1. All except one patient had provoking factors for PE, included major surgery (61.9%), active cancer (33.3%), and prolonged bed rest (23.8%). More than half of the patients experienced worsening dyspnea (61.9%) and unexplained tachycardia (52.4%) before diagnosis of PE. Two hospitalized patients remained asymptomatic until sudden cardiac arrest occurred and 4 patients presented with cardiogenic shock on arrival to the emergency department.
Table 1. Baseline clinical and demographic characteristics (N = 21)
Characteristic
|
Value
|
Age, years
|
54.8 ± 16.1
|
Male sex, n (%)
|
15 (71.4)
|
Obesity (BMI > 27 kg/m2)
|
6 (28.6)
|
Hypertension, n (%)
|
7 (33.3)
|
Diabetes mellitus, n (%)
|
2 (9.5)
|
Smoking, n (%)
|
6 (28.6)
|
Hyperlipidemia, n (%)
|
2 (9.5)
|
Congestive heart failure, n (%)
|
1 (4.8)
|
Chronic kidney disease, n (%)
|
1 (4.8)
|
History of stroke, n (%)
|
1 (4.8)
|
Liver cirrhosis, n (%)
|
0 (0.0)
|
Predisposing factors for PE
|
|
Clinical sign of DVT, n (%)
|
3 (14.3)
|
Major surgery, n (%)
|
13 (61.9)
|
Major trauma, n (%)
|
3 (14.3)
|
Active cancer, n (%)
|
7 (33.3)
|
Recent myocardial infarction, n (%)
|
1 (4.8)
|
History of VTE, n (%)
|
2 (9.5)
|
ICU length of stay > 72 hours, n (%)
|
5 (23.8)
|
Immobilization of the lower limbs, n (%)
|
3 (14.3)
|
Postpartum period, n (%)
|
2 (9.5)
|
Clinical presentation
|
|
Tachycardia, n (%)
|
11 (52.4)
|
Fever, n (%)
|
6 (28.6)
|
Chest pain, n (%)
|
2 (9.5)
|
Cold sweating, n (%)
|
7 (33.3)
|
Dyspnea, n (%)
|
13 (61.9)
|
Hemoptysis, n (%)
|
2 (9.5)
|
Syncope, n (%)
|
1 (4.8)
|
Altered mental status, n (%)
|
1 (4.8)
|
Hypotension or cardiac arrest, n (%)
|
6 (28.6)
|
BMI, body mass index; DVT, deep vein thrombosis; ECMO, veno-arterial extracorporeal membrane oxygenation; PE, pulmonary embolism; ICU, intensive care unit; VTE, venous thromboembolism.
The pre-ECMO clinical condition, risk stratification, and various parameters were summarized in Figure 1 and Table 2. Before initiation of ECMO, mechanical ventilation was used in 4 patients for postoperative respiratory assistance and 15 patients for acute respiratory failure. The remaining 2 patients received emergent intubation during extracorporeal CPR period. Unfractionated heparin or low molecular weight heparin was used in 7 patients with confirmed PE and 1 patient with highly suspected PE before ECMO initiation. More than 90% of patients had ECG findings of RV strain prior to initiating ECMO and imaging signs of RV dysfunction before or during ECMO support. Pre-ECMO blood gases showed severe metabolic acidosis (pH < 7.2) in 9 patients (9/18, 50.0%), and moderate to severe hypoxemia (PaO2/FiO2 < 200 mmHg) in 16 patients (16/18, 88.9%). Elevated cardiac troponin I (≥ 0.04 ng/mL) was seen in 14 patients (14/21, 66.7%). Including 6 patients presenting cardiogenic shock or cardiac arrest as initial presentation, 17 patients (81.0%) progressed to refractory circulatory collapse within the first day after onset of symptoms, and 16 patients (76.2%) experienced cardiac arrest requiring CPR or refractory cardiogenic shock requiring ECMO support within 2 hours after the presentation of refractory circulatory collapse.
