Improved outcome of extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest – A comparison with that for extracorporeal rescue for in-hospital cardiac arrest

Resuscitation 85 (2014) 1219–1224

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Clinical Paper

Improved outcome of extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest – A comparison with that for extracorporeal rescue for in-hospital cardiac arrest夽,夽夽 Chih-Hsien Wang a,b,d,1 , Nai-Kuan Chou a,1 , Lance B. Becker b , Jou-Wei Lin c , Hsi-Yu Yu a,d , Nai-Hsin Chi a , Shu-Chien Hunag a , Wen-Je Ko a , Shoei-Shen Wang a , Li-Jung Tseng a , Ming-Hsien Lin a,d , I-Hui Wu a , Matthew Huei-Ming Ma e , Yih-Sharng Chen a,∗ a

Department of Cardiovascular Surgery, National Taiwan University Hospital, Taipei, Taiwan Center for Resuscitation Science, Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA c Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Doulu, Yun-lin, Taiwan d Department of Surgery, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan e Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan b

a r t i c l e

i n f o

Article history: Received 24 April 2014 Accepted 13 June 2014 Keywords: Extracorporeal membrane oxygenation In-hospital cardiac arrest Out-of-hospital cardiac arrest Cardiopulmonary resuscitation

a b s t r a c t Purpose: The aim was to investigate the effects of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) and compare the results with those of in-hospital cardiac arrest (IHCA). Methods: We analyzed our extracorporeal membrane oxygenation (ECMO) results for patients who received ECPR for OHCA or IHCA in the last 5 years. Pre-arrest, resuscitation, and post-resuscitative data were evaluated. Results: In the last 5 years, ECPR was used 230 times for OHCA (n = 31) and IHCA (n = 199). The basic demographic data showed significant differences in age, cardiomyopathy, and location of the initial CPR. Duration of ischemia was shorter in the IHCA group (44.4 ± 24.7 min vs. 67.5 ± 30.6 min, p < 0.05). About 50% of each group underwent a further intervention to treat the underlying etiology. ECMO was maintained for a shorter duration in the OHCA patients (61 ± 48 h vs. 94 ± 122 h, p < 0.05). Survival to discharge was similar in the two groups (38.7% for OHCA vs. 31.2% for IHCA, p > 0.05), as was the favorable outcome rate (25.5% for OHCA vs. 25.1% for IHCA, p > 0.05). Survival was acceptable (about 33%) in both groups when the duration of ischemia was no longer than 75 min. Conclusions: In addition to having a beneficial effect in IHCA, ECPR can lead to survival and a positive neurological outcome in selected OHCA patients after prolonged resuscitation. Our results suggest that further investigation of the use of ECMO in OHCA is warranted. © 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction There is growing evidence that extracorporeal cardiopulmonary resuscitation (ECPR) can save lives when standard advanced

夽 A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2014.06.022. 夽夽 Some of the data were presented at the American College of Cardiology Foundation Annual Meeting, San Francisco, March 9–14, 2013. ∗ Corresponding author at: National Taiwan University Hospital, Taipei, Taiwan. Fax: +886 2 2395 6934. E-mail addresses: [email protected], [email protected] (Y.-S. Chen). 1 Drs. N.K. Chou and C.H. Wang contributed equally as first authors. http://dx.doi.org/10.1016/j.resuscitation.2014.06.022 0300-9572/© 2014 Elsevier Ireland Ltd. All rights reserved.

cardiac life support fails.1–6 While ECPR has saved the lives of many adults1,3,5,6 and children2,7,8 with in-hospital cardiac arrest (IHCA), its usefulness for out-of-hospital cardiac arrest (OHCA) victims is less certain. When ECPR is used to treat in-hospital cardiac arrest patients, rather than having poor survival rates less than 10% seen with standard advanced cardiac life support (ACLS),9 survival rates reportedly increase to 20–30%.1,3 OHCA is a complex disease category10,11 and is treated using different resuscitative methods and different strategies.12,13 The use of ECPR for OHCA victims that fail to respond to standard ACLS is gaining international momentum, but there are many obstacles to the rapid implementation of the technology and questions regarding which patients will benefit from its use. Current survival rates are dismal (near zero) when ACLS procedures have been

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attempted but failed. ECPR may save lives in this nearly hopeless situation; however, only few studies have examined this population. However, the extent to which these strong results in IHCA will be true for OHCA is not known. OHCA differs because OHCA victims are often initially treated by less-skilled bystander rescuers and typically experience long delays in receiving ECPR.14 We therefore wished to determine whether there was benefit of ECPR in OHCA patients. To accomplish this, we developed a program of ECPR for selected patients with OHCA in 2007 and prospectively entered all patient information into our ongoing ECPR database. We also compared outcomes of OHCA and IHCA patients treated with ECPR. 2. Methods This prospective observational study was approved by the Institutional Review Board of Ethic Regulation. Informed consent was waived due to the impossibility of obtaining consent from the patient, the need for immediate implementation, and the lack of alternative therapies. As soon as possible, informed consent was sought from family members for each patient that met the indications for ECPR. If consent was not given, the patient was excluded. We started our ECMO program in 1994 and have extended its application to various critical situations, such as respiratory failure, postcardiotomy shock, and CPR. In 2003, we also set up a task force committee for ECPR, under the direct supervision of the Center of Quality Management Committee, to regularly review and monitor the indication, cause, and outcomes of every ECPR case. All data have been systemically and prospectively collected and reviewed since 2003.3,9 Our institution is located in the center of a major metropolitan area of 3 million citizens that has an established emergency medical technicians (EMTs) who are trained to comply with American Heart Association guidelines.15,16 EMT members receive comprehensive basic cardiopulmonary life support training emphasizing the immediate initiation of CPR when they arrive on the scene and will defibrillate the patients if appropriate in the prehospital setting. 2.1. Treatment of patients with OHCA In our study, OHCA was defined as any cardiac arrest outside the hospital, including in the ambulance. For patients in cardiac arrest, a rapid primary survey followed by CPR and attempted defibrillation was initiated by EMTs. Patients were transported to our institution if they were within out catchment area or at the request of family members. CPR, with an emphasis on compression only, was performed continuously during transportation. If the patient was pulseless or if temporary return of spontaneous circulation (ROSC) was not sustained, the ambulance staff called ahead to our Center and notified us of the patient’s condition and the resuscitation team was alerted. Upon arrival at the emergency department, the physicians continued advanced cardiopulmonary life support (ACLS) and secured an airway if this had not already been done. If the patient failed to achieve ROSC after administration of two doses of epinephrine and ACLS for 10 min, the physicians activated the ECMO team to decide whether the patient would be eligible for ECPR. 2.2. Selection/inclusion criteria for IHCA (Table 1) The inclusion and exclusion criteria for IHCA in our hospital have been described previously1,3 and are listed in Table 1. In the present study, although good candidates for ECPR, patients aged less than 16 years were excluded from the analysis.

Table 1 Inclusion and exclusion criteria for adult extracorporeal resuscitation for IHCA (I) and OHCA (O) patients. Exclusion criteria

Inclusion criteria

Age > 80 years (relative) [I, O], age < 16 yearsa Terminal stage malignancy [I, O]

Age ≥ 16 (I, O)

Pre-existing multi-organ dysfunction [I, O] Ventilator-dependent > 3 months [I, O] Bed-ridden > 3 months, not self-independent [I, O] Acute/active intracranial hemorrhage or infarct or severe head injury [I, O]

Possible cause of cardiac origin [I, O] Unknown origin excluding the exclusion criteria [I, O] Unconsciousness, dilated pupil during CPR [I, O] Witnessed cardiac arrest [I, O] CPR for longer than 10 min without ROSC under active CPR [I, O]

Traumatic origin, uncontrollable bleeding [I, O] Arrest without active CPR [I, O] Nonwitnessed cardiac arrest [O] Uncontrolled infection [I, O] Charlson score > 7 (relative) [I, O] ROSC for 20 min after resuscitation without repeated collapse [I, O] Conscious patient [I, O] Patient with “DNR” order [I, O] Location at which ECMO was applied IHCA

OHCA

Any location in the hospital: intensive care unit, ward, emergency room, catheterization laboratory

Emergency room/department, outside the hospital, other hospital without ECPR

CPR = cardiopulmonary resuscitation, DNR = Do-not-resuscitate, ECMO = extracorporeal membrane oxygenation, IHCA = in-hospital cardiac arrest, OHCA = out-of-hospital cardiac arrest, ROSC = return of spontaneous circulation. a Persons aged less than 16 years excluded from analysis.