Table 2. Characteristics of patients at the time of ECMO placement (N = 21)
Characteristic
|
Value
|
Pre-ECMO mechanical ventilation, n (%)
|
19 (90.5)
|
Pre-ECMO UFH/LMWH use
|
8 (38.1)
|
Inotrope use, n (%) (before CPR or ECMO initiation)
|
10 (47.6)
|
Pre-ECMO condition
|
|
Shock, n (%)
|
10 (47.6)
|
Prior cardiac arrest required CPR, n (%)
|
4 (19.0)
|
Cardiac arrest during CPR, n (%)
|
7 (33.3)
|
Pre-ECMO ECG findings (n = 15, within 24 hours before initiation of ECMO)
|
|
RV strain, n (%)
|
11 (73.3)
|
Sinus tachycardia/atrial fibrillation, n (%)
|
13 (86.7)
|
Pre- or post-ECMO finding of RV overload
|
|
Echocardiography (n = 20), n (%)
|
19 (95.0) (pre-ECMO: 13, post-ECMO: 6)
|
RV/LV diameter ratio on CT (n = 19)
|
1.6 ± 0.6 (range, 0.7 to 2.8)
|
RV/LV diameter ratio ≥ 0.9, n (%)
|
18 (94.7) (pre-ECMO: 13, post-ECMO: 5)
|
Pre-ECMO troponin I level (ng/mL) (within 24 hours before ECMO initiation)
|
0.26 ± 0.39 (range, 0.01 to 1.34)
|
Cardiac troponin I ≥ 0.04 ng/mL, n (%)
|
14 (66.7)
|
Pre-ECMO arterial blood gases (n = 18, within 24 hours before ECMO initiation)
|
|
pH
|
7.20 ± 0.18 (range, 6.82 to 7.50)
|
Bicarbonates (mmol/L)
|
18.5 ± 7.2 (range, 9.6 to 31.6)
|
SBE
|
-9.7 ± 8.6 (range, -23.7 to 4.4)
|
PaO2/FiO2 ratio (mmHg)
|
118.7 ± 93.8 (range, 21.8 to 376.8)
|
Time from symptoms to shock, hours
|
25.9 ± 54.3 (range, 0.0 to 238.2)
|
Time from shock to ECMO, hours
|
3.4 ± 4.3 (range, 0.4 to 18.3)
|
CPR, cardiopulmonary resuscitation; CT, computed tomography; ECG, electrocardiogram; ECMO, veno-arterial extracorporeal membrane oxygenation; LMWH, low-molecular-weight heparin; RV/LV, right-to-left ventricular; SBE, standard base excess; UFH, unfractionated heparin.
Management and outcomes
The management strategies and outcomes were detailed in Figure 2 and Table 3. During ECMO support, 8 patients (38.1%) were treated with thrombolytic agents and 13 patients (61.9%) received heparin alone. No patient underwent surgical embolectomy. Among patients receiving thrombolysis, tissue plasminogen activator was administered intravenously by bolus in 3 patients, catheter-directed thrombolysis with urokinase through central venous catheter was performed in 4 patients, and ultrasound-enhanced catheter-directed thrombolysis with urokinase through EkoSonic Endovascular System (EKOS Corporation, Bothwell, WA, USA) was performed in 1 patient.
Table 3. Clinical variables and outcomes of patients according to in-hospital survival status
|
Survivors (n = 11)
|
Non-survivors (n = 10)
|
p
|
Age, years
|
55.4 ± 17.7
|
54.1 ± 15.1
|
0.863
|
Male sex
|
8 (72.7%)
|
7 (70.0%)
|
0.890
|
Smoking
|
3 (27.3%)
|
3 (30.0%)
|
0.890
|
BMI (kg/m2)
|
25.8 ± 3.4
|
24.7 ± 3.9
|
0.500
|
Cardiac arrest
|
2 (18.2%)
|
9 (90.0%)
|
0.001
|
CPR duration, minutes
|
6.1 ± 14.5
|
36.3 ± 19.2
|
|
Post-ECMO thrombolytic therapy
|
6 (54.5%)
|
2 (20.0%)
|
0.104
|
Major complications
|
|
|
|
Neurologic impairment
|
0 (0.0%)
|
10 (100.0%)
|
<0.001
|
Acute kidney injury required dialysis
|
0 (0.0%)
|
7 (70.0%)
|
0.001
|
Major bleeding
|
1 (9.1%)
|
0 (0.0%)
|
0.329
|
ECMO-related complications
|
1 (9.1%)
|
1 (10.0%)
|
0.943
|
ECMO duration, days
|
5.0 ± 2.6
|
5.3 ± 5.8
|
0.454
|
MV duration, days
|
10.3 ± 8.7
|
6.3 ± 6.6
|
0.125
|
ICU LOS, days
|
15.6 ± 8.3
|
6.3 ± 6.6
|
0.012
|
Hospital LOS, days
|
29.9 ± 16.0
|
6.3 ± 6.6
|
<0.001
|
BMI, body mass index; CPR, cardiopulmonary resuscitation; ECMO, veno-arterial extracorporeal membrane oxygenation; ICU, intensive care unit; LOS, length of stay; MV, mechanical ventilation.