2.3. Selection/inclusion criteria for OHCA (Table 1) Since ECMO is a highly invasive and resource-consuming procedure, it is impossible to apply it to all patients with OHCA. We established a rapid checklist of criteria for suitability for ECPR (Table 1). We compiled a brief list of information about whether the attack had been witnessed and whether bystander resuscitation had been attempted and the time between collapse and initial resuscitation/compression. If the arrest was witnessed and basic resuscitation commenced within 6 min and CPR was continued during transportation, ECMO was considered. Other exclusion criteria were OHCA of a traumatic origin, preexisting multiple organ dysfunction, and sustained ROSC for more than 20 min after OHCA. An age greater than 80, terminal malignancy, a Charlson index17 over 7, and non-witnessed arrest were considered as relative contraindications for ECPR. 2.4. ECMO procedure The equipment and instruments required for cannulation were all pre-configured on a cart for a rapid response in an ECPR situation (Fig. 1). The on-call ECMO physicians decided whether to apply therapeutic hypothermia for OHCA ECPR. If therapeutic hypothermia was used, the patient was cooled to 33 ◦ C for at least 24 h and rewarmed at 0.5 ◦ C every 4 h until the tympanic temperature reached 37 ◦ C. In the case of IHCA, hypothermia was not used in patients with immediate recovery of consciousness after ECPR. The possible etiologies leading to the episode were investigated as soon as possible, usually with catheterization or computed tomography. Once the diagnosis had been made, the underlying disease was treated in order to correct the anatomical lesion; in

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Table 2 Basic demographic data before ECMO. OHCA, N (%) N 31 50.7 ± 15.3 Age, years (mean ± SD) Age > 60 years 7 (17) Male 23 (75) Pre-existing comorbidity 6 (19) Diabetes 15 (48.4) Hypertension 5 (16.1) Dyslipidemia Malignancy 1 (3.2) Lung insufficiency 0 (0) Stroke 0 (0) 2 (6.5) Chronic renal disease 2 (6.5) Cardiovascular disease 0 (0) Chronic hepatitis Cardiomyopathy 0 (0) Location of initial CPR 0 (0) ER 0 (0) ICU Cath lab 0 (0) 0 (0) OR Ward 0 (0) 10 (32.2) Home 19 (61.3) Public area 2 (6.5) Other clinic Location in which ECMO was applied ERa 29 (93.6) Time period of CPR episode Period A 15 (48.4) Period B 13 (41.9) Period C 3 (9.7) Fig. 1. Instruments and equipment required for cannulation pre-configured in a wheeled cart for a rapid response. (A) Cannulas of various sizes; (B) different sutures required for cannulation; (C) connectors; (D) sterile drapes, gowns, and instruments; (E) pre-assembled ECMO set; (F) various accessories for the surgical procedures.

about 50% of cases, the lesion was not found or no attempt was made to find it. Patient consciousness was evaluated every 12 h. The functional status of survivors following discharge from the hospital was also analyzed according to the Glasgow–Pittsburgh cerebral performance category (CPC) score18 [favorable neurological outcome (CPC score of 1 or 2) vs. worse outcome (CPC score of 3 or 4)]. Since OHCA patients were not taking catecholamines before collapse, the inotropic equivalent (IE) we have previously applied for evaluating pre-arrest status1,9 was used to decide when to wean the patient off ECMO. In general, the criteria for weaning were if the patient regained consciousness, the hemodynamic status could be maintained at an IE less than 15 ␮g/kg/min, and the left ventricular ejection fraction was >35%. If weaning from ECMO was not possible within 7–14 days, ventricular assistance device or heart transplantation was considered in the absence of contraindications. 2.5. End points The primary end point was survival to hospital discharge. The secondary end point was a favorable outcome, defined as a CPC score of 1 or 2. 2.6. Statistical analysis Baseline patient characteristics are reported as mean ± SD or as a percentage (%). Categorical variables were compared using the 2 -test (or Fisher’s exact test) and continuous variables were compared using Student’s t-test between the OHCA and IHCA groups. A Cox regression model was used to examine the hazard ratio (HR), 95% confidence interval (95% CI), and p-value associated with mortality. Each case in either group was followed from ECMO initiation till death or censorship at ECMO removal. The OHCA and IHCA

IHCA, N (%)

p

199 55.7 ± 15.1 76 (38.2) 155 (78)

0.05 0.07 0.65

67 (34) 95 (47.7) 67 (43.7) 2 (1) 3 (1.5) 19 (9.5) 13 (6.5) 58 (29.1) 3 (1.5) 31 (15.6)

0.01 0.55 0.04 0.35 0.49 0.07 0.67 0.01 0.06 0.02

64 (32.2) 75 (37.7) 22 (11.1) 7 (3.5) 23 (11.6) 0 (0) 8 (4.0) 0 (0)

0.00 0.00 0.04 0.36 0.03 0.00 0.00 0.00

64 (32.2)

0.00

79 (39.7) 74 (37.2) 46 (23.1)

0.24 0.38 0.07

CPR = cardiopulmonary resuscitation. ECMO = extracorporeal membrane oxygenation, ER = emergency room, IHCA = in-hospital cardiac arrest, OHCA = out-ofhospital cardiac arrest, OR = operating room, Period A = 7:01 am to 3:00 pm, Period B = 3:01 pm to 11:00 pm, Period C = 11:01 pm to 7:00 am. a ECMO was applied in another hospital without an ECPR program for two patients.

patients were initially combined for analysis in the Cox regression model, and a binary variable was used to examine HR between the two groups. Then, the patients in the two groups were analyzed separately. Prognostic variables, including age, sex, CPR sites, the presence of diabetes mellitus, hypertension, coronary artery disease, chronic renal disease, initial rhythm, and etiology of using mechanical support circulation, were added as covariates into the model. Variables were selected by a stepwise approach, i.e., pvalues <0.10 for model entry and >0.05 for removal. A two-sided p-value <0.05 was considered to be statistically significant. Statistical analyses were conducted using SPSS Statistics for Windows versions 17.0 (IBM SPSS Inc., Chicago, IL). 3. Results Between January 1, 2007, and August 31, 2012, 230 patients who underwent ECPR fulfilled the study criteria and were enrolled for analysis. These consisted of 199 patients with IHCA and 31 with OHCA. The baseline demographic data for the two groups are shown in Table 2. The variables during CPR and the post-CPR period are shown in Table 3. The arrest was witnessed in all patients in both groups and the incidence of ventricular tachycardia (VT)/ventricular fibrillation (VF) was similar in both groups. Since all patients had a witnessed arrest, CPR was started rapidly in both groups and the no-flow period in the OHCA group was <5 min. The duration of ischemia (collapse to ECMO) was significantly longer in the OHCA group (67.5 ± 30.6 min vs. 44.4 ± 24.7 min for IHCA, p < 0.001). None of the OHCA group received pre-collapse catecholamine support, whereas most of the IHCA group did, with a mean inotropic equivalent of 40 ± 98 ␮g/kg/min (Table 3). These different pre-collapse

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Table 3 CPR and post-CPR variables in ECPR patients.