The in-hospital mortality rate was 47.6%, and the most (90%) leading cause of death was prolonged CPR-related brain death. Compared with non-arrested patients, cardiac arrest prior to ECMO cannulation was a significant predictor of in-hospital mortality (81.8% versus 10.0%, p = 0.001). Among survivors, all patients discharged without additional complications, included RV dysfunction.
Comparison of CT images and cardiac biomarkers for predicting clinical course
Thirteen patients who had confirmed diagnosis of PE by CT image before cardiac arrest or ECMO initiation were included for subgroup analysis. The risk classification and various parameters of the patients were detailed in Table 4. All cardiac troponin I testing was performed within 8 hours before shock or at the time of shock event. Elevated cardiac troponin I (≥ 0.04 ng/mL) was seen in only 9 patients (69.2%). There was no association between pre-ECMO cardiac troponin-I levels and in-hospital mortality (cut-off point 0.02, area under the curve 0.556; sensitivity 100.00%; specificity 44.44%, p = 0.740). The mean time interval from onset of shock to cardiac arrest or ECMO initiation was 2.7 hours (range, 0 to 18.3 hours). In submassive PE patients, the mean time interval from CT exam to cardiac arrest or ECMO initiation was 3.1 hours in patients (n = 4) with severe RV dilation (RV/LV diameter ratio ≥ 2) and 34.3 hours in patients (n = 3) with moderate RV dilation (RV/LV diameter ratio between 1 and 2). In patients with submassive PE, the RV/LV diameter ratio was significantly negatively correlated with the time interval from CT exam to cardiac arrest or ECMO initiation (p = 0.049) (Figure 3).
Table 4. Clinical Summary of CT proven PE Patients before CPR or ECMO initiation (N = 13)
Case No.
|
Age, years
/Sex
|
Risk classification
|
Troponin-I, ng/mL
|
RV/LV diameter ratio on CT
|
Time from CT to CPR or ECMO, hours
|
Time from shock to CPR or ECMO, hours
|
ECMO indication
|
Outcome
|
1
|
66/F
|
Low
|
<0.02
|
0.8
|
149.8
|
0.0
|
During CPR
|
Alive
|
2
|
30/M
|
Submassive
|
0.05
|
1.5
|
61.3
|
0.2
|
During CPR
|
Dead
|
3
|
42/M
|
Submassive
|
0.05
|
1.6
|
36.8
|
0.6
|
During CPR
|
Dead
|
4
|
46/F
|
Submassive
|
0.181
|
1.3
|
4.8
|
0.0
|
Previous CPR
|
Dead
|
5
|
60/M
|
Submassive
|
0.66
|
2.3
|
2.5
|
0.0
|
During CPR
|
Alive
|
6
|
42/M
|
Submassive
|
0.172
|
2
|
5.6
|
1.9
|
Shock
|
Dead
|
7
|
45/M
|
Submassive
|
0.08
|
2
|
2.8
|
1.0
|
Shock
|
Alive
|
8
|
72/M
|
Submassive
|
<0.01
|
2.8
|
1.3
|
1.0
|
Shock
|
Alive
|
9
|
73/M
|
Massive
|
<0.02
|
0.9
|
15.2
|
18.3
|
Shock
|
Alive
|
10
|
26/F
|
Massive
|
1.342
|
1
|
2.4
|
3.3
|
Shock
|
Alive
|
11
|
56/M
|
Massive
|
0.08
|
1.5
|
1.4
|
4.0
|
Shock
|
Alive
|
12
|
32/F
|
Massive
|
1.244
|
2
|
1.2
|
2.8
|
Shock
|
Alive
|
13
|
83/M
|
Massive
|
<0.02
|
2.2
|
1.0
|
1.4
|
Shock
|
Alive
|
CPR, cardiopulmonary resuscitation; CT, computed tomography; ECMO, veno-arterial extracorporeal membrane oxygenation; F, female; LMWH, low-molecular-weight heparin; M, male; PE, pulmonary embolism; RV/LV, right-to-left ventricular; UFH, unfractionated heparin.