N Witnessed IE when ECMO applied (␮g/kg/min) First documented rhythm VT/VF PEA/asystole No-flow duration (min, collapse to initial CPR) Duration of ischemia (min, collapse to ECMO), mean ± SD Median (min) Range (min) Hypothermic strategy used Yes Disease diagnosed, possible cause Deteriorated cardiomyopathy Acute coronary syndrome Hypovolumia Suspected myocarditis Electric shock/CO poisoning Drug/electrolyte effect Pulmonary embolism Postcardiotomy/post-HTx Others Subsequent intervention Yes Revascularization PCI CABG Left heart drain VAD HTx IABP CAVH Catheterization Pulmonary thrombectomy Outcome Duration of ECMO Mean Median Survival to discharge CPC status at discharge 1 or 2, n (%)

OHCA, N (%)

IHCA, N (%)

p

31 31 0

199 199 40 ± 98

0.00

15 (48.4) 16 (52) 1–5

91 (45.7) 108 (54.3) 1–4

0.47 0.56 0.67

67.5 ± 30.6

44.4 ± 24.7

0.00

56 35–182

40 15–162

12 (38.7)

34 (17.1)

0.01

0 (0)

31 (15.6)

0.01

19 (61.3) 2 (6.5) 1 (3.2) 3 (9.7) 2 (6.5)

85 (42.7) 9(4.5) 11 (5.5) 0 (0) 6 (3.0) 6 (3.0) 18 (9.0) 33 (16.6)

0.04 0.64 0.59

0 (0) 0 (0) 15 (48) 0 (0) 20 (65) 0 (0)

96 (48.2) 68 (34.2) 39 (19.6) 35 (17.6) 12 (6.0) 5 (2.5) 12 (6.0) 46 (23) 66 (33) 68 (34) 5 (2.5)

0.31 0.01 <0.01 0.27 0.16 0.37 0.16 0.00 0.00 0.00 0.37

61.1 ± 48.2 63.3 12 (38.7)

94.4 ± 122.3 49.4 62 (31.2)

<0.01

8 (25.8)

50 (25.1)

0.55

4 (12.9) 18 (58.1) 18 (58.1) 17 (54.8) 3 (9.7)

0.33 0.33 0.08 0.60

0.26

CABG = coronary artery bypass grafting, CAVH = continuous arteriovenous hemodialysis, CPC = cerebral performance category, CPR = cardiopulmonary resuscitation, ECMO = extracorporeal membrane oxygenation, HTx = heart transplantation, IABP = intra-aortic balloon pump, IE = inotropic equivalent, IHCA = in-hospital cardiac arrest, OHCA = out-of-hospital cardiac arrest, PCI = percutaneous coronary intervention, PEA = pulseless electrical activity, VAD = ventricular assist device, VT/VF = ventricular tachycardia/ventricular fibrillation.

situations mean caution should be applied in comparing the two groups. A hypothermic strategy was applied in 38.7% of the OHCA group, but only in 10% of the IHCA group (p < 0.01 compared to the OHCA group), as we did not apply hypothermia in patients with return of consciousness after ECPR. The possible etiologies leading to the episode are listed in Table 3. The possible reasons for cardiac arrest were quite diverse. In the OHCA group, acute coronary syndrome was the main reason for cardiac arrest, with accidents (electric shock and drug effects) being the second, while, in the IHCA group, acute coronary syndrome was the leading cause, followed by pre-existing dilated cardiomyopathy and post-cardiotomy shock. No statistical difference in etiology was seen between the two groups. In general, uncontrolled bleeding was considered a contraindication for ECPR. However, because the real cause of the episode was not clearly identified at the time when ECPR was applied,

11 patients had hypovolumia leading to cardiac arrest, 2 in the OHCA group, and 9 in the IHCA group. Two OHCA patients who were initially diagnosed as having acute coronary syndrome were prepared for ECMO, but were then diagnosed as having aortic dissection, a contraindication for ECMO. The nine patients in the IHCA group with hypovolumia consisted of four with ventricular rupture-related infarction and five with aortic rupture after aortic stenting, and all expired in spite of ECMO, even though some underwent further surgical intervention. Half of the combined study group (114/230, 49.6%) underwent a subsequent intervention, mainly revascularization of occluded arteries. Since acute coronary syndrome was the main cause of collapse in the OHCA group, more than half of the victims (58.1%) underwent revascularization of the occluded coronary artery by catheterization and/or surgery. In the IHCA group, onethird (34.2%) of the patients had underlying cardiomyopathy or postcardiotomy cardiac arrest, so some patients (n = 17, 8.5%) underwent subsequent ventricular assist device implantation or heart transplantation after critical selection. Pulmonary embolism was the cause of collapse in 3% of the IHCA group (Table 3). As also shown in Table 3, the duration of ECMO support was 90 ± 116 h (median 50 h) for the whole ECPR group, 61 ± 48 h for the OHCA group, and 94 ± 122 h for the IHCA group (p < 0.01). The longer and more variable support duration required for the IHCA group might be due to more heterogeneous etiologies and different procedures used in this group. Survival to discharge was 32.2% for the whole ECPR group, 38.7% for the OHCA group, and 31.2% for the IHCA group (p > 0.05). At discharge, 25.2% of all patients had a favorable neurological status (CPC I or II), and there was no difference between the two groups (25.8% for the OHCA group vs. 25.1% for the IHCA group, p > 0.05). The multivariate survival analysis did not show a statistically significant difference in survival between the OHCA and IHCA groups with ECPR (HR 1.36, p = 0.37) (Table 4, left column). Age per year resulted in an increase in hazard of mortality by 2% (p < 0.01) when two groups were combined, by 10% (p < 0.01) in the OHCA group, and by 2% (p < 0.01) in the IHCA group. As expected, the initial rhythm was consistently an important factor for survival. As compared to VT/VF, patients initially presented with asystole or PEA had a higher chance of mortality when two groups were combined (HR: 2.30, p < 0.01), in the OHCA group (HR: 5.60, p = 0.04), and in the IHCA group (HR: 2.64, p < 0.01). The ischemic duration was not associated with mortality hazard (HR: 0.99, p = 0.29) in the OHCA group, but each minute increase in the ischemic time increased the hazard by 2% (p < 0.01) in the IHCA group. The OHCA patients with acute coronary syndrome had a better survival rate (HR: 0.08, p = 0.03), but IHCA patients with ACS did not have a statistically better survival than those with other etiologies (HR: 0.76, p = 0.18) (Table 4). Duration of ischemia (collapse to ECPR) was a key issue for survival (Table 4). Focusing on this factor, no patient in the OHCA group received ECPR within 30 min because of delay and difficulty in early rescue, while, in the IHCA group, there was a trend for patients with a longer duration of ischemia to have a lower survival rate and less favorable outcome (Table 5). In the present IHCA group, the overall survival rate was 31.1%, with a favorable neurological outcome of 25.1%, similar to our previously published data for the IHCA group.3 In the present OHCA group, the overall survival was 38.7%, with a favorable neurological outcome of 25.8%.

4. Discussion The present study confirmed that ECPR is beneficial for IHCA and also demonstrated a better outcome using ECPR for OHCA compared to previous studies.19–21 Some points deserve discussion.

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Table 4 Multivariate analysis of risk factors related to death. All combined HR 1.36 1.00

IHCA OHCA

Group

OHCA p

IHCA

HR

p

HR

p

0.37

Age

Per year

1.02

<0.01

1.10

<0.01

1.02

<0.01

Initial rhythm

Non-VT/VF VT/VF

2.30 1.00

<0.01

5.60 1.00

0.04

2.64 1.00

<0.01

Ischemic duration

Per min

1.01

<0.01

0.99

0.29

1.02

<0.01

ACS

ACS Non-ACS

0.84 1.00

0.35

0.08 1.00

0.03

0.76 1.00

0.18

ACS = acute coronary syndrome, IHCA = in-hospital cardiac arrest, OHCA = out-of-hospital cardiac arrest, VT/VF = ventricular tachycardia/ventricular fibrillation.

Table 5 Relationship between survival or favorable outcome and duration of ischemia in the two groups. Duration of ischemia

Case count

Survival

Favorable outcome

OHCA N (%)

IHCA N (%)

OHCA N (%)

IHCA N (%)

OHCA N (%)

IHCA N (%)

≤30 min ≤45 min ≤60 min ≤75 min ≤90 min

0 (0) 8 (25.8) 16 (51.6) 22 (71.0) 27 (87.1)

69 (34.7) 123 (61.8) 165 (82.9) 180 (90.5) 187 (94.0)

5 (62.5) 8 (50.0) 12 (54.4) 12 (44.4)

26 (37.7) 46 (37.4) 56 (33.9) 58 (32.2) 60 (32.1)

4 (50.0) 7 (43.8) 8 (36.4) 8 (26.6)

24 (34.8) 41 (33.3) 47 (28.5) 48 (26.7) 49 (26.2)

Total

31 (100)

199 (100)

12 (38.7)

62 (31.1)

8 (25.8)

50 (25.1)

Duration of ischemia = time between collapse and start of extracorporeal membrane oxygenation. Favorable outcome = CPC status 1 or 2, IHCA = in-hospital cardiac arrest, OHCA = out-of-hospital cardiac arrest.

Since our first study in the ECPR field,1 ECMO has been advocated as an adjuvant therapy in patients undergoing CPR with proven benefit.6,9,19,20 The present 5-year study confirmed the benefit of using ECMO for IHCA. Compared to the data from our previous study,9 the duration of ischemia was shorter [44.4 ± 24.7 min in IHCA cases in the present study (n = 199) vs. 55.7 ± 27.0 min (n = 135) in our previous study], indicating that a pre-equipped ECMO cart (Fig. 1) and improved recruitment and organization of an ECPR team can decrease the time for deployment. However, the shorter ischemic period did not result in a significant improvement in survival. Survival results were similar in the IHCA and OHCA groups. There are several reasons that could result in a decreased survival rate in the IHCA group. Firstly, postcardiotomy is thought to have a better outcome than other etiologies1,9 and its incidence in the IHCA group decreased from 17% in our previous study9 to 9% in the present study, which could lead to a decreased survival rate in the present IHCA group. Secondly, our IHCA group included nine patients (4.5%) with a possible etiology of hypovolumia, a group that has been usually excluded in previous studies. We included these patients in the data analysis because we did not know the real cause of collapse at the time when they received ECPR and also wanted to examine the real-world situation, rather than employ a group selected to give a good statistical result. Thirdly, dilated cardiomyopathy was seen in 15.6% of the IHCA group. Because heart transplantation was the only solution for these patients and most were unable to receive a transplantation, the result is a decreased survival rate in this group. Accordingly, there are some differences in pre-collapse data (Table 2) and CPR/post-CPR variables (Table 3), therefore we believe the OHCA and IHCA groups with ECPR may considered as basically different groups. Careful examination of the difference between IHCA and OHCA is required. Direct comparison of survival rates of OHCA ECPR group and IHCA ECPR group from literatures is not really valid without careful examination of the previous comorbidity and variables during and after CPR.

Another important point of our results is the improved outcomes in the OHCA patients receiving ECPR. Reviewing literatures of ECPR for OHCA, the survival rates were reported to be around 4 to 15%.19,21,22 Few reports with >20% survival rates were seen in cases selected either of cardiac origin only23 or by using many exclusion criteria,24 indicating that the better results may be related to a selection or publication bias. The better outcome seen in our study may be related to the following: (1) There is a well-organized and rapid-response EMT system in Taipei city.25 (2) Our facility is centrally located and adept at handling patient transportation and resuscitation. (3) We designed a protocol to initiate ECPR for OHCA using an equipped cart in the emergency room, rather than in the ICU, shortening the duration of ischemia to a mean of 67 min, shorter than the 88–120 min seen in other series.19,21

4.1. Limitations The study was not a randomized trial. We used prospectively collected data, because it is not possible to perform a randomized study for these types of critically ill patients. Although bias existed in the selection process for both groups before ECPR, we needed to make exclusions because ECMO is invasive and labor-intensive. The number of OHCA cases was low, which may affect the data analysis.

5. Conclusions Our consecutive series demonstrated that, despite some possible selection bias, the use of ECPR resulted in similar outcomes for IHCA and OHCA patients. The improved outcome in the OHCA group when ECPR was applied within 75 min should encourage further studies in this field and suggests that ECMO might be considered as an adjuvant therapy for not only IHCA, but also for OHCA.

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Acknowledgements The study was partially supported by 100-2314-B-002-018MY2, 102-2315-B-002-009-, Ministry of Science and Technology (NSC), Taiwan, and this work was supported in part by the Department of Medical Research of National Taiwan University Hospital.

13.

14.

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